bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDG-PET/CT: novel method for viability assessment of livers perfused ex vivo
Authors: Orita Erika , Becker Dustin , Mueller Matteo , Hefti Max , Schuler Martin J. , Bautista Borrego Lucia , Dutkowski Philipp , Zeimpekis Konstantinos , Treyer Valerie , Kaufmann Philipp A. , Eshmuminov Dilmurodjon , Clavien Pierre-Alain , Huellner Martin W. 
Published: March 2021

Purpose
Ex vivo liver machine perfusion is a promising option to rescue marginal liver grafts mitigating the donated organ shortage. Recently, a novel liver perfusion machine that can keep injured liver grafts alive for 1 week ex vivo was developed and reported in Nature Biotechnology. However, liver viability assessment ex vivo is an unsolved issue and the value of 18F-fluorodeoxyglucose (FDG)-PET/CT for such purpose was explored.

Materials and methods
Discarded two human and six porcine liver grafts underwent FDG-PET/CT for viability assessment after 1 week of ex vivo perfusion. PET parameters [standardized uptake value (SUV)max, SUVmean, SUVpeak and total lesion glycolysis] were compared between hepatic lobes and between porcine and human livers. The prevalence of FDG-negative organ parts was recorded. The estimated effective radiation dose for PET/CT was calculated.

Results
All organs were viable with essentially homogeneous FDG uptake. Of note, viability was preserved in contact areas disclosing the absence of pressure necrosis. Four porcine and two human organs had small superficial FDG-negative areas confirmed as biopsy sites. Total lesion glycolysis was significantly higher in the right hepatic lobe (P = 0.012), while there was no significant difference of SUVmax, SUVmean and SUVpeak between hepatic lobes. There was no significant difference in FDG uptake parameters between porcine and human organs. The estimated effective radiation dose was 1.99 ± 1.67 mSv per organ.

Conclusion
This study demonstrates the feasibility of FDG-PET/CT for viability assessment of ex vivo perfused liver grafts after 1 week.
Utility of 18F-FDG-PET/CT in management and prognostication of treatment naïve late-stage soft tissue sarcomas
Authors: Singh Tejesh Pratap , Sharma Anshul , Sharma Akshima , Bakhshi Sameer , Patel Chetan , Pandey Anil Kumar , Dhamija Ekta , Batra Atul , Kumar Rakesh 
Published: March 2021

Objective
This study evaluated the utility of 18F-fluorodexoyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in staging, grading, and prognostication of Stage III and IV soft tissue sarcomas (STSs).

Methods
Forty patients (Median age = 32.5 years; 25 men) with histologically proven STSs, prospectively underwent 18F-FDG-PET/CTs at baseline. Three-dimensional region of interests were drawn encompassing the lesions to calculate standardized uptake values (SUVs) and metabolic tumor volumes (MTVs). After segmentation, Haralick statistical texture analysis was performed. Follow-up was available for 35 patients. Survival at 6 months was 71.4% and at 1 year was 57.1%.

Results
American Joint Committee on Cancer Stage III was seen in 23 and Stage IV in 17 patients. None of the baseline quantitative and semi-quantitative parameters could predict response or progression. Only reduction in SUVmax in interim PET/CT correlated with baseline SUVmax (Spearman’s Rho = 0.533; P = 0.019). Textural parameters namely ‘contrast’ in CT (P = 0.039) and ‘difference entropy’ in PET/CT (P = 0.051) could differentiate intermediate from high-grade lesions, with corresponding area under curves being 0.736 (0.533–0.889) and 0.700 (0.518–0.882). M1 disease [Hazard ratio (HR): 3.184 (1.179–8.595); P = 0.022], absence of surgical treatment [HR 0.305 (0.106–0.873), P = 0.027 with surgery], lower MTV/total tumor volume (TTV) [HR: 0.975 (0.953–0.997; P = 0.028] and progressive disease in interim PET/CT [3.483 (0.898–13.515); P = 0.056] were predictors of lower survival in univariate analysis. Only M1 disease was found to be reaching significance in multivariate analysis [HR = 2.683 (0.949–7.580); P = 0.063]. Baseline PET/CT changed management in 12.5% of patients [compared to local-imaging and high-resolution CT chest]; with detection of extra-pulmonary metastases. Though, interim and end of treatment PET/CTs detected more metastatic lesions, management was not impacted.

Conclusion
18F-FDG-PET/CT allows for more accurate M-staging in late-stage STSs, which in turn influences the option of curative surgical resection and thus impacts patient prognosis. Lower baseline MTV/TTV and progression in interim PET/CT are also associated with lower survival. Textural analysis may have a role in noninvasive grading.
Re-188-tricarbonyl tamoxifen as a theranostic radiopharmaceutical for estrogen receptor expressing breast cancers: radiolabeling, characterization and in-vitro cytotoxic assessment
Authors: Chhabra Anupriya , Shukla Jaya , Sharma Uma , Vatsa Rakhee , Bhatia Alka , Upadhyay Deepti , Mittal Bhagwant Rai 
Published: March 2021

Purpose
Development of a novel theranostic radiopharmaceutical for estrogen receptor, expressing unresectable primary and metastatic breast cancers.

Methods
Tamoxifen was radiolabeled with Rhenium-188 (Re-188) through tricarbonyl core. Radiolabeled complex was characterized by 1proton nuclear magnetic resonance spectroscopy and Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF). Various quality control tests such as sterility, apyrogenicity, and radiochemical purity (RCP) were performed to assess the suitability of the radiopharmaceutical for intravenous administration. In-vitro cell culture studies were performed for cytotoxic assessment. In addition to this, exposure due to different doses of Re-188-tricarbonyl tamoxifen was also calculated.

Results
Re-188-tricarbonyl and Re-188-tricarbonyl tamoxifen showed more than 99% RCP. Sample was found to be sterile and pyrogens levels were within the permissible limit. Re-188-tricarbonyl tamoxifen was successfully characterized by MALDI-TOF and 1H-NMR spectroscopy. Re-188 (1.480 MBq) and tamoxifen (0.027 or 0.054 µM) individually showed 36 and 70% cell death, respectively. However, radiolabeled complex (Re-188-tricarbonyl tamoxifen) with the same amount of radioactivity (1.480 MBq) increased the cell death to more than 90% with one-fifth to one-tenth molar concentration of tamoxifen (0.0054 μM).

Conclusion
Re-188-tricarbonyl tamoxifen can be synthesized in-house in radiopharmacy lab. Radionuclide therapy with Re-188-tricarbonyl tamoxifen can be given using 10 times less amount of tamoxifen as compared to cold tamoxifen.
The role of 18F-Fluorodeoxyglucose PET/CT in restaging patients with small cell lung cancer: a systematic review
Authors: Quartuccio Natale , Salem Ahmed , Laudicella Riccardo , Spataro Alessandro , Chiaravalloti Agostino , Caobelli Federico , Cistaro Angelina , Alongi Pierpaolo , Evangelista Laura 
Published: March 2021

Aim

18F-Fluorodeoxyglucose (FDG) PET imaging may play an important role in the restaging of patients with small-cell lung cancer (SCLC),, nevertheless, a systematic review of literature was still missing in this setting. The aim of this review was to summarize the evidence on literature regarding the utility of 18F-FDG PET imaging in restaging patients with SCLC.

Methods
A literature search was performed to retrieve original studies using 18F-FDG PET or 18F-FDG PET/computed tomography (CT) in a minimum of 10 patients with SCLC at restaging.

Results
The selected literature (17 studies) was discussed in four sections: detection rate, impact on management, prediction of prognosis and evaluation of the response to therapy. According to the literature, PET imaging may result in discordance with conventional imaging, mainly contrast-enhanced CT (ceCT), and detect additional lesions in a certain proportion of cases, leading to upstaging or downstaging. A variable level of disagreement between PET and conventional imaging has been reported also in the evaluation of response to therapy. A positive PET study is associated with shorter survival, especially in the presence of distant metastases. According to some studies, semiquantitative parameters are also inversely associated with overall survival and progression-free survival. Although the retrieved articles proved the utility of 18F-FDG PET imaging in each clinical setting, literature is still limited.

Conclusions
This review encourages the use of 18F-FDG PET imaging, especially in conjunction with ceCT in recurrent SCLC patients. Further level I evidence is needed to further assess the diagnostic and prognostic capability of 18F-FDG PET/ceCT findings in SCLC.
Renogram image characteristics and the reproducibility of differential renal function measurement
Authors: Brink Anita , Libhaber Elena , Levin Michael 
Published: March 2021

Purpose
Patient factors such as age and glomerular filtration rate (GFR), have been implicated as causes for poor reproducibility of differential renal function (DRF) estimates on 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renography. This study aims to investigate factors associated with the reproducibility of DRF measurements.

Methods
The association between age, GFR and imaged derived image characteristics and reproducibility of repeated DRF estimates calculated using the area under the curve method and the Rutland Patlak method was analysed for cohort 1 (n = 127). The association between these variables and reproducibility of DRF was tested with univariate linear regression. The univariate linear regression results were used to plan the multiple linear regression combinations.
The associations between variables identified and reproducibility of DRF values were then tested in a second cohort (n = 227).

Results
The R
2 values for goodness-to-fit for the multiple regression models ranged from 0.33 to 0.49 for cohort 1 and from 0.17 to 0.22 for cohort 2. Left kidney to background ratio (LKTBR) was significant in all the multiple linear regression combinations (P < 0.05). Right kidney to background ratio (RKTBR), right renal margins well defined, right renal margins poorly visualised, time visualisation right calyces and age were significant in most combinations. The reproducibility of DRF measurement was decreased when the kidney to background ratio (KTBR) was ≤2.

Conclusion
Only LKTBR, RKTBR, right renal margins well defined, time visualisation right calyces and age predicted reproducibility for the measurement of DRF on 99mTc-MAG3 renograms. The KTBR should be incorporated into the renal processing software as a quality control step. The DRF values should be interpreted with caution if the KTBR is ≤2.0.
Fuzzy logic-based moving average filters for reducing noise from Tc-99m-sestamibi parathyroid images
Authors: Pandey Anil Kumar , Kumar Navneet , Dhiman Shweta , Patel Chetan , Bal Chandrashekhar , Kumar Rakesh 
Published: March 2021

Introduction
The objective of the study was to use fuzzy logic-based moving average filters for reducing noise from Tc-99m-sestamibi parathyroid images and to compare its performance with classical moving average filters.

Methods
Sixty-eight Tc-99m-sestamibi parathyroid images (33 image zoom 1.0, 35 images zoom 2.0) were filtered using symmetric triangular fuzzy filters with the moving average (TMAV), asymmetric triangular fuzzy filters with the moving average (ATMAV) and classical moving average filter (MAV) with moving average within a square window of dimension N × N pixels (N=3,5,7,9,11). The relative filtering performance was compared both objectively (using Brisque score) and subjectively [by two nuclear medicine physicians on a 4-point scale (1 = nondiagnostic; 2 = diagnostic; 3 = good; and 4 = excellent image quality)]. The nonparametric two-sample Kolmogorov–Smirnov test was applied to find the statistically significant difference between the quality of input and their corresponding filtered images.

Results
The Brisque score assigned to MAV filtered zoom 2.0 images (MAV_3, median = −0.61) were significantly smaller than that of their input images (median = 53.84, at P = 1) and fuzzy filtered images (TMAV_3, median = 0.44, at P = 0.89 and ATMAV_3, median =8.26, at P = 0.97). The sum of average subjective image quality score for input, MAV_3, TMAV_3, TMAV_5, ATMAV_3, and ATMAV_5 were 148, 221, 221.5, 198,171,253 and 237.5, respectively.

Conclusion
On the basis of subjective assessment, the performance of ATMAV_3 fuzzy filter was found to be better compared to the classical moving average filter in reducing noise from Tc-99m-sestambi parathyroid images.
Attenuation correction in CZT myocardial perfusion imaging comparison of supine-prone and low-dose CT-corrected supine acquisitions
Authors: Hahn Eva , Kammeier Annett , Burchert Wolfgang , Lindner Oliver 
Published: March 2021

Aims
The study aimed to investigate whether additional prone imaging delivers comparable results to supine imaging with low-dose computed tomography (CT) attenuation correction (CTAC) in cadmium, zinc and telluride (CZT) myocardial perfusion imaging.

Methods and results
Thirty-four patients with an indication for myocardial perfusion imaging were studied with a CZT camera in the supine and then prone position. Furthermore, a low-dose CT was acquired. Three data sets were reconstructed and considered for analysis: (1) supine CZT, (2) supine CZT with CTAC and (3) supine CZT with additional prone CZT. Based on 17-segment polartomograms, we compared radiopharmaceutical uptake percentage, summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), total ischemic and scarred segments, and finally scan classification and clinical decision-making. SSS of supine/supine-CTAC/supine-prone was 341/229/253 (P < 0.05), SRS was 246/156/164 (P < 0.05) and SDS was 104/88/96 (ns), respectively. Total ischemic segments were 65/67/65 (ns) and total scarred segments 96/62/69 (P < 0.05), respectively. The frequency of normal scans was highest for supine-prone, followed by supine-CTAC and supine (41/35/24%, respectively). Supine imaging indicated 23% of patients for invasive coronary angiography, both supine-CTAC and supine-prone 18%. These two showed a significant intercorrelation.

Conclusion
Additional prone imaging and CTAC are mainly correct for the amount and extent of myocardial scars. Both methods increase the frequency of normal scans and show a significant agreement in clinical decision-making. Additional prone imaging appears as a useful alternative when a low-dose CT for attenuation correction is not available.
‘Enhancing’ red cell fate through epigenetic mechanisms
Authors: Rossmann Marlies P. , Zon Leonard I. 
Published: March 2021

Purpose of review
Transcription of erythroid-specific genes is regulated by the three-dimensional (3D) structure and composition of chromatin, which dynamically changes during erythroid differentiation. Chromatin organization and dynamics are regulated by several epigenetic mechanisms involving DNA (de-)methylation, posttranslational modifications (PTMs) of histones, chromatin-associated structural proteins, and higher-order structural changes and interactions. This review addresses examples of recent developments in several areas delineating the interface of chromatin regulation and erythroid-specific lineage transcription.

Recent findings
We survey and discuss recent studies that focus on the erythroid chromatin landscape, erythroid enhancer-promotor interactions, super-enhancer functionality, the role of chromatin modifiers and epigenetic crosstalk, as well as the progress in mapping red blood cell (RBC) trait-associated genetic variants within cis-regulatory elements (CREs) identified in genome-wide association study (GWAS) efforts as a step toward determining their impact on erythroid-specific gene expression.

Summary
As one of the best characterized and accessible cell differentiation systems, erythropoiesis has been at the forefront of studies aiming to conceptualize how chromatin dynamics regulate transcription. New emerging technologies that bring a significantly enhanced spatial and temporal resolution of chromatin structure, and allow investigation of small cell numbers, have advanced our understanding of chromatin dynamics during erythroid differentiation in vivo.
Ultrasound: an emerging modality for the dysphagia assessment toolkit?
Authors: Allen Jodi E. , Clunie Gemma M. , Winiker Katharina 
Published: March 2021

Purpose of review
Videofluoroscopy (VFSS) and fibreoptic endoscopic evaluation of swallowing (FEES) are established instrumental techniques to support differential diagnosis and treatment of oropharyngeal dysphagia. Whilst their value is undisputed, each tool is not without limitations. The COVID-19 pandemic has restricted access to VFSS and FEES leading clinicians to explore alternative or augmentative tools to support swallowing assessment.
Ultrasound (US) is an established tool for visualisation of head and neck anatomy, including structures implicated in swallowing. Although US has been utilised in swallowing research for many years, its application has not translated into common clinical practice. This review presents and debates the evidence for and against use of US for clinical swallowing assessment.

Recent findings
Evaluation of swallowing muscle morphometry and measurement of isolated swallowing kinematics are two primary uses of US in swallowing assessment that have been identified in the literature. Use of US to detect bolus flow, aspiration and residues is in its early stages and needs further research.

Summary
US shows promise as an adjunctive modality to support assessment of swallowing. With standardisation, these measurements may have potential for transition into clinical care. Reliability and validity testing and development of normative data are imperative to ensure its use as an evidence-based instrumentation.
Pioneering virtual otolaryngology specialist examinations in South Africa in the COVID-19 and post-COVID-19 era
Authors: Seedat Riaz Y. 
Published: March 2021

Purpose of review
South Africa, and the African continent, have a shortage of ear, nose and throat (ENT) specialists. The coronavirus disease 2019 (COVID-19) pandemic not only had an adverse impact on specialist training, but also impacted the ability of trainees to undertake the final examinations in order to qualify as ENT specialists.

Recent findings
The response to the COVID-19 pandemic resulted in the postponement of the final examination of the Fellowship of the College of Otorhinolaryngologists of South Africa (FCORL (SA)). A virtual clinical examination was held via videoconferencing to assess clinical judgement, insight, reasoning and decision making.

Summary
The virtual clinical assessment allowed trainees to undertake the final examination despite the COVID-19 pandemic, ensuring that they could be added to the limited number of specialists in South Africa and the African continent.
How to improve outcome in nephron-sparing surgery: the impact of new techniques
Authors: Cignoli Daniele , Fallara Giuseppe , Larcher Alessandro , Rosiello Giuseppe , Montorsi Francesco , Capitanio Umberto 
Published: March 2021

Purpose of review
Nephron-sparing partial nephrectomy is the state of the art for localized small renal mass and it is gaining attention also for more advanced cases. In the present narrative review, we discuss the new developments that have occurred in the advancement of this approach over the past few years.

Recent findings
Off-clamp, selective/superselective clamp and early-unclamping techniques are safe and feasible approaches, with potentially superior functional outcomes, and noninferior complications rate and oncological outcomes, when compared with main artery clamping. Renorrhaphy must preserve the physiological vascularization of residual parenchyma. Running sutures, particularly using barbed wires, shorten the operating and ischemia times. A further advantage could derive from avoiding a double-layer suture. Transperitoneal robot-assisted partial nephrectomy (RAPN) and retroperitoneal RAPN can be considered equivalent in terms of perioperative morbidity, functional and oncologic outcomes, regardless of tumor's location, thus the choice of the approach should be driven by the surgeon's expertise. Future improvements should be introduced by the single-port robotic surgery, which seems to be safe and feasibly also in an off-clamp manner.

Summary
Significant advances have recently been achieved in nephron-sparing surgery technique. However, future studies with standardized reporting of these new techniques are needed to assess the real impact of them on early and long-term functional outcomes.
The current landscape of salvage therapies for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer
Authors: Packiam Vignesh T. , Richards Jordan , Schmautz Maximilian , Heidenreich Axel , Boorjian Stephen A. 
Published: March 2021

Purpose of review
Although radical cystectomy represents the gold standard treatment for patients with high-risk nonmuscle invasive bladder cancer (NMIBC) whose disease does not respond to bacillus Calmette-Guérin (BCG), many patients are unable or unwilling to undergo surgery. The need remains for effective bladder-preserving therapies. This review aims to describe existing treatments, contemporary research in this field and ongoing trials of salvage therapies for patients with BCG-unresponsive NMIBC.

Recent findings
Intravesical chemotherapy has been utilized frequently in this setting. Emerging data on combination regimens such as intravesical gemcitabine and docetaxel and intravesical cabazitaxel, gemcitabine and cisplatin are promising; nevertheless, larger, prospective trials are needed. Meanwhile, the intravenous checkpoint inhibitor pembrolizumab was recently FDA-approved for patients BCG-unresponsive NMIBC. Encouraging clinical trial results for intravesical nadofaragene firadenovec, oportuzumab monatox and ALT-803 + BCG have been released, while data from trials of other treatment strategies, including novel chemotherapy and drug delivery, augmented BCG immunotherapy, adenoviral and gene therapy, targeted therapy, and combination systemic immunotherapy with intravesical agents, are eagerly awaited.

Summary
Several novel salvage therapies offer promise for patients with BCG-unresponsive NMIBC. Patient selection, efficacy, safety, cost and ease of administration must be carefully considered to determine the optimal treatment approach.
Renal cell carcinoma pathology in 2021: ‘new need for renal cancer immune profiling’
Authors: Sobottka Bettina , Lorch Anja , Silina Karina , van den Broek Maries , Moch Holger 
Published: March 2021

Purpose of review
The aim of this review is to outline characteristics of the renal cell carcinoma (RCC) tumor immune microenvironment (TIME), the potential impact of tumor intrinsic alterations on the TIME and the value of metastatic tissue assessment in this context.

Recent findings
According to the latest European Association of Urology, European Society for Medical Oncology and National Comprehensive Cancer Network guidelines immune checkpoint inhibition represents a new core treatment strategy in advanced clear cell RCC (ccRCC). Despite its success, the prognosis of many RCC patients remains unsatisfactory most likely because of resistance mechanisms within the TIME. Moreover, most studies assess the primary tumor even though the advanced metastatic disease is targeted. Overall, metastatic RCC has hardly been investigated. First insights into the complexity of the genomic and immune landscape in RCC were recently provided. The functional impact of tumor intrinsic alterations on the TIME has just been described potentially contributing to therapy response in RCC.

Summary
The complexity of the RCC TIME and its potential interdependence with tumor intrinsic alterations has only just been recognized. A deeper understanding of the TIME may reveal predictive and prognostic biomarkers long-awaited in RCC, improve RCC patient stratification and could possibly be most instructive if assessed in metastatic tissue.