Objectives
Although the reliability of frozen sections for the intraoperative assessment of complete tumour excision has been established, the best location for collection and the impact of the type ...of sampling are still debated. We retrospectively investigated the reliability of frozen sections when collected from the surgical bed as tissue strips representative of the whole superficial margin and as a bowl of tissue underlying the resection site for deep margin, and the possibility of relying on frozen section negativity to consider resections complete.
Materials and Methods
Frozen section reliability was calculated by comparing histology before and after formalin embedding and then categorised by sampling type, in 182 patients undergoing transoral resection of oral cancer.
Results
Comparing frozen and permanent histology, sensitivity, specificity and accuracy were 69%, 98% and 96%, respectively; categorisation by sampling type failed to produce statistically significant differences. Based on frozen section negativity after formalin embedding, complete resections were obtained in 91.7% of patients with multiple‐strip and bowl frozen sections.
Conclusion
Frozen sections collected as tissue strips and bowl are as reliable as point sampling in the intraoperative guidance of surgical resections. They effectively provide for margin enlargement, thereby increasing the surgeon's confidence that negative margins are clear.
The COVID‐19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID‐19 has impacted transplantation worldwide. The impact has not been just ...restricted to issues pertaining to donors or recipients, but also health‐care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID‐19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant‐related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.
The authors discuss the impact of COVID‐19 on donation and transplantation and provide a global framework for donor screening and management of transplant activity during the pandemic.
The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after solid organ transplant (SOT) ...remain unknown. We report our preliminary experience with 18 SOT (kidney 44.4%, liver 33.3%, and heart 22.2%) recipients diagnosed with COVID‐19 by March 23, 2020 at a tertiary‐care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon‐β (16.7%). As of April 4, the case‐fatality rate was 27.8% (5/18). After a median follow‐up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C‐reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS‐CoV‐2 infection has a severe course in SOT recipients.
In the present experience with 18 transplant recipients diagnosed with COVID‐19 by March 23, 2020 at their institution in Madrid, the authors found a case fatality rate of 27.8%, with 30.8% of survivors developing progressive respiratory failure or acute respiratory distress syndrome.
Aging and cancer are clearly associated processes, at both the epidemiological and molecular level. Epigenetic mechanisms are good candidates to explain the molecular links between the two phenomena, ...but recent reports have also revealed considerable differences, particularly regarding the loss of DNA methylation in the two processes. The large‐scale generation and availability of genome‐wide epigenetic data now permits systematic studies to be undertaken which may help clarify the similarities and differences between aging and cancer epigenetic alterations. In addition, the development of epigenetic clocks provides a new dimension in which to investigate diseases at the molecular level. Here, we examine current and future questions about the roles of DNA methylation mechanisms as causal factors in the processes of aging and cancer so that we may better understand if and how aging‐associated epigenetic alterations lead to tumorigenesis. It seems certain that comprehending the molecular mechanisms underlying epigenetic clocks, especially with regard to somatic stem cell aging, combined with applying single‐cell epigenetic‐age profiling technologies to aging and cancer cohorts, and the integration of existing and upcoming epigenetic evidence within the genetic damage models of aging will prove to be crucial to improving understanding of these two interrelated phenomena.
Aging and cancer are interrelated processes which share common epigenetic alterations. Nonetheless, there are differences in some of the DNA methylation changes which occur in both phenomena. The recent development of epigenetic clocks will help dissect the common and specific epigenetic characteristics of aging and cancer, although the mechanisms underlying epigenetic clocks are yet to be clarified, particularly in relation to somatic stem cell epigenetic aging.
The potential use of torque teno virus load as a surrogate marker for the net state of immunosuppression after kidney transplantation is discussed in view of the findings reported by Doberer et al in ...their single‐center study (page 2081).
Purpose
Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature ...to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment.
Methods
Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance.
Results
UTUC accounts for 5–10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed.
Conclusions
Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.
The accurate detection of nucleic acids from certain biological pathogens is critical for the diagnosis of human diseases. However, amplified detection of RNA molecules from a complex sample by ...direct detection of RNA/DNA hybrids remains a challenge. Here, we show that type IIS endonuclease FokI is able to digest DNA duplexes and DNA/RNA hybrids when assisted by a dumbbell-like fluorescent sensing oligonucleotide. As proof of concept, we designed a battery of sensing oligonucleotides against specific regions of the SARS-CoV-2 genome and interrogated the role of FokI relaxation as a potential nicking enzyme for fluorescence signal amplification. FokI-assisted digestion of SARS-CoV-2 probes increases the detection signal of ssDNA and RNA molecules and decreases the limit of detection more than 3.5-fold as compared to conventional molecular beacon approaches. This cleavage reaction is highly specific to its target molecules, and no detection of other highly related B-coronaviruses was observed in the presence of complex RNA mixtures. In addition, the FokI-assisted reaction has a high multiplexing potential, as the combined detection of different viral RNAs, including different SARS-CoV-2 variants, was achieved in the presence of multiple combinations of fluorophores and sensing oligonucleotides. When combined with isothermal rolling circle amplification technologies, FokI-assisted digestion reduced the detection time of SARS-CoV-2 in COVID-19-positive human samples with adequate sensitivity and specificity compared to conventional reverse transcription polymerase chain reaction approaches, highlighting the potential of FokI-assisted signal amplification as a valuable sensing mechanism for the detection of human pathogens.
Optogenetics has been widely expanded to enhance or suppress neuronal activity and it has been recently applied to glial cells. Here, we have used a new approach based on selective expression of ...melanopsin, a G‐protein‐coupled photopigment, in astrocytes to trigger Ca2+ signaling. Using the genetically encoded Ca2+ indicator GCaMP6f and two‐photon imaging, we show that melanopsin is both competent to stimulate robust IP3‐dependent Ca2+ signals in astrocyte fine processes, and to evoke an ATP/Adenosine‐dependent transient boost of hippocampal excitatory synaptic transmission. Additionally, under low‐frequency light stimulation conditions, melanopsin‐transfected astrocytes can trigger long‐term synaptic changes. In vivo, melanopsin‐astrocyte activation enhances episodic‐like memory, suggesting melanopsin as an optical tool that could recapitulate the wide range of regulatory actions of astrocytes on neuronal networks in behaving animals. These results describe a novel approach using melanopsin as a precise trigger for astrocytes that mimics their endogenous G‐protein signaling pathways, and present melanopsin as a valuable optical tool for neuron–glia studies.
Main points
Melanopsin, a mammalian G‐protein‐coupled photopigment, engages endogenous the IP3 pathway and intracellular Ca2+ signaling in astrocytes.
By releasing ATP/Ado, melanopsin‐astrocytes differently impact synaptic plasticity enhance cognitive functions.
Spain has been one of the most affected countries by the COVID‐19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 ...admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS‐CoV‐2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.
The authors present the impact of the COVID‐19 pandemic upon organ donation and transplantation in Spain and provide guidance on donor and recipient evaluation and testing for SARS‐CoV‐2.
The high diversification rates of plant lineages in the Mediterranean Basin hotspot have been linked to a complex interaction of climatic stressors, geographic isolation and soil type, but the ...question remains as to which of these factors has been the most significant environmental driver of recent speciation.
Here, we draw on distributional data for the entire endemic flora of the Iberian Peninsula, together with DNA‐based phylogenies and spatial phylogenetic methods, to explore the patterns of relative phylogenetic endemism at different spatial resolutions and phylogenetic scales (superclades) and assess how environmental factors contribute to explain these patterns.
We found that recent diversification of angiosperms as a whole, and particularly of eudicots, has been boosted by environmental stressors including high values of soil pH and dry‐seasonal climatic conditions, while diversification of monocots has not been associated with soil conditions but with high elevation and less seasonal climate.
Synthesis. These results provide robust insights into the environmental factors driving recent plant diversification in the Mediterranean Basin, including a role of soil properties that had not been quantified before. The contrasting environmental drivers of diversification in eudicots and monocots highlight the importance of analysing spatial phylogenetic patterns at multiple phylogenetic scales to get a better understanding of the processes that shape biodiversity.
Recent diversification of angiosperms in the Mediterranean Basin has been boosted by environmental stressors including high values of soil pH and dry‐seasonal climatic conditions. The contrasting environmental drivers of diversification in eudicots and monocots highlight the importance of analysing spatial phylogenetic patterns at multiple phylogenetic scales to get a better understanding of the processes that shape biodiversity.
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