Minimally invasive strategies for the treatment of prostate cancer recurrence after radiation therapy: a systematic review

INTRODUCTION: The aim of this review was to conduct a comprehensive analysis of the role of minimally invasive salvage modalities in radio-recurrent prostate cancer and the associated clinical outcomes and toxicity profiles. EVIDENCE ACQUISITION: A systematic review of the current literature was conducted through the Medline and NCBI PubMed, Scopus databases in January 2020. All papers published after 2000, concerning studies conducted on humans for radio-recurrent prostate cancer were considered for the review. EVIDENCE SYNTHESIS: Overall, 545 studies were identified. After duplicate exclusion, initial screening, and eligibility evaluation, a total of 80 studies were included in the qualitative analysis, corresponding to a cohort of 6681 patients. The median age at initial diagnosis ranged from 59 to 75.5. Pre-treatment PSA ranged from 6.2 to 27.4 ng/mL. All patients underwent primary radiotherapy for localized prostate cancer. Cryotherapy, Brachytherapy, EBRT, HIFU were the minimally invasive options mostly used as salvage therapy. They showed to be promising approaches for recurrent prostate cancer (PCa) control, with acceptable toxicities. CONCLUSIONS: Minimally invasive therapeutic options offer promising results in terms of biochemical control in the local recurrence setting. Unfortunately, the absence of high quality and comparative studies makes it difficult to establish which method is the best in terms of oncological and safety outcomes

Prostate Indeterminate Lesions on Magnetic Resonance Imaging-Biopsy Versus Surveillance: A Literature Review

CONTEXT: The indeterminate multiparametric prostate magnetic resonance image (mpMRI) lesion is one which cannot be classified as "positive" or "negative" for suspected cancer. Currently, there is no consensus on how to manage patients with indeterminate mpMRIs where areas cannot be classified as positives or negatives (Prostate Imaging Reporting and Data System [PI-RADS] 3 or Likert 3). OBJECTIVE: To define the concept of indeterminate lesion and describe the management strategies that may be adopted for these patients. EVIDENCE ACQUISITION: A literature search of the PubMed database was performed including the search terms "prostate indeterminate lesions", "PI-RADS 3", "Likert 3", "magnetic resonance imaging", and "prostate cancer". EVIDENCE SYNTHESIS: There is no universally accepted definition of what constitutes an indeterminate lesion on mpMRI. This is partly due to the experience of the reporting radiologist and their willingness to call a lesion indeterminate, knowing that this may have consequences for biopsy decisions. This is also partly due to the significant variation in mpMRI acquisition parameters used between different sites. Strategies for managing the indeterminate lesion include: (1) biopsy, where there is a highly variable prevalence of prostate cancer (PCa), reflecting the differences in clinically significant PCa definitions, mpMRI protocols and interobserver variability in characterization of indeterminate lesions and (2) surveillance, where early results suggest that this strategy may be of value for some selected patients with prostate-specific antigen (PSA) monitoring and/or interval mpMRI. The use of prebiopsy MRI, in conjunction with traditional clinical parameters and secondary biomarkers-nomograms, may allow a more accurate selection of patients who can avoid biopsy. CONCLUSIONS: A strategy of close surveillance based on PSA monitoring and interval mpMRI is a feasible management option for motivated patients with indeterminate mpMRI. This surveillance strategy could result in fewer men needing to undergo biopsy, and although early results are promising, long-term results for such a strategy are awaited. PATIENT SUMMARY: In some patients who have an MRI scan of their prostate, the scan may identify an area which may or may not contain cancer. This area is typically called the "indeterminate" lesion. In this report, we attempted to define the concept of indeterminate lesion on multiparametric magnetic resonance (mpMRI) and described the strategies that may be performed for these patients. The use of mpMRI in conjunction with traditional clinical parameters may allow more accurate risk stratification and assessment of the need for prostate biopsy

RNA secondary structure prediction from multi-aligned sequences

It has been well accepted that the RNA secondary structures of most functional non-coding RNAs (ncRNAs) are closely related to their functions and are conserved during evolution. Hence, prediction of conserved secondary structures from evolutionarily related sequences is one important task in RNA bioinformatics; the methods are useful not only to further functional analyses of ncRNAs but also to improve the accuracy of secondary structure predictions and to find novel functional RNAs from the genome. In this review, I focus on common secondary structure prediction from a given aligned RNA sequence, in which one secondary structure whose length is equal to that of the input alignment is predicted. I systematically review and classify existing tools and algorithms for the problem, by utilizing the information employed in the tools and by adopting a unified viewpoint based on maximum expected gain (MEG) estimators. I believe that this classification will allow a deeper understanding of each tool and provide users with useful information for selecting tools for common secondary structure predictions.Comment: A preprint of an invited review manuscript that will be published in a chapter of the book `Methods in Molecular Biology'. Note that this version of the manuscript may differ from the published versio

Definitions and factors associated with subthreshold depressive conditions:a systematic review

BACKGROUND: Subthreshold depressive disorders (minor and subthrehold depression) have been defined in a wide range of forms, varying on the number of symptoms and duration required. Disability associated with these conditions has also been reported. Our aim was to review the different definitions and to determine factors associated with these conditions in order to clarify the nosological implications of these disorders. METHODS: A Medline search was conducted of the published literature between January 2001 and September 2011. Bibliographies of the retrieved papers were also analysed. RESULTS: There is a wide heterogeneity in the definition and diagnostic criteria of minor and subthreshold depression. Minor depression was defined according to DSM-IV criteria. Regarding subthreshold depression, also called subclinical depression or subsyndromal symptomatic depression, between 2 and 5 depressive symptoms were required for the diagnosis, and a minimum duration of 2 weeks. Significant impairment associated with subthreshold depressive conditions, as well as comorbidity with other mental disorders, has been described. CONCLUSIONS: Depression as a disorder is better explained as a spectrum rather than as a collection of discrete categories. Minor and subthreshold depression are common conditions and patients falling below the diagnostic threshold experience significant difficulties in functioning and a negative impact on their quality of life. Current diagnostic systems need to reexamine the thresholds for depressive disorders and distinguish them from ordinary feelings of sadness

The impact of a second MRI and re-biopsy in patients with initial negative mpMRI-targeted and systematic biopsy for PIRADS ≥ 3 lesions

Objective: To evaluate the proportions of detected prostate cancer (PCa) and clinically significant PCa (csPCa), as well as identify clinical predictors of PCa, in patients with PI-RADS > = 3 lesion at mpMRI and initial negative targeted and systematic biopsy (initial biopsy) who underwent a second MRI and a re-biopsy. Methods: A total of 290 patients from 10 tertiary referral centers were included. The primary outcome measures were the presence of PCa and csPCa at re-biopsy. Logistic regression analyses were performed to evaluate predictors of PCa and csPCa, adjusting for relevant covariates. Results: Forty-two percentage of patients exhibited the presence of a new lesion. Furthermore, at the second MRI, patients showed stable, upgrading, and downgrading PI-RADS lesions in 42%, 39%, and 19%, respectively. The interval from the initial to repeated mpMRI and from the initial to repeated biopsy was 16 mo (IQR 12–20) and 18 mo (IQR 12–21), respectively. One hundred and eight patients (37.2%) were diagnosed with PCa and 74 (25.5%) with csPCa at re-biopsy. The presence of ASAP on the initial biopsy strongly predicted the presence of PCa and csPCa at re-biopsy. Furthermore, PI-RADS scores at the first and second MRI and a higher number of systematic biopsy cores at first and second biopsy were independent predictors of the presence of PCa and csPCa. Selection bias cannot be ruled out. Conclusions: Persistent PI-RADS ≥ 3 at the second MRI is suggestive of the presence of a not negligible proportion of csPca. These findings contribute to the refinement of risk stratification for men with initial negative MRI-TBx

Psychological Health of Surgeons in a Time of COVID-19: A Global Survey

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the Depression Anxiety Stress Scale-21 (DASS-21) and Impact of Event Scale-Revised (IES-R) scores. RESULTS: 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9% and 24.0% screened positive for depression, anxiety, stress and Post-Traumatic Stress Disorder (PTSD) respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress and PTSD (OR 1.3, 1,6, 1.4, 1.7 respectively, all p < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress and PTSD (OR 1.2, 1.2 and 1.3 respectively, all p < 0.05). Surgical specialities that operated in the Head and Neck region had higher psychological distress among its surgeons. Deployment for COVID-19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19

Feeder layer- and animal product-free culture of neonatal foreskin keratinocytes: improved performance, usability, quality and safety

Since 1987, keratinocytes have been cultured at the Queen Astrid Military Hospital. These keratinocytes have been used routinely as auto and allografts on more than 1,000 patients, primarily to accelerate the healing of burns and chronic wounds. Initially the method of Rheinwald and Green was used to prepare cultured epithelial autografts, starting from skin samples from burn patients and using animal-derived feeder layers and media containing animal-derived products. More recently we systematically optimised our production system to accommodate scientific advances and legal changes. An important step was the removal of the mouse fibroblast feeder layer from the cell culture system. Thereafter we introduced neonatal foreskin keratinocytes (NFK) as source of cultured epithelial allografts, which significantly increased the consistency and the reliability of our cell production. NFK master and working cell banks were established, which were extensively screened and characterised. An ISO 9001 certified Quality Management System (QMS) governs all aspects of testing, validation and traceability. Finally, as far as possible, animal components were systematically removed from the cell culture environment. Today, quality controlled allograft production batches are routine and, due to efficient cryopreservation, stocks are created for off-the-shelf use. These optimisations have significantly increased the performance, usability, quality and safety of our allografts. This paper describes, in detail, our current cryopreserved allograft production process

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

The Role of Dicer Protein Partners in the Processing of MicroRNA Precursors

One of the cellular functions of the ribonuclease Dicer is to process microRNA precursors (pre-miRNAs) into mature microRNAs (miRNAs). Human Dicer performs this function in cooperation with its protein partners, AGO2, PACT and TRBP. The exact role of these accessory proteins in Dicer activity is still poorly understood. In this study, we used the northern blotting technique to investigate pre-miRNA cleavage efficiency and specificity after depletion of AGO2, PACT and TRBP by RNAi. The results showed that the inhibition of either Dicer protein partner substantially affected not only miRNA levels but also pre-miRNA levels, and it had a rather minor effect on the specificity of Dicer cleavage. The analysis of the Dicer cleavage products generated in vitro revealed the presence of a cleavage intermediate when pre-miRNA was processed by recombinant Dicer alone. This intermediate was not observed during pre-miRNA cleavage by endogenous Dicer. We demonstrate that AGO2, PACT and TRBP were required for the efficient functioning of Dicer in cells, and we suggest that one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of Dicer

STROCSS 2021: Strengthening the reporting of cohort, cross-sectional and case-control studies in surgery

Introduction: Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. / Methods: A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. / Results: 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. / Conclusion: We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery