Study protocol for the Intraoperative Complications Assessment and Reporting with Universal Standards (ICARUS) global cross-specialty surveys and consensus.

Annually, about 300 million surgeries lead to significant intraoperative adverse events (iAEs), impacting patients and surgeons. Their full extent is underestimated due to flawed assessment and reporting methods. Inconsistent adoption of new grading systems and a lack of standardization, along with litigation concerns, contribute to underreporting. Only half of relevant journals provide guidelines on reporting these events, with a lack of standards in surgical literature. To address these issues, the Intraoperative Complications Assessment and Reporting with Universal Standard (ICARUS) Global Surgical Collaboration was established in 2022. The initiative involves conducting global surveys and a Delphi consensus to understand the barriers for poor reporting of iAEs, validate shared criteria for reporting, define iAEs according to surgical procedures, evaluate the existing grading systems' reliability, and identify strategies for enhancing the collection, reporting, and management of iAEs. Invitation to participate are extended to all the surgical specialties, interventional cardiology, interventional radiology, OR Staffs and anesthesiology. This effort represents an essential step towards improved patient safety and the well-being of healthcare professionals in the surgical field.

Bibliometric analysis of academic journal recommendations and requirements for surgical and anesthesiologic adverse events reporting.

BACKGROUND: Standards for reporting surgical adverse events (AEs) vary widely within the scientific literature. Failure to adequately capture AEs hinders efforts to measure the safety of healthcare delivery and improve the quality of care. The aim of the present study is to assess the prevalence and typology of perioperative AE reporting guidelines among surgery and anesthesiology journals. MATERIALS AND METHODS: In November 2021, three independent reviewers queried journal lists from the SCImago Journal & Country Rank (SJR) portal (www.scimagojr.com), a bibliometric indicator database for surgery and anesthesiology academic journals. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted from Scopus journal data. Quartile 1 (Q1) was considered the top quartile and Q4 bottom quartile based on the journal impact factor. Journal author guidelines were collected to determine whether AE reporting recommendations were included and, if so, the preferred reporting procedures. RESULTS: Of 1409 journals queried, 655 (46.5%) recommended surgical AE reporting. Journals most likely to recommend AE reporting were: by category surgery (59.1%), urology (53.3%), and anesthesia (52.3%); in top SJR quartiles (i.e. more influential); by region, based in Western Europe (49.8%), North America (49.3%), and the Middle East (48.3%). CONCLUSIONS: Surgery and anesthesiology journals do not consistently require or provide recommendations on perioperative AE reporting. Journal guidelines regarding AE reporting should be standardized and are needed to improve the quality of surgical AE reporting with the ultimate goal of improving patient morbidity and mortality.

Is Artificial Intelligence Replacing Our Radiology Stars? Not Yet!

Artificial intelligence (AI) is here to stay and will change health care as we know it. The availability of big data and the increasing numbers of AI algorithms approved by the US Food and Drug Administration together will help in improving the quality of care for patients and in overcoming human fatigue barriers. In oncology practice, patients and providers rely on the interpretation of radiologists when making clinical decisions; however, there is considerable variability among readers, and in particular for prostate imaging. AI represents an emerging solution to this problem, for which it can provide a much-needed form of standardization. The diagnostic performance of AI alone in comparison to a combination of an AI framework and radiologist assessment for evaluation of prostate imaging has yet to be explored. Here, we compare the performance of radiologists alone versus a combination of radiologists aided by a modern computer-aided diagnosis (CAD) AI system. We show that the radiologist-CAD combination demonstrates superior sensitivity and specificity in comparison to both radiologists alone and AI alone. Our findings demonstrate that a radiologist + AI combination could perform best for detection of prostate cancer lesions. A hybrid technology-human system could leverage the benefits of AI in improving radiologist performance while also reducing physician workload, minimizing burnout, and enhancing the quality of patient care. Patient summary: Our report demonstrates the potential of artificial intelligence (AI) for improving the interpretation of prostate scans. A combination of AI and evaluation by a radiologist has the best performance in determining the severity of prostate cancer. A hybrid system that uses both AI and radiologists could maximize the quality of care for patients while reducing physician workload and burnout.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review

ABSTRACT Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

An Assessment Tool to Provide Targeted Feedback to Robotic Surgical Trainees: Development and Validation of the End-To-End Assessment of Suturing Expertise (EASE).

Purpose: To create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity. Materials and Methods: 5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (<100 cases) EASE scores from the non-training cases were compared using a generalized linear mixed model. Results: After two rounds of Delphi process, panelists agreed on 7 domains, 18 sub-skills, and 57 detailed sub-skill descriptions with CVI ≥ 0.80. Inter-rater reliability was moderately high (ICC median: 0.69, range: 0.51-0.97; PABAK: 0.77, 0.62-0.97). Multiple EASE sub-skill scores were able to distinguish surgeon experience. The Spearman's rho correlation between overall EASE and RACE scores was 0.635 (p=0.003). Conclusions: Through a rigorous CTA and Delphi process, we have developed EASE, whose suturing sub-skills can distinguish surgeon experience while maintaining rater reliability.

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

BACKGROUND: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa. METHODS: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold. RESULTS: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority. CONCLUSIONS: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

PURPOSE: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. MATERIAL AND METHODS: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. RESULTS: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. CONCLUSIONS: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

AMPK-deficiency forces metformin-challenged cancer cells to switch from carbohydrate metabolism to ketogenesis to support energy metabolism.

Epidemiologic studies in diabetic patients as well as research in model organisms have indicated the potential of metformin as a drug candidate for the treatment of various types of cancer, including breast cancer. To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK). However, it is becoming increasingly clear that AMPK activation may be critical to alleviate metabolic and energetic stresses associated with tumor progression suggesting that it may, in fact, attenuate the toxicity of metformin instead of promoting it. Here, we demonstrate that AMPK opposes the detrimental effects of mitochondrial complex I inhibition by enhancing glycolysis at the expense of, and in a manner dependent on, pyruvate availability. We also found that metformin forces cells to rewire their metabolic grid in a manner that depends on AMPK, with AMPK-competent cells upregulating glycolysis and AMPK-deficient cell resorting to ketogenesis. In fact, while the killing effects of metformin were largely rescued by pyruvate in AMPKcompetent cells, AMPK-deficient cells required instead acetoacetate, a product of fatty acid catabolism indicating a switch from sugar to fatty acid metabolism as a central resource for ATP production in these cells. In summary, our results indicate that AMPK activation is not responsible for metformin anticancer activity and may instead alleviate energetic stress by activating glycolysis.

Impact of Pelvic Lymph Node Dissection and Its Extent on Perioperative Morbidity in Patients Undergoing Radical Prostatectomy for Prostate Cancer: A Comprehensive Systematic Review and Meta-analysis.

CONTEXT: Pelvic lymph node dissection (PLND) yields the most accurate staging in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), although it can be associated with morbidity. OBJECTIVE: To systematically evaluate the impact of PLND extent on perioperative morbidity in patients undergoing RP. A new PLND-related complication assessment tool is proposed. EVIDENCE ACQUISITION: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was conducted. MEDLINE/PubMed, Scopus, Embase and Web of Science databases were searched to yield studies discussing perioperative complications following RP and PLND. The extent of PLND was classified according to the European Association of Urology PCa guidelines. Studies were categorized according to the extent of PLND. Intra- and postoperative complications were classified as "strongly," "likely," or "unlikely" related to PLND. Anatomical site of perioperative complications was recorded. A cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). EVIDENCE SYNTHESIS: Our search generated 3645 papers, with 176 studies meeting the inclusion criteria. Details of 77 303 patients were analyzed. Of these studies, 84 (47.7%), combining data on 28 428 patients, described intraoperative complications as an outcome of interest. Overall, 534 (1.8%) patients reported one or more intraoperative complications. Postoperative complications were reported in 151 (85.7%) studies, combining data on 73 629 patients. Overall, 10 401 (14.1%) patients reported one or more postoperative complication. The most reported postoperative complication strongly related to PLND was lymphocele (90.6%). The pooled meta-analysis revealed that RP + limited PLND/standard PLND had a significantly decreased risk of experiencing any intraoperative complication (risk ratio [RR]: 0.55; p = 0.01) and postoperative complication strongly related to PLND (RR: 0.46; p = <0.00001), particularly for lymphocele formation (RR: 0.52; p = 0.0003) and thromboembolic events (RR: 0.59; p = 0.008), when compared with extended/superextended PLND. The extent of PLND was confirmed to be an independent predictor of lymphocele formation (RR: 1.77; p < 0.00001). CONCLUSIONS: The perioperative morbidity of PLND in patients undergoing RP and PLND for PCa significantly correlates with the extent of PLND. More standardized reporting of intra- and postoperative complications is needed to better estimate the direct impact of PLND extent on perioperative morbidity. PATIENT SUMMARY: Pelvic lymph node dissection (PLND) is the most accurate method for staging in patients undergoing radical prostatectomy for prostate cancer, although it can be associated with complications. This study aims to systematically evaluate the impact of PLND extent on perioperative complications in these patients. We found that intra- and postoperative complications correlate significantly with the extent of PLND. A more rigorous assessment and thorough reporting of perioperative complications are recommended.

Epidemiology and evolution of Zika virus in Minas Gerais, Southeast Brazil.

Autochthonous Zika virus (ZIKV) transmission in Brazil was first identified in April 2015 in Brazil, with the first ZIKV-associated microcephaly cases detected in October 2015. Despite efforts on understanding ZIKV transmission in Brazil, little is known about the virus epidemiology and genetic diversity in Minas Gerais (MG), the second most populous state in the country. We report molecular and genomic findings from the main public health laboratory in MG. Until January 2020, 26,817 ZIKV suspected infections and 86 congenital syndrome cases were reported in MG state. We tested 8552 ZIKV and microcephaly suspected cases. Ten genomes were generated on-site directly from clinical samples. A total of 1723 confirmed cases were detected in Minas Gerais, with two main epidemic waves; the first and larger epidemic wave peaked in March 2016, with the second smaller wave that peaked in March 2017. Dated molecular clock analysis revealed that multiple introductions occurred in Minas Gerais between 2014 and 2015, suggesting that the virus was circulating unnoticed for at least 16 months before the first confirmed laboratory case that we retrospectively identified in December 2015. Our findings highlight the importance of continued genomic surveillance strategies combined with traditional epidemiology to assist public health laboratories in monitoring and understanding the diversity of circulating arboviruses, which might help attenuate the public health impact of infectious diseases.

Inorganic arsenic promotes luminal to basal transition and metastasis of breast cancer.

Inorganic arsenic (iAs/As2 O32- ) is an environmental toxicant found in watersheds around the world including in densely populated areas. iAs is a class I carcinogen known to target the skin, lungs, bladder, and digestive organs, but its role as a primary breast carcinogen remains controversial. Here, we examined a different possibility: that exposure to iAs promotes the transition of well-differentiated epithelial breast cancer cells characterized by estrogen and progesterone receptor expression (ER+/PR+), to more basal phenotypes characterized by active proliferation, and propensity to metastasis in vivo. Our results indicate two clear phenotypic responses to low-level iAs that depend on the duration of the exposure. Short-term pulses of iAs activate ER signaling, consistent with its reported pseudo-estrogen activity, but longer-term, chronic treatments for over 6 months suppresses both ER and PR expression and signaling. In fact, washout of these chronically exposed cells for up to 1 month failed to fully reverse the transcriptional and phenotypic effects of prolonged treatments, indicating durable changes in cellular physiologic identity. RNA-seq studies found that chronic iAs drives the transition toward more basal phenotypes characterized by impaired hormone receptor signaling despite the conservation of estrogen receptor expression. Because treatments for breast cancer patients are largely designed based on the detection of hormone receptor expression, our results suggest greater scrutiny of ER+ cancers in patients exposed to iAs, because these tumors may spawn more aggressive phenotypes than unexposed ER+ tumors, in particular, basal subtypes that tend to develop therapy resistance and metastasis.

Genomic Surveillance of Yellow Fever Virus Epizootic in São Paulo, Brazil, 2016 - 2018.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019.

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Impact of Implementation of Standardized Criteria in the Assessment of Complication Reporting After Robotic Partial Nephrectomy: A Systematic Review.

The definition of a surgical complication still lacks standardization, hampering evaluation of surgical performance in this regard. Over the years, efforts to address this issue have been carried out to improve reporting of outcomes. In 2012, the European Association of Urology (EAU) proposed a standardized reporting tool for urological complications. The aim of this study was to evaluate the impact of those recommendations on complication reporting for patients undergoing robotic partial nephrectomy (RPN). A comprehensive systematic review of all English language publications on RPN was carried out. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and Agency for Healthcare Research and Quality guidelines in evaluating articles retrieved from the PubMed, Scopus, and Web of Science databases (January 1, 2000 to October 31, 2016; updated June 2017). The quality of reporting and grading complications was assessed according to the EAU recommendations. Temporal comparison revealed an improvement in outcome reporting in terms of mortality rates and causes of death (p=0.05), definition of complications (p<0.001), procedure-specific complications (p=0.02), severity grade (p<0.001), postoperative complications presented by grade/complication type (p<0.001), and risk factors (p<0.001). Our analysis demonstrates an improvement in complication reporting and grading after the EAU recommendation on RPN. PATIENT SUMMARY: Complications are unexpected events that could negatively impact a patient's outcomes after surgery, but there is no agreement on the definition and reporting of complications. In 2012, the European Association of Urology proposed a standardized reporting tool for urological complications. This study shows an improvement in the way physicians report complications after robotic partial nephrectomy. The results underline the importance of standardization in medicine to improve clinical research.

Return of the founder Chikungunya virus to its place of introduction into Brazil is revealed by genomic characterization of exanthematic disease cases.

Between June 2017 and August 2018, several municipalities located in Bahia state (Brazil) reported a large increase in the number of patients presenting with febrile illness similar to that of arboviral infections. Using a combination of portable whole genome sequencing, molecular clock and epidemiological analyses, we revealed the return of the CHIKV-ECSA genotype into Bahia. Our results show local persistence of lineages in some municipalities and the re-introduction of new epidemiological strains from different Brazilian regions, highlighting a complex dynamic of transmission between epidemic seasons and sampled locations. Estimated climate-driven transmission potential of CHIKV remained at similar levels throughout the years, such that large reductions in the total number of confirmed cases suggests a slow, but gradual accumulation of herd-immunity over the 4 years of the epidemic in Bahia after its introduction in 2014. Bahia remains a reservoir of the genetic diversity of CHIKV in the Americas, and genomic surveillance strategies are essential to assist in monitoring and understanding arboviral transmission and persistence both locally and over large distances.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Contrast-Enhanced Transrectal Ultrasound for Follow-up After Focal HIFU Ablation for Prostate Cancer.

The optimal strategy for imaging after focal therapy for prostate cancer is evolving. This series is an initial report on the use of contrast-enhanced transrectal ultrasound (TRUS) in follow-up of patients after high-intensity focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who underwent HIFU hemiablation, contrast-enhanced TRUS findings were as follows: (1) contrast-enhanced TRUS clearly showed the HIFU ablation defect as a sharply marginated nonenhancing zone in all patients; (2) contrast-enhanced TRUS identified suspicious foci of recurrent enhancement within the ablation zone in 2 patients, facilitating image-guided prostate biopsy, which showed prostate cancer; and (3) contrast-enhanced TRUS findings correlated with multiparametric magnetic resonance imaging and biopsy histologic findings.

Contrast-Enhanced Transrectal Ultrasound in Focal Therapy for Prostate Cancer.

PURPOSE OF REVIEW: Contrast-enhanced transrectal ultrasound (CeTRUS) is an emerging imaging technique in prostate cancer (PCa) diagnosis and treatment. We review the utility and implications of CeTRUS in PCa focal therapy (FT). RECENT FINDINGS: CeTRUS utilizes intravenous injection of ultrasound-enhancing agents followed by high-resolution ultrasound to evaluate tissue microvasculature and differentiate between benign tissue and PCa, with the latter demonstrating increased enhancement. The potential utility of CeTRUS in FT for PCa extends to pre-, intra- and post-operative settings. CeTRUS may detect PCa, facilitate targeted biopsy and aid surgical planning prior to FT. During FT, the treated area can be visualized as a well-demarcated non-enhancing zone and continuous real-time assessment allows immediate re-treatment if necessary. Following FT, the changes on CeTRUS are immediate and consistent, thus facilitating repeat imaging for comparison during follow-up. Areas suspicious for recurrence may be detected and target-biopsied. Enhancement can be quantified using time-intensity curves allowing objective assessment and comparison. Based on encouraging early outcomes, CeTRUS may become an alternative imaging modality in prostate cancer FT. Further study with larger cohorts and longer follow-up are needed.