Glioblastomas are mostly resected under general anesthesia under the supervision of a general anesthesiologist. Currently, it is largely unkown if clinical outcomes of GBM patients can be improved by appointing a neuro-anesthesiologist for their cases. We aimed to evaluate whether the assignment of dedicated neuro-anesthesiologists improves the outcomes of these patients. We also investigated the value of dedicated neuro-oncological surgical teams as an independent variable in both groups.A cohort consisting of 401 GBM patients who had undergone resection was retrospectively investigated. Primary outcomes were postoperative neurological complications, fluid balance, length-of-stay and overall survival. Secondary outcomes were blood loss, anesthesia modality, extent of resection, total admission costs, and duration of surgery.320 versus 81 patients were operated under the anesthesiological supervision of a general anesthesiologist and a dedicated neuro-anesthesiologist, respectively. Dedicated neuro-anesthesiologists yielded significant superior outcomes in 1) postoperative neurological complications ; 2) fluid balance (p<0.0001); 3) length-of-stay (p = 0.0006) and 4) total admission costs (p = 0.0006). In a subanalysis of the GBM resections performed by an oncological neurosurgeon (n = 231), the assignment of a dedicated neuro-anesthesiologist independently improved postoperative neurological complications . The assignment of a dedicated neuro-oncological team improved extent of resection additionally (p = 0.0416).GBM resections with anesthesiological supervision of a dedicated neuro-anesthesiologists are associated with improved patient outcomes. Prospective evidence is needed to further investigate the usefulness of the dedicated neuro-anesthesiologist in different settings. Glioblastomas (GBM) are malignant brain tumors with an annual incidence of six per 100,000. The standard treatment consists of surgery with adjuvant chemoradiotherapy. Due to GBMs infiltrative nature, they generally have a relatively poor sensitivity to adjuvant therapy and are invariably lethal. The median overall survival of GBM is approximately 15 months . Due to Recently, the contribution of the anesthesiologist to patient outcomes was a topic of discussion since a broad variability has been found . In mostAs to date, there is no research available regarding the clinical outcomes of glioma patients operated under the supervision of general anesthesiologists versus dedicated neuro-anesthesiologists. Hence, we strive to lay the framework for further research by evaluating the outcomes of these two groups of GBM patients in a large retrospective cohort of patients from our institution. We aim to determine whether the assignment of a dedicated neuro-anesthesiologist to GBM resections results in improved outcomes of these patients.The cohort consisted of 438 supratentorial GBM patients who had undergone tumor resection at our instition between January 2008 and July 2017. 401 patients were operated under general anesthesia , 37 patients were operated with intraoperative stimulation mapping using awake craniotomy . We decided to exclude AC patients from this study, since 1) AC is used in GBM surgery, for a major part, to minimize postoperative neurological complications, which would introduce a confounder and 2) all the AC patients were operated under the supervision of a neuro-anesthesiologist, which would introduce a bias. In all cases, neuronavigation was used. Cases performed with surgical adjuncts such as 5-ALA  and intraoperative ultrasound were included. No cases with intraoperative MRI were included since this modality is not available at our institution.Eligibility criteria were: 1) isolated GBM without evidence of multicentric or multifocal enhancement; 2) pathological diagnosis of glioblastoma multiforme (WHO Grade IV); 3) supratentorial lesion; 4) preoperative KPS ≥60 and 5) planned/scheduled surgery.All patients included in this study were operated under GA. The anesthesiologist chose one of three options for anesthesia maintenance: 1) a volatile anesthetic such as isoflurane or sevoflurane balanced with intravenous opioids; 2) TIVA  with propofol and intravenous opioids; 3) a combination of a volatile anesthetic and propofol with intravenous opioids. The procedure remained constant throughout the cohort. Patients were intubated after single-bolus muscle relaxation with rocuronium or cis-atracurium and mechanically ventilated throughout the procedure. Arterial blood pressure was measured invasively via the radial artery, and all patients received a urinary catheter. Mannitol 15% was given preoperatively and/or peroperatively on discretion by the anesthesiologist or as requested by the neurosurgeon in case of relevant edema. Local anesthesia of the surgical field was performed with 10 ml lidocaine 1% and adrenaline 1:200.000. After surgical incision, craniotomy and opening of the dura, the tumor was removed using BrainLab© neuronavigation. No mapping techniques for speech or motor function using cortical or subcortical electrostimulation were used to resect the tumor. After the operation, all patients were brought to the post-anesthesia-high-care-unit (PACU), where they spent the first 24 hours postoperatively. On this high-dependency, the nurses work under supervision of a dedicated staff anesthesiologist  and follow standard protocols for all patients who have undergone brain tumor resections.Procedures were allocated to dedicated neuro-anesthesiologists either in a random manner  or specifically pre-planned (the procedure was deemed by the neurosurgeon as rather difficult due to the nature of the procudure or serious comorbidities and the planning was made depending on the availability of the dedicated anesthesiologist (estimated at 15–20% of cases)). Patients were included in the general anesthesiologist group or the dedicated neuro-anesthesiologist group based on the anesthesiologist responsible for the procedure. Dedicated neuro-anesthesiologists in this study were defined as anesthesiologists who perform >75% of their clinical activities in the perioperative care for neurosurgical patients and who have followed an accredited (inter)national dedicated training or -fellowship in which they have been exposed to an expansive neurosurgical caseload both quantitatively as qualitatively as well as having developed a research niche in the subspecialty. During the study period, there were two dedicated neuro-anesthesiologists (I.E. and M.K.), with more than 10 years of training as a staff member after their dedicated training. In general, on all days of the week one of them is available, whilst the neurosurgeons mostly have fixed days of the week on which they operate. This might contribute to fixed combinations between neurosurgeons and dedicated neuro-anesthesiologists. General anesthesiologists, on the other hand, were defined as anesthesiologists who are ‘allround’ in their daily clinical activities and do not perform the majority of those (activities) in the care for neurosurgical patients, nor have they followed dedicated training or -fellowships or performed research in this area. They rotate every day between different subspecialities. On average, the neurosurgical caseload for a dedicated neuro-anesthesiologist in our department is around 200 cases per year, of which 120–140 brain tumor operations. For general anesthesiologists, the average neurosurgical caseload is 40–50 cases per year  of which <20 brain tumor operations. We also looked at dedicated oncological neurosurgeons as a variable in this study. This group is defined as neurosurgeons whose operative load consists of oncological surgery for >80%. At our institution, there are four dedicated oncological neurosurgeons who have all more than 15 years of training as a staff member after their oncological neurosurgery fellowship.Patient characteristics were retrospectively collected the hospital records and screened for presenting symptoms, preoperative patient functioning and fitness , neuroimaging findings, neurological functioning, intraoperative variables and adjuvant treatment. Ethical approval had been obtained and the requirement for written informed consent was waived by the IRB . The study has been conducted in compliance with the principles of the Declaration of Helsinki (2013) and the General Data Protection Regulation (GDPR) (2018). Preoperative KPS is determined routinely by the clinician at the time of evaluation. Total admission costs were calculated as: (days in PACU*PACU cost/day) + (days in neurosurgery ward*ward cost/day). The recorded MRI characteristics included the lesion’s size, specific lobe involvement, multifocality, and extent of resection The lesion’s size was calculated preoperatively and postoperatively manually calculated based on T1 with contrast MR images using the frequently used method described by (among others) Shah and colleagues , which wPrimary outcomes were 1) postoperative neurological complication rate, 2) fluid balance , 3) length-of-stay (LOS) and 4) overall survival (months). Secondary outcomes were blood loss (ml), anesthesia modality, extent of resection (%), total admission costs (EUR) and OR duration (min).t test for independent samples. For categorical variables, the chi-square (χ2) test was used. Analysis of the data set for outcomes based on continuous variables was done using the Kruskal-Wallis test, whereas for categorical variables the Fisher-exact test was used. Analysis of overall survival was done with the log-rank test. Significant outcomes in the univariate analysis were further analysed using a multivariate analysis using standard logistic regression. The multivariate analysis consisted of well known predictive factors in glioblastoma patients: 1) age; 2) gender; 3) preoperative KPS; 4) tumor location and 5) preoperative tumor volume. For the comparison of multiple subgroups regarding the composition of the performing team, the one-way analysis of variance (ANOVA) test was used for continuous variables and the chi-square (χ2) test for categorical variables. The significance level for all tests was set to 5%.Statistical analyses were executed in collaboration with a senior statistician from the Department of Biostatistics of our own institution. Differences between the patients receiving anesthesia from a general anesthesiologist or a dedicated neuro-anesthesiologist for the primary and secondary outcomes were tested with univariate analyses. For statistically significant outcomes a multivariate analysis was performed in addition to the univariate analysis to minimize the risk for confounders and selection bias. Subgroup analyses were done for the assignment of a neuro-anesthesiologist and a oncological neurosurgeon to GBM cases. Analyses of differences between two groups in baseline characteristics for continuous variables were done using the two-tailed After excluding all awake cases (n = 37), a total of 401 patients were included in the cohort. All of the included patients had undergone GBM resection under general anesthesia. 320 patients were operated on with anesthesiological supervision by a general anesthesiologist (GA-group), whereas in 81 patients a dedicated neuro-anesthesiologist provided anesthesia care (NA-group). Baseline patient characteristics for both groups are shown in First, patients in the NA-group experienced fewer postoperative neurological complications Tables  and 3. ENeurological complications were specified by severity, timing and type of anesthesiologist . NotablySecond, fluid management was significantly controlled more strictly  in operations when a dedicated neuro-anesthesiologist was responsible: the mean fluid balance was -232.1 ml in those operations, whereas this was +538.3 ml when a general anesthesiologist was responsible  .Third, after operations for which a dedicated neuro-anesthesiologist was appointed, patients were discharged from the hospital sooner: they stayed on average 6.3 days in the hospital versus on average 7.8 days after an operation led by a general anesthesiologist (LOS)  .Fourth, postoperative overall survival did not differ between groups: both groups had a median OS of 13 months .General anesthesiologists use different anesthesia maintenance techniques than neuro-anesthesiologists: they used TIVA or a volatile anesthetic, whereas neuro-anesthesiologists used a combination of a volatile anesthetic with TIVA significantly more frequently (p<0.0001). The total admission costs per patient were significantly lower in the neuro-anesthesiology group: 4709.0 EUR (SD = 1927.7 EUR) compared to 5471.3 EUR (SD = 2432.6 EUR)  . No statTo evaluate the effect of the assignment of a neuro-anesthesiologist or a oncological neurosurgeon to GBM resections, we performed a subgroup analysis. We investigated the added value of a dedicated neuro-anesthesiologist for GBM resections in a cohort of more than 400 patients, which makes it the most extensive and comprehensive study about this subject to date. We found that patients undergoing resection for a single supratentorial glioblastoma under the anesthesiological supervision of a dedicated neuro-anesthesiologist 1) experienced, on average, fewer postoperative neurological complications 2) had their fluid balance controlled more strictly and 3) had a shorter postoperative length of stay which directly resulted in lower total admission costs of the operation.From 2008 to 2017, an increasing number of GBM resections was led by a neuro-anesthesiologist. Simultaneously, the incidence of early minor, early major and late minor complications remained virtually stable during these years. However, the incidence of late major complications decreased dramatically, from more than 33% in 2005 to 10–15% in the last few years. This might suggest that the implementation of dedicated neuro-anesthesia in GBM resections may be one of the factors that is associated with the decreasing incidence of these neurological complications. Other factors that may contribute to this trend include the improvement in surgical protocols  and anesthesiological protocols. Our subanalyses suggest that appointing a dedicated neuro-anesthesiologist to GBM cases, irrespective of the expertise of the neurosurgeon , provides an added benefit with regard to perioperative and postoperative outcomes,.Modern medicine is increasingly developing from specialization towards superspecialization due to the rapid expansion of specialized knowledge in various medical specialties. This holds true for the whole spectrum of medical professionals and is not only limited to adult anesthesiological care. Despite this revolution of specialty and superspecialty in many specialties–including neuroscience and neurosurgery–anesthesiologists are not superspecializing at the same pace , 10.Recently, neurosurgical patients, in particular, have a higher risk of negative outcomes than patients from other disciplines in cases of handovers of the anesthesia care . Anestheearly postoperative complications in the NA-group could have been explained by a safer resection , or a less extensive resection. Likewise, the lower incidence of late postoperative complications in the NA-group could have been explained by a higher extent of resection, potentially resulting in a longer progression-free survival. Since a) the mean extent of resection was not significantly different between the NA-group and GA-group, and b) all patients had been operated without neurophysiological mapping techniques, none of these possible explanations proved to be viable at first.We tested different hypotheses to explain why GBM patients who had undergone a resection under the supervision of a neuro-anesthesiologist experienced fewer postoperative complications than patients in the general anesthesiologist group. Generally, GBM surgery means balancing between maximizing the extent of resection while preventing neurological morbidity as much as possible. Therefore, the lower incidence of In order to evaluate the NA-group and GA-group in further detail, we divided each group in two subgroups based on the appointed surgeon , which resulted in a total of four patient subgroups. We found that the addition of a neuro-anesthesiologist to a GBM resection, irrespective of the surgeon, led to two results that were most notable: 1) fewer postoperative complications, 2) a higher prevalence of ioUS use . Moreover, the combination of a neuro-anesthesiologist with a dedicated oncological surgeon (subgroup 1) led to a higher extent of resection. These results indicate that the assignment of a neuro-anesthesiologist certainly helps in achieving a maximum safe resection and that a dedicated neuro-oncological team yields optimal results.n of ioUS patients in that subgroup). We therefore deem it unlikely that the lower incidence of postoperative complications in the NA-group is caused by the higher prevalence of ioUS use in that group.To analyze whether ioUS could explain the lower incidence of postoperative complications in the NA-group, we further evaluated all patients operated with the use of ioUS in both NA-subgroups. We found that mean extent of resection and rate of postoperative complications did not differ between patients operated with or without ioUS in both NA-subgroups , which leads to an increased progression-free survival and consequently, fewer late neurological complications. A second explanation might be the psychological part of appointing a neuro-anesthesiologist to glioblastoma cases: working with an experienced neuro-anesthesiologist makes the surgeon more relaxed and focused, which consequently may have a notable impact on the surgeon’s performance and outcomes. Multiple studies have pointed to the importance of interactive dynamics between surgical team members as key factors for surgical performance and patient outcome –19. FutuA third viable explanation might be the fact that the intravascular volume in NA-led cases proved to be more strictly controlled. Our neuro-anesthesiologists prefer a slightly negative fluid balance (with adequate systematic hemodynamics), which could contribute to less brain edema and subsequent swelling of the brain, which in its turn leads to increased intraoperative field-of-vision and intracranial maneuverability for the surgeon.While all patients were operated electively and were fasted overnight, their intravascular volume should be normal . TherefoThis results in increased intraoperative safety and decreased postoperative morbidity and could explain the lower incidence of the early postoperative complications predominantly in the NA-group.Fourth, the higher incidence of late major postoperative complications in the GA group might  be the result of the higher incidence of early major postoperative complications: early major and late major postoperative complications in the GA group were 28.8% and 26.9%, while this was 13.6% and 16.0% in the NA group. This is substantiated by the fact that more than half of the late postoperative complications was permanent in the GA group (53.0%) while this was 30.4% in the NA group.One final aspect to discuss is the fact that dedicated neuro-anesthesiologists more frequently used a combination of TIVA and volatile anesthetics than general anesthesiologists. The colleagues practicing this combination appreciate the stable anesthesia conditions. However, based on the (lack of) literature, we are unable to provide a good argument, why these differences in anesthesia technique may cause differences in outcome. While some authors support TIVA for brain tumor resection, others found recently no disadvantages for the use of volatile anesthetics in glioblastoma patients , 22. TheThe major limitation is the retrospective nature of this study. We expected a strong selection bias for patients operated under the supervision of a dedicated neuro-anesthesiologist. However, no significant differences in baseline characteristics were observed between groups, including well-known prognostic and predictive factors. Moreover, this study did only include GBM resections without mapping techniques, which might not be standard-of-care for some centers, especially for GBMs in or near eloquent areas. We therefore stress the importance of evaluating the benefit of the dedicated neuro-anesthesiologist in GBM resections with respect to (intraoperative) techniques for surgery in these areas.To minimize most other possible bias correlated with the retrospective nature of this study, we underline the importance of a prognostic study to further investigate the potential of dedicated neuro-anesthesiologists in GBM surgery. We would like to invite our colleagues to cooperate in a prospective multicnter effort to validate the findings of this first proof-of-hypothesis study. In our opnion, such a study should focus on the etiology behind the perceived lower incidence of postoperative complications in GBM resections led by a neuro-anesthesiologist and the potential synergistic benefit of dedicated onco-neurosurgical teams. Moreover, the benefit of dedicated neuro-anesthesiology in combination with mapping techniques should be evaluated, ideally in subgroups of patients. The current study was conducted in a large high-volume university hospital with high-volume neurosurgeons ; nevertheless, large university hospitals with a comparable study setting, patient selection and local procedures can expect a robustness in the external validity of our findings.


To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21%  in 2018 to 2.09%  in 2021 ; the incidence has declined from 25.94 per 1000 PYFU  in 2019 to 12.15% per 1000 PYFU  . However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination. In June 2016, the World Health Organization (WHO) announced its first global target to eliminate viral hepatitis as a major public health threat by 2030, aiming to reduce the new diagnoses of viral hepatitis by 90% and hepatitis-related deaths by 65% . MoreoveHowever, a nationwide hepatitis elimination programme could be extremely challenging and resource-consuming for many countries. Therefore, instead of pursuing population-wide HCV elimination, it is probably reasonable to start by targeting specific subpopulations who are at higher risk of acquiring HCV or developing HCV-related complications. One of the most commonly targeted subpopulations for this “microelimination” goal is people living with HIV (PLWH), as many epidemiological studies have demonstrated high rates of HCV coinfection due to the shared behavioural risk factors, such as sharing needles/syringes and diluent or unprotected sexual contacts . FurtherAs of January 2022, several European countries and Australia have reported the progress of HCV microelimination among PLWH . In the In this 10-year cohort study, we aimed to investigate the trends of HCV viremia among PLWH in Taiwan before and after the implementation of the DAA treatment programme.In Taiwan, the National Health Insurance started to reimburse DAA treatments in January 2017, which initially covered only HCV-infected patients with moderate to severe fibrosis; patients who were reinfected with HCV or had relapses after DAA treatments were not reimbursed. In 2018, the government published Taiwan Hepatitis C Policy Guidelines, aiming to reach the WHO HCV elimination targets by 2025 . As of 2In Taiwan, the total case number of PLWH diagnosed was 42,263 between 1984 and 2021 and the UNAIDS 95-95-95 targets achieved was 90-94-95 in 2021. HCV seroprevalence was estimated 43.4% among PLWH who initiated antiretroviral therapy between 2004 and 2007, which had decreased to 18.6% between 2012 and 2016, as compared to the 4% HCV seroprevalence in the general population . Among rThis was a single-centre, retrospective cohort study conducted at the National Taiwan University Hospital (NTUH), the largest designated hospitals for inpatient and outpatient HIV care in Taiwan. PLWH who were aged 18 years or older and sought HIV care at NTUH between 1 January 2011 and 31 December 2021 were included. PLWHs were included in this study since their first inpatient or outpatient visit with a confirmed diagnosis of HIV infection during the study period and were followed until death, loss to follow-up, transfer of care, or the end of observation (31 March 2022), whichever occurred first.PLWH included were first stratified according to the HCV serostatus. HCV-seronegative PLWH who remained negative for anti-HCV antibodies throughout their entire observation period were considered uninfected with HCV, and annual HCV RNA testing was not routinely performed. For HCV-seronegative PLWH, their HCV-negative follow-up duration was calculated as the interval between their first and last available anti-HCV results. HCV-seronegative PLWH who had only one test result of anti-HCV during the follow-up were therefore excluded. For those who had at least one positive result of anti-HCV antibodies, including those who were positive at the start of observation or those who had anti-HCV seroconversion during follow-up, all archived plasma samples were retrieved and tested for HCV RNA to confirm HCV viremia. An incident case of HCV viremia was defined as (1) PLWH with new HCV viremia following a previously negative result of plasma HCV RNA or (2) HCV seroconversion with the presence of HCV RNA in the plasma. The date of incident HCV viremia was arbitrarily defined as the time when the samples that tested positive for HCV RNA were collected. For those who were HCV-seropositive or seroconverted, their HCV-negative follow-up duration was calculated as the period without HCV viremia.Throughout the study period, the annual prevalence and incidence rate of HCV viremia in each calendar year were calculated. The prevalence of HCV viremia was defined as the number of PLWH who had one or more plasma samples tested positive for HCV RNA , divided by the total number of PLWH followed in the same calendar year. The annual incidence of HCV viremia was calculated by dividing the number of incident HCV infections (including reinfections) by the total HCV RNA-negative person-time observed during each calendar year. To compensate for potential time lags between HCV acquisition and sample collection, positive HCV RNA results within the first three months of each calendar year were assigned to the previous year in the estimations of incidence and prevalence.According to the national HIV treatment guidelines in Taiwan, PLWH who were on stable antiretroviral therapy were followed at the designated hospitals every three months, and laboratory tests were performed every three to six months, including plasma HIV RNA load (PVL). In this study, all archived plasma samples during the follow-up were retrieved to test for anti-HCV antibodies and HCV RNA for those testing HCV-seropositive; those who did not have available plasma samples were excluded.® 6800 system , with a detection limit of 15 IU/ml. To facilitate early detection of HCV viremia and linkage to DAA treatments, PLWH who received a diagnosis of sexually transmitted infection (STI), had elevated aminotransferases, or achieved HCV clearance spontaneously or with DAAs were enrolled in another prospective study using three-stage pooled-plasma HCV RNA testing every three months to detect HCV viremia for 12 months after June 2019 [Anti-HCV antibodies were determined using a fourth-generation enzyme immunoassay . The detection of HCV RNA was performed using the Roche Cobasune 2019 . In briet-test or Mann–Whitney U-test, and categorical variables were compared using chi-square test or Fisher’s exact test. For non-categorical data with more than two subgroups, a one-way ANOVA test was used to detect differences between groups and pairwise comparisons with Bonferroni correction would be applied if post-hoc analysis was needed. The HCV incidence and prevalence, with a 95% confidence interval (CI), were calculated as previously defined. The differences in incidence and prevalence were compared between the end of study observation (2021), the beginning of DAA reimbursement (2017), and the epidemiological peak during observation. All statistical analyses were performed using STATA software v.14.0 S/E . All p values were two-sided.The demographic and clinical characteristics of all included PLWH were summarized. Non-categorical variables were compared using Student’s During the 10-year observation period, 5514 PLWH sought HIV care at NTUH. After excluding those who had no available samples, 4199 PLWH were included and contributed to a total of 27,258.75 person-years of follow-up (PYFU). Of all included PLWH, 3375 (80.4%) remained HCV-seronegative throughout the follow-up duration, while 447 (10.6%) were HCV-seropositive at the start of observation and 377 (9.0%) had documented HCV seroconversion during the follow-up . The basp < .001) and more likely to be PWID . On the other hand, those with HCV seroconversion during the follow-up were younger  and more likely to be MSM  compared with the HCV-seronegative PLWH.Compared with those who remained HCV-seronegative throughout the entire observation, PLWH who were HCV-seropositive at baseline were older  pandemic might have hindered PLWH from seeking HIV and other medical care worldwide ,28. ThroThe incidence of HCV viremia was estimated at 4.99 per 1000 PYFU  in the beginning of this study in 2011 . The incThe prevalence of HCV viremia was estimated at 5.61%  at the beginning of observation in 2011 . The preWith each incident case of HCV viremia, we further differentiated PLWH who had the first episode of HCV infection from those who were reinfected after clearance of HCV RNA either spontaneously or by DAA treatments . Before In this cohort study examining the progress of HCV microelimination among PLWH in Taiwan, we observed significant reductions in prevalence and incidence of HCV viremia after the rollout of DAA treatments in 2017. The highest prevalence of HCV viremia was observed in 2018  and has reduced by 66.4%  at the end of observation in 2021. The incidence rate of HCV viremia has declined by 53.2%  from a peak rate of 25.94 per 1000 PYFU  to 12.15 per 1000 PYFU .To the best of our knowledge, this is the first longitudinal observational cohort study in the Asia-Pacific region to examine the progress of HCV microelimination among PLWH in the DAA era. Our findings of significant progress made towards HCV microelimination among PLWH in Taiwan are in line with the observations of a 49–78% reduction of HCV incidence in the UK, Australia, the Netherlands and Switzerland that expanding the accessibility to DAA treatments reduces the incidence of HCV infection among PLWH . It is nWe previously have shown the rate of HCV seroconversion continued to increase from 2017 to 2018 in our PLWH cohort despite the reimbursement of DAAs in 2017 . StartinIn our cohort, we observed a significantly increased proportion of incident HCV viremia attributable to reinfections, particularly after 2017. Despite the significant reductions in HCV incidence after 2019, 77.8% of incidents of HCV viremia in 2020 and 82.8% in 2021 were classified as reinfections. After the introduction of DAAs, HCV reinfections after viral clearance have raised significant concerns, especially among high-risk populations such as PWID or MSM. The rates of HCV reinfection vary widely in different geographic locations and subpopulations . StudiesOur studies had several limitations. First, the frequency of HCV RNA testing was not standardized. The inconsistency of testing might cause potential time lags between HCV acquisition and diagnosis. To compensate for this potential bias, we assessed the archived samples from their regular clinical visits. Second, we did not attempt to differentiate HCV reinfection from treatment failure in this study, which might lead to overestimating the incidence of HCV reinfection before the DAA era. However, considering the extremely high success rates of DAA treatments , we beliIn conclusion, we demonstrate that, compared to the epidemiological peaks, the incidence and prevalence of HCV viremia had a 53.2% and 66.4% reduction, respectively, with the rollout of DAA treatments in Taiwan. However, addressing HCV reinfections among high-risk subpopulations should be a critical step in sustaining the success of HCV microelimination.


Molecular imaging technologies are increasingly used to diagnose, monitor, and guide treatment of i.e., cancer. In this review, the current status and future prospects of the use of molecular imaging as an instrument to help realize precision surgery is addressed with focus on the main components that form the conceptual basis of intraoperative molecular imaging. Paramount for successful interventions is the relevance and accessibility of surgical targets. In addition, selection of the correct combination of imaging agents and modalities is critical to visualize both microscopic and bulk disease sites with high affinity and specificity. In this context developments within engineering/imaging physics continue to drive the growth of image-guided surgery. Particularly important herein is enhancement of sensitivity through improved contrast and spatial resolution, features that are critical if sites of cancer involvement are not to be overlooked during surgery. By facilitating the connection between surgical planning and surgical execution, digital surgery technologies such as computer-aided visualization nicely complement these technologies. The complexity of image guidance, combined with the plurality of technologies that are becoming available, also drives the need for evaluation mechanisms that can objectively score the impact that technologies exert on the performance of healthcare professionals and outcome improvement for patients.The online version contains supplementary material available at 10.1186/s40644-022-00482-2. Molecular imaging is increasingly being used to diagnose a range of diseases and to monitor and guide therapy, particularly in cancer. In this setting, molecular imaging often aids in the selection of systemic versus locoregional therapies . The comIn surgery, favorable outcomes are achieved by excising all diseased tissue. At the same time the severity of complications is related to the invasiveness of an intervention. Hence, a balance needs to be created between the need for radical removal of disease and minimizing the scope of surgery. Accordingly, there is a drive towards minimal-invasive and more personalized interventions, while providing patients and healthcare professionals more confidence in the efficacy of radical resection, as well as uncomplicated postoperative recovery. From the very beginning of surgical practice decision-making has been guided by the tactile and visual senses of the operating surgeon. The technological advances made in the last century now allow these senses to be complemented via the use of preoperative imaging roadmaps  and intraoperative target visualization in the form of white-light endoscopic video-image guidance. This evolution is helping minimally invasive ‘key-hole’ approaches to gradually replace open surgery. A clear example is the rise of robot-assisted laparoscopic surgery , which sHistorically, image-guided surgery has been pursued using different modalities. Since the late 1950s fluorescence imaging has been implemented during angiography The success of image-guided surgery is driven by the synergy between four main generic components: 1) relevance and accessibility of the target (medicine), 2) imaging agents (chemistry/pharmacology/pharmaceutics), 3) modalities used to detect or navigate towards the target defined in via imaging (engineering/imaging physics), and 4) interpretation of the imaging data . In this review, the status and future prospects of these four aspects of image-guided surgery is addressed. In addition, we indicate how each of the components can contribute to transition of new concepts from a laboratory setting into standard clinical care pathways .68 Ga]-octreotate, [68 Ga]-DOTATOC [68 Ga]-PSMA-11 [The concept of image-guided surgery has been most extensively pursued in the field of oncology. In this setting, molecular imaging has helped raise the diagnostic standard and increase the accuracy with which target tissues can be non-invasively identified. Key aspects herein are exemplified by the synergies of modalities such as positron emission tomography/computed tomography (PET/CT) with receptor-specific radiotracers such as [-DOTATOC  and [68 -PSMA-11 . ThroughImage guidance is routinely used to clearly delineated organs such as blood vessels . With regard to having low signal attenuation and being subject to scattering, X-ray is the superior modality, followed by radiotracer-based detection, then US and lastly, optical tracers , 37, Fig7, Fig3.  When looking at the practical implementation of the above-mentioned modalities, some basic principles can be deduced. First and foremost, all routine optical imaging indications remain confined to superficial assessment , whereby the impact of light attenuation of the emitted signal and background light can be kept to a minimum. In addition, these applications tent to rely on relatively ‘simple’ chemicals. In a relatively high dose these agents help study physiological aspects such as vascular-, lymphatic-, and bile- flow . CompareThe range of applications wherein interventional molecular imaging is having clinical impact is increasing through advances in medical chemistry and radiochemistry. In particular, there has been significant development in the design of optical-  and radioisotope-based  agents , 50.99mTc (140 keV) and, to a lesser extent, 111In (gamma rays with photon energies of 171 and 245 keV) as the most favorable radioisotopes [99Mo/99mTc generators in clinics world-wide and 111In being an accessible long-lived reactor product. This further focused tracer design, with recent examples of widely implemented agents being 99mTc-PSMA-I&S [99mTc-nanocolloid [111In-octreotide [From a chemical perspective, most of the efforts towards designing disease specific imaging agents find their origins in nuclear medicine and its subdiscipline of radiochemistry. Radioguided surgery applications for sentinel nodes , somatoisotopes  for clinPSMA-I&S , (ICG-)9ocolloid  and 111Itreotide . Besidestreotide , beta patreotide  and/or Ctreotide . AdvantaSecond in popularity is the development of fluorescent tracers intended for superficial lesion identification. Where fluorescence microscopy tends to focus on use of dyes in the 400-700 nm range, fluorescence-guided surgery efforts often tend to explore the theoretically favorable interaction between near-infrared (NIR) fluorescence (> 750 nm) and tissue . NIR wav3− has been shown to enhance the brightness [A strategy to overcome the limitations of individual modalities is the use of bimodal/hybrid imaging agents. Herein, nuclear medicine signals tend to be complemented with optical , magnetiightness .The ideal intraoperative detection modality would probably be best described as a device that: 1) has a high sensitivity for signal detection, 2) only marginally suffers from interference by non-specific background signal (high specificity) and 3) maintains or improves present surgical logistics. These are generic wishes that transcend across all modalities.It is no surprise that the imaging physics drive the design of a medical device used for interventional imaging. Conventional X-ray approaches such as CT and fluoroscopy are often impractical for implementation in the surgical suite, and accordingly, surgical interventions more often implement X-ray imaging in the form of a c-arm design . In someEffective application of imaging modalities during surgery is highly dependent on the degrees of freedom with which the modality can be positioned relative to the target. In open surgery Fig. , camerasA stated earlier surgery is increasingly performed in a minimally invasive setting  preoperative target assessment, 2) intraoperative navigation towards the target, and 3) intraoperative confirmation of the target location and margins . A way tOne key aspect is the direct registration of preoperative imaging information onto the surgical field in the OR. Here, registration can take place based on endogenous structures or exogenous fiducials . The most straight forward implementation of such registration concepts is surgical navigation, meaning that the operating surgeon can position the surgical instruments in the geographic context of preoperative images . This apAlternative to registration of preoperative images to the patient, intraoperative tracking and interventional modalities using exogenous fiducials, can help register the output of an imaging modality to a specific anatomical location in the patient; a concept used to generate so-called freehand scans. Freehand options have been reported for US , beta paAnother, perhaps more obvious, aspect of digital surgery is related to computer visualization applications. Such techniques help improve the interpretation of imaging data . IntraopWhile application of artificial intelligence in the realm of image-guided surgery is still limited , it is h99mTc-nanocolloid [99mTc-PSMA-I&S [Clinical translation of novel image-guided surgery technologies beyond research and development requires establishment of an evidence-base that demonstrates the safety and effectiveness of these procedures, while reimbursement requires evaluation of cost-effectiveness. Strictly speaking, image-guided surgery technologies need to provide either better outcome for the patient or improve the workflow for medical professionals, if not both, and at a reasonable cost. In this regard, patient benefit can be scored by looking at short-term complication rates and long-term outcomes across cohorts with and without use of image guidance. Unfortunately, availability of such data is limited as most studies seem to focus on proof-of-principle studies. Exceptions to the rule are represented by reports for 5-ALA , sentineocolloid , 188, anPSMA-I&S , 190. AsPSMA-I&S . ConceptPSMA-I&S . This apPSMA-I&S . UniquelAs image-guided surgery solutions are quite often technically challenging. In essence, ethics and regulations provide a healthy translational hurdle to protect patients, while financial aspects may also constrain development. from a practical perspective, lead compounds and detection device prototypes must be developed and refined in research setting and often not within the domain of patient care. While this helps preventing the patient exposure to potentially harmful technologies, it also means that some approaches can become more ‘technology-driven’ than ‘clinical-need-driven’. Ideally all developments should be done with clinical translation in mind and based on real-life unmet surgical needs. But even with these prerequisites, it is extremely challenging to translate laboratory findings to the clinic. An example of the challenges faced is the extrapolation of findings in small animal disease-models to patients. Besides the obvious anatomical differences, which will reflect on tracer pharmacokinetics, the performance characteristics of modalities employed in small animals are not necessarily recapitulated in human instrumentation . RegularClinically surgical tasks are divided according to anatomy, disease indication and even the type of surgical intervention. This helps ensure expertise for surgeons and helps create some form of quality assurance from a healthcare perspective. From a technological perspective, however, most of these boundaries seem irrelevant. Physical and technical factors  drives the design of new technologies. That said, most chemical and engineering efforts mentioned above still find applications in multiple settings. The success stories in the field of image-guided surgery are based on technologies that maximally align with innovations made in other fields. For example, initial work on fluorescence laparoscopy presented in prostate cancer surgery  was lateWith all the promising technologies being developed under the umbrella of image-guided surgery, it remains essential to maintain a helicopter view of this highly multidisciplinary and rapidly expanding field. Hereby, we need to make sure that the clinical needs remain aligned with tracer chemistry, device physics and the increasing digitization of the operating room.Additional file 1.


Although national and international guidelines have strongly discouraged use of antibiotics to treat COVID-19 patients with mild or moderate symptoms, antibiotics are frequently being used. This study aimed to determine antibiotics-prescribing practices among Bangladeshi physicians in treating COVID-19 patients. We conducted a cross-sectional survey among physicians involved in treating COVID-19 patients. During September–November 2021, data were collected from 511 respondents through an online Google Form and hardcopies of self-administered questionnaires. We used descriptive statistics and a regression model to identify the prevalence of prescribing antibiotics among physicians and associated factors influencing their decision making. Out of 511 enrolled physicians, 94.13% prescribed antibiotics to COVID-19 patients irrespective of disease severity. All physicians working in COVID-19–dedicated hospitals and 87% for those working in outpatient wards used antibiotics to treat COVID-19 patients. The majority (90%) of physicians reported that antibiotics should be given to COVID-19 patients with underlying respiratory conditions. The most prescribed antibiotics were meropenem, moxifloxacin, and azithromycin. Our study demonstrated high use of antibiotics for treatment of COVID-19 patients irrespective of disease severity and the duty ward of study physicians. Evidence-based interventions to promote judicious use of antibiotics for treating COVID-19 patients in Bangladesh may help in reducing an overuse of antibiotics. Antimicrobial resistance (AMR) is one of the leading public health issues mostly affecting low- and middle-income countries (LMIC), and the World Health Organization (WHO) declared AMR as one of the ten leading global public health threats . More thAs of 1 March 2022, the ongoing COVID-19 pandemic has resulted in around 435 million confirmed cases and nearly 6 million deaths globally . Althoughttps://dghs-dashboard.com/pages/covid19.php, accessed on 1 April 2022). To ensure proper clinical treatment and management of COVID-19 patients, different national and international clinical guidelines have been developed. According to the WHO guidelines, the use of antibiotics is strongly discouraged to treat COVID-19 patients with mild or moderate symptoms, and should only be used when there is a confirmed secondary bacterial or fungal co-infection [Bangladesh is a densely populated low to middle income country with a total population of 164.6 million . As of tnfection . The natnfection ,29. TherWe conducted a cross-sectional study to explore the antibiotic prescribing practices among Bangladeshi physicians who provided clinical care to COVID-19 patients in Bangladesh. Eligible criteria for study participants were: (1) medical doctors (MBBS) registered with the Bangladesh Medical and Dental Council (BMDC) and (2) involved in the treatment of COVID-19 patients. The data were collected from September through November of 2021.Due to pandemic-related lockdowns and movement restrictions, we adopted two formats for data collection modes ,31,32. TWe developed a structured, standardized, and self-administered questionnaire following an extensive literature review ,35,36,37The survey questionnaire consisted of eighteen questions separated into three sections: (a) demographic characteristics (six questions); (b) factors associated with prescribing antibiotics for COVID-19 patients (eleven questions); and (c) types of antibiotics prescribed for treatment of COVID-19 patients according to the severity of the illness (one question). The first section of the survey questionnaire was focused on collecting demographic information about participants, which included participants’ age in years, gender, highest educational level, years of work experience, type of healthcare facility, and duty wards. The second section utilized a 5-point Likert scale (strongly agree to disagree strongly) to collect physicians’ insight into the main decision-making factors in prescribing antibiotics for COVID-19 patients. Physicians’ factors associated with prescribing antibiotics were represented by 11 statements, including three statements on the patient’s underlying medical conditions, three statements on symptoms or signs that influenced physicians to prescribe antibiotics, and five statements on laboratory tests. The third section included names of different types of antibiotics and their usage based on the severity of COVID-19. The severity levels of COVID-19 illness were categorized as mild to moderate, severe, and critical ,38. The https://www.bmdc.org.bd, accessed on 1 April 2022). We could not employ the probability sampling approach, even though we computed the sample size to determine the minimal number of samples needed to produce the true population estimates. The non-probability sample designs were chosen due to the associated risk of COVID-19, physicians’ fear of transmission via contact, incapacity or unwillingness of physicians to continue patient treatment, and increased workplace absenteeism [Assuming 74.6% of patients with COVID-19 are prescribed with antibiotics, with 5% absolute precision, 1.27 design effect, a 10% non-response rate, and using a single proportional approach, we estimated that 511 physicians needed to be surveyed . The totenteeism . We usedenteeism ,31. Figuhttps://www.aapor.org/Standards-Ethics/Institutional-Review-Boards/Full-AAPOR-IRB-Statement.aspx, accessed on 1 April 2022). Participation in this survey did not put respondents at more than a minimal risk in their everyday life. Personal identifiable information was not collected, and demographic information were kept separate from the interview data in a secure and password-protected file which only study investigators had access to. For hard copies of the questionnaires, all the participants were informed about the purpose and intent of the study, as well as their requirement for their participation. They were also informed that their participation was voluntary and that they had the right to withdraw their participation at any point in time. Enrollment in this study was done only after obtaining written informed consent. To maintain confidentiality of the participants, personal identifiable data were not collected and other related data that could be linked to a participant were kept confidential to the greatest extent as possible. All the hard copies of the interviews were kept in a locked cabinet and were only used by the researchers involved in the study.All survey participants gave their consent to participate in the anonymous online survey. Prior to participation in the survey, participants were provided information on the objectives of the study, what was asked for their participation, and risk and benefits associated in this study. After reading this information, they had to check the “Yes” button confirming that they have read and understood the written informed consent form concerning data protection and accepted the regulations. Without checking the “Yes” button, participation was not possible. We strictly ensured the safety, confidentiality, and comfort of the respondents by protecting the privacy of the respondent as per the guideline of American Association for Public Opinion Research (AAPOR) for the protection of human subjects with a study involving survey interviews or questionnaires; therefore, this survey meets the requirement for the exemption of IRB process (We followed the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) for conducting our online survey . FurtherWe used Excel to enter data from paper questionnaires. The online survey used a Google Form that was linked to a Google spreadsheet, and data were automatically extracted. Following the download of the Google spreadsheet, we combined it with the Excel data and imported the data into STATA for data management and analysis. Antibiotic prescribing frequency was determined separately for each severity level of COVID-19 illness. Dichotomous variables were coded to reflect zero for no antibiotic prescription and one for antibiotic prescribing. Data collected on a five-point Likert scale were condensed to a three-point Likert scale  by combining the frequencies of agreed/strongly agreed and similarly for disagreed/strongly disagreed. We employed descriptive statistics to summarize the respondents’ demographic characteristics and other relevant factors. The chi-square or Fisher’s exact test and stepwise Poisson regression with a backward selection algorithm were employed to assess associations between the antibiotic prescribed for treating COVID-19 patients and respondents’ demographic characteristics and influential decision-making variables. Unadjusted prevalence ratios (PR) with a 95% confidence interval (CI) were reported as crude regression model estimates, whereas multivariable regression model outputs were presented as adjusted prevalence ratios (PR) with a 95% CI. All findings were considered significant when the p-value was less than 0.05. Stata 15 software was utilized for all analyses . Out of the 511 respondents, 346 (67.71%) were males, and 151 (29.55%) were females, and the majority (68.10%) of the physicians were between age 25 to 29 years, with a mean age of 28.81 ± 4.91. The majAmong all the participating physicians, 94.13% prescribed at least one or more antibiotics to COVID-19 patients irrespective of disease severity . The use of antibiotics by the physicians ranged between 86.69% for critical COVID-19 patients to 72.21% for mild to moderately ill COVID-19 patients .The majority of the study physicians believed that antibiotics should be given to COVID-19 patients based on their underlying medical conditions. Out of total 511 respondents, the majority (90.41%) of them reported that antibiotics should be given to COVID-19 patients with underlying respiratory illness. Similarly, around 76% of the physicians were in favor of providing antibiotics to elderly patients. Approximately half (49%) of the study participants disagreed about using antibiotics for ambulatory COVID-19 patients.Around 61% of physicians mentioned that antibiotics should be given to patients with a high body temperature (>37.2 °C) , diarrheStudy participants reported prescribing various types of antibiotics for treating COVID-19 patients irrespective of the bacterial etiology. The most commonly prescribed antibiotics were meropenem, moxifloxacin, and azithromycin. Meropenem and moxifloxacin were the two most common antibiotics used to treat critical and severe COVID-19 patients. Azithromycin was used commonly to treat mild to moderate COVID-19 illness. To the best of our knowledge, this is one of the initial surveys assessing the antibiotic prescribing practices among physicians for treating COVID-19 patients in Bangladesh and exploring the associated factors that influenced antibiotic prescribing practices. Our study documented a high frequency (94%) of antibiotic prescribing practices among Bangladeshi physicians for treating COVID-19 patients. Inappropriate and irrational use of antibiotics, particularly during the current COVID-19 pandemic, has evidently become a cross-cultural practice in many countries around the world, which harbors the escalation of antimicrobial resistance to most of the antibiotics that are globally used ,44.Antibiotic prescribing practices ranged between 72% and 87% based on severity of patients’ illness , which is comparable to previous studies done in other settings ,45,46. TAround 90% of the physicians in our study preferred to prescribe antibiotics to COVID-19 patients who had any pre-existing respiratory problem, and 75% of the participants preferred to prescribe antibiotics to elderly patients. These findings are similar to previous studies which also documented a high usage of antibiotic therapy among elderly (median age > 53 years) patients with COVID-19 illness and among those requiring mechanical ventilation . Almost Most of the participants (around 91%) preferred to conduct a CRP test prior to prescribing any antibiotic to a COVID-19 patient, as the test count would help them decide the next treatment regime. CRP count is generally elevated in bacterial infections and often helps physicians to differentiate between viral and bacterial infections and thus helps in prescribing required antibiotics . This isWe also looked at the type of antibiotics being reported to have been commonly prescribed by the study respondents among COVID-19 patients with varying severity. Meropenem (a third-generation antibiotic) and Moxifloxacin (a fluoroquinolone antibiotic) were reportedly frequently prescribed to treat patients with critical and severe COVID-19. As per guidelines provided by the Ministry of Health and Family Welfare (MOHFW) of Bangladesh on the clinical management of COVID-19 (version 8.00) , the useThe high frequency of irrational antibiotic prescribing practices among our study respondents can be subjected to many speculations around the potential underlying causes of such practices. One explanation might be the historic tendencies of Bangladeshi physicians to prescribe antibiotics even for the simplest form of respiratory viral infections and mostly without approaching a diagnostic test ,53. On tOur study has certain limitations. We adopted snowball and convenience sampling which use nonrandom selection procedures mostly depending on subjective judgement of the participants. These sampling techniques may also lead to selection biases which impact generalization, representativeness, and external validation of the findings as the findings might not be consistent for sub-groups of the same population or different populations. The findings of the study might not be constant for subsequent waves of this pandemic as treatment modality for SARS-CoV-2 is rapidly changing. Additionally, data about some clinical variables important for assessing decision making around antibiotic prescribing were not collected . Another issue is the utilization of the Google Form and recruitment of participants through social media invites  that might have been a barrier for older-aged physicians for participating in the study. However, this study still provides comprehensive data on antibiotic prescribing practices among physicians for treating COVID-19 patients. We also tried to capture the diversity in practices through enrolling participants from different settings including ambulatory care and inpatient settings.We have demonstrated high antibiotic prescribing practices among physicians in Bangladesh for treating COVID-19 patients, specifically COVID-19 patients with mild illness where antibiotics are not recommended by local guidelines. Such blanket use of antibiotics during the pandemic may contribute to the emergence of AMR. The study findings also highlight the need for context-specific feasible interventions for promoting, strengthening, and sustaining the anti-microbial stewardship program (ASP) to ensure judicious use of antibiotics.


There has been an increasing demand for new technologies regarding infection control in hospital settings to reduce the burden of contact tracing.This study aimed to compare the validity of a real-time locating system (RTLS) with that of the conventional contact tracing method for identifying high-risk contact cases associated with the secondary transmission of SARS-CoV-2.A retrospective case-control study involving in-hospital contact cases of confirmed COVID-19 patients, who were diagnosed from January 23 to March 25, 2022, was conducted at a university hospital in South Korea. Contact cases were identified using either the conventional method or the RTLS. The primary endpoint of this study was secondary transmission of SARS-CoV-2 among contact cases. Univariate and multivariable logistic regression analysis comparing test positive and versus negative contact cases were performed.P=.007).Overall, 509 and 653 cases were confirmed by the conventional method and the RTLS, respectively. Only 74 contact cases were identified by both methods, which could be attributed to the limitations of each method. Sensitivity was higher for the RTLS tracing method  than the conventional tracing method  considering all contact cases identified by both methods. The secondary transmission rate in the RTLS model was 8.1%, while that in the conventional model was 5.3%. The multivariable logistic regression model revealed that the RTLS was more capable of detecting secondary transmission than the conventional method (adjusted odds ratio 6.15, 95% CI 1.92-28.69; This study showed that the RTLS is beneficial when used as an adjunctive approach to the conventional method for contact tracing associated with secondary transmission. However, the RTLS cannot completely replace traditional contact tracing. Human history is characterized by the incessant influence of infectious diseases, with viruses being the most successful contender . Viral dContact tracing is an important strategy to keep disease transmission under control by isolating high-risk contacts who eventually present with the disease. Contact tracing is a time- and labor-consuming procedure, the efficiency of which is dependent on the commitment of the infection control personnel and the presence of beneficial adjunctive tools. Moreover, the importance of this method could be diminished in the era of “living with COVID-19,” wherein efforts to confine the spread of the disease are diluted with the weakening of disease severity. However, in a hospital setting, simplifying rather than eliminating the contact tracing effort is required. SARS-CoV-2 is a complicated virus to deal with, especially in the hospital setting, without sufficient data regarding its mode of transmission . FurtherTechnological efforts, such as a real-time locating system (RTLS), could be an option to overcome the limitation set by the conventional method. One type of RTLS involves radio-frequency identification (RFID) and a Wi-Fi tracking system. RFID calculates the distance and duration of human-to-human interaction by analyzing the signals from RFID tags worn by users, which are captured by exciters installed in hospital wards and working places . Using tThe aim of this study was to evaluate the validity of the RTLS compared with the conventional contact tracing method to identify high-risk contacts associated with the secondary transmission of SARS-CoV-2. Furthermore, we attempted to characterize the factors associated with secondary SARS-CoV-2 transmission using both methods.This study was conducted at a Yongin Severance University–affiliated hospital in South Korea, with 580 beds and an 82% average occupancy rate annually. This institution had RTLS location sensors since its opening in 2020. All health care workers and inpatients were issued RTLS tags that detected their locations.From the time COVID-19 was declared a pandemic, health care workers, hospitalized patients, and caregivers in this hospital were monitored for the presence of symptoms suggestive of COVID-19 on a daily basis. Caregivers included the patients’ family members or privately employed carers. Employees were mandated to report COVID-19–related symptoms through a mobile app at least once a day. Hospitalized patients and caregivers were obligated to take screening reverse transcription polymerase chain reaction (RT-PCR) tests ahead of admission, and COVID-19–related symptoms were closely monitored by attending nurses, which were recorded electronically. SARS-CoV-2 polymerase chain reaction (PCR) tests were conducted for those who developed COVID-19–related symptoms, and quarantine measures were implemented for individuals who tested positive for SARS-CoV-2. Subsequent contact tracing was carried out by the infection control office staff and the digital information team, with stratification of contacts according to the level of exposure. All contacts regardless of the exposure level were recommended to get tested for SARS-CoV-2 at least once, with specific emphasis on high-risk contacts within 14 days after exposure or on the development of symptoms. Postexposure measures, such as quarantine, were implemented for those who were identified as contacts at the discretion of staff in the infection control office. As RTLS data were collected only for research purposes, no postexposure interventions were implemented based solely on RTLS data.A retrospective case-control study involving in-hospital contact cases of confirmed COVID-19 patients, who were diagnosed from January 23 to March 25, 2022, was conducted. All contact cases of health care workers, and inpatients and their caregivers, identified either by the conventional method or the RTLS, were included in this study. The participants were followed up from the date of contact to 14 days following the last contact or the date of a follow-up SARS-CoV-2 PCR test.Contact tracing started 2 days prior to the symptom onset or positive PCR test result of a COVID-19–confirmed patient. The conventional method of contact tracing starts with an in-person interview, followed by reviewing electronic medical records and monitoring closed circuit surveillance camera feeds based on the information acquired in the interview. RTLS-based contact tracing was performed separately by the digital information team. When a patient tested positive, the digital information team extracted data from the RTLS to identify close contact cases. The radio-frequency RTLS sensors that can detect signals within a radius of 20 meters were located in every room in the hospital and at every 10 meters in open spaces. Hospital staff and inpatients were required to wear RTLS tags at all times. Signals were emitted from the tags every 1 to 3 seconds to confirm the presence of individuals in a room or confirm the distance between individuals through tag-tag signal interaction. When 2 individuals got close enough to a designated distance, the calculation of contact time was started to obtain the cumulative contact time between the 2 individuals. Generally, it took less than 30 minutes to draw data from the RTLS.The level of exposure was determined based on a Centers for Disease Control and Prevention (CDC) guideline . The CDCThe primary endpoint of this study was secondary transmission of SARS-CoV-2 among contact cases. Secondary transmission was assumed when there was a positive conversion of the SARS-CoV-2 PCR test following a negative test result within 14 days of contact. Those without previous test results were included as well, unless they had evidence of other sources of infection, such as being simultaneously diagnosed with index patients, having a known familial transmission, or showing COVID-19–related symptoms.The exclusion criteria were as follows: (1) no identifiable age or gender information; (2) no follow-up PCR results; and (3) distance of more than 3 meters from index patients among RTLS-confirmed cases.The data of in-hospital–confirmed COVID-19 patients were collected retrospectively. Data, including age, gender, vaccination history (including number of vaccinations and days passed from the last vaccination), follow-up SARS-CoV-2 PCR test results, date of diagnosis in case of a positive result, closest exposure distance, duration of exposure within a distance of 2 meters, whether personal protective equipment was used, mask-wearing habit, type of occupation, type of occupation of index patients, date of the last contact, whether the room was shared with index patients, methods used to identify contact cases and postexposure measures, and whether tags were worn, were collected by reviewing the records acquired for contact tracing. We filled up some part of the data regarding wearing masks through estimation based on the hospital policy, when fact-checking was impossible due to long hours of exposure.SARS-CoV-2 RT-PCR was performed with nasopharyngeal swab samples collected from participants. The MagNA Pure 96 System (Roche Diagnostics) was used to extract RNA from nasopharyngeal swabs in viral transport media, according to the manufacturer’s instructions. The extracted RNA was then subjected to the Allplex SARS-CoV-2 Assay, which targets 4 genes in a single tube  to detect SARS-CoV-2 infection, according to the manufacturer’s instructions. PCR amplification was performed using the CFX96 real-time PCR detection system (Bio-Rad Laboratories).U test, independent samples t test, or ANOVA for continuous variables, and the χ2 test or Fisher exact test for categorical variables. Continuous variables were expressed as means or medians (IQRs) and categorical variables as numbers with percentages for the description of baseline characteristics. Logistic regression was used to identify factors related with secondary transmission adjusting for relevant variables with a P value <.05 in univariate analysis. Cumulative hazard curves were created using the Kaplan-Meier method, and the hazards of detecting secondary transmission for each model were compared according to the study date using the log-rank test. Sensitivity analysis was conducted with participants having follow-up PCR results within 14 days available to identify either consistency of or differences in the magnitude of the effect. Missing values were removed from the analysis. All statistical analyses were performed using SPSS software version 26 (IBM Corp). Two-sided P values <.05 were considered statistically significant.Analyses comparing secondary transmission cases and test-negative cases were performed. We allowed the inclusion of multiple episodes of the same individuals because the nature of contact cases was different each time. Baseline characteristics were compared using the Mann-Whitney This study was approved by the Institutional Review Board of Yonsei University Health System Clinical Trial Centre, and the study protocol adhered to the tenets of the Declaration of Helsinki. As the study was retrospective, the Institutional Review Board waived the requirement for written informed consent from the participants .Among 1794 cases identified by the methods described above, 261 cases without age or gender information, 98 RTLS-confirmed cases that were identified more than 3 meters away from index patients, and 347 cases without follow-up test results were excluded. As a result, 1088 contact cases were included in the analysis. Among 79 cases that tested positive for SARS-CoV-2 within 14 days of exposure, 3 cases were excluded from secondary transmission owing to the presence of other sources of transmission .The baseline characteristics of all participants are presented in the following text. The mean age of the participants was 41.5 (SD 17.5) years, with 25.3% (275/1088) being male participants. Among contacts, 70.7% (769/1088) were health care workers, and among these, 6.2% (48/769) were doctors, 71.5% (550/769) were nurses, and 22.2% (171/769) were others. The percentage of those vaccinated at least once prior to contact was 83.8% (741/884), with a median of 82 (IQR 54-82) days from the last vaccination. The median contact duration was 240 (IQR 41-1675.8) minutes. Among those who were designated as index patients, 80.3% (843/1051) were health care workers. Furthermore, room sharing was confirmed in 71.9% (736/1023) of cases in the hospital. There were 63.5% (436/686) high-risk contact cases, 28.9% (198/686) intermediate-risk contact cases, and 7.6% (52/686) low-risk contact cases .P<.001), being a health care worker , being a health care worker who was an index patient , room sharing , mask wearing , and being exposed for long durations  were associated with RTLS detection. The level of exposure should be interpreted with caution, considering the large number of missing values , longer duration from the last vaccination , and using the RTLS as the contact tracing method  were associated with secondary transmission  for the secondary transmission group, with the group that tested negative for SARS-CoV-2 as a control. Variables with clinical significance and statistical significance in the univariate analysis were included in the multivariate analysis. The adjusted odds ratios (aORs) for clinically relevant variables and for variables with statistical significance in the univariate analysis revealed that male gender  additional cases that were not detected by the conventional method. The RTLS had a higher power than the conventional method for detecting high-risk contact cases that subsequently developed COVID-19. However, the technology may not be used separately from the conventional method owing to moderate sensitivity.The utility of the RTLS for tracing contacts of multiple transmissible diseases in a hospital setting has been explored in previous studies. Researchers suggested that the RTLS has moderate to high sensitivity but a low positive predictive value when compared with the conventional tracing method in detecting contact cases for droplet-transmitted diseases such as COVID-19 ,23. Our The sensitivity of the RTLS was lower when the conventional method was used as a reference . This discrepancy is associated with inherent limitations of the RTLS or conventional method. The efficacy of the RTLS is dependent on the commitment of participants to wearing tags and the frequency of the signal exciter . As was Factors indicative of prolonged exposure to the symptomatic source, such as room sharing and mask-wearing behavior, were not associated with secondary transmission, which was inconsistent with the findings of previous studies ,29. On tIt needs to be noted that contact duration was not statistically different between the 2 groups. This study has advantages in determining the significance of contact duration in the transmission of the disease owing to the implementation of methods capable of quantifying time precisely. The average time spent with confirmed patients was long, which is plausible, considering the interactions taking place between individuals in health care facilities. Maintaining strict precautions, such as frequent hand washing, would be crucial for preventing disease spread when the cumulative time surpasses a certain extent, taking into consideration previous studies that emphasized the role of fomites in disease transmission ,31. FurtThis study has some limitations that must be acknowledged. First, the assumption of index cases may not be completely accurate without a genetic analysis ,29, espeThis study showed that novel technologies, such as the RTLS, are beneficial when used as an adjunctive approach to the conventional method for contact tracing, especially when individuals share rooms with each other and under the influence of highly transmissible diseases. However, the RTLS cannot completely replace the traditional contact tracing method.


G Protein-Coupled Receptors (GPCRs) are a large family of membrane proteins with pluridimensional signaling profiles. They undergo ligand-specific conformational changes, which in turn lead to the differential activation of intracellular signaling proteins and the consequent triggering of a variety of biological responses. This conformational plasticity directly impacts our understanding of GPCR signaling and therapeutic implications, as do ligand-specific kinetic differences in GPCR-induced transducer activation/coupling or GPCR-transducer complex stability. High-resolution experimental structures of ligand-bound GPCRs in the presence or absence of interacting transducers provide important, yet limited, insights into the highly dynamic process of ligand-induced activation or inhibition of these receptors. We and others have complemented these studies with computational strategies aimed at characterizing increasingly accurate metastable conformations of GPCRs using a combination of metadynamics simulations, state-of-the-art algorithms for statistical analyses of simulation data, and artificial intelligence-based tools. This minireview provides an overview of these approaches as well as lessons learned from them towards the identification of conformational states that may be difficult or even impossible to characterize experimentally and yet important to discover new GPCR ligands. However, it is not the only element at play. Temporal analyses of ligand binding to GPCRs, as well as GPCR-induced G protein activation/coupling and β-arrestin recruitment evoked by ligands with different efficacies, demonstrate the existence of another dimension of functional bias by GPCRs that directly impacts our understanding of GPCR signaling and therapeutic implications, thus suggesting the importance of incorporating quantifications of ligand binding and signaling kinetics in modern drug discovery efforts (G Protein-Coupled Receptors (GPCRs) are important drug targets consisting of seven membrane-spanning helices connected by alternating intracellular and extracellular loops, and known for transducing extracellular signals across the cell membrane. Evidence accumulated over the past decade has suggested a pluridimensional functionality of these receptors induced by ligands with different efficacies. Specifically, ligands as diverse as photons, small molecules, and peptides can stabilize different receptor conformations which, in turn, can trigger the activation of different effectors, such as several subtypes of heterotrimeric G proteins, β-arrestins, and G protein-coupled receptor kinases . This di efforts –10.The mechanistic and kinetic bases of GPCR-mediated functional selectivity are poorly understood, notwithstanding the past decade’s technological advances in GPCR functional and structural biology. Among them are the availability of genetically-encoded biosensors for the optical detection of signals from a variety of transduction molecules in several cell types, tissues, and whole organisms , as welli.e., metadynamics (MetaD)  and macs (MSMs)  to not os (MSMs) , 38]. Th2-adrenergic receptor (β2AR) as there were no available crystal structures of opioid receptors at the time  and the distance (z) from it , using a combination of MetaD with adiabatic biased MD simulations . In part from it . The con it (2AR  (see sec it (2AR Table 1 paration . Similarparation , as wellparation . In contparation , using pparation , 70. An paration .MetaD was also recently used to propose the activation mechanisms of several prototypic class A  and clas2AR, along pre-determined activation pathways between its high-resolution inactive and active structures using adiabatic biased MD (Being able to predict the receptor conformations a drug can stabilize is considered the “holy grail” in the drug discovery field as it might inform the drug’s biological outcome. With this in mind, we developed a computational strategy to study the ligand-induced modulation of the free-energy landscape of GPCRs  see Fi to identiased MD .6.48 residue. This movement can be induced by agonists but not inverse agonists, and appears to correlate with the opening of the G protein binding site via disruption of hydrophobic packing which causes TM6 and TM5 to move away from TM3.That ligands with different efficacies shift the equilibrium between inactive and active states was recently also reported for the human adenosine A2A receptor using MetaD . Specifi2AR in the presence or absence of Gs or β-arrestin, a combination of WT-MetaD and FM was used to study the free energy landscape of activation and transducer coupling as a function of the distance between the receptor alpha-carbons of Arg3.50 and Leu6.34 and the distance between Arg3.50 and the alpha-carbons of Gαs Glu392 or β-arrestin Val71. This setup (2AR, thus providing a simple way to predict the functional bias of a ligand (MetaD was also recently used to study the interplay between GPCR ligand binding and the coupling of arrestins or G proteins . In addiis setup Table 1 a ligand .on estimates (off estimates from unbiased, standard MD simulations. To attempt more efficient predictions of dissociation rates from a GPCR, we recently designed a computational strategy that combines machine learning and infrequent MetaD (Knowledge of GPCR ligand binding kinetics, and especially drug-target residence times and involved molecular determinants, is highly desirable because it can serve as an effective guiding principle to select candidate molecules for clinical development . Howeverstimates , much lont MetaD . Specifint MetaD  to enablnt MetaD , 74 to lnt MetaD . The simnt MetaD , 65.6.52 in modulating fentanyl’s affinity and binding pose. While a recent study (Recently, MetaD was also used to investigate the dissociation of a potent drug targeting the MOR, specifically fentanyl, from the receptor . Not onlnt study  reportinnt study , 54, 77.Ligand binding kinetics is however not the only temporal aspect that is important to understand GPCR signaling. To tackle the kinetics of GPCR activation, we designed a computational strategy that uses a combination of PS-MetaD and the maximum caliber principle to not only thoroughly characterize the conformational space sampled by the receptor along its activation path, but also to derive unbiased kinetic rates from simulations with transitions accelerated by a bias potential  Figure, that weIdentifying the molecular determinants that underlie the different dynamic and kinetic behaviors of GPCRs is likely to provide fundamental information for drug discovery, and is therefore the focus of much research. However, obtaining this information is not a trivial undertaking, either experimentally or computationally. While strategies combining different variants of MetaD with state-of-the-art algorithms for statistical analyses of simulation data and/or AI-based tools have made strides in the study of GPCR ligand binding, activation, and related kinetics, the majority of studies published to date are limited to the receptors alone, although recent studies are focusing more and more on receptor complexes and the combined effect of ligand and transducer on the dynamic behavior of the receptor. To better understand the underlying principles of GPCR biased signaling, attention will probably need to be shifted more towards the appropriate characterization of the dynamic behavior of interacting signaling proteins, thus providing important insight into receptor-transducer complex stability and/or receptor-transducer activation kinetics. These studies will most likely require developing more sophisticated MetaD strategies or hybrid approaches and a community effort to disseminate best practices for MetaD simulations, as well as system setups, parameters, protocols, etc. to more expeditiously advance knowledge of GPCR dynamics and their relation to functional selectivity.MF wrote the first draft of the manuscript. LS-E and BF made the table and figure, respectively. All authors contributed to the article and approved the submitted version.


Early in the COVID-19 pandemic, it was recognized that infection with SARS-CoV-2 is associated with increased morbidity and mortality in patients with cancer; therefore, preventive vaccination in cancer survivors is expected to be particularly impactful. Heterogeneity in how a neoplastic disease diagnosis and treatment interferes with humoral and cellular immunity, however, poses a number of challenges in vaccination strategies. Herein, the available literature on the effectiveness of COVID-19 vaccines among patients with cancer is critically appraised under the lens of anti-neoplastic treatment optimization. The objective of this review is to highlight areas of uncertainty, where more research could inform future SARS-CoV-2 immunization programs and maximize benefits in the high-risk cancer survivor population, and also minimize cancer treatment deviations from standard practices. Early in the pandemic, a diagnosis of cancer was recognized as one of the top risk factors for morbidity and mortality from the infection [The ongoing global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over half a billion infections and six million deaths as of the time of this writing (nfection . AdditioThe β coronavirus family includes the Middle East respiratory syndrome (MERS) coronavirus, SARS-CoV, and SARS-CoV-2. SARS-CoV-2 is a single-stranded RNA virus with an envelope that contains glycosylated spike proteins (S) that the virus uses to bind angiotensin-converting enzyme-2 (ACE-2) and enter host cells. Cleavage of the spike protein by transmembrane serine protease-2 (TMPRSS2) generates the fragments S1 and S2. The former fragment contains the receptor binding domain that binds ACE2 and facilitates viral cellular entry via fusion between the viral and cellular membranes with the release of viral RNA in the host cell cytoplasm . AlternaA number of vaccines have been approved by regulatory agencies for use in the general population after placebo-controlled studies showed that vaccination prevents infection and complications or death from SARS-CoV-2. Among them, the mRNA 1273 and the BNT162b2 use lipid nanoparticle-encapsulated nucleoside-modified RNA that encodes the spike protein ,15. OtheA hallmark of the SARS-CoV-2 pandemic has been the emergence of variants of concern (VOCs) with mutations in the spike protein that dominated different waves of the pandemic. VOCs have variable ability to utilize the TMPRSS2 dependent versus the endocytic pathway for viral entry in the host cell, which has an impact on the types of target cells that are most vulnerable to viral infection. Specifically, S protein cleavage in the B.1.1.529 (omicron) VOC that emerged in 2021 is not as efficient as in the B.1.617.2 (delta) VOC. Consequently, this property favors omicron viral entry in cells with low expression of TMPRSS2 and leads to a milder clinical syndrome with predominantly upper respiratory symptoms . ImportaGiven the challenges with SARS-CoV-2 infection in patients with cancer, as well as the heterogeneous effect of cancer treatments on humoral and cellular immunity, it is important to clarify key areas where future research in this population can be the most impactful. In this review, the critical literature on vaccine effectiveness in cancer patients is summarized and three areas of uncertainty are pointed out. First, gaps in knowledge regarding humoral immune responses following vaccination for SARS-CoV-2 or infection in the cancer patient population are highlighted. Second, the effectiveness of cellular immunity to prevent severe disease and complications from SARS-CoV-2 VOCs in cancer patients within adequate, or waning, humoral immunity is reviewed. Finally, the need to delay or modify antineoplastic treatment and the optimal duration of interruption for patients with cancer who have been vaccinated is discussed.A number of observational studies indicated that patients with cancer, especially those with hematological malignancies or those receiving B cell depleting therapies, have reduced or no antibody responses to mRNA-based vaccination for SARS-CoV-2. A longitudinal study over six months looked at IgG antibodies against the spike protein in patients with solid tumors and hematological malignancies following vaccination with mRNA-1273 or BNT162b2 vaccines . Other sDespite these important data, a number of unanswered questions remain. In the study by Figueiredo et al. , the ranNatural infection with SARS-CoV-2 or vaccination induces antibodies that neutralize key proteins in the viral envelope. Importantly, the vaccines are designed to raise humoral responses against the spike protein of SARS-CoV-2. However, mutations in the spike protein during viral replication increase variant fitness to evade neutralizing antibodies. The effectiveness of vaccines at preventing infection following exposure to SARS-CoV-2 delta or omicron VOC is reduced for vaccines that were designed based on the index virus. On the other hand, both natural infection and vaccination also induce adaptive immunity that is maintained by memory T cells. Intriguingly, pre-existing T cell-based immunity was detected in 28–50% of individuals with no prior infection or vaccination history .Sette et al. suggested distinct kinetics of immunological response to SARS-CoV-2 that correlate with the clinical course of the disease . In theiFH) cell responses [The importance of cellular immunity following vaccination for SARS-CoV-2 to prevent severe disease in patients with cancer and patients who receive antineoplastic treatments is less-well studied. The diagnosis of hematological cancer, as well as treatment with B cell depleting drugs, are well established predictive factors for SARS-CoV-2 morbidity and mortality, paired with a compromised ability of the hosts to neutralize the virus with antibodies ,42. It iesponses . Given tMycobacterium Tuberculosis spectrum of disease by measuring IFNγ production following exposure of lymphocytes to M tuberculosis antigens [In cancer patients, the CAPTURE study prospectively studied the humoral and cellular adaptive responses to two doses of the BNT162b2 or AZD1222 vaccines administered 12 weeks apart . Patientantigens . IGRAs hantigens , as wellantigens . In COVIantigens ,51, evenantigens . A similantigens .Increased morbidity and mortality from SARS-CoV-2 infection in patients with cancer early in the pandemic necessitated the modification of treatment protocols with interruptions and delays in systemic treatments, radiation courses, and surgeries. In a single institution study  that looRadiation therapy interruptions are detrimental for cancer prognosis, given the ability of the cancer cells to repopulate during missing fractions. Ying et al. reported that, among patients who interrupted definitive radiation therapy for solid cancer diagnosis, those who discontinued radiotherapy had increased mortality (42.9%) compared to those who completed the radiotherapy despite interruption (6.2%) . An incrIn a large study from France that was undertaken early in the pandemic, a SARS-CoV-2 diagnosis led to the interruption or discontinuation of systemic cancer treatment in 39% of the 1092 cases . InteresThe SARS-CoV-2 pandemic has had a disproportionately negative impact on the quality of life and prognosis of patients with cancer and their families. The cancer survivor population has heterogeneous vulnerability to the infection that largely depends on the variability of immune system deficits imposed by the underlying malignancy, the various antineoplastics that are administered, and supportive treatments such as corticosteroids. Similarly, protective immunity that is induced from vaccination or natural infection with SARS-CoV-2 can be variable in patients with solid tumors or hematologic malignancies, as has been previously demonstrated for the seasonal flu  Therefor


Genitourinary tumor was one of the most frequent malignant tumors in the world and has received a lot of attention due to its high incidence and fatality rates . The tumImpressively, we have chosen five outstanding publications from a large number of articles for this Research Topic. Four of them offered biomarkers to predict clinical outcomes, while another examined the connection between ncRNA and autophagy and its significance in bladder cancer (BC). We expect that these findings will shed fresh light on the features of TME as well as the treatment and prognosis of genitourinary malignancies.via modulating related genes. aimed to identify the regulatory function of lncRNAs in ferroptosis and establish a theoretical foundation for their use in clear cell renal cell carcinoma (ccRCC). They constructed an ferroptosis-related lncRNAs model , and reported that this model played a significant role in the prognosis and immune microenvironment of ccRCC patients.Ferroptosis is a promising anticancer therapeutic target, and lncRNAs can influence ferroptosis N6-methyladenosine (m6A) is the most prevalent type of ncRNA-specific internal modification seen in eukaryotes, and it has a significant impact on mRNA stabilization, translations, and splice sought to evaluate five m6A-lncRNAs model  of BC patients, and discovered that this model was important in predicting the effect of immunotherapy and prognosis, as well as demonstrating its potential biological function through pathway enrichment.in vitro to build a predictive pyroptosis-related lncRNAs (PRLs) model  and two ceRNA pathways. The findings suggested that PRLs played a crucial role in immune cell infiltration and anti-tumor drug sensitivity in BC patients, and that regulatory axis OCIAD1-AS1/miR-141-3p/GPM6B and OCIAD1-AS1/miR-200a-3p/AKAP11 may perform a contribution to the growth of BC.Pyroptosis is a host cell death mechanism triggered by a variety of microbial infections and non-infectious stimuli, with caspase-1 reliance being a distinguishing feature. Due to the tight association between pyroptosis and human cancer reported in a vast number of publications used adequate bioinformatics analysis and initial RT-qPCR confirmation Together with progress of RNA-sequencing, miRNA editing events have been shown to play a key role in many cancers examined the mRNA and miRNA transcriptomes of 12 recurrent BC patients and 13 primary BC patients to identify and compare miRNA editing events. The research revealed that miR-154-5p was highly altered in recurrent BC and was related to patient prognosis, implying that A-to-I editing of miR-154-5p might be a viable target for BC therapy. Additionally, miR-154 editing events may be important in the categorization of BC consensus molecular subtypes, allowing existing therapy options to be broadened and personalized.Lastly highlighted recent results on ncRNAs and its association with numerous physiological functions such as autophagy, as well as its relevance to the pathophysiology of BC. Several researches already have proven the role of ncRNAs in modulating metastatic capability and deliberating medication sensitivity in BC. The particular functions of ncRNA in BC growth and their clinical importance, however, are still being researched. The importance of ncRNA would be described in full using new cutting-edge technologies, and prospective translational usefulness for BC patients’ management will be demonstrated. Additionally, targeting both ncRNAs and autophagy simultaneously may be a promising treatment strategy for BC.This Research Topic and existing research of ncRNAs in genitourinary tumor still have various limitations. First, many studies in this Research Topic are just the re-analysis of public databases, lacking the validation of relevant cell experiments and clinical samples, which makes the conclusions need to be carefully considered. Second, as compared to mRNAs, lncRNAs are often poorly conserved across species. Therapeutic techniques based on cellular and animal models are still far from clinical applicability and may need more study. Finally, the enrichment mechanism of ncRNAs in tumor phenotype and immunological invasion features has to be confirmed. Many recent investigations are still in the theoretical stage due to the aforementioned restrictions. These three characteristics should be given more consideration in future research.