Background
Combining radioactive colloids and a near‐infrared (NIR) fluorophore permits preoperative planning and intraoperative localization of deeply located sentinel lymph nodes (SLNs) with direct ...optical guidance by a single lymphatic tracer. The aim of this clinical trial was to evaluate and optimize a hybrid NIR fluorescence and radioactive tracer for SLN detection in patients with breast cancer.
Methods
Patients with breast cancer undergoing SLN biopsy were enrolled. The day before surgery, a periareolar injection of indocyanine green (ICG)–99mTc‐radiolabelled nanocolloid was administered and a lymphoscintigram acquired. Blue dye was injected immediately before surgery. Intraoperative SLN localization was performed using a γ probe and the Mini‐FLARETM NIR fluorescence imaging system. Patients were divided into two dose groups, with one group receiving twice the particle density of ICG and nanocolloid, but the same dose of radioactive 99mTc.
Results
Thirty‐two patients were enrolled in the trial. At least one SLN was identified before and during operation. All 48 axillary SLNs could be detected by γ tracing and NIR fluorescence imaging, but only 42 of them stained blue. NIR fluorescence imaging permitted detection of lymphatic vessels draining to the SLN up to 29 h after injection. Doubling the particle density did not yield a difference in fluorescence intensity (median 255 (range 98–542) versus 284 (90–921) arbitrary units; P = 0.590) or signal‐to‐background ratio (median 5·4 (range 3·0–15·4) versus 4·9 (3·5–16·3); P = 1·000) of the SLN.
Conclusion
The hybrid NIR fluorescence and radioactive tracer permitted accurate preoperative and intraoperative detection of the SLNs in patients with breast cancer. Registration number: NTR3685 (Netherlands Trial Register; http://www.trialregister.nl).
Go green
Purpose
Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to ...evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-
99m
Tc-nancolloid was evaluated in a large cohort of patients.
Patients and methods
A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-
99m
Tc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (
n
= 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR).
Results
A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (
n
= 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22–78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced.
Conclusion
With ICG-
99m
Tc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.
Bacterial infections have always been, and still are, a major global healthcare problem. For accurate treatment it is of upmost importance that the location(s), severity, type of bacteria, and ...therapeutic response can be accurately staged. Similar to the recent successes in oncology, tracers specific for molecular imaging of the disease may help advance patient management. Chemical design and bacterial targeting mechanisms are the basis for the specificity of such tracers. The aim of this review is to provide a comprehensive overview of the molecular imaging tracers developed for optical and nuclear identification of bacteria and bacterial infections. Hereby we envision that such tracers can be used to diagnose infections and aid their clinical management. From these compounds we have set out to identify promising targeting mechanisms and select the most promising candidates for further development.
Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas
. Novel medicines and vaccines are urgently needed
. ...An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3-10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4
T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.
ABSTRACT We report on radio and X-ray observations of the only known repeating Fast Radio Burst (FRB) source, FRB 121102. We have detected six additional radio bursts from this source: five with the ...Green Bank Telescope at 2 GHz, and one at 1.4 GHz with the Arecibo Observatory, for a total of 17 bursts from this source. All have dispersion measures consistent with a single value (∼559 pc cm−3) that is three times the predicted maximum Galactic contribution. The 2 GHz bursts have highly variable spectra like those at 1.4 GHz, indicating that the frequency structure seen across the individual 1.4 and 2 GHz bandpasses is part of a wideband process. X-ray observations of the FRB 121102 field with the Swift and Chandra observatories show at least one possible counterpart; however, the probability of chance superposition is high. A radio imaging observation of the field with the Jansky Very Large Array at 1.6 GHz yields a 5 upper limit of 0.3 mJy on any point-source continuum emission. This upper limit, combined with archival Wide-field Infrared Survey Explorer 22 m and IPHAS H surveys, rules out the presence of an intervening Galactic H ii region. We update our estimate of the FRB detection rate in the PALFA survey to be FRBs sky−1 day−1 (95% confidence) for peak flux density at 1.4 GHz above 300 mJy. We find that the intrinsic widths of the 12 FRB 121102 bursts from Arecibo are, on average, significantly longer than the intrinsic widths of the 13 single-component FRBs detected with the Parkes telescope.
Antibodies can prevent malaria by neutralizing the infectious Plasmodium falciparum sporozoites (SPZ) before they establish an infection in the liver. Circumsporozoite protein (CSP), the most ...abundant surface protein of SPZ is the leading candidate for passive (and subunit) immunization approaches against malaria. Comprehensive assessment of the parasite-inhibitory capacity of anti-CSP monoclonal antibodies (mAbs) is an important step in advancing CSP-based immunization strategies. In this study, we employed a quantitative imaging-based motility assay to quantify the effect of anti-CSP mAbs on SPZ motility, both in vitro and in human skin.Our assay provided a quantitative measure of mAb parasite-inhibitory capacity through measurement of the half-maximal motility inhibitory concentration (IC
) value for anti-CSP mAbs (IC
2A10: 24 nM, IC
3SP2: 71 nM). We found a sevenfold discrepancy between the IC
and the binding saturation concentration measured by ELISA, possibly related to the observed shedding of CSP-mAb complexes during SPZ movement. In a subset of SPZ (5%), in vitro motility was unaffected by the presence of 2A10 while 3SP2 was able to completely block movement. In our ex vivo skin explant model, SPZ proved less susceptible to anti-CSP mAbs compared to SPZ in an in vitro environment. By quantitatively assessing motility, we created a valuable tool that can be used for comprehensive assessment of anti-CSP mAb potency. Insight that will help deepen our understanding of anti-CSP mAb potency and guide selection of the most promising anti-CSP mAbs for downstream clinical development.
ABSTRACT We report the discovery of two long-term intermittent radio pulsars in the ongoing Pulsar Arecibo L-Band Feed Array survey. Following discovery with the Arecibo Telescope, extended ...observations of these pulsars over several years at Jodrell Bank Observatory have revealed the details of their rotation and radiation properties. PSRs J1910+0517 and J1929+1357 show long-term extreme bimodal intermittency, switching between active (ON) and inactive (OFF) emission states and indicating the presence of a large, hitherto unrecognized underlying population of such objects. For PSR J1929+1357, the initial duty cycle was fON = 0.008, but two years later, this changed quite abruptly to fON = 0.16. This is the first time that a significant evolution in the activity of an intermittent pulsar has been seen, and we show that the spin-down rate of the pulsar is proportional to the activity. The spin-down rate of PSR J1929+1357 is increased by a factor of 1.8 when it is in active mode, similar to the increase seen in the other three known long-term intermittent pulsars. These discoveries increase the number of known pulsars displaying long-term intermittency to five. These five objects display a remarkably narrow range of spin-down power ( ) and accelerating potential above their polar caps. If confirmed by further discoveries, this trend might be important for understanding the physical mechanisms that cause intermittency.
Background
The extent of pelvic lymphadenectomy (PLND) as part of radical cystectomy (RC) for bladder cancer (BC) remains unclear. Sentinel‐based and lymphangiographic approaches could lead to ...reduced morbidity without sacrificing oncologic safety.
Objective
To evaluate the feasibility and diagnostic value of fluorescence‐guided template sentinel region dissection (FTD) using a handheld near‐infrared fluorescence (NIRF) camera in open radical cystectomy.
Design, Setting, and Participants
After peritumoral cystoscopic injection of indocyanine green (ICG) 21 patients underwent open RC with FTD due to BC between June 2019 and June 2021. Intraoperatively, the FIS‐00 Hamamatsu Photonics® NIRF camera was used to identify and resect fluorescent template sentinel regions (FTRs) followed by extended pelvic lymphadenectomy (ePLND) as oncological back‐up.
Outcome Measurement and Statistical Analysis
Descriptive analysis of positive and negative results per template region.
Results and Limitations
FTRs were identified in all 21 cases. Median time (range) from ICG injection to fluorescence detection was 75 (55–125) minutes. On average (SD), 33.4 (9.6) lymph nodes were dissected per patient. Considering template regions as the basis of analysis, 67 (38.3%) of 175 resected regions were NIRF‐positive, with 13 (7.4%) regions harboring lymph node metastases. We found no metastatic lymph nodes in NIRF‐negative template regions. Outside the standard template, two NIRF‐positive benign nodes were identified.
Conclusion
The concept of NIRF‐guided FTD proved for this group all lymph node metastases to be found in NIRF‐positive template regions. Pending validation in a larger collective, resection of approximately 40% of standard regions may be sufficient and may result in less morbidity.
A repeating fast radio burst Spitler, L G; Scholz, P; Hessels, J W T ...
Nature (London),
03/2016, Letnik:
531, Številka:
7593
Journal Article
Recenzirano
Odprti dostop
Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find ...additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.
Purpose
The aim of the present study is to investigate the impact of the near-infrared (NIRF) technology with indocyanine green (ICG) in robotic urologic surgery by performing a systematic literature ...review and to provide evidence-based expert recommendations on best practices in this field.
Methods
All English language publications on NIRF/ICG-guided robotic urologic procedures were evaluated. We followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement to evaluate PubMed
®
, Scopus
®
and Web of Science™ databases (up to April 2019). Experts in the field provided detailed pictures and intraoperative video-clips of different NIRF/ICG-guided robotic surgeries with recommendations for each procedure. A unique QRcode was generated and linked to each underlying video-clip. This new exclusive feature makes the present the first “dynamic paper” that merges text and figure description with their own video providing readers an innovative, immersive, high-quality and user-friendly experience.
Results
Our electronic search identified a total of 576 papers. Of these, 36 studies included in the present systematic review reporting the use of NIRF/ICG in robotic partial nephrectomy (
n
= 13), robotic radical prostatectomy and lymphadenectomy (
n
= 7), robotic ureteral re-implantation and reconstruction (
n
= 5), robotic adrenalectomy (
n
= 4), robotic radical cystectomy (
n
= 3), penectomy and robotic inguinal lymphadenectomy (
n
= 2), robotic simple prostatectomy (
n
= 1), robotic kidney transplantation (
n
= 1) and robotic sacrocolpopexy (
n
= 1).
Conclusion
NIRF/ICG technology has now emerged as a safe, feasible and useful tool that may facilitate urologic robotic surgery. It has been shown to improve the identification of key anatomical landmarks and pathological structures for oncological and non-oncological procedures. Level of evidence is predominantly low. Larger series with longer follow-up are needed, especially in assessing the quality of the nodal dissection and the feasibility of the identification of sentinel nodes and the impact of these novel technologies on long-term oncological and functional outcomes.
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