Active surveillance of low-grade prostate cancer using the SurACaP Criteria: A multi-institutional series with a median follow-up of 10years.

PURPOSE: To report on the oncological outcomes of active surveillance (AS) in low-grade prostate cancer (PCa) patients using the French SurACaP protocol, with a focus on long-term outcomes. METHODS: This multicenter study recruited patients with low-grade PCa between 2007 and 2013 in four referral centers in France. The cohort included patients meeting the SurACaP inclusion criteria, i.e., aged ≤75years, with low-grade PCa (i.e., ISUP 1), clinical stage T1c/T2a, PSA ≤10ng/mL and ≤3 positive cores and tumor length ≤3mm per core. The SurACaP protocol included a digital rectal examination every six months, PSA level measurement every three months for the first two years after inclusion and twice a year thereafter, a confirmatory biopsy in the first year after inclusion, and then follow-up biopsy every two years or if disease progression was suspected. Multiparametric magnetic resonance imaging (mpMRI) was progressively included over the study period. RESULTS: A total of 86 consecutive patients were included, with a median follow-up of 10.6 years. Only one patient developed metastases and died of PCa. The estimated rates of grade reclassification and treatment-free survival at 15 years were 53.4% and 21.2%, respectively. A negative mpMRI at baseline and a negative confirmatory biopsy were significantly associated with a lower risk of disease progression (P<0.05). CONCLUSIONS: AS using the French SurACaP protocol is a safe and valuable strategy for patients with low-risk PCa, with excellent oncological outcomes after more than 10 years' follow-up. Future studies are crucial to broaden the inclusion criteria and develop a personalized, risk based AS protocol with the aim of de-escalating follow-up examinations. LEVEL OF EVIDENCE: Grade 4.

Trap-integrated fluorescence detection with silicon photomultipliers for sympathetic laser cooling in a cryogenic Penning trap.

We present a fluorescence-detection system for laser-cooled 9Be+ ions based on silicon photomultipliers (SiPMs) operated at 4 K and integrated into our cryogenic 1.9 T multi-Penning-trap system. Our approach enables fluorescence detection in a hermetically sealed cryogenic Penning-trap chamber with limited optical access, where state-of-the-art detection using a telescope and photomultipliers at room temperature would be extremely difficult. We characterize the properties of the SiPM in a cryocooler at 4 K, where we measure a dark count rate below 1 s-1 and a detection efficiency of 2.5(3)%. We further discuss the design of our cryogenic fluorescence-detection trap and analyze the performance of our detection system by fluorescence spectroscopy of 9Be+ ion clouds during several runs of our sympathetic laser-cooling experiment.

BASE-STEP: A transportable antiproton reservoir for fundamental interaction studies.

Currently, the world's only source of low-energy antiprotons is the AD/ELENA facility located at CERN. To date, all precision measurements on single antiprotons have been conducted at this facility and provide stringent tests of fundamental interactions and their symmetries. However, magnetic field fluctuations from the facility operation limit the precision of upcoming measurements. To overcome this limitation, we have designed the transportable antiproton trap system BASE-STEP to relocate antiprotons to laboratories with a calm magnetic environment. We anticipate that the transportable antiproton trap will facilitate enhanced tests of charge, parity, and time-reversal invariance with antiprotons and provide new experimental possibilities of using transported antiprotons and other accelerator-produced exotic ions. We present here the technical design of the transportable trap system. This includes the transportable superconducting magnet, the cryogenic inlay consisting of the trap stack and detection systems, and the differential pumping section to suppress the residual gas flow into the cryogenic trap chamber.

Ultra-thin polymer foil cryogenic window for antiproton deceleration and storage.

We present the design and characterization of a cryogenic window based on an ultra-thin aluminized biaxially oriented polyethylene terephthalate foil at T < 10 K, which can withstand a pressure difference larger than 1 bar at a leak rate <1×10-9 mbar l/s. Its thickness of ∼1.7 µm makes it transparent to various types of particles over a broad energy range. To optimize the transfer of 100 keV antiprotons through the window, we tested the degrading properties of different aluminum coated polymer foils of thicknesses between 900 and 2160 nm, concluding that 1760 nm foil decelerates antiprotons to an average energy of 5 keV. We have also explicitly studied the permeation as a function of coating thickness and temperature and have performed extensive thermal and mechanical endurance and stress tests. Our final design integrated into the experiment has an effective open surface consisting of seven holes with a diameter of 1 mm and will transmit up to 2.5% of the injected 100 keV antiproton beam delivered by the Antiproton Decelerator and Extra Low ENergy Antiproton ring facility of CERN.

BASE-high-precision comparisons of the fundamental properties of protons and antiprotons.

Abstract: The BASE collaboration at the antiproton decelerator/ELENA facility of CERN compares the fundamental properties of protons and antiprotons with ultra-high precision. Using advanced Penning trap systems, we have measured the proton and antiproton magnetic moments with fractional uncertainties of 300 parts in a trillion (p.p.t.) and 1.5 parts in a billion (p.p.b.), respectively. The combined measurements improve the resolution of the previous best test in that sector by more than a factor of 3000. Very recently, we have compared the antiproton/proton charge-to-mass ratios with a fractional precision of 16 p.p.t., which improved the previous best measurement by a factor of 4.3. These results allowed us also to perform a differential matter/antimatter clock comparison test to limits better than 3%. Our measurements enable us to set limits on 22 coefficients of CPT- and Lorentz-violating standard model extensions (SME) and to search for potentially asymmetric interactions between antimatter and dark matter. In this article, we review some of the recent achievements and outline recent progress towards a planned improved measurement of the antiproton magnetic moment with an at least tenfold improved fractional accuracy.

Urachal carcinoma: a large retrospective multicentric study from the French Genito-Urinary Tumor Group.

Introduction: Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC. Material and Methods: data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020. Results: The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment. Conclusion: UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.

A high-Q superconducting toroidal medium frequency detection system with a capacitively adjustable frequency range >180 kHz.

We describe a newly developed polytetrafluoroethylene/copper capacitor driven by a cryogenic piezoelectric slip-stick stage and demonstrate with the chosen layout cryogenic capacitance tuning of ≈60 pF at ≈10 pF background capacitance. Connected to a highly sensitive superconducting toroidal LC circuit, we demonstrate tuning of the resonant frequency between 345 and 685 kHz, at quality factors Q > 100 000. Connected to a cryogenic ultra low noise amplifier, a frequency tuning range between 520 and 710 kHz is reached, while quality factors Q > 86 000 are achieved. This new device can be used as a versatile image current detector in high-precision Penning-trap experiments or as an LC-circuit-based haloscope detector to search for the conversion of axion-like dark matter to radio-frequency photons. This new development increases the sensitive detection bandwidth of our axion haloscope by a factor of ≈1000.

Direct measurement of the 3He+ magnetic moments.

Helium-3 has nowadays become one of the most important candidates for studies in fundamental physics1-3, nuclear and atomic structure4,5, magnetometry and metrology6, as well as chemistry and medicine7,8. In particular, 3He nuclear magnetic resonance (NMR) probes have been proposed as a new standard for absolute magnetometry6,9. This requires a high-accuracy value for the 3He nuclear magnetic moment, which, however, has so far been determined only indirectly and with a relative precision of 12 parts per billon10,11. Here we investigate the 3He+ ground-state hyperfine structure in a Penning trap to directly measure the nuclear g-factor of 3He+ [Formula: see text], the zero-field hyperfine splitting [Formula: see text] Hz and the bound electron g-factor [Formula: see text]. The latter is consistent with our theoretical value [Formula: see text] based on parameters and fundamental constants from ref. 12. Our measured value for the 3He+ nuclear g-factor enables determination of the g-factor of the bare nucleus [Formula: see text] via our accurate calculation of the diamagnetic shielding constant13 [Formula: see text]. This constitutes a direct calibration for 3He NMR probes and an improvement of the precision by one order of magnitude compared to previous indirect results. The measured zero-field hyperfine splitting improves the precision by two orders of magnitude compared to the previous most precise value14 and enables us to determine the Zemach radius15 to [Formula: see text] fm.

A 16-parts-per-trillion measurement of the antiproton-to-proton charge-mass ratio.

The standard model of particle physics is both incredibly successful and glaringly incomplete. Among the questions left open is the striking imbalance of matter and antimatter in the observable universe1, which inspires experiments to compare the fundamental properties of matter/antimatter conjugates with high precision2-5. Our experiments deal with direct investigations of the fundamental properties of protons and antiprotons, performing spectroscopy in advanced cryogenic Penning trap systems6. For instance, we previously compared the proton/antiproton magnetic moments with 1.5 parts per billion fractional precision7,8, which improved upon previous best measurements9 by a factor of greater than 3,000. Here we report on a new comparison of the proton/antiproton charge-to-mass ratios with a fractional uncertainty of 16 parts per trillion. Our result is based on the combination of four independent long-term studies, recorded in a total time span of 1.5 years. We use different measurement methods and experimental set-ups incorporating different systematic effects. The final result, [Formula: see text], is consistent with the fundamental charge-parity-time reversal invariance, and improves the precision of our previous best measurement6 by a factor of 4.3. The measurement tests the standard model at an energy scale of 1.96 × 10-27 gigaelectronvolts (confidence level 0.68), and improves ten coefficients of the standard model extension10. Our cyclotron clock study also constrains hypothetical interactions mediating violations of the clock weak equivalence principle (WEPcc) for antimatter to less than 1.8 × 10-7, and enables the first differential test of the WEPcc using antiprotons11. From this interpretation we constrain the differential WEPcc-violating coefficient to less than 0.030.

[Does the announcement of cancer at the time of Non Muscle-Invasive Bladder Cancer diagnosis affect quality of life and adherence of patients? Data from the French prospective cohort VICAN]. / L'annonce du cancer au diagnostic de Tumeur de vessie non infiltrant le muscle modifie-t-elle la qualité de vie et l'observance des patients ? Données de la cohorte prospective française VICAN.

INTRODUCTION: The information provided at the time of diagnosis of Non Muscle-Invasive Bladder Cancer (NMIBC) is highly variable. Well-informed patient are more involved in shared decisions. The objective of our study was to assess the information perceived by the patient at the time of NMIBC diagnosis and its impact on quality of life. METHODS: The VICAN french cohort involved a representative sample of 4174 cancer patients and 5 years survivors. Patients reported outcomes (PROs) were collected by phone and self-questionnaire. Among the 118 NMIBC patients, the term used to define the pathology at diagnosis was prospectively evaluated. The impact on quality of life (using SF-12, EORTC-QLQ-C30 and HAD scale) and on adherence to the care protocol (endoscopic monitoring) has been assessed. RESULTS: Only 26.8% of patients reported hearing the word « Cancer ¼ at the time of NMIBC diagnosis. Conversely, 73.2% of them reported others terms, including « Tumor ¼ (22%), « Polyp ¼ (24%), and « Carcinoma ¼ (17.1%). There was no difference in terms of physical, mental quality of life and anxiety, regardless of the term used. Adherence to the follow-up endoscopic protocol was better in the group of patients hearing the word "Cancer". CONCLUSION: Three quarters of patients treated for NMIBC did not integrate the concept of « Cancer ¼ at the time of diagnosis. Quality of life and anxiety did not differ significantly depending on the term used at diagnosis. However, adherence to care protocol appears to be higher when using the word "Cancer". LEVEL OF EVIDENCE: 3.

Sympathetic cooling of a trapped proton mediated by an LC circuit.

Efficient cooling of trapped charged particles is essential to many fundamental physics experiments1,2, to high-precision metrology3,4 and to quantum technology5,6. Until now, sympathetic cooling has required close-range Coulomb interactions7,8, but there has been a sustained desire to bring laser-cooling techniques to particles in macroscopically separated traps5,9,10, extending quantum control techniques to previously inaccessible particles such as highly charged ions, molecular ions and antimatter. Here we demonstrate sympathetic cooling of a single proton using laser-cooled Be+ ions in spatially separated Penning traps. The traps are connected by a superconducting LC circuit that enables energy exchange over a distance of 9 cm. We also demonstrate the cooling of a resonant mode of a macroscopic LC circuit with laser-cooled ions and sympathetic cooling of an individually trapped proton, reaching temperatures far below the environmental temperature. Notably, as this technique uses only image-current interactions, it can be easily applied to an experiment with antiprotons1, facilitating improved precision in matter-antimatter comparisons11 and dark matter searches12,13.

Development of a Manually Operated Communication System (MOCS) for patients in intensive care units.

Nonvocal alert patients in the intensive care unit (ICU) setting often struggle to communicate due to inaccessible or unavailable tools for augmentative and alternative communication. Innovation of a hand-operated non-touchscreen communication system for nonvocal ICU patients was guided by design concepts including speech output, simplicity, and flexibility. A novel communication tool, the Manually Operated Communication System (MOCS), was developed for use in intensive care settings with patients unable to speak. MOCS is a speech-output technology designed for patients with manual dexterity impairments preventing legible writing. MOCS may have the potential to improve communication for nonvocal patients with limited manual dexterity.

[Tumor vaccines-therapeutic vaccination against cancer]. / Tumorvakzinierung ­ therapeutische Vakzinierung gegen Krebs.

Tumor cells always exhibit differences to normal cells. These differences can be recognized by the immune system, enabling the destruction of tumor cells by T cells, as was impressively demonstrated by the success of immune checkpoint inhibition, e.g., in malignant melanoma. Many cancers, however, do not respond to this kind of therapy. In these cases, vaccination against tumor antigens could be very helpful. Nevertheless, all of the efforts made in this respect during the past 30 years have been virtually futile. With current knowledge and technology there is new hope.

Lumbar drain complications in patients undergoing fenestrated or branched endovascular aortic aneurysm repair: Development of an institutional protocol for lumbar drain management.

OBJECTIVE: Lumbar drain placement with cerebrospinal fluid (CSF) drainage is an effective adjunct for reducing the risk of spinal cord ischemia in patients undergoing complex aortic aneurysm repair. However, lumbar drain placement is a challenging procedure with potential for significant complications. We sought to characterize complications of lumbar drain placement in a large, single-center experience of patients who underwent fenestrated or branched endovascular aneurysm repair (F/BEVAR). METHODS: All patients who underwent F/BEVAR and attempted lumbar drain placement from 2010 to 2019 were retrospectively reviewed. All lumbar drains were placed by four cardiovascular anesthesiologists who compose the complex aortic anesthesia team. Lumbar drain placement was guided by a set protocol and used whenever the aortic stent graft coverage was planned to extend more proximal than 40 mm above the celiac artery. Details relating to lumbar drain placement, management, and frequency and type of associated complications were characterized. RESULTS: During the study period, 256 patients underwent F/BEVAR, of whom 100 (39%) were planned for lumbar drain placement. Successful placement occurred in 98 (98%) of the cases. All lumbar drains were placed before induction of general anesthesia, using fluoroscopy guidance in 28 cases (28%). The most common level of placement was L4-5 (n = 42 [42%]). The majority (n = 82 [82%]) were left in place ≤48 hours; 21% were removed during the first 24 hours, and 61% were removed between 24 and 48 hours. Nonfunctionality was the most common complication, occurring in 16 (16%) patients. Catheter dislodgment or fracture, CSF leak, and postdural puncture headache were observed in 4 (4%), 7 (7%), and 4 (4%) patients, respectively. The most common bleeding complication was the presence of asymptomatic blood in the CSF (n = 11 [11%]), whereas subarachnoid hemorrhage combined with intraventricular hemorrhage occurred in three patients (3%); none of these patients required surgical drainage or intervention. No infectious complications were observed. CONCLUSIONS: Lumbar drain placement for CSF drainage is a commonly employed adjunct to prevent spinal cord ischemia in F/BEVAR. Our experience demonstrates that lumbar drain placement can be performed successfully but is associated with a significant rate of nonfunctionality and a diverse range of complications that, fortunately, do not commonly have significant long-term sequelae.

Airway Management in Critical Illness: An Update.

Expertise in airway management is a vital skill for any provider caring for critically ill patients. A growing body of literature has identified the stark difference in periprocedural outcomes of elective intubation in the operating room when compared with emergency intubation in the ICU. A number of strategies to reduce the morbidity and mortality associated with airway management in the critically ill have been described. In this review, we provide an updated framework for airway assessment before direct laryngoscopy and video laryngoscopy, and use of newer pharmacologic agents; comment on current concepts in tracheal intubation in the ICU; and address human factors around critical decision-making during ICU airway management.

[Safety of Hyperthermic IntraVEsical Chemotherapy (HIVEC) for BCG Unresponsive Non-Muscle Invasive Bladder Cancer Patients]. / Tolérance de la thermo-chimiothérapie par HIVEC® chez les patients réfractaires au BCG.

INTRODUCTION: There is increasing evidence that Hyperthermic Intravesical Chemotherapy is an effective treatment for non-muscle invasive bladder cancer (NMIBC). HIVEC (COMBAT BRS system) is an innovative hyperthermia delivering device. The aim of our study is to evaluate tolerance and safety of HIVEC in patients with BCG-refractory NMIBC. MATERIALS AND METHODS: In this study, we included 22 patients between January 2017 and April 2018. The treatment consisted in a weekly instillation of Hyperthermic Mitomycin for a total of 6 weeks, with a follow-up every 3 months. In order to evaluate the tolerance, patients filled a questionnaire before each instillation. We analyzed collected data to evaluate safety and efficiency of the treatment after one year. RESULTS: Among 22 patients included, no patient suffered from severe side effects. The minor side effects reported were : urinary urgency (40,1 %), urinary pain (40,1%), macroscopic hematuria (4,5%). The IPSS score didn't significantly varied before and after instillations (mean IPSS: 10.8 versus 10.1, p=0.77). The mean follow-up was 11.2 months. The recurrence rate was 27,3% with an average time to recurrence of 7.36 months. Two patients (9.1%) presented a progression to muscle-invasive disease. Four patients (18,2%) had a radical cystectomy. CONCLUSION: Hyperthermic Mitomycin using the HIVEC® device is a rather safe and well tolerated treatment. Efficiency remains partial as 27.3% of patients experienced recurrence during the first year. These data should be confirmed by prospective multicentric studies.

Direct limits on the interaction of antiprotons with axion-like dark matter.

Astrophysical observations indicate that there is roughly five times more dark matter in the Universe than ordinary baryonic matter1, and an even larger amount of the Universe's energy content is attributed to dark energy2. However, the microscopic properties of these dark components remain unknown. Moreover, even ordinary matter-which accounts for five per cent of the energy density of the Universe-has yet to be understood, given that the standard model of particle physics lacks any consistent explanation for the predominance of matter over antimatter3. Here we present a direct search for interactions of antimatter with dark matter and place direct constraints on the interaction of ultralight axion-like particles (dark-matter candidates) with antiprotons. If antiprotons have a stronger coupling to these particles than protons do, such a matter-antimatter asymmetric coupling could provide a link between dark matter and the baryon asymmetry in the Universe. We analyse spin-flip resonance data in the frequency domain acquired with a single antiproton in a Penning trap4 to search for spin-precession effects from ultralight axions, which have a characteristic frequency governed by the mass of the underlying particle. Our analysis constrains the axion-antiproton interaction parameter to values greater than 0.1 to 0.6 gigaelectronvolts in the mass range from 2 × 10-23 to 4 × 10-17 electronvolts, improving the sensitivity by up to five orders of magnitude compared with astrophysical antiproton bounds. In addition, we derive limits on six combinations of previously unconstrained Lorentz- and CPT-violating terms of the non-minimal standard model extension5.

Necrotizing enterocolitis after intravitreal bevacizumab in an infant with Incontinentia Pigmenti - a case report.

BACKGROUND: Incontinentia Pigmenti is a rare disease affecting multiple organs. Fifty of patients show affection of the eye with retinopathy and possible amaurosis being the worst outcome. Treatment has commonly been panretinal laser coagulation but intravitreal application of bevacizumab as VEGF-inhibitor has shown to effectively suppress retinal neovascularization. CASE PRESENTATION: A six-week-old female infant with Incontinentia Pigmenti developed a foudroyant necrotizing enterocolitis shortly after intravitreal injection of bevazicumab due to a retinopathy with impending tractional detachment of the left eye. Since the onset of abdominal symptoms occurred immediately after the intravitreal application, a link between the two events seemed likely. Sequential analyses of the VEGF serum concentrations showed a massive suppression of endogenous VEGF with only a very slow recovery over weeks. Such a severe systemic adverse event has not been reported after intravitreal treatment with bevacizumab in an infant. CONCLUSION: This case report shows a relevant systemic uptake of bevacizumab after intravitreal application as suppressed VEGF levels show. There seems to be a connection between suppressed VEGF levels and the onset of necrotizing enterocolitis. Therefore, treatment with bevacizumab should be carefully considered and further research is needed to assess this drug's safety profile.