DEPROMP Trial: the additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men-study protocol for a randomized trial.

BACKGROUND: The primary objective is to determine the proportion of men with suspected prostate cancer (PCA) in whom the management plans are changed by additive gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) guided prostate biopsy (PET-TB) in combination with standard of care (SOC) using systematic (SB) and multiparametric magnetic resonance imaging-guided biopsy (MR-TB) compared with SOC alone. The major secondary objectives are to determine the additive value of the combined approach of SB + MR-TB + PET-TB (PET/MR-TB) for detecting clinically significant PCA (csPCA) compared to SOC; to determine sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of imaging techniques, respective imaging classification systems, and each biopsy method; and to compare preoperatively defined tumor burden and biomarker expression and pathological tumor extent in prostate specimens. METHODS: The DEPROMP study is a prospective, open-label, interventional investigator-initiated trial. Risk stratification and management plans after PET/MR-TB are conducted randomized and blinded by different evaluation teams of experienced urologists based on histopathological analysis and imaging information: one including all results of the PET/MR-TB and one excluding the additional information gained by PSMA-PET/CT guided biopsy. The power calculation was centered on pilot data, and we will recruit up to 230 biopsy-naïve men who will undergo PET/MR-TB for suspected PCA. Conduct and reporting of MRI and PSMA-PET/CT will be performed in a blinded fashion. DISCUSSION: The DEPROMP Trial will be the first to evaluate the clinically relevant effects of the use of PSMA-PET/CT in patients with suspected PCA compared to current SOC. The study will provide prospective data to determine the diagnostic yields of additional PET-TB in men with suspected PCA and the impact on treatment plans in terms of intra- and intermodal changes. The results will allow a comparative analysis of risk stratification by each biopsy method, including a performance analysis of the corresponding rating systems. This will reveal potential intermethod and pre- and postoperative discordances of tumor stage and grading, providing the opportunity to critically assess the need for multiple biopsies. TRIAL REGISTRATION: German Clinical Study Register DRKS 00024134. Registered on 26 January 2021.

Measurements of Phase Dynamics in Planar Josephson Junctions and SQUIDs.

We experimentally investigate the stochastic phase dynamics of planar Josephson junctions (JJs) and superconducting quantum interference devices (SQUIDs) defined in epitaxial InAs/Al heterostructures, and characterized by a large ratio of Josephson energy to charging energy. We observe a crossover from a regime of macroscopic quantum tunneling to one of phase diffusion as a function of temperature, where the transition temperature T^{*} is gate-tunable. The switching probability distributions are shown to be consistent with a small shunt capacitance and moderate damping, resulting in a switching current which is a small fraction of the critical current. Phase locking between two JJs leads to a difference in switching current between that of a JJ measured in isolation and that of the same JJ measured in an asymmetric SQUID loop. In the case of the loop, T^{*} is also tuned by a magnetic flux.

Out-of-equilibrium phonons in gated superconducting switches.

Recent experiments have suggested that superconductivity in metallic nanowires can be suppressed by the application of modest gate voltages. The source of this gate action has been debated and either attributed to an electric-field effect or to small leakage currents. Here we show that the suppression of superconductivity in titanium nitride nanowires on silicon substrates does not depend on the presence or absence of an electric field at the nanowire, but requires a current of high-energy electrons. The suppression is most efficient when electrons are injected into the nanowire, but similar results are obtained when electrons are passed between two remote electrodes. This is explained by the decay of high-energy electrons into phonons, which propagate through the substrate and affect superconductivity in the nanowire by generating quasiparticles. By studying the switching probability distribution of the nanowire, we also show that high-energy electron emission leads to a much broader phonon energy distribution compared with the case where superconductivity is suppressed by Joule heating near the nanowire.

Prostate cancer treatment costs increase more rapidly than for any other cancer-how to reverse the trend?

According to GLOBOCAN, about 1.41 million new prostate cancer (PCa) cases were registered in the year 2020 globally. The corresponding socio-economic burden is enormous. Anti-cancer mRNA-based therapy is a promising approach, the principle of which is currently applied for anti-COVID-19 vaccination, undergoing a detailed investigation in populations considering its short- and long-term effectiveness and potential side effects. Pragmatically considered, it will take years or even decades to make mRNA therapy working for any type of cancers, and if possible, for individual malignancy sub-types which are many specifically for the PCa. Actually, the costs of treating PCa are increasing more rapidly than those of any other cancer. The trend has to be reversed now, not in a couple of years. In general, two main components are making currently applied reactive (management of clinically manifested disease) PCa treatment particularly expensive. On one hand, it is rapidly increasing incidence of the disease and metastatic PCa as its subtype. To this end, rapidly increasing PCa incidence rates in young and middle-aged male sub-populations should be taken into account as a long-term contributor to the metastatic disease potentially developed later on in life. On the other hand, patient stratification to differentiate between non-metastatic PCa (no need for an extensive and costly treatment) and particularly aggressive cancer subtypes requiring personalised treatment algorithms is challenging. Considering current statistics, it becomes obvious that reactive medicine got at its limit in PCa management. Multi-professional expertise is unavoidable to create and implement anti-PCa programmes in the population. In our strategic paper, we exemplify challenging PCa management by providing detailed expert recommendations for primary (health risk assessment), secondary (prediction and prevention of metastatic disease in PCa) and tertiary (making palliative care to the management of chronic disease) care in the framework of predictive, preventive and personalised medicine.

Punzi-loss:: a non-differentiable metric approximation for sensitivity optimisation in the search for new particles.

We present the novel implementation of a non-differentiable metric approximation and a corresponding loss-scheduling aimed at the search for new particles of unknown mass in high energy physics experiments. We call the loss-scheduling, based on the minimisation of a figure-of-merit related function typical of particle physics, a Punzi-loss function, and the neural network that utilises this loss function a Punzi-net. We show that the Punzi-net outperforms standard multivariate analysis techniques and generalises well to mass hypotheses for which it was not trained. This is achieved by training a single classifier that provides a coherent and optimal classification of all signal hypotheses over the whole search space. Our result constitutes a complementary approach to fully differentiable analyses in particle physics. We implemented this work using PyTorch and provide users full access to a public repository containing all the codes and a training example.

Impact of COVID-19 on gynaecological patient care: results of patient's survey with 327 patients.

PURPOSE: The pandemic SARS-CoV-2 poses new and unprecedented challenges for health care systems on a national and global level. Although the current situation has been going on for more than 1 year, there is limited data on the impact of the pandemic on general hospital and medical practice care. This survey captures the perspective of patients with gynaecological diseases of this impact. METHODS: Using a paper-based questionnaire, 327 patients were asked about medical care and their experiences during the pandemic at the University Hospital Bonn and the University Hospital Charité Berlin. The study was performed from the 1st June to 30th September 2020. RESULTS: A total of 327 patients participated in the study: 156 stated to have been tested for coronavirus, and 1 patient reported a positive test. 41.3% of the patients felt insecure about the current situation, 30.4% were concerned about the risk of infection during the hospital stay. The pandemic-specific measures in hospitals and medical practices unsettled 6.8% of patients. 18.1% of patients feared that their gynaecological disease would not be treated adequately due to the pandemic. 55.7% of patients reported that their confidence in their physicians has increased during the pandemic. CONCLUSION: The results show that patients' confidence in the healthcare system and the physicians acting significantly increased during the COVID-19 crisis. Transparent and comprehensive information policy regarding actions and restrictions within the COVID-19 crisis eases patients concerns and improves patients' confidence in their physicians, which is crucial for a successful treatment's outcome.

[Clinical aspects in the diagnosis and treatment of prostate cancer]. / Klinische Aspekte bei der Diagnose und Therapie des Prostatakarzinoms.

BACKGROUND: Diagnosis and treatment of primary prostate cancer (PCA) have undergone significant changes in the last few years due to modern imaging. OBJECTIVES: Established and modern diagnostic and therapeutic modalities for detection and treatment of primary PCA are presented and discussed critically. MATERIALS AND METHODS: Background knowledge and guideline recommendations on primary PCA are summarized and additional information from relevant publications is given. RESULTS: Modern imaging, in particular multiparametric magnetic resonance imaging (mpMRI), has revolutionized the diagnostic work-up of primary PCA. Due to mpMRI, tumors are detected significantly better in both initial and re-biopsy with a significant reduction of overdiagnosis of clinically insignificant PCA. Therapeutic approaches such as active surveillance, radical prostatectomy and focal therapies are increasingly being planned and carried out relying on MR-imaging information concerning tumor extent and tumor aggressiveness. In addition, prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT) has shown superiority in assessing patients with suspected biochemical recurrence and in primary staging of PCA compared to conventional imaging in terms of detection of metastases. CONCLUSIONS: Modern imaging, especially mpMRI and PSMA-PET/CT, has added substantial benefits in modern diagnosis and treatment of primary PCA. Moreover, multiparametric ultrasound is also a promising addition to the radiological armamentarium in the management of primary PCA.

Endogenous anandamide and self-reported pain are significantly reduced after a 2-week multimodal treatment with and without radon therapy in patients with knee osteoarthritis: a pilot study.

Multimodal therapies comprising spa applications are widely used as non-pharmaceutical treatment options for musculoskeletal diseases. The purpose of this randomized, controlled, open pilot study was to elucidate the involvement of the endocannabinoid system in a multimodal therapy approach. Twenty-five elderly patients with knee osteoarthritis (OA) received a 2-week spa therapy with or without combination of low-dose radon therapy in the Bad Gastein radon gallery. A 10-point numerical rating scale (pain in motion and at rest), WOMAC questionnaire, and the EuroQol-5D (EQ-5D) questionnaire were recorded at baseline, and during treatment period at weeks one and two, and at 3-month and 6-month follow-ups. Plasma levels of the endocannabinoid anandamide (AEA) were determined at baseline and at 2 weeks, and serum levels of several cartilage metabolism markers at all five time-points. A significant and sustained reduction of self-reported knee pain was observed in the study population, but no further significant effect of the additional radon therapy up and above base therapy. This pain reduction was accompanied by a significant reduction of AEA plasma levels during treatment in both groups. No significant differences were seen in serum marker concentrations between the groups treated with or without radon, but a small reduction of serum cartilage degradation markers was observed during treatment in both groups. This is the first study investigating AEA levels in the context of a non-pharmacological OA treatment. Since the endocannabinoid system represents a potential target for the development of new therapeutics, further studies will have to elucidate its involvement in OA pain.

A superconducting switch actuated by injection of high-energy electrons.

Recent experiments with metallic nanowires devices seem to indicate that superconductivity can be controlled by the application of electric fields. In such experiments, critical currents are tuned and eventually suppressed by relatively small voltages applied to nearby gate electrodes, at odds with current understanding of electrostatic screening in metals. We investigate the impact of gate voltages on superconductivity in similar metal nanowires. Varying materials and device geometries, we study the physical mechanism behind the quench of superconductivity. We demonstrate that the transition from superconducting to resistive state can be understood in detail by tunneling of high-energy electrons from the gate contact to the nanowire, resulting in quasiparticle generation and, at sufficiently large currents, heating. Onset of critical current suppression occurs below gate currents of 100fA, which are challenging to detect in typical experiments.

Defects and plasticity in ultrastrong supercrystalline nanocomposites.

Supercrystalline nanocomposites are nanoarchitected materials with a growing range of applications but unexplored in their structural behavior. They typically consist of organically functionalized inorganic nanoparticles arranged into periodic structures analogous to crystalline lattices, including superlattice imperfections induced by processing or mechanical loading. Although featuring a variety of promising functional properties, their lack of mechanical robustness and unknown deformation mechanisms hamper their implementation into devices. We show that supercrystalline materials react to indentation with the same deformation patterns encountered in single crystals. Supercrystals accommodate plastic deformation in the form of pile-ups, dislocations, and slip bands. These phenomena occur, at least partially, also after cross-linking of the organic ligands, which leads to a multifold strengthening of the nanocomposites. The classic shear theories of crystalline materials are found to describe well the behavior of supercrystalline nanocomposites, which result to feature an elastoplastic behavior, accompanied by compaction.

The impact of age on patient-reported outcomes after oncoplastic versus conventional breast cancer surgery.

PURPOSE: Some studies have indicated age-specific differences in quality of life (QoL) among breast cancer (BC) patients. The aim of this study was to compare patient-reported outcomes after conventional and oncoplastic breast surgery in two distinct age groups. METHODS: Patients who underwent oncoplastic and conventional breast surgery for stage I-III BC, between 6/2011-3/2019, were identified from a prospectively maintained database. QoL was prospectively evaluated using the Breast-Q questionnaire. Comparisons were made between women < 60 and ≥ 60 years. RESULTS: One hundred thirty-three patients were included. Seventy-three of them were ≥ 60 years old. 15 (20.5%) of them received a round-block technique (RB) / oncoplastic breast-conserving surgeries (OBCS), 10 (13.7%) underwent nipple-sparing mastectomies (NSM) with deep inferior epigastric perforator flap (DIEP) reconstruction, 23 (31.5%) underwent conventional breast-conserving surgeries (CBCS), and 25 (34.2%) received total mastectomy (TM). Sixty patients were younger than 60 years, 15 (25%) thereof received RB/OBCS, 22 (36.7%) NSM/DIEP, 17 (28.3%) CBCS, and 6 (10%) TM. Physical well-being chest and psychosocial well-being scores were significantly higher in older women compared to younger patients (88.05 vs 75.10; p < 0.001 and 90.46 vs 80.71; p = 0.002, respectively). In multivariate linear regression, longer time intervals had a significantly positive effect on the scales Physical Well-being Chest (p = 0.014) and Satisfaction with Breasts (p = 0.004). No significant results were found concerning different types of surgery. CONCLUSION: Our findings indicate that age does have a relevant impact on postoperative QoL. Patient counseling should include age-related considerations, however, age itself cannot be regarded as a contraindication for oncoplastic surgery.

[Navigation systems for the percutaneous access to the kidney]. / Navigierter perkutaner Zugang zur Niere.

BACKGROUND: Percutaneous access to the renal pelvis still remains the most difficult step before nephrolitholapaxy (PCNL). New imaging techniques, such as 3D imaging and various navigation instruments such as electromagnetic, sonographic, CT-controlled and marker-based/iPAD try to simplify this step and reduce complications. OBJECTIVES: In this review, various new techniques for puncturing the renal collecting system are presented and their advantages and disadvantages are evaluated. MATERIALS AND METHODS: A systematic literature search was carried out in MEDLINE, whereby only puncture techniques that have already been evaluated in clinical studies were included. RESULTS: Five different navigation methods for puncturing the renal pelvis before PCNL were found. CONCLUSION: Intraoperative navigation can be useful when puncturing the collecting system. The combination of ultrasound and fluoroscopy currently remains the gold standard. However, there is still a need for further, primarily clinical, prospective studies to determine which new imaging technology and navigation systems will prevail and thus facilitate the access route to the kidney, especially in the case of special anatomical conditions.

The lncRNA Fer1L4 is an adverse prognostic parameter in clear-cell renal-cell carcinoma.

PURPOSE: Long non-coding RNAs (lncRNA) are involved in oncogenesis and tumor progression in various tumor entities. At present, little is known about the role in tumor biology of the lncRNA Fer-1 like family member 4 (Fer1L4) in clear-cell renal-cell carcinoma (ccRCC). The aim of this study is to evaluate the expression of Fer1L4 in patients with ccRCC, its association with clinicopathological parameters, and value as prognostic biomarker. MATERIAL AND METHODS: The expression of Fer1L4 was analyzed in the TCGA ccRCC cohort (n = 603; ccRCC n = 522, normal n = 81) and subsequently validated by quantitative real-time PCR in an independent cohort (n = 103, ccRCC n = 69, normal n = 34). Expression profiles were statistically correlated with clinicopathological and survival data. RESULTS: Fer1L4 lncRNA is overexpressed in ccRCC compared to adjacent normal tissues. Increased expression significantly correlates with tumor aggressiveness: high expression levels of Fer1L4 RNA were found in higher grade, higher stage, and metastatic tumors. Furthermore, Fer1L4 overexpression is an independent prognostic factor for overall, cancer-specific, and progression-free survival of patients with ccRCC. CONCLUSION: Fer1L4 expression significantly correlates with aspects of tumor aggressiveness. Based on this impact on tumor progression and its influence as an independent prognostic factor, Fer1L4 appears to exert properties as an oncogene in ccRCC. As a prognostic tissue biomarker, further functional investigations are warranted to investigate Fer1L4 as a potential therapeutic target.

BET 2: Does topical lidocaine improve oral intake in children with painful mouth ulcers?

A shortcut review was carried out to establish whether topical lidocaine was effective at reducing pain and improving oral intake in children with painful oral lesions. 34 papers were found using the reported searches, of which two presented the best available evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these two papers are tabulated. It is concluded that in otherwise healthy paediatric patients with painful oral ulcers, treatment with viscous lidocaine does not improve oral intake, although it may provide some pain relief.

[The development of real-time multispectral imaging for the diagnostics of bladder cancer]. / Entwicklung der Echtzeitmultispektralbildgebung für die Diagnostik des Harnblasenkarzinoms.

The performance of white light (WL) cystoscopy in the diagnostics of bladder cancer can be optimized by the use of modern imaging modalities, such as photodynamic diagnostics (PDD) and narrow band imaging (NBI). Real-time multispectral imaging (rMSI) enables simultaneous imaging of reflectance and fluorescence modalities in multiple spectral bands. We created a multiparametric cystoscopy image by digital overlapping of several modalities, e.g. WL, enhanced vascular contrast (EVC), raw fluorescence mode, protoporphyrin IX and autofluorescence (AF). The technical development and the subsequent clinical implementation of rMSI required a structured preclinical evaluation process, including both ex vivo and in vivo trials before the technology can be applied in patients. This review article presents the phases of testing, validation and the first clinical application of rMSI in urological endoscopy.

Radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid.

INTRODUCTION: Aim of this study was to analyse the perioperative outcome of patients undergoing radical cystectomy under continuous antiplatelet therapy with acetylsalicylic acid. MATERIALS AND METHODS: Using prospectively maintained databases of two departments of urology, we identified 461 consecutive patients who underwent radical cystectomy for bladder cancer (2011-2017). Patients were divided into three groups: 1) on-going antiplatelet therapy with acetylsalicylic acid (n = 50), 2) discontinuing antiplatelet therapy (n = 65) and 3) no antiplatelet therapy (n = 346). Perioperative outcome was compared between the three groups using ANOVA, likelihood ratio or Kruskal Wallis test with post-hoc testing. Uni- and multivariate analyses were performed to identify predictor for perioperative complications and transfusion. RESULTS: Group 1 showed an average estimated blood loss of 732 ±â€¯424, group 2 752 ±â€¯488 and group 3 810 ±â€¯544 ml (p = 0.51). There was no significant difference in transfusion rate (44% in group 1, 45% and 39% in groups 2 and 3, p = 0.63). Severe complications occurred in 26%, 15% and 15% in groups 1-3 (p = 0.19). Ischemic complications were more often observed in group 1 (n = 4, 8%) and 2 (n = 5, 8%) than group 3 (n = 7, 2%), p = 0.02. 90-day readmission (n = 99, 22%) and mortality rate (n = 10, 2.2%) were low and did not show any significant differences between the groups. In uni- and multivariate analysis ongoing therapy with acetylsalicylic acid was no independent risk factor for transfusion or severe complications. CONCLUSION: Perioperative continuation of therapy with acetylsalicylic acid in radical cystectomy is safe with no difference in intraoperative blood loss, transfusion rate, complications or mortality.

Schistosoma mansoni PCR+ -infected individuals in the Sudan present elevated systemic levels of chemokines when compared to uninfected and egg+ cohorts.

Infections with Schistosoma mansoni remain a major health problem in the Sudan where endemic communities, such as those in Kassala and Khartoum states, continue to face severe social-economic difficulties. Our previous immunoepidemiological findings revealed different immune [cytokine and S. mansoni egg (SEA) antibody] profiles in individuals with active infections (eggs in stool n = 110), individuals positive for S. mansoni via polymerase chain reaction (PCR) using sera (SmPCR+ n = 63) and those uninfected (Sm uninf). As antibody responses to eggs and worms are known to change during infection, we have expanded the profiling further by determining levels of adult worm (SWA) antibodies and nine chemokines in the serum of each individual in the three different cohorts. With the exception of C-C motif chemokine ligand (CCL)2, all measured chemokines were significantly higher in SmPCR+ individuals when compared to the egg+ group and in addition they also presented elevated levels of SWA-specific immunoglobulin (Ig)G2. Multivariable regression analysis further revealed that infection per se was strongly linked to SWA-specific IgG3 levels and CCL5 was strongly associated with a SmPCR+ diagnostic state. In the absence of PCR diagnostics that recognize juvenile worms or schistosomulae motives, identifying schistosome-specific traits should provide better insights into current prevalence rates in endemic communities and, in doing so, take into consideration PCR+ non-egg+ individuals in current treatment programmes.