Performance of an ultra-fast deep-learning accelerated MRI screening protocol for prostate cancer compared to a standard multiparametric protocol.

OBJECTIVES: To establish and evaluate an ultra-fast MRI screening protocol for prostate cancer (PCa) in comparison to the standard multiparametric (mp) protocol, reducing scan time and maintaining adequate diagnostic performance. MATERIALS AND METHODS: This prospective single-center study included consecutive biopsy-naïve patients with suspected PCa between December 2022 and March 2023. A PI-RADSv2.1 conform mpMRI protocol was acquired in a 3 T scanner (scan time: 25 min 45 sec). In addition, two deep-learning (DL) accelerated sequences (T2- and diffusion-weighted) were acquired, serving as a screening protocol (scan time: 3 min 28 sec). Two readers evaluated image quality and the probability of PCa regarding PI-RADSv2.1 scores in two sessions. The diagnostic performance of the screening protocol with mpMRI serving as the reference standard was derived. Inter- and intra-reader agreements were evaluated using weighted kappa statistics. RESULTS: We included 77 patients with 97 lesions (mean age: 66 years; SD: 7.7). Diagnostic performance of the screening protocol was excellent with a sensitivity and specificity of 100%/100% and 89%/98% (cut-off ≥ PI-RADS 4) for reader 1 (R1) and reader 2 (R2), respectively. Mean image quality was 3.96 (R1) and 4.35 (R2) for the standard protocol vs. 4.74 and 4.57 for the screening protocol (p < 0.05). Inter-reader agreement was moderate (κ: 0.55) for the screening protocol and substantial (κ: 0.61) for the multiparametric protocol. CONCLUSION: The ultra-fast screening protocol showed similar diagnostic performance and better imaging quality compared to the mpMRI in under 15% of scan time, improving efficacy and enabling the implementation of screening protocols in clinical routine. CLINICAL RELEVANCE STATEMENT: The ultra-fast protocol enables examinations without contrast administration, drastically reducing scan time to 3.5 min with similar diagnostic performance and better imaging quality. This facilitates patient-friendly, efficient examinations and addresses the conflict of increasing demand for examinations at currently exhausted capacities. KEY POINTS: Time-consuming MRI protocols are in conflict with an expected increase in examinations required for prostate cancer screening. An ultra-fast MRI protocol shows similar performance and better image quality compared to the standard protocol. Deep-learning acceleration facilitates efficient and patient-friendly examinations, thus improving prostate cancer screening capacity.

Evidence of stage progression in a novel, validated fluorescence-navigated and microsurgical-assisted secondary lymphedema rodent model.

Secondary lymphedema (SL)is a frequent and devastating complication of modern oncological therapy and filarial infections. A lack of a reliable preclinical model to investigate the underlying mechanism of clinical stage progression has limited the development of new therapeutic strategies. Current first line treatment has shown to be merely symptomatic and relies on lifetime use of compression garments and decongestive physiotherapy. In this study, we present the development of a secondary lymphedema model in 35 rats using pre- and intraoperative fluorescence-guided mapping of the lymphatics and microsurgical induction. In contrast to the few models reported so far, we decided to avoid the use of radiation for lymphedema induction. It turned out, that the model is nearly free of complications and capable of generating a statistically significant limb volume increase by water displacement measurements, sustained for at least 48 days. A translational, accurate lymphatic dysfunction was visualized by a novel VIS-NIR X-ray ICG-Clearance-Capacity imaging technology. For the first-time SL stage progression was validated by characteristic histological alterations, such as subdermal mast cell infiltration, adipose tissue deposition, and fibrosis by increased skin collagen content. Immunofluorescence confocal microscopy analysis suggested that stage progression is related to the presence of a characteristic α SMA+/HSP-47+/vimentin+ fibroblast subpopulation phenotype. These findings demonstrate that the in-vivo model is a reliable and clinically relevant SL model for the development of further secondary lymphedema therapeutic strategies and the analysis of the veiled molecular mechanisms of lymphatic dysfunction.

Wave propagation in spatially modulated tubes.

We investigate wave propagation in rotationally symmetric tubes with a periodic spatial modulation of cross section. Using an asymptotic perturbation analysis, the governing quasi-two-dimensional reaction-diffusion equation can be reduced into a one-dimensional reaction-diffusion-advection equation. Assuming a weak perturbation by the advection term and using projection method, in a second step, an equation of motion for traveling waves within such tubes can be derived. Both methods predict properly the nonlinear dependence of the propagation velocity on the ratio of the modulation period of the geometry to the intrinsic width of the front, or pulse. As a main feature, we observe finite intervals of propagation failure of waves induced by the tube's modulation and derive an analytically tractable condition for their occurrence. For the highly diffusive limit, using the Fick-Jacobs approach, we show that wave velocities within modulated tubes are governed by an effective diffusion coefficient. Furthermore, we discuss the effects of a single bottleneck on the period of pulse trains. We observe period changes by integer fractions dependent on the bottleneck width and the period of the entering pulse train.

Craniocervical manual lymphatic drainage and its impact on intracranial pressure - a pilot study.

BACKGROUND AND PURPOSE: Theoretical considerations and the results of animal studies indicate that manual lymphatic drainage (MLD) might have an impact on intracranial pressure (ICP). There is a lack of clinically qualitative investigations on patients with severe cerebral diseases. METHODS: Between April 2013 and January 2015 a prospective observational study was performed on patients who were undergoing intracranial pressure measurement and treatment with MLD. ICP, cerebral perfusion pressure, mean arterial pressure (MAP), heart rate and oxygen saturation were recorded continuously 15 min before the procedure, during MLD (22 min) and for 15 min after the procedure. For analysis the data treatment units were divided into two groups: patients with a mean baseline ICP <15 mmHg (group 1) and patients with a mean ICP ≥15 mmHg before MLD (group 2). RESULTS: A total of 133 treatment units (61 patients) were analysed (group 1 n = 99; group 2 n = 34). The mean baseline ICP was 10.4 mmHg overall, and 8.3 mmHg and 18.6 mmHg respectively in group 1 and group 2; ICP significantly decreased during therapy with MLD and this persisted during the follow-up period in group 2. MAP did not show any significant differences between the different periods. CONCLUSIONS: Our data showed a significant reduction of ICP during therapy with craniocervical MLD in patients with severe cerebral diseases.

Management of burn wounds of the head and neck region.

Management of burn wounds of the head and neck region. Management of the severely burned patient is ery often a challenge, not only due to major disturbances in anatomy and physiological processes, but also because the relatively low incidence of this pathology in both civilian and military practice results in care providers'lack of experience. The purpose of this educational document is to provide doctors confronted with these formidable trauma patients with basic management guidelines as well as some practical tips. In summary, and most importantly, these patients should be reated as any other multitrauma patient. First aid is essential and can be provided by non-medical staff. Initial medical nanagement should focus on the usual, familiar trauma algorithms of ABCDEF from the emergency management of evere burns (EMSB) manual' or the ABCDEs of the manual of advanced trauma life support (ATLS)2 or advanced burn life support (ABLS). Medical care should proceed through the following steps - Step one: establish a reliable intravenous nfusion; step two: protect the airway; step three: establish and maintain a haemodynamic state compatible with sufficient organ perfusion in order to reduce aggravation of the burn wounds and increase overall survival likelihood; step four: provide analgesia with adequate sedation and provide anaesthesia for escharotomy, fasciotomy or other surgical injuries; step five: maintain normothermia; step six: feed the patient by starting enteral nutrition as early as possible; step seven: prevent infection using antiseptic wound management, systemic antibiotics and tetanus prophylaxis. All of these intricate steps require continuous reassessment and adjustment, but the existence of other wounds (blast injuries, penetrating and blunt trauma) even further complicates the management of burn casualties.

[Bilateral hand salvage of subtotal left hand amputation and complex right wrist destruction]. / Extremitätenerhalt bei subtotaler Handamputation links und komplexer Handgelenkzerstörung rechts.

Complex injuries of the hand and wrist lead to severe loss of function. Complex trauma of the upper extremities may lead to severe disabilities and therefore meticulous reconstruction is of utmost importance to enable good functional outcome and to assure an adequate quality of life. We demonstrate the case of a patient who suffered from complex bilateral injuries at the wrist level including a subtotal amputation of the left hand and third degree open wrist destruction on the contralateral side. Due to the immediate bilateral operation including the unilateral use of an osteocutaneous free fibula flap, both hands could be salvaged in this case. Severe hand and wrist injuries also require intensive postoperative treatment including intensive physiotherapy, occupational therapy, pain therapy and psychological support to achieve a good functional result.

Front propagation in channels with spatially modulated cross section.

Propagation of traveling fronts in a three-dimensional channel with spatially varying cross section is reduced to an equivalent one-dimensional reaction-diffusion-advection equation with boundary-induced advection term. Treating the advection term as a weak perturbation, an equation of motion for the front position is derived. We analyze channels whose cross sections vary periodically with L along the propagation direction of the front. Taking the Schlögl model as a representative example, we calculate analytically the nonlinear dependence of the front velocity on the ratio L/l where l denotes the intrinsic front width. In agreement with finite-element simulations of the three-dimensional reaction-diffusion dynamics, our theoretical results predicts boundary-induced propagation failure for a finite range of L/l values. In particular, the existence of the upper bound of L/l can be completely understood based on the linear eikonal equation. Last, we demonstrate that the front velocity is determined by the suppressed diffusivity of the reactants for L≪l.

Indocyanine green fluorescence-guided sentinel node biopsy: a meta-analysis on detection rate and diagnostic performance.

BACKGROUND: Indocyanine green (ICG) fluorescence-guided sentinel node biopsy (SLNB) has been successfully employed in various kinds of tumors. Clinical results of previous studies on this technique are at different levels of evidence. This Meta-analysis was conducted to provide a more precise estimation on its clinical performance. METHODS: Eligible studies were identified from systematical PubMed and EMBASE searches; data were extracted. A Meta-analysis was performed to generate pooled detection rate, sensitivity, specificity, diagnostic odds ratio (DOR) and summary receiver operator characteristic curves. RESULTS: Fifteen published articles were included. Clinical data of 513 patients were obtained. The pooled detection rate, the pooled sensitivity, the pooled specificity, the pooled DOR and their 95% confidence intervals (95% CI) were 0.96 (0.91-0.99), 0.87 (0.79-0.92), 1.00 (0.99-1.00) and 150.13 (57.42-392.56), respectively. Significant heterogeneities existed among studies. Significant publication bias was found in detection rate. The concentration < 5 mg/ml subgroup and the injected volume ≥2 ml subgroup had higher DORs, sensitivities and detection rates than the concentration ≥ 5 mg/ml subgroup and the injected volume <2 ml subgroup, respectively. CONCLUSION: Based on this Meta-analysis, this technique could be valued promising for detecting the presence of LN metastases. ICG injection with reduced concentration and larger volume may provide improved performance.

Current techniques for lymphatic imaging: State of the art and future perspectives.

Techniques for lymphatic imaging are aiming at accurate, simple and minimal-invasive approaches with less side-effects and repetitive application. Limitations are emerging in conventional techniques, and new techniques have shown their advantages in high resolution and sensitivity as well as transcutaneous imaging. In the present review, these techniques and their applications are reviewed and elucidated, aiming at a better understanding of recent advancements and current trends of lymphatic imaging as well as promising techniques for future research.

[Aspects of microsurgical reconstruction for lower extremity defects]. / Aspekte der mikrochirurgischen Rekonstruktion an der unteren Extremität.

The interdisciplinary approach to lower extremity reconstruction between orthopaedic and plastic surgeons is the basis for an efficient soft-tissue coverage. The joint team and the transfer of local, regional and free flaps have been shown to reduce the rate of amputation. After the spread of microsurgical techniques and further innovations, e. g., bony reconstruction by vascularized bone grafts, microsurgery now plays an important role in lower extremity reconstruction. Main considerations for the microsurgical approach are the choice of flap type aiming at good functional results with a stable soft-tissue coverage. The use of innervated flaps and functioning muscle transfer have led to an increased patient satisfaction and quality of life. Timing of reconstruction has been shown to have an impact on the results of microsurgical reconstruction. The importance of "composite tissue allotransplantation - CTA" applied for lower extremity reconstruction has to be evaluated in further studies.

Stabilization of a scroll ring by a cylindrical Neumann boundary.

We study the interaction of phase singularities with homogeneous Neumann boundaries in one, two, and three spatial dimensions for the complex Ginzburg-Landau equation. The existence of a boundary-induced drift attractor, well known for spiral waves in two spatial dimensions, is demonstrated for scroll waves in three spatial dimensions. We find that a cylindrical Neumann boundary can lock a scroll ring, thus preventing the collapse of its closed filament.

Performance of a New HPV Cervi-Collect Collection and Transportation Kit.

Background. Liquid-based Pap (L-Pap) media are used for Pap and human papillomavirus (HPV) testing. Objectives. To compare RealTime High Risk (HR) HPV testing of a new collection kit (Cervi-Collect) and PreservCyt L-Pap specimens. To determine ease of use and safety of Cervi-Collect. Methods. L-Pap samples (n = 203) were tested with HC2 and RealTime HR HPV and Cervi-Collect with RealTime HR HPV. Discordant samples were genotyped. Results. L-Pap and Cervi-Collect specimens tested by RealTime HR HPV showed 93.1% agreement (Kappa 0.86). RealTime HR HPV and HC2 on L-Pap had 90.3% agreement (Kappa 0.80). RealTime HR HPV on Cervi-Collect and HC2 on L-Pap showed 88.2% agreement (Kappa 0.76). Sixteen of 21 samples which were HC2 negative and RealTime HR HPV positive on L-Pap or Cervi-Collect contained HR HPV genotypes. Eleven healthcare collectors were in strong agreement on a usability and safety questionnaire. Conclusion. Cervi-Collect samples were easy to collect and showed strong agreement with L-Pap samples tested with RealTime HR HPV or HC2.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

[The "Orf" virus: focus and review of the literature]. / Le virus "Orf": mise au point et revue de la littérature.

Orf is an infection often unknown to practicians throughout the world. The first known cases were registered at the end of the 19th century. The virus affects ovines and caprins and is characterized by cutaneous and/or mucosae lesions. It is strongly resistant and the survival time is important in the outside environment. The morbidity of Orf is far higher than its mortality. The virus is transmitted by direct and indirect contact among humans, who became vectors themselves. Those subjects that are in contact with the animals in question due to professional reasons are at risk in particular. The same goes for attendants and participants of religious feasts. The preferred localization of lesions in humans is the hands. The diagnostic is easily set by the anamnesis and the clinical characteristics of the lesions except when it happens to be a particular form. The complications are nearly exclusively related to the unawareness of the virus in form of inappropriate medical acts. The evolution is spontaneous and the unique treatment is the prophylaxis of bacterial infection as well as a constant surveillance.

Second universal limit of wave segment propagation in excitable media.

A free-boundary approach is applied to derive universal relationships between the excitability and the velocity and the shape of stabilized wave segments in a broad class of excitable media. In the earlier discovered low excitability limit wave segments approach critical fingers. We demonstrate the existence of a second universal limit (a motionless circular shaped spot) in highly excitable media. Analytically obtained asymptotic relationships and interpolation formula connecting both excitability limits are in good quantitative agreement with results from numerical simulations.

Modeling of the modulation by buffers of Ca2+ release through clusters of IP3 receptors.

Intracellular Ca(2+) release is a versatile second messenger system. It is modeled here by reaction-diffusion equations for the free Ca(2+) and Ca(2+) buffers, with spatially discrete clusters of stochastic IP(3) receptor channels (IP(3)Rs) controlling the release of Ca(2+) from the endoplasmic reticulum. IP(3)Rs are activated by a small rise of the cytosolic Ca(2+) concentration and inhibited by large concentrations. Buffering of cytosolic Ca(2+) shapes global Ca(2+) transients. Here we use a model to investigate the effect of buffers with slow and fast reaction rates on single release spikes. We find that, depending on their diffusion coefficient, fast buffers can either decouple clusters or delay inhibition. Slow buffers have little effect on Ca(2+) release, but affect the time course of the signals from the fluorescent Ca(2+) indicator mainly by competing for Ca(2+). At low [IP(3)], fast buffers suppress fluorescence signals, slow buffers increase the contrast between bulk signals and signals at open clusters, and large concentrations of buffers, either fast or slow, decouple clusters.

Serratia sp. bacteremia in Canberra, Australia: a population-based study over 10 years.

The purpose of this paper was to determine the population incidence and clinical features of Serratia sp. bacteremia in Canberra, Australia. Demographic and clinical data were collected prospectively for episodes of Serratia sp. bacteremia over a 10-year period, and was confined to Canberra residents using residential postal codes. Thirty-eight episodes of Serratia sp. bacteremia occurred, with a yearly incidence of 1.03 per 100,000 population. The majority of episodes occurred in males (68%). The respiratory tract was the most common focus of infection (21%). Twenty-nine percent of episodes were community-associated. A further 18% of episodes had their onset in the community but were healthcare-associated. The 7-day and 6-month mortality rates were 5 and 37%, respectively. Antibiotic resistance to gentamicin (3%) and ciprofloxacin (0%) was low. Serratia sp. bacteremia is more common than generally appreciated, with a large proportion (47%) of episodes having their onset in the community.

The endoplasmic reticulum in apoptosis and autophagy: role of the BCL-2 protein family.

Apoptosis is essential for normal development and maintenance of homeostasis, and disruption of apoptotic pathways is associated with multiple disease states, including cancer. Although initially identified as central regulators of apoptosis at the level of mitochondria, an important role for BCL-2 proteins at the endoplasmic reticulum is now well established. Signaling pathways emanating from the endoplasmic reticulum (ER) are involved in apoptosis initiated by stimuli as diverse as ER stress, oncogene expression, death receptor (DR) ligation and oxidative stress, and the BCL-2 family is almost invariably implicated in the regulation of these pathways. This also includes Ca(2+)-mediated cross talk between ER and mitochondria during apoptosis, which contributes to the mitochondrial dynamics that support the core mitochondrial apoptosis pathway. In addition to the regulation of apoptosis, BCL-2 proteins at the ER also regulate autophagy, a survival pathway that limits metabolic stress, genomic instability and tumorigenesis. In cases where apoptosis is inhibited, however, prolonged autophagy can lead to cell death. This review provides an overview of ER-associated apoptotic and autophagic signaling pathways, with particular emphasis on the BCL-2 family proteins.