Incidence and outcome of patients with renal cell carcinoma treated with partial or radical nephrectomy in the Cantons St Gallen and Appenzell 2009-2018.

BACKGROUND: Over recent years, the incidence of renal cell carcinoma (RCC) has remained unchanged in Switzerland and is low compared with other European countries. Partial or radical nephrectomy is the mainstay of treatment in patients with localised disease. METHODS: We conducted an analysis of data from the cancer registry of Eastern Switzerland on patients with surgery for RCC from 2009 to 2018, focusing on a comparison of surgical technique and outcome in tertiary and non-tertiary hospitals. RESULTS: 492 nephrectomies were performed. Out of 441 curative procedures, 226 were radical and 195 partial nephrectomies (20 unknown). At the tertiary hospital, statistically significantly more partial nephrectomies were performed in non-metastatic patients than at non-tertiary hospitals. We demonstrate a trend towards better disease-free survival after partial compared with radical nephrectomy. The 5-year overall survival for patients diagnosed between 2009 and 2013 was 85%, 83%, and 70% in stage I, II, and III, respectively, compared with 96%, 78%, and 72% for patients diagnosed between 2014 and 2018. CONCLUSION: RCC incidence in Switzerland has been stable during the past decade in contrast to other European countries, and no stage migration occurred. We demonstrated that patients with localised renal cancer at our tertiary centre were more likely to be treated with renal preserving surgery compared with non-tertiary hospitals. This analysis underlines the importance of local cancer registries in the comparison of treatment and outcome over time.

The normalized slope conductance as a tool for quantitative analysis of current-voltage relations.

The patch-clamp method, which was awarded the Nobel Prize in 1991, is a well-established and indispensable method to study ion channels in living cells and to biophysically characterize non-voltage-gated ion channels, which comprise about 70% of all ion channels in the human genome. To investigate the biophysical properties of non-voltage-gated ion channels, whole-cell measurements with application of continuous voltage ramps are routinely conducted to obtain current-voltage (IV) relationships. However, adequate tools for detailed and quantitative analysis of IV curves are still missing. We use the example of the transient receptor potential classical (TRPC) channel family to elucidate whether the normalized slope conductance (NSC) is an appropriate tool for reliable discrimination of the IV curves of diverse TRPC channels that differ in their individual curve progression. We provide a robust calculation method for the NSC, and, by applying this method, we find that TRPC channel activators and modulators can evoke different NSC progressions independent from their expression levels, which points to distinguishable active channel states. TRPC6 mutations in patients with focal segmental glomerulosclerosis resulted in distinct NSC progressions, suggesting that the NSC is suitable for investigating structure-function relations and might help unravel the unknown pathomechanisms leading to focal segmental glomerulosclerosis. The NSC is an effective algorithm for extended biophysical characterization of non-voltage-gated ion channels.

Modulation of I-wave generating pathways by theta-burst stimulation: a model of plasticity induction.

KEY POINTS: Mechanisms underlying plasticity induction by repetitive transcranial magnetic stimulation protocols such as intermittent theta-burst stimulation (iTBS) remain poorly understood. Individual response to iTBS is associated with recruitment of late indirect wave (I-wave) generating pathways that can be probed by the onset latency of transcranial magnetic stimulation applied to primary motor cortex (M1) at different coil orientations. We found an association between late I-wave recruitment [reflected by anterior-posterior (AP)-lateromedial (LM) latency; i.e. the excess latency of motor-evoked potentials generated by transcranial magnetic stimulation with an AP orientation over the latency of motor-evoked potentials evoked by direct activation of corticospinal axons using LM stimulation] and changes in cortical excitability following iTBS, confirming previous studies. AP-LM latency significantly decreased following iTBS, and this decrease correlated with the iTBS-induced increase in cortical excitability across subjects. Plasticity in the motor network may in part derive from a modulation of excitability and the recruitment of late I-wave generating cortical pathways. ABSTRACT: Plasticity-induction following theta burst transcranial stimulation (TBS) varies considerably across subjects, and the underlying neurophysiological mechanisms remain poorly understood, representing a challenge for scientific and clinical applications. In human motor cortex (M1), recruitment of indirect waves (I-waves) can be probed by the excess latency of motor-evoked potentials elicited by transcranial magnetic stimulation with an anterior-posterior (AP) orientation over the latency of motor-evoked potentials evoked by direct activation of corticospinal axons using lateromedial (LM) stimulation, referred to as the 'AP-LM latency' difference. Importantly, AP-LM latency has been shown to predict individual responses to TBS across subjects. We, therefore, hypothesized that the plastic changes in corticospinal excitability induced by TBS are the result, at least in part, of changes in excitability of these same I-wave generating pathways. In 20 healthy subjects, we investigated whether intermittent TBS (iTBS) modulates I-wave recruitment as reflected by changes in the AP-LM latency. As expected, we found that AP-LM latencies before iTBS were associated with iTBS-induced excitability changes. A novel finding was that iTBS reduced AP-LM latency, and that this reduction significantly correlated with changes in cortical excitability observed following iTBS: subjects with larger reductions in AP-LM latencies featured larger increases in cortical excitability following iTBS. Our findings suggest that plasticity-induction by iTBS may derive from the modulation of I-wave generating pathways projecting onto M1, accounting for the predictive potential of I-wave recruitment. The excitability of I-wave generating pathways may serve a critical role in modulating motor cortical excitability and hence represent a promising target for novel repetitive transcranial magnetic stimulation protocols.

Point shear wave elastography of the pancreas in patients with cystic fibrosis: a comparison with healthy controls.

PURPOSE: Manifestations of cystic fibrosis in the pancreas are gaining in clinical importance as patients live longer. Conventional ultrasonography and point shear wave elastography (pSWE) imaging are non-invasive and readily available diagnostic methods that are easy to perform. The aim of this study was to perform conventional ultrasonography and obtain pSWE values in the pancreases of patients with cystic fibrosis and to compare the findings with those of healthy controls. METHODS: 27 patients with cystic fibrosis (13 women/14 men; mean age 27.7 ± 13.7 years; range 9-58 years) and 60 healthy control subjects (30 women/30 men; mean age 30.3 ± 10.0 years; range 22-55 years) underwent examinations of the pancreas with conventional ultrasound and pSWE imaging. RESULTS: Patients with cystic fibrosis have an echogenic pancreatic parenchyma. We found cystic lesions of the pancreas in six patients. pSWE imaging of the pancreatic parenchyma gave significantly lower shear wave velocities in patients with cystic fibrosis than in the control group (1.01 m/s vs 1.30 m/s; p < 0.001). CONCLUSIONS: Using pSWE imaging in vivo, we have shown that the pancreas is considerably softer in patients with cystic fibrosis than in a healthy control population.

Accuracy of real-time couch tracking during 3-dimensional conformal radiation therapy, intensity modulated radiation therapy, and volumetric modulated arc therapy for prostate cancer.

PURPOSE: To evaluate the accuracy of real-time couch tracking for prostate cancer. METHODS AND MATERIALS: Intrafractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study; prostate motion had been monitored with the Calypso System. An industrial robot moved a phantom along these trajectories, motion was detected via an infrared camera system, and the robotic HexaPOD couch was used for real-time counter-steering. Residual phantom motion during real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of 3-dimensional conformal radiation therapy (3D-CRT), step-and-shoot intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). RESULTS: Motion of the prostate was largest in the anterior-posterior direction, with systematic (∑) and random (σ) errors of 2.3 mm and 2.9 mm, respectively; the prostate was outside a threshold of 5 mm (3D vector) for 25.0%±19.8% of treatment time. Real-time tracking reduced prostate motion to ∑=0.01 mm and σ = 0.55 mm in the anterior-posterior direction; the prostate remained within a 1-mm and 5-mm threshold for 93.9%±4.6% and 99.7%±0.4% of the time, respectively. Without real-time tracking, pass rates based on a γ index of 2%/2 mm in film dosimetry ranged between 66% and 72% for 3D-CRT, IMRT, and VMAT, on average. Real-time tracking increased pass rates to minimum 98% on average for 3D-CRT, IMRT, and VMAT. CONCLUSIONS: Real-time couch tracking resulted in submillimeter accuracy for prostate cancer, which transferred into high dosimetric accuracy independently of whether 3D-CRT, IMRT, or VMAT was used.

Increasing the general level of academic capacity in general practice: introducing mandatory research training for general practitioner trainees through a participatory research process.

BACKGROUND: To obtain good quality evidence-based clinical work there needs to be a culture of critical appraisal, and strong bridges between the clinical and the academic worlds in general practice. AIM: The aim was to educate the general practitioner (GP) trainees to obtain critical appraisal skills, and through the development and implementation of the mandatory programme to gradually empower the GP community to achieve academic capacity by creating a link between the GP researchers and the GP training community. This was done by developing a faculty, giving teaching skills to GP academics, and research skills to GP clinicians; and creating an awareness of the potential benefits of critical appraisal in training GP surgeries. METHODS: Development and implementation of a faculty and a programme through a participatory action research-inspired project, with process evaluation from the beginning of the planning phase. RESULTS: From 2006 to 2009, we built a teaching faculty of 25 teachers among clinical GPs and GP academics; developed the training programme; and delivered the programme to 95 GP trainees. Some of the GP trainees later showed an interest in more substantial research projects, and GP trainers with no previous association with the research environment started to show an interest through their function as GP trainers. The GP academics of the faculty, however, felt that it was difficult to continue the engagement because of the still increasing demand for published knowledge production in academia. CONCLUSION: It is possible to support the development of general academic capacity in general practice using participatory design in collaboration with GP academics and clinicians, building bridges between academia and clinical work, as well as within academia between research publication and teaching. There is, however, a generic barrier in the regulation of academia itself.

Control of a HexaPOD treatment couch for robot-assisted radiotherapy.

Moving tumors, for example in the vicinity of the lungs, pose a challenging problem in radiotherapy, as healthy tissue should not be irradiated. Apart from gating approaches, one standard method is to irradiate the complete volume within which a tumor moves plus a safety margin containing a considerable volume of healthy tissue. This work deals with a system for tumor motion compensation using the HexaPOD® robotic treatment couch (Medical Intelligence GmbH, Schwabmünchen, Germany). The HexaPOD, carrying the patient during treatment, is instructed to perform translational movements such that the tumor motion, from the beams-eye view of the linear accelerator, is eliminated. The dynamics of the HexaPOD are characterized by time delays, saturations, and other non-linearities that make the design of control a challenging task. The focus of this work lies on two control methods for the HexaPOD that can be used for reference tracking. The first method uses a model predictive controller based on a model gained through system identification methods, and the second method uses a position control scheme useful for reference tracking. We compared the tracking performance of both methods in various experiments with real hardware using ideal reference trajectories, prerecorded patient trajectories, and human volunteers whose breathing motion was compensated by the system.

Advances in revascularization for acute ischemic stroke treatment: an update.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the established treatment for acute ischemic stroke patients presenting within 4.5 h of stroke onset based on the results of the National Institute of Neurological Disorders and Stroke Study Group trial and European Cooperative Acute Stroke Study III. In a significant number of patients, however, intravenous thrombolysis with rt-PA remains ineffective, with lower rates of recanalization, especially for proximal occlusions and a large thrombus burden. Newer thrombolytic agents, such as reteplase, tenecteplase or desmoteplase, offer pharmacokinetic and hemodynamic advantages over rt-PA and have been, or are currently being, tested for safety and efficacy in clinical trials. Agents such as direct fibrinolytics that do not depend on the availability of plasminogen are also being studied in ongoing trials. Endovascular revascularization is an evolving treatment option enabling mechanical clot disruption or extraction in combination with local directed pharmacological thrombolysis. Several new endovascular devices have been successfully tested for safety in acute ischemic stroke patients and are now being tested for efficacy in larger clinical trials. Continued innovation and refinement of endovascular technology and techniques, including combination therapy such as bridging therapy and the use of stent-like devices, is expected to increase technical success and improve overall efficacy and time to recanalization with minimal procedure-related morbidity in the treatment of acute ischemic stroke.

[Developing training in critical appraisal for GP trainees in the Eastern Region of Denmark]. / Udviklingen af den almenmedicinske forskningstraening i Region Øst.

In 2004 training in critical appraisal became a mandatory part of the Danish medical specialist training. In this article we describe how the course was designed and implemented on the basis of experience from previous research training initiatives targeting GPs and GP-trainees; and how we continuously develop the course and tailor the training of teachers for the course using a multi-method participatory evaluation design, theoretically based on Stenhouse's definition of the curriculum as a process and the teachers as researchers.

Prevalence, severity and determinants of asthma in Danish five-year-olds.

BACKGROUND: The prevalence of asthma and wheeze is increasing. AIM: To study the annual and cumulative prevalence of asthma and wheeze in 5-y-old Danish children. METHODS: We obtained data on 3052 (82.0% of eligible) Danish children by a postal parental questionnaire including ISAAC questions regarding respiratory symptoms and our own questions on sociodemography and tobacco exposure. RESULTS: "Wheeze ever" was reported in 38.3%, "doctor-diagnosed asthma ever" in 10.5%, "childhood bronchitis ever" in 30.0%, "current wheeze" (<12 mo) in 19.7%, and being "severe" (>3 episodes) in 3.9% of the children. Current wheeze was associated with male gender (OR 1.63, 95% CI 1.35-1.96), low parental post-primary education (OR 1.29, 95% CI 1.02-1.63 for <3 y vs > or =3 y) and current maternal smoking (OR 1.69, 95% CI 1.39-2.04). "Severe current wheeze" was recognized as asthma in six and childhood bronchitis in three of 10 cases. Nearly all diagnosed asthmatics had suffered wheeze, two-thirds recently. CONCLUSION: We found a high prevalence of asthma and wheeze in Danish late-preschool children, associated with male gender, current maternal tobacco smoking and low parental post-primary education. The majority of children with current wheeze had an early onset, and severe early symptoms tended to persist. Used with consideration, the label "childhood bronchitis" seems purposeful.

A comparison of risk factors for wheeze and recurrent cough in preschool children.

In a study of 2,978 Danish children aged 5 years from two suburban counties of Copenhagen, carried out in 1998, the authors compared risk factor profiles for wheeze and recurrent cough without wheeze by using polytomous logistic regression to clarify whether the two conditions are likely to have the same etiology. Data were obtained 1) by a mailed parental questionnaire (International Study of Asthma and Allergies in Childhood questions and supplementary questions on cough, sociodemography, perinatal factors, and environmental exposure); 2) through general practitioners (familial allergic disease); and 3) from the National Medical Birth Register (birth weight). Wheeze (WH) was defined as more than one episode of wheeze within the last 12 months (irrespective of cough status) and recurrent cough without WH (RC) as cough occurring outside colds and usually lasting for periods of more than 1 week in children with no more than one attack of wheeze within the last 12 months. Risk factors for comparison were selected as those that, after repeated stepwise logistic regression, remained significant for children with WH or RC. Significant differences were found for gender (p = 0.003), gestational age (p = 0.0002), maternal history of asthma (p = 0.0008), and standard of housing condition (p = 0.04)-all risk factors for WH but not RC. Results may suggest that the two conditions have different etiologies.