Evaluation of sensor-based health monitoring in dairy cows: Exploiting rumination times for health alerts around parturition.

The use of sensor-based measures of rumination time as a parameter for early disease detection has received significant attention in scientific research. This study aimed to assess the accuracy of health alerts triggered by a sensor-based accelerometer system within 2 different management strategies on a commercial dairy farm. Multiparous Holstein cows were enrolled during the dry-off period and randomly allocated to conventional (CON) or sensor-based (SEN) management groups at calving. All cows were monitored for disorders for a minimum of 10 DIM following standardized operating procedures (SOPs). The CON group (n = 199) followed an established monitoring protocol on the farm. The health alerts of this group were not available during the study but were later included in the analysis. The SEN group (n = 197) was only investigated when the sensor system triggered a health alert, and a more intensive monitoring approach according to the SOPs was implemented. To analyze the efficiency of the health alerts in detecting disorders, the sensitivity (SE) and specificity (SP) of health alerts were determined for the CON group. In addition, all cows were divided into 3 subgroups based on the status of the health alerts and their health status, to retrospectively compare the course of rumination time. Most health alerts (87%, n = 217) occurred on DIM 1. For the confirmation of diagnoses, health alerts showed SE and SP levels of 71% and 47% for CON cows. In SEN cows, a SE of 71% and 75% and SP of 48% and 43% were found for the detection of ketosis and hypocalcemia, respectively. The rumination time of the subgroups was affected by DIM and the interaction between DIM and the status of health alert and health condition.

Registro Argentino de Medición de la Presión Arterial en Consultorio. Estudio RAMPAC / Argentine registry of office blood pressure monitoring. RAMPAC study

Introducción: La hipertensión es el factor de riesgo más importante para la muerte cardiovascular a nivel mundial. En Argentina cerca del 44% de las personas desconocen ser hipertensos, y posiblemente sea debido a que no se les mide de la presión arterial (PA) en la consulta médica. Nuestra hipótesis es que la medición y el registro de la PA (MRPA) es omitida durante la consulta médica en Argentina. Objetivo: Determinar la frecuencia de MRPA en la consulta médica en Argentina. Métodos: Estudio multicéntrico, retrospectivo de punto de prevalencia. Se analizaron todas las consultas externas realizadas el 19/09/2019 en mayores de 18 años, en 9 instituciones sanitarias de Argentina y se evaluó la MRPA. Resultados: Se analizaron 2.982 consultas. La edad promedio fue de 52,1 años (18-103), 1.780 (59,7%) eran mujeres y 702 (36,1%) tenían antecedentes de hipertensión arterial (HTA). La PA se midió y registró en 420 consultas (14,1%; IC 95%: 12,8-15,4). En un modelo de regresión logística multivariado el antecedente de HTA (OR: 1,91; p<0,001) y de enfermedad cardiovascular (OR: 1,76; p<0,001) fueron las variables que más se asociaron a la MRPA. La presencia de cáncer se asoció un descenso de MRPA (OR: 0,51; p<0,01). Cardiología fue la especialidad que más midió la PA 49,5% (144/291 consultas), seguida por clínica médica 30% (152/507 consultas). Conclusión: La MRPA en la consulta médica ambulatoria es deficitaria y constituye una oportunidad perdida en salud. Se necesitan estrategias que mejoren la detección y el control de la HTA.

Introduction: Hypertension (HTN) is the leading cause of mortality and disability in the world. In Argentina, almost 44% of hypertensives do not know about their condition and this may be due to the low rate of blood pressure (BP) measurements during the office visit. Our hypothesis is that the measurement and electronic recording of BP (BPMR) is not a routine practice in Argentina. Objective: To describe the rate of office BP measurement in Argentina. Methods: This is a retrospective, multicentre, point prevalence study. We analysed all office visits on 9/19/2019 at 9 medical institutions in 6 provinces of Argentina. Results: Two thousand and eighty-two office visits were analysed. The patients’ mean age was 52.1 years (18-103), 1790 (59.7%) were female, and 702 (36.1%) were hypertensives. BP was measured in 420 visits (14.1%; 95% CI 12.8-15.4). In a multivariate logistic regression model, history of HTN (OR 1.91, P<.001) and previous cardiovascular event (OR 1.76, P<.001) were associated with more odds of BPMR. The presence of cancer was associated with fewer odds of BPMR (OR .51, P<.01). Cardiology measured BP up to 49.5% (144/291 visits), followed by internal medicine 30% (152/507 visits). Conclusion: BPMR during office visits is deficient in Argentina and represents a missed healthcare opportunity. Different strategies are needed to detect hypertensive patients and reduce cardiovascular events.

[Argentine registry of office blood pressure monitoring. RAMPAC study]. / Registro Argentino de Medición de la Presión Arterial en Consultorio. Estudio RAMPAC.

INTRODUCTION: Hypertension (HTN) is the leading cause of mortality and disability in the world. In Argentina, almost 44% of hypertensives do not know about their condition and this may be due to the low rate of blood pressure (BP) measurements during the office visit. Our hypothesis is that the measurement and electronic recording of BP (BPMR) is not a routine practice in Argentina. OBJECTIVE: To describe the rate of office BP measurement in Argentina. METHODS: This is a retrospective, multicentre, point prevalence study. We analysed all office visits on 9/19/2019 at 9 medical institutions in 6 provinces of Argentina. RESULTS: Two thousand and eighty-two office visits were analysed. The patients' mean age was 52.1 years (18-103), 1790 (59.7%) were female, and 702 (36.1%) were hypertensives. BP was measured in 420 visits (14.1%; 95% CI 12.8-15.4). In a multivariate logistic regression model, history of HTN (OR 1.91, P<.001) and previous cardiovascular event (OR 1.76, P<.001) were associated with more odds of BPMR. The presence of cancer was associated with fewer odds of BPMR (OR .51, P<.01). Cardiology measured BP up to 49.5% (144/291 visits), followed by internal medicine 30% (152/507 visits). CONCLUSION: BPMR during office visits is deficient in Argentina and represents a missed healthcare opportunity. Different strategies are needed to detect hypertensive patients and reduce cardiovascular events.

Radiomics in diffusion data: a test-retest, inter- and intra-reader DWI phantom study.

AIM: The aim of this study was to evaluate the robustness of radiomics features of a MRI (magnetic resonance imaging) phantom in quantitative diffusion-weighted imaging (DWI) and depending on the image resolution. MATERIALS AND METHODS: Scanning of an in-house developed DWI phantom was performed at a 1.5 T MRI scanner (Magnetom AERA, Siemens, Erlangen, Germany) using an echo planar imaging (EPI) DWI sequence (b=0,500,1,000 s/mm2) with low (3×3 mm2) and high (2×2 mm2) image resolutions. Scans were repeated after phantom repositioning to evaluate retest reliability. Radiomics features were extracted after semi-automatic segmentation and standardised pre-processing. Intra-/interobserver reproducibility and test-retest robustness were assessed using intraclass correlation coefficients (ICC). Differences were tested with non-parametric Wilcoxon's signed-rank and Friedman's test (p < 0.05) with Dunn's post-hoc analysis. RESULTS: Test-retest ICC was overall high with >0.90 for 39/46 radiomics features in all sequences/resolutions. Decreased test-retest ICCs were pronounced for conventional Min-value (overall ICC=0.817), and grey-level zone length matrix (GLZLM) features Short-Zone Emphasis (SZE) and Short-Zone Low Grey-level Emphasis (SZLGE) (for both overall ICC=0.927). Test-retest reproducibility was significantly different between b=500, 1,000 and apparent diffusion coefficient (ADC) (mean 0.975±0.050, 0.974±0.051 and 0.966±0.063), which remained significant after post-hoc analysis between b=1,000 and ADC (p = 0.022). ICCs were not significantly different between resolutions of 2×2 and 3×3 mm2 regarding b=500 (mean: 0.977±0.052 and 0.974±0.049, p = 0.612), b=1,000 (mean: 0.973±0.059 and 0.974±0.054, p = 0.516), and ADC (mean: 0.972±0.049 and 0.955±0.101, p = 0.851). Inter- and intra-observer reliability was consistently high for all sequences (overall mean 0.992±0.021 and 0.990±0.028). CONCLUSION: Under ex-vivo conditions, DWI provided robust radiomics features with those from ADC being slightly less robust than from raw DWI (b=500, 1,000 s/mm2). No significant difference was detected for different resolutions. Although, ex-vivo reliability of DWI radiomics features was high, no implications can be made regarding in-vivo analyses.

Exploring MR regression patterns in rectal cancer during neoadjuvant radiochemotherapy with daily T2- and diffusion-weighted MRI.

BACKGROUND: To date, only limited magnetic resonance imaging (MRI) data are available concerning tumor regression during neoadjuvant radiochemotherapy (RCT) of rectal cancer patients, which is a prerequisite for adaptive radiotherapy (RT) concepts. This exploratory study prospectively evaluated daily fractional MRI during neoadjuvant treatment to analyze the predictive value of MR biomarkers for treatment response. METHODS: Locally advanced rectal cancer patients were examined with daily MRI during neoadjuvant RCT. Contouring of the tumor volume was performed for each MRI scan by using T2- and diffusion-weighted-imaging (DWI)-sequences. The daily apparent-diffusion coefficient (ADC) was calculated. Volumetric and functional tumor changes during RCT were analyzed and correlated with the pathological response after surgical resection. RESULTS: In total, 171 MRI scans of eight patients were analyzed regarding anatomical and functional dynamics during RCT. Pathological complete response (pCR) could be achieved in four patients, and four patients had a pathological partial response (pPR) following neoadjuvant treatment. T2- and DWI-based volumetry proved to be statistically significant in terms of therapeutic response, and volumetric thresholds at week two and week four during RCT were defined for the prediction of pCR. In contrast, the average tumor ADC values widely overlapped between both response groups during RCT and appeared inadequate to predict treatment response in our patient cohort. CONCLUSION: This prospective exploratory study supports the hypothesis that MRI may be able to predict pCR of rectal cancers early during neoadjuvant RCT. Our data therefore provide a useful template to tailor future MR-guided adaptive treatment concepts.

[Radium-223 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) : The androgen receptor-independent active agent in the therapeutic sequence]. / Radium-223 zur Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) : Der androgenrezeptorunabhängige Wirkstoff in der therapeutischen Sequenz.

BACKGROUND: Radium-223 improves overall survival and preserves quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases and no known visceral metastases. Radium-223 can be used in combination with a luteinizing hormone releasing hormone (LHRH) analogue and as part of a sequential treatment scheme if disease progresses after at least two prior lines of systemic mCRPC therapies or if no other available systemic treatment is eligible. OBJECTIVES: Today physicians are faced with a previously unknown multitude and complexity of options for the treatment of mCRPC. An increasing number of clinical trials contribute to the dynamics of the therapeutic landscape. Radium-223 was approved for mCRPC treatment in 2013. Up to now the recommendations of use have been adjusted several times. Highlighting recent clinical trials and practice, this paper explores the position of radium-223 within the therapeutic sequence and outlines key elements for the interdisciplinary cooperation between uro-oncologists and nuclear medicine specialists. RESULTS: The mode of action of radium-223 does not depend on the androgen receptor (AR) pathway. Thus, it is an option in the therapeutic sequence when the efficacy of other agents is reduced by resistance. Furthermore, the efficacy of prior or subsequent medications are neither reduced nor enhanced by radium-223. The opportunity of an AR-independent and survival-prolonging medication should be taken as soon as the indication criteria are met because the incidence of visceral metastases increases during disease progression. According to current mCRPC guidelines, the osteoprotective use of bisphosphonates or denosumab is recommended, before treatment with radium-223 is started or resumed.

[Diffusion-weighted imaging-diagnostic supplement or alternative to contrast agents in early detection of malignancies?] / Diffusionsbildgebung ­ diagnostische Erweiterung oder Ersatz von Kontrastmitteln in der Früherkennung von Malignomen?

Medical research in the field of oncologic imaging diagnostics using magnetic resonance imaging increasingly includes diffusion-weighted imaging (DWI) sequences. The DWI sequences allow insights into different microstructural diffusion properties of water molecules in tissues depending on the sequence modification used and enable visual and quantitative analysis of the acquired imaging data. In DWI, the application of intravenous gadolinium-containing contrast agents is unnecessary and only the mobility of naturally occurring water molecules in tissues is quantified. These characteristics predispose DWI as a potential candidate for emerging as an independent diagnostic tool in selected cases and specific points in question. Current clinical diagnostic studies and the ongoing technical developments, including the increasing influence of artificial intelligence in radiology, support the growing importance of DWI. Especially with respect to selective approaches for early detection of malignancies, DWI could make an essential contribution as an eligible diagnostic tool; however, prior to discussing a broader clinical implementation, challenges regarding reliable data quality, standardization and quality assurance must be overcome.

Pericardial tissue for cardiovascular application: an in-vitro evaluation of established and advanced production processes.

Pericardial tissue is widely used as a biomaterial, especially for cardiovascular application. Tissue processing plays a key role in developing future scaffolds derived from biological material, yet standardized evaluation is still pending. This study presents a comprehensive assessment of different treatment protocols of bovine pericardium and compares those findings to commercially available decellularized bovine (CAB) and equine (CAE) pericardial patches. Native samples were fixed with glutaraldehyde (GA) or decellularized. These decellularized samples were subsequently either treated with GA (DEC-GA) or sterilized (DEC). Treatment effects were assessed by histological evaluation of structural and biomechanical properties. Furthermore, decellularization efficacy and accuracy of the applied sterilization protocol were evaluated. Cell seeding of processed pericardial samples with human endothelial cells constituted as biocompatibility test.GA-fixed tissue revealed structural deterioration, cytotoxicity and opposed to popular believe, GA-treatment did not lead to sterility of the samples. Biomechanical assessment revealed an increase in tensile strength of GA and a decrease of DEC and DEC-GA. DEC samples were successfully sterilized and showed good decellularization results, with a significant decrease in residual DNA. Comparative assessment revealed overall good results of CAE, yet results of CAB varied largely, e.g. decellularization efficacy or tissue thickness. Biocompatibility of DEC, CAB and CAE was confirmed by successful cell adhesion. Substantial differences of native tissue properties were observed, resulting in varying treatment efficacies. This study provides a first overview describing consequential variations among biomaterials and illustrates the necessity of multidimensional assessment and tissue quality management for biological scaffold development.

Diffusion-weighted breast imaging.

Magnetic resonance imaging (MRI) of the breast represents one of the most sensitive imaging modalities in breast cancer detection. Diffusion-weighted imaging (DWI) is a sequence variation introduced as a complementary MRI technique that relies on mapping the diffusion process of water molecules thereby providing additional information about the underlying tissue. Since water diffusion is more restricted in most malignant tumors than in benign ones owing to the higher cellularity of the rapidly proliferating neoplasia, DWI has the potential to contribute to the identification and characterization of suspicious breast lesions. Thus, DWI might increase the diagnostic accuracy of breast MRI and its clinical value. Future applications including optimized DWI sequences, technical developments in MR devices, and the application of radiomics/artificial intelligence algorithms may expand the potential of DWI in breast imaging beyond its current supplementary role.

[Advanced Prostate Cancer Consensus Conference 2017 : Discussion of the recommendations for diagnosis and treatment of metastatic prostate cancer by a German panel of experts]. / Advanced Prostate Cancer Consensus Conference 2017 : Diskussion der Empfehlungen zur Diagnostik und Therapie des metastasierten Prostatakarzinoms durch ein deutsches Expertengremium.

In March 2017 the 'Advanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in "European Urology".A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective. Reasons for an additional German discussion are country-specific variations that may have influenced the APCCC-votes und recommendations. Due to the concept of the APCCC-meeting the wording of the questions could not always be as necessary.One focus of this year consensus discussion was the treatment of metastatic castration-naive prostate cancer (mCNPC). There are new data which may also influence the therapeutic situation of patients with metastatic castration-resistant prostate cancer (mCRPC). Further points of discussion were the impact of new imaging procedures in the clinical setting as well as the treatment of oligometastatic prostate cancer.

[Metastatic castration-resistant prostate cancer : Use of cabazitaxel taking into consideration current data]. / Metastasiertes kastrationsresistentes Prostatakarzinom : Neues zu Cabazitaxel unter Berücksichtigung der aktuellen Datenlage.

BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. RESULTS: The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.

Tissue-engineering acellular scaffolds-The significant influence of physical and procedural decellularization factors.

The importance of decellularized medical products has significantly increased during the last years. In this paper, we evaluated the effects of selected physical and procedural decellularization (DC) factors with the aim to systematically assess their influence on DC results. 72 porcine aortic walls (AW) were divided into three groups and exposed to a DC solution for 4 h and 8 h, either continuously or in repeated cycles. The AW were rocked (90bpm), whirled (10 l/min), sonicated (120W, 45 kHz) or exposed to a combination of these treatments, followed by 10 washing cycles. Defining successful DC as removal of nuclei while keeping an intact extracellular matrix (ECM), we equalized the efficiency to the penetration depth (PD), obtained by DAPI fluorescence and H&E staining. Additionally, we performed scanning electron microscopy (SEM), Pentachrome and Picrosirius-Red staining. Results showed that significantly higher DC depths are achieved on outer compared to inner surfaces (61 ± 7%; p < 0.001). Furthermore, the PD showed a high time dependency for all samples. Compared to continuous rocking, we achieved a significant increase in the DC efficiency through cyclic treatments ( ∼ 43%), whirling ( ∼ 19%) and sonication ( ∼ 49%). The combined treatment supported these results. In all procedures, a skeletonized but intact Collagen fibrous network was obtained as confirmed by SEM analysis. In conclusion, we systematically identified essential factors to significantly enhance DC procedures. We highly recommend considering these factors in future DC protocols. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 153-162, 2018.

Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis.

BACKGROUND: The diagnosis of multiple sclerosis (MS) is currently based solely on clinical and magnetic resonance imaging features. However, histopathological studies have revealed four different patterns of lesion pathology in patients diagnosed with MS, suggesting that MS may be a pathologically heterogeneous syndrome rather than a single disease entity. OBJECTIVE: The aim of this study was to investigate whether patients with pattern I MS differ from patients with pattern II or III MS with regard to cerebrospinal fluid (CSF) findings, especially with reference to intrathecal IgG synthesis, which is found in most patients with MS but is frequently missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive encephalomyelitis. METHODS: Findings from 68 lumbar punctures in patients who underwent brain biopsy as part of their diagnostic work-up and who could be unequivocally classified as having pattern I, pattern II or pattern III MS were analysed retrospectively. RESULTS: Oligoclonal bands (OCBs) were present in 88.2% of samples from pattern I MS patients but in only 27% of samples from patients with pattern II or pattern III MS (P < 0.00004); moreover, OCBs were present only transiently in some of the latter patients. A polyspecific intrathecal IgG response to measles, rubella and/or varicella zoster virus (so-called MRZ reaction) was previously reported in 60-80% of MS patients, but was absent in all pattern II or III MS patients tested (P < 0.00001 vs. previous cohorts). In contrast, the albumin CSF/serum ratio (QAlb), a marker of blood-CSF barrier function, was more frequently elevated in samples from pattern II and III MS patients (P < 0.002). Accordingly, QAlb values and albumin and total protein levels were higher in pattern II and III MS samples than in pattern I MS samples (P < 0.005, P < 0.009 and P < 0.006, respectively). CONCLUSIONS: Patients with pattern II or pattern III MS differ significantly from patients with pattern I MS as well as from previous, histologically non-classified MS cohorts with regard to both intrathecal IgG synthesis and blood-CSF barrier function. Our findings strongly corroborate the notion that pattern II and pattern III MS are entities distinct from pattern I MS.

[Metastatic prostate cancer : Update: position paper for the use of chemotherapy]. / Metastasiertes Prostatakarzinom : Update: Positionspapier zum Einsatz der Chemotherapie.

BACKGROUND: Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naïve metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE: This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS: A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS: In the current treatment of hormone-naïve mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response <12 months, tumor-associated complaints), first-line chemotherapy is indicated. After docetaxel failure, continuous treatment with cabazitaxel shows superior overall survival compared to sustained antihormonal therapy. CONCLUSION: Chemotherapy is firmly established in treating patients with mCRPC. Long-term, it will be important to identify molecular predictors. The authors suggest the early use of chemotherapy in hormone-naïve mPC, but note that the approval in this indication is currently nonexistent. After disease progression, patients should be treated analogous to mCRPC.

[Prostate gland - what would urologists like to know from radiologists?] / Die Vorsteherdrüse ­ was möchte der Urologe vom Radiologen wissen?

A more than 100-year period, where the prostate was only seen and treated as a whole is coming to an end right now. Finally, high resolution imaging is providing deep insights and detailed information so that new therapeutic procedures can aim for the smallest targets within the gland. The long-standing wish of patients for individual noninvasive diagnostics and treatment of prostate diseases can now be fulfilled by providing new tailored concepts; however, in order to transfer the enormous amount of new information into the specific clinical patient situation, a closely knit interdisciplinary approach is required. In this setting, the traditional outpatient consultation service is overstretched in every aspect. It is now the time for new innovative constructs. The current one-sided service concept for urologists, radiologists and radiation therapists is therefore behind the times and the development of a "prostate management team" with equally cooperating partners from each specialty is the task for the future.

[Metastatic castration-resistant prostate cancer : Clinical data, new treatment options and therapy monitoring]. / Metastasiertes kastrationsresistentes Prostatakarzinom : Aktuelle Daten, neue Therapieoptionen und strukturiertes Therapiemonitoring.

Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life.