Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023.

The 18th St Gallen International Breast Cancer Conference held in March 2023, in Vienna, Austria, assessed significant new findings for local and systemic therapies for early breast cancer with a focus on the evaluation of multimodal treatment options. The emergence of more effective, innovative agents in both the preoperative (primary or neoadjuvant) and post-operative (adjuvant) settings has underscored the pivotal role of a multidisciplinary approach in treatment decision making, particularly when selecting systemic therapy for an individual patient. The importance of multidisciplinary discussions regarding the clinical benefits of interventions was explicitly emphasized by the consensus panel as an integral part of developing an optimal treatment plan with the 'right' degree of intensity and duration. The panelists focused on controversies surrounding the management of common ductal/no special type and lobular breast cancer histology, which account for the vast majority of breast tumors. The expert opinion of the panelists was based on interpretations of available data, as well as current practices in their professional environments, personal and socioeconomic factors affecting patients, and cognizant of varying reimbursement and accessibility constraints around the world. The panelists strongly advocated patient participation in well-designed clinical studies whenever feasible. With these considerations in mind, the St Gallen Consensus Conference aims to offer guidance to clinicians regarding appropriate treatments for early-stage breast cancer and assist in balancing the realistic trade-offs between treatment benefit and toxicity, enabling patients and clinicians to make well-informed choices through a shared decision-making process.

The impact of neoadjuvant systemic treatment on postoperative complications in breast cancer surgery.

PURPOSE: The aim of the study was to analyze the impact of neoadjuvant systemic treatment (NST) on postoperative complications and the beginning of adjuvant treatment. METHODS: This study includes data from a prospectively maintained database including patients with breast cancer (BC) stage I-IV with or without NST undergoing breast cancer surgery between January 2010 and September 2021. RESULTS: Out of 517 enrolled patients, 77 received NST, 440 had primary breast surgery. After NST patients underwent surgery after a meantime of 34 days (26.5-40 days). No statistical significance could be found comparing the complication grading according to the Clavien Dindo classification. The complications were most frequently rated as grade 3b. There were no complications with grade 4 or higher. When differentiating into short and long-term, the overall rate of short-term complications was 20.3% with no significant difference between the two groups (20.8% vs. 20.2%). Regarding long-term complications, there was more impairment of shoulder mobility (26.0% vs. 9.5%, p ≤ 0.001) and chronic pain (42.9% vs. 28.6%, p ≤ 0.016) for patients with NST. The beginning of the administration of the adjuvant treatment was comparable in both groups (46.3 days vs. 50.5 days). CONCLUSION: In our cohort, complications between both groups were comparable according to Clavien Dindo. This study shows that NST has no negative impact on postoperative short-term complications and most importantly did not lead to a delay of the beginning of adjuvant treatment. Therefore, NST can be safely admitted, even when followed by extensive breast reconstruction surgery.

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [18F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0.

PURPOSE: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [18F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors. METHODS: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard. CONCLUSIONS: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [18F]FDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.

The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.

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.

Correction to: 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

The article 18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors written by Laure Michaud, B. J. Beattie, T. Akhurst, M. Dunphy, P. Zanzonico, R. Finn, A. Mauguen, H. Schöder, W. A. Weber, A. B. Lassman, R. Blasberg.

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

PURPOSE: The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. METHODS: Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. RESULTS: 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5 ± 2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p < 0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5 ± 0.2 compared to 1.3 ± 0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7 ± 2.3 h), and achieving a consistent final distribution volume averaging 1.4 ± 0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57 ± 51 min), with an average distribution volume of 3.2 ± 1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine. CONCLUSION: Tumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas.

PURPOSE: Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas. METHODS: Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging. RESULTS: In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET. CONCLUSIONS: We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

[Interdisciplinary neurovascular networks: state of the art]. / Interdisziplinäre neurovaskuläre Netzwerke: eine Standortbestimmung.

BACKGROUND: In order to treat the complete spectrum of neurovascular diseases at a high level of quality, which goes beyond the purely acute treatment of stroke, the German Stroke Society (DSG) together with the German Societies for Neurosurgery and Neuroradiology developed a certification procedure for neurovascular networks (NVN). Structurally, a NVN consists of a coordinating center with at least three neurovascular network partners with a certified stroke unit. From 2018 to 2020 a total of 15 NVN have so far been audited and certified according to this new standard. OBJECTIVE: How efficient are the NVN? Are high standards maintained? MATERIAL AND METHODS: The reports of the audits were analyzed. The data were taken from the period 2017-2019. RESULTS: The 15 NVN treated a total of 86,510 stroke patients in the years examined and were networked with a total of 107 partner clinics, which were situated an average of 25 km from the coordinating center and transferred a total of 2726 patients. The coordinating centers performed 2463 thrombectomies and treated 2383 patients with nontraumatic intracerebral bleeding. In 712 patients with acute aneurysmatic subarachnoid hemorrhages endovascular treatment was carried out and clipping in 401. The audit was successful in the majority of the NVN. CONCLUSION: The certification process of NVN has been successfully established and the audits proved to be a useful instrument for quality control and improvement. The 15 NVN are highly efficient and treat more than one quarter of stroke patients in German stroke units.

[Importance of FDG-PET/computed tomography in colorectal cancer]. / Stellenwert der FDG-PET/Computertomographie beim kolorektalen Karzinom.

BACKGROUND: Hybrid imaging FDG PET/CT (18F­fluordeoxyglucose positron emission tomography/computed tomography) has gained increasing importance in oncology in recent years. DIAGNOSIS: A focal increase in FDG uptake in the gastrointestinal tract may be due to colorectal carcinoma. Such a finding requires further clarification. PRIMARY STAGING: Staging of the primary and locoregional lymph nodes remains a domain of established imaging modalities as FDG PET/CT does not provide a clear additional benefit. Liver metastases can be detected with high sensitivity by FDG PET/CT, but MRI is superior in small lesions. RADIATION THERAPY PLANNING: So far FDG PET/CT plays a subordinate role in the radiation therapy planning of rectal cancer. However, it can potentially contribute to the optimization of planning target volumes. THERAPY MONITORING: FDG PET/CT is suitable for monitoring therapy because morphological and metabolic changes of the tumor can be detected in early stages. This enables early detection of nonresponders after beginning neoadjuvant chemoradiation therapy of rectal cancer. FDG PET/CT can also be used for therapy control of liver metastases, especially after local therapeutic procedures. DETECTION OF RECURRENCE: With clinical suspicion of local recurrence and increased tumor markers, FDG PET/CT is a valuable tool as tumor recurrence can be detected with high sensitivity and specificity.

A pilot study of neuropsychological functions, APOE and amyloid imaging in patients with gliomas.

Brain tumor patients treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the APOE ε-4 allele may influence cognitive outcome. The ε-4 allele is known to promote beta (ß) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with this process. However, it is unknown whether ß-amyloid accumulation contributes to treatment neurotoxicity. In this pilot study, we assessed neuropsychological functions and ß-amyloid retention using 18F-florbetaben (FBB) PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ε-4 carriers and 14 were non-ε-4 carriers. Patients completed a neuropsychological re-evaluation (mean time interval = 5 years, SD = 0.83) and brain MRI and FBB PET scans. Wilcoxon signed-rank test comparisons between prior and current neuropsychological assessments showed a significant decline in attention (Brief Test of Attention, p = 0.018), and a near significant decline in verbal learning (Hopkins Verbal learning Test-Learning, p = 0.07). Comparisons by APOE status showed significant differences over time in attention/working memory (WAIS-III digits forward, p = 0.028 and digits backward, p = 0.032), with a decline among APOE ε-4 carriers. There were no significant differences in any of the FBB PET analyses between APOE ε-4 carriers and non-ε-4 carriers. The findings suggest that glioma patients may experience worsening in attention and executive functions several years after treatment, and that the APOE ε-4 allele may modulate cognitive decline, but independent of increased ß-amyloid deposition.

Local Structure and Short-Range Order in a NiCoCr Solid Solution Alloy.

Multielement solid solution alloys are intrinsically disordered on the atomic scale, and many of their advanced properties originate from the local structural characteristics. The local structure of a NiCoCr solid solution alloy is measured with x-ray or neutron total scattering and extended x-ray absorption fine structure (EXAFS) techniques. The atomic pair distribution function analysis does not exhibit an observable structural distortion. However, an EXAFS analysis suggests that the Cr atoms are favorably bonded with Ni and Co in the solid solution alloys. This short-range order (SRO) may make an important contribution to the low values of the electrical and thermal conductivities of the Cr-alloyed solid solutions. In addition, an EXAFS analysis of Ni ion irradiated samples reveals that the degree of SRO in NiCoCr alloys is enhanced after irradiation.

Hepatic mRNA expression for genes related to somatotropic axis, glucose and lipid metabolisms, and inflammatory response of periparturient dairy cows treated with recombinant bovine somatotropin.

Objectives of this experiment were to evaluate the effects of recombinant bovine somatotropin (rbST) treatment of periparturient dairy cows on hepatic mRNA expression for genes related to the somatotropic axis, insulin, glucose, and lipid metabolism, inflammation, and oxidative stress. Holstein cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to 1 of 3 treatments: untreated control (n = 53), 87.5 mg of rbST (n = 56; rbST87.5), and 125 mg of rbST (n = 57; rbST125). Cows in the rbST87.5 and rbST125 treatments received weekly injections of rbST from -21 to 28 d relative to calving. A subsample of cows (control = 20, rbST87.5 = 20, rbST125 = 20) was randomly selected for collection of liver samples according to expected calving date, BCS, and previous lactation 305-d mature equivalent milk yield. Only cows that had liver sampled at -21 ± 3, -7 ± 3, and 7 ± 3 d relative to calving were used in the current experiment. Blood, sampled weekly from -28 to 21 d relative to calving, was used to determine the concentrations of growth hormone, insulin-like growth factor 1, insulin, cortisol, fatty acids, ß-hydroxybutyrate, glucose, haptoglobin, and tumor necrosis factor-α. Liver samples were used to determine hepatic mRNA expression of 50 genes. Treatment with rbST increased growth hormone concentrations during the postpartum period (control = 9.0 ± 0.7, rbST87.5 = 15.3 ± 1.0, rbST125 = 18.5 ± 1.3 ng/mL) and increased insulin-like growth factor 1 concentrations during the prepartum period (control = 107.4 ± 7.2, rbST87.5 = 126.9 ± 6.6, rbST125 = 139.4 ± 6.9 ng/mL). Control cows had greater postpartum concentrations of ß-hydroxybutyrate (control = 776.4 ± 64.0, rbST87.5 = 628.4 ± 59.7, rbST125 = 595.4 ± 60.9 µmol/L) than rbST cows. The rbST87.5 and rbST125 treatments upregulated the hepatic mRNA expression for somatotropic axis genes (GHR, GHR1A, IGF1, IGFBP3, and SOCS2) on d -7 relative to calving and upregulated the mRNA expression for SOCS2 on d 7. On d -7, rbST87.5 and rbST125 treatments increased mRNA expression for genes involved in hepatic lipid transport (ANGPTL4, APOA5, APOB100, and SCARB1) and downregulated mRNA expression for PPARD, which is involved in lipid storage. On d 7, rbST tended to upregulate the mRNA expression for genes involved in gluconeogenesis (PCK1) and fatty acid ß-oxidation (ACOX1), and downregulated the mRNA expression for genes involved in inflammation (TNFRSF1A, ICAM1, CXCL1, MYD88, HIF1A, IL1RN, NFKBIA, and SOCS3) and oxidative stress (XBP1). Administration of rbST during the periparturient period may improve liver function and health by increasing hepatic capacity for gluconeogenesis and lipid transport and by reducing inflammation and oxidative stress.

Mechanism of Radiation Damage Reduction in Equiatomic Multicomponent Single Phase Alloys.

Recently a new class of metal alloys, of single-phase multicomponent composition at roughly equal atomic concentrations ("equiatomic"), have been shown to exhibit promising mechanical, magnetic, and corrosion resistance properties, in particular, at high temperatures. These features make them potential candidates for components of next-generation nuclear reactors and other high-radiation environments that will involve high temperatures combined with corrosive environments and extreme radiation exposure. In spite of a wide range of recent studies of many important properties of these alloys, their radiation tolerance at high doses remains unexplored. In this work, a combination of experimental and modeling efforts reveals a substantial reduction of damage accumulation under prolonged irradiation in single-phase NiFe and NiCoCr alloys compared to elemental Ni. This effect is explained by reduced dislocation mobility, which leads to slower growth of large dislocation structures. Moreover, there is no observable phase separation, ordering, or amorphization, pointing to a high phase stability of this class of alloys.

Approaching Free Fall on Two Degrees of Freedom: Simultaneous Measurement of Residual Force and Torque on a Double Torsion Pendulum.

A torsion pendulum with 2 soft degrees of freedom (DOFs), realized by off-axis cascading two torsion fibers, has been built and operated. This instrument helps characterize the geodesic motion of a test mass for LISA Pathfinder or any other free-fall space mission, providing information on cross talk and other effects that cannot be detected when monitoring a single DOF. We show that it is possible to simultaneously measure both the residual force and the residual torque acting on a quasifree test mass. As an example of the investigations that a double pendulum allows, we report the measurement of the force-to-torque cross talk, i.e., the amount of actuation signal, produced by applying a force on the suspended test mass, that leaks into the rotational DOF, detected by measuring the corresponding (unwanted) torque.

The EANM practice guidelines for bone scintigraphy.

PURPOSE: The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign disease, as well as physiological processes. METHODS: The European Association of Nuclear Medicine (EANM) has written and approved these guidelines to promote the use of nuclear medicine procedures of high quality. CONCLUSION: The present guidelines offer assistance to nuclear medicine practitioners in optimizing the diagnostic procedure and interpreting bone scintigraphy. These guidelines describe the protocols that are currently accepted and used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Designed miniaturization of microfluidic biosensor platforms using the stop-flow technique.

Here, we present a novel approach to increase the degree of miniaturization as well as the sensitivity of biosensor platforms by the optimization of microfluidic stop-flow techniques independent of the applied detection technique (e.g. electrochemical or optical). The readout of the labeled bioassays, immobilized in a microfluidic channel, under stop-flow conditions leads to a rectangular shaped peak signal. Data evaluation using the peak height allows for a high level miniaturization of the channel geometries. To study the main advantages and limitations of this method by numerical simulations, a universally applicable model system is introduced for the first time. Consequently, proof-of-principle experiments were successfully performed with standard and miniaturized versions of an electrochemical biosensor platform utilizing a repressor protein-based assay for tetracycline antibiotics. Herein, the measured current peak heights are the same despite the sextuple reduction of the channel dimensions. Thus, this results in a 22-fold signal amplification compared to the constant flow measurements in the case of the miniaturized version.

[Management of Complex Tympanojugular Paragangliomas]. / Interdisziplinäres Management von komplexen tympanojugulären Paragangliomen Fisch Typ C und D.

Background: Tympanojugular paraganglioma (TJP) are benign, high vascularized, local destructive tumors. Despite many studies in the literature, the management of particularly complex TJP (e. g., posterior fossa and/or carotid artery invasion) remains controversial. In the current study we present our treatment strategies for complex TJP and long-term results. Patients and methods: Between 2003 and 2013, 17 patients with TJP Fisch types C and D were treated in our institution. Primary symptoms were hearing loss, followed by facial nerve palsy and lower cranial nerve impairments. 2 patients presented with recurrent tumors. Surgical treatment after endovascular tumor embolization was performed in 14 patients. 2 patients were treated by radiation therapy. Results: Gross tumor resection was achieved in 10 patients. A temporary postoperative facial nerve palsy occurred in 2 patients and permanent postoperative vocal cord palsy in 3 patients. During long term follow-up, one patient experienced regrowth of the residual tumor. No tumor progress was observed in both patients treated with radiation therapy. Outcome assessed by Karnofsky scale showed 100% functionality in 12 patients and 90% in 5 patients. Discussion: Surgical treatment of TJP after endovascular embolization is the treatment of choice in young and healthy patients. In older patients with premorbid conditions, radiation therapy is the main treatment option and is associated with high tumor control rates. Precise preoperative staging together with individualize risk-benefit assessment and interdisciplinary treatment strategy are essential for a favorable outcome.

Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery.

OBJECTIVE: Our aim was to evaluate the associations between quantitative (18)F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. METHODS: Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUVmax), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. RESULTS: MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUVmax and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUVmax was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. CONCLUSION: FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. KEY POINTS: • Both TLG and MTV were associated with optimal tumour debulking. • There was no significant association between SUVmax and tumour debulking status. • Patients with higher MTV and/or TLG had significantly shorter PFS. • SUVmax was not significantly related to PFS.