Effect of 12-months testosterone replacement therapy on bone mineral density and markers of bone turnover in testicular cancer survivors - results from a randomized double-blind trial.

BACKGROUND: Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. METHODOLOGY: In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). RESULTS: After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): -0.01 - 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: -0.01-0.03), BMD of the left femoral neck: 0.00, (95% CI: -0.01-0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. CONCLUSION: 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort.

Actionable reporting versus unwanted advice in PET-CT reports.

AIM: To investigate the opinions of clinician referrers on the presence and type of management advice in reports of positron-emission tomography (PET)-computed tomography (CT) examinations. MATERIALS AND METHODS: Eighteen clinicians were interviewed using a structured questionnaire about their opinions on further management advice in PET-CT reports. RESULTS: Opinions varied amongst clinicians, but some themes predominated: (1) advice on further imaging tests and areas outside the referrer's area of expertise are more welcome than other types of advice; (2) a differential diagnosis or clinical significance is of greater value than specific management advice; (3) some referrers do not want any further advice. CONCLUSION: Before advising on further management, reporters should consider clinicians' opinions regarding this. Seeking the opinion of clinicians in other hospitals may be necessary. A review of the Royal College of Radiologists Actionable Reports standard to ensure it is more in line with the opinions of clinicians may be useful.

Absence of clinical benefit of FDG PET-CT in staging T1 part-solid lung adenocarcinoma.

AIM: To assess the rates of nodal and metastatic disease and change in management when staging part-solid T1 lung adenocarcinomas using integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) in a UK population. MATERIALS AND METHODS: This was a retrospective review of PET-CT examinations performed to stage radiologically suspected T1 part-solid lung adenocarcinoma (n=58) from two different centres. Rates of detection of nodal and metastatic disease, change in management, and final patient outcome were recorded. RESULTS: PET-CT changed the stage in one patient from N0 to N1. It did not change final management in any patient. CONCLUSIONS: In this UK population, PET-CT had minimal additional diagnostic benefit in staging patients with T1 part-solid lung adenocarcinoma. Especially given its cost, the inclusion of PET-CT for this indication in guidelines should be reviewed.

Real-time, large-depth holographic 3D head-up display: selected aspects.

Today's state-of-the-art automotive head-up displays (HUD) possess single- or double layer focal planes that limit the observers' eye focus to these planes when crucial information is shown. Other visual 3D cues such as motion parallax also suffer from this limitation. The resulting viewing experience contradicts the natural way of viewing during driving or interaction, when alerts and hints should appear at the correct projection depth where real objects of interest are located. Here we present a real-time holographic HUD with continuous depth that supports the intuitive and natural way of viewing and interacting with virtual environments outside and inside the car. We demonstrate full-color, 3D real-time encoding within a field-of-view of 5∘×3∘.

Behind the hedges: how to convey uncertainty in imaging reports.

The imaging report is a summary document of findings and the primary form of communication of such to referring clinicians. Expressing uncertainty in the summary report is clearly difficult and the literature is unanimous that there is no agreement between imaging consultants and clinicians, and even between imaging consultants themselves, as to the meaning of uncertainty phrases. It is important for the imaging consultants to express uncertainty in the imaging report, but it is equally important that the referring clinician understands the degree of that uncertainty. Individual terminology does not bridge that gap. The present study reviews the literature in order to differentiate between uncertainty phrasing and hedging, and to find best practice examples to inform practice. We suggest three approaches that may be applied.

Unilateral axillary adenopathy following COVID-19 vaccination: a multimodality pictorial illustration and review of current guidelines.

We present a multimodality pictorial review of axillary lymphadenopathy in patients recently vaccinated against COVID-19. As the mass vaccination programme continues to be rolled out worldwide in an effort to combat the pandemic, it is important that radiologists consider recent COVID-19 vaccination in the differential diagnosis of unilateral axillary lymphadenopathy and are aware of typical appearances across all imaging methods. We review current guidelines on the management of unilateral axillary lymphadenopathy in the context of recent COVID-19 vaccination.

The effects of a training program using a phantom to accustom heifers to the automatic milking system.

The introduction of heifers into the automatic milking system (AMS) can be associated with considerable stress for both animals and farm employees, as completely inexperienced heifers initially do not independently enter the unknown milking robot. This study investigated whether training heifers on an AMS phantom provides the possibility of preparing heifers for the following lactation at the AMS. For this purpose, 77 Holstein-Friesian heifers were randomly assigned to one of 2 experimental groups: control (CON) or phantom (PHAN). Four weeks before calving, the PHAN group was given free access to the phantom, which was similar to the actual milking robot, so that they could explore it and be positively conditioned by feeding concentrate in the phantom. The heifers of the CON group had no contact with the phantom or the AMS before the first milking at the AMS. The milking frequency per animal per day was recorded, and the proportion of animals that had to be fetched for milking was determined, to evaluate how the animals accepted the AMS after calving. To assess the stress level of the animals before and after introduction into the AMS, fecal cortisol concentrations and rumination times of the animals were measured. Additionally, lactation performance characteristics (milk yield, milk flow, electrical conductivity of milk, and milk composition) were recorded for 77 animals. The animals trained on the phantom showed a higher milking frequency (DIM 7: 2.70 ± 0.14 visits/d) than the control animals (DIM 7: 2.41 ± 0.14 visits/d) between the 4th and 10th day of lactation. In addition, between d 1 and d 5, the proportion of animals that had to be fetched for milking was lower in PHAN (DIM 1: 35.18 ± 4.16%) than in CON (DIM 1: 48.03 ± 4.46%). The PHAN heifers had unexpectedly high fecal cortisol levels (1 wk prepartum: 43.50 ± 0.93 ng/g of feces), although not considerably elevated compared with CON (1 wk prepartum: 40.76 ± 1.05 ng/g of feces). Training on the phantom had no appreciable influence on rumination time and lactation performance parameters. The increased number of milking visits and the reduced proportion of animals that had to be fetched into the AMS for milking indicate that training on the phantom prepares the animals well for being milked in the AMS. Therefore, training heifers on the phantom offers the possibility to facilitate the start into early lactation for the animals, providing a valuable contribution to improvement of animal welfare.

Granular measures of agricultural land use influence lake nitrogen and phosphorus differently at macroscales.

Agricultural land use is typically associated with high stream nutrient concentrations and increased nutrient loading to lakes. For lakes, evidence for these associations mostly comes from studies on individual lakes or watersheds that relate concentrations of nitrogen (N) or phosphorus (P) to aggregate measures of agricultural land use, such as the proportion of land used for agriculture in a lake's watershed. However, at macroscales (i.e., in hundreds to thousands of lakes across large spatial extents), there is high variability around such relationships and it is unclear whether considering more granular (or detailed) agricultural data, such as fertilizer application, planting of specific crops, or the extent of near-stream cropping, would improve prediction and inform understanding of lake nutrient drivers. Furthermore, it is unclear whether lake N and P would have different relationships to such measures and whether these relationships would vary by region, since regional variation has been observed in prior studies using aggregate measures of agriculture. To address these knowledge gaps, we examined relationships between granular measures of agricultural activity and lake total phosphorus (TP) and total nitrogen (TN) concentrations in 928 lakes and their watersheds in the Northeastern and Midwest U.S. using a Bayesian hierarchical modeling approach. We found that both lake TN and TP concentrations were related to these measures of agriculture, especially near-stream agriculture. The relationships between measures of agriculture and lake TN concentrations were more regionally variable than those for TP. Conversely, TP concentrations were more strongly related to lake-specific measures like depth and watershed hydrology relative to TN. Our finding that lake TN and TP concentrations have different relationships with granular measures of agricultural activity has implications for the design of effective and efficient policy approaches to maintain and improve water quality.

Outcomes of extended radical resections for locally advanced and recurrent pelvic malignancy involving the aortoiliac axis.

AIM: Currently, there is no clear consensus on the role of extended pelvic resections for locally advanced or recurrent disease involving major vascular structures. The aims of this study were to report the outcomes of consecutive patients undergoing extended resections for pelvic malignancy involving the aortoiliac axis. METHODS: Prospective data were collected on patients having extended radical resections for locally advanced or recurrent pelvic malignancies, with aortoiliac axis involvement, requiring en bloc vascular resection and reconstruction, at a single institution between 2014 and 2018. RESULTS: Eleven patients were included (median age 60 years; range 31-69 years; seven women). The majority required resection of both arterial and venous systems (n = 8), and the technique for vascular reconstruction was either interposition grafts or femoral-femoral crossover grafts. The median operative time was 510 min (range 330-960 min). Clear resection margins (R0) were achieved in nine patients. The median length of stay was 25 days (range 7-83 days). Seven patients did not suffer an early complication. There was one serious complication (Clavien-Dindo ≥ 3), an arterial graft occlusion secondary to thrombus in the immediate postoperative period, requiring a return to theatre and thrombectomy. The median length of follow-up in this study was 22 months (range 4-58 months). CONCLUSION: This series demonstrates that en bloc major vascular resection and reconstruction can be performed safely and can achieve clear resection margins in selected patients with locally advanced or recurrent pelvic malignancy at specialist surgery centres.

Improved algorithm with adaptive regularization for tomographic reconstruction of gas distributions using DOAS measurements.

Differential optical absorption spectroscopy (DOAS) is notably well suited for the retrieval of UV-absorbing trace gases present in the atmosphere. We combine multi-axis DOAS observations to perform a tomographic reconstruction of the distribution of gases emitted from different sources. We use a new algorithm based on a regularized minimization approach embedding key physical aspects of the solution to constrain the inversion. In this work, we take into account that the spatial sampling of the plume being scanned by the instruments is not homogeneous. Therefore, we introduce an adaptive approach with a locally tuned regularization weight according to the uncertainty levels introduced by the sampling scheme. We tested our approach on reconstructions of simulated gas distributions and different configurations applicable to multi-axis DOAS. Finally, our approach is applied to experimental data for the retrieval of the distribution of ${\rm NO}_2$NO2 within a plume cross section emitted from a group of stacks.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) as a therapeutic target in psoriasis: randomized, controlled investigation using namilumab, a specific human anti-GM-CSF monoclonal antibody.

BACKGROUND: The relevance of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the management of psoriasis has not been studied previously. GM-CSF is important in the initiation and maintenance of chronic inflammatory processes. OBJECTIVES: To investigate the clinical use of GM-CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM-CSF inhibitor, in patients with moderate-to-severe plaque psoriasis. METHODS: A phase II, multicentre, randomized, double-blind, placebo-controlled, parallel-group, dose-finding, proof-of-concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point - the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) - was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777. RESULTS: In total, 122 patients were enrolled and 106 (86·9%) completed the double-blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration-time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment-related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis. CONCLUSIONS: GM-CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis.

Improving diagnostic performance of 18F-FDG-PET/CT for assessment of regional nodal involvement in non-small cell lung cancer.

AIM: To assess the diagnostic performance of combined 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) mediastinal blood pool (MBP) activity cut-off for staging nodal involvement, and to examine other variables that may improve the diagnostic performance of PET/CT in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: All patients diagnosed with NSCLC who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and 18F-FDG-PET/CT between June 2016 and August 2018 were included. Nodal station and nodal staging-based analyses were performed, comparing the MBP cut-off and five other PET/CT parameters (node maximum standardised uptake value [SUVmax], node/MBP SUVmax ratio, node/tumour SUVmax ratio, node short axis diameter, and node SUVmax/node short axis diameter ratio) with histopathology results. The optimal cut-off value for each PET/CT parameter was determined using receiver operating characteristic curve analysis. RESULTS: One hundred and thirteen patients with a total of 321 nodes with pathological sampling were included. Nodal activity above MBP on PET/CT demonstrated 97.4% sensitivity, 35.8% specificity, 32.8% positive predictive value, and 97.8% negative predictive value. Of the five other PET/CT parameters examined, the two most promising were node SUVmax and node/MBP SUVmax. The node SUVmax cut-off of 3.9 demonstrated 90.9% sensitivity and 61.9% specificity, and the node/MBP SUVmax cut-off of 1.7 demonstrated 90.9% sensitivity and 60.7% specificity. CONCLUSION: Compared to the MBP cut-off, use of a higher node/MBP SUVmax ratio cut-off and use of other PET/CT variables can improve the diagnostic performance of PET/CT for NSCLC nodal staging. In particular, specificity for detecting malignant nodal involvement is improved while maintaining high sensitivity.

Extracardiac 18F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds.

PURPOSE: 18F-Florbetapir has been reported to show cardiac uptake in patients with systemic light-chain amyloidosis (AL). This study systematically assessed uptake of 18F-florbetapir in patients with proven systemic amyloidosis at sites outside the heart. METHODS: Seventeen patients with proven cardiac amyloidosis underwent 18F-florbetapir PET/CT imaging, 15 with AL and 2 with transthyretin amyloidosis (ATTR). Three patients had repeat scans. All patients had protocolized assessment at the UK National Amyloidosis Centre including imaging with 123I-serum amyloid P component (SAP). 18F-Florbetapir images were assessed for areas of increased tracer accumulation and time-uptake curves in terms of standardized uptake values (SUVmean) were produced. RESULTS: All 17 patients showed 18F-florbetapir uptake at one or more extracardiac sites. Uptake was seen in the spleen in 6 patients (35%; 6 of 9, 67%, with splenic involvement on 123I-SAP scintigraphy), in the fat in 11 (65%), in the tongue in 8 (47%), in the parotids in 8 (47%), in the masticatory muscles in 7 (41%), in the lungs in 3 (18%), and in the kidney in 2 (12%) on the late half-body images. The 18F-florbetapir spleen retention index (SRI) was calculated. SRI >0.045 had 100% sensitivity/sensitivity (in relation to 123I-SAP splenic uptake, the current standard) in detecting splenic amyloid on dynamic imaging and a sensitivity of 66.7% and a specificity of 100% on the late half-body images. Intense lung uptake was seen in three patients, one of whom had lung interstitial infiltration suggestive of amyloid deposition on previous high-resolution CT. Repeat imaging showed a stable appearance in all three patients suggesting no early impact of treatment response. CONCLUSION: 18F-Florbetapir PET/CT is a promising tool for the detection of extracardiac sites of amyloid deposition. The combination of uptake in the heart and uptake in the spleen on 18F-florbetapir PET/CT, a hallmark of AL, suggests that this tracer holds promise as a screening tool for AL.

[Assessment of ability to drive in patients with MCI and dementia]. / Beurteilung der Fahrtauglichkeit bei Patienten mit MCI und demenziellen Syndromen.

People with mild cognitive impairment and dementia are a frequent and continuously increasing patient group in practically all fields of medicine. The associated challenges involve nearly all areas of life in addition to the direct medical treatment. Assessment of the ability to drive in patients with cognitive deficits is becoming increasingly more important. What are the options available to physicians in order to make a valid assessment? Which legal aspects must be taken into consideration? Which rights and obligations arise from the framework conditions? These questions nowadays give rise to great uncertainty for many medical personnel; however, the increasing importance of these problems necessitates a clear procedure, which allows difficult decisions to be made with utmost sovereignty and legal certainty and to be able to give patients and relatives a plausible explanation. Because age is a substantial risk factor for the development of cognitive disorders, the question of the ability to drive is affected not only by neuropsychiatric diseases, such as mild cognitive disorders or dementia but also the frequently occurring somatic comorbidities. Estimation of the ability to drive is therefore a complex approach, which should be standardized in order to appreciate all relevant aspects. It would be desirable to have a practice-oriented algorithm, the formulation of which is the aim of this article. Additionally, we would like to make a contribution to road safety and make medical personnel fully aware of this topic.

[Possible Significance of Bronchoalveolar Lavage Cytology at Initial Diagnosis and Follow-up of Lung Cancer]. / Evaluation zum möglichen Stellenwert der Bronchiallavagezytologie bei Erstdiagnose und Nachsorge des Lungenkarzinoms.

Bronchoalveolar lavage [BAL] is an important procedure in the diagnosis of a variety of lung diseases. While it has enormous value in the diagnostics of inflammatory parenchymal diseases, its significance in lung cancer is unclear. Keeping in mind that immune therapy (e. g. application of checkpoint inhibitors) is gaining importance in the management of lung carcinoma, it is important to know if there are typical cellular patterns in BAL of lung cancer patients. Methods In a retrospective proof of principle-study, we analyzed 38 patients who underwent BAL at the initial diagnosis of lung cancer. Results We observed an elevated level of CD25 lymphocytes as well as an increased expression of DR antigen, both signaling lymphocyte activation. We could not find a typical cytologic pattern of inflammatory cells in lung carcinoma patients. Sensitivity of BAL to malignant cells was rare, thus confirming earlier analysis. Conclusion We could not demonstrate typical cellular patterns in BAL of lung cancer patients. Evaluation of specific microRNA patterns might play a supporting role in the initial diagnosis as well as follow-up of lung cancer patients.

Disclosing large scale adverse events in the US Veterans Health Administration: lessons from media responses.

OBJECTIVES: We examined print, broadcast and social media reports about health care systems' disclosures of large scale adverse events to develop future effective messaging. STUDY DESIGN: Directed content analysis. METHODS: We systematically searched four communication databases, YouTube and Really Simple Syndication (RSS) feeds relating to six disclosures of lapses in infection control practices in the Department of Veterans Affairs occurring between 2009 and 2012. We assessed these with a coding frame derived from effective crisis and risk communication models. RESULTS: We identified 148 unique media reports. Some components of effective communication (discussion of cause, reassurance, self-efficacy) were more present than others (apology, lessons learned). Media about 'promoting secrecy' and 'slow response' appeared in reports when time from event discovery to patient notification was over 75 days. Elected officials' quotes (n = 115) were often negative (83%). Hospital officials' comments (n = 165) were predominantly neutral (92%), and focused on information sharing. CONCLUSIONS: Health care systems should work to ensure that they develop clear messages focused on what is not well covered by the media, including authentic apologies, remedial actions taken, and shorten the timeframe between event identification and disclosure to patients.

[Epitheloid cell granulomas in bronchial invasive mucinous adenocarcinoma]. / Epitheloidzellige Granulome bei bronchialem Adenokarzinom vom überwiegend muzinösen Typ.

Granulomatous lung diseases are frequently occurring pulmonary diseases.Important granulomatous lung diseases are sarcoidosis and pulmonary tuberculosis. Furthermore, granulomas can be caused by foreign body reactions like berylliosis or silicosis as well as by other infections (e. g. by nocardia spp.).Granulomatous systemic inflammatory diseases such as the Churg Strauss syndrome or the Wegener's granulomatosis can harm the lung as well.In this case report, we describe a patient who visited our emergency room because of apparent refractory pneumonia. First histologic specimens showed sarcoid-like lesions. Subsequent investigation showed invasive mucinous adenocarcinoma of the lung.

Impact of constant storage temperatures and multiple warming cycles on the quality of stored red blood cells.

BACKGROUND: Red blood cells (RBCs) are routinely stored in liquid state at temperatures below 6°C, and RBC unit core temperature should not exceed 10°C during transport. Since the critical temperature of 10°C was chosen mostly arbitrarily, this study investigated the effect of both constant temperature settings as well as multiple rewarming cycles on stored RBCs with respect to morphology, biochemical parameters and haemolysis. MATERIALS AND METHODS: Buffy coat-depleted filtered RBCs were used as standard products. RBCs were stored at 1-6°C (reference group, n = 12), 13 and 22°C (test groups, n = 12 each) or stored at 1-6°C and warmed up five times to 10, 13, or 22°C for a period of 24 h each. Various biochemical parameters were measured weekly. RBCs were further investigated using electron microscopy. RESULTS: Red blood cells stored constantly at 13 or 22°C showed stable haemolysis rates until day 28 and day 14, respectively. RBCs stored at 1-6°C with five warming-up periods to 10, 13 or 22°C each lasting 24 h (total 120 h) did not exceed the limit of the haemolysis rate at the end of storage. Differently shaped erythrocytes were found in all samples, but more crenate erythrocytes appeared after 42 days of storage independent of temperature profiles. CONCLUSION: Red cells can be kept at constant temperatures above 6°C without apparent harmful effects at least until day 14, whereas multiple warming cycles for no longer than 24 h at 10, 13 or 22°C with subsequent cooling do not cause quality loss as assessed using the in vitro assays employed in this study.

Imaging in Erdheim-Chester disease: classic features and new insights.

Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis. Osseous involvement is the most frequent feature with bilateral and symmetric osteosclerotic changes in long bone diaphyseal and metaphyseal regions, classically sparing epiphyses. 99mTc scintigraphy shows bilateral and symmetrical metaphysal and diaphyseal increased uptake in almost all the patients, even asymptomatic. Other classical features on CT-scan, very evocative of Erdheim-Chester disease, must be recognised: e.g. 'coated' aorta, 'hairy kidney' patterns. New imaging techniques such as MRI have led to a better description of cardiac and central nervous system involvements. Pachymeningitis and right atrium wall infiltration are new evocative images of this disease. Fluorodeoxyglucose Positron Emission Tomography in the diagnosis or prognosis assessment is still discussed. The objective of this review is to discuss the place of each imaging technique in Erdheim-Chester disease in 2013.