Expanding the medical physicist curricular and professional programme to include Artificial Intelligence.

PURPOSE: To provide a guideline curriculum related to Artificial Intelligence (AI), for the education and training of European Medical Physicists (MPs). MATERIALS AND METHODS: The proposed curriculum consists of two levels: Basic (introducing MPs to the pillars of knowledge, development and applications of AI, in the context of medical imaging and radiation therapy) and Advanced. Both are common to the subspecialties (diagnostic and interventional radiology, nuclear medicine, and radiation oncology). The learning outcomes of the training are presented as knowledge, skills and competences (KSC approach). RESULTS: For the Basic section, KSCs were stratified in four subsections: (1) Medical imaging analysis and AI Basics; (2) Implementation of AI applications in clinical practice; (3) Big data and enterprise imaging, and (4) Quality, Regulatory and Ethical Issues of AI processes. For the Advanced section instead, a common block was proposed to be further elaborated by each subspecialty core curriculum. The learning outcomes were also translated into a syllabus of a more traditional format, including practical applications. CONCLUSIONS: This AI curriculum is the first attempt to create a guideline expanding the current educational framework for Medical Physicists in Europe. It should be considered as a document to top the sub-specialties' curriculums and adapted by national training and regulatory bodies. The proposed educational program can be implemented via the European School of Medical Physics Expert (ESMPE) course modules and - to some extent - also by the national competent EFOMP organizations, to reach widely the medical physicist community in Europe.

Enhancement of the Inelastic Nuclear Interaction Rate in Crystals via Antichanneling.

The interaction rate of a charged particle beam with the atomic nuclei of a target varies significantly if the target has a crystalline structure. In particular, under specific orientations of the target with respect to the incident beam, the probability of inelastic interaction with nuclei can be enhanced with respect to the unaligned case. This effect, which can be named antichanneling, can be advantageously used in the cases where the interaction between beam and target has to be maximized. Here we propose to use antichanneling to increase the radioisotope production yield via cyclotron. A dedicated set of experimental measurements was carried out at the INFN Legnaro Laboratories with the AN2000 and CN accelerators to prove the existence of the antichanneling effect. The variation of the interaction yield at hundreds of keV to MeV energies was observed by means of sapphire and indium phosphide crystals, achieving an enhancement of the interaction rate up to 73% and 25%, respectively. Such a result may pave the way to the development of a novel type of nozzle for the existing cyclotrons, which can exploit crystalline materials as targets for radioisotope production, especially to enhance the production rate for expensive prime materials with minor upgrades of the current instrumentation.

Acute pancreatitis and acute kidney injury in dogs.

Acute pancreatitis and acute kidney injury are well-documented comorbidities in human medicine. Dogs that develop acute kidney injury during hospitalization have significantly higher mortality rates than those that do not. The aim of this study was to evaluate the prevalence of acute kidney injury in dogs with acute pancreatitis and the prognostic value of various clinicopathological parameters. Cases of acute pancreatitis presented between January 2012 and June 2016 were identified. The diagnosis of acute pancreatitis was based on two or more of the following clinical signs: abdominal pain, diarrhea, vomiting or anorexia/hyporexia, no other abdominal extra-pancreatic diseases at abdominal ultrasound, and abnormal SNAP cPL test. Diagnosis of acute kidney injury was based on the guidelines of the International Renal Interest Society. Dogs were classified into survivors and non-survivors. Serum creatinine, urea, amylase, total calcium, total cholesterol, C-reactive protein, WBC and band neutrophils were evaluated at admission. Clinical severity index was calculated at admission. Clinical and clinicopathological data were compared between survivors and non-survivors. Sixty-five dogs with acute pancreatitis were assessed. Clinical severity index≥6.5 were associated with poor outcome (P=0.0011). Serum urea and creatinine concentrations at admission were significantly lower in survivors than non-survivors (P<0.0001 and P=0.0002, respectively). Acute kidney injury was diagnosed in 17/65 dogs (26.2%) and was associated with poor outcome (P<0.0001). Oligo-anuria was associated with poor outcome (P=0.0294). Increased clinical severity index and azotemia in dogs with acute pancreatitis were associated with an increased risk of mortality. Acute kidney injury may be a comorbidity of canine acute pancreatitis. The presence of oligo-anuria is associated with poor outcome.

Correction to: Plasma alpha-tocopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study.

The above article originally published with an error present in the article title, "Plasma alpha-tochopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study" this should instead have read, "Plasma alpha-tocopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study" [bold text used to highlight problem area].

Clinical utility of urine kidney injury molecule-1 (KIM-1) and gamma-glutamyl transferase (GGT) in the diagnosis of canine acute kidney injury.

The aim of the present study was to evaluate the sensitivity and specificity of urine KIM-1 and urine GGT for the detection of naturally-occurring AKI, compared to healthy control dogs, dogs with stable chronic kidney disease (CKD), and dogs with lower urinary tract disorders (LUTD). The study included AKI grade 1 (n = 21), AKI grade 2 to 5 (n = 11), stable CKD (n = 11), LUTD (n = 15), and healthy dogs (n = 37). Urine KIM-1 (ng/mg) and GGT (U/l) were normalized to urine creatinine (uCr). Statistically significant difference in KIM/uCr (p = 0.0007) and GGT/uCr (p < 0.0001) was found among the study groups. Area under the curve (AUC) for KIM-1/uCr and GGT/uCr as predictors of AKI was 0.81 and 0.91 respectively. Values of KIM-1/uCr of 0.73 ng/mg and of GGT/uCr of 54.33 showed the best combination of sensitivity and specificity (75% and 75.6%; 85.7% and 89.1% respectively). A significant positive correlation (p < 0.0001) between KIM-1/uCr and GGT/uCr was found. Both urine KIM-1/uCr and GGT/uCr seemed to be potentially good markers for the diagnosis of AKI. Dogs with AKI showed significantly higher levels of urine KIM-1/uCr and urine GGT/uCr, compared with healthy dogs. Caution should be used in the evaluation of elevated urine KIM-1/uCr and GGT/uCr in dogs with pre-existing CKD and/or LUTD. Urine KIM-1/uCr and GGT/uCr might have a significant clinical utility, as complementary test, particularly in diagnosis early, non-azotemic stages of AKI.

Plasma alpha-tochopherol determined by HPLC in dogs at different stages of chronic kidney disease: a retrospective study.

The aim of the present study was to investigate retrospectively the plasma concentration of alpha-tocopherol in dogs with naturally acquired chronic kidney disease (CKD), at different stages of severity. Forty dogs (CKD group) with different stages of CKD (IRIS 1 n=12, IRIS 2 n=8, IRIS 3 n=11, IRIS 4 n=9) and 20 clinically healthy dogs were considered. Plasma alpha-tocopherol was assessed in both groups through high performance liquid chromatography (HPLC). Dogs of CKD group showed significantly lower (p=0.0002) levels of plasma alpha-tocopherol compared with clinically healthy dogs. A significant difference (p<0.04) in the number of patients with plasma alpha-tocopherol > or ≤ 21.5 ppm was found in CKD patients at different stages of severity. No significant correlation between plasma levels of alpha-tocopherol and plasma creatinine was found. In the present study, dogs affected by spontaneous CKD showed significantly lower plasma concentrations of alpha-tocopherol compared with clinically healthy dogs. Plasma alpha-tocopherol deficiency seems to be more severe in IRIS stage 1 and 4, compared with IRIS stage 2 and 3. The finding of marked alpha-tocopherol deficiency in patients in IRIS stage 1 should encourage further studies on the early use of prescription renal diet and antioxidant in this group of patients.

A machine learning tool for re-planning and adaptive RT: A multicenter cohort investigation.

PURPOSE: To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset. MATERIALS AND METHODS: 90 patients (pts) treated for head-neck cancer (H&N) formed a multicenter data-set. 41 H&N pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG). Using deformable image registration (DIR) and GPU, patients' conditions were analyzed automatically. Support Vector Machines (SVM) was used for time-series evaluation. "Inadequate" class identified patients that might benefit from replanning. Double-blind evaluation by two radiation oncologists (ROs) was carried out to validate day/week selected for re-planning by the classifier. RESULTS: The cohort was affected by PG mean reduction of 23.7±8.8%. During the first 3weeks, 86.7% cases show PG deformation aligned with predefined tolerance, thus not requiring re-planning. From 4th week, an increased number of pts would potentially benefit from re-planning: a mean of 58% of cases, with an inter-center variability of 8.3%, showed "inadequate" conditions. 11% of cases showed "bias" due to DIR and script failure; 6% showed "warning" output due to potential positioning issues. Comparing re-planning suggested by tool with recommended by ROs, the 4th week seems the most favorable time in 70% cases. CONCLUSIONS: SVM and decision-making tool was applied to overcome ART challenges. Pts would benefit from ART and ideal time for re-planning intervention was identified in this retrospective analysis.

Urinary capillariosis in six dogs from Italy.

Canine urinary capillariosis is caused by the nematode Pearsonema plica. P. plica infection is seldomly detected in clinical practice mainly due to diagnostic limitations. This report describes six cases of urinary capillariosis in dogs from Italy. Recurrent cystitis was observed in one dog, whereas another patient was affected by glomerular amyloidosis. In the remaining animals, the infection was considered an incidental finding. Immature eggs of the parasite were observed with urine sediment examination in 3/6 patients. Increased awareness of the potential pathogenic role of P. plica and clinical disease presentation could help identify infected animals.

Relationship between pharmacokinetics and pharmacodynamics of clopidogrel in patients undergoing percutaneous coronary intervention: comparison between vasodilator-stimulated phosphoprotein phosphorylation assay and multiple electrode aggregometry.

UNLABELLED: ESSENTIALS: The reliability of platelet tests as markers of the variable bioavailability of clopidogrel is not yet defined. Kinetics of clopidogrel active metabolite (CAM) and platelet response were studied in ischemic heart disease. CAM plasma maximum concentration (Cmax ) predicted vasodilator-stimulated phosphoprotein (VASP-P). Timely performed VASP-P, not an aggregation-based test, may be a surrogate for clopidogrel bioavailability. BACKGROUND: The high inter-individual variability in the inhibition of platelet function by clopidogrel is mostly explained by high variability in its transformation to an active metabolite (CAM). Objective We investigated the relations between pharmacokinetics and pharmacodynamics of CAM by comparing two methods of platelet function. METHODS: We enrolled 14 patients undergoing percutaneous coronary interventions for non-ST-segment elevation acute coronary syndrome or inducible myocardial ischemia. Plasma concentrations of clopidogrel and CAM, phosphorylation of vasodilator-stimulated phosphoprotein (VASP-P), expressed as a platelet reactivity index (PRI) and whole-blood platelet aggregation (multiple electrode aggregometer, MEA) were measured before and after a 600-mg clopidogrel loading dose (nine time-points) and before and after 75-mg maintenance doses on days 2, 7 and 30. RESULTS: Plasma concentrations of clopidogrel and CAM were highly variable. CAM reached maximal concentration (Cmax ) (median, 110.8 nm; range, 41.9-484.8) 0.5-2 h after the loading dose. A sigmoid dose-response curve defined the relations between CAMCmax and PRI after 3 to 24 h (IC50 , 459.6 nm; 95% confidence interval, 453.4-465.7; R(2) = 0.82). PRI was unchanged from baseline in patients with the lowest CAMCmax (< 83 nm, n = 7), indicating low sensitivity of VASP-P. PRI values were also predicted by CAMCmax at days 2, 7 and 30. Platelet aggregation measured by MEA did not show significant relations with either PRI or with CAM pharmacokinetics at any time-point. CONCLUSIONS: After 600 mg clopidogrel, VASP-P, but not whole-blood platelet aggregation measured by MEA, is almost entirely predicted by CAMCmax . VASP-P could be useful in studies aimed at investigating relations between CAM bioavailability and clinical events.

Voluntary and controlled weight loss can reduce symptoms and proton pump inhibitor use and dosage in patients with gastroesophageal reflux disease: a comparative study.

A wide variety of pieces of evidence has suggested that obesity is associated with a significant increase in the risk for gastroesophageal reflux disease (GERD) symptoms and its complications. The aim of this study was to evaluate the effect of weight loss on reflux symptoms in overweight/obese patients with proven GERD. We enrolled overweight/obese patients with typical GERD symptoms and erosive esophagitis. At baseline, patients underwent detailed reflux symptoms evaluation and anthropometric assessment, and were divided into two treatment groups: group A received proton pump inhibitor (PPI) and a personalized hypocaloric diet and aerobic exercise; and group B received PPI and a 'standard of care diet'. The dietetic treatment was considered effective if at least 10% of weight loss was achieved within 6 months. All patients were evaluated in terms of anthropometric data, GERD symptoms, and PPI use. In group A, mean body mass index (BMI) decreased from 30.3 ± 4.1 to 25.7 ± 3.1 (P < 0.05), and mean weight decreased from 82.1 ± 16.9 kg to 69.9 ± 14.4 kg (P < 0.05). In group B, there was no change in BMI and weight. Symptom perception decreased (P < 0.05) in both groups during PPI therapy, but a higher improvement was recorded in group A. In group A, PPI therapy was completely discontinued in 27/50 of the patients, and halved in 16/50. Only 7/50 continued the same PPI dosage. In group B, 22/51 halved the therapy and 29/51 maintained full dosage of therapy, but none was able to discontinue PPI due to a symptom recurrence. Overall, weight loss of at least 10% is recommended in all patients with GERD in order to boost the effect of PPI on reflux symptom relief and to reduce chronic medication use.

Double filtration plasmapheresis in a dog with multiple myeloma and hyperviscosity syndrome.

A 12 year old, 38 kg, mix-breed, intact male dog presented with a 20 day history of clinical signs consistent with hyperviscosity syndrome secondary to multiple myeloma. The dog received three double filtration plasmapheresis treatments on day 0, 7 and 22 after presentation. A significant (p<0.05) reduction in serum total protein, alpha-2 and gamma globulins was found following each treatment. These reductions were accompanied by a complete resolution, although temporary, of the clinical signs of hyperviscosity syndrome. The present study reported for the first time the use of double filtration plasmapheresis to reduce clinical signs of hyperviscosity syndrome in a dog with multiple myeloma.

Plasma Procalcitonin Concentration in Healthy Horses and Horses Affected by Systemic Inflammatory Response Syndrome.

BACKGROUND: The diseases most frequent associated with SIRS in adult horses are those involving the gastrointestinal tract. An early diagnosis should be the goal in the management of horses with SIRS. OBJECTIVE: The objective of this study was to evaluate the plasma procalcitonin (PCT) concentration in healthy and SIRS horses to assess differences between the two groups. ANIMALS: Seventy-eight horses (30 healthy and 48 SIRS). METHODS: Prospective in vivo multicentric study. Horses were classified as SIRS if at least 2 of the following criteria were met: abnormal leukocyte count or distribution, hyperthermia or hypothermia, tachycardia, tachypnea. Healthy horses showed no clinical or laboratory signs of SIRS. Plasma PCT concentrations were measured with a commercial ELISA assay for equine species. Results were expressed as mean±standard deviation. T-test for unpaired data was performed between healthy and SIRS group. SIRS group was divided in 4 subgroups and t-test was performed between healthy versus each subgroup. RESULTS: PCT concentrations in healthy and SIRS horses were 18.28 ± 20.32 and 197.0 ± 117.0 pg/mL, respectively. T-test showed statistical differences between healthy versus SIRS group and between healthy versus all subgroups. CONCLUSIONS AND CLINICAL IMPORTANCE: Results showed an increase in PCT concentration in SIRS horses as previously reported in humans and dogs. PCT could be used as a single assay in equine practice for detection of SIRS.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

Sodium citrate blood contamination by K2 -ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing.

INTRODUCTION: The potential cross-contamination of additives between primary blood tubes is a well-known problem during sample collection. The aim of this study was to assess the impact of citrated blood contamination with different amounts of dipotassium ethylenediaminetetraacetic (K2 EDTA blood) on activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen. METHODS: Blood was collected from 15 ostensibly healthy volunteers into four 0.109 m citrate blood tubes followed by one K2 EDTA blood tube. The citrate tubes of each subject were pooled and divided in five aliquots. The whole blood of the K2 EDTA tube was then added in scalar amounts to autologous citrated blood aliquots, to obtain K2 EDTA contamination ranging from 0% to 43%, and thus mimic potential pre-analytical contamination. RESULTS: A statistically and clinically significant prolongation was observed for both APTT and PT between 29% and 43% K2 EDTA contamination, whereas the decrease of fibrinogen values became statistically and clinically significant at 43% K2 EDTA contamination. CONCLUSION: The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management.

Retrospective study of 14 cases of canine arthritis secondary to Leishmania infection.

OBJECTIVE: To describe the clinical appearance, laboratory findings and response to treatment of dogs with inflammatory joint disease associated with Leishmania infection. METHODS: Retrospective analysis of case records of dogs with serologically confirmed leishmaniasis and concurrent inflammatory joint disease presented between 2005 and 2011. RESULTS: In total, 14 cases met the inclusion criteria. Of these, five (36%) dogs were presented with monoarthritis, five (36%) with oligoarthritis and four (28%) with polyarthritis. The most frequently affected joint was the carpus. Both erosive and non-erosive disease was identified on radiographic examination. All dogs had an inflammatory synovial fluid with a high white cell count and a preponderance of neutrophils, and in eight (57%) cases Leishmania amastigotes were found in the synovial fluid smears. Dogs were treated with 50 mg/kg N-methylglucamine antimoniate twice a day for 1 month and 10 mg/kg allopurinol twice a day for 6 to 9 months combined with prednisolone in five cases. At the 6-month follow-up, eight (57%) dogs showed improvement in general and orthopaedic signs and four (28%) dogs were stable. CLINICAL SIGNIFICANCE: Leishmaniasis should be considered a differential diagnosis in dogs with inflammatory arthritis in endemic areas.

Bimatoprost 0.01% vs bimatoprost 0.03%: a 12-month prospective trial of clinical and in vivo confocal microscopy in glaucoma patients.

PURPOSE: To evaluate the safety of two commercially available formulations of bimatoprost eye drops: 0.03 and 0.01% ophthalmic solutions. METHODS: This was a randomized, prospective, parallel-group, open-label, cohort study. A total of 60 glaucoma patients (60 eyes) under bimatoprost 0.03% monotherapy since at least 1 year were enrolled. Selected patients were randomized to receive a single drop of bimatoprost 0.01% (n=30) or bimatoprost 0.03% (n=30) ophthalmic solutions for 12 months. Statistical analysis was performed using paired t-test and repeated measures ANOVA test. RESULTS: Global clinical score (the sum of pruritus, stinging/burning, blurred vision, sticky eye sensation, eye dryness sensation, and foreign body sensation) significantly decreased in the bimatoprost 0.01% group from baseline 4.7 ± 3.8 to 2.9 ± 2.3 (P < 0.001) and 2.5 ± 2.0 (P < 0.001) at 6-month and 12-month follow-ups, respectively. Comparison between groups showed differences at both follow-up visits (P = 0.003 and P < 0.001, respectively). In vivo confocal microscopy revealed a significant increase in goblet cell density in the bimatoprost 0.01% group compared with the bimatoprost 0.03% group (P<0.001 at both follow-up visits). All functional parameters and conjunctival hyperemia improved in the bimatoprost 0.01% group at each follow-up visit (P < 0.05) and in comparison with bimatoprost 0.03% (P < 0.05). CONCLUSION: The results of this trial suggest that bimatoprost 0.01% eye drops seem to decrease the ocular discomfort with respect to bimatoprost 0.03% eye drops.

High sodium intake is associated with increased glucocorticoid production, insulin resistance and metabolic syndrome.

OBJECTIVE: High sodium (HS) diet is associated with hypertension (HT) and insulin resistance (IR). We evaluated whether HS diet was associated with a dysregulation of cortisol production and metabolic syndrome (MetS). PATIENTS AND MEASUREMENTS: We recruited 370 adults (18-85 years, BMI 29·3 ± 4·4 kg/m(2) , 70% women, 72% HT, 61% MetS). HS diet (urinary sodium >150 mEq/day) was observed in 70% of subjects. We measured plasma hormones, lipid profile, urinary free cortisol (UFC) and cortisol tetrahydrometabolites (THM). RESULTS: Urinary sodium was correlated with UFC (r = +0·45, P < 0·001), cortisol THM (r = +0·41, P < 0·001) and inversely with adiponectin, HDL and aldosterone, after adjusting by age, gender and BMI. Subjects with high, compared with adequate sodium intake (50-149 mEq/day) had higher UFC (P < 0·001), THM (P < 0·001), HOMA-IR (P = 0·04), HT (81% vs 50%, P < 0·001), MetS (69% vs 41%, P < 0·001) and lower adiponectin (P = 0·003). A multivariate predictive model adjusted by confounders showed a high discriminative capacity for MetS (ROC curve 0·878) using four clinical variables: HS intake [OR = 5·6 (CI 2·3-15·3)], HOMA-IR [OR 1·7 (1·3-2·2)] cortisol THM [OR 1·2 (1·1-1·4)] and adiponectin [OR = 0·9 (0·8-0·9)], the latter had a protective effect. CONCLUSIONS: High sodium diet was associated with increased urinary cortisol and its metabolites. Also, HS diet was associated with HT, insulin resistance, dyslipidaemia and hypoadiponectinaemia, even when adjusting by confounding variables. Further, we observed that high salt intake, IR and higher cortisol metabolites, alone or combined in a clinical simple model, accurately predicted MetS status, suggesting an additive mechanism in obesity-related metabolic disorders.

Redox status evaluation in dogs affected by mast cell tumour.

Oxidative stress status has been evaluated in depth in human medicine and its role in carcinogenesis has been clearly established. The purpose of this prospective study was to evaluate antioxidant concentrations and oxidative stress in dogs with mast cell tumours (MCTs) that had received no previous treatments, and to compare them to healthy controls. In 23 dogs with mast cell tumour and 10 healthy controls, oxidative status was assessed using the Reactive Oxygen Metabolites-derived compounds (d-ROMs) test, antioxidant activity was measured by the Biological Antioxidant Potential (BAP) test, and α-tocopherol levels were evaluated using high-performance liquid chromatography and ultraviolet analysis. At baseline, dogs with MCT had significantly higher d-ROMs (P < 0.00001) and lower BAP (P < 0.0002) compared with healthy controls. However, no significant difference was observed for α-tocopherol (P = 0.95). Results suggest that oxidative stress pattern and oxidative defence barrier are altered in dogs with newly diagnosed MCT compared with control dogs. Future studies are needed in order to assess the prognostic role of oxidative stress and to evaluate the impact of different therapeutic approaches.