Concept Development of an On-Chip PET System.

Organs-on-Chips (OOCs), microdevices mimicking in vivo organs, find growing applications in disease modeling and drug discovery. With the increasing number of uses comes a strong demand for imaging capabilities of OOCs. Positron Emission Tomography (PET) would be ideal for OOC imaging, however, current PET systems have insufficient spatial resolution for this task. In this work, we propose the concept of an On-Chip PET system capable of imaging OOCs. Our system consists of four detectors arranged around the OOC device. Each detector is made of two monolithic Lutetium-yttrium oxyorthosilicate (LYSO) crystals and covered with Silicon photomultipliers (SiPMs) on multiple surfaces. We use a Convolutional Neural Network (CNN) trained with data from a Monte Carlo Simulation (MCS) to predict the first gamma-ray interaction position inside the detector from the light patterns that are recorded by the SiPMs on the detector's surfaces. With the Line of Responses (LORs) created by the predicted interaction positions, we reconstruct with Simultaneous Algebraic Reconstruction Technique (SART). The CNN achieves a mean average prediction error of 0.78 mm in the best configuration. We use the trained network to reconstruct an image of a grid of 21 point sources spread across the field-of-view and obtain a mean spatial resolution of 0.53 mm. We demonstrate that it is possible to achieve a spatial resolution of almost 0.5 mm in a PET system made of multiple monolithic LYSO crystals by directly predicting the scintillation position from light patterns created with SiPMs. We observe that CNNs from the ResNet family perform better than those from the EfficientNet family and that certain surfaces encode significantly more information for the scintillation-point prediction than others.

Highly luminescent scintillating hetero-ligand MOF nanocrystals with engineered Stokes shift for photonic applications.

Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm-1), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.

Reduction in broad-spectrum antimicrobial prescriptions by primary care pediatricians following a multifaceted antimicrobial stewardship program.

Background: Since 2016, following the Italian "National Plan to Contrast Antimicrobial Resistance", Campania Region has implemented an antimicrobial stewardship program, including the obligation to associate an appropriate International Classification of Diseases-9 code to each antibiotic prescription, the publication of schemes for empirical antibiotic therapy and educational interventions. Methods: To evaluate the impact of these interventions on the prescribing habits of family pediatricians, we conducted a retrospective cohort study (January 2016-December 2020), including all patients registered in an associate practice of Primary Care Pediatricians. We collected data on antibiotic prescriptions through a specific study management software; our primary outcomes were the annual prescription rates, calculated for both the number of patients in follow-up and the number of medical consultations, and the annual prescription rates for selected antibiotic classes and molecules. To investigate the hypothesis that chronic conditions would be associated with an increased rate of prescription, we also tested the association between underlying conditions and the number of antibiotics received. Results: During the study period, 2,599 children received 11,364 antibiotic prescriptions (mean 4.37, SD 4.28). From 2016 to 2020 we observed a substantial reduction in both the annual prescription rate per 100 patients (9.33 to 3.39; R 2 = 0.927, p = 0.009), and the annual prescription rate per 100 medical consultations (25.49 to 15.98; R 2 = 0.996, p < 0.01). The prescription rates of Amoxicillin-Clavulanate (50.25 to 14.21; R 2 = 0.983, p = 0.001) and third generation Cephalosporins (28.43 to 5.43; R 2 = 0.995, p < 0.01) significantly decreased; we didn't find significant modifications in the prescription rates of Amoxicillin and Quinolones; finally, we observed a trend toward reduction in the prescription of Macrolides. No statistical association was found between antibiotics prescribing frequency and history of chronic diseases. Discussion: Following the implementation of the regional interventions on antimicrobial stewardship, we observed a substantial reduction in the overall antibiotic prescription per patients and per medical consultations, with a statistically significant reduction in the use of broad-spectrum molecules. Considering the results of our analysis, new guidance and training interventions addressed to specialists in the primary care sector should be implemented to further limit antibiotic resistance.

Deep Learning for Predicting Gamma-Ray Interaction Positions in LYSO Detector.

Positron Emission Tomography (PET) is among the most commonly used medical imaging modalities in clinical practice, especially for oncological applications. In contrast to conventional imaging modalities like X-ray Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), PET retrieves in vivo information about biochemical processes rather than just anatomical structures. However, physical limitations and detector constraints lead to an order of magnitude lower spatial resolution in PET images. In recent years, the use of monolithic detector crystals has been investigated to overcome some of the factors limiting spatial resolution. The key to increasing PET systems' resolution is to estimate the gamma-ray interaction position in the detector as precisely as possible.In this work, we evaluate a Convolutional Neural Network (CNN) based reconstruction algorithm that predicts the gamma-ray interaction position using light patterns recorded with Silicon photomultipliers (SiPMs) on the crystal's surfaces. The algorithm is trained on data from a Monte Carlo Simulation (MCS) that models a gamma point source and a detector consisting of Lutetium-yttrium oxyorthosilicate (LYSO) crystals and SiPMs added to five surfaces. The final Mean Absolute Error (MAE) on the test dataset is 1.48 mm.

Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532).

BACKGROUND: Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections. MATERIALS AND METHODS: We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT. RESULTS: There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55-10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88-12.56). CONCLUSION: Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.

Cytoprotective and Antioxidant Effects of Steen Solution on Human Lung Spheroids and Human Endothelial Cells.

Respiratory diseases represent a major healthcare burden worldwide. Lung transplantation (LTx) is the "gold standard" for end-stage patients, strongly limited by shortage of available/suitable donor lungs. Normothermic ex vivo lung perfusion (EVLP) has significantly increased the number of lungs suitable for transplantation. Steen solution is used for EVLP, but the mechanisms involved in its beneficial properties remain to be clarified. We investigated the effects of Steen solution in an in vitro protocol of cold starvation and normothermic recovery on human lung spheroids, named pneumospheres (PSs), containing epithelial/basal cells, and on endothelial human umbilical vein endothelial cells (HUVEC). Steen solution significantly preserved the viability of PSs, reduced reactive oxygen species (ROS) release by PSs and HUVECs, decreased NADPH-oxidase (NOX) activity in PSs, and reduced inflammatory cytokines expression levels in HUVECs. Steen solution was able to specifically reduce NADPH oxidase 2 (NOX2) isoform activation, particularly in PSs, as detected by soluble-NOX2 peptide and p47-phosphorylation. Interestingly, a specific NOX2 inhibitor could partly mimic the pro-survival effect of Steen on PSs. We provide the first evidence that Steen solution can preserve lung epithelial/progenitor cells viability partially through NOX2 downregulation, and exert antioxidant effects on parenchymal cells, with consequent ROS reduction. These results suggest that NOX2 inhibition might be an additional strategy to reduce cellular damage during LTx procedures.

Evaluation of heart rate recovery in relation to playing position in professional soccer players.

AIM: The aim of the study was the evaluation of the autonomic cardiac function in professional soccer players by heart rate recovery (HRR) measurement after 1' or 2' of active recovery (HRR1 or HRR2, respectively) from an exercise stress test. METHODS: Ninety-two adult professional soccer players (aged 25.27 ± 4.06 years). The exercise test was performed using a cycle ergometer with a ramp protocol. The subjects began with a load of 25W that was increased by 3W every 6 seconds, followed by an active recovery phase. We assessed the heart rate at rest (HRr), the PR interval, the QT and QTc intervals, the QRS axis, the QRS duration, the maximal heart rate, and the heart rate and heart rate recovery after 1 or 2 minutes from suspension of the load. RESULTS: The HRR1 was significantly slower (20.53 SD 6.67) among goalkeepers in comparison with other roles (HRR1 30.7 SD 6.62; P<0.01). There were also significant differences among the HRR1 values of forwards (27.11 SD 4.04), midfielders (HRR1 31.31 SD 7.43), and defenders (HRR1 32.10 SD 9.55). Goalkeepers had a significantly higher heart rate at rest (HRr, 65.69 SD 10.90) than other players (HRr 57.24 SD 6.21; P<0.01). CONCLUSION: These data show better autonomic function in roles with alternate aerobic-anaerobic activity compared to other roles. The results agree with the data in other literature about the positive action of intense aerobic-anaerobic physical activity on cardiovascular autonomic system adjustment.

Aerobic exercise and non-alcoholic fatty liver disease: a case report.

Non-alcoholic steatosis (non-alcoholic fatty liver disease [NAFLD]), now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma, can also be explained by physical inactivity and increased dietary fat intake. No established treatment exists for this potentially serious disorder. The authors present the case of a 29-year-old man with NALFD who followed a restricted diet and practiced aerobic exercise for 16 weeks. Outcome after a combination therapy of aerobic exercise and diet was good, suggesting that treatment with a restricted diet and physical exercise can improve blood biochemical values in patients with NAFLD. Moderate-intensity aerobic exercise may help to normalize liver enzyme values and the quality of life of patients with fatty liver diseases.

[Dislocation of a total hip prosthesis: etiology and treatment]. / Luxation d'une arthroplastie totale de la hanche: étiologie et prise en charge.

Dislocation of a total hip prosthesis is a substantial burden in terms of morbidity and health care costs. The incidence of dislocation is highest during the first postoperative months but the risk persists throughout the entire life of the patient. The first dislocation is treated by an emergency closed reduction of the hip undergeneral anaesthesia, following which about three out of four patients will have a stable hip. In cases of recurrent dislocation the treatment is difficult, depending upon the time between surgery and dislocation, the identification of an etiologic factor, and the general status of the patient. Patients in which a specific cause can be identified have better results after surgical revision. When no causal factor is detected several surgical options are possible, but the results are less consistent.

Molecular genetics of prostate cancer: clinical translational opportunities.

Prostate cancer (PC) development reflects a complex sequence of biologic and molecular events. Several inheritable and somatic genetic changes have been identified. The knowledge of the molecular basis of PC can improve our understanding of the causes of this common cancer and provide information on prognosis and treatment. To date, however, no molecular studies have yet yielded consistent information that is ready to be incorporated into clinical practice. We reviewed the current literature on the molecular biology of prostate cancer and analyzed different potential tumor markers according to the classical concepts of oncogenes, suppressor genes, and the more modern concepts of genes involved in detoxification or inflammatory pathways of cancer progression. This review aims to identify trends in PC research and suggests potential clinical applications for diagnosis, prognosis, prevention and treatment.

In a prospective observational study, influenza vaccination prevented hospitalization among older home care patients.

OBJECTIVE: The aim of the study is (1) to describe the prevalence of vaccination against influenza in older home care patients and (2) to investigate the protective effect of influenza vaccination for hospitalization events. STUDY DESIGN AND SETTING: This is an observational study conducted in four large cohorts of elderly patients in home care during the 1998-1999, 1999-2000, 2000-2001, and 2001-2002 influenza seasons. We analyzed data from the Italian Silver Network Home Care project. A total of 2,201 patients were enrolled in the present study. The main outcome measures were prevalence of vaccination against influenza and the rate of hospitalization according to vaccination status and influenza season. RESULTS: The rate of influenza vaccination was around 48% of the studied sample. During the follow-up including the peak of influenza and the total influenza season, 412 subjects (40%) were hospitalized among vaccinated compared to 610 subjects (59%) among not vaccinated (P<0.001). After adjusting for age, gender, location of home care program, and all the variables significantly different between vaccinated and not-vaccinated subjects, vaccinated subjects were less likely to be hospitalized compared to not-vaccinated subjects (OR, 0.73; 95% CI 0.60-0.90). CONCLUSIONS: Vaccination against influenza has an important prognostic implication for frail geriatric patients living in the community.

Clinical and pathological characteristics of patients presenting with biochemical progression after radical retropubic prostatectomy for pathologically organ-confined prostate cancer.

INTRODUCTION: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). MATERIALS AND METHODS: Clinical and pathological features of 350 consecutive patients with pathologically OC PCa treated only with RP and bilateral pelvic lymphadenectomy were analyzed, retrospectively, to identify predictor parameters of prostate-specific antigen (PSA) failure (PSA>or=0.4 ng/ml). The median follow-up was 58.6 months (range: 3.9-183 months). All pathological specimens were step sectioned at 4-mm intervals. Kaplan-Meier progression-free survival rates and chi2 test were adopted for statistical analyses. Multivariate Cox proportional hazard regression models were used to test the association between pathological Gleason score and surgical margin status. RESULTS: 67 patients (19.1%) failed at a median follow-up of 40.2 months (range 1.9-123.3). Age and preoperative PSA failed to reveal significance also in patients with serum PSA>or=20 ng/ml (p=0.46). Patients with T3 clinical stage had a higher progression rate compared to T1C and T2 (43.5 vs. 27.8 and 17.3%, respectively) even if no high statistical significance was pointed out. Presence of perineural infiltration (p=0.04) and prostatic apex infiltration (p=0.74) in the prostatectomy specimens failed to reveal significance. A high pathological Gleason score (>or=7; p=0.0003) and surgical margin status (p<0.0001) were shown to be the most powerful predictive parameters of biochemical progression. CONCLUSIONS: In patients with pathologically OC PCa the presence of a high pathological Gleason score and positive surgical margins appear to represent the most important factors for prediction of outcome following RP.

A novel approach for accurate prediction of spontaneous passage of ureteral stones: support vector machines.

The objective of this study was to optimally predict the spontaneous passage of ureteral stones in patients with renal colic by applying for the first time support vector machines (SVM), an instance of kernel methods, for classification. After reviewing the results found in the literature, we compared the performances obtained with logistic regression (LR) and accurately trained artificial neural networks (ANN) to those obtained with SVM, that is, the standard SVM, and the linear programming SVM (LP-SVM); the latter techniques show an improved performance. Moreover, we rank the prediction factors according to their importance using Fisher scores and the LP-SVM feature weights. A data set of 1163 patients affected by renal colic has been analyzed and restricted to single out a statistically coherent subset of 402 patients. Nine clinical factors are used as inputs for the classification algorithms, to predict one binary output. The algorithms are cross-validated by training and testing on randomly selected train- and test-set partitions of the data and reporting the average performance on the test sets. The SVM-based approaches obtained a sensitivity of 84.5% and a specificity of 86.9%. The feature ranking based on LP-SVM gives the highest importance to stone size, stone position and symptom duration before check-up. We propose a statistically correct way of employing LR, ANN and SVM for the prediction of spontaneous passage of ureteral stones in patients with renal colic. SVM outperformed ANN, as well as LR. This study will soon be translated into a practical software toolbox for actual clinical usage.

Plasma chromogranin A in patients with prostate cancer improves the diagnostic efficacy of free/total prostate-specific antigen determination.

INTRODUCTION: We ascertained whether plasma chromogranin A enhances the power of serology assessing prostate cancer (PC). MATERIALS AND METHODS: We studied 56 PC and 83 benign prostatic hyperplasia (BPH) patients. In the sera we measured total prostate-specific antigen (tPSA) and free PSA (fPSA) and calculated the ratio between fPSA and tPSA (f/tPSA). In plasma samples the levels of chromogranin A (CgA) were also assayed. RESULTS: PC patients had higher CgA (p < 0.005) and tPSA (p < 0.05) levels, and a lower f/tPSA ratio (p < 0.001), than BPH patients. When f/tPSA and CgA were combined, the diagnostic sensitivity was enhanced (57-73%), while the specificity had only an 8% reduction (from 89 to 80%). CgA was only correlated to the Gleason PC score (p < 0.05). CONCLUSIONS: CgA determination in PC may enhance the diagnostic accuracy of the f/tPSA assay and provides useful information on the tumor grade.

[Usefulness of directional power Doppler sonography in the ultrasound-guided percutaneous native kidney biopsy]. / Utilita' dell'Eco Power Doppler direzionale nella biopsia transcutanea su rene nativo.

BACKGROUND: The study was aimed to analyze the pattern of bleeding throughout the kidney tissue after renal biopsy and evaluate its relationship with the onset of renal biopsy side effects by using directional power-Doppler sonography. PATIENTS: Eighty-five consecutive subjects with clinical evidence of renal disease underwent to percutaneous renal biopsy using directional power Doppler sonography. In each patient, the pattern of kidney hemorrhage immediately after the renal biopsy was evaluated. RESULTS: Fifty-seven patients, representing 67% of all biopsies performed, evidenced renal bleeding lasting 5.3+/-5.7 min; fifty-five patients, representing 65% of all biopsies, developed a post biopsy hematoma (x = 2.9+/-2.0 cm); 36% of patients developed a perirenal hematoma (x = 1.8+/-2.1 cm). A subcapsular hematoma was experienced by 45% of patients (x = 2.7+/-1.1 cm); 16% of these patients had a combined perirenal-subcapsular hematoma; 5% of hematomas were larger than 5 cm. Hematoma dimensions were related to the length of bleeding (r = 0.6331; p < 0.0001). Hemoglobin and hematocrit levels significantly reduced from 12.7+/-2.3 g/dL to 11.7+/-2.3 g/dL (-7%, p < 0.0001) and 37.6+/-6.5% to 35.4+/-6.5% (-6%, p < 0.0001) respectively, and such variations were related to the hematoma size (Delta Hb: r = -0.5171; p < 0.0001; Delta Htc: r = -0.3465; p < 0.0001). CONCLUSIONS: This study demonstrates that directional power Doppler sonography allows medical personnel to clearly evidence all renal biopsy-related side effects and identify, through the evaluation of renal bleeding immediately after the kidney biopsy, those patients who will develop renal hematomas.

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

OBJECTIVES: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS: Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS: This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-alpha aopototic signaling.

We have investigated the effects of arachidonic and palmitic acids in isolated rat liver mitochondria and in rat hepatoma MH1C1 cells. We show that both compounds induce the mitochondrial permeability transition (PT). At variance from palmitic acid, however, arachidonic acid causes a PT at concentrations that do not cause PT-independent depolarization or respiratory inhibition, suggesting a specific effect on the PT pore. When added to intact MH1C1 cells, arachidonic acid but not palmitic acid caused a mitochondrial PT in situ that was accompanied by cytochrome c release and rapidly followed by cell death. All these effects of arachidonic acid could be prevented by cyclosporin A but not by the phospholipase A(2) inhibitor aristolochic acid. In contrast, tumor necrosis factor alpha caused phospholipid hydrolysis, induction of the PT, cytochrome c release, and cell death that could be inhibited by both cyclosporin A and aristolochic acid. These findings suggest that arachidonic acid produced by cytosolic phospholipase A(2) may be a mediator of tumor necrosis factor alpha cytotoxicity in situ through induction of the mitochondrial PT.