Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition.

Injuries to skeletal muscle are among the most common injuries in civilian and military populations, accounting for nearly 60% of extremity injuries. The standard of care for severe extremity injury has been focused upon limb salvage procedures and the utilization of tissue grafts or orthotics in conjunction with rehabilitation to avoid amputation. Nonetheless, many patients have persistent strength and functional deficits that permanently impact their quality of life. Preclinical and clinical studies have shown that partial restoration of functional skeletal muscle tissue following injury can be achieved by the implantation of a biologic scaffold composed of extracellular matrix (ECM). These favorable outcomes are mediated, at least in part, through local immunomodulation. The mechanisms underlying this immunomodulatory effect, however, are poorly understood. The present study investigates a potential mechanistic driver of the immunomodulatory effects; specifically, the effect of selected ECM components upon inflammation resolution and repair. Results show that the host response to skeletal muscle injury is profoundly altered and functional recovery decreased in il33-/- mice compared to age- and sex-matched wildtype counterparts by 14 days post-injury. Results also show that IL-33, contained within matrix-bound nanovesicles (MBV), supports skeletal muscle regeneration by regulating local macrophage activation toward a pro-remodeling phenotype via canonical and non-canonical pathways to improve functional recovery from injury compared to untreated il33-/- counterparts. Taken together, these data suggest that MBV and their associated IL-33 cargo represent a novel homeostatic signaling mechanism that contributes to skeletal muscle repair.

Uncovering the "riddle of femininity" in osteoarthritis: a systematic review and meta-analysis of menopausal animal models and mathematical modeling of estrogen treatment.

OBJECTIVE: Post-menopausal women are disproportionately affected by osteoarthritis (OA). As such, the purpose of this study was to (1) summarize the state-of-the-science aimed at understanding the effects of menopause on OA in animal models and (2) investigate how dosage and timing of initiation of estrogen treatment affect cartilage degeneration. DESIGN: A systematic review identified articles studying menopausal effects on cartilage in preclinical models. A meta-analysis was performed using overlapping cartilage outcomes in conjunction with a rigor and reproducibility analysis. Ordinary differential equation models were used to determine if a relationship exists between cartilage degeneration and the timing of initiation or dosage of estrogen treatment. RESULTS: Thirty-eight manuscripts were eligible for inclusion. The most common menopause model used was ovariectomy (92%), and most animals were young at the time of menopause induction (86%). Most studies did not report inclusion criteria, animal monitoring, protocol registration, or data accessibility. Cartilage outcomes were worse in post-menopausal animals compared to age-matched, non-menopausal animals, as evidenced by cartilage histological scoring [0.75, 1.72], cartilage thickness [-4.96, -0.96], type II collagen [-4.87, -0.56], and c-terminal cross-linked telopeptide of type II collagen (CTX-II) [2.43, 5.79] (95% CI of Effect Size (+greater in menopause, -greater in non-menopause)). Moreover, modeling suggests that cartilage health may be improved with early initiation and higher doses of estrogen treatment. CONCLUSIONS: To improve translatability, animal models that consider aging and natural menopause should be utilized, and more attention to rigor and reproducibility is needed. Timing of initiation and dosage may be important factors modulating therapeutic effects of estrogen on cartilage.

Assessment of SARS-CoV-2 airborne infection transmission risk in public buses.

Public transport environments are thought to play a key role in the spread of SARS-CoV-2 worldwide. Indeed, high crowding indexes (i.e. high numbers of people relative to the vehicle size), inadequate clean air supply, and frequent extended exposure durations make transport environments potential hotspots for transmission of respiratory infections. During the COVID-19 pandemic, generic mitigation measures (e.g. physical distancing) have been applied without also considering the airborne transmission route. This is due to the lack of quantified data about airborne contagion risk in transport environments. In this study, we apply a novel combination of close proximity and room-scale risk assessment approaches for people sharing public transport environments to predict their contagion risk due to SARS-CoV-2 respiratory infection. In particular, the individual infection risk of susceptible subjects and the transmissibility of SARS-CoV-2 (expressed through the reproduction number) are evaluated for two types of buses, differing in terms of exposure time and crowding index: urban and long-distance buses. Infection risk and reproduction number are calculated for different scenarios as a function of the ventilation rates (both measured and estimated according to standards), crowding indexes, and travel times. The results show that for urban buses, the close proximity contribution significantly affects the maximum occupancy to maintain a reproductive number of <1. In particular, full occupancy of the bus would be permitted only for an infected subject breathing, whereas for an infected subject speaking, masking would be required. For long-distance buses, full occupancy of the bus can be maintained only if specific mitigation solutions are simultaneously applied. For example, for an infected person speaking for 1 h, appropriate filtration of the recirculated air and simultaneous use of FFP2 masks would permit full occupancy of the bus for a period of almost 8 h. Otherwise, a high percentage of immunized persons (>80%) would be needed.

Combined treatment of myo-inositol and d-chiro-inositol (80:1) as a therapeutic approach to restore inositol eumetabolism in patients with bipolar disorder taking lithium and valproic acid.

OBJECTIVE: Patients with bipolar disorder (BD) experience a poor quality of life (QoL) and a weak adherence to the therapy due to the various side effects occurring during the pharmacological therapy. To date clinicians have no tools to intervene on such effects, considering them as an unavoidable part of the therapy. This review paves the way for a step forward in the management of patients with BD bridging the therapeutic gap in clinical practice. MATERIALS AND METHODS: We reviewed the literature, searching through different databases (MEDLINE, Scopus, Google Scholar). We used different keywords, including bipolar disorder, lithium and valproic acid, inositol role in bipolar disorder, side effects, inositol depletion, supplementation of inositols under lithium treatment, inositol role in metabolism, hypothyroidism, renal and cardiac functionality. In particular, we narrowed the search down to English literature, excluding works before 1980s. Regarding clinical studies, we included case reports and both preclinical and clinical studies, especially only those exhibiting a control group. The outcome of the database search was to highlight the threat of side effects and the relationship with inositol lower levels, paving the way for a step forward in the management of patients with BD. RESULTS: Based on the collected evidence, the combined administration of myo-inositol (myo-ins) and d-chiro-inositol (d-chiro-ins) is strongly recommended in order to restore levels and metabolism of inositols. Previous studies pointed out the beneficial effects of inositols in recovering pathological conditions, like polycystic ovary syndrome (PCOS), hypothyroidism, weight gain, cardiac functionality, being all these conditions related to the depletion of inositols. Furthermore, a controlled dosage of inositols, up to 6 grams/daily, may reduce the side effects caused by lithium therapy, without hindering its central therapeutic role on patients' mood. CONCLUSIONS: Considering the iatrogenic depletion of inositols, the tailored ratio 80:1 in favour of myo-ins, may become a safe and effective strategy to counteract side effects, by providing a large amount of myo-ins and an adequate one of d-chiro-ins. The clinical dosage of inositols used as dietary supplementation is 4 grams/daily, and it may allow the recovery of the side effects and improve patients' QoL, without reducing the central therapeutic effect of the pharmacological therapy.

Gemelli decision tree Algorithm to Predict the need for home monitoring or hospitalization of confirmed and unconfirmed COVID-19 patients (GAP-Covid19): preliminary results from a retrospective cohort study.

OBJECTIVE: To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring. PATIENTS AND METHODS: We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity. RESULTS: Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G2 value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G2 and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated. CONCLUSIONS: We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.

Fast off-line FPSE-HPLC-PDA determination of six NSAIDs in saliva samples.

A fast off-line FPSE-HPLC-PDA method has been reported that allows simultaneous clean up and determination of six non-steroidal anti-inflammatory drugs (NSAIDs) in saliva samples from healthy volunteers. Particularly, furprofen, indoprofen, ketoprofen, fenbufen, flurbiprofen, and ibuprofen were chromatographically resolved. Benzyl paraben was chosen as the internal standard (BzPB, IS). These target compounds were successfully extracted from human saliva using fabric phase sorptive extraction (FPSE) and then analysed in the liquid chromatographic system by means of a short analytical column (Symmetry C18, 75 × 4.6 mm, 3.5 µm) using acetonitrile (AcN) and phosphate buffer (PBS, 30 mM; pH = 2.5) as the mobile phases. The method, validated through the calculation of all analytical parameters in accordance of International Guidelines, was applied to real saliva sample analysis collected from informed volunteers. The proposed approach that included the use of sol-gel polytetrahydrofuran (sol-gel PTHF) sorbent immobilized on cellulose support and C18 stationary phase used in HPLC, showed high potential as a fast tool for future clinical and forensic applications. The herein reported results encourage potential future application of FPSE in the forensic field. Furthermore, the FPSE membrane was tested in dried saliva spot mode (DSS) in order to check its potential use as a sampling device, also for forensic applications.

Biofluid sampler: A new gateway for mail-in-analysis of whole blood samples.

The current study reports the development of a novel biofluid sampler (BFS) which is capable of sampling and sample preparation of whole blood without converting it into plasma or serum. The sampler can retain a whole blood sample from 10 to 1000 µL. Although the device shares the same working principle of dried blood spot (DBS) cards, it eliminates most of the technological shortcomings of DBS cards such as low maximum sample volume (~50 µL), sample inhomogeneity due to haematocrit, and poor physical adsorption driven analyte retention by incorporating sol-gel derived high efficiency, multi-functional sorbents on cellulose fabric substrate. The performance of BFS was tested via "Mail-in-Analysis" using three non-steroidal anti-inflammatory drugs (NSAIDs, ketoprofen, carprofen and diclofenac) as the test compounds. Human whole blood samples were fortified with the test compounds and sampled on conventional DBS cards and biofluid samplers (BFSs) in the USA. After drying the blood samples at room temperature, the samples were shipped to Italy for chromatographic analysis. The analytes were back-extracted from the DBS cards and BFSs using methanol and subsequently analysed using a short Symmetry C18 column (75 × 4.6 mm, 3.5 µm). Acetonitrile (ACN) and PBS (30 mM; pH = 2.5) were used as the mobile phases and the elution was performed under isocratic conditions. Compared to the classical dried blood spot cards (DBS), BFSs offer better performance in retaining the selected NSAIDs under conventional postal shipment. By substantially expanding the sampling capacity, eliminating most of the shortcomings of classical DBS cards and exploiting the better materials properties of sol-gel based functional sorbents, BFSs offer a new and profoundly simplified approach for whole blood sampling and analysis and is expected to change the current practice of blood analysis, allowing accurate quantitative analyses either in a local laboratory (on site) or using mail-in-analysis (off site) without compromising the quality of bioanalytical data.

Dietary solutions to dyslipidemia: Milk protein-polysaccharide conjugates as liver biochemical enhancers.

Protein-polysaccharide interactions have been a focus of scientific attention. This study aimed to improve the antioxidant and hepatoprotective effects of buffalo total milk proteins and whey protein hydrolysate (WPH) through noncovalent interactions with Psyllium husk (ispaghula) mucilage (PHM) and Nabq mucilage (NabM). Chemical composition, phenolic content, and antioxidant activities of milk protein-mucilage complexes were explored. The effects of resulting complexes on liver function, hyperlipidemia, and histopathology of the liver in rats fed high-fat diet (HFD) were investigated. The results showed that the complexes exerted significant effect on normalizing tested parameters; WPH-NabM had the most significantly decreased level of malondialdehyde content and the liver histopathological examination proved an improvement in all groups fed with these complexes. These complexes can be used as functional protection elements against the nonalcoholic fatty liver disease. PRACTICAL APPLICATIONS: PHM, NabM, and their complexes with milk proteins were proved to improve liver function, enhancing most of its measurable parameters and also diminishing the risk of cardiovascular disease. Mice with HFD achieved better health circumstances by combining these ingredients in their diet. Knowing how much these diseases proliferate in the western world and its correlation with high-fat consumption and modern lifestyle, its conjugation with PHM/NabM-MP complexes may reduce the negative impact of unhealthy food intake and, on some parameters, even improving the whole liver function. For that reason, the present study supports and pushes forward the dissemination and consumption of ispaghula or Nabq (the polysaccharides sources) or supplements originating from them. Although many interactions concerning milk proteins have already been analyzed, our study also proposes the interaction with bioactive polysaccharides as useful, opening a field of research aimed at the better application of milk proteins.

Multiparametric ultrasound evaluation with CEUS and shear wave elastography for carotid plaque risk stratification.

PURPOSE: To assess the diagnostic effectiveness of Multiparametric ultrasound (MPUS), which includes color Doppler ultrasound (CDUS), CEUS and Shear wave elastography (SWE), for evaluating carotid plaque as compared with CT-angiography (CTA) and histology. MATERIALS AND METHODS: Forty-three consecutive patients scheduled to undergo carotid endarterectomy underwent MPUS. Then, after periods ranging from 2 days to 2 weeks, all underwent CTA. Each plaque was classified by means of dedicated scores for CEUS and SWE as compared with CTA features. At surgery, each plaque was removed in a single fragment to facilitate histological analysis, which evaluated 4 features: extension of the lipid core, thickness of the fibrous cap, inflammatory infiltrate (CD68 + and CD3 + markers) and the presence of intraplaque microvessels. For the CEUS, SWE and CTA, the following values for identifying plaque vulnerability were evaluated: sensitivity, specificity, accuracy, negative predictive value (NPV), positive predictive value (PPV) and Area under the curve (AUC). Cohen's kappa was used to evaluate the concordance between measurements in the different imaging methods. A p < 0.05 was considered statistically significant. RESULTS: At histology, 31 out of 43 plaques were identified as vulnerable because of the presence of at least one of the following criteria: fibrous cap < 200 µm, lipid core, intraplaque hemorrhage, inflammatory infiltrate or intraplaque neovascularization. CTA showed a sensitivity of 87.1%, a specificity of 100%, a PPV of 100%, an NPV of 75% and an AUC of 93.5%. SWE showed a sensitivity of 87.1%, a specificity of 66.7%, a PPV of 87.1%, an NPV of 66.7% and an AUC of 76.9%. CEUS showed a sensitivity of 87.1%, a specificity of 58.3%, a PPV of 84.4%, an NPV of 63.6% and an AUC of 72.7%. CONCLUSIONS: Multiparametric ultrasound is an effective modality to obtain comprehensive information on carotid plaques. Further studies are needed to determine whether it can be considered a diagnostic standard.

Age-related declines in α-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration.

While young muscle is capable of restoring the original architecture of damaged myofibers, aged muscle displays a markedly reduced regeneration. We show that expression of the "anti-aging" protein, α-Klotho, is up-regulated within young injured muscle as a result of transient Klotho promoter demethylation. However, epigenetic control of the Klotho promoter is lost with aging. Genetic inhibition of α-Klotho in vivo disrupted muscle progenitor cell (MPC) lineage progression and impaired myofiber regeneration, revealing a critical role for α-Klotho in the regenerative cascade. Genetic silencing of Klotho in young MPCs drove mitochondrial DNA (mtDNA) damage and decreased cellular bioenergetics. Conversely, supplementation with α-Klotho restored mtDNA integrity and bioenergetics of aged MPCs to youthful levels in vitro and enhanced functional regeneration of aged muscle in vivo in a temporally-dependent manner. These studies identify a role for α-Klotho in the regulation of MPC mitochondrial function and implicate α-Klotho declines as a driver of impaired muscle regeneration with age.

Age-dependent changes in intervertebral disc cell mitochondria and bioenergetics.

Robust cellular bioenergetics is vital in the energy-demanding process of maintaining matrix homeostasis in the intervertebral disc. Age-related decline in disc cellular bioenergetics is hypothesised to contribute to the matrix homeostatic perturbation observed in intervertebral disc degeneration. The present study aimed to measure how ageing impacted disc cell mitochondria and bioenergetics. Age-related changes measured included matrix content and cellularity in disc tissue, as well as matrix synthesis, cell proliferation and senescence markers in cell cultures derived from annulus fibrosus (AF) and nucleus pulposus (NP) isolated from the discs of young (6-9 months) and older (36-50 months) New Zealand White rabbits. Cellular bioenergetic parameters were measured using a Seahorse XFe96 Analyzer, in addition to quantitating mitochondrial morphological changes and membrane potential. Ageing reduced mitochondrial number and membrane potential in both cell types. Also, it significantly reduced glycolytic capacity, mitochondrial reserve capacity, maximum aerobic capacity and non-glucose-dependent respiration in NP. Moreover, NP cells exhibited age-related decline in matrix synthesis and reduced cellularity in older tissues. Despite a lack of changes in mitochondrial respiration with age, AF cells showed an increase in glycolysis and altered matrix production. While previous studies report age-related matrix degenerative changes in disc cells, the present study revealed, for the first time, that ageing affected mitochondrial number and function, particularly in NP cells. Consequently, age-related bioenergetic changes may contribute to the functional alterations in aged NP cells that underlie disc degeneration.

What is the role of contrast-enhanced ultrasound in the evaluation of the endoleak of aortic endoprostheses? A comparison between CEUS and CT on a widespread scale.

OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in comparison to CT angiography (CTA) to identify and classify endoleaks following abdominal aortic aneurism repair with endoprosthesis. MATERIALS AND METHODS: A retrospective analysis of 181 patients treated with EVAR, from September 2009 to September 2014, was performed. Patients were evaluated with CEUS, CTA and angiography in the cases requiring treatment. Sac diameter, sac integrity, identification and classification of endoleaks were taken into consideration. Sensitivity, specificity, accuracy and negative predictive values were considered for each modality of endoleak identification. RESULTS: Forty-two endoleaks (23.2%; type II: 39 cases, type III: 3 cases) were documented. Sensitivity and specificity of CEUS and CT were, respectively, 97.6 and 90.5, 100 and 100%. In two cases, CEUS was able to better classify endoleaks compared to CT. CONCLUSIONS: CEUS accuracy to identify endoleaks following EVAR is similar to CT. CEUS should be considered as an effective modality for the long-term surveillance of EVAR because of its capability to correctly classify endoleaks with no ionizing radiation exposure.

Application of capsular sequence typing (CST) to serotype non-viable Streptococcus pneumoniae isolates from an old collection.

Serotyping of Streptococcus pneumoniae is essential for monitoring changes in the pneumococcal population and the impact of vaccines. Recently, various DNA-based methods have become available and are increasingly used because they are cheaper and easier to perform than the Quellung reaction. Our aim was to apply a DNA-based method, capsular sequence typing (CST), to a collection of non-viable lyophilized pneumococcal isolates dating from the 1980s to elucidate the serotypes circulating in Italy 30 years ago. As a preliminary evaluation of the method, CST was applied to 68 recent pneumococcal isolates representative of the most common serotypes circulating in Italy in invasive pneumococcal disease (IPD) previously serotyped by the Quellung reaction. CST was then applied to 132 lyophilized non-viable isolates. A serotype-specific polymerase chain reaction (PCR), using primers suggested by the Centers for Disease Control and Prevention (CDC), was performed when CST did not yield a univocal serotype. Considering the control isolates, CST concordance with the Quellung reaction was 95.6 %. For the non-viable lyophilized isolates, CST identified a univocal serotype for 59.4 % of the isolates. This percentage increased to 78.1 % if CST was combined with serotype-specific PCR. The most frequent serotypes in the collection of non-viable strains were: 3 (15.6 %), 14 (11.7 %), 35B (5.5 %), 19A (5.5 %), and 8 (4.7 %). CST proved to be a valid method for serotyping pneumococcal strains and provided information about pneumococcal serotypes present in Italy 30 years ago. The combination of CST with serotype-specific PCR was an effective strategy to identify pneumococcal serotypes that can be suggested also for routine laboratories.

Contrast-enhanced ultrasound in the evaluation of parotid gland lesions: an update of the literature.

High-resolution ultrasound is the first line examination for parotid gland diffuse disease and focal lesions, normally using grey-scale and colour-Doppler ultrasound. Unfortunately, grey-scale and colour-Doppler ultrasound features of benign and malignant salivary gland lesions may overlap, particularly with benign tumors, where pleomorphic adenomas are often indistinguishable from malignant lesions. With atypical lesions, contrast-enhanced magnetic resonance imaging is usually the second level imaging modality requested. The introduction of ultrasound contrast agents has opened further possible perspectives to improve the interpretation of parotid diseases, particularly the differentiation between benign and malignant lesions. We present a review of the current literature on contrast-enhanced ultrasound for the assessment of parotid gland lesions, considering all characteristics of the technique, evidence of usefulness, future perspectives and limitations.

Parotid Gland Lesions: Multiparametric Ultrasound and MRI Features.

High-resolution ultrasound (US), as a readily available, cost-effective and harmless imaging technique, is appropriately the initial imaging modality for salivary gland lesions. Benign tumors are reported to present with regular and well-defined margins, a homogeneous hypoechoic structure and demarcated vessel distribution, whereas malignant lesions are irregular, heterogeneous and diffusely perfused. Ultrasound and color Doppler features of benign and malignant salivary gland lesions overlap, and many benign tumors, particularly pleomorphic adenomas, may appear irregularly shaped, with a heterogeneous echo-structure indistinguishable from a malignant lesion. Often skilled US operators are not always able to differentiate benign from malignant lesions. The introduction of US contrast agents has allowed further perspectives in the possible improvement of lesion characterization, and the emergence of US elastography, an innovative tool for assessing lesion stiffness/elasticity characteristics, has been advocated for differentiating salivary gland lesions. When lesions are atypical on US, contrast-enhanced magnetic resonance (MR) imaging is usually the definitive imaging modality. We present a current review of benign and malignant parotid gland tumors with emphasis on the role of multiparametric US and MR imaging.

Detection of small testicular masses in monorchid patients using US, CPDUS, CEUS and US-guided biopsy.

PURPOSE: Testis sparing surgery (TSS) is a well-known technique in the treatment of small testicular masses. Grayscale ultrasound (US), color/power Doppler US (CPDUS) and contrast-enhanced ultrasound (CEUS) are considered the best diagnostic imaging tools in those patients. Aim of this study was to assess the role of US imaging in the detection of small testicular masses in monorchid patients after orchiectomy for malignant neoplasm, and in guiding surgery to reach the target and also to differentiate lesions which presented vascular activity within the mass. METHODS: From January 2011 to October 2014, 18 patients were enrolled in this study. They had previously undergone orchiectomy and were investigated for suspected contralateral disease. During routine follow-up, all patients underwent grayscale US. If findings were positive, CPDUS and CEUS were performed and eventually all patients underwent surgery. After exteriorization of the testis, the small mass was identified by intraoperative US, and a needle was placed under US guidance. After excision of the mass, frozen section examination was performed. When malignancy was found, radical orchiectomy was performed; if histological outcome was negative, the healthy testis was conserved. RESULTS: All patients underwent grayscale US examination, which showed small hypoechoic masses. Each mass identified at US imaging was confirmed at surgery. All patients underwent CPDUS; 12/19 lesions showed blood flow while 7/19 showed absence of blood flow. At CEUS, 16/19 lesions showed enhancement and subsequent histological examination revealed that 8 were seminomas and 3 were Leydig cell tumors. In 5/19 cases CEUS showed the presence of lesions (focal inflammatory lesions) and in 3/19 cases CEUS was negative. CONCLUSIONS: TSS in monorchid patients may be a safe procedure leading to excellent results. We therefore consider it a valid alternative to radical orchiectomy, and US imaging is essential to guide the resection of non-palpable neoplasms and to exclude concomitant lesions.

CEUS Time Intensity Curves in the Differentiation Between Leydig Cell Carcinoma and Seminoma: A Multicenter Study.

PURPOSE: Ultrasound (US) is the main imaging technique in the assessment of testicular masses, as it has proved to be highly accurate in the visualization of these pathologies. Identification of a Leydig cell tumor is essential since the lesion is benign in 90% of cases. The aim of this multicenter study is to assess the effectiveness of contrast-enhanced ultrasound (CEUS) in differentiating Leydig cell tumors from seminoma using qualitative and quantitative features. MATERIALS AND METHODS: From February 2011 to December 2013, 31 patients (mean age: 34 years; range: 25 - 52) were recruited for this prospective study. Three of them were monorchid. Therefore, a total of 59 testicles were assessed. All patients underwent grayscale US, color Doppler ultrasound (CDUS), CEUS and orchiectomy. The paired one-tailed Student's t-test was carried out to differentiate between Leydig cell tumors and seminomas. RESULTS: 31 lesions suspicious for malignancy were hypoechoic on grayscale US while they did not show a typical pattern on CDUS. CEUS qualitative analysis, based on contrast enhancement pattern, during the arterial and venous phases, did not allow discrimination of Leydig cell tumors from seminoma. Quantitative analysis of time-intensity curves (TICs) demonstrated that only three parameters presented statistical significance, i. e. wash-in rate (WiR) p = 0.014, peak enhancement (PE) p = 0.001 and time to peak (TTP) p = 0.003. CONCLUSION: The vascular bed of a Leydig cell tumor is wider and the blood flow velocity is higher than that of a seminoma due to more regular neovascularization. In contrast, a seminoma presents large areas of necrosis due to irregular neovascularization. This explains the different PE and WiR values. Further studies involving larger patient populations are mandatory to confirm these encouraging preliminary results.

Growing indications for CEUS: The kidney, testis, lymph nodes, thyroid, prostate, and small bowel.

Contrast enhanced ultrasonography (CEUS) is increasingly used for non-hepatic applications as well, so that nearly all organs have been investigated. Among them, there is a growing clinical use for a variety of pathologies of the kidney, testis, and small bowel. The possibility to differentiate benign from malignant nodes in cancer patients has been investigated. A new application is in the detection of sentinel nodes after intradermal microbubble injection. The need to distinguish thyroid nodules eligible for fine needle aspiration cytology has led to the use of CEUS in thyroid examinations as well. The potential of CEUS for prostate cancer detection has been extensively investigated, with encouraging initial results. Early promise, however, has not been fulfilled. New perspective regards evaluation of the extent of prostate tissue devascularization following ablative treatments.

Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC).

BACKGRAUND: Pain is the primary reason for admission to the Emergency Department (ED). However, the management of pain in this setting is often inadequate because of opiophagia, fear of excessive sedation, and fear of compromising an adequate clinical assessment. METHODS: An intersociety consensus conference was held in 2010 on the assessment and treatment of pain in the emergency setting. This report is the Italian Intersociety recommendations on pain management in the emergency department setting. RESULTS: The list of level A recommendations includes: 1) use of IV acetaminophen for opioid sparing properties and reduction of opioid related adverse events; 2) ketamine-midazolam combination preferred over fentanyl-midazolam fentanyl-propofol in pediatric patients; 3) boluses of ketamine IV (particularly in the population under the age of 2 years and over the age of 13) can lead to impairment of the upper airways, including the onset of laryngospasm, requiring specific expertise and skills for administration; 4) the use of ketamine increases the potential risk of psychomotor agitation, which can happen in up to 30% of adult patients (this peculiar side effect can be significantly reduced by concomitant systemic use of benzodiazepines); 5) for shoulder dislocations and fractures of the upper limbs, the performance of brachial plexus block reduces the time spent in ED compared to sedation; 6) pain relief and the use of opioids in patients with acute abdominal pain do not increase the risk of error in the diagnostic and therapeutic pathway in adults; 7) in newborns, the administration of sucrose reduces behavioural responses to blood sampling from a heel puncture; 8) in newborns, breastfeeding or formula feeding during the procedure reduces the measures of distress; 9) in pediatric patients, non-pharmacological techniques such as distraction, hypnosis and cognitive-behavioural interventions reduce procedural pain caused by the use of needles; 10) in pediatric patients, preventive application of eutectic mixtures of prilocaine and lidocaine allows arterial and venous samples to be taken in optimum conditions; 11) in pediatric patients, the combination of hypnotics (midazolam) and N2O is effective for procedural pain, but may be accompanied by loss of consciousness. CONCLUSION: The diagnostic-therapeutic pathway of pain management in emergency should be implemented, through further interdisciplinary trials, in order to improve the EBM level of specific guidelines.