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A polygenic inheritance involving high, medium and low penetrance genes has been suggested for melanoma susceptibility in adults, but genetic information is scarce for paediatric patients.We aim to analyse the major high and intermediate melanoma risk genes, CDKN2A, CDK4, POT1, MITF and MC1R, in a large multicentre cohort of Italian children and adolescents in order to explore the genetic context of paediatric melanoma and to reveal potential differences in heritability between children and adolescents.One-hundred-twenty-three patients (21 years) from nine Italian centres were analysed for the CDKN2A, CDK4, POT1, MITF, and MC1R melanoma predisposing genes. The rate of gene variants was compared between sporadic, familial and multiple melanoma patients and between children and adolescents, and their association with clinico-pathological characteristics was evaluated.Most patients carried MC1R variants (67%), while CDKN2A pathogenic variants were found in 9% of the cases, the MITF E318K in 2% of patients and none carried CDK4 or the POT1 S270N pathogenic variant. Sporadic melanoma patients significantly differed from familial and multiple cases for the young age at diagnosis, infrequent red hair colour, low number of nevi, low frequency of CDKN2A pathogenic variants and of the MC1R R160W variant. Melanoma in children (≤12 years) had more frequently spitzoid histotype, were located on the head/neck and upper limbs and had higher Breslow thickness. The MC1R V92M variant was more common in children than in adolescents. CDKN2A common polymorphisms and MC1R variants were associated with a high number of nevi.Our results confirm the scarce involvement of the major high-risk susceptibility genes in paediatric melanoma and suggest the implication of MC1R gene variants especially in the children population.

Intraarticular corticosteroid (IAC) injection is a safe and rapidly effective treatment for synovitis in children with juvenile idiopathic arthritis (JIA). This procedure can be performed in an ambulatory care setting using local anaesthesia, with or without conscious sedation. Younger children, or those candidate to multiple injections, require general anaesthesia. Triamcinolone hexacetonide is the optimal corticosteroid preparation. However, for smaller joints or joints that are not easy to assess clinically, use of a more soluble corticosteroid drug is advised. Imaging guidance may facilitate accurate placement of the needle within the joint space. Use of ultrasound for this purpose has gained increasing popularity in the recent years. IAC injections are used most frequently to treat oligoarthritis, but the strategy of performing multiple IAC injections to induce disease remission, while simultaneously initiating therapy with second-line or biologic agents, has been proposed also for children with polyarticular JIA. However, the current place of IAC therapy in the management of children with JIA is uncertain due to the lack of controlled studies. Furthermore, it is still unknown whether this therapy has a disease-modifying effect over the long-term. This review summarises the present information about the use of IAC therapy in children with JIA.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20–0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17–0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

Several studies have investigated the beneficial effects of vitamin D on survival of cancer patients. Overall evidence has been accumulating with contrasting results. This paper aims at narratively reviewing the existing articles examining the link between vitamin D supplementation and cancer mortality. We performed two distinct searches to identify observational (ObS) studies and randomized clinical trials (RCTs) of vitamin D supplementation (VDS) in cancer patients and cohorts of general population, which included cancer mortality as an outcome. Published reports were gathered until March 2021. We identified 25 papers published between 2003 and 2020, including n. 8 RCTs on cancer patients, n. 8 population RCTs and n. 9 ObS studies. There was some evidence that the use of VDS in cancer patients could improve cancer survival, but no significant effect was found in population RCTs. Some ObS studies reported evidence that VDS was associated with a longer survival among cancer patients, and only one study found an opposite effect. The findings do not allow conclusive answers. VDS may have the potential as treatment to improve survival in cancer patients, but further investigations are warranted. We strongly support investment in well-designed and sufficiently powered RCTs to fully evaluate this association.

Objective. To analyze peripheral nerves with ultrasonography (US) and magnetic resonance imaging (MR) in leprosy and assess the role of imaging in leprosy patients. Design and patients. Fifty-eight nerves with abnormal clinical features or electromyograms were examined in 23 leprosy patients by means of gray-scale US, Doppler US and MR imaging. Image analysis included: measurement of nerve cross-sectional area; assessment of nerve structure and MR signal intensities; identification of nerve compression within osteofibrous tunnels; detection of endoneural color flow signals and Gd-DTPA enhancement. Correlations were made with clinical findings and a control group of 20 subjects. Fourteen nerves in active reversal reaction were followed up after therapy. Results. Leprosy nerves were classified into three groups based on imaging appearance: group I consisted of 17 normal-appearing nerves; group II, of 30 enlarged nerves with fascicular abnormalities; group III, of 11 nerves with absent fascicular structure. Group II nerves were from patients subjected to reversal reactions; 75% of patients with group III nerves had a history of erythema nodosum leprosum. Nerve compression in osteofibrous tunnels was identified in 33% of group II and 18% of group III nerves. Doppler US and MR imaging were 74% and 92% sensitive in identifying active reactions, based on detection of endoneural color flow signals, long T2 and Gd enhancement. In 64% of cases, follow-up studies showed decreased color flow and Gd uptake after steroids and decompressive surgery. Conclusions. US and MR imaging are able to detect nerves abnormalities in leprosy. Active reversal reactions are indicated by endoneural color flow signals as well as by an increased T2 signal and Gd enhancement. These signs would suggest rapid progression of nerve damage and a poor prognosis unless antireactional treatment is started.

BACKGROUND AND AIMS: Triggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation. METHODS: We measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin. RESULTS: TREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c+ cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice. CONCLUSIONS: TREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target. © 2013 by the AGA Institute.

SummaryThe aim of this study was to develop a simplified ultrasound scanning procedure and scoring method, named Haemophilia Early Arthropathy Detection with UltraSound [HEAD-US], to evaluate joints of patients with haemophilic arthropathy. After an initial consensus-based process involving a multidisciplinary panel of experts, three comprehensive and evidence-based US scanning procedures to image the elbow, knee and ankle were established with the aim to increase sensitivity in detection of early signs of joint involvement while keeping the technique easy and quick to perform. Each procedure included systematic evaluation of synovial recesses and selection of a single osteochondral surface for damage analysis. Based on expert consensus, a simplified scoring system based on an additive scale was created to define the joint status and, in perspective, to offer a tool to evaluate disease progression and monitor the result of treatment in follow-up studies.

Purpose. To illustrate the sonographic and Doppler features of the different types of intrahepatic vascular shunts. Methods. Patients presenting in our department with intrahepatic vascular shunts with healthy livers or with a variety of liver pathologies underwent color Doppler interrogation and spectral analysis. Results. Intrahepatic vascular shunts may involve all liver vessels. Arterioportal and arteriosystemic venous connections can be recognized in normal and cirrhotic livers, following trauma, within tumors, and within nontumoral arteriovenous malformations. Portosystemic intrahepatic venous shunts are categorized into 4 morphologic types. Systemic-to-systemic shunts are more often recognized in patients with chronic hepatic venous congestion or with Budd-Chiari syndrome. Portal-to-portal intrahepatic venous shunts are rare, with few cases described. Conclusion. In general, all the liver vessels can be associated with formation of arterioportal, arteriosystemic, and portosystemic venous shunts and, rarely, systemic venous shunts and portal-to-portal communications. Sonography allows characterization of the different intrahepatic shunts. © 2008 Wiley Periodicals, Inc. J Clin Ultrasound, 2008

Our objective was to investigate the prevalence and Doppler characteristics of penile cavernosal-spongiosal communications (CSC) in patients with severe Peyronie's disease. These vessels are either anastomoses connecting the cavernosal arteries with the urethral arterial network or afferent vessels to the corpus spongiosum. Twenty patients with severe Peyronie's disease underwent penile color Doppler US after intracavernous injection of prostaglandin E(1). Study inclusion criteria were penile curvature or shortening which made intercourse difficult or impossible. The quality of erectile response was subjectively scored. The spectral characteristics of CSC were evaluated in comparison with waveform changes in cavernosal artery. There were 4 patients with normal erectile response, 10 with discrepancy in rigidity of the penile base and tip, 4 with veno-occlusive dysfunction and 2 with arteriogenic dysfunction. The CSC just proximal to the plaques had peak systolic velocity (PSV) significantly higher and resistance index (RI) significantly lower than the other CSC. The PSV in CSC near the plaques of patients with base-tip discrepancy and with veno-occlusive dysfunction were significantly higher than in the other patients. In patients with severe Peyronie's disease CSC near the plaques remain patent with low-resistance flow supporting the hypothesis that blood leakage can occur through these vessels.

To evaluate, with power Doppler (PD) ultrasound (US), the normal interlobular vasculature in patients who underwent renal transplantation and to assess if defects of the PD signal at the interlobular level correspond to cortical areas that lack blood perfusion at magnetic resonance (MR) imaging.Thirty-two normal and 33 malfunctioning transplanted kidneys were studied with PD US (6.5 MHz). PD images of interlobular vessels were graded on a scale of normal (pattern I) and decreasing visualization. In kidneys with focal (pattern II) and diffuse (pattern III) absence of interlobular signal, correlative dynamic MR imaging was performed.Interlobular vessels were consistently depicted with PD US in the proximal cortex of normally functioning transplanted kidneys. Of kidneys with a pattern II appearance, five had no contrast material enhancement in the cortical sites in which the interlobular PD signal was detected and three were contrast enhanced but it was less intense than that in adjacent cortical sites with normal interlobular vasculature. All transplanted kidneys with a pattern III appearance had delayed contrast enhancement.Although PD US appears to depict the interlobular vasculature up to the renal capsule, care should be taken in the diagnosis of perfusion defects, since absence of detectable flow at the interlobular level does not always correspond to cortical areas that lack perfusion on MR images.

PURPOSE: To correlate the histologic structure and echotexture of peripheral nerves and verify if ultrasound (US) findings can be used to differentiate nerve from tendon. MATERIALS AND METHODS: In an in vitro study, the echotexture of normal peripheral nerves was correlated with the histologic findings. In an in vivo study, US was used to differentiate median nerve from flexor pollicis longus tendon in healthy volunteers (12 male and eight female subjects 7-68 years of age; mean age, 35 years). RESULTS: US examination of the peripheral nerve specimens showed hypoechoic areas separated by hyperechoic bands. The hypoechoic areas corresponded to neuronal fascicles at histologic examination. This fascicular pattern was clear in all median and ulnar nerves, 15 of 20 vagus nerves, and 19 of 20 sciatic nerves in the volunteers but not in recurrent laryngeal nerves. CONCLUSION: Peripheral nerves have a typical US pattern that correlates with histologic structure and facilitates differentiation between nerves and ...

The preoperative assessment of the extent of biliary and vascular involvement by hilar cholangiocarcinoma is clinically important because resectability may be limited by tumor extension along the bile ducts into the hepatic parenchyma or to the adjacent hilar vessels. Thirty-five patients with hilar cholangiocarcinoma were studied with ultrasound, and the results were compared with operative findings and other diagnostic modalities. The level of intrahepatic biliary obstruction was determined in 100% of patients with ductal ectasia, and a tumor mass was shown in 37.1%. Imaging and Doppler ultrasound proved accurate in detecting the neoplastic involvement of the portal vein. Both correctly diagnosed portal occlusion and wall infiltration in 4 of 4 and 15 of 18 (83%) patients, respectively, without any false-positives. On the contrary, imaging ultrasound had poor sensitivity in detecting infiltration of the hepatic artery (43%) and metastases in regional lymph nodes (37%), liver (66%), and peritoneum (33%). In conclusion, ultrasound may be valuable in the preoperative staging of hilar cholangiocarcinoma, specially in predicting ductal and portal involvement. © 1995 John Wiley & Sons, Inc.

To evaluate the ultrasound (US) appearance of the normal Achilles tendon at increasing frequency and establish an anatomical correlation for US findings, 30 normal tendons were examined in vivo and three in vitro with 10 MHz and 15 MHz mechanical sector probes. Side-by-side comparison was performed in vitro between the sonograms and the corresponding anatomical sections. Two tendinous portions were detected by presence of an internal acoustic interface which had different appearances: one (type I) or two (type II) continuous lines of increased thickness and greater reflectivity than adjacent fibrils; or displacement (type III) of the distal portion of the well insonated sector of the tendon body. When, on coronal scans of the tendon, no intratendinous linear echoes of increased reflectivity were visible, the two portions of the tendon were identified through the converging course of their bundles (type 0 pattern). Different echogenicity allowed the detection of two tendinous portions, also on axial images. Scanning of isolated tendons allowed precise location of these interfaces at the boundary between anatomically distinct tendinous portions arising from the soleus and gastrocnemius muscles. Although the normal Achilles tendon is commonly regarded as a uniform structure by US, the use of high resolution probes allows identification of its constituent portions. Their identification may be useful to avoid misdiagnoses of pathological findings.

To evaluate changes in echotexture of normal tendons at different frequencies and establish an anatomic correlation for fibrillar echoes, normal calcaneal tendons were examined in vitro at 7.5, 10, 13, and 15 MHz in calves (n = 8) and sheep (n = 6) and in vivo in humans (n = 8). Histologic correlation was obtained in vitro with 22-gauge needles that marked the position of echogenic fibrils under ultrasound (US) guidance. The human study group consisted of 25 patients with a clinical diagnosis of calcaneal tendon disease and 15 patients who underwent surgery for rupture of the Achilles tendon. At all four frequencies, normal tendons showed an internal network of fine parallel and linear fibrillar echoes that became more numerous and thinner as US frequency increased. These echoes were caused by specular reflections at the interface between collagen bundles and endotendineum septa. In patients, tendons showed a variety of basic changes in fibrillar pattern: increased fibrillar thickness (33 patients), interruption (17 patients), fragmentation (12 patients), and disappearance of echotexture (15 patients). It is concluded that US holds promise in detection of minimal changes in tendinous structure.

A case of primary non-Hodgkin's lymphoma (NHL) of the mandible with unusual radiographic presentation is reported. The panoramic radiography revealed diffuse widening of the right mandibular canal with ill-defined margins and absence of edge sclerosis. Computed tomography showed infiltration of the superior portion of the canal with involvement of the vestibular cortex of the bone and of the alveolar ridge.

Our objective was to investigate prevalence and Doppler characteristics of penile cavernosal–spongiosal communications (CSC). These vessels are either anastomoses connecting the cavernosal arteries with the urethral arterial network or afferent vessels to the corpus spongiosum. Sixty-one consecutive patients underwent penile color Doppler US. Waveform changes in CSC were evaluated in comparison with changes in the cavernosal artery. Eighteen of 61 patients had normal erection, 17 of 61 had arterial insufficiency, and 26 of 61 had veno-occlusive dysfunction. Resistance index (RI) in CSC was significantly lower than in cavernosal arteries in all patients and increased during phases 1–2 (positive diastolic flow). Peak systolic velocity (PSV) in CSC was significantly higher in the patients with veno-occlusive dysfunction. During cavernosal phase 4 (diastolic flow reversal) CSC of patients with normal erection or with arterial insufficiency disappeared, underwent markedly reduced diastolic flow, or had systolic flow inversion. Conversely, low resistance flow was appreciable in CSC of patients with veno-occlusive dysfunction who reached phase 4. During phase 5 (systolic peak reduction) all CSC disappeared. Color Doppler US allows evaluation of CSC both in patients with normal and impaired erection.

Pancreaticobiliary diversion is a surgical procedure undertaken for obesity. It consists of a distal gastrectomy with a long Roux-en-Y reconstruction, the enteroenterostomy being placed 200 cm distal to the gastroenterostomy and 50 cm proximal to the ileocaecal valve. Three intestinal limbs are recognized: (a) the alimentary loop from the gastroenterostomy to the enteroenterostomy; (b) common loop from the enteroenterostomy to the ileocaecal valve and (c) pancreaticobiliary loop from the duodenum to the enteroenterostomy. The radiological findings in 15 pancreaticobiliary diversion patients with small bowel obstruction were reviewed (15 plain abdominal radiographs, 13 ultrasound (US), 8 CT) and compared with 20 plain abdominal radiographs, 10 US, and 10 CT studies performed for other causes in patients with pancreaticobiliary diversion and 15 CT scans from non-operated patients. After pancreaticobiliary diversion the pancreaticobiliary loop was completely air-free. In the patients operated on more than 1 year previously, alimentary and common loops were significantly larger than the pancreaticobiliary loop and small bowel loops of non-operated subjects. Obstruction of the pancreaticobiliary loop arrests only the flow of pancreaticobiliary secretions with non-specific clinical findings. Plain abdominal radiographs were not diagnostic in all but two cases with radiographically detectable dilated fluid filled loops. Air-fluid levels were never apparent. US and CT showed markedly dilatated intestinal loops and duodenum. Obstruction of the alimentary and common loops presented with symptoms, clinical signs, and radiological findings more typical for bowel obstruction in intact subjects.