A multicenter observational study on Medication-Related Osteonecrosis of the Jaw (MRONJ) in advanced cancer and myeloma patients of a cancer network in North-Western Italy.

BACKGROUND: Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) related to cancer and myeloma treatments is undetermined, with scarce data varying from 2 to 7.8/million/year in limited investigated populations. A 9-years [2009-2018] regional-wide survey was conducted, deploying the North-Western Italy Cancer Network ("Rete Oncologica Piemonte e Valle d'Aosta"), to assess number and main characteristics of MRONJ cases among myeloma/cancer patients, within a population of 4.5 million inhabitants. MATERIAL AND METHODS: MRONJ cases were collected retrospectively from January 2009 to June 2015; from July 2015 to December 2018, data were collected prospectively. Number of new MRONJ cases per year, underlying disorder, drug(s) administered, treatment duration, site and onset timing of MRONJ were detailed. RESULTS: 459 MRONJ cases were identified. Primary diseases were breast cancer (46%), prostate cancer (21%), myeloma (19%), and other types of carcinoma (14%). Patients received antiresorptive treatment either alone (399; 88.47%) or in combination with biological agents (52; 11.53%); 8 patients (1.7%) received only antiangiogenic drugs. Zoledronic acid [388] and denosumab [59] were the most frequently administered drugs. Mandible was involved in 296 (64,5%) cases. Number of new MRONJ cases was stable from 2009 to 2015, with a mean of 51.3 cases per year (raw incidence: 11.6/million/year), declining in the 2016-2018 years to 33.3 cases per year (raw incidence: 7.5/million/year). CONCLUSIONS: With such discrepancy of cases overtime being partially explicable, number of new MRONJ cases per year are consistent with those observed in a previous study [2003-2008] in the same region, being instead higher than those reported in other populations.

Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

High levels of donor CCL2/MCP-1 predict graft-related complications and poor graft survival after kidney-pancreas transplantation.

In this study we analyzed the role of CCL2, a member of the chemokine family, in early graft damage. Using simultaneous kidney-pancreas transplantation (SPK) as a model, we showed that brain death significantly increases circulating CCL2 levels in humans. We found that in such situations, high donor CCL2 levels (measured before organ recovery and at the onset of cold preservation) correlate with increased postreperfusion release of CCL2 by both the graft and recipient throughout the week following transplantation (n = 28). In a retrospective study of 77 SPK recipients, we found a significant negative association between high donor levels of CCL2 and graft survival. Decreased survival in these patients is related to early posttransplant complications, including a higher incidence of pancreas thrombosis and delayed kidney function. Taken together our data indicate that high CCL2 levels in the donor serum predict both an increase in graft/recipient CCL2 production and poor graft survival. This suggests that the severity of the inflammatory response induced by brain death influences the posttransplant inflammatory response, independent of subsequent ischemia and reperfusion.

Facial soft tissue changes after transverse palatal distraction in adult patients.

This longitudinal study investigated the 3-D facial soft-tissue response to transverse palatal bone-anchored osteodistraction in 18 adult patients. Laser-scanned facial surface data were obtained for all patients before (T(0)), 6 months (T(1)) and 1 year (T(2)) after transverse palatal distraction. The averaged facial morphologies at T(0), T(1) and T(2) were calculated and compared. Sagittal and vertical measurements were obtained from lateral cephalograms to evaluate skeletal and dental movements. Pre- and immediate post-distraction dental casts were used to investigate transverse maxillary movements. Cutaneous changes were mainly observed in the paranasal regions and cheeks, in the range 1-3 mm, reflecting the underlying increase in the maxillary width. A significant enlargement of the nasal base was also demonstrated. The absolute magnitude of these facial changes was limited but clinically relevant. Variable skeletal movements were observed. These were of low magnitude and no systematic tendency could be demonstrated statistically. Significant changes were documented only with regard to orthodontic repositioning of the upper and lower incisors. The mean transverse increases in the maxillary dental arch were 6.7 mm at the intercanine, 6.8 mm at the interpremolar, and 6.1 mm at the intermolar levels.

High-resolution computed tomography in cystic fibrosis.

The sensitivity of high-resolution computed tomography (HRCT) in identifying the pulmonary lesions of cystic fibrosis (CF) was evaluated. Thirty-nine patients (16 males, 23 females; mean age 19.1 years) were examined by chest HRCT. According to Shwachman and Kulczycki criteria, the clinical score of the patients ranged from 40 to 95, thus covering most possible variations of lung disease severity. All the patients presented diffuse thickening of bronchial walls, expression of the characteristic CF bronchial inflammation. Bronchiectases were the second most common lung lesions: discrete dilatation of bronchi was observed in 87% of cases; the localization, pattern and extent of bronchiectasis were accurately detected by HRCT. Pleural thickening and hilar adenopathy were frequently identified (in 64% and 82% of the patients, respectively). Bronchoceles were seen in 64% of the patients; atelectasis (33%) and subpleural bullous dystrophic emphysema (28%) were observed less frequently. On HRCT, the localization of the disease processes within the secondary pulmonary lobule was possible in all patients. In agreement with international literature, the identification of these lesions confirms HRCT as the more sensitive technique for early visualization and location of the manifestations of CF bronchopathy. A larger range of experience coming from a systematic use of HRCT in chronic inflammatory lung diseases would increase our knowledge of pathogenetic processes and allow improvement of therapeutic perspectives.

[The echographic follow-up of patients treated with an external fixator in childhood and adolescence]. / Controllo ecografico di pazienti trattati con fissatore esterno nell'età pediatrica e giovanile.

In the last few years external fixation has started to be extensively used in pediatric orthopedics and traumatology and ultrasound (US) monitoring has been adopted. The role of US was investigated in a study on 64 patients aged 2 to 30 years treated from November, 1989, to December, 1993. Some patients underwent several interventions with different methods and therefore belong to more than one of the three considered groups. In case of surgical lengthening (group A), the role of US was investigated in a study on 54 patients aged 2 to 26 years. The following variables were studied with US: diastasis entity, stump axis and the evolution of regenerated tissue within 10 days of the beginning of lengthening (first follow-up), at 20 days (second follow-up) and at 30 days (third follow-up). Ilizarov and Wagner fixators and one external fixation reduction fixator were used on 54 patients in 83 segments (43 femurs, 39 tibias and 1 humerus). In all, 104 corticotomies were performed. In fractures treated with external fixators (group B), US allowed the study of the hematoma surrounding the lesion and of its progressive evolution from fibrous tissue to bone callus, within 30 days of external fixation (first follow-up), at 60 days (second follow-up) and at 90 days (third follow-up). Eight patients were treated. The segments treated were 9 femurs and 2 tibias, 11 fixators in all. Patients age ranged 9 to 19 years. Five patients underwent corrective osteotomies with external fixators (group C), in which group US follow-up exams were not standardized. For all 252 US examinations, performed in real time, an Acuson 128 unit with a 5-MHz linear probe was used and anterior, median and lateral longitudinal scans were acquired.

[Echographic finding of a liver mass in the first years of life]. / Reperto ecografico di massa epatica nei primi anni di vita.

On the basis of personal experience of echographic finding of liver mass in the early years of life, the origin is recalled and symptomatology with ultrasounds outlined: 1) they may be occasional findings without corresponding clinical signs (cystic dysplasic forms); 2) they may be metastases of known tumours (neuroblastoma); 3) they may be primary neoplasias (haemangiomas); 4) they may be signs of a state of immunodeficiency (abscess foci). It is stated that the data supplied by echography are often aspecific or permit diagnosis only if integrated with elements provided by other techniques and/or by clinical and biohumoral data.

[Echotomography diagnosis of congenital hip dysplasia. Experience with 1120 cases]. / Diagnosi ecotomografica di displasia congenita dell'anca. Esperienza su 1120 casi.

The congenital hip dysplasia is based on an abnormal acetabular rim, with pathologic capsula and ligaments. These pathologic structures can lead to the subtotal or total dislocation of the hips. In newborns the joint cartilaginous structures, can be visualized by sonography and it is possible to diagnose the different grade of dysplasia. Our series, in part previously selected, consist in 1120 joints. The results in newborns up to 3 months of age are: normal joints 79.5%, immature 10.7%, pathologic 9.8%. After 3 months of age: normal joints 93%, dysplastic 5.2%, subdislocated 0.6%, dislocated 1.2%. In all the cases we used the morphologic Graf technique and in newborns also the dynamic examination according to Novick to precise the minimal degree of the instability of the hips. Sonography permits an early diagnosis of hip dysplasia without false positive or negative results.

MRI "road-map" of normal age-related bone marrow. I. Cranial bone and spine.

We retrospectively reviewed 733 cranial and 250 spinal T1-weighted MR images of patients younger than 24 years to evaluate the bone marrow changes. The signal intensity of the bone marrow on short-TR/TE images was compared with that of fat and normal muscles in the contiguous region and graded. The signal intensity of all anatomic segments was as low as that of muscle, or inferior, in all patients younger than 3 months because of hematopoietic tissue and probably greater amounts of trabecular bone. The first anatomic segments of cranial bone to become hyperintense were the zygomatic bone and mandibular symphysis, followed by the presphenoid bone, basisphenoid, basiocciput, calvaria, and the petrous apex. After 3 years of age, most patients demonstrated pneumatization of the sphenoid sinus. We describe the most interesting changes in the developing spine, which occur in the first 2 years of life. The morphology of the vertebral bodies was evaluated. The variability of the signal and the morphology of the disks were also evaluated. Regional patterns of bone marrow signal intensity and age-related differences should not be misinterpreted as a pathologic condition.

MRI "road-map" of normal age-related bone marrow. II. Thorax, pelvis and extremities.

We retrospectively reviewed T1-weighted MR images of 381 patients aged from 7 days to 24 years to evaluate the bone marrow change in thoracic wall and shoulder, pelvis and proximal femur and upper and lower extremities. The patients included in the study were without history of bone marrow disease. A grade of from 1 to 4 was assigned to the marrow signal intensity of the examined anatomic segments. The signal intensity of all anatomic segments was as low as or lower than that of muscle in all patients younger than 2 months, reflecting underlying hematopoietic marrow. The first segments to become hyperintense were the epiphyseal/round bone ossification centers, followed by the phalanges, diaphysis, flat bones and metaphysis. Marrow signal intensity increased in all regions with age. While in the epiphysis, round bones and diaphysis bone marrow shows a diffuse and homogeneous increased signal intensity with age, in the sternum, ribs, scapulae, posterior ilium and metaphysis varying percentages of intermediate signal intensity are maintained. An orderly progression of red to yellow marrow was established.

Mucopolysaccharidosis: thickening of dura mater at the craniocervical junction and other CT/MRI findings.

Cranial CT and/or MRI imaging of 8 patients with mucopolysaccharidosis (MPS) was retrospectively evaluated. Two patients had MPS IH, 1 had MPS IS, 1 had MPS IVA and 4 had MPS IV. CT and MRI showed thickening of dura mater at the cranio-cervical junction, causing narrowing of the subarachnoid space, in all the patients examined. Spinal cord compression was detected in 4 patients. Other findings were: white matter alterations, mild to severe hydrocephalus, skull dysplasia and odontoid dysplasia. White matter alterations were evident as large areas and as multiple dispersed spots of prolonged T1 and T2 value. Reduced gray/white matter contrast was demonstrated on T2-weighted MRI images. It is important to examine the cranio-cervical junction carefully for thickening of dura mater in all patients with mucopolysaccharidosis examined by CT or MRI, because of the generally progressive clinical course of MPS. In patients with symptomatic cord compression, surgical intervention should be considered.

[Transcranial Doppler for the monitoring of gas embolism in neurosurgical operations in the sitting position]. / Doppler transcranico per il monitoraggio dell'embolia gassosa negli interventi neurochirurgici in posizione seduta.

The risk of venous air embolism is significant in neurosurgical procedures performed in the sitting position. Monitoring for venous air embolism, therefore, is crucial and can be approached from several aspects. The most sensitive generally applicable clinical method for the detection of intracardiac gas is based on an application of the Doppler principle. The Authors describe the technique used to adapt a transcranial Doppler (TC 2-64 B, EME, Germany), and a probe designed to record the Doppler signal from intracranial arteries (Transcran FP 2, EME, Germany), as precordial Doppler in order to monitor venous air embolism in neurosurgical procedures performed in the sitting position.

[High-resolution computerized tomography. Staging of lobular lesions in cystic fibrosis]. / Tomografia computerizzata ad alta risoluzione. Stadiazione delle lesioni lobulari nella fibrosi cistica.

Forty-four patients affected with cystic fibrosis (CF) were examined by means of high-resolution Computed Tomography (HRCT) of the chest; the sensitivity of this technique was evaluated in identifying small pulmonary structure alterations, and its role outlined. In all cases, HRCT scans allowed early lobular shape anomalies to be detected and secondary pulmonary lobular lesions to be correlated with disease evolution. A classification for lobular lesions was proposed: Stage I - Thickening of the bronchovascular bundle and/or intralobular septa and/or middle interstitial compartment. Unessential changes in lobular ventilation. Preservation of lobular shape. Stage II - Intralobular emphysema. Acinar filling with normal ventilation (A) or diffuse hypoventilation of the lobule (B). Preservation of lobular shape. Stage III - Lobular consolidations. Preservation of lobular shape. Stage IV - Patch distribution of lesions characterized by derangement of lobular structures. Changes in normal lobular shape. The identification of these lesions confirms HRCT as the most sensitive technique for the early visualization and localization of signs of CF bronchopneumonopathy. A broader experience coming from the systematic use of HRCT in chronic inflammatory lung diseases would increase our knowledge of pathogenetic processes and allow therapeutic perspectives to be improved.

[Ultrasonics in the study of periencephalic post-traumatic effusions in the newborn and suckling infants]. / L'ecotomografia nello studio delle raccolte periencefaliche post-traumatiche nel neonato-lattante.

The authors report their experience in 8 cases of cranial post-traumatic superficial collections, studied by US. Traumatic cranial injuries with superficial collections are not rare in newborns; their early and complete diagnosis is necessary for a correct therapeutic approach. Sonography could be used as a first choice procedure but presents some limitations in the study of the posterior fossa. Therefore CT remains the technique of choice.

[Malformations of the fetal urinary tract of surgical significance. Diagnosis on the basis of pre- and post-natal imagings]. / Malformazioni dell'apparato urinario fetale di interesse chirurgico. Diagnostica per immagini pre- e post-natale.

Out of the 29 cases of fetal urinary tract anomalies detected by sonography, the authors report on the 17 cases with potentially correctable malformations. A critical analysis of the diagnostic contribution offered by the radiologic and sonographic studies is presented. The role of ultrasound examination in the choice of a suitable investigation strategy is emphasized, underlining the importance of an accurate approach to avoid diagnostic errors and unuseful procedures. The indications for fetal and neonatal antegrade pyelography are discussed.

[Ultrasonic diagnosis of cerebellar hemorrhage in newborn infants. Apropos of 2 cases]. / Diagnosi ecotomografica di emorragia cerebellare nel neonato. A proposito di 2 casi.

The sonographic diagnosis of cerebral hemorrhage, in preterm infants is quite easy. On the contrary the prematurity degree of the patient and the anatomic location of the intracerebellar hemorrhage makes of this important lesion a difficult diagnosis to achieve. We present our results of 248 preterm infants scanned by ultrasound, in our Institute, to detect intraventricular or subependymal hemorrhage. Out of the 248 patients the incidence of SEH or IVH was 21%, only 1 case of intracerebellar hemorrhage, as complication of IVH-SHE, was found. Another intracerebellar hemorrhage was diagnosed in a full term newborn without other signs of hemorrhage.

[Non-Hodgkin's lymphoma with hepatosplenic involvement. The importance of imaging diagnosis using magnetic resonance tomography]. / Linfoma non-Hodgkin con interessamento epatosplenico. Importanza della diagnostica per immagini mediante tomografia a risonanza magnetica.

This study evaluates the importance of magnetic resonance imaging (MR) in the exploration of the abdomen in a case of non-Hodgkin lymphoma diagnosed in a 14-year-old boy. Results are compared with those obtained using two widely used diagnostic methods: CT and ultrasonography (US). US revealed a prevalent involvement of the spleen, whereas CT showed a marked hepatic infiltration. The role of MR seems important because it allowed the contemporary and careful evaluation of hepatolienal involvement. The main advantages and drawbacks of using MR in pediatrics, and in particular in the study of the metastatic involvement of hypochondriac organs are discussed.

[Mucopolysaccharidoses: evaluation of the cranium by computed tomography and magnetic resonance]. / Mucopolisaccaridosi: valutazione del cranio con tomografia computerizzata e risonanza magnetica.

Cranial CT and/or MRI examinations were performed in 8 patients affected with mucopolysaccharidosis. Two patients were affected with mucopolysaccharidosis IH,1 had mucopolysaccharidosis IS, 1 had mucopolysaccharidosis IV A and 4 presented mucopolysaccharidosis VI. CT and MRI showed white matter changes consisting of symmetric and diffuse hypodense areas on CT, large areas and multiple spots of prolonged T1 and T2 value on MRI. Reduced gray/white matter contrast was demonstrated on T2-weighted sequences. Furthermore, CT and MRI showed thickening of the dura mater at the cranio-cervical junction, which caused subarachnoid space narrowing in all patients. Spinal cord compression was detected in 4 patients. Additional findings were mild to severe hydrocephalus, skull dysplasia and odontoid dysplasia. Owing to the progressive clinical course of all mucopolysaccharidosis, the authors stress the importance of a careful study of the cranio-cervical junction in all the patients with mucopolysaccharidosis examined by CT or MRI in order to demonstrate essential thickening of the dura mater. In the patients with symptomatic cord compression, surgery should be considered.

Testicular microlithiasis: US findings in six pediatric cases and literature review.

The aim of this article is to report on six pediatric cases of testicular microlithiasis (TM) and to review literature reports, in order to schedule US and/or other control examinations, particularly when concomitant focal or diffuse alterations of the testicular parenchymal structure are present, considering the possible association of TM with testicular tumors. Six patients (age range 4-12 years) underwent US examination for scrotal trauma (two cases) unilateral cryptorchidism (one case) follow-up after orchidopexy for bilateral cryptorchidism (one case), and varicocele (two cases). Five examinations were performed with high-frequency probes (10/13 MHz) and seven with 5/7.5-MHz frequency transducers. Follow-up US examinations were performed at different times depending on initial clinical indications, presence of underlying disease, and initial US findings. Two of the six patients underwent three US examinations, two patients underwent two US examinations, and the remaining two patients underwent only one US examination. The patients underwent a total of 12 US examinations. Microliths were bilateral in four patients and unilateral in two patients. In these two latter cases, the contralateral testis was, in one case, cryptorchid and could not be evaluated by US; in the other case it was small and hyperechogenic with orchidopexy sequelae. In three cases microliths were distributed throughout the testis. In the remaining three cases they were present in limited areas of parenchyma. As to the importance of microliths, it was defined as mild in three cases and moderate/severe in three cases. Intratubular testicular microlithiasis is a well-proved histological finding (biopsy or autopsy). More recent is the US demonstration of TM with consequent definition of its pattern: usually bilateral hyperechogenic multiple small foci without acoustic shadows with complete or partial extension to the parenchyma. Testicular microlithiasis is a rare finding. Moreover, the pediatric cases reported in the literature are very few. However, the use of high-frequency US transducers (10-13 MHz) has recently allowed an easier demonstration of this disease also in children. Of particular interest is the study of the still-debated association of microliths with other diseases such as neoplasms. Some aspects need further investigation, namely the real incidence of microliths in the healthy population, the incidence of tumors in patients with microliths, the differences between adults and children, and the different types of follow-up at different ages. In pediatric age, if TM represents an isolated sign, patients need non-invasive US follow-up until adult age. Only if TM is in association with focal lesions of testis parenchyma is it mandatory to perform biopsy or surgical treatment.