Strategies to develop radiomics and machine learning models for lung cancer stage and histology prediction using small data samples.

Predictive models based on radiomics and machine-learning (ML) need large and annotated datasets for training, often difficult to collect. We designed an operative pipeline for model training to exploit data already available to the scientific community. The aim of this work was to explore the capability of radiomic features in predicting tumor histology and stage in patients with non-small cell lung cancer (NSCLC). We analyzed the radiotherapy planning thoracic CT scans of a proprietary sample of 47 subjects (L-RT) and integrated this dataset with a publicly available set of 130 patients from the MAASTRO NSCLC collection (Lung1). We implemented intra- and inter-sample cross-validation strategies (CV) for evaluating the ML predictive model performances with not so large datasets. We carried out two classification tasks: histology classification (3 classes) and overall stage classification (two classes: stage I and II). In the first task, the best performance was obtained by a Random Forest classifier, once the analysis has been restricted to stage I and II tumors of the Lung1 and L-RT merged dataset (AUC = 0.72 ± 0.11). For the overall stage classification, the best results were obtained when training on Lung1 and testing of L-RT dataset (AUC = 0.72 ± 0.04 for Random Forest and AUC = 0.84 ± 0.03 for linear-kernel Support Vector Machine). According to the classification task to be accomplished and to the heterogeneity of the available dataset(s), different CV strategies have to be explored and compared to make a robust assessment of the potential of a predictive model based on radiomics and ML.

Humeral fractures due to low-energy trauma: an epidemiological survey in patients referred to a large emergency department in Northern Italy.

UNLABELLED: This survey describes the epidemiology of approximately 1800 low-energy humeral fractures seen in a large emergency department in Northern Italy over 7 years (2007-2013), highlighting the differences from previous Italian studies. PURPOSE: The purpose of this study was to determine the incidence of humeral fractures due to low-energy trauma in patients 40 years of age or older referred to a large Emergency Department (Parma, Northern Italy) in a 7-year period (2007-2013). METHODS: All humeral fractures referred to the emergency department of the Academic Hospital of Parma (the main hospital in the province with a catchment area of approximately 345,000) were retrieved from the hospital database using both ICD-9CM codes and text strings. The diagnosis of humeral fracture due to low-energy trauma was confirmed by medical records and X-ray reports, after exclusion of injuries due to a clear-cut high-energy trauma or cancer. RESULTS: The query identified 1843 humeral fractures (1809 first fractures), with a clear predominance in women (78 %). Fractures of the proximal humerus represented the large majority of humeral fractures (more than 85 %), with an incidence progressively increasing with age (more than 60-fold in women and 20-fold in men). Simultaneous fractures (hip in particular) were frequent especially after 85 years of age (1 out of 8 cases). When compared to other Italian studies, the incidence of humeral fractures was significantly lower than that derived from discharge data corrected for hospitalization rate (standardized rate ratio 0.74; p < 0.001), while the pattern of age-related changes was significantly different from that computed by applying the ratio between hip and humeral fractures observed in Malmö, Sweden, to the Italian hip fracture rates. CONCLUSIONS: This study gives an up-to-date description of the epidemiology of low-energy humeral fractures in Italy. Our results partly differ from previous Italian studies based on indirect estimations.

Hospital admission rates for distal forearm fractures: an epidemiological survey in patients referred to a large emergency department in Northern Italy.

UNLABELLED: In this survey, the proportion of patients with distal forearm fractures admitted to the Parma University Hospital during 2012 (13 %) was relatively low and generally lower than that reported in other studies. In our region, the main orthopedic approach remains conservative. PURPOSE: The purpose of this study was to define the ratio between hospitalized and non-hospitalized fragility fractures of the distal forearm in our province (Parma, Northern Italy). METHODS: All forearm fractures referred during 2012 to the emergency department of the Parma University Hospital (the main hospital in the province with a catchment area of approximately 345,000) were retrieved from the hospital database using both ICD-9-CM codes and text strings. The diagnosis of distal forearm fracture due to low-energy trauma and the need for hospitalization were individually confirmed by medical records and X-ray reports. The analysis was limited to subjects aged 40 years and over. RESULTS: In both sexes combined, 66 subjects out of 505 were hospitalized (13.1 %; confidence interval (CI) 95 % 10.4-16.3 %), 47 immediately (8.1 %) and 25 (5 %) after a few days. The percentage of cases hospitalized was 12 % in women (CI 95 % 9.2-15.6 %) and 17 % in men (CI 95 % 11.1-25 %; p = 0.16). CONCLUSIONS: The percentage of fragility distal forearm fractures hospitalized in our area is relatively low and generally lower than that reported in other studies.

Longitudinal changes of trabecular bone score after estrogen deprivation: effect of menopause and aromatase inhibition.

PURPOSE: To examine the effects of the menopausal transition and treatment with aromatase inhibitors (AI) on trabecular bone score (TBS, a newly proposed index of bone architecture derived from DXA vertebral scans) and vertebral bone mineral density (BMD). METHODS: Retrospective cohort study on 29 women who became postmenopausal during a mean follow-up of 2.9 years (MP group) and 34 women treated with AI during a mean follow-up of 2.1 years (AI group). BMD was measured by DXA and TBS with a specific software. RESULTS: TBS decreased after menopause, but the change was significantly lower than that of the lumbar BMD (-4.6 vs. -6.8 %; mean difference: 2.2 %; p = 0.016). An even larger difference was observed in the AI group (-2.1 vs. -5.9 %; mean difference: 3.8 %; p = 0.002). CONCLUSIONS: The decrease of TBS induced by menopause or treatment with AI is significantly lower than that of lumbar BMD.

[Plastic and esthetic surgery on children with Down's syndrome: ethical and technical aspects]. / La chirurgia plastica estetica nei bambini con sindrome di Down: aspetti tecnici ed etici.

One of the most commonly shared characteristics of children with Down's syndrome is the effect on facial features. The vast majority of children with Down's syndrome have an epicanthal folds, a slanted palpebral fissures and a flattened nasal bridge. Another common feature is a protruding tongue with an open mouth. The surgeries can be categorized into two groups: techniques aimed at reducing the size of the tongue, and surgeries aimed at improving the appearance of the face, called "facial reconstruction". Indications and limits of these categories are discussed separately. Moreover, the tongue reduction presents further anesthesiological problems. Parents should be not pressured into consenting to plastic surgery, and plastic surgery should never be considered a stand-alone therapy. Parents should get all information about the procedures, including risks, performed on their children to best make an informed decision, also in order to avoid unnecessary pain to the children and the adolescents with Down's syndrome.

[Urethral duplication in pediatric age. A case report]. / Duplicazione uretrale in età pediatrica. Presentazione di un caso.

Urethral duplication is a rare congenital anomaly, resulting from a wide range of malformations of the urogenital sinus. Generally, the duplication develops on the sagittal plane; the accessory urethra may run dorsally or ventrally to the orthotopic one. The duplication is defined as epispadic in the first case, and hypospadic in the second. In the medical literature approximately 150 cases have been reported. Relatively more frequent among males, it is often associated with other malformations of the urogenital tract or other organs. The authors present a case of a 4 year old child with a complete epispadic duplication, that is, two external meatus, one of which the dorsal aspect of the glans, and the other orthotopic. Clinically, duplication and weakening of the stream, urinary incontinence and UTI were present. US examination documented the normality of the upper urinary tract and of the bladder. Retrograde urethrocystography showed a completely permeable urethral duplication, with two external meatus. The excision of the accessory urethra was carried out together with the reconstruction of the hypospadic meatus with an "overlap anastomosis". The post-operatory period was uneventful, and one year after surgery the patient is asymptomatic, with normal uroflowmetric readings and echographically documented complete bladder emptying. In the opinion of the authors, the treatment is indicated in symptomatic forms and the surgical options varies, depending on the type and grade of malformation, its clinical manifestations and the presence of associated anomalies. Antibiotic treatment is not effective and other treatments, such as diathermocoagulation or the injection of caustic substances into the accessory duct have been abandoned.

[Head injuries in children. Considerations on 3,715 consecutive cases]. / Il trauma cranico in età pediatrica. Considerazioni a proposito di 3715 casi consecutivi.

BACKGROUND: The authors present their personal experience of 3715 cases of head injury in pediatric patients, occurring during the last three years (1997-1999), admitted to the Emergency ward at the "Anna Meyer" children's hospital in Florence. METHODS: A prospective study was made, starting from the evaluation made by the paediatric surgeon and following the subsequent diagnostic and clinical course. Depending on the severity of injury, this took the form of immediate discharge with a written sheet of instructions, "short observation" (up to 12 hours) in an Emergency ward and/or admission to neurosurgery or general medicine or to intensive care. The authors also analyse the diagnostic and instrumental tests carried out at the various stages (cranial X-ray, direct cranial CT, EEG) and the specialist consultations required (neurosurgery, neurology, paediatrics, resuscitation). Data for injured children transferred from other hospitals for neurosurgery were excluded from the study which only included patients examined primarily at our hospital. If admitted for more than 48 hours, a neurosurgical outpatient check-up was programmed one week later. In more severe cases, patients were admitted to day hospital between six months and one year later. RESULTS: Injuries were minor in 91% of cases and the age of patients ranged between 5 days and 14 years; moreover, 60% of the patients observed were male. Only 1.5% of cases seen in Emergency were admitted to hospital and 8.4% of all head injuries, with a total stay of between 1 and 6 days. There were 4 deaths in severely polytraumatised patients. There was only one case of firearm injury which was not fatal. Head X-rays were performed in 13.4% of patients showing evidence of fracture in 19.1% of cases. Direct cranial CT was performed in 10.2% of cases with pathological findings in 23.9% of cases. Neurosurgery was performed in one of the 5.9% patients admitted to hospital. The late sequelae to head injury included one case of epilepsy that occurred 7 months after injury. CONCLUSIONS: Anamnesis showed that the most frequent reason leading to head injury was lack of adult supervision and that the majority of severe injuries were caused by road accidents, both as pedestrians and as passengers. Lastly, the authors emphasise the importance of recognising and correctly treating so-called secondary cerebral damage, which has a non-immediate onset but is potentially severe, and identifying the risk factors for head injury in order to reduce the incidence and severity.

[Acute scrotal involvement as onset of a testicular Sertoli cell tumor in a two-month-old baby]. / Scroto acuto come segno di esordio di un tumore a cellule di Sertoli del testicolo in un bambino di due mesi.

Sertoli cell tumour is an uncommon neoplasm, either in the adult and in the pediatric age groups. An intrascrotal, slowly growing, painless swelling generally represents its clinical onset. Orchiectomy definitively is successful in these patients, since Sertoli cell tumour very rarely metastatise elsewhere. The case of a two-month old baby in which an acute intrascrotal involvement (requiring immediate surgical therapy), was the atypical onset of a testicular Sertoli cell tumour, is described. The hystogenesis as well as the clinical and pathological peculiarities of this neoplasm in pediatric patients are discussed.

[Congenital anomalies of the penis in children. A few consideration about 92 cases]. / Malformazioni congenite del pene in età pediatrica. Alcune considerazioni a proposito di 92 casi.

The authors present their experience of 92 cases of anomalies of the penis, hypospadias excepted, occurring in children between 12 months and 10 years old, during the last 5 years, in their Pediatric Surgical Department. In the literature, there are reported only many single cases of these anomalies, for the most part associated in serious multiple malformations, or with hypospadias. The children included in this report present the anomalies of the penis as a sole malformations. The classification of these anomalies was made by embryological criteria and by the frequency of occurrence. In 41 cases there was congenital curvature of the penis, in 9 cases there was a webbed penis, in 6 cases a concealed penis. Torsion of the penis occurred in 6 cases (in 5 anticlockwise) the microphallus in 5 cases. The "hypospadias without hypospadias" occurred in 5 cases, in the others there was an association among these anomalies. The authors emphasize the importance of these malformations for the children and their families, also in order to prevent, also serious, psychological effects.

[Genetic aspects of hypospadias: considerations apropos of 362 cases]. / Aspetti genetici dell'ipospadia: considerazioni a proposito di 362 osservazioni.

The Authors present 362 cases of hypospadias, during 10 years, considering genetical aspects of the malformation. The mean frequency rate of hypospadias is 0.32%. In 60 of the examined patients (17.1%) there was another subject with hypospadias and in 12 cases (4.3%) there was a third subject with the malformation. In 32 cases (9.1%) the relationship was between brothers and in 15 cases (4.2%) the fathers were concerned. Thus, each group had a clean increasing risk in comparison with the mean frequency rate. From the analysis of the results appears a not mendelian inheritance and not even sex linked or single locus linked, in the transmission of the characters. The Authors emphasize the role of some hereditary predisposition in concomitance of environmental conditions, to date not well known. The hypospadias, thus, to fit in the "mid-line pathology", a recent chapter of genetics, characterized by a lack of coalescence, just in the mid-line of embryonal development, during organogenesis.

[Xanthogranulomatous pyelonephritis in childhood: considerations on 2 new cases]. / La pielonefrite xantogranulomatosa in età pediatrica: considerazioni a proposito di 2 nuovi casi.

The Authors report their experience about two cases of xanthogranulomatous pyelonephritis in childhood. The clinical history, diagnostic procedures and surgical treatment are described. The xanthogranulomatous pyelonephritis is a rare form of chronic inflammatory disease of the kidney, in which pre-operative differential diagnosis with renal cancer or with extra renal neoplastic and inflammatory diseases is very difficult. The signs and symptoms are not characteristic, such as renal tumour, recurrent UTI, abdominal pain, fever. Also non characteristic are the findings, performed with diagnostic ultra sound and computed tomography. The surgical treatment is always effective in the xanthogranulomatous pyelonephritis. About 500 cases are described in adults and about 80 cases in children, from the first description in 1963. The first of our cases, occurring in a boy 6 years old, was treated with nephrectomy, because of the pre-operatory aspect was like tumour. In the second of the cases described, occurring in a girl 11 years old, the nephrectomy was performed because the chronic purulent inflammatory process had involved all the kidney. In the post-operative, in the first case was performed a relaparotomy for intestinal occlusion in 12th day, in the second case the post-operative was uneventful. The Authors emphasize the importance of the xanthogranulomatous pyelonephritis in the differential diagnosis in children with recurrent UTI, renal masses, fever, in the clinical history.

[Acute scrotum in childhood: considerations on 457 cases]. / Lo scroto acuto in età pediatrica: considerazioni a proposito di 457 osservazioni.

The Authors present their experience about 457 consecutive cases of acute scrotum, occurring from 1980 to 1990, at their Pediatric Surgery Unit. The condition is caused by torsion of the appendage of the testis (78.1%), torsion of the funicle (9.6%), acute idiopathic oedema of the scrotum (2.87%), and also tumours (1.17%). Also in their experience, the surgical approach is the correct treatment for the acute scrotum in order to prevent the irreversible damage of the testis. The surgical treatment present no problem and all the post-operatives were uneventful. In children under 2 years, the interventions were performed by inguinal incision, above 2 years by scrotal incision. The contralateral orchiopexy, in case of torsion of the funicle, was performed in the same session, or performed later, because of the anesthetic consideration.

Low density lipoprotein retention by aortic tissue. Contribution of extracellular matrix.

We compared in vitro heparin binding activity and in vivo intravascular clearance and aortic uptake in rabbits of native, reductively methylated and heparin-complexed low density lipoprotein (LDL) in order to explore the extracellular matrix binding vs cellular metabolism of LDL. Reductively methylated LDL formed soluble and insoluble complexes with heparin which was comparable to native LDL. Reductive methylation of LDL produced only 30% reduction in aortic uptake vs 60% reduction in plasma clearance, reflecting the relatively smaller contribution of receptor-mediated pathway in aortic tissue vs whole animal. The intravascular clearance of native and heparin-complexed LDL remained essentially the same, indicating similarities in cellular metabolism of LDL in both cases. But the aortic uptake of the heparin bound LDL was 30% less than the native LDL, suggesting an inhibition in binding of heparin-complexed LDL to tissue proteoglycans. Saline extraction accounted for only part (53-66%) of the LDL preparations that were retained by the tissue while subsequent collagenase and elastase treatments extracted 3-5% and 17-22% of the materials respectively. These results favor the contribution of arterial extracellular matrix components to the retention of LDL.

Dynamics of lipoprotein-glycosaminoglycan interactions in the atherosclerotic rabbit aorta in vivo.

Dynamics of lipoprotein-glycosaminoglycan interactions in aortas were studied in vivo using the atherosclerotic rabbit model. Severe hypercholesterolemia and atherosclerosis were produced by relatively long-term feeding of a high cholesterol diet. [35S]Sulfate uptake by aorta was measured to assess the sulfated glycosaminoglycan metabolism while the plasma and aorta distribution of 125I-labeled LDL after intravascular injection was determined to monitor aortic LDL uptake and complex formation with glycosaminoglycans. The retention and distribution of LDL as lipoprotein-glycosaminoglycan complexes in different extracellular connective tissue elements were evaluated by extracting the tissues with saline, collagenase and elastase. Hypercholesterolemia with atherosclerosis resulted in a several-fold increase in the uptake of LDL by aorta despite a marked reduction of 125I-labeled LDL in the plasma compartment and in a significant increase in glycosaminoglycan content of aorta coupled with an increased 35S incorporation into glycosaminoglycans. Elastase-solubilized fractions from normal aortas and collagenase-solubilized fractions from atherosclerotic aortas contained maximum labeled and nonlabeled glycosaminoglycan, suggesting alterations in the make-up of fibrous structures of connective tissue matrix in atherosclerosis. Saline extraction and collagenase and elastase digestions solubilized varied proportions of lipoprotein-cholesterol and 125I-labeled LDL, thereby representing different pools of extracellular matrixbound lipoproteins. A tendency for 125I-labeled LDL to increase in collagenase- and elastase-solubilized fractions with time (4 h vs. 24 h) was noted. The occurrence of both lipoproteins and glycosaminoglycan (labeled and nonlabeled) in the ultracentrifugal floating fraction at solvent density 1.063 g/ml demonstrated that the lipoproteins solubilized by different extraction procedures occur in part as lipoprotein-glycosaminoglycan complexes. The specific activities of glycosaminoglycan in the complexes obtained by different extraction procedures differed markedly (elastase greater than collagenase greater than saline), emphasizing the presence of different pools of complexes. Thus, besides arterial cell-mediated processes, extracellular matrix components are important in affecting the retention and accumulation of LDL in atherosclerosis.