New Segmentation Models for the Radiologic Characterization of Polycystic Kidney Disease Patients from MR and CT Images

Recent advances in genomics have contributed to a better understanding of the pathogenesis of the polycystic kidney disease (PKD), suggesting new treatment strategies to inhibit or delay cyst formation and expansion. The efficacy of these therapies is evaluated by estimation of cystic burden measured by magnetic resonange imaging (MRI) as total kidney volume (TKV). In this Thesis, different imaging approaches are proposed for a correct characterization of the PKD patient by the estimation of renal and cyst volume from magnetic resonance and computed tomography (CT) images. TKV estimation method from MRI relies on a previously validated method developed for axial images that has been adapted and validated to work on coronal images. The results have been compared with the ones obtained from axial images and validated with volume estimation obtained from manual tracing. The performace of the semi-automated method in terms of misclassification of the PKD patient was also evaluated in comparison with other radiologic approaches currently usedfor TKV assessment such as the ellipsoid method and the mid-slice method. A novel method for TKV computation from CT images is proposed. This multi- step approach is completely automated and includes the use of a level set approach to identify the renal contour and so extrapolate the renal volume. The segmented kidneys obtained with the developed methods where used for the segmentation of the cysts. A similar strategy was used for cyst segmentation and counting from MR images. Every cyst agglomerate underwent a voting mechanism based on the curvature of the object interface to distinguish the single cysts. The results of this approach for TCV computation was validated through comparison with TCV obtained by manual segmentation. The last chapter is dedicated to the research activity conducted in the area of diffussion weighted imaging

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Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity

15noMitochondrial ferritin is a functional ferritin that localizes in themitochondria.Itisexpressedinthetestis, heart,brain,and cells with active respiratory activity. Its overexpression in culturedcellsprotectedagainstoxidativedamageandreduced cytosolic iron availability. However, no overt phenotype was describedinmicewithinactivationoftheFtMtgene.Here,we usedthe doxorubicin model ofcardiac injuryina novel strain of FtMt-null mice to investigate the antioxidant role of FtMt. These mice did not show any evident phenotype, but after acute treatment to doxorubicin, they showed enhanced mortalityandaltered heartmorphologywithfibrildisorganization and severe mitochondrial damage. Signs of mitochondrial damage were present also in mock-treated FtMt−/− mice. The hearts of saline- and doxorubicin-treated FtMt−/− mice had higher thiobarbituric acid reactive substance levels, heme oxygenase 1 expression, and protein oxidation, but did not differ from FtMt+/+ in the cardiac damage marker B-type natriureticpeptide(BNP),ATP levels, and apoptosis.However,the autophagy marker LC3 was activated. The results show that the absence of FtMt, which is highly expressed in the heart, increases the sensitivity of heart mitochondria to the toxicity of doxorubicin. This study represents the first in vivo evidence of the antioxidant role of FtMt.openopenMaccarinelli, Federica; Gammella, Elena; Asperti, Michela; Mariaregon, ; Donetti, Elena; Recalcati, Stefania; Poli, Maura; Finazzi, Dario; Arosio, Paolo; Biasiotto, Giorgio; Emiliaturco, ; Altruda, Fiorella; Lonardi, Silvia; Cornaghi, Laura; Cairo, GaetanoMaccarinelli, Federica; Gammella, Elena; Asperti, Michela; Mariaregon, ; Donetti, Elena; Recalcati, Stefania; Poli, Maura; Finazzi, Dario; Arosio, Paolo; Biasiotto, Giorgio; Emiliaturco, ; Altruda, Fiorella; Lonardi, Silvia; Cornaghi, Laura; Cairo, Gaetan

Chronic constipation diagnosis and treatment evaluation: The "CHRO.CO.DI.T.E." study

Background: According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy. Methods: During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded. Results: Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC. Conclusions: Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the "first line" diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a "second line" approach. Diagnostic tests and prescribed therapies increased by increasing CC severity

Long‐term variability and trends in meteorological droughts in Western Europe (1851–2018)

We analysed long‐term variability and trends in meteorological droughts across Western Europe using the Standardized Precipitation Index (SPI). Precipitation data from 199 stations spanning the period 1851–2018 were employed, following homogenisation, to derive SPI‐3 and SPI‐12 series for each station, together with indices on drought duration and severity. Results reveal a general absence of statistically significant long‐term trends in the study domain, with the exception of significant trends at some stations, generally covering short periods. The largest decreasing trends in SPI‐3 (i.e., increasing drought conditions) were found for summer in the British and Irish Isles. In general, drought episodes experienced in the last two or three decades have precedents during the last 170·years, emphasizing the importance of long records for assessing change. The main characteristic of drought variability in Western Europe is its strong spatial diversity, with regions exhibiting a homogeneous temporal evolution. Notably, the temporal variability of drought in Western Europe is more dominant than long‐term trends. This suggests that long‐term drought trends cannot be confirmed in Western Europe using precipitation records alone. This study provides a long‐term regional assessment of drought variability in Western Europe, which can contribute to better understanding of regional climate change during the past two centuries

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research