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Background Rare diseases are chronic and life-threatening disorders affecting Results To the purpose of our analysis, we considered heart, lung, liver and kidney transplants included in the Transplant Registry (TR) of the Italian National Transplantation Center in the 2002–2019 timeframe. Overall, 49,404 recipients were enrolled in the cohort, 5.1% of whom in the pediatric age. For 40,909 (82.8%) transplant recipients, a disease diagnosis was available, of which 38,615 in the adult cohort, while 8,495 patients (17.2%) were undiagnosed. There were 128 disease categories, and of these, 117 were listed in the main rare disease databases. In the pediatric cohort, 2,294 (5.6%) patients had a disease diagnosis: of the 2,126 (92.7%) patients affected by a rare disease, 1,402 (61.1%) presented with a monogenic condition. As expected, the frequencies of pathologies leading to organ failure were different between the pediatric and the adult cohort. Moreover, the pediatric group was characterized, compared to the adult one, by an overall better survival of the graft at ten years after transplant, with the only exception of lung transplants. When comparing survival considering rare vs non-rare diseases or rare and monogenic vs rare non-monogenic conditions, no differences were highlighted for kidney and lung transplants, while rare diseases had a better survival in liver as opposed to heart transplants. Conclusions This work represents the first national survey analyzing the main genetic causes and frequencies of rare and/or monogenic diseases leading to organ failure and requiring transplantation both in adults and children.

Background/Purpose: Quality measures in surgery are important to establish appropriate levels of care and to develop improvement strategies. The purpose of this study was to provide risk-adjusted outcome measures after laparoscopic liver resection (LLR). Methods: Data from a prospective, multicenter database involving 4318 patients submitted to LLRs in 41 hospitals from an intention-to-treat approach (2014–2020) were used to analyze heterogeneity (I2) among centers and to develop a risk-adjustment model on outcome measures through multivariable mixed-effect models to account for confounding due to case-mix. Results: Involved hospitals operated on very different patients: the largest heterogeneity was observed for operating in the presence of previous abdominal surgery (I2:79.1%), in cirrhotic patients (I2:89.3%) suffering from hepatocellular carcinoma (I2:88.6%) or requiring associated intestinal resections (I2:82.8%) and in regard to technical complexity (I2 for the most complex LLRs: 84.1%). These aspects determined substantial or large heterogeneity in overall morbidity (I2:84.9%), in prolonged in-hospital stay (I2:86.9%) and in conversion rate (I2:73.4%). Major complication had medium heterogeneity (I2:46.5%). The heterogeneity of mortality was null. Risk-adjustment accounted for all of this variability and the final risk-standardized conversion rate was 8.9%, overall morbidity was 22.1%, major morbidity was 5.1% and prolonged in-hospital stay was 26.0%. There were no outliers among the 41 participating centers. An online tool was provided. Conclusions: A benchmark for LLRs including all eligible patients was provided, suggesting that surgeons can act accordingly in the interest of the patient, modifying their approach in relation to different indications and different experience, but finally providing the same quality of care.

Laparoscopic liver resection (LLR) for Hepatocellular carcinoma (HCC) is a safe procedure. Repeat surgery is more often required, and the role of minimally invasive liver surgery (MILS) is not yet clearly defined. The present study analyzes data compiled by the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) on LLR. To compare repeated LLR with the first LLR for HCC is the primary endpoint. The secondary endpoint was to evaluate the outcome of repeat LLR in the case of primary open versus primary MILS surgery. The data cohort is divided into two groups. Group 1: first liver resection and Group 2: Repeat LLR. To compare the two groups a 3:1 Propensity Score Matching is performed to analyze open versus MILS primary resection. Fifty-two centers were involved in the present study, and 1054 patients were enrolled. 80 patients underwent to a repeat LLR. The type of resection was different, with more major resections in the group 1 before matching the two groups. After propensity score matching 3:1, each group consisted of 222 and 74 patients. No difference between the two groups was observed. In the subgroup analysis, in 44 patients the first resection was performed by an open approach. The other 36 patients were resected with a MILS approach. We found no difference between these two subgroups of patients. The present study in repeat MILS for HCC using the IGoMILS Registry has observed the feasibility and safety of the MILS procedure.

Objective: To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme. Patients and Methods: Patients with metastatic renal cell cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Results: A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non-clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any-grade treatment-related AEs were fatigue (13%) and rash (9%). Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no treatment-related deaths. The objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% confidence interval 3.7–6.2) and the 12-month overall survival rate was 63%. Similar survival rates were reported among patients with non-clear-cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first-line sunitinib or pazopanib, or prior everolimus. Conclusion: The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients. © 2018 The Authors BJU International

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.

Objective A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. Design/methods 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. Results In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. Conclusions LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD-based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients' associations and organ-sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.

Background Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage ≥3 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage ≥3 CKD in a large cohort of patients affected by T1DM. Methods A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage ≥3 CKD (eGFR 30% from baseline was evaluated. Results The mean estimated GFR was 98 ± 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions Albuminuria and eGFR reduction represent independent risk factors for incident stage ≥3 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening. Electronic supplementary material The online version of this article (10.1186/s12882-018-1136-6) contains supplementary material, which is available to authorized users.

Background Management of Anderson–Fabry disease (AFD) is contentious, particularly regarding enzyme replacement therapy (ERT). We report results of a Delphi consensus panel on AFD management. Methods A survey to gauge consensus among AFD experts was distributed online and responses were analysed. Statements on: 1) diagnosis; 2) when starting ERT; 3) management of ERT infusion and adverse reactions; and 4) follow-up/monitoring response to therapy and progression of disease were included. Responses without consensus were discussed with an enlarged panel and modified to reach consensus. Results 15 experts responded to the survey. After plenary discussion among the enlarged panel, consensus was reached on most statements. Key points were the use of a target organ biopsy to show Gb3 deposits in symptomatic women with negative molecular analysis, the need for ERT in symptomatic women and in all patients with persistent signs and symptoms ± organ damage. It was agreed to assess vital signs before ERT administration and use a 0.2 μL filter on infusion to reduce the risk of adverse reactions, that serum should be drawn prior to the first infusion for anti-agalsidase antibody analysis to have a baseline value if a subsequent adverse reaction appears, and that pre-medication is required in those with prior infusion reactions. Holter ECG monitoring, cardiac and brain MRI, renal parameters, and abdominal ultrasound were considered important for the assessment of disease progression and response at ERT. Conclusions This consensus supplies guidance to healthcare providers on best practice in the management of patients with AFD and indicates a need for more guidance.

We suggest an alternative endovascular treatment for gluteal artery aneurysm using Floseal a matrix of bovine gel and thrombin component. A 70-year-old woman, presented with claudicatio of the lower left limb after 150 m walking and pain at the sciatic nerve irradiation. A pulsating and painful mass was present in the lower gluteal region. No history for previous trauma, nor for orthopedic surgery. The suspect of aneurysm of the left gluteal artery was confirmed by Color Doppler Ultrasound and by computed tomography (CT) showing a fusiform aneurysm in the lower gluteus artery. In order to rule out infective cause, blood coltures were taken. Compression of the sciatic nerve was confirmed by electromyography study. Patient was treated by endovascular treatment. We performed angiography, with a selective study of the lower left gluteus artery, and embolization of the aneurysm by an injection of FloSeal (hemostatic) and fibered platinum coil. At the discharge, we observed absence of pulsation in gluteus region and the complete resolution of clinical symptom. The Color Doppler Ultrasound scan showed a complete occlusion of the aneurysm. This case appears quite peculiar, for the absence of any pelvic trauma, orthopedic operations or previous penetrating lesions, responsible of vascular lesions as reported in literature. The large aneurysm dimensions made the embolization procedure quite difficult, and brought us to use FloSeal. The treatment we proposed may be useful in the treatment of peripheral aneurysms of great dimension, and may be an alternative to the more traditional ones.

The objective of this systematic review of the literature is to evaluate whether a laparoscopic operation can be performed on patients with occlusive or abdominal aortic aneurysm as a minimally invasive and durable alternative. For this purpose, the literature was reviewed and laparoscopic surgery results were compared with those of conventional and endovascular surgery. All series were included, even when containing also one case. Operative and clamping times, mortality and morbidity and hospital stay were evaluated. Thirty-five studies were identified about conventional (4), minilaparotomy (4), endovascular (4), total (12) and video-assisted (11) laparoscopic surgery. Operative and clamping times were shorter for video-assisted procedures than total-laparoscopic procedures. The mortality rate ranged from 3% to 4.5% for conventional surgery, from 0% to 3% for endovascular surgery, from 0% to 6% for total-laparoscopic surgery and from 0% to 4.2% for video-assisted laparoscopic surgery. A variable morbidity was described for all techniques, with a higher incidence in total-laparoscopic surgery. Mean hospital stay was similar for laparoscopic surgery procedures. The learning curve of a surgical team performing laparoscopic surgery improves theLaparoscopic abdominal aortic surgery is feasible and may offer good postoperative recovery with excellent mid-term patency. Shorter hospital stay and simple mid-term follow-up allow more comfort for the patient and probably monetary savings for the community. A steep learning curve is needed. For these reasons laparoscopic video-assisted technique can be considered a third means of treating severe occlusive and aortic aneurysm, but only new instruments for performing aortoprosthetic anastomoses can diffuse the total laparoscopic technique as a routine approach.

Chemoresistance is currently the main cause of failure in the treatment of cancer which, despite extensive research, remains unsolved. In this report the theoretical assumptions underlying antiangiogenic therapy are described and future perspectives and limits are discussed.

Leiomyosarcoma of the inferior vena cava (IVC) is a rare tumor that frequently produces non-specific symptoms. Surgical treatment is complex. In this review of our experience, we highlight replacement modalities of the vena cava or other vessels after complete tumor resection.During the last 20 years, we treated 12 patients (6 women and 6 men; age range, 38-72 years) with IVC leiomyosarcoma, all apparently free of distant metastases. Tumor location, graft patency, long-term survival and tumor recurrence were recorded. The tumor arose from the IVC in 8 patients; in 2 cases the intracaval mass reached the right atrium; in 4 patients the tumor arose from the femoroiliac axis. Surgical approach was by sternolaparotomy in 5 cases and by median xyphopubic access in 7. Extracorporeal circulation (ECC) was needed in 2 cases. All tumors were removed by en bloc resection. The IVC was directly sutured in 2 patients and patched in 4; no reconstruction was necessary in 2 patients; the IVC was replaced in the remaining cases. Four patients had an additional arteriovenous fistula. One patient underwent bifurcated Dacron graft replacement of the aortic carrefour involved by tumor.Two patients died postoperatively. One patient developed late stenosis of the polytetrafluoroethylene (PTFE) graft, which was treated by stenting. The mean follow-up period was 35 months. The 4-year survival rate was 51% and survival free of recurrence was 63%.Leiomyosarcoma of the IVC is an uncommon tumor that produces non-specific symptoms. In the absence of distant malignancy, an aggressive approach can obtain late survival free of recurrence.

The aim of the study was to evaluate the possibility of reducing the blood loss during elective surgery for abdominal aortic aneurysms using particular intraoperative surgical expedients. From 1993 to 1999, 200 patients were recruited into the study. We performed 90 aorto-aortic, 84 aorto-bisiliac, 4 aorto-iliac-femoral, 12 aorto-bisiliac-hypogastric, and 10 aorto-bifemoral reconstructions. Several surgical techniques were used and are described in detail. The mortality rate was 3.5%. Haemoglobinaemia 24 hours after the operation had decreased by 2.5 +/- 0.9 g/dl. In 67% of cases the estimated blood loss was lower than 300 ml. There were no transfusions in 44% of cases, and autologous transfusions in 17%. The average estimated blood loss was 350 ml, with mean reinfusion of 0.98 blood units. Our study suggests the possibility (44%) of avoiding the use of blood transfusions thanks to intraoperative blood saving by means of particular surgical techniques.

Primary aortoenteric fistula is a very rare consequence of the evolution of an abdominal aortic aneurysm (AAA). The 3rd and 4th portion of the duodenum are involved in up to 80% of all cases. Frequently, gastrointestinal bleeding represents the first symptom, and diagnosis is difficult because of the aspecific clinical presentation and course, characterized by alternating remission and relapse; this is the reason why surgical treatment is usually delayed and therefore such events are managed as emergencies with a preoperative and intraoperative high death rate. We report the case of a 76-year-old man with a primary aortoduodenal fistula, who was submitted to gastric resection according to Billroth II 20 years before. This case could be interesting for its anatomical peculiarities favourable to the formation of the fistula.

To estimate from 2D and 3D-CT the anatomical defects that are most likely to be responsible for posttraumatic enophthalmos.The morphology and dimensions of the orbit and of fat content were investigated in 25 patients 6-12 months after treatment for complex orbital fractures by image analysis and volumetric estimation from 2D and 3D-CT.The shape of orbit was very often changed from conical to more rounded due to enlargement of the posterior segment. The retrobulbar fat appeared fragmented and dislocated posteriorly. No changes were observed in the structural appearance or radiodensity of either the orbital fat or muscles. There was reduced sagittal eye projection, increased width of the orbital rim, downward dislocation of the posteromedial orbital floor, and increased volume in the posttraumatic orbits which was significantly different (P0.05). Enophthalmos was correlated with orbital volume and height of the retrobulbar portion of the orbit. The volume of fat did not correlate with enophthalmos.Posttraumatic enophthalmos appears to be more commonly related to failure in correcting the orbital volume and in reducing the outward dislocation of the posterior orbital floor and not to changes in the fat content.

This article describes the metabolic investigations to be applied in any clinical situation consistent with a late acute form of inborn error of metabolism: unexplained coma with or without focal neurological manifestations, recurrent vomiting with lethargy, episodes of ataxia with or without behaviour disorder, fits of psychiatric troubles. In each of these situations, careful medical history is of major importance searching for previous clinical manifestations such as episodes of coma, ataxia or vomiting, anorexia, failure to thrive, developmental delay, all very suggestive of metabolic disorder. The association of neurological symptoms and abnormal hepatic tests is also of great value and must not lead to the diagnosis of Reye's syndrome without considering a metabolic defect of fatty acid oxidation, urea cycle, respiratory chain, or Wilson's disease. When looking for an etiological origin, it is mandatory to collect all the biological information at the same time, also knowing that metabolic abnormalities may be mild and transitory, and that many of them are non specific (metabolic acidosis, hyperlactacidemia, hyperammonemia, hepatic tests disturbances) being encountered in collapsus, shock and multiple organ failure syndrome.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.

The aim of this study was to retrospectively compare early and one-year results of open surgery (OS) for critical limb ischemia (CLI) in patients who underwent primary surgery and in patients operated after a previous failure of endovascular treatment (EV).Between January 2004 and December 2007, 460 patients (304 males, 156 females) aged between 46 and 95 (average age 72) underwent OS or EV for CLI. We performed 273 EV (47%) and 307 OS (53%) procedures. In 98 patients (21.3%) the procedures were bilateral. EV procedures were intraluminal, subintimal or both, with selective stenting. OS procedures were distal bypass grafts. OS involved 34 dialysed patients, 159 patients with CLI non-dialysed and not previously submitted to EV treatment (group 1, control group) and 114 patients with failure of previous EV treatment (group 2), frequently performed in different and non surgical centers, 8% of EV failure in our series in this time. We retrospectively compared the early and one-year results in the last two groups of patients in terms of level of revascularization, primary patency, amputation and mortality.By-pass grafts were autologous vein in 94% and PTFE in 6%. Revascularizations have been directed to the tibial or to the plantar arteries at the ankle or foot. Those directed to the plantars were respectively 54% (52% dorsalis pedis, 36% retromalleolar posterior tibial, 12% medial plantar artery) in the control group and 76% (66% dorsalis pedis, 18% retromalleolar posterior tibial, 16% medial plantar artery) in patients with previous failed PTA (P0.001). Early primary patency, mortality and amputation free survival were respectively in the control group and in patients with previous failure of PTA: 93.7% vs. 76.3% (P0.001), 2.5% vs. 3.5% (P0.5), 95% vs. 93% (P0.5). One-year primary patency, mortality and amputation free survival were respectively in the control group and patients with previous failure of PTA: 86.03% vs. 70.87% (P0.25), 14.93% vs. 17.56% (P0.5), 78.1% vs. 68.5% (P0.1).After failure of EV therapy, the subsequent open surgery was more distal and technically demanding. Its results were significantly worse when compared with standard CLI patients, with an increase rate of redo. Our data suggest that EV should not be attempted as the first choice in every patient affected by CLI, and we believe that OS still is the primary treatment for the most advanced clinical situations.

The traumatic rupture of thoracic aorta is a surgical emergency with high risk of morbidity and mortality.We describe the case of an atypical rupture of retro-cardiac thoracic aorta with dissection of brachiocephalic trunk and spleen trauma occurred after a road accident. TC scan and perioperative angiography showed an atypical rupture of thoracic aorta.A combined treatment, endovascular for retro-cardiac thoracic aorta and surgical for brachiocephalic artery, has been useful to diminish the hemodynamic and organ ischemic problems associated with open surgery.

Concomitant abdominal aortic and common iliac artery aneurysms occur in 40% of cases. However, giant common iliac artery aneurysms were rarely described in the current literature. The aim of the present study is to describe the successful treatment of a giant right common iliac artery aneurysm associated with infrarenal abdominal aortic aneurysm.We present a case of aorto-iliac aneurysm, with giant right common iliac artery aneurysm, responsible of bladder and right psoas muscle compression. Through a midline laparotomy, an aortobisiliac prosthetic repair was performed, associated with prosthetic revascularization of the right internal iliac artery and inferior mesenteric artery.Postoperative recovery was uncomplicated and the patient was discharged on postoperative day 7 in good health and has remained so up to the most recent 12-month follow-up.Giant common IA aneurysms represent a very rare pathology, more often associated with infrarenal abdominal aortic aneurysm. After clinical examination, ultrasonography represents the first imaging modality to make diagnosis but CT scan is the gold standard for definitive conclusions, offering accurate anatomical details that are essential to choose the better strategy of treatment. Open surgery represents the gold standard, while endovascular repair has emerged more recently. However results about interventional treatment are not yet described in literature.La presenza contemporanea di un aneurisma dell’aorta addominale sottorenale e delle arterie iliache comuni ricorre nel 40% dei casi. Gli aneurismi giganti delle arterie iliache rappresentano una patologia rara. Lo scopo del presente studio è quello di descrivere un caso di aneurisma gigante dell’arteria iliaca comune di destra associato ad un aneurisma dell’aorta addominale sottorenale, trattato chirurgicamente con successo.Nel presente studio descriviamo un caso di aneurisma aorto-iliaco, con un aneurisma gigante dell’arteria iliaca comune di destra, responsabile di compressione della vescica e del muscolo psoas, che rappresenta il più grande aneurisma iliaco descritto fino ad ora in letteratura. Attraverso una laparotomia mediana, è stato eseguito un bypass protesico aorto-bisiliaco, associato alla rivascolarizzazione protesica dell’arteria iliaca interna destra e dell’arteria mesenterica inferiore. Non ci sono state complicanze nel periodo postoperatorio.Non ci sono state complicanze postoperatorie ed il paziente è stato dimesso in settima giornata in buone condizioni cliniche. A 1 anno dall’intervento il paziente ha eseguito Angio-TC di controllo che dimostra regolare pervietà del bypass, in assenza di complicanze.Gli aneurismi iliaci giganti rappresentano una patologia molto rara. Dopo l’esame clinico, l’ecocolor- doppler rappresenta la prima tecnica diagnostica ma solamente l’Angio-TC può dare tutti i dettagli anatomici necessari per scegliere il trattamento più adeguato. La chirurgia open rappresenta il gold standard per il trattamento, tuttavia recentemente è stato descritto un caso di trattamento endovascolare, ma non sono ancora noti i risultati a lungo termine di quest’ultimo tipo di trattamento.

Tetrahydrobiopterin deficiency, a variant of hyperphenylalaninemia, may be caused by deficiency of one of the following enzymes: guanosine triphosphate cyclohydrolase 1,6-pyruvoyltetrahydropterin synthase, dihydropteridin reductase and pterin-4a-carbinolamine dehydratase. The first two enzymes are involved in the biosynthesis of tetrahydrobiopterin, the last two in its regeneration. Although these diseases are rare, early detection by selective screening is essential for the treatment and outcome. Tetrahydrobiopterin deficiencies are very heterogenous ranging from mild forms requiring only marginal if any treatment to severe forms which are in some cases very difficult to treat. All variants of tetrahydrobiopterin deficiency can be differentiated from the classical phenylketonuria (PKU) by measurement of pterin metabolites in patients' urine, tetrahydrobiopterin loading test, and by dihydropteridine reductase activity in erythrocytes from the Guthrie card.

Objectives A prospective cohort study was conducted in Italy in order to describe the microbiologic aspects of colonization/infection by carbapenemase-producing Enterobacteriaceae (CPE) in donors and recipients of lung and liver transplants and the possible CPE transmission from donors to recipients. Methods Between 15 January 2014 and 14 January 2015, all recipients of solid organ transplants (SOT) at ten lung and eight liver transplantation centres and the corresponding donors were enrolled. Screening cultures to detect CPE were performed in donors, and screening and clinical cultures in recipients with a 28-day microbiologic follow-up after receipt of SOT. Detection of carbapenemase genes by PCR, genotyping by multilocus sequence typing, and pulsed-field gel electrophoresis and whole-genome sequencing were performed. Results Of 588 screened donors, 3.4% were colonized with CPE. Of the liver first transplant recipients (n = 521), 2.5% were colonized before receipt of SOT and 5% acquired CPE during follow-up. CPE colonization was higher in lung first transplant recipients (n = 111, 2.7% before SOT and 14.4% after SOT). CPE infections occurred in 1.9% and 5.3% of liver or lung recipients, respectively. CPE isolates were mostly Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae belonging to CG258. Three events of donor–recipient CPE transmission, confirmed by whole-genome sequencing and/or pulsed-field gel electrophoresis, occurred in lung recipients: two involving K. pneumoniae sequence type 512 and one Verona integron-encoded metallo-β-lactamase (VIM)-producing Enterobacter aerogenes. Conclusions This study showed a low risk of donor–recipient CPE transmission, indicating that donor CPE colonization does not necessarily represent a contraindication for donation unless colonization regards the organ to be transplanted. Donor and recipient screening remains essential to prevent CPE transmission and cross-infection in transplantation centres.

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially “splittable” donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P=.009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P=.045]). The pediatric (4.5% vs 2.5% [P=.398]) and adult (9.7% to 5.2% [P20kg (HR=5.113, P=.048) in LLS, and ischemic time >8hours (HR=2.475, P=.048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme &alpha, galactosidase A (&alpha, Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the &alpha, Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. &alpha, Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, &alpha, Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.

BACKGROUND: Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. METHODS: A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). RESULTS: Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. CONCLUSIONS: These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained confirmed the better outcome of the CRIM-positive patients but at the same time, showed the inability of the current therapeutic approach to reverse or stabilize the disease progression. The results also evidenced the involvement of central nervous system in Pompe disease. To better understand the disease clinical history and to improve treatment efficacy larger multicentre studies are needed as well as the development of new therapeutic approaches.

Split-liver transplantation has been proposed as an alternative to whole liver (WL) transplantation to expand the donor pool, but studies comparing adult longterm outcomes between the 2 methods are conflicting and limited. This is the first Italian multicenter study that retrospectively analyzed 119 matched-pair recipients of whole and extended right grafts (ERGs) for longterm survival outcomes. In the overall population, WL recipients showed higher patient survival at 1 (93% versus 73%), 5 (87% versus 65%), and 10 years (83% versus 60%) after transplantation compared with split-liver recipients (P < 0.001); graft survivals of WL recipients were also superior at 1 (90% versus 76%), 5 (84% versus 57%), and 10 years (81% versus 52%) posttransplant (P < 0.001). However, among the 81 matched pairs that survived the first posttransplant year, 5- and 10-year patient survivals were 90% and 81% for split recipients and 99% and 96% for whole recipients, respectively (P = 0.34). The 5- and 10-year graft survivals were also comparable: 87% and 77% for split recipients, and 86% and 82% for whole recipients (P = 0.86). Cox regression analysis identified donor age >50, donor-to-recipient weight ratio < 1, retransplantation status, and United Network for Organ Sharing I-IIA status as risk factors for partial graft use. There were no significant differences in 5-year outcomes based on center volume. In conclusion, we demonstrate that adult liver transplantation with ERGs can achieve longterm success comparable with that of whole grafts in appropriate patients but should be selectively used in patients with risk factors. Liver Transplantation 23 1384–1395 2017 AASLD.

Objectives To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD). Methods 119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n = 88, 60%) and validation cohorts (n = 57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort. Results Sokolow-Lyon index (AUC = 0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC = 0.778), QRS duration (AUC = 0.703), QT (AUC = 0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram = 0.90 in the test group; 0.81 in the validation group). Conclusion We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.

Despite the worldwide acceptance of split liver transplantation (SLT) as a strategy to expand a limited donor pool, problems still exist in its widespread application.1 The technique of “conventional” SLT divides the liver of a heart-beating donor into an extended right graft (ERG) and a left lateral segment graft (LLS), including Couinaud segments I, IV–VIII, and segments II–III, respectively.2,3 Recent single-center series of either in situ or ex situ SLT reported results comparable to whole liver transplantation (WLT).3–16 The ideal split liver donor should be between 14 and 50 years of age, with good liver function, serum sodium level

BACKGROUND: Outcomes of split-liver transplantation (SLT) with pediatric donors have never been specifically reported. METHODS: A prospective multicenter study on SLT using donors younger than 15 years was conducted. Thirty-nine split-liver procedures generating a left lateral segment (LLS) and an extended right graft (ERG) were performed. In three cases, no recipient was found for ERG. In all but one case, the celiac trunk was maintained with LLS. Data were available for 67 grafts (90% of the total): 38 LLSs and 9 ERGs transplanted into 46 children and 20 ERGs transplanted into 20 adults. Sixty-two (93%) grafts were used for primary transplants and five (7%) for retransplantation. SLT were performed with 15 donors 10 years of age and less and with 24 between 11 and 15 years. RESULTS: Median follow-up was 24 months. Two-year patient and graft survival were 87% and 82%. Patient and graft survivals were not significantly different between pediatric and adult recipients, between recipients from donors 10 years of age and less and those between 11 and 15 years, and between recipients of LLS and ERG. Arterial complications occurred in 6% of cases (8% in the < or = 10 year donors group, 5% in the 11-15 year donors group). The incidence of other complications was similar between groups. CONCLUSIONS: SLT with pediatric donors, even younger than 10 years, provided results comparable with those achievable using adult donors. The similar incidence of arterial complications among patients receiving LLS or ERG suggests that maintenance of the celiac trunk with LLS is not detrimental for right-sided grafts

INTRODUCTION: We report our experience of in situ split-liver transplantation (SLT) for adult patients and compare the results with those achieved with whole-liver transplantation (WLT). METHOD: From November 1997 to December 2003, 109 liver transplantation were performed in 104 adult patients including 90 WLT (83%) and 19 SLT (17%) grafts. Fifteen extended right grafts (ERG, segments I + IV to VIII) were obtained with in situ split-liver procedures, generating also left lateral segment grafts, which were transplanted at our institution or elsewhere. Four left lobe (LL, segments I to IV) and right lobe (segments V to VIII) grafts were obtained by a modified in situ procedure for adult recipients. UNOS status, percentage of primary or secondary transplantation, and underlying liver disease were similar among patients receiving whole versus split grafts. Donors were older in whole than ERG cohorts (53 vs 26 years, P < .001). Procurement parameters and intraoperative profiles of transplant procedure were comparable among the groups. RESULTS: Median follow-up was 18 months (range: 1 to 73). Four patients with whole (4%) and no patient with ERG underwent retransplantation (P = NS). One- and 3-year patient survivals were 86% and 79% with WLT versus 93% and 93% with ERG (P = NS). One- and 3-year graft survivals were 84% and 75% with WLT versus 93%, and 93% with ERG (P = NS). Incidence of vascular complications was 8% with WLT, 13% with ERG (P = NS). The incidence of biliary complications was 13% in WLT, 27% in ERG (P = NS). CONCLUSIONS: The use of ERG from in situ split livers for adult transplantation allowed us to obtain results comparable or even better than those obtained with WLT. Split-liver transplantation is an effective, safe mechanism to expand the cadaveric donor pool.

Contains fulltext : 220431.pdf (Publisher’s version ) (Closed access) BACKGROUND: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. METHODS: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1.5 years and between patients who were or were not underweight by age 1-3 years (defined as a bodyweight-for-age Z score

Introduction: Best care of esophagogastric junction and gastric cancer (EGC) requires a complex, timely interaction between members of a multi-disciplinary team (MDT). An integrated clinical pathway (ICP) is necessary to achieve this goal as well as the implementation of its use in daily practice. The objective of this study was to elaborate on an integrated clinical pathway for the multi-disciplinary management of ECG. Authors also put in act an implementation program to improve adherence to guidelines thought an ICP. Method: This prospective work carried out by a multi-institutional MDT in Italy identified expert panel extracted relevant recommendations and/or statements from published papers and guidelines obtaining a set of crucial interventions employed the Estimate-Talk-Estimate method. A flow-chart diagram was elaborated to elicit the process at a glance. The primary outcome measure was the elaboration of an ICP with a high consensus rate also reported as a snapshot diagram and its implementation in daily clinical practice. An accredited certification body agency validated results, and an implementation process was started in several hospitals known to treat ECG. Results: A methodologist aggregated a multi-disciplinary panel of experts from different institutions. The panel elaborated a flow-chart diagram with crucial intervention highlight and connecting lines, as well as outcome measures. An accredited certification body agency validated the entire process, representing the basis for empowerment and implementation among patients and oncological professionals in various hospitals. Conclusion: The multi-disciplinary and multi-institutional expert panel successfully elaborated on a validated ICP for all stages ECG. An in-hospital implementation program has been programmed.

Background: Using the Self-Regulatory Executive Function model as a basis, this study explored whether, in both general population and clinical samples, metacognitive beliefs and repetitive negative thinking (i.e., rumination and worry) are associated with higher levels of emotion dysregulation. Methods: 395 participants from the general population and 388 outpatients seeking psychological treatment were recruited. Emotion dysregulation, metacognitive beliefs, rumination, worry, anxiety, depression, personality disorders were assessed. ANOVA and Welch's tests, correlation and path analyses were run. Results: Repetitive negative thinking was found to play a mediating role in the relationship between metacognitive beliefs and emotion dysregulation in both general population and clinical samples. Moreover, metacognitive beliefs were found to be directly associated to emotion dysregulation. Limitations: The cross-sectional design. Conclusions: Emotion dysregulation appears to be associated with the tendency to engage in repetitive negative thinking and metacognitive beliefs. Repetitive negative thinking and metacognitive beliefs could be a suitable therapeutic target to reduce difficulties in emotion regulation.

Background: Over the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities. Aim: To investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy. Methods: We recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004–2011),2(2012–2014) and 3(2015–2020). Results: Waitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%. Conclusions: A sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis.

Objective: The aim of this study was (1) to investigate the application of texture analysis of choline PET/CT images in prostate cancer (PCa) patients and (2) to propose a machine-learning radiomics model able to select PET features predictive of disease progression in PCa patients with a same high-risk class at restaging. Material and methods: Ninety-four high-risk PCa patients who underwent restaging Cho-PET/CT were analyzed. Follow-up data were recorded for a minimum of 13 months after the PET/CT scan. PET images were imported in LIFEx toolbox to extract 51 features from each lesion. A statistical system based on correlation matrix and point-biserial-correlation coefficient has been implemented for features reduction and selection, while Discriminant analysis (DA) was used as a method for features classification in a whole sample and sub-groups for primary tumor or local relapse (T), nodal disease (N), and metastatic disease (M). Results: In the whole group, 2 feature (HISTO_Entropy_log10; HISTO_Energy_Uniformity) results were able to discriminate the occurrence of disease progression at follow-up, obtaining the best performance in DA classification (sensitivity 47.1%, specificity 76.5%, positive predictive value (PPV) 46.7%, and accuracy 67.6%). In the sub-group analysis, the best performance in DA classification for T was obtained by selecting 3 features (SUVmin; SHAPE_Sphericity; GLCM_Correlation) with a sensitivity of 91.6%, specificity 84.1%, PPV 79.1%, and accuracy 87%; for N by selecting 2 features (HISTO = _Energy Uniformity; GLZLM_SZLGE) with a sensitivity of 68.1%, specificity 91.4%, PPV 83%, and accuracy 82.6%; and for M by selecting 2 features (HISTO_Entropy_log10 - HISTO_Entropy_log2) with a sensitivity 64.4%, specificity 74.6%, PPV 40.6%, and accuracy 72.5%. Conclusion: This machine learning model demonstrated to be feasible and useful to select Cho-PET features for T, N, and M with valuable association with high-risk PCa patients’ outcomes. Key Points: • Artificial intelligence applications are feasible and useful to select Cho-PET features. • Our model demonstrated the presence of specific features for T, N, and M with valuable association with high-risk PCa patients’ outcomes. • Further prospective studies are necessary to confirm our results and to develop the application of artificial intelligence in PET imaging of PCa.

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p

Aims Fabry cardiomyopathy is characterized by glycosphingolipid storage and increased myocardial trabeculation has also been demonstrated. This study aimed to explore by cardiac magnetic resonance whether myocardial trabecular complexity, quantified by endocardial border fractal analysis, tracks phenotype evolution in Fabry cardiomyopathy. Methods and results Study population included 20 healthy controls (12 males, age 32±9) and 45 Fabry patients divided into three groups: 15 left ventricular hypertrophy (LVH)-negative patients with normal T1 (5 males, age 28±13; Group 1); 15 LVH-negative patients with low T1 (9 males, age 33±9.6; Group 2); 15 LVH-positive patients (11 males, age 53.5±9.6; Group 3). Trabecular fractal dimensions (Dfs) (total, basal, mid-ventricular, and apical) were evaluated on cine images. Total Df was higher in all Fabry groups compared to controls, gradually increasing from controls to Group 3 (1.27±0.02 controls vs. 1.29±0.02 Group 1 vs. 1.30±0.02 Group 2 vs. 1.34±0.02 Group 3; P Conclusion Fabry cardiomyopathy is characterized by a progressive increase in Df of endocardial trabeculae together with shortening of T1 values. Myocardial trabeculation is increased before the presence of detectable sphingolipid storage, thus representing an early sign of cardiac involvement.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.MethodsThis survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2–positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher’s exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options.ResultsThis is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2–positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients’ planned treatment approach). The results from responders in Campania did not differ significantly from the national ones.ConclusionOur study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.

Background How to address the counseling of lifetime risk of developing Parkinson’s disease in patients with Gaucher disease and their family members carrying a single variant of the GBA1 gene is not yet clearly defined. In addition, there is no set way of managing Gaucher disease patients, taking into account the possibility that they may show features of Parkinson’s disease. Methods Starting from an overview on what has recently changed in our knowledge on this issue and grouping the experiences of healthcare providers of Gaucher disease patients, we outline a path of counseling and management of Parkinson’s disease risk in Gaucher disease patients and their relatives. Conclusion The approach proposed here will help healthcare providers to communicate Parkinson’s disease risk to their patients and will reduce the possibility of patients receiving inaccurate information from inadequate sources. Furthermore, this resource will help to empower healthcare providers to identify early signs and/or symptoms of Parkinson’s disease and decide when to refer these patients to the neurologist for appropriate specific therapy and follow-up.

Purpose: To evaluate the fracture risk and survival outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) who received sequentially abiraterone acetate (AA) and radium 223 [223Ra]RaCl2 in the daily clinical practice. Materials: We retrospectively reviewed the records of mCRPC patients who received [223Ra]RaCl2 immediately after progressing during an AA treatment line in everyday clinical practice. Results: We reviewed data of a consecutive series of 94 mCRPC patients. Most of the patients (85.1%) received [223Ra]RaCl2 as second- or third-line treatment. [223Ra]RaCl2 treatment was well-tolerated; there were only four cases of grade 3 anaemia, two cases of grade 3 leukopenia and one case of grade 3 neutropenia. The overall fracture rate is 2.1%; one fracture was recorded during the course of [223Ra]RaCl2 treatment, and one was recorded 1 month after its end. The fractures both occurred at metastatic sites. Median OS from [223Ra]RaCl2 start was more than 14 months regardless of the treatment line when [223Ra]RaCl2 was administered. Conclusion: The findings of this study show that the treatment with [223Ra]RaCl2 immediately after AA was active and safe with a very low risk of a fracture. Thus, the present observational report makes a valuable contribution to the current debate concerning the risks and benefits of including [223Ra]RaCl2 in the therapeutic algorithm.

Anderson-Fabry disease (AFD) cardiomyopathy is characterized by glycosphingolipid (Gb3) storage in all cellular components, with consequent left ventricular hypertrophy (LVH). Gb3 accumulation also involves atrial myocytes ([1][1]), ultimately leading to left atrial (LA) enlargement and reduced

Fenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention.

Background: In prehypertrophic Fabry disease, low myocardial T1 values, reflecting sphingolipid storage, are associated with early structural and ECG changes. The correlations between T1 values and functional parameters have not been explored. Furthermore, the potential prognostic role of T1 in predicting disease worsening is still unknown. Methods: ECG, 2D echocardiography, cardiopulmonary test, and cardiac magnetic resonance were performed in 44 Fabry patients without left ventricular hypertrophy (35.7±14.5 years, 68.2% females). After a 12-month follow-up, clinical stability was evaluated using Fabry Stabilization Index. Results: At baseline, T1 values showed a negative correlation with left ventricular mass ( r =−0.79; P r =−0.79; P r =−0.54; P r =−0.49; P r =−0.61; P 20%) at follow-up. Higher left ventricular wall thickness (odds ratio, 2.61; CI, 1.04–6.57; P =0.04), left atrial volume (odds ratio, 1.24; CI, 1.02–1.51; P =0.03), and lower T1 values (odds ratio, 0.98; CI, 0.96–0.99; P =0.03) at baseline were independently associated with clinical worsening at follow-up. Conclusions: In prehypertrophic Fabry disease, low T1 values correlate with early electrocardiographic, morphological cardiac changes, and worsening of global disease severity but are not associated with functional abnormalities. The presence of low T1 values is a risk factor for disease worsening, thus representing a potential new tool in prognostic stratification and therapeutic approach.

Spatial neglect is a debilitating disorder frequently observed after damage to the right cerebral hemisphere. Previous investigations have revealed that prism adaptation (PA) therapy can lead to improvements in neglect-related symptoms. In the typical PA protocol patients repeatedly point toward a visual target while wearing prism goggles. A few years ago, a novel PA procedure, involving a variety of more "ecological" visuo-motor activities during adaptation, less repetitive than a sequence of pointings, was introduced by our research group, and shown to be able to improve neglect-related symptoms to the same extent as the standard pointing task. The ecological procedure was easy to administer and pleasant for the patients. In all previous studies, patients were treated by specialized personnel during hospitalization. In the current study, we investigated the effectiveness of the ecological PA method when performed in a home-based setting, with the help of caregivers and family members. Seven right-brain-damaged patients with chronic left spatial neglect underwent a two-week ecological PA treatment, extended, for two extra weeks, in 6 patients, who were available for this additional rehabilitation session. As a control treatment, patients performed the same activities while wearing neutral goggles, before the PA procedure. Two weeks of ecological PA training proved to be able to significantly improve performance in neuropsychological tests (BIT, Cancellation tasks), a neurological scale (NIH), and functional abilities (CBS), when compared to both the baseline and the neutral control treatment, with improvements being maintained over 6 months. The ecological home-based PA training is effective in alleviating signs of spatial neglect. Importantly, this training is affordable, pleasant, and feasible to be performed in the comfort of the patient's home. Easily extendable to larger patient populations and prolonged periods, this method has a real potential to benefit the quality of life of brain-damaged patients with left spatial neglect.

BACKGROUND: Ramucirumab-alone or combined with paclitaxel-represents one of the main options for patients failing first-line treatment for advanced gastric cancer. OBJECTIVE: The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the "real-life setting". PATIENTS AND METHODS: Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m2 i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: One hundred sixty-seven patients with disease progression on first-line therapy received ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median treatment duration was 4 months (1-17 months). Global incidence of grade (G) 3-4 toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to toxicity in 3% of patients. The most frequent adverse events (AE) were G1-2 fatigue (27.5%), G1-2 neuropathy (26.3%), and G1-2 neutropenia (14.9%). ORR was 20.2%. Stable disease was observed in 39.2% of patients, with a disease control rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months (95% confidence interval [CI] 4.1-4.7), whereas median OS was 8.0 months (95% CI: 7.09-8.9). In a multivariate analysis, ECOG performance status