New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study.

PURPOSE: Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. METHODS: A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. RESULTS: The study cohort was followed up for a median of 27 years (IQR 12-42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. CONCLUSIONS: This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.

Endocrine dysfunction in hereditary hemochromatosis.

Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.

Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolisation (TACE) is the treatment of choice for intermediate stage hepatocellular carcinoma (HCC). Doxorubicin-loaded drug-eluting beads (DEB)-TACE is expected to improve the performance of conventional TACE (cTACE). The aim of this study was to compare DEB-TACE with cTACE in terms of time-to-tumour progression (TTP), adverse events (AEs), and 2-year survival. METHODS: Patients were randomised one-to-one to undergo cTACE or DEB-TACE and followed-up for at least 2 years or until death. Transcatheter arterial chemoembolisation was repeated 'on-demand'. RESULTS: We enrolled 177 patients: 89 underwent DEB-TACE and 88 cTACE. The median number of procedures was 2 in each arm, and the in-hospital stay was 3 and 4 days, respectively (P=0.323). No differences were found in local and overall tumour response. The median TTP was 9 months in both arms. The AE incidence and severity did not differ between the arms, except for post-procedural pain, more frequent and severe after cTACE (P<0.001). The 1- and 2-year survival rates were 86.2% and 56.8% after DEB-TACE and 83.5% and 55.4% after cTACE (P=0.949). Eastern Cooperative Oncology Group (ECOG), serum albumin, and tumour number independently predicted survival (P<0.05). CONCLUSIONS: The DEB-TACE and the cTACE are equally effective and safe, with the only advantage of DEB-TACE being less post-procedural abdominal pain.

Graft vessel wall pathology in a case of hepatic artery pseudo-aneurysm in a liver transplant recipient.

Pseudo-aneurysms (PAs) of the hepatic artery are rare complications of liver transplantation, which are characterized by a high mortality rate. The majority occur within the first 2 months after orthotopic liver transplantation. They become clinically manifest with sudden hypotension, gastrointestinal bleeding, and abnormal liver function test results. Early diagnosis and treatment are essential to prevent life-threatening hemorrhage. Conventional treatment consists of surgical resection and vascular reconstruction, but a feasible treatment option involves an angiographic approach with the positioning of a stent or transarterial coil embolization followed by revascularization. We report a case of posttransplantation hepatic artery PA (HA-PA) with bleeding into the duodenum, diagnosed using abdominal computed tomography (CT). Arterial kinking prevented a covered stent graft from being inserted successfully using X-ray angiography, so the patient underwent emergency surgery in an attempt to exclude the PA and revascularize the organ via an aorto-hepatic bypass with an iliac vascular graft obtained from the donor. The surgical procedure failed due to progressive macroscopic dissection of the HA wall up to the bifurcation. The patient underwent retransplantation but died 25 days later due to multiple-organ failure. Histopathology of the first liver graft confirmed arterial graft dissection and pathological changes in the donor HA wall.

[The role of medical examiner and Conciliation Courts in the disputes between surgeon and patient]. / Il ruolo del medico legale e delle Commissioni Conciliative nella soluzione delle controversie tra medico e paziente.

The Author examines the present conditions of the professional medical liability and considers his own disadvantages. He proposes the possible solutions on the basis of the recent initiatives grow up in Italy.

Intraperitoneal Tenckhoff catheter for the treatment of recurrent lymphoceles after kidney transplantation: our early experience.

Lymphoceles may occur as frequently as 16% of the time after kidney transplantation, becoming clinically evident between 18 and 180 days after surgery. The management of lymphoceles is unclear. Percutaneous needle aspiration and external drainage are associated with high recurrence and complications. Surgical intraperitoneal marsupialization of lymphocele is considered the treatment of choice, but requires hospital admission, general anesthesia, and sometimes extensive surgical dissection. We discuss our experience in the treatment of recurrent symptomatic lymphocele intraperitoneally drained using a Tenckhoff catheter in 7 consecutive patients. Clinical manifestations became evident between 26 and 90 days after transplantation. The diagnosis was obtained with abdominal ultrasound in all cases; mean lymphocele diameter was 14 +/- 6 cm. After percutaneous drainage, performed to differentiate urinoma/lymphocele and to rule out infections, the lymphocele recurred within 1 month. Thereafter, we decided to treat recurrent lymphatic collection using a Tenckhoff catheter. The lymphocele was located during the operative procedure using a sterile 3.5-MHz ultrasound probe. With the patient under local anesthesia, we performed 2 vertical 1-cm incisions to the lymphocele and peritoneum, respectively. The Tenckoff catheter was first positioned into the lymphocele and the tunneled inside the peritoneal cavity. One cuff of the Tenckhoff was fixed to the fascia to avoid possible delocalization. The patients were discharged the same day. The catheter was removed 6 months later with no evidence of lymphocele recurrence.

A multicentric phase II clinical trial on intra-arterial hepatic radiotherapy with 90yttrium SIR-spheres in unresectable, colorectal liver metastases refractory to i.v. chemotherapy: preliminary results on toxicity and response rates.

BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.

Percutaneous mechanical fragmentation and stent placement for the treatment of early posttransplantation portal vein thrombosis.

BACKGROUND: Early portal vein thrombosis is a rare but severe complication of liver transplantation requiring retransplantation or at least surgical thrombectomy, both hampered by high morbidity and mortality. METHODS: We describe of a case of successful long-term recanalization of early posttransplantation portal vein thrombosis by a minimally invasive percutaneous transhepatic angiographic approach using both mechanical fragmentation and pharmacological lysis of the thrombus followed by stent placement. RESULTS: Mechanical fragmentation and contemporaneous local urokinase administration resulted in complete removal of the clot; the use of a vascular stent after balloon dilatation allowed restoration of normal blood flow to the liver after 9 months of follow-up. CONCLUSIONS: This case report confirms the possibility of successful recanalization of the portal vein after early posttransplantation thrombosis by a minimally invasive angiographic approach. Balloon dilatation and placement of a vascular stent could help to decrease the risk of recurrent thrombosis.

A comparison of scintigraphy, thermography, ultrasound and phlebography in grading of clinical varicocele.

Varicocele, a varicosity of the pampiniform plexus, usually on the left side, is a common urologic problem. It may be associated with symptoms of local discomfort or abnormal spermatogenesis. Internal spermatic vein phlebography is the "gold standard" investigative technique, but it is invasive. Noninvasive studies include: labeled blood-pool scintigraphy, thermography and ultrasound. Two hundred sixty-three patients were investigated with various combinations of these modalities. The degree of abnormality for each modality was graded semiquantitatively and the results compared. In addition, the results of semen analysis were correlated to imaging results. Ninety-six patients were investigated with all four tests (scintigraphy, thermography, ultrasound and phlebography). The correlation of positive phlebography to positive scintigraphy was 98%, to thermography 100% and to ultrasound 98%. The concordance (grade for grade) was 71% for scintigraphy, 68% for thermography and 62% for ultrasound. There was no obvious correlation between abnormalities of semen analysis and grading of varicocele. We conclude that the diagnostic accuracy and grading of severity by noninvasive techniques (including scintigraphy) compare very favorably with that of phlebography. Moreover, scintigraphy allows the noninvasive evaluation of reflux through the internal spermatic vein, which may be useful in planning therapy.

Preparation and analysis of fetal liver extracts.

The aim of this work is to describe the techniques that have been used for preparation and analysis of whole fetal liver extracts destined for in utero transplantation. Nine fetal livers between 12 and 17 weeks of gestation were prepared: cell counts and assessment of the hematopoietic cell viability were performed on cell suspensions. Hepatocytes represented 40 to 80% of the whole cell population. The remaining cells were constituted by hematopoietic cells (mainly erythroblasts), as well as by endothelial cells. The latter expressed CD34 on their surface, interfering with the assessment of CD34+ hematopoietic cells by flow cytometry. Direct visual morphologic control using alkaline phosphatase anti-alkaline phosphatase techniques was needed to differentiate hematopoietic from extra-hematopoietic CD34+ cells. Between 3.0 and 34.6 x 10(6) CD34+ viable hematopoietic cells were collected per fetal liver. Adequate differentiation of these cells into burst-forming units erythroid (BFU-E), colony-forming units granulocyte-macrophage (CFU-GM), and colony-forming units granulocyte erythroid macrophage megakaryocyte (CFU-GEMM) has been shown for each sample in clonogeneic cultures. In conclusion, fetal liver is a potential source of hematopoietic stem cells. Their numeration, based on the presence of CD34, is hampered by the expression of this antigen on other cells contained in the liver cell extract, in particular endothelial cells.

'Agglutination and flocculation' of stem cells collected by apheresis due to cryofibrinogen.

Collection of peripheral stem cells by apheresis is a well-described process. Here, investigations concerning 'agglutination and flocculation' of stem cells collected from two patients are described. In both cases, cryoproteins were observed and cryofibrinogen was identified using high-resolution two-dimensional electrophoresis. In one case, peripheral stem cells were collected after a second course of mobilization, and the cells were immediately washed at 37 degrees C before being frozen, allowing their use, despite the presence of cryofibrinogen. In the other case, 'agglutination' was reversed by warming the bag, and plasma was removed before freezing.

Iliolumbar ligament insertions. In vivo anatomic study.

STUDY DESIGN: Using magnetic resonance imaging, this study analyzed the anatomic characteristics of the iliolumbar ligament insertion on humans. OBJECTIVES: To resolve certain anatomic questions about the manner of insertion of the iliolumbar ligament. SUMMARY OF BACKGROUND DATA: The data of the postmortem studies of the iliolumbar ligament are controversial because of the number, complexity, and variability of the structures present in the lumbosacral region. METHODS: Twenty-eight iliolumbar ligaments of 14 adult volunteers were analyzed with magnetic resonance imaging. The images were acquired along the transversal planes (from inferior to superior) and coronal planes (from the ventral to the dorsal) of the lumbosacral region. RESULTS: The anterior band of the iliolumbar ligament (broad and flat) originates from the anterior-inferior-lateral part of the L5 transverse process and expands as a wide fan before inserting on the anterior part of the iliac tuberosity below the posterior band. The posterior band of the iliolumbar ligament originates from the apex of the L5 transverse process and is thinner than the anterior with a round section, and it inserts on the iliac crest (from the anterior margin to the apex). CONCLUSIONS: The minor width of the area of insertion on the iliac crest of the posterior band (and therefore its lower resistance with the mechanical overloads) could explain the frequency of the painful syndromes related, by some authors, to an enthesopathy of this ligament.

Successful minimally invasive management of late portal vein thrombosis after splenectomy due to splenic artery steal syndrome following liver transplantation: a case report.

Portal vein thrombosis (PVT) after liver transplantation (OLT), which occurs in 1% to 2.7% of cases, can compromise patient and graft survival. Percutaneous transhepatic portal vein angioplasty offers an option to treat PVT, diminishing surgically related morbidity and the need for retransplantation. We describe a case of late PVT after OLT, which was successfully treated by a minimally invasive percutaneous transhepatic approach using both mechanical fragmentation and pharmacologic lysis of the thrombus followed by anticoagulation. The patient has had a good clinical course with normal graft function and patent portal blood flow at 6-month follow-up. This case report confirms the possibility of successful recanalization of the portal vein in a patient with late PVT after liver transplantation. Sustained anticoagulation/antiaggregation therapy for at least 6 months after the procedure is advisable.

[Difficult digestive hemorrhage: angiodysplasia]. / Emorragie digestive difficili: le angiodisplasie.

The authors report 7 cases of ileal and colonic angiodysplasia observed over a 3 year period (1992-1994). After a review of literature concerning etiology, pathology, diagnosis, and treatment emphasize the use of angiography for preoperatory diagnosis an intraoperatory localization of the lesion when this one is localized in the ileum. After review of usefull therapies, they stress the role of surgery as the most used therapy and only really complete.

Female "varicocele": two cases diagnosed by labeled red blood cell angioscintigraphy and treated by percutaneous phlebography and embolization.

Varicocele, a varicosity of the gonadal venous plexus, is a well-recognized disorder occurring in up to 10% of men. In women, an analogous varicosity of the salpingo-ovarian plexus is rare. This may be explained, in part, by the lack of obvious findings on clinical examination in women compared with men and the need, until recently, to use invasive venographic methods to confirm the diagnosis. Two cases of "female varicocele" diagnosed by means of echo Doppler and Tc-99m red blood cell scintigraphy and their cure by percutaneous phlebographic occlusion of the ovarian venous varicosity are described.

[Isolated jejunal angiomatosis. A rare cause of intestinal hemorrhage]. / Angiomatosi digiunale isolata. Una causa rara di emorragia intestinale.

The Authors report a case of solitary small bowel angiodysplasia and emphasise the rarity of this site. The importance of angiography is stressed in terms of its fundamental role in the diagnostic process and in its ability to evaluate not only the site but the extension of this type of lesion, thus enabling a surgical approach to be defined.

BRAVISSIMO: 12-month results from a large scale prospective trial.

The BRAVISSIMO study is a prospective, non-randomized, multi-center, multi-national, monitored trial, conducted at 12 hospitals in Belgium and 11 hospitals in Italy. This manuscript reports the findings up to the 12-month follow-up time point for both the TASC A&B cohort and the TASC C&D cohort. The primary endpoint of the study is primary patency at 12 months, defined as a target lesion without a hemodynamically significant stenosis on Duplex ultrasound (>50%, systolic velocity ratio no greater than 2.0) and without target lesion revascularization (TLR) within 12 months. Between July 2009 and September 2010, 190 patients with TASC A or TASC B aortoiliac lesions and 135 patients with TASC C or TASC D aortoiliac lesions were included. The demographic data were comparable for the TASC A/B cohort and the TASC C/D cohort. The number of claudicants was significantly higher in the TASC A/B cohort, The TASC C/D cohort contains more CLI patients. The primary patency rate for the total patient population was 93.1%. The primary patency rates at 12 months for the TASC A, B, C and D lesions were 94.0%, 96.5%, 91.3% and 90.2% respectively. No statistical significant difference was shown when comparing these groups. Our findings confirm that endovascular therapy, and more specifically primary stenting, is the preferred treatment for patients with TASC A, B, C and D aortoiliac lesions. We notice similar endovascular results compared to surgery, however without the invasive character of surgery.

Structure-based secondary structure-independent approach to design protein ligands: Application to the design of Kv1.2 potassium channel blockers.

We have developed a structure-based approach to the design of protein ligands. This approach is based on the transfer of a functional binding motif of amino acids, often referred as to the "hot spot", on a host protein able to reproduce the functional topology of these residues. The scaffolds were identified by a systematic in silico search in the Protein Data Bank for proteins possessing a group of residues in a topology similar to that adopted by the functional motif in a reference ligand of known 3D structure. In contrast to previously reported studies, this search is independent of the particular secondary structure supporting the functional motif. To take into account the global properties of the host protein, two additional criteria were taken into account in the selection process: (1) Only those scaffolds sterically compatible with the positioning of the functional motif as observed in a reference complex model were retained. (2) Host proteins displaying electrostatic potentials, in the region of the transferred functional motif, similar to that of the reference ligand were selected. This approach was applied to the development of protein ligands of the Kv1.2 channel using BgK, a small protein isolated from the sea anemone Bunodosoma granulifera, as the reference ligand. Four proteins obtained by this approach were produced for experimental evaluation. The X-ray structure of one of these proteins was determined to check for similarity of the transferred functional motif with the structure it adopts in the reference ligand. Three of these protein ligands bind the Kv1.2 channel with inhibition constants of 0.5, 1.5, and 1.6 microM. Several mutants of these designed protein ligands gave binding results consistent with the presumed binding mode. These results show that protein ligands can be designed by transferring a binding motif on a protein host selected to reproduce the functional topology of this motif, irrespective to the secondary structure supporting the functional motif, if the host protein possesses steric and electrostatic properties compatible with the binding to the target. This result opens the way to the design of protein ligands by taking advantage of the considerable structural repertoire of the Protein Data Bank.