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1.
JACC Case Rep ; 29(7): 102273, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38645293

ABSTRACT

An 84-year-old man presented with dyspnea at rest due to severe mitral regurgitation. He first underwent transventricular mitral valve repair with the Harpoon system, which relapsed owing to rupture of neochords. He was definitively treated with transcatheter mitral valve implantation of the Tendyne system 8 months later.

3.
J Med Chem ; 66(15): 10681-10693, 2023 08 10.
Article in English | MEDLINE | ID: mdl-37490408

ABSTRACT

New chemical modalities in drug discovery include molecules belonging to the bRo5 chemical space. Because of their complex and flexible structure, bRo5 compounds often suffer from a poor solubility/permeability profile. Chameleonicity describes the capacity of a molecule to adapt to the environment through conformational changes; the design of molecular chameleons is a medicinal chemistry strategy simultaneously optimizing solubility and permeability. A default method to quantify chameleonicity in early drug discovery is still missing. Here we introduce Chamelogk, an automated, fast, and cheap chromatographic descriptor of chameleonicity. Moreover, we report measurements for 55 Ro5 and bRo5 compounds and validate our method with literature data. Then, selected case studies (macrocycles, nonmacrocyclic compounds, and PROTACs) are used to illustrate the application of Chamelogk in combination with lipophilicity (BRlogD) and polarity (Δ log kwIAM) descriptors. Overall, we show how Chamelogk deserves being included in property-based drug discovery strategies to design oral bioavailable bRo5 compounds.


Subject(s)
Chemistry, Pharmaceutical , Drug Discovery , Solubility , Permeability , Pharmaceutical Preparations
4.
Molecules ; 28(3)2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36770875

ABSTRACT

Proteolysis-Targeting Chimeras (PROTACs) have recently emerged as a promising technology in the drug discovery landscape. Large interest in the degradation of the androgen receptor (AR) as a new anti-prostatic cancer strategy has resulted in several papers focusing on PROTACs against AR. This study explores the potential of a few in silico tools to extract drug design information from AR degradation data in the format often reported in the literature. After setting up a dataset of 92 PROTACs with consistent AR degradation values, we employed the Bemis-Murcko method for their classification. The resulting clusters were not informative in terms of structure-degradation relationship. Subsequently, we performed Degradation Cliff analysis and identified some key aspects conferring a positive contribution to activity, as well as some methodological limits when applying this approach to PROTACs. Linker structure degradation relationships were also investigated. Then, we built and characterized ternary complexes to validate previous results. Finally, we implemented machine learning classification models and showed that AR degradation for VHL-based but not CRBN-based PROTACs can be predicted from simple permeability-related 2D molecular descriptors.


Subject(s)
Receptors, Androgen , Ubiquitin-Protein Ligases , Ubiquitin-Protein Ligases/metabolism , Proteolysis , Receptors, Androgen/metabolism , Drug Design , Drug Discovery/methods
5.
Cells ; 11(22)2022 11 18.
Article in English | MEDLINE | ID: mdl-36429091

ABSTRACT

Potential intrinsic resistance mechanisms to regorafenib were explored after short exposure (3 days) on five CRC cell lines (HCT-116, SW1116, LS-1034, SW480, Caco-2). The observation of senescence-like features led to the investigation of a drug-initiated phenotype switch. Following long-term exposure (12 months) of HCT-116 and SW480 cell lines to regorafenib, we developed resistant models to explore acquired resistance. SW480 cells demonstrated senescent-like properties, including a cell arrest in the late G2/prophase cell cycle stage and a statistically significant decrease in the expression of G1 Cyclin-Dependent Kinase inhibitors and key cell cycle regulators. A specific senescence-associated secretome was also observed. In contrast, HCT-116 treated cells presented early senescent features and developed acquired resistance triggering EMT and a more aggressive phenotype over time. The gained migration and invasion ability by long-exposed cells was associated with the increased expression level of key cellular and extracellular EMT-related factors. The PI3K/AKT pathway was a significant player in the acquired resistance of HCT-116 cells, possibly related to a PI3KCA mutation in this cell line. Our findings provide new insights into the phenotypic plasticity of CRC cells able, under treatment pressure, to acquire a stable TIS or to use an early senescence state to undergo EMT.


Subject(s)
Colorectal Neoplasms , Epithelial-Mesenchymal Transition , Humans , Epithelial-Mesenchymal Transition/genetics , Phosphatidylinositol 3-Kinases , Caco-2 Cells , Drug Resistance, Neoplasm , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism
6.
Neuropsychologia ; 148: 107641, 2020 11.
Article in English | MEDLINE | ID: mdl-33058921

ABSTRACT

Being aware of one's own ability to interact socially is crucial to everyday life. After a brain injury, patients may lose their capacity to understand others' intentions and beliefs, that is, the Theory of Mind (ToM). To date, the debate on the association between ToM and other cognitive deficits (in particular executive functions and behavioural disorders) remains open and data regarding awareness of ToM deficits are meagre. By means of an ad-hoc neuropsychological battery of tests, we report on a patient who suffers from ToM deficits and is not aware of these disorders, although aware of his other symptoms. The study is accompanied by a review of the literature (PRISMA guidelines) demonstrating that ToM deficits are independent of executive functions. Furthermore, an advanced lesion analysis including tractography was executed. The results indicate that: i) ToM deficits can be specific and independent of other cognitive symptoms; ii) unawareness may be specific for ToM impairment and not involve other disorders and iii) the medial structures of the limbic, monitoring and attentional systems may be involved in anosognosia for ToM impairment.


Subject(s)
Agnosia , Cognition Disorders , Theory of Mind , Agnosia/etiology , Executive Function , Humans , Neuropsychological Tests
7.
Med Oncol ; 37(4): 26, 2020 Mar 12.
Article in English | MEDLINE | ID: mdl-32166542

ABSTRACT

RENAL score has been validated on predicting adverse events and relapses in percutaneous treatments of renal lesions. To better fit interventional issues a modified score (mRENAL) has been introduced, but the only difference from the RENAL score is on the dimensional parameter. However, it remains of surgical derivation while a specific interventional score is missing. This study aims to obtain a specific score (ABLATE) to better quantify the risk of complications and relapses in percutaneous kidney ablation procedures compared to the existing surgical scores. Taking inspiration from previous papers, a score was built to quantify the real difficulties faced in percutaneous treatment of renal lesions. The ABLATE score was used on 71 cryoablations to evaluate its predictivity of complications and relapses. Logistic regression was used to predict complication incidence; Cox-regression was used for relapses; ROC analysis was used to evaluate the accuracy of the different scores. Between January 2014 and November 2019, 71 lesions in 68 patients were treated. Overall, malignant histology was found in 62 lesions (87.3%). Mean and median RENAL, mRENAL, and ABLATE scores were 7.04 and 7, 7.19 and 7, and 5.11 and 4, respectively. Out of 71 treatments, we experienced 3 bleeding with anemia (4.2%), only 2 of which needed further treatment (2.82%). The mean and median RENAL, mRENAL, and ABLATE scores in those with complications were 7.66 and 7.01 (p = 0.69), 8.0 and 7.1 (p = 0.54), and 6.6 and 5.0 (p = 0.38), respectively. Out of 62 malignant lesions, we experienced 2 persistent and 6 recurrent lesions (3.2% and 8.4%, respectively). At Cox-regression analyses, mABLATE score outperformed both RENAL and mRENAL scores in predicting recurrences (HR 1.48; p < 0.001 vs. 1.41; p = 0.1 vs. 1.38: p = 0.07, respectively). The ABLATE score showed to be a better predictor of relapses than RENAL and mRENAL. The small number of complications conditioned a lack of statistic power on complications for all the scores. At the moment to quantify the risks in percutaneous kidney ablation procedures, surgical scores are used. A specific score better performs this task.


Subject(s)
Kidney Diseases/pathology , Kidney Diseases/surgery , Nephrostomy, Percutaneous/methods , Ablation Techniques/adverse effects , Ablation Techniques/methods , Aged , Female , Humans , Male , Nephrostomy, Percutaneous/adverse effects , Postoperative Complications , Predictive Value of Tests , Recurrence , Treatment Outcome
8.
Pharmacol Res ; 135: 127-135, 2018 09.
Article in English | MEDLINE | ID: mdl-30055250

ABSTRACT

Diabetes mellitus is associated with both microvascular and macrovascular complications, which can result in visceral aneurysms as for example splenic artery aneurysms: in their management, an endovascular treatment, less invasive than surgery, is generally preferred. Endovascular treatment of splenic artery aneurysms can be based either on covered stenting (CS) or transcatheter embolization (TE). CS generally allows aneurysm exclusion with vessel preservation, while TE usually determines target artery occlusion with potential risk of distal ischemia. We performed a review of the existing literature on endovascular treatment of visceral artery aneurysms (VAAs) and psudoaneurysms (VAPAs) in the current era.


Subject(s)
Aneurysm/therapy , Diabetes Mellitus/therapy , Embolization, Therapeutic , Splenic Artery , Stents , Aneurysm/diagnostic imaging , Diabetes Mellitus/diagnostic imaging , Humans
9.
Gland Surg ; 7(2): 117-131, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29770308

ABSTRACT

Although the life expectancy of patients with type 1 diabetes mellitus (T1DM) has improved since the introduction of insulin therapy, the acute life-threatening and long-term complications from diabetes mellitus are significant causes of both mortality and morbidity. Percutaneous intra-portal pancreatic islet transplantation (PIPIT) is a minimally invasive, repeatable procedure which allows a ß-cell replacement therapy through a liver islet engraftment, leading to insulin release and glycaemic control restoration in patients with diabetes. Allo-PIPIT, in which isolated and purified islets from cadaveric donor are used, does not require major surgery, and is potentially less expensive for the recipient. In case of long-term T1DM, islet-after-kidney (IAK) transplantation can simultaneously cure diabetes and chronic renal failure, while islet-transplant-alone (ITA) is performed in brittle, short-term T1DM, based on the infusion of an adequate islet mass and on a steroid-free immunosuppressive regimen according to the Edmonton protocol. Results of the Collaborative Islet Transplant Registry (CITR) demonstrate that allo-PIPIT reduces episodes of hypoglycemia and diabetic complications, and improves quality of life of diabetic patients. Auto-PIPIT, in which the own patient's islets are used, has been investigated as a preventive treatment for pancreatogenic diabetes in patients who undergo extensive pancreatectomy for malignant and non-malignant disease. This Review outlines the role of imaging and interventional radiology in allo- and auto-PIPIT.

10.
Cardiovasc Intervent Radiol ; 41(3): 385-397, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29164308

ABSTRACT

PURPOSE: Endovascular repair of true visceral artery aneurysms (VAAs) and pseudoaneurysms (VAPAs) with stent-grafting (SG) can simultaneously allow aneurysm exclusion and vessel preservation, minimizing the risk of ischemic complications. Our aim was to report a single-center experience on SG of visceral aneurysms, focusing on technical aspects, clinical outcome and mid-term patency. MATERIALS AND METHODS: Consecutive patients affected by VAAs-VAPAs and submitted to endovascular treatment were retrospectively reviewed, and SG cases with the self-expandable peripheral Viabahn stent-graft were analyzed (2003-2017). Aneurysm type, patient number, SG clinical setting, procedural data, peri-procedural complications, technical success, 30-day clinical success, 30-day mortality and follow-up period (aneurysm exclusion, stent-graft patency, ischemic complications) were analyzed. RESULTS: SG was performed in 40 patients (24 VAPAs/16 VAAs) and in 44 procedures (25 in emergency, 19 in elective treatments), via transfemoral in 37 cases (transaxillary in 7 cases). One peri-procedural complication was recorded (a splenic artery dissection successfully converted to transcatheter embolization). The overall technical and clinical success rates were, respectively, 96 and 84%, with excellent trend in elective treatments (both 100%). Overall 30-day mortality was 12.5% (septic shock after pancreatic surgery). Stent-graft thrombosis occurred in 2 patients within 3 months, with aneurysm exclusion and without ischemic complications. Stent-graft patency and aneurysm exclusion were confirmed at 6, 12 and 36 months in 18, 12 and 7 patients, respectively. CONCLUSION: SG of VAAs and VAPAs was safe and effective, particularly in elective treatments. The Viabahn stent-graft, flexible and without shape memory, is suitable for endovascular repair of tortuous visceral arteries.


Subject(s)
Aneurysm/surgery , Endovascular Procedures/methods , Gastrointestinal Tract/blood supply , Renal Artery/surgery , Splenic Artery/surgery , Stents , Vascular Patency/physiology , Adult , Aged , Aged, 80 and over , Aneurysm/diagnostic imaging , Aneurysm/physiopathology , Aneurysm, False/diagnostic imaging , Aneurysm, False/physiopathology , Aneurysm, False/surgery , Blood Vessel Prosthesis Implantation/methods , Female , Follow-Up Studies , Gastrointestinal Tract/diagnostic imaging , Gastrointestinal Tract/surgery , Hepatic Artery/diagnostic imaging , Hepatic Artery/physiopathology , Hepatic Artery/surgery , Humans , Male , Middle Aged , Prospective Studies , Radiography, Interventional/methods , Renal Artery/diagnostic imaging , Renal Artery/physiopathology , Retrospective Studies , Splenic Artery/diagnostic imaging , Splenic Artery/physiopathology , Time Factors , Treatment Outcome
11.
J Endovasc Ther ; 24(5): 709-717, 2017 10.
Article in English | MEDLINE | ID: mdl-28659059

ABSTRACT

PURPOSE: To retrospectively report a large single-center experience of visceral artery aneurysms (VAAs) and pseudoaneurysms (VAPAs) treated with covered stenting (CS) as the first therapeutic option vs transcatheter embolization (TE). METHODS: One hundred patients (mean age 59±14 years; 58 men) underwent 59 elective and 41 emergent endovascular procedures to treat 51 VAAs and 49 VAPAs. Seventy patients had TE and 30 received CS (27 Viabahn and 3 coronary stent grafts). Both TE and CS were performed in 10 cases. RESULTS: Technical success was 96% (97% CS, 96% TE), and 30-day clinical success was 83% (87% CS, 81.4% TE). Four major complications occurred; 30-day mortality was 7%, mainly due to septic shock following pancreatic surgery. The midterm follow-up was 20.8 months in the total population and 32.8 months in the CS group. More than 6 months after CS all aneurysms remained excluded; stent patency was achieved in 88%. Twelve CS patients with >3 years' follow-up had maintained stent patency. CONCLUSION: In endovascular treatment of visceral aneurysms, covered stenting was feasible in 30%. CS showed a slightly better efficacy than TE and good midterm patency. The Viabahn covered stent seems to be suitable for endovascular repair of tortuous visceral arteries affected by true or false aneurysms.


Subject(s)
Aneurysm, False/therapy , Aneurysm/therapy , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Embolization, Therapeutic , Endovascular Procedures/instrumentation , Stents , Viscera/blood supply , Adult , Aged , Aneurysm/diagnostic imaging , Aneurysm/mortality , Aneurysm/physiopathology , Aneurysm, False/diagnostic imaging , Aneurysm, False/mortality , Aneurysm, False/physiopathology , Angiography, Digital Subtraction , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Computed Tomography Angiography , Databases, Factual , Embolization, Therapeutic/adverse effects , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Humans , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/therapy , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Vascular Patency
12.
Br J Radiol ; 89(1067): 20160247, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27558984

ABSTRACT

OBJECTIVE: The aim of our preliminary study was to compare the efficacy of drug-eluting beads preloaded with irinotecan (DEBIRI) vs drug-eluting beads preloaded with doxorubicin (DEBDOX) as second-line treatment of unresectable liver metastases from cholangiocarcinoma (CCA). METHODS: In 2013, 10 patients affected by multiple liver metastases from CCA, resistant to the first-line chemotherapy regimen, were enrolled: 5 patients were submitted to lobar/segmental transarterial chemoembolization (TACE) with DEBIRI (100-mg irinotecan/1 vial) and 5 patients with DEBDOX (50-mg doxorubicin/1 vial), performed every 3 weeks. Patients treated with DEBIRI received antipain premedication consisting of 30-mg of morphine and 3-4 ml of intra-arterial lidocaine. Complications and efficacy were assessed (response evaluation criteria in solid tumour 1.1). RESULTS: A total of 32 TACE were performed (mean: 3.2 TACE/patient), all well tolerated, with only 1 case of asymptomatic cholecystitis spontaneously recovered. Response rates of patients treated with DEBDOX and DEBIRI were: 4/5 progressive disease and 1/5 partial response vs 2/5 partial response, 2/5 stable disease and 1/5 progressive disease, respectively, with the appearance of variable necrosis percentage. Progression-free survival from the first procedure and progressive disease were 12.67 weeks for DEBIRI and 15.78 weeks for DEBDOX, respectively. Overall survival from time of primary diagnosis was 176 weeks for DEBIRI and 125 weeks for DEBDOX, respectively. CONCLUSION: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment for hepatic metastases from CCA. Antipain drug administration and the use of the microcatheter led to a good treatment tolerability and a low complication rate. Advances in knowledge: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment of hepatic metastases from CCA; further studies involving a larger cohort of patients are needed.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Bile Duct Neoplasms/pathology , Camptothecin/analogs & derivatives , Chemoembolization, Therapeutic/methods , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/secondary , Doxorubicin/administration & dosage , Drug Delivery Systems , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Camptothecin/administration & dosage , Contrast Media , Female , Humans , Irinotecan , Male , Tomography, X-Ray Computed , Treatment Outcome
13.
Br J Radiol ; 89(1064): 20160246, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27327404

ABSTRACT

OBJECTIVE: Islet allotransplantation is a less invasive alternative to surgical pancreas transplantation for Type 1 diabetes, while percutaneous intraportal islet autotransplantation (PIPIAT) is usually performed after pancreatic surgery to prevent diabetes. Our aim was to assess the feasibility, radiological aspects, complications and clinical outcome of PIPIAT following pancreatic surgery for not only chronic pancreatitis but also benign and malignant nodules. METHODS: From 2008 to 2012, 41 patients were enrolled for PIPIAT 12-48 h after pancreatic surgery (extended pancreatic surgery for chronic pancreatitis and benign/malignant neoplasms). PIPIAT was performed using a combined ultrasonography and fluoroscopy-guided technique (4-F catheter). PIPIAT feasibility, median follow-up and metabolic (insulin independence rate, graft function based on C-peptide levels) and oncologic outcomes were recorded. RESULTS: PIPIAT was not performed in 7/41 patients (4 cases for an inadequate islet mass, 2 cases for haemodynamic instability and 1 case for islet culture contamination), while it was successfully performed in 34/34 patients. Procedure-related major complications occurred in four patients: two bleedings requiring transfusions, one patient with left portal vein thrombosis and one patient with sepsis. Median follow-up duration was 546 days. Insulin independence was achieved in 15/34 (44%) patients, partial graft function in 16/34 (47%) patients and no function in 3/34 (9%) patients. None of the 17 patients with malignant nodules developed liver metastases during follow-up. CONCLUSION: PIPIAT, performed under ultrasound and fluoroscopy combined guidance and not requiring immunosuppression, is feasible, with a relatively low complication rate and a better metabolic outcome than allotransplantation. ADVANCES IN KNOWLEDGE: PIPIAT can prevent pancreatogenic diabetes. Ultrasound is a useful tool for the guidance and monitoring of PIPIAT.


Subject(s)
Diabetes Mellitus, Type 1/prevention & control , Islets of Langerhans Transplantation , Pancreas/surgery , Feasibility Studies , Fluoroscopy , Humans , Islets of Langerhans Transplantation/adverse effects , Islets of Langerhans Transplantation/methods , Pancreatic Diseases/surgery , Pancreatic Neoplasms/surgery , Pancreatitis, Chronic/surgery , Transplantation, Autologous , Ultrasonography
14.
Radiol Med ; 121(4): 301-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26639150

ABSTRACT

PURPOSE: To investigate the role of orbital color Doppler ultrasound (OCDUS) in the diagnosis of carotid-cavernous fistula (CCF) with anterior drainage and particularly whether a negative OCDUS could avoid an invasive diagnostic cerebral angiography (DSA). MATERIALS AND METHODS: Twenty-two consecutive patients with ophthalmic signs suspecting CCF were submitted to ophthalmologic examination, OCDUS and DSA. CCF diagnosis with OCDUS was based on the finding of a reversed, arterialized and low-resistive-index (RI <0.5) blood flow in the superior ophthalmic vein (SOV). Sensibility, specificity, PPV, NPV, and accuracy of OCDUS were calculated considering both patients and eyes, using DSA as gold standard. RESULTS: DSA demonstrated 20 CCFs in 18 patients. Considering the patients, in 18/22 CCF diagnosis was positive at OCDUS and DSA while 4/22 were negative at both. Considering the eyes, in 24/43 CCF diagnosis was positive at both DSA and OCDUS (total eyes = 43, due to one case of SOV thrombosis). In 19/43 eyes diagnosis was negative at both OCDUS and DSA. So sensitivity, specificity, PPV, NPV, and accuracy of OCDUS in the patients and eyes analysis were all 100 %. CONCLUSIONS: OCDUS is a reliable, noninvasive tool in the diagnosis of CCF; a negative OCDUS could avoid an invasive DSA in patients suspected for anterior-draining CCF.


Subject(s)
Carotid-Cavernous Sinus Fistula/diagnostic imaging , Ultrasonography, Doppler, Color , Female , Humans , Male , Middle Aged , Retrospective Studies
15.
Environ Sci Technol ; 49(11): 6943-52, 2015 Jun 02.
Article in English | MEDLINE | ID: mdl-25932966

ABSTRACT

Citizens are exposed to microbial hazards in urban waters. To quantify health risks associated with this exposure, pathogen concentrations in an urban river, lake, rainwater sedimentation pond, a pond in a park, and a wadi, were assessed. E. coli concentrations were variable in all locations, with mean values ranging between 1.2 × 10(2) (lake) and 1.7 × 10(4) (sedimentation pond) cfu (colony forming units)/100 mL. High concentrations of Campylobacter were found, being the lowest in the lake (4.2 × 10(1) gc (genomic copies)/L) and the highest in the wadi (1.7 × 10(4) gc/L). Cryptosporidium was not found in any sample. Low levels of adenovirus 40/41 were found in some samples in the river (1.8 × 10(1) gc/L) and lake (7.2 × 10° gc/L), indicating human fecal contamination. Legionella pneumophila was found in the sedimentation pond, with higher concentrations after rain events (1.3 × 10(2) gc/L). Cyanochlorophyll-a was found in the lake (7.0 × 10(-1) µg/L), the sedimentation pond (1.1 × 10° µg/L), and the pond in the park (2.9 × 10(1) µg/L), where low levels of microcystin were found (2.1 × 10° µg/L). Campylobacter data were used to estimate gastrointestinal risks from recreational exposure. This revealed risks above the annual disease incidence of campylobacteriosis in The Netherlands, being highest in the wadi and river. Measures are proposed to reduce the health risks.


Subject(s)
Cities , Public Health , Water Microbiology , Campylobacter/physiology , Campylobacter Infections/microbiology , Environmental Monitoring , Humans , Microcystins/analysis , Netherlands , Rain , Risk Factors , Water
16.
PLoS One ; 10(4): e0122832, 2015.
Article in English | MEDLINE | ID: mdl-25897796

ABSTRACT

INTRODUCTION: Abdominal pain in PNH has never been investigated by in-vivo imaging studies. With MRI, we aimed to assess mesenteric vessels flow and small bowel wall perfusion to investigate the ischemic origin of abdominal pain. MATERIALS AND METHODS: Six PNH patients with (AP) and six without (NOP) abdominal pain underwent MRI. In a blinded fashion, mean flow (MF, quantity of blood moving through a vessel within a second, in mL·s-1) and stroke volume (SV, volume of blood pumped out at each heart contraction, in mL) of Superior Mesenteric Vein (SMV) and Artery (SMA), areas under the curve at 60 (AUC60) and 90 seconds (AUC90) and Ktrans were assessed by two operators. RESULTS: Mean total perfusion and flow parameters were lower in AP than in NOP group. AUC60: 84.81 ± 11.75 vs. 131.73 ± 18.89 (P < 0.001); AUC90: 102.33 ± 14.16 vs. 152.58 ± 22.70 (P < 0.001); Ktrans: 0.0346 min-1 ± 0.0019 vs. 0.0521 ± 0.0015 (P = 0.093 duodenum, 0.009 jejunum/ileum). SMV: MF 4.67 ml/s ± 0.85 vs. 8.32 ± 2.14 (P = 0.002); SV 3.85 ml ± 0.76 vs. 6.55 ± 1.57 (P = 0.02). SMA: MF 6.95 ± 2.61 vs. 11.2 ± 2.32 (P = 0.07); SV 6.52 ± 2.19 vs. 8.78 ± 1.63 (P = 0.07). We found a significant correlation between MF and SV of SMV and AUC60 (MF:ρ = 0.88, P < 0.001; SV: ρ = 0.644, P = 0.024), AUC90 (MF: ρ = 0.874, P < 0.001; SV:ρ = 0.774, P = 0.003) and Ktrans (MF:ρ = 0.734, P = 0.007; SV:ρ = 0.581, P = 0.047). CONCLUSIONS: Perfusion and flow MRI findings suggest that the impairment of small bowel blood supply is significantly associated with abdominal pain in PNH.


Subject(s)
Abdominal Pain/diagnosis , Hemoglobinuria, Paroxysmal/pathology , Abdominal Pain/etiology , Abdominal Pain/physiopathology , Adult , Area Under Curve , Duodenum/blood supply , Female , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/physiopathology , Humans , Ileum/blood supply , Ischemia/diagnosis , Jejunum/blood supply , Magnetic Resonance Imaging , Male , Middle Aged , Prospective Studies , Regional Blood Flow , Splanchnic Circulation , Stroke Volume , Young Adult
17.
Pharmacol Res ; 98: 52-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25814187

ABSTRACT

Percutaneous intra-portal islet transplantation (PIPIT) is a less invasive, safer, and repeatable therapeutic option for brittle type 1 diabetes, compared to surgical pancreas transplantation. Hepatic steatosis is a consequence of the islet engraftment but it is curiously present in a limited number of patients and its meaning is controversial. The aims of this study were to assess hepatic steatosis at ultrasound (US) after PIPIT investigating its relationship with graft function and its role in predicting the clinical outcome. From 1996 to 2012, 108 patients underwent PIPIT: 83 type-1 diabetic patients underwent allo-transplantation, 25 auto-transplantation. US was performed at baseline, 6, 12, and 24 months, recording steatosis prevalence, first detection, duration, and distribution. Contemporaneously, steatotic and non-steatotic patients were compared for the following parameters: infused islet mass, insulin independence rate, ß-score, C-peptide, glycated hemoglobin, exogenous insulin requirement, and fasting plasma glucose. Steatosis at US was detected in 21/108 patients, 20/83 allo-transplanted and 1/25 auto-transplanted, mostly at 6 and 12 months. Infused islet mass was significantly higher in steatotic than non-steatotic patients (IE/kg: S=10.822; NS=6138; p=0.001). Metabolically, steatotic patients had worse basal conditions, but better islet function when steatosis was first detected, after which progressive islet exhaustion, along with steatosis disappearance, was observed. Conversely, in non-steatotic patients these parameters remained stable in time. Number of re-transplantations was significantly higher in steatotic than in non-steatotic patients (1.8 vs 1.1; p=0.001). Steatosis at US seems to be related to the islet mass and local overworking activity. It precedes metabolic alterations and can predict graft dysfunction addressing to therapeutic decisions before islet exhaustion. If steatosis does not appear, no conclusion can be drawn.


Subject(s)
Fatty Liver/diagnostic imaging , Fatty Liver/etiology , Islets of Langerhans Transplantation/adverse effects , Adult , Aged , Diabetes Mellitus, Type 1/therapy , Fatty Liver/epidemiology , Female , Humans , Insulin-Secreting Cells/transplantation , Liver/pathology , Longitudinal Studies , Male , Middle Aged , Pancreatic Function Tests , Predictive Value of Tests , Prevalence , Transplantation, Autologous , Treatment Outcome , Ultrasonography , Young Adult
19.
J Clin Ultrasound ; 43(7): 421-30, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25703863

ABSTRACT

PURPOSE: Our aim was to prospectively analyze the use of contrast-enhanced ultrasound (CEUS) in the quantitative assessment of the response of uveal melanoma (UM) to gamma-knife radiosurgery (GKR), investigating whether changes in tumor vascularization precede thickness reduction, which on average occurs at 12 months after GKR. METHODS: Ten patients with UM treated with GKR underwent sonography (US) and CEUS at baseline and at 3, 6, and 12 months after GKR. The transverse diameter, thickness, and quantitative parameters of the UM (ie, area under the curve in the wash-in phase, wash-in perfusion index, peak enhancement, and wash-in rate) were calculated by using dedicated software and compared by using Wilcoxon's signed-rank test. RESULTS: The mean tumor thickness on US was significantly less at both 6 (6.6 mm) and 12 months after GKR (5.8 mm) than it was at baseline (8.3 mm; p < 0.05, both comparisons). Compared with baseline data, the median flow quantitative parameters on CEUS were significantly changed as follows: the peak enhancement (in arbitrary units [au]) at baseline was 5 × 10(6) ; 6 months after GKR, it was 2 × 10(1) (p < 0.05), and 12 months after GKR, it was 4 × 10(1) (p < 0.05). The wash-in rate (in au) at baseline was 1 × 10(6) ; 6 months after GKR, it was 2.1 (p < 0.05), and 12 months after GKR, it was 9.3 (p < 0.05). The wash-in perfusion index (in au) at baseline was 2 × 10(7) ; 6 months after GKR, it was 7 × 10(1) (p < 0.05), and 12 months after GKR, it was 1 × 10(2) (p < 0.05). The area under the curve during the wash-in phase (in au) at baseline was 1 × 10(8) ; 12 months after GKR, it was reduced to 6 × 10(2) (p < 0.05). CONCLUSIONS: At 6 months after GKR, a reduction of tumor thickness, as detected on US, occurred in 6 of the 10 patients, whereas a reduction in all the quantitative parameters measured on CEUS occurred in all 10 patients. However, a larger population is needed to investigate whether CEUS could become the first-choice technique for monitoring the response of UM to GKR.


Subject(s)
Contrast Media , Image Enhancement , Melanoma/diagnostic imaging , Melanoma/surgery , Radiosurgery , Uveal Neoplasms/diagnostic imaging , Uveal Neoplasms/surgery , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prospective Studies , Ultrasonography , Uvea/diagnostic imaging , Uvea/surgery
20.
J Clin Ultrasound ; 42(2): 112-5, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23606604

ABSTRACT

Cardiac surgery can have severe neurologic complications. The noninvasive monitoring of intracranial circulation during heart surgery is usually performed with transcranial Doppler ultrasonography. We present the case of a 66-year-old man who underwent elective cardiac surgery for aortic valve replacement and coronary artery bypass graft, in whom monitoring was performed by simultaneously assessing blood flow velocity in the central retinal artery and vein.


Subject(s)
Coronary Artery Bypass , Heart Valve Prosthesis Implantation , Monitoring, Intraoperative/methods , Retinal Artery/diagnostic imaging , Retinal Vein/diagnostic imaging , Ultrasonography, Doppler, Color , Aged , Humans , Male , Ultrasonography, Doppler, Transcranial
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