Pararenal Aortic Thrombus in Patients Undergoing Aortic Aneurysm Repair With Chimney Technique.

INTRODUCTION: Chimney technique (chimney graft in abdominal aortic aneurysm repair [ChEVAR]) can be used to treat patients with pararenal aortic aneurysm unfit for open surgery and not suitable for custom-made fenestrated endograft. Since almost 1 in 5 patients undergo a reintervention within 3 years, features associated with higher risk of complications need to be investigated to tailor the follow-up schedule to each patient. The aim of our study was to assess the impact of mural thrombus in the pararenal aorta on perioperative and follow-up complications after ChEVAR. METHODS: All consecutive patients undergoing ChEVAR at our center from 2015 to 2022 were included in this retrospective study. Collected variables included number of target vessels, stent graft size, presence, and severity of mural thrombus in pararenal aorta, which was reported with a scoring system from 0 to 10 based on thrombus type, thickness area, and circumferenceAnalyzed outcomes included perioperative and follow-up complications. RESULTS: Thirty-one patients underwent ChEVAR during the study period. In 4 patients the indication for ChEVAR was type 1A endoleak after a previous endovascular aneurysm repair (EVAR). The number of target vessels was 1 in 17 patients (55%), 2 in 12 (39%), 3 in 1 (3%), and 4 in 1 (%). The mean mural thrombus score was 5.9. Complications were the following: type 1A endoleak in 4 cases (13%), chimney stent complications in 7 cases (23%) (including partial or total thrombosis, intrastent stenosis, displacement), renal function worsening during follow-up in 8 cases (26%). Overall survival was 90% at 2 years. Patients with severe mural thrombus showed lower freedom from ChEVAR-related complications (28% vs 59% at 2 years, p=0.023). CONCLUSIONS: The presence of severe pararenal aortic mural thrombus was associated with lower freedom from ChEVAR-related complications in patients undergoing ChEVAR for pararenal aortic aneurysm repair. Further research with a larger number of patients is required to confirm these results. CLINICAL IMPACT: The analysis of severity of mural thrombus in pararenal aorta, which was reported with a scoring system from 0 to 10 based on thrombus type, thickness area and circumference, can be useful and can be represent an important predictor element for complications in patient submitted to Chimney tecnique; in fact the presence of severe pararenal aortic mural thrombus was associated with lower freedom from ChEVAR-related complications in patients undergoing ChEVAR for pararenal aortic aneurysm repair. Then, in patient with pararenal aortic aneurysm, a preoperative evaluation could be focused on severity of mural thrombus to minimize the complications in ChEVAR tecnique or to change the surgical strategy.

In silico Design, Synthesis and Biological Evaluation of Novel Thieno[3,2-d]pyrimidine Derivatives for Cancer Therapy - A Preliminary Study on the Inhibitory Potential towards ATR Kinase Domain and PIKK Family.

Continuing our studies in the field of new heterocyclic compounds with biological interest, herein we report the synthesis and anticancer activity of new N- and S-substituted derivatives of tetracyclic pyrido[3',2' : 4,5]thieno[3,2-d]pyrimidines. In this regard, starting from the thieno[2,3-b]pyridine-2-carboxylates, the corresponding 8(9)-aminopyrido[3',2' : 4,5]thieno[3,2-d]pyrimidin-7(8)-ones, as well as chloro derivatives were obtained. Based on the latter, amino, hydrazino and S-alkyl derivatives of pyrido[3',2' : 4,5]thieno[3,2-d]pyrimidines were synthesized subsequently. The current study focuses on identifying the potential of thieno[3,2-d]pyrimidine derivatives primarily towards ATR kinase inhibition, through computational predictions, followed by synthesis and cancer cell viability studies, along with an aim to develop the core as PIKK inhibitors for cancer therapy.

New Bicyclic Pyridine-Based Hybrids Linked to the 1,2,3-Triazole Unit: Synthesis via Click Reaction and Evaluation of Neurotropic Activity and Molecular Docking.

The synthesis of new original bicyclic pyridine-based hybrids linked to the 1,2,3-triazole unit was described via a click reaction. The anticonvulsant activity and some psychotropic properties of the new compounds were evaluated. The biological assays demonstrated that some of the studied compounds showed high anticonvulsant and psychotropic properties. The five most active compounds (7a, d, g, j, and m) contain a pyrano [3,4-c]pyridine cycle with a methyl group in the pyridine ring in their structures. Furthermore, molecular docking studies were performed, and their results are in agreement with experimental data.

Individual patient data meta-analysis of patients treated with a heparin-bonded Viabahn in the femoropopliteal artery for chronic limb-threatening ischemia.

OBJECTIVES: The aim of the study was to analyze available data on patients treated for chronic limb-threatening ischemia (CLTI) with the heparin-bonded Viabahn endoprosthesis. BACKGROUND: The patency of self-expanding covered stents in patients with complex femoropopliteal lesions is encouraging. However, data were mostly derived in patients with intermittent claudication. Patients with CLTI often have more advanced disease and worse outcome. METHODS: After the abstract screening, full-text papers were checked. Authors were approached to consider joining the consortium. Data were sent anonymously, databases were merged and an individual patient data meta-analysis was performed. Kaplan-Meier curves were used to calculate the freedom from amputations, the amputation-free survival, and patency rates. RESULTS: Seven studies were enrolled, representing 161 limbs that were treated for CLTI. Median lesion length was 28.0 cm (interquartile range 25.0-33.0 cm) and 82.7% were chronic total occlusions. The technical success rate was 98.1% and the 30-day mortality 1.9%. Through 2-year follow-up, the freedom-from-major-amputations was 99.3%, with an amputation-free survival of 78.8%. The freedom-from-loss-of primary, primary-assisted, and secondary patency was 70.4%, 71.8%, and 88.2%, respectively, at 1-year and 59.5%, 62.7%, and 86.1% at 2-year follow-up, respectively. The reintervention-free survival was 62.2% at a 2-year follow-up. CONCLUSIONS: Treatment of femoropopliteal disease in CLTI patients with the use of the heparin-bonded Viabahn is safe and effective with favorable clinical outcomes and low amputation rates. Reinterventions are needed in a subset of the population to maintain endoprosthesis patency. Close follow-up using duplex is recommended to detect potential edge stenosis, allowing treatment before device occlusion.

Synthesis of 1-Amino-3-oxo-2,7-naphthyridines via Smiles Rearrangement: A New Approach in the Field of Chemistry of Heterocyclic Compounds.

In this paper we describe an efficient method for the synthesis of new heterocyclic systems: furo[2,3-c]-2,7-naphthyridines 6, as well as a new method for the preparation of 1,3-diamino-2,7-naphthyridines 11. For the first time, a Smiles rearrangement was carried out in the 2,7-naphthyridine series, thus gaining the opportunity to synthesize 1-amino-3-oxo-2,7-naphthyridines 4, which are the starting compounds for obtaining furo[2,3-c]-2,7-naphthyridines. The cyclization of alkoxyacetamides 9 proceeds via two different processes: the expected formation of furo[2,3-c]-2,7-naphthyridines 10 and the 'unexpected' formation of 1,3-diamino-2,7-naphthyridines 11 (via a Smiles type rearrangement).

An Easy Access to Furan-Fused Polyheterocyclic Systems.

Nitrostilbenes characterized by two different or differently substituted aryl moieties can be obtained from the initial ring-opening of 3-nitrobenzo[b]thiophene with amines. Such versatile building blocks couple the well-recognized double electrophilic reactivity of the nitrovinyl moiety (addition to the double bond, followed by, e.g., intramolecular replacement of the nitro group) with the possibility to exploit a conjugated system of double bonds within an electrocyclization process. Herein, nitrostilbenes are reacted with different aromatic enols provided by a double (carbon and oxygen) nucleophilicity, leading to novel, interesting naphthodihydrofurans. From these, as a viable application, aromatization and electrocyclization lead in turn to valuable polycondensed, fully aromatic O-heterocycles.

Benzothiazole and Chromone Derivatives as Potential ATR Kinase Inhibitors and Anticancer Agents.

Despite extensive studies and the great variety of existing anticancer agents, cancer treatment remains an aggravating and challenging problem. Therefore, the development of novel anticancer drugs with a better therapeutic profile and fewer side effects to combat this persistent disease is still necessary. In this study, we report a novel series of benzothiazole and chromone derivatives that were synthesized and evaluated for their anticancer activity as an inhibitor of ATR kinase, a master regulator of the DDR pathway. The cell viability of a set of 25 compounds was performed using MTT assay in HCT116 and HeLa cell lines, involving 72 h incubation of the compounds at a final concentration of 10 µM. Cells incubated with compounds 2c, 7h and 7l were found to show viability ≤50%, and were taken forward for dose-response studies. Among the tested compounds, three of them (2c, 7h and 7l) showed higher potency, with compound 7l exhibiting the best IC50 values in both the cell lines. Compounds 2c and 7l were found to be equally cytotoxic towards both the cell lines, namely, HCT116 and HeLa, while compound 7h showed better cytotoxicity towards HeLa cell line. For these three compounds, an immunoblot assay was carried out in order to analyze the inhibition of phosphorylation of Chk1 at Ser 317 in HeLa and HCT116 cells. Compound 7h showed inhibition of pChk1 at Ser 317 in HeLa cells at a concentration of 3.995 µM. Further analysis for Chk1 and pChk1 expression was carried out in Hela cells by treatment against all the three compounds at a range of concentrations of 2, 5 and 10 µM, wherein compound 7h showed Chk1 inhibition at 2 and 5 µM, while pChk1 expression was observed for compound 7l at a concentration of 5 µM. To support the results, the binding interactions of the compounds with the ATR kinase domain was studied through molecular docking, wherein compounds 2c, 7h and 7l showed binding interactions similar to those of Torin2, a known mTOR/ATR inhibitor. Further studies on this set of molecules is in progress for their specificity towards the ATR pathway.

A Multifield Study on Dimethyl Acetylenedicarboxylate: A Reagent Able to Build a New Cycle on Diaminoimidazoles.

A new effective method for the synthesis of imidazo[1,5-b]pyridazines derivatives (yields = 68-89%) by the interaction of 1,2-diamino-4-phenylimidazole with DMAD, in methanol and in the presence of a catalytic amount of acetic acid, is proposed. The course of reaction has been examined by classical organic methods, HPLC-MS analysis, and quantum-chemical calculations.

Inframalleolar bypass for chronic limb-threatening ischemia.

The aims of this study were to analyze the results of inframalleolar bypass for chronic limb-threatening ischemia (CLTI) and to identify outcome-predicting factors. All consecutive patients undergoing inframalleolar bypass for CLTI between 2015 and 2018 were included in this retrospective, single-center study. Outflow artery was the most proximal patent vessel segment in continuity with inframalleolar arteries. Bypasses originating from the popliteal artery were defined as 'short bypasses'. Sixty patients underwent inframalleolar bypass, with four patients undergoing bilateral procedures, making a total of 64 limbs included. The mean age was 73 ± 14 and 52 (81%) were male. The great saphenous vein was the preferred conduit (n = 58, 91%), in a devalvulated fashion (n = 56, 88%). Superficial femoral artery was the most common inflow artery for 'long' grafts (n = 22, 34%), while popliteal artery was the inflow artery for all 'short' grafts (n = 25, 39%). Dorsalis pedis artery was chosen as an outflow artery in 41 patients (63%). Median follow-up was 21 months. Two-year primary and secondary patency, limb salvage, amputation-free survival, and overall survival rates were 67 ± 6%, 88 ± 4%, 84 ± 4%, 72 ± 6%, and 85 ± 4%, respectively. At multivariate analysis, dialysis was an independent predictor for poor primary patency (HR, 4.6; 95% CI, 1.62-13.05; p = 0.004), whereas a short bypass was independently associated with an increased primary patency (HR, 0.3; 95% CI, 0.10-0.89; p = 0.03). In conclusion, bypass grafting to the inframalleolar arteries resulted in good patency rates, limb salvage and overall survival. Dialysis patients had lower primary patency but still had good limb salvage and survival. Short bypass was a predictor of improved primary patency.

Synthesis and antimicrobial activity of new 2-piperazin-1-yl-N-1,3-thiazol-2-ylacetamides of cyclopenta[c]pyridines and pyrano[3,4-c]pyridines.

In this study, we report the synthesis and antimicrobial activity of some new disubstituted piperazines. Thus, 3-chlorocyclopenta[c]pyridines and 6-chloropyrano[3,4-c]pyridine 1 under mild reaction conditions with piperazine gave the 3(6)-piperazine-substituted cyclopenta[c]pyridines and pyrano[3,4-c]pyridine 2. Furthermore, the latter, by alkylation with 2-chloro-N-1,3-thiazol-2-ylacetamide, led to the formation of the target compounds. The evaluation of the antibacterial activity revealed that 3k was the most potent compound. The most sensitive bacterium was found to be Listeria monocytogenes, whereas Staphylococcus aureus was the most resistant one. Three compounds, 3d, 3g, and 3k, were tested also against the following resistant strains: methicillin-resistant S. aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa. All three compounds appeared to be more potent than ampicillin against MRSA. Moreover, compound 3d showed a better activity than the reference drug ampicillin against P. aeruginosa, whereas 3g was more efficient against E. coli. The best antifungal activity was observed again for compound 3k. The most resistant fungi appeared to be Aspergillus fumigatus, whereas Trichoderma viride seemed the most sensitive one toward the compounds tested. Molecular docking studies on E. coli MurB, as well as on Candida albicans CYP51 and dihydrofolate reductase, were used for the prediction of the mechanisms of the antibacterial and antifungal activities, confirming the experimental results.

4,6-Dichloro-5-Nitrobenzofuroxan: Different Polymorphisms and DFT Investigation of Its Reactivity with Nucleophiles.

This research focuses on the X-ray structure of 4,6-dichloro-5-nitrobenzofuroxan 1 and of some of its amino derivatives (4a, 4e, 4g, and 4l) and on DFT calculations concerning the nucleophilic reactivity of 1. We have found that by changing the solvent used for crystallization, it is possible to obtain 4,6-dichloro-5-nitrobenzofuroxan (1) in different polymorphic structures. Moreover, the different torsional angles observed for the nitro group in 1 and in its amino derivatives (4a, 4e, 4g, and 4l) are strictly dependent on the steric hindrance of the substituent at C-4. DFT calculations on the course of the nucleophilic substitution confirm the role of the condensed furoxan ring in altering the aromaticity of the carbocyclic frame, while chlorine atoms strongly influence the dihedral angle and the rotational barrier of the nitro group. These results corroborate previous observations based on experimental kinetic data and give a deep picture of the reaction with amines, which proceeds via a "non-aromatic" nucleophilic substitution.

Cyclodextrin Polymers as Delivery Systems for Targeted Anti-Cancer Chemotherapy.

In the few last years, nanosystems have emerged as a potential therapeutic approach to improve the efficacy and selectivity of many drugs. Cyclodextrins (CyDs) and their nanoparticles have been widely investigated as drug delivery systems. The covalent functionalization of CyD polymer nanoparticles with targeting molecules can improve the therapeutic potential of this family of nanosystems. In this study, we investigated cross-linked γ- and ß-cyclodextrin polymers as carriers for doxorubicin (ox) and oxaliplatin (Oxa). We also functionalized γ-CyD polymer bearing COOH functionalities with arginine-glycine-aspartic or arginine moieties for targeting the integrin receptors of cancer cells. We tested the Dox and Oxa anti-proliferative activity in the presence of the precursor polymer with COOH functionalities and its derivatives in A549 (lung, carcinoma) and HepG2 (liver, carcinoma) cell lines. We found that CyD polymers can significantly improve the antiproliferative activity of Dox in HepG2 cell lines only, whereas the cytotoxic activity of Oxa resulted as enhanced in both cell lines. The peptide or amino acid functionalized CyD polymers, loaded with Dox, did not show any additional effect compared to the precursor polymer. Finally, studies of Dox uptake showed that the higher antiproliferative activity of complexes correlates with the higher accumulation of Dox inside the cells. The results show that CyD polymers could be used as carriers for repositioning classical anticancer drugs such as Dox or Oxa to increase their antitumor activity.

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines, Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3',2':4,5]pyrimido[1,2-a]azepines.

BACKGROUND: Neurotic disturbances, anxiety, neurosis-like disorders, and stress situations are widespread. Benzodiazepine tranquillizers have been found to be among the most effective antianxiety drugs. The pharmacological action of benzodiazepines is due to their interaction with the supra-molecular membrane GABA-a-benzodiazepine receptor complex, linked to the Cl-ionophore. Benzodiazepines enhance GABA-ergic transmission and this has led to a study of the role of GABA in anxiety. The search for anxiolytics and anticonvulsive agents has involved glutamate-ergic, 5HT-ergic substances and neuropeptides. However, each of these well-known anxiolytics, anticonvulsants and cognition enhancers (nootropics) has repeatedly been reported to have many adverse side effects, therefore there is an urgent need to search for new drugs able to restore damaged cognitive functions without causing significant adverse reactions. OBJECTIVE: Considering the relevance of epilepsy diffusion in the world, we have addressed our attention to the discovery of new drugs in this field Thus our aim is the synthesis and study of new compounds with antiepileptic (anticonvulsant) and not only, activity. METHODS: For the synthesis of compounds classical organic methods were used and developed. For the evaluation of biological activity some anticonvulsant and psychotropic methods were used. RESULTS: As a result of multistep reactions 26 new, five-membered heterocyclic systems were obtained. PASS prediction of anticonvulsant activity was performed for the whole set of the designed molecules and probability to be active Pa values were ranging from 0.275 to 0.43. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures, anti-thiosemicarbazides effect as well as some psychotropic effect. The biological assays evidenced that some of the studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of compounds is low and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity it was found that the selected compounds have an activating behavior and anxiolytic effects on the models of "open field" and "elevated plus maze" (EPM). The data obtained indicate the anxiolytic (anti-anxiety) activity of the derivatives of pyrimidines, especially pronounced in compounds 6n, 6b, and 7c. The studied compounds increase the latent time of first immobilization on the model of "forced swimming" (FST) and exhibit some antidepressant effect similarly to diazepam. Docking studies revealed that compound 6k bound tightly in the active site of GABAA receptor with a value of the scoring function that estimates free energy of binding (ΔG) at -7.95 kcal/mol, while compound 6n showed the best docking score and seems to be dual inhibitor of SERT transporter as well as 5-HT1A receptor. CONCLUSIONS: Тhe selected compounds have an anticonvulsant, activating behavior and anxiolytic effects, at the same time exhibit some antidepressant effect.

On the Nucleophilic Reactivity of 4,6-Dichloro-5-nitrobenzofuroxan with Some Aliphatic and Aromatic Amines: Selective Nucleophilic Substitution.

The reaction rates for the nucleophilic aromatic substitution of 4,6-dichloro-5-nitrobenzofuroxan 1 with eight aliphatic amines (characterized by very different basicities/nucleophilicities) and three anilines have been measured in both methanol and toluene. The obtained rates have been related to the basicity (pKaH in water and Kb in benzene) or nucleophilicity (N Mayr constants) of the tested amines. The whole of the obtained kinetic data has furnished useful information on the high nucleophilic reactivity of benzofuroxan derivatives, which has been related essentially to two factors: the high electron-drawing ability/power of the condensed furoxan ring and the low aromatic character of the benzofuroxan system.

Intra-Arterial Administration of Iloprost in Patients Undergoing Endovascular or Hybrid Revascularization Procedures for Peripheral Arterial Disease.

BACKGROUND: The aim of this study was to find out if intra-arterial intraoperative iloprost administration, in selected patients undergoing endovascular revascularization procedures, could lead to better results compared with a control group of patients with similar clinical background and risk factors. METHODS: We prospectively collected data of consecutive patients undergoing endovascular or hybrid revascularization in the period from June 2017 to August 2019, which were then retrospectively analyzed. Those patients were divided into 2 groups: iloprost and control groups. Inclusion criteria were as follows: the presence of an arteriography that included the foot; Rutherford class 4-6; and Rutherford class 3 with at least 2 cardiovascular risk factors or previous revascularization procedures on the same limb. The intraoperative intra-arterial administration of iloprost was the inclusion criterion for the iloprost group. Patients with a compromised cardiological condition were excluded, as this was a contraindication for iloprost administration. Patients from the 2 groups were matched using the propensity score matching (PSM) methodology of Rosenbaum and Rubin. The primary outcome was freedom from target lesion revascularization (TLR). The secondary outcomes were limb salvage and overall survival. RESULTS: During the mentioned period, we treated 190 consecutive limbs. The mean follow-up was 11.73 months (median, 10; interquartile range, 5-19). After PSM, the freedom from TLR was significantly better in the iloprost group (78 ± 7%, 74 ± 8%, and 63 ± 9% vs. 67 ± 8%, 50 ± 9%, and 38 ± 10% at 3, 6, and 12 months, respectively; P = 0.043). No significant difference was found in terms of limb salvage (92 ± 5%, 88 ± 6%, and 88 ± 6% vs. 92 ± 4%, 85 ± 6%, and 81 ± 7% at 3, 6, and 12 months, respectively; P = 0.52) and survival (95 ± 3%, 95 ± 3%, and 95 ± 3% vs. 95 ± 4%, 92 ± 5%, and 71 ± 9% at 3, 6, and 12 months, respectively; P = 0.14) between the 2 groups. CONCLUSIONS: These results seem to encourage considering intraoperative use of this adjunct, at least in endovascular revascularization procedures, to improve distal outflow.

Simultaneous Superficial Femoral Artery Angioplasty/Stent Plus Popliteal Distal Bypass for Limb Salvage.

BACKGROUND: Treatment of severe critical limb ischemia (CLI) due to superficial femoral artery (SFA) and below-the-knee (BTK) vessels' involvement could be compromised by the lack of a great saphenous vein (GSV) suitable in its entire length. The purpose of this study is to assess the efficacy of a hybrid endovascular and open lower limbs arterial reconstruction in these patients with multilevel, advanced CLI. METHODS: From 2005 to 2019, we performed hybrid endovascular and surgical treatment for limb salvage in SFA-BTK CLI. This consisted of percutaneous transluminal angioplasty (PTA) with or without stenting of the SFA, along with distal origin vein graft bypass. Inclusion criteria were Rutherford category 5 or 6, lack of a suitable GSV, patency of the popliteal artery, steno-obstructive lesions of the SFA, lesions of the 3 crural vessels >5 cm in length each. The follow-up was performed with duplex scan surveillance of both the bypass graft and PTA sites. RESULTS: The hybrid treatment could be performed in 34 patients. Fifty-six percent of the SFA steno-obstructive lesions were treated with simple PTA, except for the application of a bare metal stent in one patient (3%), while in all the SFA occlusions PTA was completed with covered stents (41%). Thirty-four popliteal-to-distal vein bypass grafts bypass grafts have been performed. There were no perioperative PTA or bypass graft failures. Clinical improvement was achieved in 26 (76%) patients. Overall, primary and secondary patency, limb salvage, and survival rates were 65%, 68%, 75%, and 75% at 5 years, respectively. CONCLUSIONS: A hybrid strategy in multilevel SFA-BTK CLI is a well-established approach. Additional studies are warranted to validate these results.

3-Aryl-4-nitrobenzothiochromans S,S-dioxide: From Calcium-Channel Modulators Properties to Multidrug-Resistance Reverting Activity.

Our research groups have been involved for many years in studies aimed at identifying new active organic compounds endowed with pharmacological properties. In this work, we focused our attention on the evaluation of cardiovascular and molecular drug resistance (MDR) reverting activities of some nitrosubstituted sulphur-containing heterocycles. Firstly, we have examined the effects of 4-nitro-3-(4-methylphenyl)-3,6-dihydro-2H-thiopyran S,S-dioxide 5, and have observed no activity. Then we have extended our investigation to the 3-aryl-4-nitrobenzothiochromans S,S-dioxide 6 and 7, and have observed an interesting biological profile. Cardiovascular activities were assessed for all compounds using ex vivo studies, while the MDR reverting effect was evaluated only for selected compounds using tumor cell lines. All compounds were shown to affect cardiovascular parameters. Compound 7i exerted the most effect on negative inotropic activity, while 6d and 6f could be interesting molecules for the development of more active ABCB1 inhibitors. Both 6 and 7 represent structures of large possible biological interest, providing a scaffold for the identification of new ABCB1 inhibitors.

Hybrid arteriovenous graft for hemodialysis vascular access in a multicenter registry.

OBJECTIVE: The aim of our study was to identify patients' characteristics that predicted a higher chance of arteriovenous graft patency in patients undergoing Gore Hybrid Vascular Graft (GHVG; W. L. Gore & Associates, Flagstaff, Ariz) implantation for hemodialysis access. The GHVG is a polytetrafluroethylene (PTFE) prosthesis with a nitinol-reinforced section (NRS) at the venous end. METHODS: All consecutive patients undergoing GHVG implantation for hemodialysis access at 10 tertiary referral centers between December 2013 and January 2018 were included in the study and compared with a control group of patients undergoing standard PTFE graft implantation. Selection of patients for hybrid graft implantation was based on the impossibility of autogenous vascular access creation. RESULTS: There were 145 patients included in the GHVG group and 218 in the PTFE group. In the GHVG and the PTFE groups, the mean age was 67 ± 13 years and 65 ± 13 years, and male patients totaled 52% and 46%, respectively. The technical success was 99%. The mean duration of the intervention was 100 minutes (median, 95 minutes; interquartile range, 80-120 minutes). The brachial-axillary configuration was used in the majority of cases (n = 78 [54%]). The 5-cm NRS length was prevalent (n = 108 [75%]). The median NRS oversize was 14% (interquartile range, 0%-21%). Mean follow-up was 13 months (range, 0-55 months). Seventy-one patients (49%) underwent at least one reintervention. Primary, assisted primary, and secondary patency estimates at 12 months were 44% ± 5%, 47% ± 5%, and 65% ± 4% for the GHVG group and 41% ± 4%, 53% ± 4%, and 75% ± 3% for the control group, respectively (P = NS). One-year survival was 90% ± 3%. On multivariable Cox regression analysis, hypotension (P < .001; hazard ratio [HR], 5.8; confidence interval [CI], 2.6-13) and diabetes (P = .024; HR, 1.9; CI, 1.1-3.2) were significant predictors of GHVG loss. A larger graft size was protective against GHVG loss (P = .042; HR, 0.73; CI, 0.54-0.99). The 10-cm-long graft showed a tendency toward improved patency but did not reach statistical significance (P = .074; HR, 0.48; CI, 0.21-1.07). CONCLUSIONS: Diabetes and hypotension were predictors of loss of hybrid arteriovenous access. Smaller diameters of NRS were more prone to thrombosis, whereas the 10-cm length seemed to perform better than the 5-cm one.

Mononuclear Rearrangement of the Z-Phenylhydrazones of Some 3-Acyl-1,2,4-oxadiazoles: Effect of Substituents on the Nucleophilic Character of the >C═N-NH-C6 H5 Chain and on the Charge Density of N-2 of the 1,2,4-Oxadiazole Ring (Electrophilic Counterpart).

The reaction rates for the mononuclear rearrangement of the Z-phenylhydrazones of 3-acyl-1,2,4-oxadiazoles 3a-c into the relevant 2-phenyl-2 H-1,2,3-triazoles (4a-c) have been measured in dioxane/water at different temperatures in a large range of proton concentrations. The occurrence of two different reaction pathways (one uncatalyzed, water assisted, and the other general base catalyzed) has- been observed. The obtained results have been able to furnish information about the effects of the nature of the 3-acyl structure and of the 5-substituents in the 1,2,4-oxadiazole ring on the reactivity of the examined rearrangements: they are well in line with the previsions carried out considering some our previous computational results as well as experimental kinetic ones.

Unexpected Substituent Effects in the Iso-Heterocyclic Boulton-Katritzky Rearrangement of 3-Aroylamino-5-methyl-1,2,4-oxadiazoles: A Mechanistic Study.

The kinetics of the iso-heterocyclic mononuclear rearrangement of some 3-aroylamino-5-methyl-1,2,4-ozadiazoles was carefully examined under largely variable acidic or alkaline conditions. This reaction may proceed via two different mechanistic pathways (an uncatalyzed and a base-catalyzed one), as accounted for also by the evaluation of the relevant activation parameters. Substituent effects, as quantified by means of the Hammett's equation, appear relatively modest; however, they reveal some interesting anomalies, which enabled us to draw a very precise picture of the intimate reaction course.