In Vitro Assessment of Cortisol Release Inhibition, Bioaccessibility and Bioavailability of a Chemically Characterized Scutellaria lateriflora L. Hydroethanolic Extract.

Excess cortisol release is associated with numerous health concerns, including psychiatric issues (i.e., anxiety, insomnia, and depression) and nonpsychiatric issues (i.e., osteoporosis). The aim of this study was to assess the in vitro inhibition of cortisol release, bioaccessibility, and bioavailability exerted by a chemically characterized Scutellaria lateriflora L. extract (SLE). The treatment of H295R cells with SLE at increasing, noncytotoxic, concentrations (5-30 ng/mL) showed significant inhibition of cortisol release ranging from 58 to 91%. The in vitro simulated gastric, duodenal, and gastroduodenal digestions, induced statistically significant reductions (p < 0.0001) in the bioactive polyphenolic compounds that most represented SLE. Bioavailability studies on duodenal digested SLE, using Caco-2 cells grown on transwell inserts and a parallel artificial membrane permeability assay, indicated oroxylin A glucuronide and oroxylin A were the only bioactive compounds able to cross the Caco-2 cell membrane and the artificial lipid membrane, respectively. The results suggest possible applications of SLE as a food supplement ingredient against cortisol-mediated stress response and the use of gastroresistant oral dosage forms to partially prevent the degradation of SLE bioactive compounds. In vivo studies and clinical trials remain necessary to draw a conclusion on the efficacy and tolerability of this plant extract.

Effect of fasting on short-term visual plasticity in adult humans.

Brain plasticity and function is impaired in conditions of metabolic dysregulation, such as obesity. Less is known on whether brain function is also affected by transient and physiological metabolic changes, such as the alternation between fasting and fed state. Here we asked whether these changes affect the transient shift of ocular dominance that follows short-term monocular deprivation, a form of homeostatic plasticity. We further asked whether variations in three of the main metabolic and hormonal pathways affected in obesity (glucose metabolism, leptin signalling and fatty acid metabolism) correlate with plasticity changes. We measured the effects of 2 h monocular deprivation in three conditions: post-absorptive state (fasting), after ingestion of a standardised meal and during infusion of glucagon-like peptide-1 (GLP-1), an incretin physiologically released upon meal ingestion that plays a key role in glucose metabolism. We found that short-term plasticity was less manifest in fasting than in fed state, whereas GLP-1 infusion did not elicit reliable changes compared to fasting. Although we confirmed a positive association between plasticity and supraphysiological GLP-1 levels, achieved by GLP-1 infusion, we found that none of the parameters linked to glucose metabolism could predict the plasticity reduction in the fasting versus fed state. Instead, this was selectively associated with the increase in plasma beta-hydroxybutyrate (B-OH) levels during fasting, which suggests a link between neural function and energy substrates alternative to glucose. These results reveal a previously unexplored link between homeostatic brain plasticity and the physiological changes associated with the daily fast-fed cycle.

Pathophysiology and Management of Glycemic Alterations before and after Surgery for Pheochromocytoma and Paraganglioma.

Glycemic alterations are frequent in patients with pheochromocytoma and paraganglioma (PPGL), but the real incidence of secondary diabetes mellitus (DM) is uncertain, because prospective multicenter studies on this topic are lacking in the literature. The main pathophysiological mechanisms of glucose homeostasis alterations in PPGL, related to catecholamine hypersecretion, are impaired insulin and glucagon-like peptide type 1 (GLP-1) secretion and increased insulin resistance. Moreover, it has been reported that different pathways leading to glucose intolerance may be related to the secretory phenotype of the chromaffin tumor. Predictive factors for the development of glucose intolerance in PPGL patients are a higher age at diagnosis, the need for a higher number of anti-hypertensive drugs, and the presence of secreting neoplasms. Tumor resection is strongly related to the resolution of DM in PPGL patients, with a significant improvement of glycemic control in most cases. We can hypothesize a different personalized therapeutic approach based on the secretory phenotype. The adrenergic phenotype is more closely related to reduced insulin secretion, so insulin therapy may be required. On the other hand, the noradrenergic phenotype mainly acts by increasing insulin resistance and, therefore, insulin-sensitizing antidiabetic agents can find a greater application. Regarding GLP-1 receptor agonists, the data suggest a possible promising therapeutic effect, based on the assumption that GLP-1 secretion is impaired in patients with PPGL. The principal predictors of remission of glycemic alterations after surgery for PPGL are a lower preoperative body mass index (BMI), a larger tumor, higher preoperative catecholamine levels, and a shorter duration of the disease (under three years). Otherwise, after resection of PPGL, hypoglycemia can occur as the result of an excessive rebound of preoperative hyperinsulinemia. It is a rare, but potentially severe complication reported in a lot of case reports and a few small retrospective studies. Higher 24-h urinary metanephrine levels, longer operative times and larger tumors are predictive factors for hypoglycemia in this setting. In conclusion, alterations of carbohydrate metabolism are clinically relevant manifestations of PPGL before and after surgery, but there is the need to conduct multicenter prospective studies to obtain an adequate sample size, and to allow the creation of shared strategies for the clinical management of these potentially severe manifestations of PPGL.

Brain effect of bariatric surgery in people with obesity.

BACKGROUND/OBJECTIVES: The link between obesity and brain function is a fascinating but still an enigmatic topic. We evaluated the effect of Roux-en-Y gastric bypass (RYGB) on peripheral glucose metabolism, insulin sensitivity, brain glucose utilization and cognitive abilities in people with obesity. SUBJECTS/METHODS: Thirteen subjects with obesity (F/M 11/2; age 44.4 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) underwent 75-g OGTT during a [18F]FDG dynamic brain PET/CT study at baseline and 6 months after RYGB. At the same timepoints, cognitive performance was tested with Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail making test (TMT) and Token test (TT). Glucose, insulin, C-peptide, GLP-1, GIP, and VIP levels were measured during OGTT. Leptin and BDNF levels were measured before glucose ingestion. RESULTS: RYGB resulted in significant weight loss (from 46.1 ± 4.9 to 35.3 ± 5.0 kg/m2; p < 0.01 vs baseline). Insulin sensitivity improved (disposition index: from 1.1 ± 0.2 to 2.9 ± 1.1; p = 0.02) and cerebral glucose metabolic rate (CMRg) declined in various brain areas (all p ≤ 0.01). MMSE and MoCA score significantly improved (p = 0.001 and p = 0.002, respectively). TMT and TT scores showed a slight improvement. A positive correlation was found between CMRg change and HOMA-IR change in the caudate nucleus (ρ = 0.65, p = 0.01). Fasting leptin decreased (from 80.4 ± 13.0 to 16.1 ± 2.4 ng/dl; p = 0.001) and correlated with CMRg change in the hippocampus (ρ = 0.50; p = 0.008). CMRg change was correlated with cognitive scores changes on the TMT and TT (all p = 0.04 or less). CONCLUSIONS: Bariatric surgery improves CMRg directly related to a better cognitive testing result. This study highlights the potential pleiotropic effects of bariatric surgery. TRIAL REGISTRY NUMBER: NCT03414333.

Insulin secretion and action affect glucose variability in the early stages of glucose intolerance.

AIMS: Since it is unknown whether glucose variability (GV) is increased and whether this is related to worsening of insulin secretion and action in prediabetes, we have assessed insulin secretion and sensitivity, and daily GV in early stages of dysglycemia. MATERIALS AND METHODS: Twenty subjects with normal glucose tolerance (NGT; age 45.0 ± 9.5 years; BMI 31.1 ± 6.4 kg/m2), 25 with NGT and 1hrOGTT>8.6 mmol/L (1hrOGTT; 45.7 ± 8.5 years; 32.4 ± 7.0 kg/m2), and 59 with isolated impaired glucose tolerance (iIGT; 47.7 ± 11.2 years; 31.3 ± 6.1 kg/m2) underwent OGTT and MMTT. CGM was performed with blinded FreeStyle Libre Pro for 24 h under standard conditions. Parameters of beta-cell function, insulin sensitivity and GV were calculated. RESULTS: Overall insulin secretion and action as well as GV progressively worsened across glucose tolerance categories. On a matrix analysis, GV parameters were inversely related to ISSI-2; r = -0.37 to -0.52; p < 0.0001; and IGI; r = -0.28 to -0.48; p < 0.0001 for CV, SD, J-index, LI, HBGI and MAGE. Insulin secretion (IGI) and b-cell function (ISSI-2) emerged as independent contributors to GV in early stage of dysglycemia accounting for about 16%-38% of its variability. CONCLUSIONS: Our results show that daily GV worsens already with mild impairment of glucose tolerance. The increase in GV is inversely related to insulin secretion and action.

Technical note and first results on JET 7 thromboaspiration device for T-ICA occlusions.

BACKGROUND: To describe technical features and initial results of a novel large-bore reperfusion catheter as first thromboaspiration approach for endovascular stroke treatment in terminal internal carotid artery (T-ICA) occlusions. METHODS: All patients treated with A Direct Aspiration first-Pass Technique (ADAPT) using JET 7 "Standard Tip" Penumbra Reperfusion catheter for acute T-ICA occlusion were retrospectively included in the study. Baseline data, puncture to recanalization time, number of attempts, switch to second device/technique rate and successful recanalization rate were assessed. Successful recanalization was defined by a thrombolysis in cerebral infarction (TICI) score ≥ 2b and favorable functional outcome was defined according to modified Rankin scale (score, 0-2). Catheter specifics and thromboaspiration reperfusion technique with JET 7 were reported. RESULTS: A total of 21 patients who underwent ADAPT with JET 7 Reperfusion catheter were enrolled for the final analysis. ADAPT was performed as first approach in all cases (100%). First attempt successful recanalization (eTICI ≥2b) was obtained in 90,5% of cases. Mean puncture to recanalization time was 16 minutes. Final successful recanalization was reached in 96.5%. Functional independence at 90 was achieved in 57,1% cases. Symptomatic intracranial hemorrhage occurred in one patient within 24 h. CONCLUSION: The large-bore JET 7 reperfusion catheter could be considered as first-line in patients with acute T-ICA occlusion, allowing rapid recanalization and low rate of rescue therapy with stent retriver. Further series and/or trial evaluation are required to confirm our results.

Trends of recanalization therapies and state of art for ischemic stroke treatment in Campania region, Italy.

BACKGROUND: According to the last Italian report by the Ministry of Health in 2018, the estimated number of acute ischemic strokes (AIS) in Campania is 10,000/year, with an expected number of 1390 intravenous thrombolysis (IVT) and 694 mechanical thrombectomies (MT). In 2017, only 1.5% of expected patients received IVT and 0.2% MT. This study analyzed the trend of IVT and MT in 2019-2020 and depicted the state of art of Stroke Care in Campania. METHODS: From the regional health task force, we obtained the hospital discharge forms from all private and public hospitals in Campania; we selected patients with a principal diagnosis of AIS and measured the rate of patients admitted to neurology units and the rate of IVT, MT, and IVT + MT for both 2019 and 2020. RESULTS: In 2019, we observed 4817 admissions for AIS; 2858/4817 (59.3%) patients were admitted to neurology units. Out of 4817 patients, 192 received IVT, 165 MT, and 131 IVT + MT (488 treated patients; 10.1%). In 2020, we observed 4129 admissions for AIS; 2502/4129 (62.7%) patients were admitted to neurology units. Out of 4129 patients, 198 received IVT, 250 MT, and 180 IVT + MT (628 treated patients; 15.2%). These results showed that despite a reduction of AIS admissions in 2020, the relative and absolute rate of recanalization treatments increased. However, the number of patients who were not admitted to neurology units nor received acute treatments remained dramatically high. CONCLUSION: Despite the development of acute treatments, the Campania Stroke Network still needs significative efforts to improve.

JET 7 catheter for direct aspiration in carotid T occlusions: preliminary experience and literature review.

OBJECTIVE: We report our preliminary experience with the Penumbra JET 7 reperfusion catheter (JET 7), a new large-bore (0.072″) aspiration catheter, in patients with acute ischemic stroke (AIS) due to carotid T occlusion. METHODS: Data of all eligible patients who received A Direct Aspiration First Pass Technique (ADAPT) for AIS due to carotid T occlusion at our center from March 2018 through June 2020 were retrospectively reviewed. The safety and performance of JET 7 cases and smaller large-bore catheters (LBCs) were compared. RESULTS: JET 7 was used in 19 patients, and smaller LBCs were used in 41 patients. Median puncture to revascularization time was significantly different between the JET 7 and the smaller LBCs (16 vs. 27 min; P = 0.011). The rate of patients who received rescue therapy with a stent retriever was also significantly different between the JET 7 cases and the smaller LBCs cases (5.3% vs. 22.0%; P = 0.046). Successful revascularization (TICI ≥ 2b) was achieved in 94.7% of JET 7 cases and 75.6% of smaller LBCs cases (P = 0.148). Good functional outcome (mRS 0-2) at 90 days occurred in 63.2% of JET 7 cases and 46.3% of smaller LBCs cases (P = 0.274). CONCLUSIONS: In this early experience, ADAPT with JET 7 could be considered as one of the possible first-line therapies in carotid T occlusion, showing good rate of vascularization and lower rate of rescue therapy in comparison with smaller LBCs.

Bariatric surgery restores visual cortical plasticity in nondiabetic subjects with obesity.

BACKGROUND/OBJECTIVES: Obesity leads to changes in synaptic plasticity. We aimed at investigating the impact of bariatric surgery (RYGB) on visual neural plasticity (NP) and its relationship with the main gut peptides, leptin, and brain-derived neurotrophic factor (BDNF). SUBJECTS/METHODS: NP was assessed testing binocular rivalry before and after 2 h of monocular deprivation (index of visual brain plasticity) in 15 subjects with obesity (age 42.3 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) before and after RYGB. Gut peptides, leptin, and BDNF were obtained at baseline and 6 months after surgery in 13 subjects. RESULTS: A significant reduction in BMI (p < 0.001 vs. baseline) and a significant increase of disposition index (DI, p = 0.02 vs baseline) were observed after RYGB. Total and active GLP-1 release in response to glucose ingestion significantly increased after RYGB, while no changes occurred in VIP, GIP, and BDNF levels. Fasting leptin concentration was lower after RYGB (p = 0.001 vs. baseline). Following RYGB, NP was progressively restored (p < 0.002). NP was correlated with DI and fasting glucose at baseline (r = 0.75, p = 0.01; r = -0.7, p = 0.02; respectively), but not with BMI. A positive correlation between post-pre-RYGB changes in AUCactive GLP-1 and NP was observed (r = 0.70, p < 0.01). Leptin was inversely correlated with NP 6 months after surgery (r = -0.63, p = 0.02). No correlation was observed between GIP, VIP, BDNF, and NP. CONCLUSIONS: Visual plasticity is altered in subjects with obesity, and it can be restored after RYGB. The improvement may be mediated by amelioration of insulin sensitivity, increased GLP-1 levels, and reduced leptin levels.

Acute ischemic stroke with cervical internal carotid artery steno-occlusive lesion: multicenter analysis of endovascular approaches.

BACKGROUND: Occlusion of the internal carotid artery (ICA), whether isolated or in the setting of a tandem lesion (TL) have a poor response to treatment with intravenous thrombolysis. Previous studies ​​have demonstrated the superiority of mechanical thrombectomy in the treatment of acute ischemic stroke (AIS) following large vessel occlusion, compared to standard intravenous fibrinolysis. The aim of our study was to describe endovascular treatment (EVT) in AIS due to isolated ICA occlusion or TL. METHODS: We assessed the association between 90-day outcome and clinical, demographic, imaging, and procedure data in 51 consecutive patients with acute isolated ICA occlusion or TL who underwent EVT. We evaluated baseline NIHSS and mRS, ASPECTS, type of occlusion, stent placement, use of stent retrievers and/or thromboaspiration, duration of the procedure, mTICI, postprocedural therapy and complications. RESULTS: A favorable 90-day outcome (mRS 0-2) was achieved in 34 patients (67 %) and was significantly associated with the use of dual antiplatelet therapy after the procedure (p = 0.008), shorter procedure duration (p = 0.031), TICI 2b-3 (p < 0.001) and lack of post-procedural hemorrhagic transformation (p = 0.001). Four patients did not survive, resulting in a mortality rate of 8 %. CONCLUSIONS: Our study has shown that EVT in the treatment of AIS due to ICA occlusion is safe, and effective in determining a good functional outcome. ICA stenting led to good angiographic results and therapy with a glycoprotein IIb / IIIa inhibitor immediately after stent release did not result in a greater risk of hemorrhage. The use of post-procedural dual antiplatelet therapy was associated with favorable outcome, without a significant increase in hemorrhagic transformation.

Watershed subarachnoid hemorrhage after middle cerebral artery rescue stenting in patients with acute ischemic stroke.

Cortical subarachnoid hemorrhage is an infrequent subtype of non-aneurysmal subarachnoid hemorrhage, rarely reported in watershed territories (wSAH) after carotid stenting. It has never been reported after treatment of middle cerebral artery stenosis (MCAS) that is increasingly used in selected patients, as rescue treatment of failed mechanical thrombectomy, due to recent advancements in endovascular interventions. We present a series of patients with MCAS that developed a wSAH after stenting.

Endovascular treatment of acute ischemic stroke due to tandem lesions of the anterior cerebral circulation: a multicentric Italian observational study.

PURPOSE: Acute ischemic stroke (AIS) due to tandem lesions (TLs) of extracranial Internal Carotid Artery and Anterior Cerebral Circulation are challenging for endovascular treatment (EVT). This study aims to evaluate feasibility, safety and efficacy of EVT for TLs' AIS, with or without emergent carotid artery stenting (eCAS), in a real-life scenario. METHODS: Retrospective review of prospectively collected non-randomized thrombectomy databases from five stroke centers between 2015 and 2019. Consecutive patients with TLs' AIS were selected. Clinical, neuroimage and procedure features, as well as antiplatelet therapy regimen, were evaluated. Primary outcome was 90-day mRS ≤ 2. Secondary outcomes included: mTICI score 2b-3, extracranial recanalization, procedural complications, symptomatic intracerebral hemorrhage (SICH) and 90-day mortality. RESULTS: Two hundred twenty-seven patients were enrolled (67.8% males; mean age 65.9 ± 12.9 years). We obtained mTICI 2b-3 in 77.1%, extracranial recanalization in 86.8%, 90-day mRS (available in 201/227 cases) ≤ 2 in 49.8%. Procedural complications occurred in 16.7%, SICH in 9.7%; 90-day mortality rate (available in 201/227 cases) was 14.4%. The strongest predictors of good clinical outcome were young age (p < 0.0001), low baseline NIHSS (p = 0.008), high baseline ASPECTS (p < 0.0001), good collateral flow (p = 0.013) and extracranial recanalization (p = 0.001). The most significant predictors of SICH were low baseline ASPECTS (p < 0.0001), occurrence of complications (p < 0.0001) and eCAS (p = 0.002). CONCLUSION: In our real-life series, the EVT for TLs' AIS was feasible, safe and effective in improving 90-day functional outcome with acceptable morbi-mortality rates. ECAS increased the risk of SICH, independently from the antiplatelet therapy regimen.

Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy.

AIMS/HYPOTHESIS: The glucosuria induced by sodium-glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA1c. We hypothesised that, in response to glucosuria, a renal signal is generated and stimulates EGP. To examine the effect of acute administration of SGLT2 inhibitors on EGP, we studied non-diabetic individuals who had undergone renal transplant with and without removal of native kidneys. METHODS: This was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30-65 years old, with a BMI of 25-35 kg/m2 and stable body weight (±2 kg) over the preceding 3 months, and HbA1c <42 mmol/mol (6.0%). Participants had undergone renal transplant with and without removal of native kidneys and were on a stable dose of immunosuppressive medications. Participants received a single dose of dapagliflozin 10 mg or placebo on two separate days, at a 5- to 14-day interval, according to randomisation performed by our hospital pharmacy, which provided dapagliflozin and matching placebo, packaged in bulk bottles that were sequentially numbered. Both participants and investigators were blinded to group assignment. RESULTS: Twenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6 ± 1.1 vs 5.5 ± 0.5 g/6 h; p = 0.02; data not shown). During the 6 h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (Δ = 1.11 ± 0.72 µmol min-1 kg-1) was significantly lower (p = 0.03) than in the residual native kidney group (Δ = 2.56 ± 0.33 µmol min-1 kg-1). In the population treated with dapagliflozin, urinary glucose excretion was correlated with EGP (r = 0.34, p < 0.05). Plasma insulin, C-peptide, glucagon, prehepatic insulin:glucagon ratio, lactate, alanine and pyruvate concentrations were similar following placebo and dapagliflozin treatment. ß-Hydroxybutyrate increased with dapagliflozin treatment in the residual native kidney group, while a small increase was observed only at 360 min in the nephrectomy group. Plasma adrenaline (epinephrine) did not change after dapagliflozin and placebo treatment in either group. Following dapagliflozin administration, plasma noradrenaline (norepinephrine) increased slightly in the residual native kidney group and decreased in the nephrectomy group. CONCLUSIONS/INTERPRETATION: In nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal-hepatic axis). TRIAL REGISTRATION: ClinicalTrials.gov NCT03168295 FUNDING: This protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38. Graphical abstract.

Eradication of a Multidrug-Resistant, Carbapenemase-Producing Klebsiella pneumoniae Isolate Following Oral and Intra-rectal Therapy With a Custom Made, Lytic Bacteriophage Preparation.

In July 2017, a patient presented colonization with a multidrug-resistant, carbapenemase (KPC-3)-producing Klebsiella pneumoniae isolate. A custom-made, lytic bacteriophage preparation was administered to the patient in December 2017, with subsequent eradication of the microorganism and without adverse effects.

Effects of treatment with metformin and/or sitagliptin on beta-cell function and insulin resistance in prediabetic women with previous gestational diabetes.

AIM: To investigate the effect of sitagliptin (SITA) and metformin (MET) monotherapy as well as in combination (MET+SITA) on beta-cell function and insulin sensitivity in women with recent gestational diabetes (GDM) and impaired glucose regulation (IGR: impaired fasting glucose and/or impaired glucose tolerance). MATERIAL AND METHODS: Forty women were randomly assigned to receive SITA (100 mg qd), MET (850 mg bid) or MET+SITA (50 + 850 mg bid) for 16 weeks. A 75 g oral glucose tolerance test (OGTT) and +125 mg/dL hyperglycaemic clamp followed by 5 g i.v. L-arginine were performed at baseline and end of study. The primary outcome of the study was the mean change in arginine-stimulated insulin secretion rate during the hyperglycaemic clamp test from baseline to 16-week therapy. RESULTS: At week 16, body mass index declined in all groups (-1.2 ± 0.2 kg/m2 ; P < 0.05). MET+SITA gave a greater increase of first phase(2-10 min) insulin secretion and arginine-stimulated response (720.3 ± 299.0 to 995.5 ± 370.3 pmol/L and 3.2 ± 0.6 to 4.8 ± 1.0 pmoL/min, respectively, both P < 0.05) compared with MET and SITA. Similarly, MET+SITA was more effective in increasing OGTT-based glucose sensitivity (55.7 ± 11.3 to 108 ± 56.2 pmol x min-1 m-2 x mM-1 ; P = 0.04) and insulin-stimulated glucose disposal (M/I: 2.2 ± 0.5 to 4.6 ± 1.3 mg/kg/min÷µIU/min/ml; P = 0.04; Matsuda index [SI]: 3.1 ± 0.4 to 5.7 ± 1.1; P = 0.03) compared with either MET or SITA. Disposition index (ISSI-2) increased with MET+SITA and SITA (both P < 0.05), while no significant change was observed in MET. Among MET+SITA women, 33% reverted to normal glucose tolerance (NGT) compared with 14% with MET and 7% with SITA (P < 0.05). CONCLUSION: This study shows that MET+SITA is superior to SITA and MET monotherapy regarding beta-cell function and insulin sensitivity improvement in IGR women with previous GDM, and may offer a potential pharmacologic intervention to reduce the risk of type 2 diabetes in this high-risk population.

Efficacy of ADAPT with large-bore reperfusion catheter in anterior circulation acute ischemic stroke: a multicentric Italian experience.

INTRODUCTION: A direct aspiration first pass technique (ADAPT) is an alternative technique as first-line thrombectomy for large vessel occlusion in acute ischemic stroke, still debated when compared to first-line stent retriever. To retrospectively evaluate technical and clinical outcomes of the ADAPT as first-line treatment for anterior circulation acute ischemic stroke with large-bore reperfusion catheters. METHODS: A multicentric data collection from 14 medical centers was retrospectively analyzed. Large-bore catheters had a distal diameter between 0.64 and 0.71 in; stent retriever was added when aspiration alone failed. Baseline characteristics, technical and clinical variables were collected, including NIHSS, thrombolysis in cerebral infarction (TICI), peri-procedural complications, 90-day mRS and 90-day mortality. RESULTS: Overall, 501 patients were treated. No statistically significant difference in terms of baseline features or tPA administration was recorded between patients treated with ADAPT and with additional stent retriever. ADAPT alone was successful in achieving TICI ≥ 2b in 71.8% with a median of 1.55 aspiration attempts. In terms of TICI ≥ 2b, ADAPT alone was better than additional stent retriever (p < 0.001), while no statistical difference was achieved from catheter diameter. Embolization to a new territory was less frequent in ADAPT group (5.2 vs 18%; p = 0.0026). Patients treated with ADAPT alone had better clinical outcomes in terms of mRS ≤ 2 (p < 0.001). CONCLUSIONS: ADAPT is a valid technique with respect to the rates of TICI 2b/3 recanalization and 90-day mRS scores. In this series, an attempt at recanalization with ADAPT with larger-bore reperfusion catheter may be warranted prior to stentriever thrombectomy.

Multicentric Experience with an Intermediate Aspiration Catheter for Distal M2 Ischemic Stroke.

BACKGROUND: To assess technical and clinical outcomes of an intermediate bore aspiration catheter (AXS Catalyst 5; Stryker) as front-line therapy for M2-M3 acute occlusions. METHODS: A multicentric, retrospective data collection of patients with symptomatic M2-M3 ischemic stroke, treated with direct aspiration first-pass technique was obtained. Time to recanalization, first attempt recanalization, and number of attempts were recorded. Successful recanalization was defined as a modified thrombolysis in cerebral infarction score ≥2b; incidence of procedure-related complications was recorded. National Institutes of Health Stroke Scale at discharge and modified Rankin Scale score at 90 days were evaluated by a dedicated neurologist. RESULTS: A total of 44 acute occlusions of distal M2-M3 segment were treated with a direct aspiration first-pass technique using CAT 5 (mean age 68,4 years). Median NIHSS at baseline was 10. Overall modified thrombolysis in cerebral infarction score ≥2b was obtained in 90,9% of patients with mean time to recanalization of 49,7 minutes and a mean of 1.6 attempts. First-attempt recanalization with CAT 5 was obtained in 52,3% of patients with a mean time to recanalization of 29.2 min. A stent retriever with proximal aspiration was incorporated as a rescue device in 3 cases. No major complications was detected. The median National Institutes of Health Stroke Scale score at discharge was 4. At 90 days, a modified Rankin Scale score of 0-2 was achieved in 70,5% of patients. CONCLUSIONS: ADAPT technique with the intermediate aspiration catheter CAT 5 system achieves successful revascularization and functional independence for patients with acute ischemic stroke secondary to distal M2 occlusions.

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study.

BACKGROUND: Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. METHODS: We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. RESULTS: Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59-7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65-15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42-94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88-4.76), 2 MC 1.98 (95% CI 0.75-5.21), 3 MC 7.02 (95% CI 2.44-20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96-5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82-28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59-74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65-3.88), 2 MC 4.33 (95% CI 1.75-10.74), 3 MC 9.31 (95% CI 3.18-27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001). CONCLUSIONS: In type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

Exenatide modulates visual cortex responses.

BACKGROUND: Increasing evidence suggests that metabolism affects brain physiology. Here, we examine the effect of GLP-1 on simple visual-evoked functional Magnetic Resonance Imaging (fMRI) responses in cortical areas. METHODS: Lean (n = 10) and nondiabetic obese (n = 10) subjects received exenatide (a GLP-1 agonist) or saline infusion, and fMRI responses to visual stimuli (food and nonfood images) were recorded. We analysed the effect of exenatide on fMRI signals across the cortical surface with special reference to the visual areas. We evaluated the effects of exenatide on the raw fMRI signal and on the fMRI signal change during visual stimulation (vs rest). RESULTS: In line with previous studies, we find that exenatide eliminates the preference for food (over nonfood) images present under saline infusion in high-level visual cortex (temporal pole). In addition, we find that exenatide (vs saline) also modulates the response of early visual areas, enhancing responses to both food and nonfood images in several extrastriate occipital areas, similarly in obese and lean participants. Unexpectedly, exenatide increased fMRI raw signals (signal intensity during rest periods without stimulation) in a large occipital region, which were negatively correlated to BMI. CONCLUSIONS: In both lean and obese individuals, exenatide affects neural processing in visual cortex, both in early visual areas and in higher order areas. This effect may contribute to the known effect of GLP1 analogues on food-related behaviour.

Intra-arterial chemotherapy for retinoblastoma: the dosimetric impact.

PURPOSE: Purposes are (1) to measure main radiation parameters and (2) to propose a method to estimate the absorbed doses of internal organs starting from DAP values. Measuring the exposition of internal organs by repeated irradiations on an anthropomorphic phantom with the same settings used in vivo, we could establish correlations between (1) DAP and the dose recorded by a dosimeter placed along the X-ray beam entrance pathway; (2) the dose recorded by the same dosimeter and the absorbed dose in internal organs. METHODS: Forty-four consecutive patients (16 males, 28 females) (mean age 35.4 months) treated at our institution with IAC (216 procedures: 196 via the ICA and 20 into branches of the ECA) were included in this prospective study. IAC was divided into 5 phases. Fluoroscopic time, DAP, and ESD were measured. RESULTS: The mean DAP was 595 ± 445 cGy cm2 and the mean fluoroscopic time was 540 ± 403 s. ESD was on average 9.59 mGy (range 0.8-165 mGy). The absorbed dose was lower than 12.1 mGy in the left retina (the more exposed organ) in 75% of single treatments and lower than 25 mGy in 95% of treatments. In the cases of 3 and 6 sessions, the left retina of 75% of patients absorbed respectively less than 36.3 and 72.7 mGy, whereas the left retina of 95% of patients received less than 75.2 and 150.4 mGy. Other organs were less exposed. CONCLUSION: This paper describes a method of absorbed dose estimation providing ranges used clinically in a single practice and the basis for further prospective studies.