STEATOEPATITE NON ALCOLICA E FIBROSI EPATICA IN UNA CASISTICA DI PAZIENTI OBESI SOTTOPOSTI A CHIRURGIA BARIATRICA

Obiettivi dello studio: Valutare la prevalenza di epatopatia steatosica non alcolica (NAFLD) ed in particolare di steatoepatite non alcolica (NASH) e fibrosi epatica in pazienti con obesit\ue0 grave, che sono candidati ad intervento di chirurgia bariatrica. E\u2019 stato inoltre valutato l\u2019andamento delle transaminasi plasmatiche, adiponectina e di alcuni scores non invasivi di fibrosi epatica avanzata dopo 6 e 12 mesi dall\u2019intervento chirurgico.Popolazione e Metodi: Abbiamo studiato un campione di 28 pazienti affetti da obesit\ue0 grave (75% donne, et\ue0 mediana 41 anni, BMI mediano 45 kg/m\ub2), che sono stati sottoposti ad intervento in elezione di sleeve gastrectomy (19 pazienti) o bypass gastrico (9 pazienti). In tutti i pazienti sono stati eseguiti accertamenti metabolici (incluso 2-h clamp euglicemico iperinsulinemico) al baseline ed \ue8 stata eseguita una biopsia epatica durante l\u2019intervento chirurgico. Nessuno di questi pazienti aveva un eccessivo consumo di alcoolici n\ue9 una precedente storia di cirrosi e/o altre epatopatie croniche note.Risultati: Dei 28 pazienti inclusi nello studio, 16 (57%) hanno soddisfatto i criteri istologici per una diagnosi di NASH, mentre i restanti 12 (43%) pazienti non avevano NASH al baseline. Di questi 12 pazienti privi di NASH alla biopsia, 8 pazienti avevano steatosi macrovescicolare di grado lieve o severo (NAFL), mentre solo 4 pazienti (pari al 14.3% del campione totale) erano esenti da NAFLD alla biopsia epatica. Per quanto riguarda il grado di fibrosi epatica, 4 pazienti (14.3%) non avevano fibrosi (stadio F0), 14 (50%) pazienti avevano fibrosi moderata (F2) e 10 (35.7%) avevano \u201cbridging fibrosis\u201d (F3). Nessuno dei pazienti aveva cirrosi epatica precedentemente misconosciuta (F4). Quando i pazienti venivano suddivisi sulla base della presenza/assenza di NASH e/o della severit\ue0 di fibrosi epatica (F3 vs. F0-2), i due gruppi di pazienti erano comparabili per et\ue0, sesso e le principali variabili biochimiche esaminate, incluso transaminasi, APRI index, FIB-4 score e sensibilit\ue0 insulinica (M-clamp). L\u2019intervento chirurgico induceva, sia dopo 6 che 12 mesi, un marcato calo ponderale ed una significativa riduzione dei livelli circolanti di adiponectina in entrambi i gruppi. Al contrario, i valori di transaminasi e gli scores non invasivi di fibrosi epatica avanzata non hanno mostrato alcuna significativa variazione dopo 6 e 12 mesi dall\u2019intervento chirurgico in nessuno dei gruppi di pazienti considerati (NASH vs. no-NASH e F3 vs. F0-2).Conclusioni: Nei nostri pazienti con obesit\ue0 grave, candidati a chururgia bariatrica, la NAFLD \ue8 una patologia assai comune (essendo presente in circa 85% del campione) ed \ue8 gi\ue0 presente anche nelle sue forme istologiche pi\uf9 severe (NASH nel 57% dei casi e fibrosi avanzata nel 35.7% dei casi), pur rimanendo queste forme spesso clinicamente silenti (o pauci-sintomatiche) e senza accompagnarsi a significative alterazioni delle transaminasi circolanti e degli scores non-invasivi di fibrosi avanzata. Questi dati suggeriscono la necessit\ue0 di una diagnosi precoce e tempestiva delle forme pi\uf9 severe della NAFLD (che sono quelle associate ad un maggior rischio di progressione verso la cirrosi e l\u2019epatocarcinoma) in tutti i soggetti obesi che vengono sottoposti a chirurgia bariatrica (da eseguirsi almeno in fase intra-operatoria)

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Association between specific plasma ceramides and high-sensitivity C-reactive protein levels in postmenopausal women with type 2 diabetes

AIM: Emerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, only scanty information is currently available on the association between distinct plasma ceramides (those associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group at high risk of developing CVD and other chronic inflammation-related conditions. METHODS: Previously, six high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] were identified in 92 postmenopausal women with T2DM attending a diabetes outpatients service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. RESULTS: Plasma hs-CRP levels were positively associated with all measured ceramides on univariable linear regression analyses, but only plasma Cer(d18:1/16:0) (standard \u3b2 coefficient: 0.27, P = 0.015), Cer(d18:1/22:0) (standard \u3b2 coefficient: 0.25, P = 0.032) and Cer(d18:1/24:1) (standard \u3b2 coefficient: 0.30, P = 0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA1c, insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs. CONCLUSION: In postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors

From lipoprotein apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients

In this observational study, we compared the effect of lipoprotein apheresis and evolocumab or alirocumab on levels of lipoprotein cholesterol, triglycerides and inflammatory markers (C reactive protein and interleukin 6) in cardiovascular patients ( n\u2009=\u20099). Patients were monitored during the last year of lipoprotein apheresis followed by six months of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors. The biochemical parameters were determined pre- and post- every apheresis procedure for 12 months and then after one, three and six months of treatment with evolocumab (140\u2009mg every two weeks [Q2W]) or alirocumab (75\u2009mg or 150\u2009mg every two weeks [Q2W]). Lipoprotein apheresis significantly reduced low-density lipoprotein cholesterol levels from 138\u2009\ub1\u200932\u2009mg/dl to 46\u2009\ub1\u200916\u2009mg/dl ( p\u2009<\u20090.001), with an inter-apheresis level of 114\u2009\ub1\u200926\u2009mg/dl. Lipoprotein(a) was also reduced from a median of 42\u2009mg/dl to 17\u2009mg/dl ( p\u2009<\u20090.01). Upon anti-proprotein convertase subtilisin/kexin type 9 therapy, low-density lipoprotein cholesterol levels were similar to post-apheresis (59\u2009\ub1\u200925, 41\u2009\ub1\u200922 and 42\u2009\ub1\u200921mg/dl at one, three and six months, respectively) as well as those of lipoprotein(a) (18\u2009mg/dl). However, an opposite effect was observed on high-density lipoprotein cholesterol levels: -16.0% from pre- to post-apheresis and +34.0% between pre-apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors. Apheresis significantly reduced high-sensitivity C-reactive protein levels (1.5\u2009\ub1\u20091.2\u2009mg/l pre-apheresis to 0.6\u2009\ub1\u20090.6\u2009mg/l post-apheresis), while no changes were found upon proprotein convertase subtilisin/kexin type 9\u2009mAbs administration. In conclusion, our study demonstrated that, by switching from lipoprotein apheresis to anti-proprotein convertase subtilisin/kexin type 9 therapies, patients reached similar low-density lipoprotein cholesterol and lipoprotein(a) levels, increased those of high-density lipoprotein cholesterol, and showed no changes on high-sensitivity C-reactive protein

Association between helicobacter pylori infection and risk of nonalcoholic fatty liver disease: an updated meta-analysis

Although clinical studies have shown possible links of Helicobacter pylori infection with the development of nonalcoholic fatty liver disease (NAFLD), the results remain controversial. The aim of this meta-analysis is to investigate the association between H. pylori infection and NAFLD. A comprehensive search of relevant studies was performed up to November 2018. Data on H. pylori infection in NAFLD patients and controls were extracted. Odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Twelve studies involving 27 400 NAFLD patients and 60 347 controls were included. The pooled overall OR of H. pylori infection in NAFLD patients compared with controls was 1.36 (95% CI: 1.22–1.53, I2=89.6%, P=0.000). Meta-regression and subgroup analysis showed that the sample size and the case–control ratio may have accounted for some of the heterogeneity. When stratified by publication year, the diagnostic method used for H. pylori, and Newcastle–Ottawa Scale scores, the OR remained significant. However, possible publication bias was observed. Of the 12 studies, six had carried out multivariable analysis after adjusting for potential confounders. The pooled results from these studies still indicated a higher risk of NAFLD in patients infected with H. pylori (OR=1.17, 95% CI: 1.01–1.36, I2=72.4%, P=0.003). There is a 36% increased risk of NAFLD in patients with H. pylori infection. Further studies are warranted to investigate whether eradication of H. pylori is useful in the prevention and treatment of NAFLD

Changes induced by metabolic surgery on the main components of glucose/insulin system in patients with diabetes and obesity

Bariatric surgery is able to induce remission of type 2 diabetes (T2D). Several studies reported an improvement of insulin sensitivity after surgery [1], but data about insulin secretion and insulin clearance are less abundant and somewhat controversial. Aim of our study was to assess the changes of the determinants of glucose regulation, i.e., insulin secretion, insulin sensitivity and insulin clearance in a group of T2D patients with obesity one month and over 1 year after metabolic surgery

Impact of bariatric surgery-induced weight loss on circulating PCSK9 levels in obese patients

Background and aims: To investigate the effect of obesity and bariatric-induced weight loss on circulating levels of proprotein convertase subtilisin/kexin 9 (PCSK9) in severely obese patients. Methods and results: In this non-randomized interventional study, we enrolled 36 severely obese patients (BMI 43.7 +/- 5.6 kg/m2), of which 20 underwent bariatric surgery, and 12 nonobese healthy controls. An oral glucose tolerance test (75-g OGTT) was performed in 31 of these obese patients at baseline (T0) and in 14 patients at 6 months after bariatric surgery (T6) to assess plasma glucose, insulin and PCSK9 levels. Plasma PCSK9 levels were also measured in 18 of these obese patients at T0 during a 2-h hyperinsulinemic-euglycemic clamp (HEC). At T0, PCSK9 levels were higher in obese patients than in controls (274.6 +/- 76.7 ng/mL vs. 201.4 +/- 53.3 ng/mL) and dropped after bariatric surgery (T6; 205.5 +/- 51.7 ng/mL) along with BMI (from 44.1 +/- 5.9 kg/m(2) to 33.1 +/- 5.6 kg/m(2)). At T6, there was also a decrease in plasma glucose (T0 vs. T6: 6.0 +/- 1.8 vs. 5.0 +/- 0.5 mmol/L) and insulin (15.7 +/- 8.3 vs. 5.4 +/- 2.1 mU/L) levels. At T0, plasma PCSK9 levels decreased during OGTT in obese patients, reaching a nadir of 262.0 +/- 61.4 ng/mL at 120 min with a hyperinsulinemic peak of 75.1 +/- 40.0 mU/L, at 60 min. Similarly, at T0 insulin infusion during 2-h HEC acutely reduced plasma PCSK9 levels in obese patients. The aforementioned OGTT-induced changes in plasma PCSK9 levels were not observed neither in nonobese healthy controls nor in obese patients after bariatric-surgery weight loss. Conclusions: These results suggest a pivotal role of adipose tissue and insulin resistance on PCSK9 homeostasis in severely obese patients. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved

Positive Touch Deprivation during the COVID-19 Pandemic: Effects on Anxiety, Stress, and Depression among Italian General Population

Physical distancing due to the COVID-19 Pandemic has limited the opportunities for family members, friends, and significant others to show physical affection (i.e., hugs, kisses, caresses, holding hands) during social interactions. The present study investigated the effects of positive touch and psychological distress in 991 Italian participants (Mage = 34.43, SD = 14.27). Results showed the frequency of hugs with the cohabiting partner significantly decreased the symptoms of depression (β = −1.187, p = 0.018, eβ = 0.30, 95% CI = 0.11–0.82), whereas the frequency of caresses with cohabiting relatives predicted the symptoms of anxiety (β = 0.575, p = 0.034, eβ = 1.78, 95% CI = 1.04–3.03). The frequency of hugs (β = −0.609, p = 0.049, eβ = 0.54, 95% CI = 0.30–1.00), and kisses (β = 0.663, p = 0.045, eβ = 1.94, 95% CI = 1.01–3.71) with non-cohabiting relatives predicted the symptoms of anxiety (χ2 = 1.35, df = 5, p = 0.93). These results suggest the importance of positive touch on psychological well-being in the social context