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1.
Metabolism ; : 156028, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270816

RESUMEN

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.

2.
Int J Mol Sci ; 25(16)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39201548

RESUMEN

The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-ß1 (TGF-ß1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-ß1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-ß1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.


Asunto(s)
Budesonida , Transición Epitelial-Mesenquimal , Fibrosis , Enfermedades Inflamatorias del Intestino , Factor de Crecimiento Transformador beta1 , Humanos , Células CACO-2 , Transición Epitelial-Mesenquimal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Budesonida/farmacología , Adalimumab/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Metilprednisolona/farmacología , Mesalamina/farmacología , Prednisona/farmacología , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Antiinflamatorios/farmacología , Infliximab/farmacología , Infliximab/uso terapéutico , Azatioprina/farmacología , Metotrexato/farmacología , Intestinos/efectos de los fármacos , Intestinos/patología , Diferenciación Celular/efectos de los fármacos
3.
Intest Res ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39129357

RESUMEN

Background/Aims: Patients with diverticular disease (DD) frequently have abnormal bowel movements. However, it is unknown whether the entity of these alterations is associated with the severity of DD. We aimed to assess bowel habits and their relationship with the severity of DD according to Diverticular Inflammation and Complication Assessment (DICA) classification, Combined Overview on Diverticular Assessment (CODA) score, and fecal calprotectin (FC). Methods: An international, multicenter, prospective cohort study was conducted in 43 centers. A 10-point visual analog scale (VAS) was used to assess the severity of constipation and diarrhea. The association of constipation and diarrhea with DICA classification, CODA score, and basal FC was tested using non-parametric tests. Survival methods for censored observations were applied to test the association of constipation and diarrhea with the incidence of acute diverticulitis over a 3-year follow-up. Results: Of 871 patients with DD were included in the study. Of these, 208 (23.9%) and 199 (22.9%) reported a VAS score for constipation and diarrhea at least 3 at baseline, respectively. Higher constipation and diarrhea scores were associated with increasing DICA classification, CODA score and basal FC (P< 0.001). Constipation and diarrhea scores were independently associated with an increased hazard of developing acute diverticulitis (hazard ratio [HR]constipation = 1.15 per 1-VAS point increase, 95% confidence interval [CI], 1.04-1.27; P=0.004; and HRdiarrhea =1.14; 95% CI, 1.03-1.26; P=0.014, respectively). Conclusions: In newly diagnosed patients with DD, higher endoscopic and combined scores of DD severity were associated with higher scores of constipation and diarrhea at baseline. Both constipation and diarrhea were independent prognostic factors of acute diverticulitis.

4.
J Clin Med ; 13(14)2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39064033

RESUMEN

Ustekinumab is a monoclonal antibody approved for the treatment of IBD. This drug has a well-established efficacy; however, patients may not respond or lose response. The availability of other biological therapies prompts the need for comparative data between different agents to suggest first- or second-line strategies. Aim of this review is to compare the effectiveness of ustekinumab to other biologics in Crohn's disease and ulcerative colitis, as well as report the available data on dose escalation and reinduction. A systematic electronic search of the English literature was performed up to November 2023, using Medline (PubMed), Web of Science, Scopus and the Cochrane Library. Conference proceedings were also screened. Out of 659 citations, 80 relevant articles were selected and included in the present narrative review. Head-to-head comparisons of different biological drugs are relatively scarce, mostly deriving from indirect comparison or retrospective studies. Overall available data indicate similar effectiveness in the treatment of IBD patients. Dose escalation and reinduction strategies are well documented, but the optimal treatment schedule is still to be defined. Response and remission rates vary in different studies, and a proportion of patients fail to achieve clinical and endoscopic outcomes. However, both approaches are effective and safe in nonresponders and secondary loss of response. IBD patients may benefit from dose escalation or reinduction. Both strategies prove effective in regaining response in a proportion of patients, avoiding unnecessary early switch. Head-to-head trials are still needed to determine the exact placement of this drug compared to other biologics.

5.
Vaccines (Basel) ; 12(5)2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38793802

RESUMEN

BACKGROUND: Immunomodulating therapies, which are commonly used in patients with Crohn's disease (CD) and ulcerative colitis (UC), have been linked to an increased risk of contracting opportunistic infectious diseases, the majority of which are preventable through vaccination. Nonetheless, vaccination rates in these patients are suboptimal, and frequently lower than in the general population. The COVID-19 immunization schedule provided a new scenario for investigating vaccine acceptance in patients with inflammatory bowel disease (IBD), with uncertainty and concerns emerging and the number of subjects receiving the third and fourth doses of the vaccine gradually decreasing. This study investigated IBD patients' attitudes towards previous COVID-19 vaccine programs and identified the factors that influence their adherence. It considered demographic and disease-related factors as well as the role of gastroenterologists and primary care physicians (PCPs). METHODS: Data were collected through a self-completed questionnaire administered to all adult IBD patients (age > 18) who visited the Gastroenterology, Hepatology, and Nutrition division at the University of L'Aquila (Italy) for a regular follow-up between November 2021 and December 2022. Non-IBD gastroenterological outpatients who visited during the same period were included as a control group. RESULTS: A total of 178 patients were included in the analysis. The IBD group consisted of 77 patients, 48.1% with CD and 51.9% with UC; the mean age was 49.5 years and 51.9% were female. Overall, 94.8% of IBD patients had undergone at least one vaccine dose and 79.2% had received two doses, versus 8% of the control group (p < 0.0001). A total of 84.4% of IBD patients reported their propensity towards COVID-19 vaccination, with an average agreement score significantly higher than the controls (p = 0.0044). The trust of IBD patients in the effectiveness of the COVID-19 vaccine (p < 0.0001) and its role in hastening pandemic resolution (p < 0.0001) is strongly related to motivation and propensity. Concerns about the safety of the COVID-19 vaccine in IBD (p = 0.0202) and fear of vaccine-induced flare-ups (p = 0.0192) were reported as the main barriers. No correlation was found between COVID-19 vaccine propensity and clinical features like the type of IBD, years of disease, activity, and ongoing treatment. Regarding the recommendations received from physicians to get vaccinated against COVID-19, IBD patients relied heavily on their gastroenterologists for advice, while the control group relied mainly on their PCPs. CONCLUSIONS: The overall positive attitude towards vaccinations reported in our study was better than that observed for other vaccines. The relationship of trust with the gastroenterologist should be used to boost vaccination against other preventable diseases in IBD patients. Our findings add information on the factors influencing vaccine propensity, which can be used to improve current vaccination strategies.

7.
J Clin Apher ; 38(6): 746-754, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37787399

RESUMEN

Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.


Asunto(s)
Biosimilares Farmacéuticos , Colitis Ulcerosa , Humanos , Anciano , Colitis Ulcerosa/terapia , Biosimilares Farmacéuticos/uso terapéutico , Citaféresis , Corticoesteroides/uso terapéutico , Inducción de Remisión , Factor de Necrosis Tumoral alfa , Resultado del Tratamiento , Granulocitos , Monocitos
8.
Medicina (Kaunas) ; 59(10)2023 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-37893427

RESUMEN

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.


Asunto(s)
COVID-19 , Enfermedades Gastrointestinales , Hepatopatías , Humanos , SARS-CoV-2 , Tracto Gastrointestinal , Enfermedades Gastrointestinales/epidemiología
9.
Nutrients ; 15(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37686856

RESUMEN

During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Desnutrición , Hipernutrición , Adulto , Humanos , Estado Nutricional , Calidad de Vida , Progresión de la Enfermedad , Micronutrientes
10.
Rev Endocr Metab Disord ; 24(6): 1011-1029, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37665480

RESUMEN

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Deficiencia de Vitamina D , Humanos , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/etiología , Suplementos Dietéticos , Vitaminas/uso terapéutico
11.
Int J Mol Sci ; 24(16)2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37628981

RESUMEN

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.


Asunto(s)
Enfermedad Celíaca , Humanos , Enfermedad Celíaca/terapia , Atención Odontológica , Glútenes , Dieta Sin Gluten , Predisposición Genética a la Enfermedad
12.
United European Gastroenterol J ; 11(7): 642-653, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37550901

RESUMEN

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) classification and the Combined Overview on Diverticular Assessment (CODA) were found to be effective in predicting the outcomes of Diverticular Disease (DD). We ascertain whether fecal calprotectin (FC) can further aid in improving risk stratification. METHODS: A three-year international, multicentre, prospective cohort study was conducted involving 43 Gastroenterology and Endoscopy centres. Survival methods for censored observations were used to estimate the risk of acute diverticulitis (AD) in newly diagnosed DD patients according to basal FC, DICA, and CODA. The net benefit of management strategies based on DICA, CODA and FC in addition to CODA was assessed with decision curve analysis, which incorporates the harms and benefits of using a prognostic model for clinical decisions. RESULTS: At the first diagnosis of diverticulosis/DD, 871 participants underwent FC measurement. FC was associated with the risk of AD at 3 years (HR per each base 10 logarithm increase: 3.29; 95% confidence interval, 2.13-5.10) and showed moderate discrimination (c-statistic: 0.685; 0.614-0.756). DICA and CODA were more accurate predictors of AD than FC. However, FC showed high discrimination capacity to predict AD at 3 months, which was not maintained at longer follow-up times. The decision curve analysis comparing the combination of FC and CODA with CODA alone did not clearly indicate a larger net benefit of one strategy over the other. CONCLUSIONS: FC measurement could be used as a complementary tool to assess the immediate risk of AD. In all other cases, treatment strategies based on the CODA score alone should be recommended.


Asunto(s)
Enfermedades Diverticulares , Diverticulosis del Colon , Divertículo , Humanos , Diverticulosis del Colon/diagnóstico , Diverticulosis del Colon/terapia , Diverticulosis del Colon/complicaciones , Colonoscopía , Complejo de Antígeno L1 de Leucocito , Estudios Prospectivos , Enfermedades Diverticulares/complicaciones , Enfermedades Diverticulares/diagnóstico , Enfermedades Diverticulares/terapia , Divertículo/complicaciones , Inflamación/diagnóstico , Inflamación/complicaciones
13.
Am J Gastroenterol ; 118(11): 2088-2092, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37314163

RESUMEN

INTRODUCTION: We assessed the prevalence and clinical outcomes of segmental colitis associated with diverticulosis (SCAD) in patients with newly diagnosed diverticulosis. METHODS: A 3-year international, multicenter, prospective cohort study was conducted involving 2,215 patients. RESULTS: SCAD diagnosis was posed in 44 patients (30 male patients; median age: 64.5 years; prevalence of 1.99%, 95% confidence interval, 1.45%-2.66%). Patients with SCAD types D and B showed worse symptoms, higher fecal calprotectin values, needed more steroids, and reached less likely complete remission. DISCUSSION: Although SCAD generally had a benign outcome, types B and D were associated with more severe symptoms and worse clinical course.


Asunto(s)
Colitis , Divertículo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Resultado del Tratamiento , Colitis/complicaciones , Colitis/epidemiología , Colitis/diagnóstico , Divertículo/complicaciones
14.
J Clin Med ; 12(9)2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37176570

RESUMEN

About 50% of Crohn's Disease (CD) patients undergo an intestinal resection during their lifetime. Although the patients experience a fairly long period of well-being after the intestinal resection, they presented a postoperative recurrence (POR) in 40% of cases within 5 years. In this case series, we aimed to evaluate the incidence of POR in CD patients with high risk for early POR, prophylactically treated with Vedolizumab. All consecutive CD patients (followed from 2017 to 2020) who underwent ileocolonic resection after the loss of response at anti-Tumor Necrosis Factor α (anti-TNFα) and with one or more risk factors for early POR were included. POR was defined as a Rutgeerts score (Ri) > 1 at the colonoscopic evaluation. All the included patients underwent a Magnetic resonance enterography (MRE) at least one year after the surgical resection. Six patients (4 Female; 2 Males) were included. At the first endoscopic evaluation, all patients were in endoscopic remission (5 patients Ri 0; 1 patient Ri 1). No stenosis nor other intestinal wall changes or complications were observed at MRE. Five patients underwent colonoscopy over two years of follow-up (median: 32 months; range 25-33). The Ri score was 0 in four patients, while the fifth patient showed severe endoscopic relapse. The same patient presented a clinical relapse (Harvey-Bradshaw index = 10) with a flare of disease in the colonic mucosa. These data suggest that early post-operative treatment with Vedolizumab could be a valuable strategy to be submitted to a prospective controlled trial for preventing POR.

15.
Int J Mol Sci ; 24(9)2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-37175841

RESUMEN

Hypoxia-inducible factor-1α (HIF-1α), a central player in maintaining gut-microbiota homeostasis, plays a pivotal role in inducing adaptive mechanisms to hypoxia and is negatively regulated by prolyl hydroxylase 2 (PHD2). HIF-1α is stabilized through PI3K/AKT signaling regardless of oxygen levels. Considering the crucial role of the HIF pathway in intestinal mucosal physiology and its relationships with gut microbiota, this study aimed to evaluate the ability of the lysate from the multi-strain probiotic formulation SLAB51 to affect the HIF pathway in a model of in vitro human intestinal epithelium (intestinal epithelial cells, IECs) and to protect from lipopolysaccharide (LPS) challenge. The exposure of IECs to SLAB51 lysate under normoxic conditions led to a dose-dependent increase in HIF-1α protein levels, which was associated with higher glycolytic metabolism and L-lactate production. Probiotic lysate significantly reduced PHD2 levels and HIF-1α hydroxylation, thus leading to HIF-1α stabilization. The ability of SLAB51 lysate to increase HIF-1α levels was also associated with the activation of the PI3K/AKT pathway and with the inhibition of NF-κB, nitric oxide synthase 2 (NOS2), and IL-1ß increase elicited by LPS treatment. Our results suggest that the probiotic treatment, by stabilizing HIF-1α, can protect from an LPS-induced inflammatory response through a mechanism involving PI3K/AKT signaling.


Asunto(s)
Lipopolisacáridos , Proteínas Proto-Oncogénicas c-akt , Humanos , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células CACO-2 , Fosfatidilinositol 3-Quinasas/metabolismo , Hipoxia/metabolismo , Células Epiteliales/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo
16.
Int J Mol Sci ; 24(10)2023 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-37240299

RESUMEN

Intestinal fibrosis, the most common complication of inflammatory bowel disease (IBD), is characterized by an uncontrolled deposition of extracellular matrix proteins leading to complications resolvable only with surgery. Transforming growth factor is the key player in the epithelial-mesenchymal transition (EMT) and fibrogenesis process, and some molecules modulating its activity, including peroxisome proliferator-activated receptor (PPAR)-γ and its agonists, exert a promising antifibrotic action. The purpose of this study is to evaluate the contribution of signaling other than EMT, such as the AGE/RAGE (advanced glycation end products/receptor of AGEs) and the senescence pathways, in the etiopathogenesis of IBD. We used human biopsies from control and IBD patients, and we used a mouse model of colitis induced by dextran-sodium-sulfate (DSS), without/with treatments with GED (PPAR-gamma-agonist), or 5-aminosalicylic acid (5-ASA), a reference drug for IBD treatment. In patients, we found an increase in EMT markers, AGE/RAGE, and senescence signaling activation compared to controls. Consistently, we found the overexpression of the same pathways in DSS-treated mice. Surprisingly, the GED reduced all the pro-fibrotic pathways, in some circumstances more efficiently than 5-ASA. Results suggest that IBD patients could benefit from a combined pharmacological treatment targeting simultaneously different pathways involved in pro-fibrotic signals. In this scenario, PPAR-gamma activation could be a suitable strategy to alleviate the signs and symptoms of IBD and also its progression.


Asunto(s)
Colitis , Enfermedades Inflamatorias del Intestino , Humanos , Ratones , Animales , PPAR gamma/metabolismo , Transición Epitelial-Mesenquimal , Colon/patología , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Epitelio/metabolismo , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL
17.
J Diabetes Res ; 2023: 9516059, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37096234

RESUMEN

Optical coherence tomography angiography (OCTA) is an innovative and reliable technique detecting the early preclinical retinal vascular change in patients with diabetes. We have designed our study to evaluate whether an independent relationship exists between continuous glucose monitoring (CGM)-derived glucose metrics and OCTA parameters in young adult patients with type 1 diabetes without diabetic retinopathy (DR). Inclusion criteria were age ≥ 18 years, diagnosis of type 1 diabetes from ≥ 1 year, stable insulin treatment in the last three months, use of real-time CGM, and CGM wear time ≥ 70%. Each patient underwent dilated slit lamp fundus biomicroscopy to exclude the presence of DR. A skilled operator performed OCTA scans in the morning to avoid possible diurnal variation. CGM-derived glucose metrics from the last 2 weeks were collected through the dedicated software during OCTA. Forty-nine patients with type 1 diabetes (age 29 [18; 39] years, HbA1c 7.7 ± 1.0%) and 34 control subjects participated in the study. Vessel density (VD) of the whole image and parafoveal retina in the superficial (SCP) and deep capillary plexus (DCP) was significantly lower in patients with type 1 diabetes compared to controls. The coefficient of variation of average daily glucose, evaluated by CGM, significantly correlated with foveal and parafoveal VD in SCP and with foveal VD in DCP. High glucose variability might be responsible for the early increase of VD in these areas. Prospective studies may help understand if this pattern precedes DR. The difference we detected between patients with and without diabetes confirms that OCTA is a reliable tool for detecting early retinal abnormalities.


Asunto(s)
Diabetes Mellitus Tipo 1 , Retinopatía Diabética , Adulto Joven , Humanos , Adolescente , Adulto , Diabetes Mellitus Tipo 1/diagnóstico , Retinopatía Diabética/diagnóstico , Angiografía con Fluoresceína/métodos , Vasos Retinianos , Estudios Prospectivos , Benchmarking , Automonitorización de la Glucosa Sanguínea , Glucemia , Tomografía de Coherencia Óptica/métodos
18.
Rev Endocr Metab Disord ; 24(2): 121-138, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36813995

RESUMEN

This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.


Asunto(s)
Fracturas Óseas , Deficiencia de Vitamina D , Humanos , Vitamina D/fisiología , Deficiencia de Vitamina D/epidemiología , Fracturas Óseas/tratamiento farmacológico , Huesos , Progresión de la Enfermedad
20.
Dig Liver Dis ; 55(6): 743-750, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36567177

RESUMEN

BACKGROUND: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD). AIMS: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD. METHODS: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted. RESULTS: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay. CONCLUSION: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented.


Asunto(s)
Enfermedad Celíaca , Humanos , Adulto , Persona de Mediana Edad , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/epidemiología , Diagnóstico Tardío , Estudios Retrospectivos , Italia/epidemiología , Oportunidad Relativa
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