RESUMO
INTRODUCTION: The aim of these evidence-based guidelines is to present a consensus position from members of the Italian Unitary Society of Colon-Proctology (SIUCP: Società Italiana Unitaria di Colon-Proctologia) on the diagnosis and management of anal fissure, with the purpose to guide every physician in the choice of the best treatment option, according with the available literature. METHODS: A panel of experts was designed and charged by the Board of the SIUCP to develop key-questions on the main topics covering the management of anal fissure and to performe an accurate search on each topic in different databanks, in order to provide evidence-based answers to the questions and to summarize them in statements. All the clinical questions were discussed by the expert panel in different rounds through the Delphi approach and, for each statement, a consensus among the experts was reached. The questions were created according to the PICO criteria, and the statements developed adopting the GRADE methodology. CONCLUSIONS: In patients with acute anal fissure the medical therapy with dietary and behavioral norms is indicated. In the chronic phase of disease, the conservative treatment with topical 0.3% nifedipine plus 1.5% lidocaine or nitrates may represent the first-line therapy, eventually associated with ointments with film-forming, anti-inflammatory and healing properties such as Propionibacterium extract gel. In case of first-line treatment failure, the surgical strategy (internal sphincterotomy or fissurectomy with flap), may be guided by the clinical findings, eventually supported by endoanal ultrasound and anal manometry.
Assuntos
Cirurgia Colorretal , Fissura Anal , Humanos , Fissura Anal/diagnóstico , Fissura Anal/cirurgia , Lidocaína/uso terapêutico , Colo , Doença Crônica , Canal Anal/cirurgia , Resultado do TratamentoRESUMO
Male obesity is known to be associated with hypogonadism, which can be reverted after surgical weight reduction. However, the evidence about how rapidly this effect rises after surgery and what consequences each procedure have on prostate function and prostatic-specific antigen (PSA) concentration is scarce. So, we evaluated total testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone and PSA plasma levels in a group of 29 Caucasian obese men (BMI - 43.4 ± 8.5 kg/m2) before and one month after sleeve gastrectomy. 19 lean healthy male subjects were considered as controls. As expected, obese patients showed a high prevalence of hypogonadism (51.6%) at baseline, with reduced total testosterone compared to lean controls (10.8 ± 3.5 vs 15.7 ± 4.2 nmol/l, p < .01), higher estradiol (124.4 ± 46.5 vs 78.7 ± 39.6 pmol/l, p < .01), lower luteinizing hormone and follicle stimulating hormone (3.6 ± 1.3 and 2.5 ± 0.9 vs 5.2 ± 2.4 and 5.9 ± 3.8 U/L, respectively, p < .05) plasma levels. One month after surgery, patients showed a significant body weight reduction (-17.2 ± 6.7 kg) with increased total testosterone (from 10.8 ± 3.5 to 18.9 ± 4.9 nmol/l, p < .001), reduced estradiol (from 124.4 ± 46.5 to 96.1 ± 34.3 pmol/l, p < .05) and increased PSA (from 0.74 ± 0.38 to 1.0 ± 0.51 µg/l, p < .001). These results confirm that hypogonadism is highly prevalent in obese males, but they also show that it can be early reversed after sleeve gastrectomy, further confirming the strong indication to surgery of hypogonadal patients with severely reduced quality of life. Higher testosterone levels may be responsible for the increase of PSA observed after surgery; however, PSA concentration has to be monitored over time to avoid underrating of potential severe prostate diseases.
Assuntos
Hipogonadismo , Obesidade Mórbida , Gastrectomia , Humanos , Masculino , Obesidade Mórbida/cirurgia , Antígeno Prostático Específico , Qualidade de Vida , Testosterona , Redução de PesoRESUMO
Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Tocotrienóis/química , Tocotrienóis/farmacologia , Animais , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Suplementos Nutricionais , Humanos , Estresse Oxidativo/efeitos dos fármacos , Tocoferóis/química , Tocoferóis/farmacologia , Vitamina E/administração & dosagemRESUMO
OBJECTIVE: Multiple studies investigated preclinical markers of peripheral vascular damage in acromegaly (ACRO) reporting discordant results. The aim of this study was to run a meta-analysis to examine whether intima media thickness (IMT), flow mediated dilation (FMD) and arterial pulse wave velocity (PWV) are affected in acromegalic patients and to assess the impact of effective treatment of growth hormone excess on these outcomes. STUDY SELECTION: Twenty-seven studies comparing ACRO vs control (CON) populations and active (ACT) vs inactive (INACT) ACRO were included in the meta-analysis. DATA SYNTHESIS: ACRO compared to CON have higher IMT (ES = 0.83, 95% C.I. 0.35-1.30), p = 0.001, impaired FMD (ES = - 1.59, 95% C.I. - 2.33 to - 0.85, p < 0.0001) and higher PWV (ES = 0.76 95% C.I. 0.37-1.16, p = 0.0001). When patients with ACT vs INACT disease were considered IMT was higher (ES = 0.43, 95% C.I. 0.02-0.84, p = 0.041) and FMD was impaired (ES = - 0.66, 95% C.I. - 1.28 to 0.04, p = 0.038) in ACT patients. Meta-regression analysis of studies comparing IMT in ACT vs INACT acromegalic patients showed a significant and inverse association between the effect size and the percent of hypertensive (p = 0.025) and diabetic (p = 0.041) patients. CONCLUSIONS: IMT, FMD and arterial stiffness are impaired in acromegaly showing that these patients may be at increased risk of atherosclerosis. In patients with active disease these preclinical markers of atherosclerosis are worse compared to patients with inactive disease but the role of diabetes and hypertension is prevailing on growth hormone excess.
Assuntos
Acromegalia/metabolismo , Aterosclerose/metabolismo , Biomarcadores/metabolismo , HumanosRESUMO
Introduction: Eating Disorders (EDs) affect individuals globally and are associated with significant physical and mental health challenges. However, access to adequate treatment is often hindered by societal stigma, limited awareness, and resource constraints. Methods: The project aims to utilize the power of Artificial Intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), to improve EDs diagnosis and treatment. The Master Data Plan (MDP) will collect and analyze data from diverse sources, utilize AI algorithms for risk factor identificat io n, treatment planning, and relapse prediction, and provide a patient-facing chatbot for information and support. This platform will integrate patient data, support healthcare professionals, and empower patients, thereby enhancing care accessibility, personalizing treatment plans, and optimizing care pathways. Robust data governance measures will ensure ethical and secure data management. Results: Anticipated outcomes include enhanced care accessibility and efficiency, personalized treatment plans leading to improved patient outcomes, reduced waiting lists, heightened patient engagement, and increased awareness of EDs with improved resource allocation. Discussion: This project signifies a pivotal shift towards data-driven, patient-centered ED care in Italy. By integrat ing AI and promoting collaboration, it seeks to redefine mental healthcare standards and foster better well- being among individuals with EDs.
RESUMO
Background: Major Depressive Disorder (MDD) is a prevalent mental health condition characterized by persistent low mood, cognitive and physical symptoms, anhedonia (loss of interest in activities), and suicidal ideation. The World Health Organization (WHO) predicts depression will become the leading cause of disability by 2030. While biological markers remain essential for understanding MDD's pathophysiology, recent advancements in social signal processing and environmental monitoring hold promise. Wearable technologies, including smartwatches and air purifiers with environmental sensors, can generate valuable digital biomarkers for depression assessment in real-world settings. Integrating these with existing physical, psychopathological, and other indices (autoimmune, inflammatory, neuroradiological) has the potential to improve MDD recurrence prevention strategies. Methods: This prospective, randomized, interventional, and non-pharmacological integrated study aims to evaluate digital and environmental biomarkers in adolescents and young adults diagnosed with MDD who are currently taking medication. The study implements a sensor-integrated platform built around an open-source "Pothos" air purifier system. This platform is designed for scalability and integration with third-party devices. It accomplishes this through software interfaces, a dedicated app, sensor signal pre-processing, and an embedded deep learning AI system. The study will enroll two experimental groups (10 adolescents and 30 young adults each). Within each group, participants will be randomly allocated to Group A or Group B. Only Group B will receive the technological equipment (Pothos system and smartwatch) for collecting digital biomarkers. Blood and saliva samples will be collected at baseline (T0) and endpoint (T1) to assess inflammatory markers and cortisol levels. Results: Following initial age-based stratification, the sample will undergo detailed classification at the 6-month follow-up based on remission status. Digital and environmental biomarker data will be analyzed to explore intricate relationships between these markers, depression symptoms, disease progression, and early signs of illness. Conclusion: This study seeks to validate an AI tool for enhancing early MDD clinical management, implement an AI solution for continuous data processing, and establish an AI infrastructure for managing healthcare Big Data. Integrating innovative psychophysical assessment tools into clinical practice holds significant promise for improving diagnostic accuracy and developing more specific digital devices for comprehensive mental health evaluation.
RESUMO
Introduction: Depression is the leading cause of worldwide disability, until now only 3% of patients with major depressive disorder (MDD) experiences full recovery or remission. Different studies have tried to better understand MDD pathophysiology and its resistant forms (TRD), focusing on the identification of candidate biomarkers that would be able to reflect the patients' state and the effects of therapy. Development of digital technologies can generate useful digital biomarkers in a real-world setting. This review aims to focus on the use of digital technologies measuring symptom severity and predicting treatment outcomes for individuals with mood disorders. Methods: Two databases (PubMed and APA PsycINFO) were searched to retrieve papers published from January 1, 2013, to July 30, 2023, on the use of digital devices in persons with MDD. All papers had to meet specific inclusion criteria, which resulted in the inclusion of 12 articles. Results: Research on digital biomarkers confronts four core aspects: (I) predicting diagnostic status, (II) assessing symptom severity and progression, (III) identifying treatment response and (IV) monitoring real-word and ecological validity. Different wearable technologies have been applied to collect physiological, activity/sleep, or subjective data to explore their relationships with depression. Discussion: Depression's stable rates and high relapse risk necessitate innovative approaches. Wearable devices hold promise for continuous monitoring and data collection in real world setting. Conclusion: More studies are needed to translate these digital biomarkers into actionable interventions to improve depression diagnosis, monitoring and management. Future challenges will be the applications of wearable devices routinely in personalized medicine.
RESUMO
BACKGROUND: Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia, and alterations of glucose metabolism that often lead to the development of type 2 diabetes at a young age. OBJECTIVE: To study the relationship between weight and metabolism in a group of ALMS patients and matched controls. RESEARCH DESIGN AND METHODS: Fifteen ALMS patients (eight males, seven females; aged 3-51) were compared in a cross-sectional study with an age- and weight-matched control population. Anthropometric parameters, fat mass, glucose and insulin secretion in basal and dynamic oral glucose tolerance test (OGTT) conditions were measured. Furthermore, anthropometric and body composition data were obtained from an international group of 27 ALMS patients (13 males, 14 females, age range: 4-29 yr). RESULTS: In ALMS we observed an inverse correlation between age and standard deviation scores for height, weight, and body mass index. The OGTT glycemic curves of ALMS subjects were similar to those of age-matched controls, whereas insulin response was clearly greater. In ALMS individuals the insulin response showed a reduction with age. We documented pathologic values of the derived indices homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index, HOMA%ß-cell and insulinogenic index in ALMS, but unlike the insulin-resistance indices, the ß-cell function indices showed a significant reduction with age. CONCLUSIONS: In ALMS the progression from the early onset obesity toward the impaired fasting glucose or impaired glucose tolerance and overt diabetes is mostly because of a progressive failure of ß-cell insulin secretion without any further worsening of insulin resistance with age, even in the presence of weight reduction.
Assuntos
Síndrome de Alstrom/complicações , Diabetes Mellitus Tipo 2/etiologia , Obesidade/complicações , Adolescente , Adulto , Síndrome de Alstrom/epidemiologia , Composição Corporal/genética , Composição Corporal/fisiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Adulto JovemRESUMO
In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show mtDNA depletion, but only after several culturing passages, or in a serumless culturing medium. In spite of severe mtDNA depletion, only moderate decrease in respiratory chain enzymatic activities, and mild cytoarchitectural alterations, were observed in the Mpv17(-/-) livers, but neither cirrhosis nor failure ever occurred in this organ at any age. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensate the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf1, a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear and kidney. The coat of the Mpv17(-/-) mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter lifespan. Coincidental with the onset of FSGS, there was hardly any mtDNA left in the glomerular tufts. These results demonstrate that Mpv17 controls mtDNA copy number by a highly tissue- and possibly cytotype-specific mechanism.
Assuntos
DNA Mitocondrial/metabolismo , Glomerulosclerose Segmentar e Focal/metabolismo , Fígado/metabolismo , Proteínas de Membrana/genética , Proteinúria/metabolismo , Idade de Início , Animais , Células Cultivadas , DNA Mitocondrial/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomerulosclerose Segmentar e Focal/genética , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Especificidade de Órgãos , Proteinúria/epidemiologia , Proteinúria/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcrição GênicaRESUMO
Background: The COVID-19 pandemic severely strained the already unprepared Italian healthcare system. This had repercussions on healthcare workers, stemming, in particular, from a lack of clear guidelines, adequate protective equipment, and professional preparedness. Such conditions were especially prevalent in Northern Italy. Objectives: This study aimed to examine COVID-19-related professional and psychoemotional stress among nurses and doctors in two hospitals in Northern Italy, along with the worst critical incidents affecting healthcare personnel. A parallel objective was to elicit healthcare professionals' opinions about what changes are needed in the healthcare system's operations, as well as about the relational/emotional skills that are needed to better manage relationships with patients in emergency situations. Participants: Snowball sampling was used to recruit participants and yielded 17 hospital professionals: six nurses (five female and one male) and 11 doctors (seven male and four female). Three of these professionals worked in intensive care and the others in different wards. All had close contact with COVID-19 patients. Methods: The study employed a qualitative research design, using in-depth interviews of ~60 min each that were conducted via Skype video calls. The interviews were recorded and transcribed, then analysed. The qualitative analysis employed mixed methods to identify the most relevant and recursive themes from the interviews. Results: Four fundamental themes emerged from our analysis of the interview texts: (1) disorganisation and psychoemotional stress; (2) urgency and critical incidents; (3) everything surreal; and (4) disruptions in empathetic relationships with patients. Conclusions: Through our analysis of the interview narratives, we found that systematic and in-depth psychological training is needed to prepare professionals for (1) altered relationships with patients in emergencies; (2) use of exceptional medical equipment; (3) elaboration of new bioethical models suitable for disasters and pandemics; and (4) engagement with the themes of death and dying.
RESUMO
BACKGROUND: Fixed dose unfractionated or low molecular weight heparin is the recommended treatment for venous thromboembolism (VTE) prevention in hospitalized patients. However, its efficacy has been questioned in obese population. Results of previous studies on weight-adjusted doses of heparin for VTE prevention are contradictory. Different anticoagulant regimens are used in clinical practice, but their role remains to be elucidated. AIMS: To clarify the efficacy and safety of weight-adjusted dose heparin for VTE prevention in obese subjects hospitalized for medical and surgical conditions. METHODS: Twelve studies were identified as reporting VTE occurrence, major or minor bleeding and anti-Xa levels. A random-effect meta-analysis was conducted to derive odds ratios (OR) comparing fixed vs weight adjusted-doses heparins on VTE occurrence, bleeding, anti-Xa levels. Medical and surgical patients, prospective vs retrospective and quality of studies were extracted for moderators and meta-regression analysis. RESULTS: Weight-adjusted dose heparin administration was not associated with reduced VTE occurrence (6320/13317 patients, OR 1.03, 95% C.I. 0.79 to 1.35), nor increased bleeding (5840/10906 patients, OR 0.84, 95% C.I. 0.65 to 1.08), but it was associated with higher anti-Xa levels (284/294 patients, ES 2.04, 95% C.I. 1.16 to 2.92, p<0.0001). A significant heterogeneity was present for comparison of anti-Xa levels (I2=94%, p=0.0001) but not for VTE occurrence or bleeding (I2=7.6% and 12.8% respectivel). None of the moderators explained the heterogeneity of the results among primary studies. CONCLUSION: Weight-adjusted dose as compared to fixed-dose of heparins in the prevention of VTE in obese patients was not associated with a lower risk of VTE nor a higher risk of bleeding.
Assuntos
Heparina , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Heparina de Baixo Peso Molecular , Humanos , Obesidade/complicações , Estudos Prospectivos , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controleRESUMO
CONTEXT: Melanocortin receptor-4 (MC4R) gene mutations are associated with early-onset severe obesity, and the identification of potential pathological variants is crucial for the clinical management of patients with obesity. OBJECTIVE: To explore whether and how a novel heterozygous MC4R variant (MC4R-F313Sfs*29), identified in a young boy (body mass index [BMI] 38.8 kg/m2) during a mutation analysis conducted in a cohort of patients with obesity, plays a determinant pathophysiological role in the obesity development. DESIGN SETTING AND PATIENTS: The genetic screening was carried out in a total of 209 unrelated patients with obesity (BMIâ¯≥â¯35â¯kg/m2). Structural and functional characterization of the F313Sfs*29-mutated MC4R was performed using computational approaches and in vitro, using HEK293 cells transfected with genetically encoded biosensors for cAMP and Ca2+. RESULTS: The F313Sfs*29 was the only variant identified. In vitro experiments showed that HEK293 cells transfected with the mutated form of MC4R did not increase intracellular cAMP or Ca2+ levels after stimulation with a specific agonist in comparison with HEK293 cells transfected with the wild type form of MC4R (∆R/R0â =â -90% ± 8%; Pâ <â 0.001). In silico modeling showed that the F313Sfs*29 mutation causes a major reorganization in the cytosolic domain of MC4R, thus reducing the affinity of the putative GalphaS binding site. CONCLUSIONS: The newly discovered F313Sfs*29 variant of MC4R may be involved in the impairment of α-MSH-induced cAMP and Ca2+ signaling, blunting intracellular G protein-mediated signal transduction. This alteration might have led to the dysregulation of satiety signaling, resulting in hyperphagia and early onset of obesity.
Assuntos
Obesidade Mórbida/genética , Receptor Tipo 4 de Melanocortina/genética , Adolescente , Adulto , Idade de Início , Criança , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Gráficos de Crescimento , Células HEK293 , Humanos , Itália/epidemiologia , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Obesidade Mórbida/epidemiologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/genética , Receptor Tipo 4 de Melanocortina/químicaRESUMO
BACKGROUND AND OBJECTIVE: Laparoscopic treatment of incisional hernias can be performed using different types of fixation devices and prosthesis. We present a case series of 19 patients with incisional hernias with a diameter of < 6 cm, who underwent laparoscopic repair using Hi-tex dual-side mesh, positioned intraperitoneally, fixed to the abdominal wall by fibrin glue (Tissucol). METHODS: Nineteen patients with incisional hernias < 6 cm in diameter were enrolled in this study and treated laparoscopically with Hi-tex and Tissucol. Surgical complications and patient outcomes were assessed with a clinical follow-up. RESULTS: Laparoscopic repair of incisional hernias by using Hi-tex mesh affixed to the parietal wall with fibrin glue was feasible and easy in patients with parietal defects < 6 cm in diameter. Mean operating time was 30 minutes. Mean hospital stay was 1.5 days. Almost no postoperative pain, major surgical complications, seroma formation, relapses, or prosthesis infection occurred during a mean follow-up of 20 months. CONCLUSIONS: In select patients, Hi-tex mesh affixed using fibrin glue allows laparoscopic repair of incisional hernias with very good patient outcomes, especially in terms of postoperative pain and seroma formation.
Assuntos
Adesivo Tecidual de Fibrina/uso terapêutico , Hérnia Abdominal/cirurgia , Laparoscopia/métodos , Adesivos Teciduais/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/epidemiologiaRESUMO
PURPOSE: Treatment of rectocele associated with prolapsed hemorrhoids is a debated topic. Transanal stapling achieved good midterm results in patients with symptoms of obstructed defecation, nevertheless a number of severe complications have been reported. The aim of this study was to evaluate the safety and efficacy of a new endorectal manual technique in patients with obstructed defecation due to the combination of muco-hemorrhoidal prolapse and rectocele. METHODS: Patients enrolled after preoperative obstructed defecation syndrome (ODS) score, defecography and anoscopy were submitted to the novel Mucopexy-Recto Anal Lifting (MuRAL) combined with a modified Block procedure, and followed up by independent observers with digital exploration 3 weeks postoperatively, and digital exploration plus anoscopy at 3, 6, and 12 months. Operative time, hospital stay, numerating rating scale (NRS), ODS, satisfaction scores, and recurrence rate were recorded. RESULTS: Mean operative time was 35.7 minutes. Fifty-six patients completed 1-year follow-up: 7.1% had acute urinary retention, NRS score was < 3 from the third postoperative day, mean time of daily activity resumption was 12 days, none had persistent fecal urgency, 82% declared excellent/good satisfaction score, significant improvement of 6- and 12-month ODS score, no recurrence of rectocele, and 7.1% recurrence of prolapsed hemorrhoids were observed. CONCLUSION: MuRAL associated with modified Block technique gave no severe complications and resulted in a safe and effective approach to symptomatic rectocele associated with muco-rectal prolapse. Further randomized studies, larger series, and longer follow-up are needed.
RESUMO
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and its prevalence is reaching epidemic characteristics both in adults and in children. The increase of NAFLD prevalence parallels that of obesity, now representing the major cause of liver inflammation, increasing the risk of cirrhosis and hepatocarcinoma. Furthermore, NAFLD is a risk factor for cardiovascular diseases and type 2 diabetes, two of the major leading causes of morbidity and mortality in western countries. Thus a significant amount of studies have dealt with the evaluation of the possible molecular mechanisms leading to NAFLD and its inflammatory consequences within the liver, the non-alcoholic steatohepatitis, and cirrhosis. The inflammasome is a key player in the inflammation and fibrogenic responses in many different tissues, including the liver. The activation of the NLRP3 inflammasome requires the activation by extracellular adenosine tri-phosphate (ATP) of a specific purinergic receptor named P2X7 located in the target cells, although other pathways have been described. To this regard, extracellular ATP acts as an internal danger signal coming from damaged cells participating in the activation of the inflammatory process, a signaling pathway common to many different tissues. Here, we briefly review the involvement of the P2X7 receptor/inflammasome NLRP3 axis in the pathophysiological events leading to NAFLD and its inflammatory and fibrotic evolutions, reporting the possible therapeutical strategies targeting the P2X7 receptor/NLRP3 inflammasome.
Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Transdução de Sinais , Trifosfato de Adenosina/metabolismo , Humanos , Inflamação/patologiaRESUMO
BACKGROUND: The aim of this study was to perform a meta-analysis on the effect of weight loss obtained by bariatric surgery or behavioral intervention on migraine frequency and indices of severity. MATERIALS AND METHODS: A search through Pubmed/Medline, ISI-web of knowledge, and Google Scholar retrieved 10 studies (n = 473). Selected outcomes were Headache Frequency, Pain Severity, Disability, and Attack Duration while BMI, BMI change, type of intervention (bariatric vs. behavioral), and type of population (adult vs. pediatric) were used for moderators and meta-regression analysis. RESULTS: Random effect meta-analysis shows that weight loss yields significant reductions in Headache Frequency (ES - 0.78, p < 0.0001), Pain Severity (ES - 1.04, p < 0.0001), Disability (ES -0.68, p < 0.0001), and Attack Duration (ES - 0.25, p = 0.017). Improvement in migraine was not correlated either to the degree of obesity at baseline or the degree of weight reduction. The effect on migraine was similar when weight reduction was obtained with bariatric surgery or behavioral intervention and was comparable in adult and pediatric populations. CONCLUSIONS: Weight loss improves characteristics of migraine headache in patients who have obesity independently of the type of intervention and the amount of weight loss. The mechanisms underlying the link between obesity, weight loss, and migraine headache may include chronic inflammation, obesity comorbidities, and overlapping behavioral and psychological risk factors.
Assuntos
Cirurgia Bariátrica , Transtornos de Enxaqueca , Obesidade Mórbida , Adulto , Criança , Humanos , Obesidade , Obesidade Mórbida/cirurgia , Redução de PesoRESUMO
BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway collapse requiring nocturnal ventilatory assistance. Multiple studies have investigated the relationship between acromegaly and OSA, reporting discordant results. AIM: To conduct a meta-analysis on the risk for OSA in acromegaly, and in particular to assess the role of disease activity and the effect of treatments. METHODS AND STUDY SELECTION: A search through literature databases retrieved 21 articles for a total of 24 studies (n = 734). Selected outcomes were OSA prevalence and apnea-hypopnea index (AHI) in studies comparing acromegalic patients with active (ACT) vs inactive (INACT) disease and pretreatment and posttreatment measures. Factors used for moderator and meta-regression analysis included the percentage of patients with severe OSA, patient sex, age, body mass index, levels of insulin-like growth factor 1, disease duration and follow-up, and therapy. RESULTS: OSA prevalence was similar in patients with acromegaly who had ACT and INACT disease (ES = -0.16; 95% CI, -0.47 to 0.15; number of studies [k] = 10; P = 0.32). In addition, AHI was similar in ACT and INACT acromegaly patients (ES = -0.03; 95% CI, -0.49 to 0.43; k = 6; P = 0.89). When AHI was compared before and after treatment in patients with acromegaly (median follow-up of 6 months), a significant improvement was observed after treatment (ES = -0.36; 95% CI, -0.49 to -0.23; k = 10; P < 0.0001). In moderator analysis, the percentage of patients with severe OSA in the populations significantly influenced the difference in OSA prevalence (P = 0.038) and AHI (P = 0.04) in ACT vs INACT patients. CONCLUSION: Prevalence of OSA and AHI is similar in ACT and INACT patients in cross-sectional studies. However, when AHI was measured longitudinally before and after treatment, a significant improvement was observed after treatment.
Assuntos
Acromegalia/terapia , Apneia Obstrutiva do Sono/epidemiologia , Acromegalia/complicações , Índice de Massa Corporal , Humanos , Prevalência , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Coronavirus Disease 2019 (COVID-19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality. The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID-19 patients. Information on the benefit/risk ratio of this approach is still lacking. OBJECTIVE: To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug. METHODS: Consecutive COVID-19 patients admitted between February and April 2020 were included in a retrospective analysis. Major bleedings (MB) and clinically relevant non-major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee. RESULTS: Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants. The rate of the composite endpoint of MB or CRNMB was 6.9 per 100-person/months in patients who had been given prophylactic doses, and 26.4 per 100-person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90-7.97). The corresponding rates for overall mortality were 12.2 and 20.1 per 100-person/months, respectively. CONCLUSIONS: The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants. In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher. Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non-critically ill patients with COVID-19.
Assuntos
Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Hemorragia/induzido quimicamente , Trombose/prevenção & controle , Tromboembolia Venosa/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , COVID-19/sangue , COVID-19/epidemiologia , Tomada de Decisão Clínica , Feminino , Hemorragia/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/epidemiologiaRESUMO
OBJECTIVES: Testicular function declines with obesity as a result of central and peripheral mechanisms, including a primary dysfunction of the Leydig cells. The levels of insulin-like factor 3 (INSL3), a sensitive marker of Leydig cell impairment, have never been evaluated in obese men. To better evaluate the hormonal function of the testis in obese men, we analysed their INSL3 plasma levels and compared them with the obesity status and the other reproductive hormones. DESIGN: Cross-sectional study. PATIENTS: Thirty-one obese men [body mass index (BMI) >30 kg/m(2)) aged 22-49 years and 64 age-matched nonobese men. MEASUREMENTS: Plasma concentrations of INSL3, testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E(2)), LH, FSH. Free testosterone (FT) levels were calculated. RESULTS: Obese men had significantly lower plasma concentrations of total T, SHBG, FT and INSL3, and higher levels of E(2) with respect to nonobese men. LH and FSH values were not different from controls. In obese men, we found a significant negative correlation between BMI and INSL3, and a positive correlation between INSL3 and T. Only one (1/31, 3.2%) obese man had subnormal T levels. On the contrary, 10/31 (32.3%) obese men had low INSL3 values. CONCLUSIONS: This study showed for the first time that INSL3 levels decrease with obesity, probably as a result of a primary dysfunction of the Leydig cells. INSL3 is a reliable marker of Leydig cell general impairment, whereas T mainly reflects the steroidogenic activity of these cells.
Assuntos
Biomarcadores/sangue , Insulina/sangue , Obesidade/sangue , Obesidade/metabolismo , Testículo/metabolismo , Adulto , Estudos Transversais , Estradiol/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Proteínas , Globulina de Ligação a Hormônio Sexual/metabolismo , Testículo/patologia , Testosterona/sangue , Adulto JovemRESUMO
Twenty-five medical centers and the Prader-Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4-46.7). Two hundred thirty-eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity-related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.