Early and accurate diagnosis of steatotic liver by artificial intelligence (AI)-supported ultrasonography.

OBJECTIVES: Steatotic liver disease is the most frequent chronic liver disease worldwide. Ultrasonography (US) is commonly employed for the assessment and diagnosis. Few information is available on the possible use of artificial intelligence (AI) to ameliorate the diagnostic accuracy of ultrasonography. MATERIALS AND METHODS: An AI-based algorithm was developed using a dataset of US images. We prospectively enrolled 134 patients for algorithm validation. Patients underwent abdominal US and Proton Density Fat Fraction MRI scans (MRI-PDFF), assumed as reference technique. The hepatorenal index was manually calculated (HRIM) by 4 operators. An automatic hepatorenal index (HRIA) was obtained by the algorithm. The accuracy of HRIA to discriminate steatosis grades was evaluated by ROC analysis using MRI-PDFF cut-offs. RESULTS: Overweight was 40 % of subjects (BMI 26.4 kg/cm2). The median HRIA was 1.11 (IQR 0.32) and the average of 4 manually calculated HRIM was 1.08 (IQR 0.26), with a 15 % inter-operator variability. Both HRIA (R = 0.79, P < 0.0001) and HRIM (R = 0.69, P < 0.0001) significantly correlated with liver fat percentage (MRI-PDFF). According to MRI-PDFF, 32 % of enrolled subjects had steatosis. Discrimination capacity by AUC between patient with steatosis and patient without steatosis was better for HRIA than HRIM (AUC: 0.87 vs. 0.82, respectively). ROC analysis showed an AUC = 0.98 for HRIA with 1.64 cut-off in distinguishing between mild and moderate/severe groups. CONCLUSIONS: The use of AI improves accuracy and speed of ultrasonography in the diagnosis of liver steatosis. Further studies should evaluate the routine use of this technique in the management of liver steatosis at high cardio-metabolic risk.

Neutrophil degranulation, endothelial and metabolic dysfunction in unvaccinated long COVID patients.

BACKGROUND: Long COVID symptoms are widely diffused and have a poorly understood pathophysiology, with possible involvement of inflammatory cytokines. MATERIALS AND METHODS: A prospective follow-up study involved 385 unvaccinated patients, started 1 month after SARS-CoV-2 infection and continued for up to 12 months. We compared circulating biomarkers of neutrophil degranulation, endothelial and metabolic dysfunction in subjects with long COVID symptoms and in asymptomatic post-COVID controls. RESULTS: The highest occurrence of symptoms (71%) was after 3 months from the infection, decreasing to 62.3% and 29.4% at 6 and 12 months, respectively. Compared to controls, long COVID patients had increased levels of the neutrophilic degranulation indices MMP-8 and MPO, of endothelial dysfunction indices L-selectin and P-selectin. Among indices of metabolic dysfunction, leptin levels were higher in long COVID patients than in controls. CONCLUSION: In unvaccinated patients, symptoms may persist up to 1 year after acute COVID infection, with increased indices of neutrophil degranulation, endothelial and metabolic dysfunction. The clinical implications of specific inflammatory biomarkers require further attention, especially in individuals with fatigue and long COVID-linked cognitive dysfunctions.

Pediatric Type 1 Diabetes: Mechanisms and Impact of Technologies on Comorbidities and Life Expectancy.

Type 1 diabetes (T1D) is one of the most common chronic diseases in childhood, with a progressively increasing incidence. T1D management requires lifelong insulin treatment and ongoing health care support. The main goal of treatment is to maintain blood glucose levels as close to the physiological range as possible, particularly to avoid blood glucose fluctuations, which have been linked to morbidity and mortality in patients with T1D. Indeed, the guidelines of the International Society for Pediatric and Adolescent Diabetes (ISPAD) recommend a glycated hemoglobin (HbA1c) level < 53 mmol/mol (<7.0%) for young people with T1D to avoid comorbidities. Moreover, diabetic disease strongly influences the quality of life of young patients who must undergo continuous monitoring of glycemic values and the administration of subcutaneous insulin. In recent decades, the development of automated insulin delivery (AID) systems improved the metabolic control and the quality of life of T1D patients. Continuous subcutaneous insulin infusion (CSII) combined with continuous glucose monitoring (CGM) devices connected to smartphones represent a good therapeutic option, especially in young children. In this literature review, we revised the mechanisms of the currently available technologies for T1D in pediatric age and explored their effect on short- and long-term diabetes-related comorbidities, quality of life, and life expectation.

Ramadan intermittent fasting reduces visceral fat and improves gastrointestinal motility.

BACKGROUND: Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan intermittent fasting (RIF) on anthropometric and metabolic indices, gastrointestinal symptoms, and motility. METHODS: In 21 healthy Muslims, we assessed the impact of RIF on caloric intake, physical activity, gastrointestinal symptoms and motility (gastric/gallbladder emptying by ultrasonography, orocaecal transit time by lactulose breath test), anthropometric indices, subcutaneous and visceral fat thickness (ultrasonography), glucose and lipid homeostasis. RESULTS: Mean caloric intake decreased from a median of 2069 kcal (range 1677-2641) before Ramadan to 1798 kcal (1289-3126) during Ramadan and increased again to 2000 kcal (1309-3485) after Ramadan. Although physical activity remained stable before, during, and after RIF, body weight, body mass index and waist circumference decreased in all subjects and in both genders, together with a significant decrease in subcutaneous and visceral fat thickness and insulin resistance. The postprandial gastric emptying speed was significantly faster after than before RIF. Fasting gallbladder volume was about 6% smaller after, than before Ramadan, with a stronger and faster postprandial gallbladder contraction. After RIF, lactulose breath test documented increased microbiota carbohydrate fermentation (postprandial H2 peak), and faster orocaecal transit time. RIF also significantly improved gastric fullness, epigastric pain and heartburn. CONCLUSIONS: RIF generates, in healthy subjects, multiple systemic beneficial effects in terms of fat burden, metabolic profile, gastrointestinal motility and symptoms. Further comprehensive studies should assess the potential beneficial effects of RIF in diseased people.

Gender-dependent impact of COVID-19 lockdown on metabolic and psychological aspects.

The first COVID-19 lockdown resulted in enforced quarantine of heavily affected areas with social isolation and related measures by several governments to slow the spread of the disease. The general population experienced several mental and lifestyle changes. Herein, we aimed to evaluate the metabolic and psychological effects induced by lifestyle changes during COVID-19 self-isolation among an Apulian overweight/obese cohort with metabolic disturbances. The study assessed anthropometric data (weight, abdominal circumferences), dietary habits (adherence to the Mediterranean diet, junk food score), lifestyle habits (i.e., smoking, and physical activity), levels of stress and anxiety, and depression. Subjects underwent bioumoral exams before and after self-isolation to monitor glycemic and lipid profiles. A total of 245 subjects (M:F = 118:127) have been included in the study. After lockdown, the number of obese subjects significantly increased in both sexes, and was higher in females than in males (P < 0.0001). Glycemic and lipid profiles worsened, with higher levels of insulinemia, lower levels of HDL cholesterol, and higher levels of triglycerides in females than in males. Adherence to the Mediterranean diet and consumption of junk foods were altered in both groups, especially in females. Psychological aspects were significantly higher in females than in males. Finally, work activities and familial status strongly affected the metabolic and psychological profile. In conclusion, COVID-19 self-isolation induced changes in lifestyle and dietary habits with psychological distress and detrimental effects on metabolic patterns, which were more pronounced in female gender.

Relapse rate in children with nephrotic syndrome during the SARS-CoV-2 pandemic.

BACKGROUND: Viral upper respiratory tract infections trigger nephrotic syndrome relapses. Few data exist on the impact of the SARS-CoV-2 pandemic on the risk of relapse in children with idiopathic nephrotic syndrome (INS). METHODS: In a Belgian and Italian cohort of children with INS, we performed a retrospective analysis on the number and duration of relapses observed in 3 different periods in 2020: first COVID period, February 15-May 31; second COVID period, June 1-September 14; third COVID period, September 15-December 31. Relapse rates were compared to those of the previous 5 years (PRECOVID period). For the years 2019 and 2020, all causes and INS relapse-related hospitalizations were recorded. Hospitalizations and deaths due to SARS-CoV-2 infection were also recorded. In the Belgian cohort, SARS-CoV-2 serologies were performed. RESULTS: A total of 218 patients were enrolled, and 29 (13.3%) were diagnosed with new-onset INS during the COVID period. Relapse rates per 1000 person-days were as follows: 3.2 in the PRECOVID period, 2.7 in the first COVID period, 3.3 in the second COVID period, and 3.0 in the third COVID period. The incidence rate ratio for the total COVID period was 0.9 (95%CI 0.76 to 1.06; P = 0.21) as compared to the PRECOVID period. During 2020, both the proportion of patients hospitalized for recurrence (14.2% vs. 7.6% in 2019; P = 0.03) and the rate of hospitalization for recurrence (IRR 1.97 (95%CI 1.35 to 2.88); P = 0.013) were higher compared to 2019. In December 2020, anti-SARS-CoV-2 antibodies were detected in 31% of the Belgian cohort. Patients with positive and negative SARS-CoV-2 serology did not differ significantly in relapse rate (2.4 versus 4.2 per 1000 person-days). The number of new INS cases remained similar between 2020, 2019, and 2018. CONCLUSION: The first year of the SARS-CoV-2 pandemic did not significantly affect the relapse rate in children with INS. No serious infections were reported in this population of immunosuppressed patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Mediterranean Diet in Developmental Age: A Narrative Review of Current Evidences and Research Gaps.

Numerous studies in recent decades have shown that Mediterranean diet (MD) can reduce the risk of developing obesity in pediatric patients. The current narrative review summarizes recent evidence regarding the impact of MD across the different stages of child development, starting from fetal development, analyzing breastfeeding and weaning, through childhood up to adolescence, highlighting the gaps in knowledge for each age group. A literature search covering evidence published between 1 January 2000 and 1 March 2022 and concerning children only was conducted using multiple keywords and standardized terminology in PubMed database. A lack of scientific evidence about MD adherence concerns the age group undergoing weaning, thus between 6 months and one year of life. In the other age groups, adherence to MD and its beneficial effects in terms of obesity prevention has been extensively investigated, however, there are still few studies that correlate this dietary style with the incidence of non-communicable diseases. Furthermore, research on multi-intervention strategy should be implemented, especially regarding the role of education of children and families in taking up this healthy dietary style.

Cows' Milk Allergy-Associated Constipation: When to Look for It? A Narrative Review.

Constipation is a very common disorder, mostly functional in nature, that may persist for years in up to 35-52% of children. Food allergy prevalence, severity and persistence are increasing over time, and cows' milk protein is the commonest food allergen recognised to affect gastrointestinal motility in children. There is mounting evidence of the role of cows' milk (CM) allergy (CMA) in children with constipation. With this narrative review, we aim to provide clinicians with an updated and critical overview of food allergy-associated constipation. We searched Embase, Medline and the Cochrane Library, using keywords related to the topic. Only reviews and studies including children aged 0-17 years that were published in English were considered. Constipation has been reported in 4.6% of infants with CMA; the prevalence of food allergy underlying chronic constipation in children resistant to conventional treatment and presenting to tertiary clinics ranges between 28% and 78%. The identification of predisposing risk factors and of a specific phenotype of food allergy-induced constipation remains elusive. No allergic tests, radiological or motility investigations achieve sufficient sensitivity and specificity to screen children for CMA-related constipation. A 4-week cows' milk protein (CMP) elimination diet may be considered for children with chronic constipation resistant to conventional treatment and who lack alarm sign/symptoms of organic diseases. In subjects with ameliorated symptoms on CMP elimination, the diagnosis of CMA should be confirmed by a food challenge to avoid an unnecessary protracted diet.

Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis.

Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes. Thus, diet might influence gut microbiota composition and activity, SCFAs production, and metabolic effects. In this narrative review, we discuss the relevant research focusing on the relationship between gut microbiota, SCFAs, and glucose metabolism.

Lecithinized superoxide dismutase in the past and in the present: Any role in the actual pandemia of COVID-19?

The Coronavirus disease 19 (Covid-19) pandemic is devastating the public health: it is urgent to find a viable therapy to reduce the multiorgan damage of the disease. A validated therapeutic protocol is still missing. The most severe forms of the disease are related to an exaggerated inflammatory response. The pivotal role of reactive oxygen species (ROS) in the amplification of inflammation makes the antioxidants a potential therapy, but clinical trials are needed. The lecitinized superoxide dismutase (PC-SOD) could represent a possibility because of bioaviability, safety, and its modulatory effect on the innate immune response in reducing the harmful consequences of oxidative stress. In this review we summarize the evidence on lecitinized superoxide dismutase in animal and human studies, to highlight the rationale for using the PC-SOD to treat COVID-19.

The Difficult Alliance between Vegan Parents and Pediatrician: A Case Report.

The number of children on a vegetarian or vegan diet is gradually increasing. If not balanced and adequately supplemented, these dietary regimes can seriously impact the growth of children. Often the pediatrician is not perceived as a figure to rely on in the event of parents' willingness to follow an alternative diet for their child. The feeling of distrust of parents towards the pediatrician can be dangerous for the health of the child. We present a 22-month-old boy with failure to thrive probably induced by an unbalanced vegetarian diet. The acquisition of the anamnestic data concerning the child's diet was difficult because initially omitted by the parents. The poor compliance and the difficult follow-up highlights the difficulty in establishing a therapeutic alliance between parents who follow alternative regimens and the pediatrician.

Vegetarian and Vegan Weaning of the Infant: How Common and How Evidence-Based? A Population-Based Survey and Narrative Review.

BACKGROUND: Vegetarian and vegan weaning have increasing popularity among parents and families. However, if not correctly managed, they may lead to wrong feeding regimens, causing severe nutritional deficiencies requiring specific nutritional support or even the need for hospitalization. AIM: To assess the prevalence of vegetarian and vegan weaning among Italian families and to provide an up-to-date narrative review of supporting evidence. MATERIALS AND METHODS: We investigated 360 Italian families using a 40-item questionnaire. The narrative review was conducted searching scientific databases for articles reporting on vegetarian and vegan weaning. RESULTS: 8.6% of mothers follow an alternative feeding regimen and 9.2% of infants were weaned according to a vegetarian or vegan diet. The breastfeeding duration was longer in vegetarian/vegan infants (15.8 vs. 9.7 months; p < 0.0001). Almost half of parents (45.2%) claim that their pediatrician was unable to provide sufficient information and adequate indications regarding unconventional weaning and 77.4% of parents reported the pediatrician's resistance towards alternative weaning methods. Nine studies were suitable for the review process. The vast majority of authors agree on the fact that vegetarian and vegan weaning may cause severe nutritional deficiencies, whose detrimental effects are particularly significant in the early stages of life. DISCUSSION AND CONCLUSION: Our results show that alternative weaning methods are followed by a significant number of families; in half of the cases, the family pediatrician was not perceived as an appropriate guide in this delicate process. To date, consistent findings to support both the safety and feasibility of alternative weaning methods are still lacking. Since the risk of nutritional deficiencies in the early stages of life is high, pediatricians have a pivotal role in guiding parents and advising them on the most appropriate and complete diet regimen during childhood. Efforts should be made to enhance nutritional understanding among pediatricians as an unsupervised vegetarian or vegan diet can cause severe nutritional deficiencies with possible detrimental long-term effects.