Oral manifestations after vaccinations: A systematic review of observational studies.

OBJECTIVE: This study aimed to assess the prevalence and types of oral adverse events following immunization (AEFIs) in people who received at least one dose of any type of vaccine. MATERIALS AND METHODS: We conducted a bibliographic search about oral AEFIs in MEDLINE, Embase, PubMed, and Ovid from database inception to November 07, 2022. Risk of bias was assessed using the MURAD or the Quality In Prognosis Studies tools. Random-effects proportional meta-analysis was applied. RESULTS: A total of 119 studies involving 343 people were eligible. These reported AEFIs occurred following administration of the coronavirus disease 2019 vaccine, anti-influenza vaccine, hepatitis B vaccine, and anti-smallpox vaccine. The most common to be affected in vaccinated people were buccal mucosa (63.1%; 95% confidence interval (CI) 33.4-88.2) and lips (55.7%; 95% CI, 41.1-69.8). The most prevalent oral AEFIs were ulceration (55.2%; 95% CI 24.4-84.0), swelling (65.2%; 95% CI 34.9-89.8), and burning sensation (18.3%; 95% CI 7.9-31.8). CONCLUSIONS: The mechanisms underlying oral AEFIs should be further investigated to promptly recognize oral manifestations and provide optimal management for people undergoing vaccination.

Bronchiolitis 2021-2022 epidemic: multicentric analysis of the characteristics and treatment approach in 214 children from different areas in Italy.

Bronchiolitis causes a remarkable number of hospitalizations; its epidemiology follows that of respiratory syncytial virus (RSV), its main pathogen. The aim of this study was to evaluate the presenting features, treatment approach, and impact of medical therapy in four pediatric hospitals in Italy. Data on infants < 24 months of age hospitalized with bronchiolitis in the 2021-2022 season were collected. Between October 2021 and February 2022, 214 children were admitted. Median hospital stay was 5 days; none of the patients died. The distribution of the presenting features is largely comparable in the 33 (15.8%) RSV-negative versus the 176 (84.2%) RSV-positive children; also, no difference was observed in medical therapy provided: duration of oxygen therapy, administration of steroid, and duration of hospital stay. Systemic steroids, inhalation, or antibiotic therapy were given to 34.6%, 79.4%, and 49.1% of children respectively. Of the 214 patients with bronchiolitis, only 19 (8.8%) were admitted to ICU.   Conclusion: Our data suggest that, irrespective of treatments provided, RSV-positive and RSV-negative children had a similar clinical course. The results of our retrospective study further underline the need to improve adherence to existing guidelines on bronchiolitis treatment. What is Known: • Bronchiolitis is a common diseases with seasonal peak. The outcome is usually favorable but hospitalization and even ICU admission is not exceptional. What is New: • Children with RSV associated bronchiolitis do not have a different course and outcome. The analysis of the 2021-2022 cohort, following COVID pandemic peaking, did not show a different course and outcome. • Adherence to literature recommendation, i.e. to focus on oxygen and hydration therapy while avoiding unnecessary systemic therapy with steroid and antibiotics, should be improved.

Correlation between functional outcome and the SAMEO-ATO framework.

PURPOSE: To evaluate the recently proposed SAMEO-ATO framework for middle ear and mastoid surgery, by correlating it with the functional outcome in a large cohort of patients operated for middle ear and mastoid cholesteatoma in a tertiary referral center. METHODS: We retrospectively included all surgeries for middle ear and mastoid cholesteatoma undergone in our Department between January 2009 and December 2014, by excluding revision surgeries, congenital and petrous bone cholesteatoma. All surgeries were classified according to the SAMEO-ATO framework. The post-operative air bone gap (ABG) was calculated and chosen as benchmark parameter for the correlation analysis. RESULTS: 282 consecutive surgeries for middle ear and mastoid cholesteatoma were released in the study period on a total of 273 patients, with a mean age of 41.2 years. All patients were followed for an average period of 55.3 months. 54% of patients underwent M2c mastoidectomy (Canal Wall Down, CWD), while the remaining underwent Canal Wall Up (CWU) procedures, being M1b2a mastoidectomy the most common one (33%). Mean pre-operative and post-operative ABGs were 29.2 and 23.5 dB, with a significant improvement (p < 0.0001). 'Mastoidectomy' and 'Ossicular reconstruction' parameters of SAMEO-ATO showed significant association with postoperative ABG, with smaller residual gaps for the classes Mx and On, and worse hearing results for M3a and Ox. CONCLUSION: Our results show the utility of SAMEO-ATO framework, and in particular of 'M' (Mastoidectomy) and 'O' (Ossicular reconstruction) parameters, in predicting the hearing outcome.

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study.

BACKGROUND: The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. METHODS: The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. RESULTS: Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. CONCLUSIONS: A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.

Large-scale IgM and IgG SARS-CoV-2 serological screening among healthcare workers with a low infection prevalence based on nasopharyngeal swab tests in an Italian university hospital: Perspectives for public health.

BACKGROUND: Healthcare workers (HCWs) are highly exposed to SARS-CoV-2 infection given their specific tasks. The IgG-IgM serological assay has demonstrated good accuracy in early detection in symptomatic patients, but its role in the diagnosis of asymptomatic patients is uncertain. The aim of our study was to assess IgM and IgG prevalence in sera in a large cohort of HCWs previously subjected to Nasopharyngeal swab test (NST) after accurate risk assessment due to positive COVID-19 patient exposure during an observation period of 90 days. METHODS: 2407 asymptomatic HCWs that had close contact with COVID-19 patients in the period between April 8th and June 7th were screened with NST based on the RT-PCR method. In parallel, they underwent large-scale chemiluminescence immunoassays involving IgM-IgG serological screening to determine actual viral spread in the same cohort. RESULTS: During the 90-day observation period, 18 workers (0.75%) resulted positive for SARS-CoV-2 infection at the NST, whereas the positivity rates for IgM and IgG were 11.51% and 2.37%, respectively (277 workers). Despite high specificity, serological tests were inadequate for detecting SARS-CoV-2 infection in patients with previous positive NST results (IgM and IgG sensitivities of 27.78% and 50.00%, respectively). CONCLUSIONS: These findings indicate a widespread low viral load of SARS-CoV-2 among hospital workers. However, serological screening showed very low sensitivity with respect to NST in identifying infected workers, and negative IgG and IgM results should not exclude the diagnosis of COVID-19. IgG-IgM chemiluminescence immunoassays could increase the diagnosis of COVID-19 only in association with NST, and this association is considered helpful for decision-making regarding returning to work.

Anxiety, sleep disorders and self-efficacy among nurses during COVID-19 pandemic: A large cross-sectional study.

AIM AND OBJECTIVES: To assess the prevalence of anxiety, sleep disorders and self-efficacy and their predicting factors among nurses facing COVID-19. BACKGROUND: The spread of COVID-19 throughout the world determined a series of modifications of several National Health Service organisations, with a potential series of psychological consequences among nurses, who were particularly afflicted by this situation of changes and precariousness. DESIGN: A cross-sectional study was carried out from February-April 2020. METHODS: A total of 1,005 nurses employed in different Italian hospital wards, during the COVID-19 pandemic, were recruited. Analyses were based on descriptive statistics and multivariate logistic regression. The STROBE checklist for cross-sectional studies was used in this study. RESULTS: The prevalence of sleep disturbances, moderate anxiety and low self-efficacy was 71.4%, 33.23% and 50.65%, respectively. We found a positive correlation between anxiety and sleep quality (0.408; p < .0001) and negative correlations between self-efficacy and anxiety (-0.217; p < .0001) and sleep quality and self-efficacy (-0.134; p < .0001). The factor independently associated with all variables was gender. Females were more prone to sleep disturbances, anxiety and low levels of self-efficacy than males (p < .05). CONCLUSIONS: The prevalence of anxiety, sleep disorders and low self-efficacy among Italian nurses during the COVID-19 pandemic was high. Healthcare managers should recognise and consider these results to reduce the risk of the onset of major mental problems that could result in post-traumatic stress disorder. RELEVANCE TO CLINICAL PRACTICE: Nurses facing major incidents as COVID-19 pandemic are among healthcare personnel exposed to a high risk to develop psychological disturbance that should be assessed and recognised, in order to find helpful coping strategies to inform support services and avoid to hesitate in post-traumatic stress disorders.

Psychosocial distress in oncology: using the distress thermometer for assessing risk classes.

PURPOSE: Cancer patients often suffer for psychological distress, which can compromise their quality of life. Our study aimed to recognize risk classes for the development of psychosocial distress. METHODS: Three hundred seventy-two adult cancer patients were assessed by the Distress Thermometer (DT) and Problem List at the National Cancer Research Centre "Giovanni Paolo II" of Bari. We also compiled a socio-medical and clinical-medical record survey ad hoc for collecting socio-demographic information and clinical variables. To examine the interplay among the different variables and distinguish internally homogeneous subgroups of patients with diverse risks of distress, the RECursive Partitioning and Amalgamation (RECPAM) technique was used. RESULTS: Most of patients were female and the most frequent diagnosis was breast cancer, followed by gastro-intestinal cancer and hematological cancer. Distress was present in 43% of the sample, with a total of 156 patients with a DT > 5. The RECPAM analysis identified three distinct and homogeneous patient subgroups (RECPAM classes) with different risks of distress: diagnosis, marital status, and Eastern Cooperative Oncology Group Performance Status. CONCLUSION: The use of the distress thermometer allows clinicians to identify patients with certain characteristics that may increase the risk of developing psychosocial distress. This evaluation can allow timely psychological intervention and improve the patient's therapeutic program.

Hepatic microRNA Expression by PGC-1α and PGC-1ß in the Mouse.

The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism.

Genes and miRNA expression signatures in peripheral blood mononuclear cells in healthy subjects and patients with metabolic syndrome after acute intake of extra virgin olive oil.

Extra virgin olive oil (EVOO) consumption has been associated with reduced cardiovascular risk but molecular mechanisms underlying its beneficial effects are not fully understood. Here we aimed to identify genes and miRNAs expression changes mediated by acute high- and low-polyphenols EVOO intake. Pre- and post-challenge gene and miRNAs expression analysis was performed on the peripheral blood mononuclear cells (PBMCs) of 12 healthy subjects and 12 patients with metabolic syndrome (MS) by using microarray and RT-qPCR. In healthy subjects, acute intake of EVOO rich in polyphenols was able to ameliorate glycaemia and insulin sensitivity, and to modulate the transcription of genes and miRNAs involved in metabolism, inflammation and cancer, switching PBMCs to a less deleterious inflammatory phenotype; weaker effects were observed in patients with MS as well as in healthy subjects following low-polyphenol EVOO challenge. Concluding, our study shows that acute high-polyphenols EVOO intake is able to modify the transcriptome of PBMCs through the modulation of different pathways associated with the pathophysiology of cardio-metabolic disease and cancer. These beneficial effects are maximized in healthy subjects, and by the use of EVOO cultivars rich in polyphenols. Nutrigenomic changes induced by EVOO thus legitimate the well-known beneficial effects of EVOO in promoting human health and, potentially, preventing the onset of cardiovascular disease and cancer.

Short-term benefits of an unrestricted-calorie traditional Mediterranean diet, modified with a reduced consumption of carbohydrates at evening, in overweight-obese patients.

The Mediterranean diet (MeD) is believed to promote health; nevertheless, changes in the nutritional patterns in the Mediterranean area (increased intake of refined carbohydrates/saturated fats; reduced fibers intake; main calorie load shifted to dinner) led to reduced MeD benefits in recent decades. We retrospectively investigated the effects of a MeD with a low intake of refined carbohydrates in the evening ("MeDLowC") on body weight (BW) and metabolic profile of overweight/obese subjects. According to their adherence to MeDLowC, subjects were classified into 44 (41%) individuals with "excellent" adherence and 63 (59%) with "poor" adherence. Nutritional counseling induced an improvement in BW, glucose metabolism and liver transaminases in both groups, with an increased magnitude of these effects in the "Excellent" adherence group. "Excellent" adherence to MeDLowC improved insulin sensitivity and lipid metabolism. In conclusion, MeD with a restriction of carbohydrates in the evening significantly ameliorates obesity and associated metabolic complications.

Is immunohistochemistry of BRAF V600E useful as a screening tool and during progression disease of melanoma patients?

BACKGROUND: In clinical practice the gold standard method to assess BRAF status in patients with metastatic melanoma is based on molecular assays. Recently, a mutation-specific monoclonal antibody (VE1), which detects the BRAF V600E mutated protein, has been developed. With this study we aimed to confirm the clinical value of the VE1 Ventana® antibody, as today a univocal validated and accredited immunohistochemical procedure does not exist, to preliminary detect BRAF status in our routine diagnostic procedures. Moreover, we explored the biological meaning of BRAF immunohistochemical labeling both as a predictor marker of response to target therapy and, for the first time, as a player of acquired tumor drug resistance. METHODS: We analyzed a retrospective series of 64 metastatic melanoma samples, previously investigated for molecular BRAF status, using a fully automatized immunohistochemical method. We correlated the data to the clinicopathologic characteristics of patients and their clinical outcome. RESULTS: The sensitivity and the specificity of the Ventana® VE1 antibody were 89.2 and 96.2% respectively, while the positive predictive value and negative predictive value were 97.1 and 86.2%, respectively. For six mutated patients the histological sample before treatment and when disease progressed was available. The immunohistochemical BRAF V600E expression in the specimens when disease progressed was less intense and more heterogeneous compared to the basal expression. Multivariate analysis revealed that a less intense grade of positive expression is an independent predictor of a less aggressive stage at diagnosis (p = 0.0413). CONCLUSIONS: Our findings encourage the introduction of immunohistochemistry as a rapid screening tool for the assessment of BRAF status in melanoma patients in routine diagnostic procedures and prepare the ground for other studies to highlight the role of immunohistochemical BRAF V600E expression in patients at the time of progression.

Nuclear receptors expression chart in peripheral blood mononuclear cells identifies patients with Metabolic Syndrome.

BACKGROUND: Nuclear receptors are a class of 48 ligand-activated transcription factors identified as key players of metabolic and developmental processes. Most of these receptors are potential targets for pharmacological strategies in the Metabolic Syndrome. In the present study, we analyzed changes in the mRNA expression of nuclear receptors in the peripheral blood mononuclear cells of patients with Metabolic Syndrome, in order to identify novel biomarkers of disease and candidate targets for putative therapeutical approaches. METHODS AND RESULTS: We enrolled thirty healthy controls (14 M:16 F) and thirty naïve patients (16 M: 14 F; >3 criteria for Metabolic Syndrome upon Adult Treatment Panel III) without organ damage. Using quantitative real-time PCR, we assessed the expression patterns of nuclear receptors in peripheral blood mononuclear cells. 33/48 nuclear receptors were expressed in peripheral blood mononuclear cells. In patients with Metabolic Syndrome, we found a significant down-regulation of the entire PPAR, NR4A and RAR families, together with a repression of RXRα, VDR, and Rev-Erbα. Furthermore, we performed a novel statistical analysis with classification trees, which allowed us to depict a predictive core of nuclear receptor expression patterns characterizing subjects with Metabolic Syndrome. Random Forest Analysis identified NOR1 and PPARδ, which were both reduced in peripheral blood mononuclear cells and specifically in CD14(+) cells (mostly monocytes), as classifiers of Metabolic Syndrome, with high specificity and sensitivity. CONCLUSIONS: Our results point to the use of PPAR and NR4A mRNA levels in the overall peripheral blood mononuclear cells as biomarkers of Metabolic Syndrome and bona fide putative targets of pharmacological therapy.

Neuron-derived orphan receptor 1 promotes proliferation of quiescent hepatocytes.

BACKGROUND & AIMS: Studies of the transcriptional networks that regulate nuclear receptor-mediated proliferation of quiescent hepatocytes could lead to new information about liver growth and hepatoprotective strategies. METHODS: We used quantitative real-time PCR to analyze expression of neuron-derived orphan receptor 1 (Nor-1) and its target genes during liver regeneration after hepatectomy in mice, and in hepatocellular carcinoma (HCC) samples from patients. We used adenoviral vectors to express Nor-1 in normal liver (Ad/CMV/V5-Nor-1), or reduce its level with small hairpin RNAs (Ad/BLOCK-iT/Nor-1(small hairpin RNA)) after partial hepatectomy. RESULTS: Levels of Nor-1 messenger RNA and protein, and transcription of Nor-1 target genes (Ccnd1 and Vcam-1), increased during the late priming and proliferative phases of liver regeneration after partial hepatectomy. Levels of NOR-1 messenger RNA and transcription of its target gene CCND1 and of the NOR-1 subfamily member NUR-77 also increased in human HCC samples compared with paired HCC-free tissue. Ad-Nor-1(small hairpin RNA) reduced the hepatocyte proliferation after hepatectomy. Overexpression of Nor-1 in normal livers of mice induced proliferation of quiescent hepatocytes independently of interleukin-6 and tumor necrosis factor-α signaling. In gene expression profile analysis, Nor-1 altered expression of genes involved in the cell cycle, proliferation, and tumorigenesis. CONCLUSIONS: In mice, the orphan nuclear receptor Nor-1 activates proliferation of quiescent hepatocytes and is required for hepatocyte proliferation after partial hepatectomy. Nor-1 and its gene targets are also up-regulated in human HCC samples. Nor-1 activates a transcriptional program that induces hepatocyte proliferation independently of inflammatory signaling pathways.

Advances in meta-analysis: examples from internal medicine to neurology.

OBJECTIVE: We review the state of the art in meta-analysis and data pooling following the evolution of the statistical models employed. METHODS: Starting from a classic definition of meta-analysis of published data, a set of apparent antinomies which characterized the development of the meta-analytic tools are reconciled in dichotomies where the second term represents a possible generalization of the first one. Particular attention is given to the generalized linear mixed models as an overall framework for meta-analysis. Bayesian meta-analysis is discussed as a further possibility of generalization for sensitivity analysis and the use of priors as a data augmentation approach. RESULTS: We provide relevant examples to underline how the need for adequate methods to solve practical issues in specific areas of research have guided the development of advanced methods in meta-analysis. CONCLUSIONS: We show how all the advances in meta-analysis naturally merge into the unified framework of generalized linear mixed models and reconcile apparently conflicting approaches. All these complex models can be easily implemented with the standard commercial software available.

Continuous improvement of quality of care in pediatric diabetes: the ISPED CARD clinical registry.

AIM: In Italy, the ISPED CARD initiative was launched to measure and improve quality of care in children and adolescents with type 1 diabetes. METHODS: Process and outcome indicators and the related information derived from electronic medical records were identified. A network of pediatric diabetes centers was created on a voluntary basis. RESULTS: Overall, 20 centers provided data on 3284 patients aged < = 18 years. HbA1c was monitored ≥ 2/year in 81.2% of the cases. BMI was monitored ≥ 1/year in 99.0%, lipid profile in 45.3%, and blood pressure in 91.7%. Pubertal status, albuminuria, eye examination, and screening of celiac disease and thyroiditis were underreported. From 2017 to 2021, average HbA1c levels decreased from 7.8 ± 1.2 to 7.6 ± 1.3%, while patients with LDL cholesterol > 100 mg/dl increased from 18.9 to 36.7%. Prevalence of patients with elevated blood pressure and BMI/SDS values also increased. In 2021, 44.7% of patients were treated with the newest basal insulins, while use of regular human insulin had dropped to 7.7%. Use of insulin pump remained stable (37.9%). CONCLUSIONS: This report documents the feasibility of the ISPED CARD initiative and shows lights and shadows in the care provided. Improving care, increasing number of centers, and ameliorating data recording represent future challenges.

Effectiveness of switching from first-generation basal insulin to Glargine 300 U/mL in children and adolescents with type 1 diabetes: results from the ISPED CARD database.

AIMS: Glargine 300 U/mL (Gla-300) has been recently approved for use in children and adolescents with type 1 diabetes (T1D). However, real-world effectiveness data are scarce, and aim of this analysis was to assess clinical outcomes in young patients with T1D switching from 1st generation basal insulin (1BI) to Gla-300. METHODS: ISPED CARD is a retrospective, multicenter study, based on data anonymously extracted from Electronic Medical Records. The study involved a network of 20 pediatric diabetes centers. Data on all patients aged < 18 years with T1D switching from 1BI to Gla-300 were analyzed to assess clinical characteristics at the switch and changes after 6 and 12 months in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and standardized body mass index (BMI/SDS). Titration of basal and short-acting insulin doses was also evaluated. RESULTS: Overall, 200 patients were identified. The mean age at the switch to Gla-300 was 13 years, and mean duration of diabetes was 3.9 years. Average HbA1c levels at switch were 8.8%. After 6 months, HbA1c levels decreased by - 0.88% (95% CI - 1.28; - 0.48; p < 0.0001). The benefit was maintained after 12 months from the switch (mean reduction of HbA1c levels - 0.80%, 95% CI - 1.25; - 0.35, p = 0.0006). Trends of reduction in FBG levels were also evidenced both at 6 months and 12 months. No significant changes in short-acting and basal insulin doses were documented. CONCLUSIONS: The study provides the first real-world evidence of the effectiveness of Gla-300 in children and adolescents with T1D previously treated with 1BI. The benefits in terms of HbA1c levels reduction were substantial, and sustained after 12 months. Additional benefits can be expected by improving the titration of insulin doses.

Fasting hyperglycaemia and fatty liver drive colorectal cancer: a retrospective analysis in 1145 patients.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumourigenic triggers for colorectal cancer (CRC). We aim to identify specific metabolic signatures involved in CRC development that may be used as non-invasive biomarkers, paving the way for specific and personalized strategies of CRC prevention and early detection. METHODS: We retrospectively assessed CRC onset during a time frame of 8 years in a cohort of 1145 out-patients individuals who had previously been evaluated for Metabolic Syndrome. RESULTS: 28 patients developed CRC. No association between CRC development and visceral and general obesity was detected, while baseline fasting plasma glucose (FPG) and non-invasive liver fibrosis scores were significantly higher in patients with CRC, compared to those who did not develop cancer. Liver steatosis and MASLD were more frequently diagnosed in patients who developed CRC compared to no cancer developers. Canonical correlations among metabolic biomarkers were not present in CRC developers, differently from no cancer group. In ROC analysis, FPG and non-invasive scores also showed good sensitivity and specificity in predicting colon cancer. We then calculated ORs for metabolic biomarkers, finding that higher FPG and non-invasive scores were associated with an increased risk of developing CRC. CONCLUSION: MASLD and increased FPG may play a role in the clinical background of CRC, bringing to light the fascinating possibility of a reversed gut-liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of fatty liver may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.

Hyperhomocysteinemia is linked to MASLD.

BACKGROUND AND AIMS: Homocysteine (Hcy) levels are elevated in different conditions, including cardiovascular diseases (CVD), diabetes, and metabolic-associated steatotic liver disease (MASLD). In this observational retrospective study, we analyzed Hcy levels in a population of 901 outpatients, considering its putative etiological role in MASLD. METHODS: A total of 901 outpatients underwent physical and biochemical evaluations. Abdominal and carotid ultrasound were performed to assess liver steatosis, carotid intima-media thickness (IMT) and presence of atherosclerotic plaque. RESULTS: Hyperhomocysteinemia (HHcy) was identified in 140 subjects (16 %). Patients with HHcy showed glucose metabolism impairment (p < 0.001), altered lipid profile (p < 0.001), low Vitamin D levels (p < 0.0001), increased cardiovascular risk (p < 0.001). We then investigated the relationship between Hcy and MASLD (OR=3.6, p < 0.0001), finding that the relationship remained significant also when accounting for confounding variables (age, sex) (OR=3.2, p < 0.0001). Hcy values were significantly higher (p < 0.0001) in patients with MASLD (n = 78, 29.4 ± 10.1µmol/l) compared to those without MASLD (20.4 ± 4.8 1µmol/l). Furthermore, in MASLD patients we found a direct correlation between Hcy level and waist circumference (r = 0.3, p < 0.001) and an inverse correlation with both HDL-c (r=-0.4, p < 0.001) and Vitamin D levels (r=-0.24, p < 0.05). CONCLUSIONS: Our data suggest an intriguing scenario whereby HHcy is present in patients with MASLD and is associated to lower vitamin D and altered glucose and lipid profile. Thus, considering Hcy levels may help clinicians with the management of patients with increased MASLD risk.

Noonan Syndrome Growth Charts and Genotypes: 15-Year Longitudinal Single-Centre Study.

INTRODUCTION: Growth patterns in Noonan syndrome (NS) remain relatively unknown. The objective of this study was to provide growth reference curves for patients with NS and identify correlations between their growth, genotype, and clinical features. METHODS: This was a 15-year-long, monocentric, observational, retrospective, non-interventional study. Children with NS followed up between 2005 and 2022 at "Bambino Gesù" Children's Hospital, Italy, were included and excluded if they had received growth hormone treatment. Comparison of growth curves of participants with NS versus the general Italian population and further genotypic analyses were performed. RESULTS: Overall, 190 eligible participants with NS were identified, with median (interquartile range) age of 14.01 (9.05-19.25) years (55.8% male). Cardiovascular anomalies were present in 85.3% of participants, most commonly pulmonary stenosis (52.6%) and atrial septal defects (36.8%); 48.1% of male participants had cryptorchidism. The most frequently detected mutations were in PTPN11 (66.3%) and SOS1 (13.9%). NS sex-specific centile curves for height, weight, body mass index, and height velocity were produced. For both sexes, the 50th percentile of height and weight for participants with NS overlapped with the 3rd percentile for the general Italian population. Both sexes with a PTPN11 mutation had a significantly lower height and weight than those with "other mutations" at 5 years old. No significant associations were observed between cardiac anomalies and PTPN11 mutation status. CONCLUSION: We present longitudinal data describing growth curves and trends, the natural history, and genotypes of the NS population, which provide a useful tool for clinicians in the management of NS.

Severe Hypertriglyceridemia in Patients with Type 2 Diabetes Mellitus Participating in the AMD Annals Initiative.

Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels (n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present.