Background/objectivesMalan syndrome (MALNS) is a rare overgrowth disorder caused by pathogenic Nuclear Factor I × (NFIX) gene variants, and characterized by postnatal overgrowth, macrocephaly, developmental delay, intellectual disability and distinctive facial features. Chiari type I malformation (CMI), a condition where the cerebellar tonsils extend below the foramen magnum, has been observed in some patients with MALNS, although the exact relationship between these disorders remains unclear. The objective of this case report is to describe a novel NFIX variant in a patient with MALNS and associated CMI. This case adds to the literature on NFIX variants in patients with CMI and underscores the potential benefit of early genetic testing for diagnosis and management.Case presentationWe describe a patient with clinical features consistent with MALNS, including macrocephaly, developmental delay, and typical craniofacial features. Brain Magnetic Resonance Imaging (MRI) revealed the presence of CMI. Genetic testing identified a novel heterozygous variant in NFIX, not previously described in the literature.ConclusionThis case contributes to the clinical and molecular characterization of MALNS by linking a previously unreported NFIX variant to CMI. The case underlines the importance to take into account MALNS in patients presenting with overgrowth and CMI. Furthermore, we report a novel variant to improve diagnostic accuracy and genotype-phenotype correlation. Indeed, timely molecular diagnosis is essential to differentiate among overgrowth syndromes and to establish appropriate long-term clinical follow-up.
Background and Aims The optimal approach to coronary revascularization in patients undergoing transcatheter aortic valve implantation (TAVI) remains debated. Fractional flow reserve (FFR) may improve the identification of ischaemia-producing lesions compared to angiographic assessment alone, but data in the TAVI population are lacking.Methods In this multicentric, open-label, randomized, superiority trial with blind adjudication of adverse events, patients with aortic stenosis and intermediate coronary lesions undergoing TAVI were randomized 1:1 to FFR-guided or angiography-guided percutaneous coronary intervention (PCI). The trial was registered at ClinicalTrials.gov (NCT03360591). All randomized patients were included in the primary analysis according to the intention-to-treat principle. The primary endpoint was a major adverse cardiac and cerebrovascular event (MACCE) at 12 months of follow-up, defined as a composite of all-cause death, myocardial infarction, ischaemia-driven target vessel revascularization, disabling stroke, or major bleeding.Results A total of 320 patients were enrolled across 15 Italian centres. The median age of the patients was 86 years [interquartile range (IQR) 83-90], and the median STS score was 3% (IQR 2-5). The median SYNTAX score was 7 (IQR 5-11). FFR-guided PCI was associated with a significantly lower rate of MACCE at 12 months compared with angiography-guided PCI (8.5% vs 16.0%; hazard ratio .52; 95% confidence interval .27-.99; P = .047). The difference in the primary endpoint was primarily driven by a reduction in all-cause mortality (hazard ratio .31; 95% confidence interval .10-.96). Other components of the composite were numerically lower but not statistically significant.Conclusions In patients undergoing TAVI with intermediate coronary lesions, FFR-guided PCI was associated with a reduced risk of MACCE at 12 months. These findings support a physiology-based revascularization strategy in this frail, elderly population.
This review explores the integration of chronobiology and chronotype-specific factors into the Mediterranean Diet (MD) framework. While the MD is widely recognized for its cardiometabolic and neuroprotective effects, current guidelines do not address the timing of food intake or the influence of individual chronotype. Given the growing evidence linking circadian alignment, meal timing, and metabolic health, we propose a revised Mediterranean Diet pyramid tailored to chronotype and lifestyle determinants, herein referred to as the chronotype-based Mediterranean Diet Pyramid of the Italian Society of Endocrinology (SIE) and the Italian Society of Dietetics and Clinical Nutrition (ADI). Chrononutrition emphasizes the timing, frequency, and regularity of meals as key elements for metabolic regulation. Early-day energy intake, time-restricted eating, and alignment with circadian rhythms improve glycemic control, weight management, and cardiovascular outcomes. Morning chronotypes tend to show higher adherence to the MD, whereas evening chronotypes more frequently delay meals, skip breakfast, and consume energy-dense foods at night, contributing to poorer metabolic profiles. Sleep duration and quality further modulate appetite regulation and dietary adherence. Building on these insights, the proposed pyramid integrates circadian cues, represented by sun and moon symbols, to guide nutrient timing. Foods rich in carbohydrates and fiber (whole grains, legumes, fruits) are emphasized earlier in the day, while protein- and vegetable-based meals are prioritized in the evening, alongside sleep-promoting foods such as dairy, nuts, and seeds. Lifestyle pillars, including physical activity, adequate sleep, and the alignment of eating schedules with chronotype, form the foundation of the pyramid. The integration of chronobiological principles into the MD offers a novel paradigm that couples dietary quality with circadian alignment. A chronotype-oriented MD pyramid may enhance adherence, optimize metabolic flexibility, and reinforce the MD as a holistic model encompassing nutrition, lifestyle, and sustainability.
BACKGROUND:The Mediterranean diet (MD), characterized by high consumption of plant-based foods, olive oil, moderate intake of fish and poultry, and limited red and processed meats, has been associated with various health benefits, but its role in cancer prevention remains under debate. METHODS:This review was conducted in accordance with PRISMA 2020 and MOOSE guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and Cochrane Library was performed up to February 28, 2024. Study quality was assessed using the Newcastle-Ottawa Scale, and the certainty of evidence was evaluated with the NUTRIGRADE approach. Pooled effect sizes were computed using a random-effects model and expressed as risk ratios (RR), hazard ratios, or odds ratios, as appropriate. RESULTS:A total of 126 studies, including more than 8 million participants, across all included studies, were included. High adherence to the MD, as one point increase in the adherence, was significantly associated with a modest reduced risk of several site-specific cancers, including head and neck (RR = 0.88, 95% CI 0.78-0.98), oral cavity (RR = 0.83, 95% CI 0.73-0.95), stomach (RR = 0.93, 95% CI 0.88-0.97), liver/gallbladder (RR = 0.94, 95% CI 0.93-0.96), colorectal (RR = 0.95, 95% CI 0.92-0.98), bladder (RR = 0.96, 95% CI 0.92-0.995), and breast cancer (RR = 0.95, 95% CI 0.92-0.98). Higher adherence was also associated with lower cancer-related mortality (RR = 0.97, 95% CI 0.96-0.99). Certainty of evidence was rated as moderate for the main outcomes. CONCLUSIONS:Greater adherence to the MD is associated with a lower risk of several site-specific cancers and reduced cancer mortality. These findings support the promotion of the MD as a preventive dietary strategy within public health policies.
Abstract Background Amniotic Band Syndrome (ABS) is a rare congenital disorder caused by fibrous amniotic strands that can entangle fetal structures, producing defects ranging from constriction rings to severe limb malformations. Prenatal detection remains challenging because diagnosis often relies on indirect imaging findings rather than direct visualization of amniotic bands. We report a severe four-limb ABS case with postnatal diagnosis, genetic evaluation, and multidisciplinary management. Case presentation A male neonate was delivered at 31 + 6 weeks after an uncomplicated pregnancy with normal prenatal ultrasounds. Postnatally, malformations involved all four limbs: severe right‑hand acrosyndactyly with thumb hypoplasia; left hand distal phalanx aplasia of the third digit with a circumferential constriction band and a rudimentary distal phalanx of the fourth digit; and lower‑limb syndactyly/hypoplasia with amniotic rings. Color Doppler ultrasound confirmed distal perfusion. No visceral or craniofacial anomalies were detected. Genetic testing identified a heterozygous FAM20C variant of uncertain significance. Orthopaedic and plastic surgery assessments recommended staged reconstructive procedures to optimize function. Conclusions Severe ABS may present unexpectedly despite normal prenatal imaging. The clinical relevance of this case lies in the extent of four-limb involvement, the postnatal phenotypic classification, and the need for early multidisciplinary planning. Early postnatal assessment and coordinated multidisciplinary care are essential for surgical planning, follow‑up, and optimization of limb function.
