Clinical Approach in the Management of Paediatric Patients with Familial Hypercholesterolemia: A National Survey Conducted by the LIPIGEN Paediatric Group.

Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.

A Case of Wernicke's Encephalopathy After Sleeve Gastrectomy.

BACKGROUND: Wernicke's encephalopathy, resulting from thiamine deficiency, is a rare but serious neurological complication of bariatric procedures. A clinical and radiologic diagnosis is often difficult, and thiamine blood tests are not broadly available. Only a few cases of Wernicke's encephalopathy after sleeve gastrectomy have been reported in the literature, nonetheless, subjects can be underdiagnosed, and their cases can be underreported. CASE PRESENTATION: We present the case of a 20-year-old female patient who developed Wernicke's encephalopathy after sleeve gastrectomy for grade II obesity with metabolic complications. She was presented to the Emergency Department showing confusion, gait ataxia and horizontal nystagmus two months after surgery. Persistent vomiting and lack of compliance with vitamin intake were reported. Cerebral MRI showed acute bilateral lesions in the periaqueductal and periventricular regions. Parenteral thiamine supplementation was administered, obtaining a progressive resolution of altered mental status, motor ataxia, and nystagmus. She was discharged on oral thiamine supplementation and underwent a multidisciplinary rehabilitation program, since anterograde, retrograde, and working memory impairment persisted. After a 2-year follow-up, she was compliant with a balanced fractionated diet and vitamin supplementation. A new cerebral MRI showed regression of the neuroradiological findings, but minimal memory impairment remained. CONCLUSION: Wernicke's encephalopathy is a concrete possibility after sleeve gastrectomy and should always be suspected in patients with recurrent vomiting, poor nutritional intake, and non-compliance to vitamin supplementation. Immediate and aggressive thiamine supplementation is mandatory to prevent patients from irreversible neurological impairment, even though full recovery is not always achieved.

[Identifying possible homozygous familial hypercholesterolemia patients: an Italian experts' opinion]. / Inquadramento diagnostico del paziente con possibile ipercolesterolemia familiare omozigote: il parere di un gruppo italiano di esperti.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) and massive risk of premature atheromasia and cardiovascular events. HoFH is caused by mutations in several genes, such as LDLR, APOB, PCSK9 and LDLRAP1. If untreated, the average age of death is 18 years old, but fatalities within the first 5 years of age have been recorded. Therefore, early diagnosis and treatment are crucial, in order to prevent and/or delay the cardiovascular complications of LDL-C exposure. Because HoFH is a rare disorder, it is not frequently encountered in daily clinical practice at the primary/secondary unspecialized cardiological centers. Then the availability of practical indications helping to identify HoFH patients or to arise a suspect of HoFH is particularly strategic to promptly start the appropriate lipid-lowering therapy. For such a purpose, a group of Italian experts suggests three useful algorithms to identify cases requiring accurate and specialized clinical evaluation as potential HoFH patients. These cases with suspected HoFH should be addressed to specialized centres for the optimal management of these patients.

Effects of Semaglutide on Glycemic Control and Weight Loss in a Patient with Prader-Willi Syndrome: A Case Report.

BACKGROUND: Prader-Willi syndrome is the most frequent genetic cause of obesity and is often complicated by glucose metabolism alterations. Conventional therapies prescribed for type 2 diabetes frequently failed to achieve adequate glycemic control in patients with Prader-Willi syndrome. Beneficial effects of glucagon like peptide-1 receptor agonists exenatide and liraglutide have been reported for the management of type 2 diabetes in Prader-Willi syndrome, but no data are currently available in this population on the use of semaglutide. CASE PRESENTATION: We report for the first time the use of semaglutide 1 mg per week in a 33-yearold man with Prader-Will syndrome complicated by poorly controlled diabetes and severe obesity. After 12 months of semaglutide treatment, we observed an important reduction in glycated hemoglobin levels (11.1% to 7.2%) and body weight (99.5 kg to 94.3 kg), with a notable decrease in fat mass and insulin requirements. Interestingly, our patient had already tried liraglutide therapy in adjunction to metformin and insulin therapy, reporting no substantial efficacy. CONCLUSION: The beneficial effects of semaglutide on glycemic control and weight reduction provide a promising treatment for diabetes and obesity in Prader-Willi syndrome, even where other glucagons like peptide-1 receptor agonists have failed. Further studies are required to confirm the efficacy and safety of semaglutide in patients with Prader-Willi syndrome.

Lipoprotein Apheresis and PCSK9-Inhibitors. Impact on Atherogenic Lipoproteins and Anti-Inflammatory Mediators in Familial Hypercholesterolaemia.

BACKGROUND: A combination therapy with PCSK9-inhibitors (PCSK9-I) and lipoprotein-apheresis (LA) may have synergistic effects on circulating lipid and lipoprotein levels, in particular in Homozygous Familial Hypercholesterolaemic (HoFH) subjects. The relationships between the above mentioned novel therapeutic approaches as highly effective treatment option for Dyslipidemia in Heterozygous Familial Hypercholesterolaemic (HeFH) patients deserve further investigation in larger datasets. OBJECTIVE: This review aims to present the role of lipoprotein apheresis in the management of familial hypercholesterolaemia and discuss the potential advantages and disadvantages of its combination with PCSK9 inhibitors. METHODS: A comprehensive literature search regarding lipoprotein apheresis in patients with familial hypercholesterolaemia and its combination with PCSK9 inhibitors has been performed. RESULTS: LA is also a potent therapeutic player having impact on inflammation and related mediators. A large body of evidence on this is available. On the contrary, only few observations are available on PCSK9-I effects on inflammation. CONCLUSIONS: It is quite clear that further investigation on possible direct and/or indirect pleiotropic effects of PCSK9-I on inflammatory molecules is necessary and to be expected. Evidence on both arguments with regard to HoFH and HeFH, are reported in short.

Clinical factors that predict remission of diabetes after different bariatric surgical procedures: interdisciplinary group of bariatric surgery of Verona (G.I.C.O.V.).

AIMS: The aims of the study were to investigate weight loss and glycemic control parameters after different bariatric surgical procedures in type 2 diabetes (T2D) obese patients and identify patients' factors that predict diabetes remission. METHODS: The study included 105 obese T2D patients (66 women and 39 men) who underwent laparoscopic gastric banding (LAGB, 11 subjects, age 47 ± 10 years, BMI 42.3 ± 8.3 kg/m(2)), or laparoscopic Roux-en-Y gastric bypass (RYBP, 77 subjects, age 50 ± 8 years, BMI 45.7 ± 6.8 kg/m(2)), or sleeve gastrectomy (SG, 17 subjects, age 49 ± 11 years, BMI 50.2 ± 8.8 kg/m(2)) during 2005-2012 period. RESULTS: The average percentage of weight loss at 12 months after surgery was 26.4 ± 9.8 %, and it was maintained at 24 and 36 months of follow-up. Diabetes remission occurred in 68.6 % of study participants (4/11 of LAGB, 54/77 of RYBP and 14/17 of SG). In multivariate Cox analysis, age, duration of diabetes, surgical procedure and glycated hemoglobin <53 mmol/mol (7 %) resulted significant predictors of diabetes remission (age RR = 0.97, 95 %CI 0.94-1.0, p = 0.05; diabetes duration RR = 0.93, 95 % CI 0.86-0.99, p = 0.036; rif LAGB, RYBP RR = 3.9, 95 % CI 1.31-11.57, p = 0.014; SG RR = 5.6, 95 % CI 1.67-18.64, p = 0.005; glycated hemoglobin RR = 0.54, 95 % CI 0.32-0.92, p = 0.024). CONCLUSIONS: Bariatric surgical procedures that modify the upper gastrointestinal tract anatomy (RYBP and SG) are more successful in producing weight loss and remission of T2D than those that simply restrict stomach capacity (LAGB). Younger age, short duration of diabetes and better glucose control confer higher probability of achieving remission of diabetes.