Multicentric Italian case-control study on 25OH vitamin D levels in children and adolescents with Prader-Willi syndrome.

PURPOSE: 25OHD levels in patients with Prader-Willi Syndrome (PWS), the most frequent cause of genetic obesity with a peculiar fat mass distribution, are still debated. Insulin resistance (IR), Body Mass Index-SDS (BMI-SDS), Growth Hormone Therapy (GHT), and puberty onset seem to interact with 25OHD levels. The objectives of the study are: (1) To analyze 25OHD levels in pediatric PWS patients in comparison with a control group (CNT) (2) To evaluate a possible correlation between BMI-SDS, HOMA-IR, puberty, GHT, and 25OHD levels. METHODS: This is a retrospective case-control, multicenter study. Data were collected among 8 different Italian Hospitals (outpatient clinics), over a period of four years (2016-2020). We included 192 genetically confirmed PWS and 192 CNT patients, aged 3-18 years, matched 1:1 for age, gender, BMI-SDS, Tanner stage, sun exposure, and month of recruitment. RESULTS: No statistically significant differences in 25OHD levels were observed between the PWS population and the CNT (PWS 24.0 ng/mL vs CNT 22.5 ng/mL, p > 0.05), OR = 0.89 (95% CI 0.58-1.35). We observed a slight, although non-significant, reduction in 25OHD levels comparing NW and OB populations. HOMA-IR, puberty onset, genotype and GHT (previous or ongoing) did not show statistically significant correlation with 25OHD levels. CONCLUSIONS: Our findings could be useful for clinicians to optimize the therapeutic management as well as to increase awareness of PWS.

MKRN3 circulating levels in Prader-Willi syndrome: a pilot study.

CONTEXT: Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect. MKRN3, a maternal imprinted gene located on 15q11.2-q13 region, encodes makorin ring finger protein 3, whose deficiency causes precocious puberty, an extremely rare symptom in PWS. OBJECTIVE: This study aimed to evaluate MKRN3 levels in patients with PWS and to analyze its correlation with sexual hormone levels, insulin resistance and Body Mass Index (BMI). METHODS: We performed an observational cross-sectional study and enrolled 80 patients with genetically confirmed diagnosis of PWS with median age of 9.6 years. RESULTS: MKRN3 levels were measurable in 49 PWS patients with a geometric mean of 34.9 ± 22 pg/ml (median: 28.4). Unmeasurable levels of MKRN3 were found in 31 patients. No statistically significant differences were found between patients with and without measurable MKRN3 levels for any clinical, biochemical, or genetic characteristics. However, MKRN3 levels were inversely correlated with HOMA-IR index (p: 0.005) and HbA1c (p: 0.046) values. No statistically significant correlations were found between MKRN3 and LH, estradiol and testosterone concentrations, pubertal development and genetic defect, whereas a direct correlation with FSH was found (p: 0.007). CONCLUSIONS: The typical genetic defect of PWS should lead to unmeasurable levels of the MKRN3 protein due to the inactivation of the paternal allele. Measurable circulating MKRN3 could suggest the possible involvement of tissue-specific imprinting mechanisms and other regulatory factors in gene expression. Correlations with HOMA-IR index, HbA1c, and FSH suggest peripheral actions of MKRN3, but future studies are warranted to investigate this topic.

Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome.

PURPOSE: Angiopoietin-like 8 (ANGPTL8) is a liver- and adipose tissue-produced protein that predicts non-alcoholic fatty liver disease (NAFLD) and altered metabolic homeostasis in the general population as well as in persons with common and genetic obesity, including the Prader-Willi syndrome (PWS). However, its metabolic correlate in paediatric patients with respect to PWS is unknown. METHODS: This cross-sectional study investigated circulating ANGPTL8 and adipocytokines levels in 28 PWS and 28 age-, sex- and BMI-matched children and adolescents (age, 7.0-17.8y) in relation to NAFLD and metabolic homeostasis assessed by OGTT, paediatric metabolic index (PMI) and fatty liver index (FLI), liver ultrasonography (US), as well as dual-energy X-ray absorptiometry (DEXA) for analysis of fat (FM) and fat-free mass (FFM). RESULTS: At the set level of significance, PWS children showed lower values of FFM (p < 0.01) but healthier insulin profiles (p < 0.01) and PMI values (p < 0.05) than matched controls. By US, the prevalence of NAFLD was similar between groups but less severe in PWS than controls. Analysis of ANGPTL8 levels showed no difference between groups, yet only in PWS ANGPTL8 levels were associated with ALT levels, FLI values and NAFLD. In stepwise multivariable regression analysis on merged data, ANGPTL8 levels were independently predicted by BMI SDS, leptin levels and NAFLD. CONCLUSION: ANGPTL8 levels are similar in PWS and controls and, overall, they are directly associated with the presence and severity of NAFLD in patients with PWS.

25OH vitamin D levels in pediatric patients affected by Prader-Willi syndrome.

PURPOSE: Obesity, insulin resistance, and puberty seem to influence and been inversely associated with 25-hydroxy vitamin D (25OHD) levels. To our knowledge, a study on 25OHD in children and adolescents with Prader-Willi syndrome (PWS), a genetic form of obesity, is not yet available. OBJECTIVE: To analyze the 25OHD values in pediatric PWS subjects in comparison with a control group (CNT), highlighting the possible correlations with IR, BMD, body composition, pubertal stage, and GH therapy (GHT). METHODS: Auxological and laboratory parameters, HOMA-IR, Vitamin D status, and bone density and body composition by DEXA scan were analyzed in 52 PWS and 110 controls (CNT), gender-, age-, and BMI-SD matched. None of them was on calcium or vitamin D. 20 PWS were on growth hormone (GH) therapy and 32 were previously treated. RESULTS AND CONCLUSION: Altogether, PWS had similar values of 25OHD compared to CNT.16 PWS (30.7%) and 27 CNT (24.5%) had low 25OHD levels (< 20 ng/ml) (p = NS). 25OHD of PWS on GHT were comparable to those previously treated. In both groups, univariate analysis showed a negative correlation between 25OHD and fat mass% (FM%). GH therapy and pubertal stage were positively correlated with bone parameters analyzed by DXA. Multivariate regression confirmed only FM% as negative predictor of 25HOD in PWS patients, as previously described. GHT does not seem to influence 25OHD in PWS. CONCLUSION: Our data showed that PWS had similar values of 25OHD compared to CNT. As already described, FM seems to be the only parameter influencing 25OHD levels. Finally, GHT does not seem to influence 25OHD metabolism in PWS.

Disorders of glucose metabolism in Prader-Willi syndrome: Results of a multicenter Italian cohort study.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS) is characterized by a high incidence of altered glucose metabolism (AGM). However, epidemiological data on impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) are still discordant. METHODS AND RESULTS: We performed a multicenter study based on 274 PWS patients [144 females, aged 20.3 ± 10.4 yrs (range: 8.1-50.1 years)] evaluating the prevalence for AGM in the entire group, and according to age (children <10 yrs; adolescents 10-18 yrs, and adults >18 yrs), Body Mass Index (BMI = kg/m(2)), gender, genotypes (deletion or uniparental disomy for chromosome 15), and GH therapy (GHT) (untreated, previously or currently treated). Altogether, AGM was detected in 67 (24.4%) of patients (0.7% IFG, 10.2% IGT, 13.5% T2DM). The prevalence of AGM was correlated to age (p = 0.001), BMI (p = 0.001) and HOMA-IR (p = 0.001). However, gender, genotype, and GHT did not influence AGM development in univariate analysis. These data were confirmed as positive predictors when inserted in a multivariate analysis model. CONCLUSION: This study is the first report on the prevalence of AGM in a large population of PWS. Overall, PWS subjects show a high prevalence of AGM that appears more common in obese and adult subjects. Our data confirm the main role of obesity on the individual metabolic risk clustering in PWS, and thus reinforce the concept that improvement in weight control remains the most important goal of any PWS treatment program.

Non-Alcoholic Fatty Liver Disease (NAFLD) in children and adolescents with Prader-Willi Syndrome (PWS).

We tested the hypothesis that patients with Prader-Willi syndrome (PWS) may be at lower risk of developing non-alcoholic fatty liver disease (NAFLD) because of a higher insulin sensitivity. Twenty-one PWS patients and 42 control subjects closely similar for age, gender, pubertal stage and body mass index (CNT), were studied. Metabolic profile and body composition were assessed. NAFLD was established by a validated method of US grading (range from G0 to G3). PWS patients showed a significantly better metabolic profile (lower waist circumference, fasting glucose levels, HOMA-IR, cholesterol, transaminase levels and trunk fat mass/fat mass ratio). Furthermore, NAFLD G1stage was significantly more frequent in PWS subjects (P < 0.05), whereas G2 stage was significantly more frequent in control patients (P < 0.05). NAFLD grading seems to correlate with body composition in PWS, also after adjustment for sex and GH treatment. To our knowledge, this is the first report suggesting a reduced risk of NAFLD in PWS children.

Takotsubo syndrome and brachydactyly: a new heart-hand syndrome?

The Takotsubo syndrome (TTS) is a transient myocardic hypoadyskinesis so called for its typically aspect like the cages used by Japanese fisherman to trap octopus. Presently, several etiologies were considered for the development of TTS, the most accredited ones suggest that stress, adrenoreceptor hyperactivity and estrogens are the most important causes of transient morphofunctional alterations of left ventricle. We describe the case of 60 year-old woman with a chest pain occurred after a quarrel. Because of this, she went to the Emergency Department (ED) where T wave flat in lead D-I, increase of CK-MB mass and Troponin I were found. Subsequently, a coronary-ventriculography was performed and a diagnosis of Takotsubo syndrome was made. Also a bilateral IV toe brachydactyly was noted. In medical literature, there are many syndromes described about the association between skeletal alteration of the hands and heart abnormalities (heart-hand syndrome). The Authors wonder if this case can belong to this kind of complex malformations as well as if a molecular-genetic trait can link the two clinical aspects.

Radiation-induced total regression of a highly recurrent giant perianal condyloma: report of case.

We report a case of a highly recurrent giant perianal condyloma, or Buschke-Lowenstein tumor, which was successfully treated by telecobalt therapy. We conclude that radiation therapy is an optional treatment modality for the management of giant perianal condylomata in selected cases.

Seroprevalence of Helicobacter pylori infection in a group of hospitalized geriatric patients.

BACKGROUND: In recent years several epidemiological surveys have reported the association between Helicobacter Pylori (HP), chronic ischemic heart disease (CHD) and cerebrovascular disease (CVD). None involved the geriatric population in which these diseases are prevalent. METHODS: We investigated the HP seropositivity prevalence in a group of over 75-year-old subjects recruited among all patients consecutively admitted for various diseases in an Internal Medicine Department during a period of 9 months. INTERVENTION: We measured HP IgG antibodies employing a commercially available kit based on reverse flow chromatography highly feasible and simple to perform and we investigated all patients for past or present CHD/CVD. RESULTS: From our data, the prevalence of seropositivity to Hp does not differ from other wider age stratified studies; more in detail; in the over 90-year-old patients we found the same HP seropositivity prevalence as in younger group but were not able to confirm the progressive lowering or seroprevalence in extreme geriatric age. CONCLUSIONS: No clear correlation between HP seroprevalence and CHD and CVD was found, but a link with CHD seems possible for the determinant (age) is common to both conditions.

Diphtheria antitoxin levels in the 14-30-year age group in Italy.

In order to verify diphtheria immunity a seroepidemiological survey was performed in 1996-1997. Serum samples were obtained from 501 subjects 14 years old, recruited at 8 schools in Rome, and from 490 subjects 20-30 years old recruited from 15 Italian regions. Serum diphtheria antitoxin was titrated using the Vero cell assay. The minimum protection level of antitoxin was set at 0.01 IU ml-1. The results show that the younger population have a good immunity to diphtheria while a large proportion of young adults is devoid of protective levels of diphtheria antitoxin. Out of the 501 subjects 14 years old, 495 (98.8%) had a diphtheria antitoxin titre > or = 0.01 IU ml(-1). Only 6 (1.2%) teenagers were susceptible. Out of the 490 subjects 20-30 years old, 109 (22.2%) were susceptible, 381 (77.8%) had a diphtheria antitoxin titre > or = 0.01 IU ml(-1). The data stress for booster immunization at the end of junior high school.

[Chagasic megacolon. Treatment by abdominal recto-sigmoidectomy with mechanical colo-rectal termino-lateral anastomosis. Preliminary results]. / Megacólon chagásico. Tratamento pela retossigmoidectomia abdominal com anastomose mecânica colorretal término-lateral. Resultados preliminares.

Abdominal rectosigmoidectomy with end to side colorectal mechanical anastomosis is proposed as a new technique for surgical treatment of Chagasic megacolon. The rectum is sectioned and closed at the level of the peritoneal reflexion. The end of the descending colon is anastomosed to the posterior surface of the rectum, as distal as possible, using the intraluminal stapler (Ethicon CDH33). The final result of the operation is similar to Duhamel-Haddad technique with the advantage of being a one stage operation. Forty-three patients with chagasic megacolon were operated on during the period 1989-1994. Twenty-seven were female and 16 were male with ages ranging from 23 to 76 and a mean of 46.1 years. Results obtained were satisfactory; there were no deaths; only three postoperative complications occurred (6.9%). Only one of these (dehiscence of the rectal cupula) was specific for the proposed technique. The two others were intestinal obstruction, due to volvulus of the small intestine in one case and to adhesions in the other. All complications were managed by surgery. All patients are being followed regularly and up to the present time they report daily bowel movements, passing well-formed stools. There are no complaints of fecal incontinence sexual function or disturbed formation of fecaloma in the rectal stump. The colorectal anastomosis was ample in all patients. Since this is a one stage operation with a low rate of complications, the short hospital stay largely compensates the cost of the mechanical suturing device. Regarding recurrences, a long follow-up period of at least 10 years is necessary to evaluate the real effectiveness of this technique.

[Tertiary hyperparathyroidism during chronic kidney failure under dialysis treatment. Apropos a clinical case]. / Iperparatiroidismo terziario in corso di insufficienza renale cronica in trattamento dialitico. Considerazioni a proposito di un caso clinico.

The authors describes a case of tertiary hyperparathyroidism (HPTH) in a uremic patient on intermittent dialysis treatment: the term refers to an adenoma with ensuing uncontrolled parathormone (PTH) secretion rate arising on the ground of hyperstimulated hypertrophied parathyroid glands. The syndrome was heralded clinically by bone pain, psychiatric disorder and biochemically by increased levels of calcium and alkaline phosphatase (AP), while parathormone (PTH), did not change from basal very high levels as commonly found in uraemic patients. As hypercalcemia in the hemodialyzed is an infrequent finding the only alternative explanation could have been hypercalcemic secondary HPTH related to hyperplastic autonomous parathyroids. For no clinical and laboratory findings as well as US findings and double scintigraphy (99mTc and 201mTl) may suggest differential diagnosis the patient underwent total parathyroidectomy which actually revealed an adenoma of the left superior parathyroid gland. Bone pain and psychiatric disturbances disappeared and now get well on chronic dialysis treatment and 1.25-OH Vit D3 supplement.

[Anaphylaxis after dextran 40 infusion: report of a case and review of the literature]. / Anafilaxia após infusão de dextran 40: relato de caso e revisão bibliográfica.

Anaphylactic reactions to colloid volume substitutes, such as dextran, are rare, however, with their increasing utilization in clinical practice an increasing awareness of their potential antigenicity is required. This article reports a severe allergic reaction induced by infusion of dextran 40 during the beginning of a general anesthesia in a 59 year old patient who was going to be submitted to an operation for treatment of chagasic megacolon. The patient died from this complication after 28 days. A review of literature of this complication and a discussion about its physiopathological mechanism and prevention is presented.

[Abdominal lymph nodes: the echographic evaluation criteria]. / Linfonodi addominali: criteri di valutazione ecografica.

US patterns of abdominal lymph nodes were investigated in patients with neoplastic and non-neoplastic diseases, and in randomly-chosen subjects with no evidence of any pathologic condition. Major longitudinal diameter (DMax) was statistically evaluated, together with minor transverse diameter (DMin), roundness index (RI), and structural index (IS)-i.e., the presence of a central hyperechoic line (as the US sign of normal lymph node architecture). DMax proved to be useless for distinguishing between groups. The presence of a central hyperechoic line was the most useful parameter, although the extant 3 (DMin, RI, IS) were also useful for distinguishing between groups. By correlating each numerical parameter with the hyperechoic line sign an even better discrimination was obtained. Thus, it can be assumed that only a combined and comprehensive evaluation of the above parameters makes the best criterion to differentiate between neoplastic and non-neoplastic abdominal lymph nodes.

[Enlargement of the lymph nodes of the hilus hepatis: a further ultrasonographic sign of acute viral hepatitis]. / Ingrandimento dei linfonodi ilari epatici: ulteriore segno ultrasonografico di epatite virale acuta.

Enlarged hilar lymph nodes are usually reported as the most frequent US finding in acute viral hepatitis. The authors compared this finding with other pathologic conditions--i.e., asymptomatic cholelithiasis and acute cholecystitis--and with gallbladder wall thickening, which is also observed in acute hepatitis. From their results, they drew the following conclusions: a) lymph node enlargement at the hepatic hilum was a very frequent finding (11/15) at US in the patients with acute viral hepatitis; b) its occurrence was statistically more frequent than in both cholelithiasis and cholecystitis; c) gallbladder wall thickening was found in 53.3% of the patients with acute hepatitis; d) lymph node enlargement and gallbladder wall thickening were not related. The authors suppose enlarged lymph nodes to be suggestive of hepatic damage in a pattern of immunological hyperactivity rather than the result of inflammatory gallbladder conditions during acute hepatitis. Since only 2 cases could be followed, the authors cannot discuss the prognostic significance of enlarged lymph nodes after cytolytic enzymatic signs of viral hepatitis have disappeared.

[Kinetic analysis of bromosulfophthalein in alcoholic liver disease]. / L'analisi della cinetica della bromosulfonftaleina (BSF) nell danno epatico da alcool.

The Authors evaluated BSF kinetics in 100 subjects affected by hepatic disorders of different degrees of progression produced by chronic alcoholic abuse in comparison with 22 healthy subjects. CBSF and Ke, model independent parameters, were found to discriminate better among groups; model dependent parameters showed, above all, a progressive reduction of fractional hepatic uptake (a) as liver damage worsens and a typical pattern of cirrhosis, especially of decompensated form, characterized by a high fractional hepatic plasma reflux (b). BSF kinetics also showed the early cholestatic effect produced by alcohol. Even if kinetic analysis proved useful, from a clinical point of view, the Authors feel that the simple 45 min BSF retention test and still better the one for Ki (uncorrected initial slope of the disappearance curve) are sufficient to detect and discriminate among the different stages of liver alcoholic diseases.

[Sulfobromophthalein kinetics in normal subjects and patients with alcoholic cirrhosis (author's transl)]. / La cinetica di scomparsa della sulfobromoftaleina: confronto dei parametri modello-dipendenti e modello-indipendenti nella cirrosi postalcoolica.

The AA. studied sulfobromophthalein kinetics in normal subjects and patients with alcoholic cirrhosis by compartmental analysis and by mathematical resolution of disappearance plasmatic curve of BSF. The comparison between the two methods gave some interesting clues for understanding BSF metabolism in alcoholic cirrhosis. From obtained data it seems that BSF clearance in these patients, besides on hepatic uptake, like normal subjects, largerly depends on intact secretory function of the liver.