Implementing a Transition Program from Paediatric to Adult Services in Phenylketonuria: Results after Two Years of Follow-Up with an Adult Team

We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7–15) vs. 14 (7–20); p = 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L; p = 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4–96)% vs. 37 (5–85)%; p = 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4–6) vs. 11 (8–13); p < 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.     

A Three-Year Longitudinal Study Comparing Bone Mass,Density, and Geometry Measured by DXA,pQCT, and Bone Turnover Markers in Children with PKU Taking L-Amino Acid or Glycomacropeptide Protein Substitutes

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–16 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16 years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16 years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15 years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm²), bone mineral apparent density (L2–L4 BMAD g/cm³) and total body less head BMDa (TBLH g/cm²). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.     

Analytical Assessment and Nutritional Adequacy of School Lunches in Sintra’s Public Primary Schools

School meals present several cost benefits overtime at the short, medium, and long term for individuals and society. This cross-sectional study aims to analyse the nutritional composition and evaluate the adequacy of school lunches. One hundred and fifty-eight samples were collected and analysed from 10 primary schools in Sintra’s municipality, served during one week. On average, energy (27.7% daily energetic requirements) and carbohydrate (48.1%) contents did not reach the reference values, and the content of protein (19.5%) exceeded the reference value (p < 0.05). The mean total fat (28.8%) and saturated fatty acids (5.4%) content complied with the recommendations. The mean salt (1.7 g) and dietary fibre (8.3 g) content exceeded the reference value but did not differ significantly from the recommendations. Addressing school canteens is crucial, not only in a nutritional approach, but also as an opportunity to achieve healthier, sustainable, and accessible food systems, aligned with the Sustainable Development Goals 2030. We highlighted the importance of evaluating evidence-based practices and disseminated practice-based evidence regarding the adequacy of school lunches.     

Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex^®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex^® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex^® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex^® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex^® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.     

Genomic Analysis of Novel Poxvirus Brazilian Porcupinepox Virus,Brazil, 2019

We obtained the complete sequence of a novel poxvirus, tentatively named Brazilian porcupinepox virus, from a wild porcupine (Coendou prehensilis) in Brazil that had skin and internal lesions characteristic of poxvirus infection. The impact of this lethal poxvirus on the survival of this species and its potential zoonotic importance remain to be investigated.     

Management of functioning pediatric adrenal tumors

AimThe aim of this study is to present our experience in the management of hormonally active adrenal tumors in children.Material and methodsWe did a retrospective chart review of all children with hormonally active adrenal tumors evaluated at the endocrinology clinic and operated at our institution between 1983 and 2019.ResultsThere were 75 patients included in the study, 58 with adrenocortical tumors (ACTs) and 17 with pheochromocytomas (PCCs). Within the group of patients with ACTs, there were 41 females and 17 males. The mean age was 58.3 (SD: 87.9; range: 9–211) months. The clinical manifestation of the tumor's hormonal activity was virilization in 37 cases, Cushing syndrome in 5, and mixed in 16. A positive family history was present in 11 patients (18.9%). The mean tumor size was 48.2 (SD: 22.4; range: 7–120) mm. The pathological diagnosis was adenoma in 42 cases, carcinoma in 15 cases, and macronodular hyperplasia in 1. Median follow-up was 192 (range: 50–290) months. Tumor recurrence occurred in 6 patients (10.3%), and there were three disease-related deaths (5%). Within the group of patients with PCCs, there were 11 males and 6 females. The mean age was 146.7 (SD: 71.2; range: 60–216) months. A positive family history was present in 7 patients (41.2%). The mean tumor size was 36.6 (SD: 16.7; range: 7–120) mm. The pheochromocytoma was classified as benign in 15 cases and as malignant in 2. During a median follow-up of 180 (range: 127–300) months, recurrence was observed in 6 cases (35.3%) and disease-related death in 1 case (5.9%).ConclusionsProper diagnosis and management at our referral center were associated with a high cure rate, even in cases of malignant tumors. Familial surveillance is highly recommended.Level of evidenceLevel IV.     

Subtype‐specific differences in transmission cluster dynamics of HIV‐1 B and CRF01_AE in New South Wales,Australia

IntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.     

Pseudoangiosarcomatous squamous cell carcinoma: first case report on penis

Pseudoangiosarcomatous squamous cell carcinoma, also called pseudovascular, pseudoangiomatoid or adenoid pseudovascular carcinoma, is an uncommon and highly aggressive variant of squamous cell carcinoma. Histologically, it is characterized by proliferation of atypical keratinocytes with acantholysis and formation of pseudovascular spaces, forming anastomosed channels lined with neoplastic cells that invade the dermis. These cells are positive for cytokeratin and negative for vascular markers such as CD31 and CD34. There are few reports of this variant in the literature. Skin, breast, lung and vulva involvement have been described, but to the best of our knowledge, no cases involving the penis has been described. This study aims to describe the first case of angiosarcomatous squamous cell carcinoma of the penis. The patient presented with a painful lesion in the penis associated with urinary retention. Macroscopic findings exhibited an ulcerative vegetating lesion that involving the entire glans and part of the penile body, as well as infiltration of penile structures and scrotal skin. Microscopy shows atypical proliferation of sarcomatous keratinocyte pattern mimicking vascular spaces. Human papilloma virus (HPV) biomarkers and polymerase chain reaction (PCR) were all negative. Advanced penile squamous cell carcinoma with aggressive lymph node metastasis. This report presents the first case of penile pseudoangiosarcomatous squamous cell carcinoma, as an important differential diagnosis.