Relationship and New Prospectives in Joint Hypermobility in Children with Autism Spectrum Disorder: Preliminary Data.

Autism spectrum disorder (ASD) and joint hypermobility (JH) are considered two different etiological and clinical entities that most often appear in childhood. Despite growing increased research showing a co-occurrence for both conditions, a link between them is rarely established in clinical settings, and the relationship between ASD and JH has not so far been completely investigated in all age groups of ASD children. This preliminary study examined a cohort of 67 non-syndromic ASD children aged 2-18 years (sex ratio M:F = 12:1) showing different degrees of cognitive impairment and autism severity, using the Beighton scale and its revised version. A total of 63% of ASD patients aged 2-4 years and 73% of ASD patients aged ≥5 years presented significant scores of hypermobility. No significant correlation was found comparing total laxity score and cognitive assessments and severity of autistic symptomatology (p > 0.05). The results suggest that JH could be considered as a clinical characteristic of ASD patients and it needs to be assessed in order to schedule a better rehabilitation program.

Perinatal Cerebral Ischemic Lesion and SARS-CoV-2 Infection during Pregnancy: A Case Report and a Review of the Literature.

Perinatal stroke is related to possible differences in predisposing factors and outcomes between acutely and retrospectively diagnosed cases. In most cases, there are different risk factors and infections that could play an important role. Thus far, different clinical manifestations have been reported in children presenting with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ranging from asymptomatic status to severe disease sustained by an immune-mediated inflammatory response. SARS-CoV-2 has been associated with severe neurological diseases including seizures and encephalitis in both adults and children. However, there are still few reports regarding the possible relation between SARS-CoV-2 infection of mothers during pregnancy and the neurologic outcome of the newborns. We described the case of a newborn diagnosed with a perinatal stroke, born at 35 weeks of gestation from a mother presenting with SARS- CoV-2 infection during the last months of pregnancy. We also added a brief review of the literature with similar cases. Close monitoring and early intervention in young children born to infected mothers would be highly recommended for the potential neurodevelopmental risk.

Longitudinal Cognitive Assessment in Low-Risk Very Preterm Infants.

Background and Objectives: Preterm infants are at higher risk of neurodevelopmental impairment both at preschool and school ages, even in the absence of major neurological deficits. The early identification of children at risk is essential for early intervention with rehabilitation to optimize potential outcomes during school years. The aim of our study is to assess cognitive outcomes at preschool age in a cohort of low-risk very preterm infants, previously studied at 12 and 24 months using the Griffiths scales. Materials and Methods: Sixty-six low-risk very preterm infants born at a gestational age of <32 weeks were assessed at 12 and 24 months corrected age using the Griffiths Mental Development Scales (second edition) and at preschool age with the Wechsler Preschool and Primary Scales of Intelligence (third edition) (WPPSI-III). Results: At 12 and 24 months and at preschool age, low-risk very preterm infants showed scores within normal ranges with similar scores in males and females. A statistically significant correlation was observed in the general developmental quotient between 12 and 24 months; a further significant correlation was observed between the early cognitive assessments and those performed at preschool age, with a better correlation using the assessments at 24 months. Conclusion: The present study showed a favourable trajectory of cognitive development in low-risk very preterm infants, from 12 months to preschool age.

Glucose metabolism outcomes in acromegaly patients on treatment with pasireotide-LAR or pasireotide-LAR plus Pegvisomant.

INTRODUCTION: Disorders of glucose metabolism are a serious acromegaly comorbidity and may be differently impacted by medical treatments of acromegaly. In this retrospective longitudinal multicenter study, we investigated the outcome of glucose metabolism and its predictors in patients treated with Pasireotide LAR (PAS-LAR) alone or in combination with Pegvisomant (PAS-LAR + Peg-V). SUBJECTS AND METHODS: Acromegaly patients treated continously with PAS-LAR or PAS-LAR + Peg-V for at least 6 months. RESULTS: Forty patients (25 females, 15 males) were enrolled. At last visit, 27/40 patients (67.5%) reached biochemical control of acromegaly. Overall, glucose metabolism improved in 3 (all in PAS-LAR + Peg-V; 7.5%), worsened in 26 (65%) and remained unchanged in 11 patients (27.5%). Glucose metabolism worsened in 25 patients (73.5%) treated with PAS-LAR and in a single patient (16.7%) treated with PAS-LAR + Peg-V (p < 0.001). Among patients treated with Pas-LAR alone, GH at baseline was higher in those with worsening of glucose metabolism (p = 0.04) as compared to those with stable glucose status. A significantly higher reduction of HbA1c was observed in patients treated with PAS-LAR + Peg-V, as compared with those treated with PAS-LAR alone (p = 0.005). CONCLUSIONS: Our data confirmed that glucose metabolism in patients treated with PAS-LAR is often worsened, and may be predicted by entity of baseline GH hypersecretion and by the dose of PAS-LAR. Moreover, our data, although limited by small numbers, may suggest that the combination treatment PAS-LAR + Peg-V can improve glucose homeostasis in selected patients.

Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response.

BACKGROUND: The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. METHODS: Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. RESULTS: Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2-4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4-4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1-6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4-3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4-8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3-6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3-20.0). CONCLUSION: Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.

The Role of Growth Hormone Receptor Isoforms and Their Effects in Bone Metabolism and Skeletal Fragility.

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

Study of vessel density in adult-onset foveomacular vitelliform dystrophy with optical coherence tomography angiography.

BACKGROUND: To evaluate retinal and choriocapillaris (CC) vessel density in macular region in patients affected by adult-onset foveomacular vitelliform dystrophy (AOFVD) using optical coherence tomography angiography (OCTA) METHODS: A total forty-four right eyes of 44 AOFVD patients (20 females, 24 males, mean age 69.17 ± 11.57 years) divided in 3 stages (vitelliform, pseudohypopyon and vitelliruptive) and 60 normal right eyes of 60 controls (20 females, 40 males, mean age 66.04 ± 6.40 years) were included in this prospective study. We evaluated the vessel density of superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC in different macular areas (whole image, parafovea and fovea). We also analyzed the subfoveal choroidal thickness (SFCT) with Enhanced Depth Image (EDI)-OCT. RESULTS: The vessel density of SCP and of DCP did not differ between patients and controls in all macular sectors. The vessel density of CC was lower in patients compared to controls but the difference turned out to be statistically significant only in foveal region (p < 0.001). We found that the foveal vessel density of the CC was lower in vitelliform stage and significantly increased in vitelliruptive stage (p = 0.031). At EDI-OCT, the SFCT revealed a statistically significant increase in patients compared to controls (p = 0.002) whereas it was similar in the different stages of this dystrophy (p = 0.276). CONCLUSIONS: In vitelliform stage of AOFVD, OCTA and EDI-OCT can be useful to avoid mistakes of evaluation, due to the masking effect artifact. OCTA provides us a better understanding of the vascular role in the physiopathology of the macular diseases.

Choriocapillary vascular density in central serous chorioretinopathy complicated by choroidal neovascularization.

BACKGROUND: To evaluate choriocapillary vascular density (CVD) in eyes with central serous chorioretinopathy (CSC) complicated by choroidal neovascularization (CNV), at baseline and after intravitreal injections (IVR) of Ranibizumab, using optical coherence tomography angiography (OCTA). METHODS: Twelve eyes of 12 patients were enrolled as group 1 and 12 unaffected fellow eyes formed group 2. Twelve eyes of 12 healthy controls were the control group. RESULTS: CVD in Group 1 did not differ before and after treatment. CVD of Group 1 was significantly lower compared with controls at baseline (whole, parafovea and fovea p < 0.05). CVD of controls resulted significantly higher than Group 2 at baseline (whole, parafovea and fovea p < 0.05). There were not significant differences in CVD between Groups 1 and 2 at baseline (p > 0.05). CONCLUSIONS: OCTA revealed a choriocapillary hypoperfusion that may be responsable for the beginning of this disease and the late development of CNV.

Optical coherence tomography angiography to assess vascular remodeling of the choriocapillaris after low-fluence photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: To evaluate the efficacy of optical coherence tomography angiography (OCTA) in identifying changes in the choriocapillaris layer after low-fluence verteporfin photodynamic therapy (vPDT) in patients affected by chronic central serous chorioretinopathy (CSCR). METHODS: Low-fluence vPDT was performed on 28 eyes of 27 patients with CSCR. All patients underwent the following tests at baseline and 6 months after treatment: best corrected visual acuity (BCVA), fluorescein angiography, indocyanine green angiography, enhanced depth imaging OCT and OCTA. RESULTS: Subretinal fluid was completely absorbed in 18 of the 28 affected eyes (64.3%) after low-fluence vPDT ("responders"), and incompletely absorbed in 10 eyes (35.7%) ("non responders"). BCVA was significantly improved (p = 0.006) whereas central foveal thickness and choroidal foveal thickness were significantly decreased (p = 0.001 and p = 0.00 respectively) 6 months after treatment in responders. CONCLUSIONS: OCTA revealed a different pattern of vascular remodeling of the choriocapillaris between CSC patients who responded and those who did not respond to low-fluence vPDT.

Combined intravitreal ranibizumab and verteporfin photodynamic therapy versus ranibizumab alone for the treatment of age-related macular degeneration.

PURPOSE: To compare same-day combined therapy of photodynamic therapy with verteporfin (PDT-V) and intravitreal ranibizumab versus monotherapy with ranibizumab for the treatment of choroidal neovascularization. METHODS: IN THIS PROSPECTIVE STUDY, THE TOTAL NUMBER OF EYES WAS RANDOMIZED INTO TWO GROUPS: in the first, treatment consisted of a combined therapy of PDT-V and ranibizumab 0.5 mg on the same day; in the second, ranibizumab 0.5 mg in 3 monthly injections. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) on optical coherence tomography (OCT) were recorded before and 6 months after treatment. RESULTS: A total of 47 eyes of 47 subjects were enrolled in the study. In the combined-therapy group (group 1), the mean baseline BCVA ± standard deviation (SD) was 32.65 ± 11.09 letters (Snellen equivalent, 20/59); in the ranibizumab-alone group (group 2), 29.13 ± 9.03 letters (20/70). At 6 months' follow-up, in group 1 the mean baseline BCVA was 39.06 ± 10.12 letters (20/42); in group 2, 33.87 ± 12.06 letters (20/57). Improvement was significant in both group 1 (P = 0.03) and group 2 (P = 0.002). In group 1, the mean CMT at baseline ± SD was 315 ± 95.49 µm; in group 2, 306.33 ± 71.61 µm. At 6 months' follow-up, in group 1 it was 202 ± 52.02 µm; in group 2, 226 ± 65.58 µm. Reduction was significant in both group 1 (P = 0.0007) and group 2 (P = 0.00001). After 6-months, the rate of retreated eyes was 29.4% in group 1 and 43.3% in group 2. The need for retreatment did not depend on the treatment protocol (P = 0.34). CONCLUSIONS: From a functional and anatomic point of view, the two treatments showed equivalent efficacy, with fewer retreatments in group 1. No serious adverse events, such as retinal detachment, endophthalmitis, or ocular hypertension occurred in either group.