Lethal COG6-CDG in neonatal patient with arachnodactyly, joint contractures, and skin manifestations: Founder mutation in the Southeastern European population?

Herein, we report a lethal case of the ultra-rare COG6-congenital disorder of glycosylation (CDG) presenting with skin manifestations (scaling and erosions) and joint contractures in a neonate of Albanian origin. The patient was homozygous for a COG6 pathogenic variant, previously reported in another three individuals of Greek, Bulgarian and Turkish descent. The presence of a founder mutation in the geographical area is possible. The index case emphasizes the need to consider CDGs in neonatal patients with skin manifestations and joint contractures, particularly patients of Southeastern European or West Asian origin.

Intertemporal Improvement in Physicians' Perceptions of the Short-Term Adverse Outcomes of Neonatal Pain: Results of a Two-Time-Point National Survey.

Pain in early life may seriously impact neonatal outcomes. This study aimed to evaluate whether the perceptions of physicians working in neonatal intensive care units (NICUs) of the short-term adverse outcomes associated with neonatal pain have changed over a 20-year period. Self-administered questionnaires were distributed to 117 and 145 neonatologists, pediatricians, and fellows working in level III NICUs in 2000 (T1) and 2019 (T2), respectively. The questionnaire consisted of four domains, including the central nervous, cardiovascular, and respiratory systems, as well as "other systems" (metabolic/endocrine system, growth, and general condition), with 21 total items overall. Although the proportion of positive (correct) responses to the total and system-specific domain scores was significantly higher at T2 than T1, the knowledge of certain short-term adverse outcomes was suboptimal even at T2. Adjustment for cofactors confirmed the independent association of the survey time-point with the total and system-specific domain scores. Moreover, NICU type was an independent significant factor associated with the adjusted total and central nervous system scores, while young doctors had a better knowledge of adverse cardiovascular effects. Conclusions: The perceptions of NICU physicians concerning the short-term outcomes associated with neonatal pain have significantly improved over the past 20 years, although remaining knowledge gaps mandate ongoing efforts to achieve an improvement in neonatal care.

Adverse drug event prevention in neonatal care: a rule-based approach.

Adverse drug events (ADE) in a neonatal unit can be of great importance due to the underlying nature and the special characteristics of the patients. This paper presents our work on the development of a knowledge base (KB) for supporting the identification and prevention of ADEs. First, a literature review was conducted to identify ADEs observed through the use of the most commonly-used drugs in a specific neonatal unit. Then, the acquired knowledge was encoded according to an ontological data model developed for the representation of the specific facts for the neonatal unit. Finally, a rule-based prototype consisting of 164 rules was implemented in order to represent and simulate the inference procedure about preventing ADEs.

Changes in Physicians' Perceptions and Practices on Neonatal Pain Management Over the Past 20 Years. A Survey Conducted at Two Time-Points.

Intense research for more than three decades expelled the view that neonates do not experience pain. The aim of this survey was to investigate whether the Greek physicians involved in neonatal intensive care have changed their perceptions regarding neonatal pain, adapting their management practices to the knowledge that have emerged in the past 20-years. This study is a survey conducted at two time-points, 20 years apart. Anonymous questionnaires were distributed to 117 and 145 physicians working in neonatal intensive care units (NICUs) all over Greece in years 2000 and 2019, respectively. The response rate was 90.6 and 80.7% in 2000 and 2019, respectively. All respondents, at both time-points, believed that neonates experience pain, which has serious acute and long-term consequences, while the vast majority considered analgesia-sedation (A-S) during painful interventions as obligatory. Utilization of NICU protocols and pain assessment tools remained low although increased significantly between 2000 and 2019. The use of systemic A-S postoperatively was high at both time-points, while its implementation in infants subjected to prolonged pain, specifically mechanical ventilation, increased significantly by 2019. Systemic or local analgesia for acute procedural pain was used by lower proportions of physicians in 2019, except for the tracheal intubation. In contrast, the use of sweet solutions and non-pharmacological measures prior to or during bedside procedures significantly increased over time. Opioid administration significantly increased, while a shift from morphine to fentanyl was observed. International literature and perinatal-neonatal congresses were stated as the main sources of updating physicians' knowledge and improving management practice on neonatal pain prevention and treatment. In conclusion, Greek NICU-physicians' perceptions that neonates can experience pain with potentially serious acute and long-term consequences remained strong over the past 20 years. Although physicians' practices on neonatal pain management improved, they are still suboptimal, while significant differences exist among centers. Continuing education, globally accepted management protocols, and readily applied pain assessment tools would further improve the management of procedural pain and stress in neonates.

A Novel Mutation of VPS33B Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the VPS33B encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of VPS33B. A female patient of Greek origin presented on the 14th day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs∗17) mutation of exon 14 of VPS33B gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same VPS33B mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published VPS33B mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated VPS33B mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and/or renal tubular dysfunction, even in the absence of arthrogryposis.