DOCK8 Deficiency Presenting as an IPEX-Like Disorder.

PURPOSE: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. METHODS: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (Treg) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing. RESULTS: Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C>T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G→A). Treg cell function was severely compromised by both DOCK8 mutations. CONCLUSION: DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.

In Situ Simulation: An Essential Tool for Safe Preparedness for the COVID-19 Pandemic.

INTRODUCTION: Working under extreme stress can cause medical professionals to deviate from clinical guidelines even if they know of their existence, let alone in situations such as COVID-19 where guidelines are unclear, fluid, and resources limited. In situ simulation has been proven an effective tool for training medical professionals during previous healthcare crises, eg, Ebola, influenza, as well as for assessing the preparedness of centers by identifying potential latent safety threats. In this article, we describe our ongoing simulation activities to ensure that our staff is best prepared to adapt to the challenges of COVID-19. METHODS: This is a prospective preparedness assessment and training intervention at a tertiary care academic center in Lebanon during the COVID-19 pandemic. In situ simulations followed by debriefing with good judgment occur daily involving native teams of 3 to 5 professionals in the newly established COVID intensive care unit and wards, the adult and pediatric intensive care unit and wards, and the emergency department. The simulations are assessed by the instructor using the Simulation Team Assessment Tool and by the participants using the Simulation Effectiveness Tool. Transcripts of recorded simulation debriefings are analyzed for content for latent safety threats using the SHELL Framework (Software-Hardware-Equipment-Liveware). RESULTS: In 2 weeks, we conducted 15 simulations with 106 participants and 47 observers. Simulation Team Assessment Tool scores show an overall improvement across the hospital over time [101.5 ± 13 (80-134)]. Participants' feedback on the Simulation Effectiveness Tool has been predominantly positive on the educational and practical benefits of the simulation activity. Data from debriefings and observations demonstrated the following categories of latent safety threats: inadequate preparedness on infection control, uncertainty of guidelines on oxygen supplementation and intubation protocols, lack of leadership and communication, overall panic, and others. CONCLUSIONS: Our single-center preparedness intervention demonstrated multiple latent safety threats in relation to COVID-19, which can be recognized through simulation before translating into actual patient care.

In-situ simulations for COVID-19: a safety II approach towards resilient performance.

BACKGROUND: COVID-19 has taken the world by surprise; even the most sophisticated healthcare systems have been unable to cope with the volume of patients and lack of resources. Yet the gradual spread of the virus in Lebanon has allowed healthcare facilities critical time to prepare. Simulation is the most practical avenue not only for preparing the staff but also for troubleshooting system's latent safety threats (LSTs) and for understanding these challenges via Hollnagel's safety I-II approaches. METHODS: This is a quality improvement initiative: daily in situ simulations were conducted across various departments at the American University of Beirut Medical Center (AUBMC), a tertiary medical care center in Beirut, Lebanon. These simulations took place in the hospital with native multidisciplinary teams of 3-5 members followed by debriefing with good judgment using the modified PEARLS (Promoting Excellence and Reflective Learning in Simulation) for systems integration. All participants completed the simulation effectiveness tool (SET-M) to assess the simulation. Debriefings were analyzed qualitatively for content based on the Safety Model and LST identification, and the SET-Ms were analyzed quantitatively. RESULTS: Twenty-two simulations have been conducted with 131 participants. SET-M results showed that the majority (78-87%) strongly agreed to the effectiveness of the intervention. We were able to glean several clinical and human factor safety I-II components and LSTs such as overall lack of preparedness and awareness of donning/doffing of personal protective equipment (PPE), delayed response time, lack of experience in rapid sequence intubation, inability to timely and effectively assign roles, and lack of situational awareness. On the other hand, teams quickly recognized the patient's clinical status and often communicated effectively. CONCLUSION: This intervention allowed us to detect previously unrecognized LSTs, prepare our personnel, and offer crucial practical hands-on experience for an unprecedented healthcare crisis.

Ultrasound guided central line insertion in neonates: Pain score results from a prospective study.

BACKGROUND: Central lines can be placed through different techniques, either peripherally or centrally. Although they have the same aim, decision to use one of these modalities depends on the patient outcomes. The aim is to compare pain scores between ultrasound-guided central line insertion and peripherally inserted catheter in neonates in a prospective randomized single center study. METHODS: A randomized controlled trial was conducted in neonates requiring central venous access for any of the following reasons: total parenteral nutrition (TPN), antibiotics treatment for at least 7 days and having poor or difficult venous access. The study compared pain difference, in neonates, that were randomized between peripherally and ultra-sound guided centrally placed central lines using the validated pain score N - PASS. RESULTS: 61 neonates were enrolled in the study. US-guided CICC was associated with less pain as reported by the statistically significant lower pain score difference (p-value <0.001) than the standard PICC. Additionally, the US-guided CICC had a higher rate of successful first attempt (p = 0.012), lower overall number of attempts (p < 0.001), and shorter procedure duration (p < 0.001) as compared to standard PICC. CONCLUSION: US-guided CICC is a less painful technique than PICC line insertion associated with higher rate of successful first attempt, lower overall number of attempts and shorter procedure duration.