Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient.

We present a unique and unusual case of a male patient diagnosed with two coexisting and typically unassociated X-linked conditions: he was initially diagnosed with X-linked agammaglobulinemia (XLA) followed by a diagnosis of X-linked chronic granulomatous disease (XCGD) and an as of yet unpublished hypomorphic gp91phox variant in the CYBB gene. The latter was tested after the finding of granulomatous gingivitis. Hematopoietic stem cell transplant (HSCT) was performed due to severe colitis and nodular regenerative hyperplasia (NRH) of the liver. Following transplant, complete donor engraftment was observed with the restoration of a normal oxidative burst and full restoration of normal levels of circulating, mature CD19+ B cells. This case is singular in that it does not involve a contiguous gene syndrome in which deleted genes are in close proximity to either BTK and CYBB, which has been previously reported. To our knowledge, this is the first reported case of XLA and XCGD co-existing in a single patient and of having both inborn errors of immunity successfully treated by HSCT.

Improvement of SLC29A3 spectrum disorder-related sensorineural hearing loss after initiation of IL-6 inhibitor.

Tocilizumab is reported to reduce systemic inflammation in individuals with SLC29A3 spectrum disorder, but its effect on hearing loss has not been described. The authors present a boy toddler with a history of prematurity, dysphagia, hypersplenism, hyperpigmentation, short height and hearing loss who was referred to the immunology clinic. He initially presented shortly after birth with abnormal hearing screens followed by positive urine test for cytomegalovirus. However, the infection was determined to be postnatally acquired and hearing loss most likely from genetic causes given a family history of hearing loss and consanguinity. A pathogenic variant in SLC29A3 was found on whole-exome sequencing and given concern for SLC29A3 spectrum disorder, steroids were started. Following concerns for development of side effects with chronic steroid use, he was switched to interleukin 6 inhibitor therapy. The patient's inflammatory markers decreased on tocilizumab, and his sensorineural hearing loss was notable for improvement and stabilisation on therapy.

Improving Delivery of Care through Standardized Monitoring in Children with Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic, antigen-driven disorder for which endoscopic monitoring and multidisciplinary care are recommended to achieve histologic remission. The EoE team at our large academic center developed a quality improvement (QI) initiative aimed to reduce variability in monitoring. This QI project focused on completing 3 process metrics within 6 months of diagnosis: (1) outpatient follow-up with a gastroenterologist; (2) referral to an allergist; and (3) Follow-up esophagogastroduodenoscopy (EGD). METHODS: In January 2015, our QI team developed a registry of newly diagnosed EoE patients and maintained ongoing, weekly tracking of the process measures. Interventions to increase the completion of the process metrics included educational sessions, proactive reminders to providers, and targeted communications with patient families. Missed opportunities were evaluated by more in-depth chart review and categorized as provider- or patient-driven. RESULTS: We tracked 6-month process metrics from 2015 through 2018. During this interval, follow-up visit rates in GI improved from 77% to 86%, and the percentage of referrals placed to allergy increased from 65% to 77%. The percentage of patients completing a repeat EGD improved from 33% to 61%. Among patients without a repeated EGD, nearly 70% of those missed opportunities were provider-driven. CONCLUSIONS: In patients newly diagnosed with EoE, QI interventions, including patient registry development, implementation of a local standard of care, and creating a patient tracking system, improved adherence with national EoE monitoring guidelines.

16S rRNA Gene-Based Metagenomic Analysis of Ozark Cave Bacteria.

The microbial diversity within cave ecosystems is largely unknown. Ozark caves maintain a year-round stable temperature (12-14 °C), but most parts of the caves experience complete darkness. The lack of sunlight and geological isolation from surface-energy inputs generate nutrient-poor conditions that may limit species diversity in such environments. Although microorganisms play a crucial role in sustaining life on Earth and impacting human health, little is known about their diversity, ecology, and evolution in community structures. We used five Ozark region caves as test sites for exploring bacterial diversity and monitoring long-term biodiversity. Illumina MiSeq sequencing of five cave soil samples and a control sample revealed a total of 49 bacterial phyla, with seven major phyla: Proteobacteria, Acidobacteria, Actinobacteria, Firmicutes, Chloroflexi, Bacteroidetes, and Nitrospirae. Variation in bacterial composition was observed among the five caves studied. Sandtown Cave had the lowest richness and most divergent community composition. 16S rRNA gene-based metagenomic analysis of cave-dwelling microbial communities in the Ozark caves revealed that species abundance and diversity are vast and included ecologically, agriculturally, and economically relevant taxa.