Progressive decline of T and B cell numbers and function in a patient with CDC42 deficiency.

Single allele mutations in the Cell Division Control protein 42 homolog (CDC42) gene were recently shown to cause Takenouchi-Kosaki syndrome with diverse manifestations. These include persistent mild thrombocytopenia with large platelet size, severe developmental delay, growth retardation, facial dysmorphism, and other neurodevelopmental and hematological anomalies. CDC42 deficiency might also cause myelofibrosis, myeloproliferation, and severe autoinflammation. CDC42 closely interacts with the Wiskott-Aldrich Syndrome Protein, but little is still known about the immune abnormalities associated with CDC42 deficiency. Detailed immune evaluations were performed in a patient diagnosed with a CDC42 Tyr64Cys mutation. The 19-year-old female suffered from recurrent pneumonia, otitis media, and bacteremia, which resolved at 10 years of age, concordant with the initiation of amoxicillin prophylaxis. In addition, the patient had frequent viral upper respiratory tract infections, which resolved without need for medical interventions. Immune evaluations demonstrated decreased immunoglobulin levels, inability to maintain antibody responses, progressive decline in the number of CD19+ B cells, and decreased switched memory B cells. There was also a decrease in CD4+ and CD8+ T cells, markedly reduced naïve T cells, and intermittent depressed proliferation of T cells to stimulation. Natural killer cells' number and functions were normal. However, no opportunistic infections were observed, nor was there evidence for autoinflammation. CDC42 deficiency might also be associated with decline in T and B cell function. Therefore, immunity in patients with CDC42 defects should be closely monitored, particularly among those with frequent infections or systemic autoinflammation.

The Association of Pseudohypoparathyroidism Type Ia with Chiari Malformation Type I: A Coincidence or a Common Link?

A 19-month-old boy was referred for progressive weight gain. His past medical history included congenital hypothyroidism and developmental delay. Physical examination revealed characteristics of Albright Hereditary Osteodystrophy, macrocephaly, and calcinosis cutis. He had hypocalcemia, hyperphosphatemia, and elevated Parathyroid Hormone levels. Genetic testing revealed a known mutation of GNAS gene, confirming the diagnosis of Pseudohypoparathyroidism Type Ia (PHP-Ia) (c.34C>T (p.G1n12X)). He had a normal brain MRI at three months, but developmental delay prompted a repeat MRI that revealed Chiari Malformation Type I (CM-I) with hydrocephalus requiring neurosurgical intervention. This was followed by improvement in attaining developmental milestones. Recently, he was diagnosed with growth hormone deficiency. This case suggests the potential association of CM-I with PHP-Ia. Larger studies are needed to assess whether CM-I with hydrocephalus are common associations with PHP-Ia and to define potential genetic links between these conditions. We propose a low threshold in performing brain MRI on PHP-1a patients, especially those with persistent developmental delay to rule out CM-I. Early intervention may improve neurodevelopmental outcomes and prevent neurosurgical emergencies.

Impact of an in-house emergency radiologist on report turnaround time.

BACKGROUND: One of the many challenges facing emergency departments (EDs) across North America is timely access to emergency radiology services. Academic institutions, which are typically also regional referral centres, frequently require cross-sectional studies to be performed 24 hours a day with expedited final reports to accelerate patient care and ED flow. OBJECTIVE: The purpose of this study was to determine if the presence of an in-house radiologist, in addition to a radiology resident dedicated to the ED, had a significant impact on report turnaround time. METHODS: Preliminary and final report turnaround times, provided by the radiology resident and staff, respectively, for patients undergoing computed tomography or ultrasonography of their abdomen/pelvis in 2008 (before the implementation of emergency radiology in-house staff service) were compared to those performed during the same time frame in 2009 and 2010 (after staffing protocols were changed). RESULTS: A total of 1,624 reports were reviewed. Overall, there was no statistically significant decrease in the preliminary report turnaround times between 2008 and 2009 (p = 0.1102), 2009 and 2010 (p = 0.6232), or 2008 and 2010 (p = 0.0890), although times consistently decreased from a median of 2.40 hours to 2.08 hours to 2.05 hours (2008 to 2009 to 2010). There was a statistically significant decrease in final report turnaround times between 2008 and 2009 (p < 0.0001), 2009 and 2010 (p < 0.0011), and 2008 and 2010 (p < 0.0001). Median final report times decreased from 5.00 hours to 3.08 hours to 2.75 hours in 2008, 2009, and 2010, respectively. There was also a significant decrease in the time interval between preliminary and final reports between 2008 and 2009 (p < 0.0001) and 2008 and 2010 (p < 0.0001) but no significant change between 2009 and 2010 (p = 0.4144). CONCLUSION: Our results indicate that the presence of a dedicated ED radiologist significantly reduces final report turnaround time and thus may positively impact the time to ED patient disposition. Patient care is improved when attending radiologists are immediately available to read complex films, both in terms of health care outcomes and regarding the need for repeat testing. Providing emergency physicians with accurate imaging findings as rapidly as possible facilitates effective and timely management and thus optimizes patient care.