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PurposeThe purpose of this study was to compare the natural history of visual function change in cohorts of patients affected with retinal degeneration due to biallelic variants in Bardet-Biedl syndrome genes: BBS1 and BBS10.MethodsPatients were recruited from nine academic centers from six countries (Belgium, Canada, France, New Zealand, Switzerland, and the United States). Inclusion criteria were: (1) female or male patients with a clinical diagnosis of retinal dystrophy, (2) biallelic disease-causing variants in BBS1 or BBS10, and (3) measures of visual function for at least one visit. Retrospective data collected included genotypes, age, onset of symptoms, and best corrected visual acuity (VA). When possible, data on refractive error, fundus images and autofluorescence (FAF), optical coherence tomography (OCT), Goldmann kinetic perimetry (VF), electroretinography (ERG), and the systemic phenotype were collected.ResultsSixty-seven individuals had variants in BBS1 (n = 38; 20 female patients and 18 male patients); or BBS10 (n = 29; 14 female patients and 15 male patients). Missense variants were the most common type of variants for patients with BBS1, whereas frameshift variants were most common for BBS10. When ERGs were recordable, rod-cone dystrophy (RCD) was observed in 82% (23/28) of patients with BBS1 and 73% (8/11) of patients with BBS10; cone-rod dystrophy (CORD) was seen in 18% of patients with BBS1 only, and cone dystrophy (COD) was only seen in 3 patients with BBS10 (27%). ERGs were nondetectable earlier in patients with BBS10 than in patients with BBS1. Similarly, VA and VF declined more rapidly in patients with BBS10 compared to patients with BBS1.ConclusionsRetinal degeneration appears earlier and is more severe in BBS10 cases as compared to those with BBS1 variants. The course of change of visual function appears to relate to genetic subtypes of BBS.

Author(s): Naohiro Shioji [sup.1] [sup.2], Kazuyoshi Aoyama [sup.3] [sup.4], Marina Englesakis [sup.5], Gail Annich [sup.1], Jason T. Maynes [sup.3] [sup.6] Author Affiliations: (1) grid.17063.33, 0000 0001 2157 2938, Department of [...], The current coronavirus disease of 2019 (COVID-19) pandemic has presented unique health challenges in the pediatric population. Compared to adults, the most significant change in viral disease manifestation is encompassed by the multisystem inflammatory syndrome in children (MIS-C). MIS-C is a new inflammatory syndrome which develops 2-4 weeks after COVID-19 exposure, with evidence suggesting it is a post-infectious immune reaction. We describe its epidemiology, pathophysiology, diagnosis (which varies based on definition used) and treatment options based on published recommendations. A systematic literature search we conducted through MEDLINE yielded 518 abstracts and identified five studies that reported more than 100 cases of MIS-C and their mortality. Most cases developed multiorgan dysfunction, including cardiovascular, dermatologic, neurological, renal, and respiratory issues, and required intensive care unit (ICU) admission. Many patients admitted to the ICU needed inotrope support and invasive mechanical ventilation, and the most severe cases required extracorporeal membrane oxygenation support. Most clinicians treated MIS-C with intravenous immunoglobulin, systemic steroids, and biological therapies. Overall mortality was low (2-3%) in all studies. Further research is needed to: understand if early intervention can prevent its progression; optimize its treatment; and improve outcomes of this new syndrome for the patients who develop MIS-C.

Author(s): Nan Gai [sup.1], Jason T. Maynes [sup.1] [sup.2], Kazuyoshi Aoyama [sup.1] [sup.3] Author Affiliations: (1) grid.42327.30, 0000 0004 0473 9646, Department of Anesthesia and Pain Medicine, The Hospital for [...], Coronavirus disease 2019 (COVID-19) has affected anesthetic care worldwide, including the provision of anesthesia for pediatric patients. Hospitals have balanced the risks associated with the potential surges of resource-intensive COVID-19 patients against the probable morbidity of delaying elective surgical procedures. These decisions are complicated by the unclear influence that COVID-19 has on the perioperative risk for disease-positive pediatric patients. We conducted a comprehensive literature search on MEDLINE for publications involving pediatric patients with COVID-19 who underwent general anesthesia. A total of eight publications met inclusion criteria, and together described 20 patients. Nine patients had documented preoperative COVID-19 symptoms and one perioperative death was reported. Overall, further studies are needed to increase patient numbers and properly assess the perioperative risk. As we continue to provide care without clear guiding data, we present a discussion of modified anesthetic techniques for pediatric patients with suspected or confirmed COVID-19.

Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain P o 2 (PBr o 2) in a rat model. Changes in PBr o 2 (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, n = 5–8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution). Outcomes were assessed by ANOVA with significance assigned at P < 0.05. At baseline, 2Nx rats demonstrated reduced CO (49.9 ± 9.4 vs. 66.3 ± 19.3 mL/min; P = 0.014) and PBr o 2 (21.1 ± 2.9 vs. 32.4 ± 3.1 mmHg; P < 0.001) relative to Sham 2Nx rats. Following hemodilution, 2Nx rats demonstrated a further decrease in PBr o 2 (15.0 ± 6.3 mmHg, P = 0.022). Hemodiluted 2Nx rats did not demonstrate a comparable increase in CO after hemodilution compared with Sham 2Nx (74.8 ± 22.4 vs. 108.9 ± 18.8 mL/min, P = 0.003) that likely contributed to the observed reduction in PBr o 2. This impaired CO response was associated with reduced fractional shortening (33 ± 9 vs. 51 ± 5%) and increased left ventricular end-systolic volume (156 ± 51 vs. 72 ± 15 µL, P < 0.001) suggestive of systolic dysfunction. By contrast, hemodiluted Sham 2Nx animals demonstrated a robust increase in CO and preserved PBr o 2. These data support the hypothesis that the kidney plays a central role in maintaining cerebral perfusion and initiating the adaptive increase in CO required to optimize PBr o 2 during acute anemia. NEW & NOTEWORTHY: This study has demonstrated that bilateral nephrectomy acutely impaired cardiac output (CO) and microvascular brain P o 2 (PBr o 2), at baseline. Following acute hemodilution, nephrectomy prevented the adaptive increase in CO associated with acute hemodilution leading to a further reduction in PBr o 2, accentuating the degree of cerebral tissue hypoxia. These data support a role for the kidney in maintaining PBr o 2 and initiating the increase in CO that optimized brain perfusion during acute anemia. [ABSTRACT FROM AUTHOR]

Purpose: Neonatal sepsis is a systemic inflammatory infection common in premature infants and a leading cause of mortality. Argon is an emerging interest in the field of noble gas therapy. Neonates with severe sepsis are frequently mechanically ventilated creating an opportunity for inhalation therapy. We aimed to investigate argon inhalation as a novel experimental therapy in neonatal sepsis. Methods: Sepsis was established in C57BL/6 neonatal mice by a lipopolysaccharide intraperitoneal injection on postnatal day 9. Septic pup mice were exposed to room air as well as non-septic controls. In the argon group, septic pup mice were exposed to argon (70% Ar, 30% O2) for 6 h in a temperature-controlled environment. Results: At 6 h, survival was significantly enhanced when septic mice received argon compared to septic controls. Serum profiles of cytokine release were significantly attenuated as well as lung architecture restored. Conclusions: Our findings suggest that argon inhalation as a novel treatment for neonatal sepsis, reducing mortality and counteracting the acute systemic inflammatory response in the blood and preserving the architecture of the lung. This research can contribute to a paradigm shift in the treatment and outcome of neonates with sepsis. [ABSTRACT FROM AUTHOR]