Research Spotlight

Bellomo, R., R. G. Wunderink, H. Szerlip, S. W. English, L. W. Busse, A. M. Deane, A. K. Khanna, M. T. McCurdy, M. Ostermann, P. J. Young, D. R. Handisides, L. S. Chawla, G. F. Tidmarsh and T. E. Albertson (2020). “Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock.” Crit Care 24(1): 43.

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BACKGROUND: In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. METHODS: We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. RESULTS: Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30-676.00 pg/mL] vs 42 pg/mL [IQR 30.46-87.34 pg/mL] in controls; P < 0.0001) and median ANG I/II ratio (1.63 [IQR 0.98-5.25] vs 0.4 [IQR 0.28-0.64] in controls; P < 0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85-299.50 pg/mL] vs 97 pg/mL [IQR 35.27-181.01 pg/mL] in controls; P = 0.9895). At baseline, patients with a ratio above the median (>/=1.63) had higher ANG I levels (P < 0.0001), lower ANG II levels (P < 0.0001), higher albumin concentrations (P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors (P < 0.00001), and they received a higher norepinephrine-equivalent dose (P = 0.003). In the placebo group, a baseline ANG I/II ratio <1.63 was associated with improved survival (hazard ratio 0.56; 95% confidence interval 0.36-0.88; P = 0.01) on unadjusted analyses. CONCLUSIONS: Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02338843. Registered 14 January 2015.

Baxter, R. D., K. Vaquera and T. J. George (2020). “Extracorporeal Membrane Oxygenation Support for Vaping-induced Acute Lung Injury.” Ann Thorac Surg Feb 27. [Epub ahead of print].

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Cases of vaporizer-induced acute lung injury are increasing in frequency as the use of these recreational products have become more popular. Such pathology can result in life-threatening conditions for otherwise healthy patients with diagnostic difficulties and complex treatment plans. Presented is a case of severe acute lung injury due to vaporizing substances in a young male requiring extracorporeal membranous oxygenation (ECMO) as a bridge to recovery. Recovery was successful despite rapid-onset of adult respiratory distress syndrome with prompt utilization of ECMO and appropriate lung-protective strategies.

Stanzo, K., S. Desai and A. Chiruvolu (2020). “Effects of Dextrose Gel in Newborns at Risk for Neonatal Hypoglycemia in a Baby-Friendly Hospital.” J Obstet Gynecol Neonatal Nurs 49(1): 55-64.

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OBJECTIVE: To describe the effects of the introduction of dextrose gel to the neonatal hypoglycemia (NH) protocol on exclusive breastfeeding rates at discharge and NICU admission rates among clinically well newborns born at 35 weeks gestation or greater who were at risk for NH in a Baby-Friendly hospital. DESIGN: Quasi-experimental, pre- and postintervention. SETTING: A suburban, Baby-Friendly hospital with approximately 2,000 births annually. PARTICIPANTS: Clinically well newborns born at 35 weeks gestation or greater at risk for NH who were admitted to the mother-baby unit. METHODS: We compared 198 newborns at risk for NH born in the 6-month period before the introduction of dextrose gel (November 15, 2016, through May 14, 2017) versus 203 newborns born in the 6-month period after the introduction (May 15, 2017, through November 14, 2017). In the preintervention group, the NH protocol included blood glucose monitoring, prolonged skin-to-skin contact, feeding, and dextrose administered intravenously. In the postintervention group, oral dextrose gel was added to the NH protocol. RESULTS: We found no differences in maternal or newborn characteristics between the pre- and postintervention groups. Dextrose gel was given to 50 newborns (approximately 25%) of 203 in the postintervention group. The proportion of newborns who were exclusively breastfed at discharge was similar between groups (56.6% of 198 vs. 59.1% of 203, p = .62), as were the NICU admission rates for hypoglycemia (2.5% of 198 vs. 1.5% of 203, p = .50). CONCLUSIONS: In a suburban Baby-Friendly hospital, introduction of dextrose gel into the NH protocol had no significant effect on exclusive breastfeeding at discharge or NICU admission rates.

Assia Batzir, N., P. Kishor Bhagwat, A. Larson, Z. Coban Akdemir, M. Baglaj, L. Bofferding, K. B. Bosanko, S. Bouassida, B. Callewaert, A. Cannon, Y. Enchautegui Colon, A. D. Garnica, M. H. Harr, S. Heck, A. C. E. Hurst, S. N. Jhangiani, B. Isidor, R. O. Littlejohn, P. Liu, P. Magoulas, H. Mar Fan, R. Marom, S. McLean, M. M. Nezarati, K. M. Nugent, M. B. Petersen, M. L. Rocha, E. Roeder, R. Smigiel, I. Tully, J. Weisfeld-Adams, K. O. Wells, J. E. Posey, J. R. Lupski, A. L. Beaudet and M. F. Wangler (2020). “Recurrent arginine substitutions in the ACTG2 gene are the primary driver of disease burden and severity in visceral myopathy.” Hum Mutat 41(3): 641-654.

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Visceral myopathy with abnormal intestinal and bladder peristalsis includes a clinical spectrum with megacystis-microcolon intestinal hypoperistalsis syndrome and chronic intestinal pseudo-obstruction. The vast majority of cases are caused by dominant variants in ACTG2; however, the overall genetic architecture of visceral myopathy has not been well-characterized. We ascertained 53 families, with visceral myopathy based on megacystis, functional bladder/gastrointestinal obstruction, or microcolon. A combination of targeted ACTG2 sequencing and exome sequencing was used. We report a molecular diagnostic rate of 64% (34/53), of which 97% (33/34) is attributed to ACTG2. Strikingly, missense mutations in five conserved arginine residues involving CpG dinucleotides accounted for 49% (26/53) of disease in the cohort. As a group, the ACTG2-negative cases had a more favorable clinical outcome and more restricted disease. Within the ACTG2-positive group, poor outcomes (characterized by total parenteral nutrition dependence, death, or transplantation) were invariably due to one of the arginine missense alleles. Analysis of specific residues suggests a severity spectrum of p.Arg178>p.Arg257>p.Arg40 along with other less-frequently reported sites p.Arg63 and p.Arg211. These results provide genotype-phenotype correlation for ACTG2-related disease and demonstrate the importance of arginine missense changes in visceral myopathy.

Ames, C. P., J. S. Smith, J. L. Gum, M. Kelly, A. Vila-Casademunt, D. C. Burton, R. Hostin, S. Yeramaneni, V. Lafage, F. J. Schwab, C. I. Shaffrey, S. Bess, F. Pellise and M. Serra-Burriel (2020). “Utilization of Predictive Modeling to Determine Episode of Care Costs and to Accurately Identify Catastrophic Cost Nonwarranty Outlier Patients in Adult Spinal Deformity Surgery: A Step Toward Bundled Payments and Risk Sharing.” Spine (Phila Pa 1976) 45(5): E252-e265.

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STUDY DESIGN: Retrospective review of prospectively-collected, multicenter adult spinal deformity (ASD) database. OBJECTIVE: The aim of this study was to evaluate the rate of patients who accrue catastrophic cost (CC) with ASD surgery utilizing direct, actual costs, and determine the feasibility of predicting these outliers. SUMMARY OF BACKGROUND DATA: Cost outliers or surgeries resulting in CC are a major concern for ASD surgery as some question the sustainability of these surgical treatments. METHODS: Generalized linear regression models were used to explain the determinants of direct costs. Regression tree and random forest models were used to predict which patients would have CC (>$100,000). RESULTS: A total of 210 ASD patients were included (mean age of 59.3 years, 83% women). The mean index episode of care direct cost was $70,766 (SD = $24,422). By 90 days and 2 years following surgery, mean direct costs increased to $74,073 and $77,765, respectively. Within 90 days of the index surgery, 11 (5.2%) patients underwent 13 revisions procedures, and by 2 years, 26 (12.4%) patients had undergone 36 revision procedures. The CC threshold at the index surgery and 90-day and 2-year follow-up time points was exceeded by 11.9%, 14.8%, and 19.1% of patients, respectively. Top predictors of cost included number of levels fused, surgeon, surgical approach, interbody fusion (IBF), and length of hospital stay (LOS). At 90 days and 2 years, a total of 80.6% and 64.0% of variance in direct cost, respectively, was explained in the generalized linear regression models. Predictors of CC were number of fused levels, surgical approach, surgeon, IBF, and LOS. CONCLUSION: The present study demonstrates that direct cost in ASD surgery can be accurately predicted. Collectively, these findings may not only prove useful for bundled care initiatives, but also may provide insight into means to reduce and better predict cost of ASD surgery outside of bundled payment plans. LEVEL OF EVIDENCE: 3.