Lipid peroxidation products as predictors of oxidant-mediated disease in preterm infants.

BACKGROUND: Preterm infants are susceptible to "oxygen radical diseases" (ORD). 8-isoprostane (8-IP) is a bioactive eicosanoid generated by reactive oxygen species-catalyzed peroxidation of arachidonic acid. Malondialdehyde (MDA) is generated by the decomposition of oxidant-induced lipid hydroperoxides. We hypothesize that the development of ORD is associated with elevated plasma 8-IP on day 0-1, and increasing urine levels of MDA in the first month. METHODS: Preterm (<32 weeks, n = 39) and term (n = 39) infants were recruited at birth. Plasma 8-IP was quantified by ELISA on day 0-1, and urine MDA by colorimetric assay of thiobarbituric acid reactive substances (TBARS) on days 0-1, 7, 14, 21, and 28. ORD was defined as retinopathy of prematurity ≥ stage 1, pneumatosis, or oxygen requirement at 36 weeks corrected gestational age. RESULTS: Plasma 8-IP was higher on day 0-1 in preterm infants who developed ORD compared to term infants. Urine TBARS levels increased in preterm infants from day 0-1 to day 28 but were not different in infants with or without ORD. Preterm infants who developed ORD demonstrated a significant rise in urine TBARS levels from day 1 to 14. CONCLUSIONS: Elevated plasma 8-IP on day 1 is associated with ORD in preterm infants. If validated as a biomarker for ORD, it may be useful in directing antioxidant therapies to the most susceptible infants. Urine TBARS during the first month are not significantly different in term infants, preterm infants with ORD, and preterm infants without ORD, but rapid rise of TBARS in the first 2 weeks may be associated with ORD.

Activity and structure of human acetyl-CoA carboxylase targeted by a specific inhibitor.

We have studied a series of human acetyl-CoA carboxylase (ACC) 1 and ACC2 proteins with deletions and/or Ser to Ala substitutions of the known phosphorylation sites. In vitro dephosphorylation/phosphorylation experiments reveal a substantial level of phosphorylation of human ACCs produced in insect cells. Our results are consistent with AMPK phosphorylation of Ser29 , Ser80 , Ser1,201 , and Ser1,216 . Phosphorylation of the N-terminal regulatory domain decreases ACC1 activity, while phosphorylation of residues in the ACC central domain has no effect. Inhibition of the activity by phosphorylation is significantly more profound at citrate concentrations below 2 mm. Furthermore, deletion of the N-terminal domain facilitates structural changes induced by citrate, including conversion of ACC dimers to linear polymers. We have also identified ACC2 amino acid mutations affecting specific inhibition of the isozyme by compound CD-017-0191. They form two clusters separated by 60-90 Å: one located in the vicinity of the BC active site and the other one in the vicinity of the ACC1 phosphorylation sites in the central domain, suggesting a contribution of the interface of two ACC dimers in the polymer to the inhibitor binding site.

Predictors of 30-day readmission following pancreatic surgery: A retrospective review.

BACKGROUND: Pancreatectomies have been identified as procedures with an increased risk of readmission. In surgical patients, readmissions within 30 days of discharge are usually procedure-related. We sought to determine predictors of 30-day readmission following pancreatic resections in a large healthcare system. METHODS: We retrospectively collected information from the records of 383 patients who underwent pancreatic resections from 2004-2013. To find the predictors of readmission in the 30 days after discharge, we performed a univariate screen of possible variables using the Fisher's exact test for categorical variables and the Mann-Whitney U test for continuous variables. Multivariate analysis was used to determine the independent factors. RESULTS: Fifty-eight (15.1%) patients were readmitted within 30 days of discharge. Of the patients readmitted, the most common diagnoses at readmission were sepsis (17.2%), and dehydration (8.6%). Multivariate logistic regression found that the development of intra-abdominal fluid collections (OR = 5.32, P < 0.0001), new thromboembolic events (OR = 4.08, P = 0.016), and pre-operative BMI (OR = 1.06, P = 0.040) were independent risk factors of readmission within 30 days of discharge. CONCLUSION: Our data demonstrate that factors predictive of 30-day readmission are a combination of patient characteristics and the development of post-operative complications. Targeted interventions may be used to reduce the risk of readmission.

Characterization of Patients Who Present With Insomnia: Is There Room for a Symptom Cluster-Based Approach?

STUDY OBJECTIVES: This study examined empirically derived symptom cluster profiles among patients who present with insomnia using clinical data and polysomnography. METHODS: Latent profile analysis was used to identify symptom cluster profiles of 175 individuals (63% female) with insomnia disorder based on total scores on validated self-report instruments of daytime and nighttime symptoms (Insomnia Severity Index, Glasgow Sleep Effort Scale, Fatigue Severity Scale, Beliefs and Attitudes about Sleep, Epworth Sleepiness Scale, Pre-Sleep Arousal Scale), mean values from a 7-day sleep diary (sleep onset latency, wake after sleep onset, and sleep efficiency), and total sleep time derived from an in-laboratory PSG. RESULTS: The best-fitting model had three symptom cluster profiles: "High Subjective Wakefulness" (HSW), "Mild Insomnia" (MI) and "Insomnia-Related Distress" (IRD). The HSW symptom cluster profile (26.3% of the sample) reported high wake after sleep onset, high sleep onset latency, and low sleep efficiency. Despite relatively comparable PSG-derived total sleep time, they reported greater levels of daytime sleepiness. The MI symptom cluster profile (45.1%) reported the least disturbance in the sleep diary and questionnaires and had the highest sleep efficiency. The IRD symptom cluster profile (28.6%) reported the highest mean scores on the insomnia-related distress measures (eg, sleep effort and arousal) and waking correlates (fatigue). Covariates associated with symptom cluster membership were older age for the HSW profile, greater obstructive sleep apnea severity for the MI profile, and, when adjusting for obstructive sleep apnea severity, being overweight/obese for the IRD profile. CONCLUSIONS: The heterogeneous nature of insomnia disorder is captured by this data-driven approach to identify symptom cluster profiles. The adaptation of a symptom cluster-based approach could guide tailored patient-centered management of patients presenting with insomnia, and enhance patient care.

Outcomes following operative vs. non-operative management of blunt traumatic pancreatic injuries: a retrospective multi-institutional study.

BACKGROUND: Traumatic pancreatic injuries are rare, and guidelines specifying management are controversial and difficult to apply in the acute clinical setting. Due to sparse data on these injuries, we carried out a retrospective review to determine outcomes following surgical or non-surgical management of traumatic pancreatic injuries. We hypothesize a higher morbidity and mortality rate in patients treated surgically when compared to patients treated non-surgically. METHODS: We performed a retrospective review of data from four trauma centers in New York from 1990-2014, comparing patients who had blunt traumatic pancreatic injuries who were managed operatively to those managed non-operatively. We compared continuous variables using the Mann-Whitney U test and categorical variables using the chi-square and Fisher's exact tests. Univariate analysis was performed to determine the possible confounding factors associated with mortality in both treatment groups. RESULTS: Twenty nine patients were managed operatively and 32 non-operatively. There was a significant difference between the operative and non-operative groups in median age (37.0 vs. 16.2 years, P = 0.016), grade of pancreatic injury (grade I; 30.8 vs. 85.2%, P value for all comparisons <0.0001), median injury severity score (ISS) (16.0 vs. 4.0, P = 0.002), blood transfusion (55.2 vs. 15.6%, P = 0.0012), other abdominal injuries (79.3 vs. 38.7%, P = 0.0014), pelvic fractures (17.2 vs. 0.00%, P = 0.020), intensive care unit (ICU) admission (86.2 vs. 50.0%, P = 0.003), median length of stay (LOS) (16.0 vs. 4.0 days, P <0.0001), and mortality (27.6 vs. 3.1%, P = 0.010). CONCLUSIONS: Patients with traumatic pancreatic injuries treated operatively were more severely injured and suffered greater complications than those treated non-operatively. The greater morbidity and mortality associated with these patients warrants further study to determine optimal triage strategies and which subset of patients is likely to benefit from surgery.