Citations

Abstract Background The assessment of kidney function and detection of acute kidney injury (AKI) remain cumbersome. On the one hand, because of limited accuracy of established tests: The most widely used methods are creatinine based, which lack in sensitivity, as creatinine is not purely filtrated by the kidney and rises relatively late after onset of AKI. On the other hand, because of labor-intensiveness: Gold standard inulin clearance and comparable methods involve intravenous compound infusion, blood sampling at several time points, and have error-sensitive determination methods. In recent years, several biomarkers have been put forward (e.g., NGAL, KIM-1, TIMP-2*IGFBP-7), but clinical implementation is limited up to now. Content Proenkephalin (PENK) represents a new candidate to determine kidney function. This peptide is cleaved from the precursor peptide preproenkephalin A alongside enkephalins (endogenous opioids) and is filtrated in the glomerulus. PENK plasma concentration appears to accurately represent glomerular filtration rate in patients diagnosed with sepsis or cardiac diseases. Moreover, increased PENK concentration is found to be associated with longer-term outcome concerning AKI and cardiac diseases. Lastly, the predominant receptor of enkephalins, the δ-opioid receptor, is expressed with the highest density in the kidney, suggesting that enkephalins could also exert a direct effect on kidney function. Summary In this review, we present an overview of enkephalins and the assessment of kidney function using this possible new functional biomarker PENK and compare it with established and novel biomarkers.

Objective: The aim of this study was to conduct a prospective, multicenter survey of patients regarding postoperative opioid use to inform development of standardized, evidence-based, procedure-specific opioid prescribing guidelines. Summary of Background Data: Previous work has shown significant variation in the amount of opioids prescribed after elective procedures, calling for optimization of prescribing. Methods: Adults (n = 3412) undergoing 25 elective procedures were identified prospectively from 3 academic centers (March 2017 to January 2018) to complete a 29-question telephone interview survey 21 to 35 days post-discharge (n = 688 not contacted, n = 107 refused). Discharge opioids were converted into Morphine Milligram Equivalents (MMEs). Results: Of the 2486 patients who completed the survey, 91.2% received opioids at discharge [median 225 (interquartile range, IQR 125 to 381) MME]. A median of 43 (0 to 184) MMEs were consumed after discharge with 77.3% of patients having leftover opioids at the time of the survey. In total, 61.5% of prescribed opioids were unused; 31.4% of patients used no opioids, and 52.6% required <50 MME. Overall, 90.6% of patients were satisfied with their postdischarge pain control. While 28.3% reported being prescribed too many opioids, 9.0% felt they were not prescribed enough. Only 9.6% of patients disposed of remaining opioids. Of the 2068 opioid-naive respondents (83.2%), 33.6% consumed no opioids (range 5.2% to 80.0% by procedure) and 57.0% (65.7% nonorthopedic) consumed <50 MME. Utilization data and predictors of low/high opioid consumption informed development of postoperative prescribing guidelines. Conclusion: A large proportion of postoperative patients reported using no or few opioids following discharge. Guidelines were developed to minimize opioid prescribing and identify patients requiring low doses or additional multimodal pain control.

OBJECTIVEIn children, the repair of skull defects arising from decompressive craniectomy presents a unique set of challenges. Single-center studies have identified different risk factors for the common complications of cranioplasty resorption and infection. The goal of the present study was to determine the risk factors for bone resorption and infection after pediatric cranioplasty.METHODSThe authors conducted a multicenter retrospective case study that included all patients who underwent cranioplasty to correct a skull defect arising from a decompressive craniectomy at 13 centers between 2000 and 2011 and were less than 19 years old at the time of cranioplasty. Prior systematic review of the literature along with expert opinion guided the selection of variables to be collected. These included: indication for craniectomy; history of abusive head trauma; method of bone storage; method of bone fixation; use of drains; size of bone graft; presence of other implants, including ventriculoperitoneal (VP) shunt; presence of fluid collections; age at craniectomy; and time between craniectomy and cranioplasty.RESULTSA total of 359 patients met the inclusion criteria. The patients’ mean age was 8.4 years, and 51.5% were female. Thirty-eight cases (10.5%) were complicated by infection. In multivariate analysis, presence of a cranial implant (primarily VP shunt) (OR 2.41, 95% CI 1.17–4.98), presence of gastrostomy (OR 2.44, 95% CI 1.03–5.79), and ventilator dependence (OR 8.45, 95% CI 1.10–65.08) were significant risk factors for cranioplasty infection. No other variable was associated with infection.Of the 240 patients who underwent a cranioplasty with bone graft, 21.7% showed bone resorption significant enough to warrant repeat surgical intervention. The most important predictor of cranioplasty bone resorption was age at the time of cranioplasty. For every month of increased age the risk of bone flap resorption decreased by 1% (OR 0.99, 95% CI 0.98–0.99, p < 0.001). Other risk factors for resorption in multivariate models were the use of external ventricular drains and lumbar shunts.CONCLUSIONSThis is the largest study of pediatric cranioplasty outcomes performed to date. Analysis included variables found to be significant in previous retrospective reports. Presence of a cranial implant such as VP shunt is the most significant risk factor for cranioplasty infection, whereas younger age at cranioplasty is the dominant risk factor for bone resorption.

Background and Objectives Patients with colorectal cancer with synchronous liver metastases may undergo a staged or a simultaneous resection. This study aimed to determine whether the time to adjuvant chemotherapy was delayed in patients undergoing a simultaneous resection. Methods A retrospective cohort study was conducted between 2005 and 2016. The primary outcome was time to adjuvant chemotherapy. A multivariate linear regression was conducted to ascertain the adjusted effect of a simultaneous versus a staged approach on time to adjuvant chemotherapy. Results A total of 155 patients were included. A total of 127 patients underwent a staged resection, whereas 28 patients underwent a simultaneous resection. Age, sex, and American Society of Anesthesiologists class as well tumor, node, metastasis stage, tumor location, and number and size of metastases were not significantly different between the groups. The median time to adjuvant chemotherapy was 70 and 63 days for the staged and simultaneous groups, respectively ( P = .27). Multivariate analysis did not demonstrate an increased propensity for prolonged time to chemotherapy after simultaneous resection (rate ratio: 0.97, 95% CI: 0.71‐1.32, P = .84). There were no significant differences in the length of stay, complications, overall survival, and disease‐free survival between the groups ( P > .05). Conclusions This study demonstrated that simultaneous resection does not result in significant delay of adjuvant chemotherapy compared with a staged approach.

Excess fat intake can increase lipid oxidation and expression of mitochondrial proteins, indicating remodeling of the mitochondrial proteome. Yet intermediates of lipid oxidation also accumulate, indicating a relative insufficiency to completely oxidize lipids. We investigated remodeling of the mitochondrial proteome to determine mechanisms of changes in lipid oxidation following high-fat feeding. C57BL/6J mice consumed a high-fat diet (HFD, 60% fat from lard) or a low-fat diet (LFD, 10% fat) for 12 wk. Mice were fasted for 4 h and then anesthetized by pentobarbital sodium overdose for tissue collection. A mitochondrial-enriched fraction was prepared from gastrocnemius muscles and underwent proteomic analysis by high-resolution mass spectrometry. Mitochondrial respiratory efficiency was measured as the ratio of ATP production to O2 consumption. Intramuscular acylcarnitines were measured by liquid chromatography-mass spectrometry. A total of 658 mitochondrial proteins were identified: 40 had higher abundance and 14 had lower abundance in mice consuming the HFD than in mice consuming the LFD. Individual proteins that changed with the HFD were primarily related to β-oxidation; there were fewer changes to the electron transfer system. Gene set enrichment analysis indicated that the HFD increased pathways of lipid metabolism and β-oxidation. Intramuscular concentrations of select acylcarnitines (C18:0) were greater in the HFD mice and reflected dietary lipid composition. Mitochondrial respiratory ATP production-to-O2 consumption ratio for lipids was not different between LFD and HFD mice. After the 60% fat diet, remodeling of the mitochondrial proteome revealed upregulation of proteins regulating lipid oxidation that was not evident for all mitochondrial pathways. The accumulation of lipid metabolites with obesity may occur without intrinsic dysfunction to mitochondrial lipid oxidation.

Summary Objective Patient–provider communication has been found to be less patient centred, on average, with patients who are members of stigmatized or minority groups. Obesity is a stigmatized condition, and thus, people with obesity may experience less patient‐centred communication (PCC). The objective of this study was to assess the association between patient body mass index (BMI) and self‐reported quality of PCC experienced over a 12‐month period and whether that relationship differed for men and women. Methods Data collected for the National Cancer Institute's Health Information National Trends Survey were analysed. Respondents who reported a BMI ≥ 18.5 kg/m 2 and indicated having seen a healthcare provider outside of an emergency room in the last 12 months were included. PCC was measured using a validated six‐item scale. Multivariate logistic regression was used to model the odds of reporting PCC greater than the sample median. Results Compared with people with normal weight BMIs, no associations were found between overweight (odds ratio [OR] = 0.84, p = 0.17), class I & II obesity (OR = 0.94, p = 0.68) or class III obesity (OR = 0.86, p = 0.47) and PCC. There was a significant interaction ( p = 0.015) such that for men, but not women, higher BMI was associated with less PCC. Conclusion Unlike evidence that women experience more weight stigma, in the healthcare domain, men may be at elevated risk of experiencing communication influenced by weight stigma.