Danielle Fritze

Antibiotic choice is independently associated with risk of surgical site infection after colectomy: A population-based cohort study

Objective: To determine which perioperative care practices are associated with decreased risk of surgical site infection (SSI) after colectomy surgery. Background: Optimization of perioperative care has been a common strategy for improving surgical safety, but the relationship between process measure compliance and surgical complication rates is controversial. Methods: This is a retrospective cohort study performed within the Michigan Surgical Quality Collaborative (MSQC), an organization of hospitals that prospectively collects patient data, processes of care, and 30-day outcomes. Patients undergoing colectomy surgery (n = 4331) were studied. Factors potentially associated with SSI were tested using univariate statistical tests, and a hierarchical generalized linear model was created to test for independent associations between processes of care and SSI, while adjusting for patient risk factors and clustering of patients within hospitals. Results: Several perioperative care practices were independently associated with lower risk of SSI after adjustment for patient risk, procedure type/duration, and clustering of patients by hospital site. Best practices include selection of a Surgical Care Improvement Project (SCIP-2)-compliant prophylactic intravenous antibiotic, postoperative normothermia, postoperative day 1 glucose control, and oral antibiotics given when bowel prep used (SCIP-1 was not significant). Further, several specific prophylactic antibiotic choices were independently associated with lower SSI rates, including cefazolin/metronidazole, ciprofloxacin/metronidazole, and ertapenem. Conclusions: In Michigan, several perioperative care practices are independently associated with decreased risk of SSI after colectomy, including SCIP-2-compliant prophylactic antibiotics, postoperative normothermia, glucose control, and oral antibiotics. Furthermore, specific prophylactic antibiotic choices are associated with lower risk of SSI. These results account for patient factors and unmeasured hospital effects, suggesting that dissemination of these perioperative care practices may decrease SSI rates.

Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats

Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 μg) inhibited dark-phase food intake, in a dose-dependent fashion, for >3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 μg) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 μg·kg(-1)·h(-1) iv), vagal stimulation with 2-deoxy-D-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin-stimulated gastric acid secretion, whereas 2-deoxy-D-glucose-stimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls (P < 0.01). Finally, nesfatin-induced Ca(2+) signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dose-dependent Ca(2+) increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca(2+) signaling in cultured DMNV neurons.

Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: focus on ghrelin and nesfatin‐1

•  What is the central question of this study? Does mammalian target of rapamycin (mTOR) signalling in the dorsal vagal complex contribute to the modulation of energy homeostasis? •  What is the main finding and its importance? Our study shows, for the first time, that mTOR signalling in neurons of the dorsal motor nucleus of the vagus regulates both the nutrient and the hormonal signals for the modulation of food intake. These results imply that mTOR signalling in the hindbrain may serve as a potential target for treatment of obesity and appetite‐related disorders.

Preserving operative volume in the setting of the 2011 ACGME duty hour regulations

OBJECTIVES The reported influence of Accreditation Council for Graduate Medical Education resident duty hour limitations on operative case volume has been mixed. Additional restrictions instituted in July 2011 further limited the work hours of postgraduate year 1 (PGY-1) residents, threatening to reduce availability for educational and operative activities. In this study, we evaluate our novel intern call schedule, which we hypothesized would preserve operative experience despite these increased restrictions. DESIGN A retrospective analysis of PGY-1 operative reports was conducted. Operations outside of major case categories were excluded. Operative case volumes in the Section of General Surgery for the same period were analyzed, as were average duty hours for each resident. Comparative statistics were generated using Wilcoxon rank sum tests. SETTING Single-institution study conducted at the University of Michigan, a tertiary-care academic hospital. PARTICIPANTS Overall, 50 categorical general surgery residents from 2005 to present were included. Three residents were subsequently excluded as they were preliminary interns rather than categorical; 2 residents were excluded having completed their intern years at other institutions. RESULTS The median number of major cases done during the PGY-1 for all evaluated residents was 89 (interquartile range [IQR]: 72-101). For interns between the years 2005 and 2011, the median number of major cases was 87 (IQR: 73-101), whereas interns in the 2011 to 2013 academic years performed 91.5 (IQR: 69.5-101.5, p = 0.91). Although case volume varied between intern classes, no significant differences were observed between any 2 individual classes in the study. Analysis of annual case volumes among each PGY revealed a relative increase of 29% (p < 0.001) among PGY-2 residents, and 20% (p = 0.02) by PGY-3 residents. Relative increases among senior residents (8% for both PGY-4 and PGY-5) did not reach statistical significance. CONCLUSIONS Our novel call schedule attempts to minimize prolonged night-float coverage responsibilities for interns in hopes of preserving their operative experience. In spite of increased duty hour restrictions, PGY-1 operative volume has not decreased significantly at our institution. However, in the same time period, PGY-2 and PGY-3 case volume has increased. Our findings highlight the challenges faced by surgical residencies in light of these new restrictions, particularly the 16-hour limit. Additional rigorously designed prospective studies should be conducted to better understand the influence of the most recent Accreditation Council for Graduate Medical Education work hour limitations on the subjective and objective experiences of surgical residents.

Hospital Readmissions after Colectomy: A Population-Based Study

BACKGROUND Surgical readmissions will be targeted for reimbursement cuts in the near future. We sought to understand differences between hospitals with high and low readmission rates in a statewide surgical collaborative to identify potential quality improvement targets. STUDY DESIGN We studied 5,181 patients undergoing laparoscopic or open colectomy at 24 hospitals participating in the Michigan Surgical Quality Collaborative between May 2007 and January 2011. We first calculated hospital risk-adjusted 30-day readmission rates. We then compared reasons for readmission, risk-adjusted complication rates, risk-adjusted inpatient length of stay, and composite process compliance across readmission rate quartiles. RESULTS Hospitals with the lowest 30-day readmission rates averaged 5.1%, compared with 10.3% in hospitals with the highest rates (p < 0.01). Despite wide variability in readmission rates, reasons for readmission were similar between hospitals. Compared with hospitals with low readmission rates, hospitals with high readmission rates had higher risk-adjusted complication rates (29% vs 22%, p = 0.03), but similar median lengths of stay (5.5 days vs 5.6 days, p = 0.61). Although measures to reduce complications were associated with lower surgical site infection rates, they were not associated with reduced overall complication or readmission rates. There was wide variation in complication rates among hospitals with similar readmission rates. CONCLUSIONS There is wide variation in hospital readmission rates after colectomy that correlates with overall complication rates. However, the wide variation in complication rates among hospitals with similar readmission rates suggests that hospital complication rates explain little about their readmission rates. Preventing readmissions after colectomy in hospitals with high readmission rates will require more attention to different care processes currently unmeasured in many clinical registries as well as complication prevention.

LGR4 and Its Ligands, R-Spondin 1 and R-Spondin 3, Regulate Food Intake in the Hypothalamus of Male Rats

The hypothalamus plays a key role in the regulation of feeding behavior. Several hypothalamic nuclei, including the arcuate nucleus (ARC), paraventricular nucleus, and ventromedial nucleus of the hypothalamus (VMH), are involved in energy homeostasis. Analysis of microarray data derived from ARC revealed that leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is highly expressed. LGR4, LGR5, and LGR6 form a subfamily of closely related receptors. Recently, R-spondin (Rspo) family proteins were identified as ligands of the LGR4 subfamily. In the present study, we investigated the distribution and function of LGR4-LGR6 and Rspos (1-4) in the brain of male rat. In situ hybridization showed that LGR4 is expressed in the ARC, VMH, and median eminence of the hypothalamus. LGR4 colocalizes with neuropeptide Y, proopiomelanocortin, and brain-derived neurotrophic factor neurons. LGR5 is not detectable with in situ hybridization; LGR6 is only expressed in the epithelial lining of the lower portion of the third ventricle and median eminence. Rspo1 is expressed in the VMH and down-regulated with fasting. Rspo3 is expressed in the paraventricular nucleus and also down-regulated with fasting. Rspos 1 and 3 colocalize with the neuronal marker HuD, indicating that they are expressed by neurons. Injection of Rspo1 or Rspo3 into the third brain ventricle inhibited food intake. Rspo1 decreased neuropeptide Y and increased proopiomelanocortin expression in the ARC. Rspo1 and Rspo3 mRNA is up-regulated by insulin. These data indicate that Rspo1 and Rspo3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis.

A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling.

A transcript of unknown function, regulated by fasting and feeding, was identified by microarray analysis. The transcript is up‐regulated in the fasting state. An 1168‐bp cDNA was cloned from rat hypothalamus and sequenced. This sequence is consistent with adipogenesis down‐regulating transcript 3 (AGD3) (also known as human OCC‐1) mRNA. A protein sequence identical to AGD3 was determined by mass spectrometry. In the rat brain, AGD3 mRNA is distributed in the arcuate nucleus, ventromedial hypothalamus, amygdaloid nuclei, hippocampus, and somatic cortex. Double in situ hybridisation showed that AGD3 mRNA is co‐localised with pro‐opiomelanocortin and neuropeptide Y in arcuate nucleus neurones. AGD3 binds with insulin receptor substrate 4 and increases insulin‐stimulated phospho‐Akt and regulates AMP‐activated protein kinase and mammalian target of rapamycin downstream target S6 kinase phosphorylation.

Risk of peritoneal dialysis catheter-associated peritonitis following kidney transplant

Peritoneal dialysis (PD) patients have equivalent or slightly better kidney transplant outcomes when compared to hemodialysis (HD) patients. However, given the risk for postoperative infection, we sought to determine the risk factors for PD catheter‐associated infections for patients who do not have the PD catheter removed at the time of engraftment.