Impact of total parenteral nutrition v. exclusive enteral nutrition on postoperative adverse outcomes in patients with penetrating Crohn's disease undergoing surgical resection: a retrospective cohort study.

Achieving optimal nutritional status in patients with penetrating Crohn's disease is crucial in preparing for surgical resection. However, there is a dearth of literature comparing the efficacy of total parenteral nutrition (TPN) v. exclusive enteral nutrition (EEN) in optimising postoperative outcomes. Hence, we conducted a case-matched study to assess the impact of preoperative EEN v. TPN on the incidence of postoperative adverse outcomes, encompassing overall postoperative morbidity and stoma formation, among penetrating Crohn's disease patients undergoing bowel surgery. From 1 December 2012 to 1 December 2021, a retrospective study was conducted at a tertiary centre to enrol consecutive patients with penetrating Crohn's disease who underwent surgical resection. Propensity score matching was utilised to compare the incidence of postoperative adverse outcomes. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with adverse outcomes. The study included 510 patients meeting the criteria. Among them, 101 patients in the TPN group showed significant improvements in laboratory indicators at the time of surgery compared with pre-optimisation levels. After matching, TPN increased the occurrence of postoperative adverse outcomes (92·2 % v. 64·1 %, P = 0·001) when compared with the EEN group. In the multivariate analysis, TPN showed a significantly higher OR for adverse outcomes than EEN (OR = 4·241; 95 % CI 1·567-11·478; P = 0·004). The study revealed that penetrating Crohn's disease patients who were able to fulfil their nutritional requirements through EEN exhibited superior nutritional and surgical outcomes in comparison with those who received TPN.

The impact of delayed closure of ileostomy on postoperative complications in patients with Crohn's disease: a case-matched study.

Ileostomy creation is a common procedure to mitigate postoperative complications in Crohn's disease (CD) patients. However, the optimal timing for ileostomy closure remains controversial. This study aims to investigate whether delayed ileostomy closure (> 6 months post formation) affects postoperative complications compared to early closure (≤ 6 months post formation). Consecutive CD patients who underwent ileostomy reversal at a tertiary care center between January 1, 2013, and December 1, 2021, were included. The study compared patients who underwent early ileostomy closure to matched patients undergoing delayed ileostomy closure. The 90-day postoperative complications were compared between the two groups. The study included 352 eligible patients for ileostomy reversion. Our data showed that patients undergoing delayed ileostomy closure had higher incidence of ileostomy-related infectious complications (12% vs. 4%, p = 0.008), a longer postoperative hospital stay (10 days with an IQR of 7-12 days versus 8 days with an IQR of 7-11 days, p = 0.024), and increased rate of ileus (28% versus 15%, p = 0.003). There were 256 patients included after 1:1 propensity score matching. The results revealed no significant differences in postoperative hospital stay, infectious or non-infectious complications except for a statistically significant increase in the incidence of ileus in the delayed closure group (p = 0.01). Patients undergoing delayed ileostomy closure has similar outcomes to early closure in terms of postoperative complications, except for a higher incidence of ileus.

Biologic use is not associated with postoperative complications in patients with Crohn's disease undergoing stoma reversion.

PURPOSE: Stoma creation is a common procedure in patients with Crohn's disease (CD), and early prophylaxis with biologics is recommended for high-risk patients. However, the effect of biologic exposure on morbidity after stoma closure remains unknown. Therefore, this study aimed to investigate the impact of biologic use on the occurrence of complications in CD patients following stoma closure. METHODS: Consecutive patients diagnosed with CD who underwent ileostomy reversal at a tertiary care centre between 1 January 2013 and 1 December 2021, were included in the study. The primary outcome was the occurrence of 90-day postoperative complications. RESULTS: The study included 347 eligible patients who underwent ileostomy reversal. There was no significant difference in terms of infectious complications, overall complications or length of postoperative stay between the biologic and non-biologic groups. Multivariate logistic regression analysis identified several predictors of postoperative morbidity, including preoperative haemoglobin levels below 100 g/L, CRP levels above 10 mg/L, anastomotic site, ileostomy-related infectious complications and albumin levels below 35 g/L. CONCLUSIONS: This study demonstrated that the use of biologics is not associated with adverse outcomes. However, such as high CRP levels, ileostomy-related infectious complications, hypoproteinemia, and hemoglobinemia, should be optimized prior to surgery to reduce postoperative morbidities.

Adipose afferent reflex is enhanced by TNFα in paraventricular nucleus through NADPH oxidase-dependent ROS generation in obesity-related hypertensive rats.

BACKGROUND: The adipose afferent reflex (AAR), a sympatho-excitatory reflex, can promote the elevation of sympathetic nerve activity (SNA) and blood pressure (BP). Inflammation in the paraventricular nucleus (PVN) involves sympathetic abnormality in some cardiovascular diseases such as hypertension. This study was designed to explore the effects of tumor necrosis factor alpha (TNFα) in the PVN on the AAR and SNA in rats with obesity-related hypertension (OH) induced by a high-fat diet for 12 weeks. METHODS: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were continuously recorded in anesthetized rats, and their responses to capsaicin (CAP) stimulation of the right inguinal white adipose tissue were used to evaluate the AAR. RESULTS: Compared to the control rats, the systolic blood pressure (SBP), plasma norepinephrine (NE, indicating SNA) and TNFα levels, TNFα mRNA and protein levels, reactive oxygen species (ROS) content and NADPH oxidase activity in the PVN were significantly elevated in rats with OH. TNFα in the PVN markedly enhanced sympathoexcitation and AAR. Moreover, the enhancement of AAR caused by TNFα can be significantly strengthened by the pretreatment of diethyldithiocarbamate (DETC), a superoxide dismutase inhibitor, but attenuated by TNF-α receptor antagonist R-7050, superoxide scavenger PEG-SOD and NADPH oxidase inhibitor apocynin (Apo) in rats with OH. Acute microinjection of TNF-α into the PVN significantly increased the activity of NADPH oxidase and ROS levels in rats with OH, which were effectively blocked by R-7050. Furthermore, our results also showed that the increased levels of ROS, TNFα and NADPH oxidase subunits mRNA and protein in the PVN of rats with OH were significantly reversed by pentoxifylline (PTX, 30 mg/kg daily ip; in 10% ethanol) application, a cytokine blocker, for a period of 5 weeks. PTX administration also significantly decreased SBP, AAR and plasma NE levels in rats with OH. CONCLUSIONS: TNFα in the PVN modulates AAR and contributes to sympathoexcitation in OH possibly through NADPH oxidase-dependent ROS generation. TNFα blockade attenuates AAR and sympathoexcitation that unveils TNFα in the PVN may be a possible therapeutic target for the intervention of OH.

Intermedin in Paraventricular Nucleus Attenuates Ang II-Induced Sympathoexcitation through the Inhibition of NADPH Oxidase-Dependent ROS Generation in Obese Rats with Hypertension.

Increased reactive oxygen species (ROS) induced by angiotensin II (Ang II) in the paraventricular nucleus (PVN) play a critical role in sympathetic overdrive in hypertension (OH). Intermedin (IMD), a bioactive peptide, has extensive clinically prospects in preventing and treating cardiovascular diseases. The study was designed to test the hypothesis that IMD in the PVN can inhibit the generation of ROS caused by Ang II for attenuating sympathetic nerve activity (SNA) and blood pressure (BP) in rats with obesity-related hypertension (OH). Male Sprague-Dawley rats (160-180 g) were used to induce OH by feeding of a high-fat diet (42% kcal as fat) for 12 weeks. The dynamic changes of sympathetic outflow were evaluated as the alterations of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to certain chemicals. The results showed that the protein expressions of Ang II type 1 receptor (AT1R), calcitonin receptor-like receptor (CRLR) and receptor activity-modifying protein 2 (RAMP2) and RAMP3 were markedly increased, but IMD was much lower in OH rats when compared to control rats. IMD itself microinjection into PVN not only lowered SNA, NADPH oxidase activity and ROS level, but also decreased Ang II-caused sympathetic overdrive, and increased NADPH oxidase activity, ROS levels and mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) activation in OH rats. However, those effects were mostly blocked by the adrenomedullin (AM) receptor antagonist AM22-52 pretreatment. The enhancement of SNA caused by Ang II can be significantly attenuated by the pretreatment of AT1R antagonist lorsatan, superoxide scavenger Tempol and NADPH oxidase inhibitor apocynin (Apo) in OH rats. ERK activation inhibitor U0126 in the PVN reversed Ang II-induced enhancement of SNA, and Apo and IMD pretreatment in the PVN decreased Ang II-induced ERK activation. Chronic IMD administration in the PVN resulted in significant reductions in basal SNA and BP in OH rats. Moreover, IMD lowered NADPH oxidase activity and ROS level in the PVN; reduced the protein expressions of AT1R and NADPH oxidase subunits NOX2 and NOX4, and ERK activation in the PVN; and decreased Ang II levels-inducing sympathetic overactivation. These results indicated that IMD via AM receptors in the PVN attenuates SNA and hypertension, and decreases Ang II-induced enhancement of SNA through the inhibition of NADPH oxidase activity and ERK activation.