Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness. Methods: Levels of IL-1β, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVID stable patients), patients with COVID-19 requiring ICU admission (COVID ICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAP ICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated. Measurements and Main Results: IL-1β, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVID ICU patients could be clearly differentiated from COVID stable patients, and demonstrated higher levels of IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAP ICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission ( P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution ( P < 0.0001). Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

SummaryIn this prospective randomised study, pruritus and pain were evaluated in patients undergoing abdominal surgery in which intrathecal morphine was administered. Each patient received intrathecal morphine 0.3 mg prior to induction, followed by a standard anaesthetic. The patients were randomly allocated to one of two groups. One group received 100 mg of rectal diclofenac immediately post-induction. Patients receiving diclofenac had signi®cantly lower pruritus scores at 30 min (p 0.0076), 2, 4, 8 and 24 h postoperatively, as well as signi®cantly reduced pain scores at each time point (p < 0.0001 at each study interval). Morphine consumption in the ®rst 24 h was also signi®cantly lower in this group. In conclusion, rectal administration of diclofenac signi®cantly reduces the incidence and severity of postoperative pruritus. It also signi®cantly reduces pain and further analgesic requirements postoperatively.

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Aim: Surgery for Crohn’s disease (CD) is characterized by an enhanced inflammatory response. While inflammation can induce hyperalgesia, post-operative pain following surgery for CD has not been characterized. This retrospective study compared a consecutive series of patients undergoing laparoscopic right hemicolectomy for CD and neoplasia performed by a single surgeon. Method: Elective resections performed between Jan-2016 and Aug-2017 managed in an enhanced recovery pathway were eligible for inclusion. Patients were excluded if open surgery was performed, an ileostomy was fashioned, no patient-controlled analgesia (PCA) was used or data were incomplete. Results : 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. Results: 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. Conclusions: CD patients experience increased post-operative pain, require more post-operative analgesia and have an enhanced post-operative inflammatory response. Further studies to elucidate the mechanism of this hyperalgesia and strategies to obviate it are required.

This chapter on the topic of cardiac surgery–associated acute kidney injury (CS-AKI) examines the risk factors for and the prevention, diagnosis, and management of this serious and common consequence of cardiothoracic surgery. The chapter follows the clinical course of a patient with a moderate risk of CS-AKI undergoing an aortic valve replacement and coronary artery bypass grafting. The risk factors, both patient- and surgery-specific, are demonstrated in tabular form. Methods to mitigate against these risk factors are explained, including optimizing the timing of surgery. The most up-to-date diagnostic criteria for AKI are compared. It also recommends the most accurate formulae to evaluate the severity of CS-AKI. The value of medical therapies prior to renal replacement therapy (RRT) is examined. The clinical decisions regarding the mode of RRT, timing of RRT, anticoagulation methods, and vascular access are highlighted. Patients with already established end-stage renal disease are discussed as a separate cohort. The chapter concludes by discussing the short- and longer-term prognosis associated with CS-AKI.