Ontogeny and thermogenic role for sternal fat in female sheep

Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat. In adult sheep, implanted temperature probes were used to characterise the thermogenic response of fat and muscle to feeding and the effects of reduced or increased adiposity. UCP1 was more abundant within sternal than retroperitoneal fat and was only retained in the sternal depot of adults. Distinct differences in the abundance of gene pathway markers were apparent between tissues, with sternal fat exhibiting some similarities with muscle that were not apparent in the retroperitoneal depot. In adults, the post-prandial rise in temperature was greater and more prolonged in sternal than retroperitoneal fat and muscle, a difference that was maintained with altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into adulthood when it shows a greater thermogenic response to feeding than muscle and retroperitoneal fat. Sternal fat may be more amenable to targeted interventions that promote thermogenesis in large mammals

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Incidence and consequence of acute kidney injury in unselected emergency admissions to a large acute UK hospital trust

BACKGROUND: AKI is common among hospital in-patients and places a huge financial burden on the UK National Health Service, causing increased length of hospital stay and use of critical care services, with increased requirement for complex interventions including dialysis. This may account for up to 0.6% of the total Health Service budget. To investigate the incidence and consequences of AKI, all unselected emergency admissions to a large acute UK single centre University Teaching Hospital over two separate 7 day periods were reviewed. METHODS: A retrospective audit of 745 case records was undertaken (54.6% male) including laboratory data post-discharge or death, with classification of AKI by RIFLE, AKIN and AKIB criteria. Participants were included whether admitted via their general practitioners, the emergency department, or as tertiary specialty transfers. Outcome measures were presence or absence of AKI recorded using each of the three AKI criteria, length of hospital stay (LOS), admission to, and LOS in critical care, and mortality. The most severe grade of AKI only, at any time during the admission, was recorded to prevent double counting. Renal outcome was determined by requirement for renal replacement therapy (RRT), and whether those receiving RRT remained dialysis dependent or not. RESULTS: AKI incidence was 25.4% overall. With approximately one third present on admission and two thirds developing post admission. The AKI group had LOS almost three times higher than the non AKI group (10 vs 4 days). Requirement for critical care beds was 8.1% in the AKI group compared to 1.7% in non AKI group. Overall mortality was 5.5%, with the AKI group at 11.4% versus 3.3% in the non AKI group. CONCLUSIONS: AKI in acute unselected hospital admissions is more common than existing literature suggests, affecting 25% of unselected admissions. In many this is relatively mild and may resolve spontaneously, but is associated with increased LOS, likelihood of admission to critical care, and risk of death. If targeted effective interventions can be developed it seems likely that substantial clinical benefits for the patient, as well as financial and structural benefits for the healthcare organisation may accrue