Association between inflammation and post-intensive care syndrome: a systematic review.

Post-intensive care syndrome describes the physical, cognitive and emotional symptoms which persist following critical illness. At present there is limited understanding of the pathological mechanisms contributing to the development of post-intensive care syndrome. The aim of this systematic review was to synthesise current evidence exploring the association between inflammation and features of post-intensive care syndrome in survivors of critical illness. Relevant databases were systematically searched for studies of human participants exposed to critical illness. We sought studies that reported results for biomarkers with an identified role in the pathophysiology of inflammation obtained at any time-point in the patient journey and an outcome measure of any feature of post-intensive care syndrome at any point following hospital discharge. We included 32 studies, with 23 in the primary analysis and nine in a brain injury subgroup analysis. In the primary analysis, 47 different biomarkers were sampled and 44 different outcome measures were employed. Of the biomarkers which were sampled in five or more studies, interleukin-8, C-reactive protein and interleukin-10 most frequently showed associations with post-intensive care syndrome outcomes in 71%, 62% and 60% of studies, respectively. There was variability in terms of which biomarkers were sampled, time-points of sampling and outcome measures reported. Overall, there was mixed evidence of a potential association between an inflammatory process and long-term patient outcomes following critical illness. Further high-quality research is required to develop a longitudinal inflammatory profile of survivors of critical illness over the recovery period and evaluate the association with outcomes.

Hospital re-admission after critical care survival: a systematic review and meta-analysis.

Survivors of critical illness frequently require increased healthcare resources after hospital discharge. We undertook a systematic review and meta-analysis to assess hospital re-admission rates following critical care admission and to explore potential re-admission risk factors. We searched the MEDLINE, Embase and CINAHL databases on 05 March 2020. Our search strategy incorporated controlled vocabulary and text words for hospital re-admission and critical illness, limited to the English language. Two reviewers independently applied eligibility criteria and assessed quality using the Newcastle Ottawa Score checklist and extracted data. The primary outcome was acute hospital re-admission in the year after critical care discharge. Of the 8851 studies screened, 87 met inclusion criteria and 41 were used within the meta-analysis. The analysis incorporated data from 3,897,597 patients and 741,664 re-admission episodes. Pooled estimates for hospital re-admission after critical illness were 16.9% (95%CI: 13.3-21.2%) at 30 days; 31.0% (95%CI: 24.3-38.6%) at 90 days; 29.6% (95%CI: 24.5-35.2%) at six months; and 53.3% (95%CI: 44.4-62.0%) at 12 months. Significant heterogeneity was observed across included studies. Three risk factors were associated with excess acute care rehospitalisation one year after discharge: the presence of comorbidities; events during initial hospitalisation (e.g. the presence of delirium and duration of mechanical ventilation); and subsequent infection after hospital discharge. Hospital re-admission is common in survivors of critical illness. Careful attention to the management of pre-existing comorbidities during transitions of care may help reduce healthcare utilisation after critical care discharge. Future research should determine if targeted interventions for at-risk critical care survivors can reduce the risk of subsequent rehospitalisation.

A prospective cohort study characterising patients declined emergency laparotomy: survival in the 'NoLap' population.

Patients eligible for emergency laparotomy who do not proceed to surgery are not as well characterised as patients who do proceed to surgery. We studied patients eligible for laparotomy, as defined by National Emergency Laparotomy Audit criteria, from August 2015 to October 2016. We analysed the association of individual variables with survival and two composite scores: P-POSSUM and a general survival model. Out of 314 patients, 214 (68%) underwent laparotomy and 100 (32%) did not. Median (IQR [range]) follow-up was 1.3 (0.1-1.8 [0.0-2.5]) years for the cohort, 1.5 (1.1-2.0 [0.0-2.6]) years after laparotomy and 0.0 (0.0-1.1 [0.0-2.2]) years without laparotomy. There were 126/314 (40%) deaths in the follow-up period, 52/214 (24%) deaths after laparotomy and 74/100 (74%) deaths without surgery. Ninety out of 126 deaths (71%) were within one month of hospital admission. Patient variables were different for the two groups, which when combined in the general survival model generated background median (IQR [range]) life expectancies of 12 (6-21 [0-49]) and 4 (2-6 [0-36]) years, respectively, p < 0.0001. 'Poor fitness' precluded laparotomy in 74/100 (74%) patients. The decision to not operate involved a consultant less often than the decision to operate: 66/100 (66%) vs. 178/214 (83%), p = 0.001. Our study supports the contention that survival beyond 30 postoperative days could be predicted reasonably accurately. Survival in patients who did not have laparotomy was shorter than expected. Emergency laparotomy might have prolonged survival in some patients.

Critical care provision after colorectal cancer surgery.

BACKGROUND: Colorectal cancer (CRC) is the 2nd largest cause of cancer related mortality in the UK with 40 000 new patients being diagnosed each year. Complications of CRC surgery can occur in the perioperative period that leads to the requirement of organ support. The aim of this study was to identify pre-operative risk factors that increased the likelihood of this occurring. METHODS: This is a retrospective observational study of all 6441 patients who underwent colorectal cancer surgery within the West of Scotland Region between 2005 and 2011. Logistic regression was employed to determine factors associated with receiving postoperative organ support. RESULTS: A total of 610 (9 %) patients received organ support. Multivariate analysis identified age ≥65, male gender, emergency surgery, social deprivation, heart failure and type II diabetes as being independently associated with organ support postoperatively. After adjusting for demographic and clinical factors, patients with metastatic disease appeared less likely to receive organ support (p = 0.012). CONCLUSIONS: Nearly one in ten patients undergoing CRC surgery receive organ support in the post operative period. We identified several risk factors which increase the likelihood of receiving organ support post operatively. This is relevant when consenting patients about the risks of CRC surgery.

Recombinant activated protein C usage in Scotland: a comparison with published guidelines and a survey of attitudes.

Severe sepsis is a common cause of admission to the intensive care unit and is associated with a high hospital mortality. This audit explored the current use of, and attitudes towards, recombinant activated protein C therapy across Scotland, and compared these with current guidance. Patients with severe sepsis were followed for three days. Consideration and/or usage of recombinant activated protein C were compared with two different guidelines. Ninety-seven patients were admitted to the intensive care unit over the audit period. Recombinant activated protein C was used in nine of these patients. Depending on the criteria used, between 50% and 81% of the patients who qualified for recombinant activated protein C therapy did not receive it. Subsequent to the audit, a survey was performed to study intensive care unit consultants' attitudes to recombinant activated protein C therapy. A total of 125 consultants responded to the survey (77%). Of these, 104 (83%) stated that they used recombinant activated protein C in their clinical practice, 56 (52%) of whom prescribed it to patients with two-organ failures and an Acute Physiology and Chronic Health Evaluation II score of ≥ 25. Thirty-nine respondents (38%) stated that two-organ failures alone would be an adequate trigger for therapy. We conclude that recombinant activated protein C is potentially under-used to treat severe sepsis. Many consultants seem to reserve the drug for the most severely ill sub group of patients.

Decision making in emergency laparotomy: the role of predicted life expectancy.

INTRODUCTION: Increasing numbers of older patients are undergoing emergency laparotomy (EL). They are at increased risk of adverse outcomes, making the shared decision on whether to operate challenging. This retrospective cohort study aimed to assess the role of age and life-expectancy predictions on short- and long-term survival in patients undergoing EL. METHODS: All patients who underwent EL at one hospital in the West of Scotland between March 2014 to December 2016 were included. Clinical parameters were collected, and patients were followed up to allow reporting of 30-, 60- and 90-day and 1-year mortality rates. Period life expectancy was used to stratify patients into below life expectancy (bLEP) and at-or-above life expectancy (aLEP) groups at presentation. Remaining life expectancy was used to calculate the net years of life gained (NYLG). RESULTS: Some 462 patients underwent EL: 20 per cent in the aLEP group. These patients were older (P < 0.001), had more co-morbidities (P < 0.001) and were high risk on P-POSSUM scoring (P = 0.008). The 30-, 60- and 90-day and 1-year mortality rates were 11, 14, 16 and 23 per cent respectively. Advanced age (P = 0.011) and high ASA score (P = 0.004) and P-POSSUM score (P < 0.001) were independent predictors of death at 1 year on multivariable analysis. The cohort NYLG were 19.2 years. Comparing patients aged less than 70 with those aged 70 years or older, the NYLG were 25.9 versus 5.5 years. Comparing bLEP and aLEP, the NYLG were 22.2 versus 4.4 years. In patients aged 70 years and older, NYLG decreased by more than half in patients with co-morbidities (ASA score 3,4,5) (9.3 versus 4.3 years). CONCLUSION: Discussions around long-term outcomes after emergency surgery remain difficult. Although age is an influencing factor, predicted life expectancy alone does not provide additional value to shared decision making.

Provision of trauma teams in Scotland: a national survey.

BACKGROUND AND AIMS: Trauma is still the leading cause of mortality in the first four decades of life. Despite numerous reports on how trauma care could be improved in the UK, treatment has been shown to be inconsistent and of poor quality. Trauma teams have been shown to have a positive effect on outcome. A study was undertaken to determine the prevalence of trauma teams in Scotland. METHODS: A telephone survey was performed of 24 hospitals with emergency departments in which the senior clinician was interviewed regarding the provision of trauma teams. RESULTS: Five (21%) of the hospitals questioned had trauma teams. The most common reasons for not having one were no problem with the current system in eight cases (44%) and an inability to include sufficiently senior staff on the team in six cases (24%). CONCLUSIONS: There are few trauma teams in Scottish acute hospitals. There was little enthusiasm for introducing them for a variety of reasons. Local evidence of benefit is probably needed before their adoption becomes widespread.

Frailty Exists in Younger Adults Admitted as Surgical Emergency Leading to Adverse Outcomes.

BACKGROUND: Frailty is prevalent in the older adult population (≥65 years of age) and results in adverse outcomes in the emergency general surgical population. OBJECTIVE: To determine whether frailty exists in the younger adult emergency surgical population (<65 years) and what influence frailty may have on patient related outcomes. DESIGN: Prospective observational cohort study. SETTING: Emergency general surgical admissions. PARTICIPANTS: All patients ≥40 years divided into 2 groups: younger adults (40-64.9 years) and older adult comparative group (≥65). MEASUREMENTS: Over a 6-month time frame the following data was collected: demographics; Scottish Index of Multiple Deprivation (SIMD); blood markers; multi-morbidities, polypharmacy and cognition. Frailty was assessed by completion of the Canadian Study of Health and Ageing (CSHA). Each patient was followed up for 90 days to allow determination of length of stay, re-admission and mortality. RESULTS: 82 young adults were included and the prevalence of frailty was 16% (versus older adults 38%; p=0.001) and associated with: multi-morbidity; poly-pharmacy; cognitive impairment; and deprivation. Frailty in older adults was only significantly associated with increasing age. CONCLUSIONS: This novel study has found that frailty exists in 16% of younger adults admitted to emergency general surgical units, potentially leading to adverse short and long-term outcomes. Strategies need to be developed that identify and treat frailty in this vulnerable younger adult population.

Lower concentrations of carotenoids in the critically ill patient are related to a systemic inflammatory response and increased lipid peroxidation.

BACKGROUND: Critically-ill patients have low circulating concentrations of vitamin antioxidants. The functional significance of such reductions is not clear. AIMS: To determine whether the presence of a systemic inflammatory response was associated with reduced circulating alpha-tocopherol and carotenoid concentrations and an increase in lipid peroxidation as evidenced by malondialdehyde. METHODS: Healthy controls (n=24) and critically-ill patients (n=43) had circulating concentrations of C-reactive protein, cholesterol, triglycerides, malondialdehyde, alpha-tocopherol, lutein, lycopene, alpha- and beta-carotene measured during ITU stay. RESULTS: In the critically-ill group circulating concentrations of C-reactive protein and malondialdehyde were significantly higher (P<0.05) and cholesterol, triglyceride, alpha-tocopherol, lutein, lycopene, alpha- and beta-carotene were all significantly lower (P<0.01) compared with the control group. In the critically-ill group alpha- and beta-carotene were below detection limits for many patients. After adjusting for cholesterol, lycopene concentrations remained significantly lower (P<0.001) compared with the control group. In the critically-ill patients circulating concentrations of C-reactive protein and malondialdehyde were significantly correlated (r=0.502,P<0.01). CONCLUSIONS: The systemic inflammatory response is associated with increased lipid peroxidation and low carotenoid concentrations indicating that inflammation driven breakdown of carotenoids is an important factor in lowering circulating carotenoid concentrations in the critically-ill patient.

Severe abdominal pain in women: a case report of an hepatic adenoma.

As the use of the oral contraceptive pill increases, so does the incidence of hepatic adenomata. This condition can present as an acute surgical emergency in the previously healthy female but is often overlooked as a possible diagnosis. This report illustrates such a case and its sometimes unusual presentation.

Zwitterionic detergent solubilisation of HSV-1 surface antigens.

A preparation was obtained from herpes simplex virus type 1 (HSV-1)-infected cells using a zwitterionic detergent, Empigen BB. The preparation was partially-purified either by ultracentrifugation over a cusion of 20% sucrose or on a sucrose density gradient. Partial characterisation of these materials by ELISA, using both polyclonal and monoclonal antibodies showed them to contain at least four major HSV glycoproteins, gB, gC, gD and gE. Comparison of Empigen-extracted HSV-1 antigen preparations with preparations obtained using the non-ionic detergents Nonidet P40 or Triton-X-100 indicate that, using conventional procedures, separation of glycoproteins, B, C, D, and E from unwanted proteins may be facilitated using the former detergent. Immunization of mice with Empigen-extracted, partially-purified or gradient-purified antigen preparations elicited good levels of antibody detectable by ELISA and a high degree of protection against both HSV-1 and HSV-2 challenge infection. Such protection could be achieved using aqueous antigen preparations, but was augmented using aluminium hydroxide gel as an adjuvant. In general, Empigen-extracted HSV-1 antigen preparations elicited higher ELISA antibody levels and more complete protection against HSV challenge infection than NP40 or Triton-X-100-extracted preparations. The value and usefulness of the detergent Empigen for obtaining HSV surface antigen preparations and the role of these as potential vaccines against HSV infections, is discussed.

Characterization and immunogenicity of HSV-1 antigens obtained following zwitterionic detergent treatment.

A preparation was obtained from herpesvirus hominis type 1 (HSV-1) infected cells using the zwitterionic detergent, Empigen BB. The preparation was partially purified by ultracentrifugation over a cushion of 20% sucrose. Serological characterization by ELISA and immuno double diffusion, using both polyclonal and monoclonal antibodies shows this preparation to contain HSV glycoproteins, including gC, gD and gE. Immunization of Balb/c mice elicited serum antibody responses against both HSV-1 and HSV-2 viruses, complete protection against HSV-1 (strain WAL) and partial protection against HSV-2 (strain 333).