Autoantibody-Based Diagnostic Biomarkers: Technological Approaches to Discovery and Validation

Autoantibodies produced against self-antigens, or ‘autoantigens’, result from a loss of self-tolerance triggered by genetic and/or environmental factors which induce the immune system to attack the host’s own cells, resulting in a condition referred to as autoimmunity. In classic autoimmune diseases, it is well established that the pathology relates directly to the autoantibodies. However, it is increasingly recognised that autoantibodies are also found in many other disease areas, including cancers, cardiovascular and neurodegenerative diseases, as well infectious diseases such as malaria, albeit in such diseases it is unclear whether the autoantibodies play a direct role in the pathology or whether they are merely symptomatic of disease. Irrespective of whether they are causative or symptomatic of specific diseases though, there is increasing interest globally in exploring the clinical potential of circulating autoantibodies as diagnostic biomarkers. This chapter provides an overview of the diagnostic utility of autoantibody biomarkers in a range of disease areas and discusses their potential utility in disease staging, treatment monitoring and in prediction of immune-related adverse events. It also provides an overview of traditional and contemporary technological approaches to autoantibody biomarker discovery and validation, focusing on protein microarrays that are ideally suited to this important area of research

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

Better characterization of operation for ulcerative colitis through the National surgical quality improvement program: A 2-year audit of NSQIP-IBD

IntroductionThere is little consensus of quality measurements for restorative proctocolectomy with ileal pouch-anal anastomosis(RPC-IPAA) performed for ulcerative colitis(UC). The National Surgical Quality Improvement Program(NSQIP) cannot accurately classify RPC-IPAA staged approaches. We formed an IBD-surgery registry that added IBD-specific variables to NSQIP to study these staged approaches in greater detail.MethodsWe queried our validated database of IBD surgeries across 11 sites in the US from March 2017 to March 2019, containing general NSQIP and IBD-specific perioperative variables. We classified cases into delayed versus immediate pouch construction and looked for independent predictors of pouch delay and postoperative Clavien-Dindo complication severity.Results430 patients received index surgery or completed pouches. Among completed pouches, 46(28%) and 118(72%) were immediate and delayed pouches, respectively. Significant predictors for delayed pouch surgery included higher UC surgery volume(p = 0.01) and absence of colonic dysplasia(p = 0.04). Delayed pouch formation did not significantly predict complication severity.ConclusionsOur data allows improved classification of complex operations. Curating disease-specific variables allows for better analysis of predictors of delayed versus immediate pouch construction and postoperative complication severity.Short summaryWe applied our previously validated novel NSIP-IBD database for classifying complex, multi-stage surgical approaches for UC to a degree that was not possible prior to our collaborative effort. From this, we describe predictive factors for delayed pouch formation in UC RPC-IPAA with the largest multicenter effort to date

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)