The effect of diabetes mellitus on perioperative outcomes after colorectal resection: a national cohort study.

BACKGROUND: Diabetes mellitus is a significant modulator of postoperative outcomes and is an important risk factor in the patient selection process. We aimed to investigate the effect of diabetes mellitus and use of insulin on outcomes after colorectal resection using a national cohort. METHODS: Adults with a recorded colorectal resection in England between 2010 and 2020 were identified from Hospital Episode Statistics data linked to the Clinical Practice Research Database. The primary outcome was 90-day mortality. Secondary outcomes included hospital length of stay (LOS) and readmission within 90 days. RESULTS: Of the 106 139 (52 875, 49.8% male) patients included, diabetes mellitus was prevalent in 10 931 (10.3%), 2145 (19.6%) of whom had a record of use of insulin. Unadjusted 90-day mortality risk was 5.7%, with an increased adjusted hazard ratio (aHR) for people with diabetes mellitus (aHR 1.28, 95% confidence interval [CI] 1.19-1.37, P<0.001). This risk was higher in both people with diabetes using insulin (aHR 1.51, 95% CI 1.31-1.74, P<0.001) and not using insulin (aHR 1.22, 95% CI 1.13-1.33, P<0.001), compared with those without diabetes. Ninety-day readmission occurred in 20 542 (19.4%) patients and this was more likely in those with diabetes mellitus (aHR 1.23, 95% CI 1.18-1.29, P<0.001). Median (inter-quartile range) LOS was 8 (5-15) days and was higher in people with diabetes mellitus (adjusted time ratio 1.10, 95% CI 1.08-1.11, P<0.001). CONCLUSIONS: People with diabetes mellitus undergoing colorectal resection are at a higher risk of 90-day mortality, prolonged LOS, and 90-day readmission, with use of insulin associated with additional risk.

Ethnicity and socio-economic status affects the incidence and survival of hepatosplenic T-cell lymphoma.

To address the lack of contemporary population-based epidemiological studies of hepatosplenic T-cell lymphoma (HSTCL), we undertook a population-based study of ICD-O-3-coded HSTCL in England. We used the National Cancer Registration Dataset and linked datasets on hospital admissions, Systemic Anti-Cancer Therapy, socio-demographics, comorbidities and death, identifying cases from 1 January 2013 to 31 December 2019 with survival data up to 5 January 2021. Crude and directly age-standardised incidence rates per million persons per year were calculated. Crude and adjusted incidence rate ratios compared incidence between groups using Poisson regression. A Cox proportional hazards model estimated mortality risks adjusted for age, sex, ethnicity, deprivation and allogenic stem cell transplant (allo-SCT; time varying). We identified 44 patients, mean age 42 years. Median survival was 11 months, and 1 and 5 year survivals were 48% (95% CI 29%-43%) and 22% (95% CI 12%-42%) respectively. The age-standardised incidence was 0.1 per million/year. Incidence was higher in areas with greater deprivation (0.15 per million/year), and more cases than expected were in non-White patients (39%). Non-Whites had a twofold increased risk of death (adjusted hazard ratio 2.21 [95% CI 1.03-4.78]) even after adjusting for deprivation, younger age and allo-SCT. In conclusion, ethnicity and socio-economic status affect both the incidence and survival of HSTCL.

Smoking is a Risk Factor for Autoimmune Hepatitis: An English Registry-Based Case-Control Study.

Purpose: Smoking is a risk factor for some autoimmune diseases, but its association with autoimmune hepatitis remains unknown. We conducted a population-based matched case-control study to examine the association between tobacco smoking and the risk of autoimmune hepatitis in England. Patients and Methods: From the Clinical Practice Research Datalink and linked Hospital Episode Statistics, 2005-2017, we included 987 cases diagnosed with autoimmune hepatitis after age 18 years and up to 10 frequency-matched population controls per case. We used multiple logistic regression to estimate the odds ratio of autoimmune hepatitis in ever-smokers vs never-smokers, adjusting for sex, age, general practice, calendar time of registration with the general practice, and socioeconomic status. Results: The autoimmune hepatitis cases were more likely to be ever-smokers than the controls (44% vs 37%). The ever-smokers had an increased risk of autoimmune hepatitis compared with the never-smokers (adjusted odds ratio = 1.20, 95% confidence interval 1.03-1.39). Conclusion: Smoking was associated with an increased risk of autoimmune hepatitis.

Outcomes after emergency appendicectomy in patients with liver cirrhosis: a population-based cohort study from England.

INTRODUCTION: The mortality risk after appendicectomy in patients with liver cirrhosis is predicted to be higher than in the general population given the associated risk of perioperative bleeding, infections and liver decompensation. This population-based cohort study aimed to determine the 90-day mortality risk following emergency appendicectomy in patients with cirrhosis. METHODS: Adult patients undergoing emergency appendicectomy in England between January 2001 and December 2018 were identified from two linked primary and secondary electronic healthcare databases, the clinical practice research datalink and hospital episode statistics data. Length of stay, re-admission, case fatality and the odds ratio of 90-day mortality were calculated for patients with and without cirrhosis, adjusting for age, sex and co-morbidity using logistic regression. RESULTS: A total of 40,353 patients underwent appendicectomy and of these 75 (0.19%) had cirrhosis. Patients with cirrhosis were more likely to be older (p < 0.0001) and have comorbidities (p < 0.0001). Proportionally, more patients with cirrhosis underwent an open appendicectomy (76%) compared with 64% of those without cirrhosis (p = 0.03). The 90-day case fatality rate was 6.67% in patients with cirrhosis compared with 0.56% in patients without cirrhosis. Patients with cirrhosis had longer hospital length of stay (4 (IQR 3-9) days versus 3 (IQR 2-4) days and higher readmission rates at 90 days (20% vs 11%, p = 0.019). Most importantly, their odds of death at 90 days were 3 times higher than patients without cirrhosis, adjusted odds ratio 3.75 (95% CI 1.35-10.49). CONCLUSION: Patients with cirrhosis have a threefold increased odds of 90-day mortality after emergency appendicectomy compared to those without cirrhosis.

Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England.

BACKGROUND: A faecal immunochemical tests (FIT) cut-off of ≥10 µg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. AIMS: To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata. METHODS: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. RESULTS: In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 µg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%-2.86%]). Non-anaemic patients with a FIT < 100 µg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%-7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160-220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1-2 CRCs. CONCLUSIONS: FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 µg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.

Respiratory rate responses to both hypercapnia and acidaemia are modified by age in patients with acidosis.

OBJECTIVE: To explore the associations between arterial pO2, pCO2 and pH and how these are modified by age. METHODS: An analysis of 2598 patients admitted with a diagnosis of Covid-19 infection to a large UK teaching hospital. RESULTS: There were inverse associations for arterial pO2, pCO2 and pH with respiratory rate. The effects of pCO2 and pH on respiratory rate were modified by age; older patients had higher respiratory rates at higher pCO2 (p = 0.004) and lower pH (p = 0.007) values. CONCLUSIONS: This suggests that ageing is associated with complex changes in the physiological feedback loops that control respiratory rate. As well as having clinical relevance, this may also impact on the use of respiratory rate in early warning scores across the age range.

Risk of Postoperative Venous Thromboembolism After Benign Colorectal Surgery: Systematic Review and Meta-analysis.

BACKGROUND: Venous thromboembolism is a well-established preventable complication after colectomy. Specific guidance on venous thromboembolism prevention after colectomy for benign disease is limited. OBJECTIVE: This meta-analysis aimed to quantify the venous thromboembolism risk after benign colorectal resection and determine its variability. DATA SOURCES: Following Preferred Reporting Items for Systematic Review and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology Guidelines (PROSPERO: CRD42021265438), Embase, MEDLINE, and 4 other registered medical literature databases were searched from the database inception to June 21, 2021. STUDY SELECTION: Inclusion criteria: randomized controlled trials and large population-based database cohort studies reporting 30-day and 90-day venous thromboembolism rates after benign colorectal resection in patients aged ≥18 years. Exclusion criteria: patients undergoing colorectal cancer or completely endoscopic surgery. MAIN OUTCOME MEASURES: Thirty- and 90-day venous thromboembolism incidence rates per 1000 person-years after benign colorectal surgery. RESULTS: Seventeen studies were eligible for meta-analysis reporting on 250,170 patients. Pooled 30-day and 90-day venous thromboembolism incidence rates after benign colorectal resection were 284 (95% CI, 224-360) and 84 (95% CI, 33-218) per 1000 person-years. Stratified by admission type, 30-day venous thromboembolism incidence rates per 1000 person-years were 532 (95% CI, 447-664) for emergency resections and 213 (95% CI, 100-453) for elective colorectal resections. Thirty-day venous thromboembolism incidence rates per 1000 person-years after colectomy were 485 (95% CI, 411-573) for patients with ulcerative colitis, 228 (95% CI, 181-288) for patients with Crohn's disease, and 208 (95% CI, 152-288) for patients with diverticulitis. LIMITATIONS: High degree of heterogeneity was observed within most meta-analyses attributable to large cohorts minimizing within-study variance. CONCLUSIONS: Venous thromboembolism rates remain high up to 90 days after colectomy and vary by indication for surgery. Emergency resections compared to elective benign resections have higher rates of postoperative venous thromboembolism. Further studies reporting venous thromboembolism rates by type of benign disease need to stratify rates by admission type to more accurately define venous thromboembolism risk after colectomy. REGISTRATION NO: CRD42021265438.

Anaemia of acute inflammation: a higher acute systemic inflammatory response is associated with a larger decrease in blood haemoglobin levels in patients with COVID-19 infection.

AIMS: The study tests the hypothesis that a higher acute systemic inflammatory response was associated with a larger decrease in blood hemoglobin levels in patients with Coronavirus 2019 (COVID-19) infection. METHODS: All patients with either suspected or confirmed COVID-19 infection admitted to a busy UK hospital from February 2020 to December 2021 provided data for analysis. The exposure of interest was maximal serum C-reactive protein (CRP) level after COVID-19 during the same admission. RESULTS: A maximal serum CRP >175mg/L was associated with a decrease in blood haemoglobin (-5.0 g/L, 95% confidence interval: -5.9 to -4.2) after adjustment for covariates, including the number of times blood was drawn for analysis.Clinically, for a 55-year-old male patient with a maximum haemoglobin of 150 g/L who was admitted for a 28-day admission, a peak CRP >175 mg/L would be associated with an 11 g/L decrease in blood haemoglobin, compared with only 6 g/L if the maximal CRP was <4 mg/L. CONCLUSIONS: A higher acute systemic inflammatory response is associated with larger decreases in blood haemoglobin levels in patients with COVID-19. This represents an example of anaemia of acute inflammation, and a potential mechanism by which severe disease can increase morbidity and mortality.

Venous thromboembolism following colectomy for diverticular disease: an English population-based cohort study.

AIM: This study reports venous thromboembolism (VTE) rates following colectomy for diverticular disease to explore the magnitude of postoperative VTE risk in this population and identify high risk subgroups of interest. METHOD: English national cohort study of colectomy patients between 2000 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type, absolute incidence rates (IR) per 1000 person-years and adjusted incidence rate ratios (aIRR) were calculated for 30- and 90-day post-colectomy VTE. RESULTS: Of 24,394 patients who underwent colectomy for diverticular disease, over half (57.39%) were emergency procedures with the highest VTE rate seen in patients ≥70-years-old (IR 142.27 per 1000 person-years, 95%CI 118.32-171.08) at 30 days post colectomy. Emergency resections (IR 135.18 per 1000 person-years, 95%CI 115.72-157.91) had double the risk (aIRR 2.07, 95%CI 1.47-2.90) of developing a VTE at 30 days following colectomy compared to elective resections (IR 51.14 per 1000 person-years, 95%CI 38.30-68.27). Minimally invasive surgery (MIS) was shown to be associated with a 64% reduction in VTE risk (aIRR 0.36 95%CI 0.20-0.65) compared to open colectomies at 30 days post-op. At 90 days following emergency resections, VTE risks remained raised compared to elective colectomies. CONCLUSION: Following emergency colectomy for diverticular disease, the VTE risk is approximately double compared to elective resections at 30 days while MIS was found to be associated with a reduced risk of VTE. This suggests advancements in postoperative VTE prevention in diverticular disease patients should focus on those undergoing emergency colectomies.

Inverse association between blood pressure and pulse oximetry accuracy: an observational study in patients with suspected or confirmed COVID-19 infection.

BACKGROUND: Pulse oximeters are a standard non-invasive tool to measure blood oxygen levels, and are used in multiple healthcare settings. It is important to understand the factors affecting their accuracy to be able to use them optimally and safely. This analysis aimed to explore the association of the measurement error of pulse oximeters with systolic BP, diastolic BP and heart rate (HR) within ranges of values commonly observed in clinical practice. METHODS: The study design was a retrospective observational study of all patients admitted to a large teaching hospital with suspected or confirmed COVID-19 infection from February 2020 to December 2021. Data on systolic and diastolic BPs and HR levels were available from the same time period as the pulse oximetry measurements. RESULTS: Data were available for 3420 patients with 5927 observations of blood oxygen saturations as measured by pulse oximetry and ABG sampling within 30 min. The difference in oxygen saturation using the paired pulse oximetry and arterial oxygen saturation difference measurements was inversely associated with systolic BP, increasing by 0.02% with each mm Hg decrease in systolic BP (95% CI 0.00% to 0.03%) over a range of 80-180 mm Hg. Inverse associations were also observed between the error for oxygen saturation as measured by pulse oximetry and with both diastolic BP (+0.03%; 95% CI 0.00% to 0.05%) and HR (+0.04%; 95% CI 0.02% to 0.06% for each unit decrease in the HR). CONCLUSIONS: Care needs to be taken in interpreting pulse oximetry measurements in patients with lower systolic and diastolic BPs, and HRs, as oxygen saturation is overestimated as BP and HR decrease. Confirmation of the oxygen saturation with an ABG may be appropriate in some clinical scenarios.

Cholecystectomy in patients with cirrhosis: a population-based cohort study from England.

BACKGROUND: This population-based cohort study aimed to determine postoperative outcomes after emergency and elective cholecystectomy in patients with cirrhosis. METHODS: Linked electronic healthcare data from England were used to identify all patients undergoing cholecystectomy between January 2000 and December 2017. Length of stay (LOS), re-admission, case fatality and the odds ratio of 90-day mortality were calculated for patients with and without cirrhosis, adjusting for age, sex and co-morbidity using logistic regression. RESULTS: Of the total 69,141 eligible patients who underwent a cholecystectomy, 511 (0.74%) had cirrhosis. In patients without cirrhosis 86.55% underwent a laparoscopic procedure compared with 57.53% in patients with cirrhosis (p < 0.0001). LOS was longer in those with cirrhosis (3 IQR 1-8 vs 1 IQR 1-3 days,p < 0.0001). 90-day re-admission was greater in patients with cirrhosis, 36.79% compared with 14.95% in those without cirrhosis. 90-day case fatality after elective cholecystectomy in patients with and without cirrhosis was 2.79% and 0.43%; and 12.82% and 2.39% following emergency cholecystectomy. This equated to a 3-fold (OR 3.22, IQR 1.72-6.02) and a 4-fold (OR 4.52, IQR 2.46-8.33) increased odds of death at 90-days following elective and emergency cholecystectomy after adjusting for confounders. CONCLUSION: Patients with cirrhosis undergoing cholecystectomy have an increased 90-day risk of postoperative mortality, which is significantly worse after emergency procedures.

Temporal Trends in the Incidence of Hemophagocytic Lymphohistiocytosis: A Nationwide Cohort Study From England 2003-2018.

Hemophagocytic lymphohistiocytosis (HLH) is rare, results in high mortality, and is increasingly being diagnosed. We aimed to quantify the incidence of diagnosed HLH and examine temporal trends in relation to age and associated diseases. Using national linked electronic health data from hospital admissions and death certification cases of HLH that were diagnosed in England between January 1, 2003, and December 31, 2018. We calculated incidence rates of diagnosed HLH per million population by calendar year, age group, sex, and associated comorbidity (hematological malignancy, inflammatory rheumatological or bowel diseases [IBD]). We modeled trends in incidence and the interactions between calendar year, age, and associated comorbidity using Poisson regression. There were 1674 people with HLH diagnosed in England between 2003 and 2018. The incidence rate quadrupled (incidence rate ratio [IRR] 2018 compared to 2003: 3.88, 95% confidence interval [CI] 2.91 to 5.28), increasing 11% annually (adjusted IRR 1.11, 95% CI 1.09 to 1.12). There was a transition across age groups with greater increases in those aged 5-14 years of HLH associated with rheumatological disease/IBD compared with hematological malignancy, with similar increases in HLH associated with both comorbidities for those 15-54, and greater increases in HLH associated with hematological malignancies for those 55 years and older. The incidence of HLH in England has quadrupled between 2003 and 2018. Substantial variation in the incidence occurred with inflammatory rheumatological diseases/IBD-associated HLH increasing more among the younger age groups, whereas in older age groups, the largest increase was seen with hematological malignancy-associated HLH.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

Predicting Need for Escalation of Care or Death From Repeated Daily Clinical Observations and Laboratory Results in Patients With Severe Acute Respiratory Syndrome Coronavirus 2.

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n = 1,141; C statistic: C = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission.

The Duration and Magnitude of Postdischarge Venous Thromboembolism Following Colectomy.

OBJECTIVE: To assess the impact of current guidelines by reporting weekly postoperative postdischarge venous thromboembolism (VTE) rates. SUMMARY BACKGROUND DATA: Disparity exists between the postoperative thromboprophylaxis duration colectomy patients receive based on surgical indication, where malignant resections routinely receive 28 days extended thromboprophylaxis into the postdischarge period and benign resections do not. METHODS: English national cohort study of colectomy patients between 2010 and 2019 using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Stratified by admission type and surgical indication, absolute incidence rates (IRs) per 1000 person-years and adjusted incidence rate ratios (aIRRs) for postdischarge VTE were calculated for the first 4 weeks following resection and postdischarge VTE IRs for each postoperative week to 12 weeks postoperative. RESULTS: Of 104,744 patients, 663 (0.63%) developed postdischarge VTE within 12 weeks after colectomy. Postdischarge VTE IRs per 1000 person-years for the first 4 weeks postoperative were low following elective resections [benign: 20.66, 95% confidence interval (CI): 13.73-31.08; malignant: 28.95, 95% CI: 23.09-36.31] and higher following emergency resections (benign: 47.31, 95% CI: 34.43-65.02; malignant: 107.18, 95% CI: 78.62-146.12). Compared with elective malignant resections, there was no difference in postdischarge VTE risk within 4 weeks following elective benign colectomy (aIRR=0.92, 95% CI: 0.56-1.50). However, postdischarge VTE risks within 4 weeks following emergency resections were significantly greater for benign (aIRR=1.89, 95% CI: 1.22-2.94) and malignant (aIRR=3.13, 95% CI: 2.06-4.76) indications compared with elective malignant colectomy. CONCLUSIONS: Postdischarge VTE risk within 4 weeks of colectomy is ∼2-fold greater following emergency benign compared with elective malignant resections, suggesting emergency benign colectomy patients may benefit from extended VTE prophylaxis.