Exploring D-Lactate as a Biomarker for Acute Intestinal Necrosis in 2958 Patients: A Prospective Cross-Sectional Study.

BACKGROUND: Timely diagnosis of acute intestinal necrosis (AIN) is lifesaving, but challenging due to unclear clinical presentation. D-lactate has been proposed as an AIN biomarker. OBJECTIVES: We aimed to test the diagnostic performance in a clinical setting. METHODS: We performed a cross-sectional prospective study, including all adult patients with acute referral to a single tertiary gastrointestinal surgical department during 2015-2016 and supplemented by enrollment of high-risk in-hospital patients suspected of having AIN during 2016-2019. AIN was verified intraoperatively, and D-lactate was analyzed using an automatic spectrophotometric set-up. A D-lactate cut-off for AIN was estimated using the receiver operating characteristic curve. The performance according to patient subgroups was estimated using the area under the receiver operating characteristic curve (AUC). Given the exploratory nature of this study, a formal power calculation was not feasible. RESULTS: Forty-four AIN patients and 2914 controls were enrolled. The D-lactate cut-off was found to be 0.0925 mM. Due to lipemic interference, D-lactate could not be quantified in half of the patients, leaving 23 AIN patients and 1456 controls for analysis. The AUC for the diagnosis of AIN by D-lactate was 0.588 (95% confidence interval 0.475-0.712), with a sensitivity of 0.261 and specificity of 0.892. Analysis of high-risk patients showed similar results (AUC 0.579; 95% confidence interval 0.422-0.736). CONCLUSION: D-lactate showed low sensitivity for AIN in both average-risk and high-risk patients. Moreover, lipemic interference precluded valid spectrophotometric assessment of D-lactate in half of the patients, further disqualifying the clinical utility of D-lactate as a diagnostic marker for AIN.

Exploring I-FABP, endothelin-1 and L-lactate as biomarkers of acute intestinal necrosis: a case-control study.

OBJECTIVE: Acute intestinal necrosis (AIN) is a disease with devastating high mortality. AIN due to obstructed arterial blood flow has a blurred clinical presentation. Timely diagnosis is paramount, and a blood-based biomarker is warranted to increase patient survival. We aimed to assess intestinal fatty acid binding protein (I-FABP) and endothelin-1 as diagnostic biomarkers for AIN. To our knowledge, this is the first study exploring endothelin-1 in AIN patients from a general surgical population. DESIGN: We conducted a single-centre nested case-control study comparing acutely admitted AIN patients to age- and sex-matched non-AIN patients during 2015-2016. I-FABP and endothelin-1 were analysed using an enzyme-linked immunosorbent assay. L-lactate levels were also measured in all patients. Cut-offs were estimated using receiver operator characteristic curves, and the diagnostic performance was estimated using the area under the receiver operator characteristic curve (AUC). RESULTS: We identified 43 AIN patients and included 225 matched control patients. Median levels of I-FABP, endothelin-1 and L-lactate were 3550 (IQR: 1746-9235) pg/ml, 3.91 (IQR: 3.33-5.19) pg/ml and 0.92 (IQR: 0.74-1.45) mM in AIN patients and 1731 (IQR: 1124-2848) pg/ml, 2.94 (IQR: 2.32-3.82) pg/ml and 0.85 (IQR: 0.64-1.21) mM in control patients, respectively. The diagnostic performances of endothelin-1 and of I-FABP + endothelin-1 combined were moderate. Endothelin-1 alone revealed an AUC of 0.74 (0.67; 0.82). The sensitivity and specificity of endothelin-1 were 0.81 and 0.64, respectively. CONCLUSION: I-FABP and endothelin-1 are promising biomarkers for AIN, with moderate diagnostic performance compared with the commonly used biomarker L-lactate. PREREGISTRATION: ClinicalTrials.gov: NCT05665946.

Preoperative findings on non-specific CT in patients with primary acute intestinal ischemia: a case-control study.

PURPOSE: Primary acute intestinal ischaemia (AII) is an abdominal catastrophe caused by intravascular obstruction of blood supply. It is difficult to diagnose. Computerized tomography (CT) scan is the modality of choice for diagnostic evaluation. Majority of previous studies have evaluated CT findings in patients where AII was suspected. However, unveiling the unique radiological findings also in not initially suspected AII patients, might lead to the timely management of AII patients, and is the aim of this study. METHODS: In a single-center, retrospective case-control study, preoperative radiological findings from abdominal CT scans in 48 patients with primary AII were compared with 80 non-ischemic controls. Radiological findings were analyzed using multivariable logistical regression with adjustment for age and gender and reported as odds ratios (OR) with 95% confidence intervals (CI) and p values. RESULTS: Thirty-nine (81%) cases with AII were referred to an abdominal CT scan without a specific clinical suspicion of AII. Three main radiological categories (intestinal wall pathology [OR 7.4, CI 2.3-24.0, p value < 0.001], gastrointestinal vessel pathology [OR 19.3, CI 4.6-80.5, p value < 0.001) and intestinal diameter [OR 4.7, CI 1.6-13.4, p value 0.004]) were significantly different in AII patients. Subgroup analysis implied that pneumatosis intestinalis, increased contrast enhancement in the bowel wall, inferior mesenteric artery arteriosclerosis and colonic contraction were predictors of AII. CONCLUSION: Radiological changes within the intestinal wall, luminal diameter and gastrointestinal vessels are independent predictors of AII. Awareness of these radiological findings, therefore, plays a central role in patients with an indistinct clinical picture in early recognition and treatment of a life-threatening AII. TRIAL REGISTRATION NUMBER: NCT04361110 (April 24, 2020), retrospectively registered.

Fully automatic d-lactate assay using a modified commercially available method.

Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not available in the acute clinical setting. The aim of this study is implementation of d-lactate analysis in a routine clinical setting. We used a spectrophotometric method, based on enzymatic oxidation of d-lactate by d-lactate dehydrogenase (D-LDH) coupled to the reduction of nicotinamide-adenine dinucleotide (NAD+). The amount of NADH formed in this reaction is equivalent to d-lactate. The primary concern in this method is interfering NADH formed by oxidation of l-lactate by l-lactate dehydrogenase (L-LDH). A commercially available kit for d-lactate measurement was implemented on our existing automated routine laboratory equipment including pH-inactivation of L-LDH. Our setup fulfilled clinical quality goals. We were able to measure d-lactate with an acceptable performance of the analysis and a short turn-around time. The method can be used to distinguish between the expected cut-off for intestinal ischemia around 0.3 mM and the upper reference limit of 0.05 mM. With a turnaround time of just 9 min, the analysis has potential as a readily available detection of circulating d-lactate for early diagnosis of intestinal ischemia.