Integration of artificial intelligence and plasma steroidomics with laboratory information management systems: application to primary aldosteronism.

OBJECTIVES: Mass spectrometry-based steroidomics combined with machine learning (ML) provides a potentially powerful approach in endocrine diagnostics, but is hampered by limitations in the conveyance of results and interpretations to clinicians. We address this shortcoming by integration of the two technologies with a laboratory information management systems (LIMS) model. METHODS: The approach involves integration of ML algorithm-derived models with commercially available mathematical programming software and a web-based LIMS prototype. To illustrate clinical utility, the process was applied to plasma steroidomics data from 22 patients tested for primary aldosteronism (PA). RESULTS: Once mass spectrometry data are uploaded into the system, automated processes enable generation of interpretations of steroid profiles from ML models. Generated reports include plasma concentrations of steroids in relation to age- and sex-specific reference intervals along with results of ML models and narrative interpretations that cover probabilities of PA. If PA is predicted, reports include probabilities of unilateral disease and mutations of KCNJ5 known to be associated with successful outcomes of adrenalectomy. Preliminary results, with no overlap in probabilities of disease among four patients with and 18 without PA and correct classification of all four patients with unilateral PA including three of four with KCNJ5 mutations, illustrate potential utility of the approach to guide diagnosis and subtyping of patients with PA. CONCLUSIONS: The outlined process for integrating plasma steroidomics data and ML with LIMS may facilitate improved diagnostic-decision-making when based on higher-dimensional data otherwise difficult to interpret. The approach is relevant to other diagnostic applications involving ML.

High-risk breast cancer surveillance with MRI: 10-year experience from the German consortium for hereditary breast and ovarian cancer.

PURPOSE: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). METHODS: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age. RESULTS: A total of 221 primary breast cancers (185 invasive, 36 in situ) were diagnosed within 12 months of an annual screening round with MRI. Of all cancers, 84.5% (174/206, 15 unknown) were stage 0 or I. In BRCA1 carriers, 16.9% (10/59, 5 unknown) of all incident cancers (screen-detected and interval cancers combined) and in BRCA2 carriers 12.5% (3/24, 4 unknown) were stage IIA or higher, compared to only 4.8% (2/42, 2 unknown) in high-risk BRCA1/2 non-carriers. Program sensitivity was 89.6% (95% CI 84.9-93.0) with no significant differences in sensitivity between risk groups or by age. Specificity was significantly lower in the first screening round (84.6%, 95% CI 83.6-85.7) than in subsequent screening rounds (91.1%, 95% CI 90.6-91.7), p < 0.001. Cancer detection rates (CDRs) and as a result positive predictive values were strongly dependent on type of screening round, risk group and patient age. CDRs ranged from 43.5‰ (95% CI 29.8-62.9) for the first screening round in BRCA2 carriers to 2.9‰ (95% CI 1.3-6.3) for subsequent screening rounds in high-risk non-carriers in the age group 30 to 39 years. CONCLUSIONS: High-risk screening with MRI was successfully implemented in the GC-HBOC with high sensitivity and specificity. Risk prediction and inclusion criteria in high-risk non-carriers need to be adjusted to improve CDRs and thus screening efficacy in these patients.

Mass spectrometry reveals misdiagnosis of primary aldosteronism with scheduling for adrenalectomy due to immunoassay interference.

BACKGROUND: Diagnosis of primary aldosteronism (PA) involves a multistep process reliant on the accuracy of aldosterone measurements at each step. We report on immunoassay interference leading to a wrongful diagnosis and indication for surgical intervention. CASE: A 38-year old hypertensive male with a 1.4 cm left adrenal mass was diagnosed with PA based on an elevated aldosterone:renin ratio and a positive saline infusion test. Adrenal venous sampling (AVS) indicated left-sided aldosterone hypersecretion, supporting a decision to remove the left adrenal. The patient was also enrolled in a study to evaluate mass spectrometry-based steroid profiling, which indicated plasma aldosterone concentrations measured in five different peripheral samples averaging only 11% those of the immunoassay. Mass spectrometric measurements did not support left-sided adrenal aldosterone hypersecretion. Two independent laboratories confirmed differences in measurements by immunoassay and mass spectrometry. Lowered concentrations measured by the immunoassay that matched those by mass spectrometry were achieved after sample purification to remove macromolecules, confirming immunoassay interference. CONCLUSIONS: Although our patient may represent an isolated case of immunoassay interference leading to misdiagnosis of PA, unnecessary AVS and potentially wrongful removal of an adrenal, it is also possible that such inaccuracies may impact the diagnostic process and treatment for other patients.

Delayed Radiographic Manifestation of Renal Pseudoaneurysms After Blunt Trauma.

Pseudoaneurysms may cause recurrent hematuria after blunt renal trauma. We report on an 18-year-old patient with radiographic manifestation of pseudoaneurysm 41 days after blunt renal trauma. Initial and follow-up imaging for recurrent hematuria, including angiography, was without signs of pseudoaneurysm or active bleeding. This case illustrates that recurrent gross hematuria as a typical symptom of pseudoaneurysm may be present initially in the absence of radiographic signs. Repeat angiography should be taken into consideration if recurrent bleeding persists.

Endovascular Creation of an Arteriovenous Fistula (endoAVF) for Hemodialysis Access: First Results.

INTRODUCTION: Surgical creation of a radiocephalic fistula is the gold standard of vascular access for hemodialysis. Recently, an endovascular approach for upper arm fistula creation (endoAVF) has been developed, which may be an alternative to open surgery. We describe a case series of eight cases showing feasibility, early complications and outcome of this novel treatment option. MATERIALS AND METHODS: Between July 2015 and February 2016, we created an endoAVF in eight patients. Indications for endoAVF were confirmed by a multidisciplinary vascular board upon the exclusion for Cimino fistula candidates. Patients were suitable for the procedure after a pre-therapeutic ultrasound showed adequate brachial and ulnar vessels and no ipsilateral central venous stenosis. Patient characteristics, technical success, total patient radiation dose, complication rates, time to maturation of endoAVF and clinical effectiveness at six months were assessed retrospectively. RESULTS: Creation of endoAVF using the everlinQ endoAVF system (TVA Medical Inc., Austin, TX, USA) was successful in all eight cases. There were one minor intraprocedural complication and no postoperative complications. Median time to endoAVF maturation was 63 days (range 26-137 days). One patient was lost to follow-up after the first monitoring visit. In the remaining seven patients, hemodialysis was started without problems. Patency after 6 months was 100%. DISCUSSION: The endoAVF demonstrated to be feasible and safe for the creation of arteriovenous fistula suitable for hemodialysis access. Further studies with more patients and longer follow-up periods are needed to assess long-term outcomes and comparability to surgical dialysis access creation.

(68)Ga DOTATATE uptake in vertebral hemangioma.

Somatostatin receptor scintigraphy is an established modality for imaging well-differentiated neuroendocrine tumors. It is known that inflammatory diseases (eg, tuberculosis) may also accumulate somatostatin receptor analogs. Here, we present the case of a 69-year-old patient with a neuroendocrine tumor of the rectum showing uptake of Ga DOTATATE in 2 vertebrae that was caused by vertebral hemangiomas. This could be clearly demonstrated on the CT scan. Although studies outlining the normal distribution of Ga DOTATATE exist, uptake in vertebral hemangiomas has not been described yet. As the case shows, vertebral hemangiomas should be kept in mind as a benign differential diagnosis.