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Histopathology plays a fundamental role in the diagnosis and subtyping of solid tumors and has become a cornerstone of modern precision oncology. Histopathological evaluation is typically performed manually by expert pathologists due to the complexity of visual data. However, in the last ten years, new artificial intelligence (AI) methods have made it possible to train computers to perform visual tasks with high performance, reaching similar levels as experts in some applications. In cancer histopathology, these AI tools could help automate repetitive tasks, making more efficient use of pathologists’ time. In research studies, AI methods have been shown to have an astounding ability to predict genetic alterations and identify prognostic and predictive biomarkers directly from routine tissue slides. Here, we give an overview of these recent applications of AI in computational pathology, focusing on new tools for cancer research that could be pivotal in identifying clinical biomarkers for better treatment decisions.

Purpose Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio. Methods In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions. Results Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables. Conclusion We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.

Objective:The aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary aldosteronism, but its determinants in patients with essential hypertension are not fully known. The purpose of the present investigation is to identify the impact of age, sex and BMI on renin, aldosterone and the ARR when measured under strict, standardized conditions in hypertensive patients without primary aldosteronism.Methods:We analysed the data of 423 consecutive hypertensive patients with no concomitant cardiac or renal disorders from two different hospitals (Rotterdam and Maastricht) who had been referred for evaluation of their hypertension. Those who were diagnosed with secondary causes of hypertension, including primary aldosteronism, were excluded from analysis. Patients who used oral contraceptives or had hormonal replacement therapy were excluded as well. Plasma aldosterone concentration (PAC), active plasma renin concentration (APRC) and the ARR were measured under standardized conditions. All measurements were taken in the supine position at 10.00 h in the morning, with one subgroup of patients adhering to a sodium-restricted diet (55 mmol/day) for no less than 3 weeks, and the other subgroup maintaining an ad libitum diet. In those who were receiving antihypertensive treatment, all medications were discontinued at least 3 weeks before testing.Results:In neither group did aldosterone correlate with age. Renin, however, was inversely related to age both during low-salt diet (P < 0.001) and during ad lib salt intake (P = 0.05). This resulted in a significant positive correlation between age and the ARR in both groups. Although on both dietary regimens, PAC and APRC were significantly higher in men when compared with women, the ARR was not significantly different between the two sexes. The age-relationships of renin and the ARR were comparable in men and women on both diets, albeit with greater variability in women. There was an upward trend between BMI and the ARR, which reached statistical significance only in men on low-salt diet. In multivariable regression analysis, age remained the only independent determinant of the ARR.Conclusion:In our essential hypertensive population, the ARR increased significantly with age but was not affected by sex or BMI.

The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, patients often use medications that could confound the ARR and, thereby, reduce the interpretability of the test. Since it is not always feasible to stop such medication, several drugs that are supposedly neutral with respect to the ARR have been recommended as alternative treatment. The objective of the present review is to explore whether sufficient evidence exists to justify the recommendations. To this end, we performed a systematic PubMed and Cochrane literature search regarding medications that may influence the ARR. Our review revealed that many commonly prescribed antihypertensives seem to have significant effects on renin, aldosterone, and resulting ARR values. However, the magnitude of these effects is poorly quantifiable with the present level of research. We conclude that several medications can affect the ARR. Not taking this into account could lead to misinterpretation of the ARR. Therefore, standardization of the medications used during ARR measurement is advisable for a reliable and accurate interpretation. Further research is needed to ascertain how to best optimize these medications.

Deep learning (DL) can predict microsatellite instability (MSI) from routine histopathology slides of colorectal cancer (CRC). However, it is unclear whether DL can also predict other biomarkers with high performance and whether DL predictions generalize to external patient populations. Here, we acquire CRC tissue samples from two large multi-centric studies. We systematically compare six different state-of-the-art DL architectures to predict biomarkers from pathology slides, including MSI and mutations in BRAF, KRAS, NRAS, and PIK3CA. Using a large external validation cohort to provide a realistic evaluation setting, we show that models using self-supervised, attention-based multiple-instance learning consistently outperform previous approaches while offering explainable visualizations of the indicative regions and morphologies. While the prediction of MSI and BRAF mutations reaches a clinical-grade performance, mutation prediction of PIK3CA, KRAS, and NRAS was clinically insufficient.

Hydralazine, doxazosin, and verapamil are currently recommended by the Endocrine Society as acceptable bridging treatment in those in whom full cessation of antihypertensive medication is infeasible during screening for primary aldosteronism (PA). This is under the assumption that they cause minimal to no effect on the aldosterone-to-renin ratio, the most widely used screening test for PA. However, limited evidence is available regarding the effects of these particular drugs on said ratio.In the present study, we retrospectively assessed the changes in aldosterone, renin, and aldosterone-to-renin values in essential hypertensive participants before and after treatment with either hydralazine (n = 26) or doxazosin (n = 20) or verapamil (n = 15). All samples were taken under highly standardized conditions.Hydralazine resulted in a borderline significant rise in active plasma renin concentration (19 vs 25 mIU/L, p = 0.067) and a significant fall in the aldosterone-to-renin ratio (38 vs 24, p = 0.017). Doxazosin caused declines in both plasma aldosterone concentration (470 vs 330 pmol/L, p = 0.028) and the aldosterone-to-renin ratio (30 vs 20, p = 0.020). With respect to verapamil, we found no statistically significant effect on any of these outcome variables.We conclude that the assumption that these drugs can be used with little consequence to the aldosterone-to-renin cannot be substantiated. While it is possible that they are indeed the best option when full antihypertensive drug cessation is infeasible, the potential effects of these drugs must still be taken into account when interpreting the aldosterone-to-renin ratio.

The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, there are many factors which could confound the ARR test result and reduce the accuracy of this test. The present review's objective is to identify these factors and to describe to what extent they affect the ARR. Our analysis revealed that sex, age, posture, and sodium‐intake influence the ARR, whereas assay techniques do not. Race and body mass index have an uncertain effect on the ARR. We conclude that several factors can affect the ARR. Not taking these factors into account could lead to misinterpretation of the ARR., The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. Our analysis revealed that several factors can affect the ARR. Not taking these factors into account could lead to misinterpretation of the ARR.

Objective:Currently, the aldosterone-to-renin ratio (ARR) is widely used as a screening test for primary hyperaldosteronism (PA). However, many factors could variably influence the levels of renin and/or aldosterone and potentially lead to inaccurate screening of PA. The purpose of our study is to i