Sparing confirmatory testing in primary aldosteronism (SCIPA): a multicenter retrospective diagnostic accuracy study.

BACKGROUND: The diagnosis of primary aldosteronism (PA) is comprehensive, which includes case-detection testing, case confirmation followed by subtype classification. In certain instances, such as in the setting of spontaneous hypokalemia, suppressed renin activity (PRA) plus plasma aldosterone concentration (PAC) of > 15 ng/dL, one may not proceed with confirmatory tests. However, the quality of evidence behind this approach is very low. This study sought to evaluate the proposed "simplified confirmatory pathway" that can spare confirmatory testing for primary aldosteronism by evaluating the diagnostic performances of the various pre-specified PAC thresholds in combination with findings of suppressed renin and spontaneous hypokalemia. METHODS: This is a multi-center, retrospective diagnostic accuracy cohort-selected cross-sectional study. A total of 133 participants aged 18 years and above underwent saline infusion test between January 2010 to March 2024. The outcome measures comprise of the diagnostic performances of the different index test combinations (baseline PAC, baseline PRA and presence of spontaneous hypokalemia): sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy. Data analysis was performed using SPSS 29.0.1.0 & MedCalc 20.218. RESULTS: Of the 133 patients who underwent saline infusion test, 88 (66.17%) were diagnosed with PA. A PAC of > 25 ng/dL plus PRA < 1.0 ng/dL/hr with spontaneous hypokalemia showed the highest specificity at 100% (95% CI 90.51%, 100.00%) and positive predictive value at 100% (85.18 - 100.00%). The minimum acceptable combination criteria were determined to be a PAC of > 20 ng/dL plus PRA < 0.6 ng/dL/hr, and presence of spontaneous hypokalemia. It has high specificity (94.59%; 95% CI 81.81%, 99.34%), positive predictive value (93.55%, 95% CI 78.49%, 98.29%), and moderate positive likelihood ratio (LR+) (6.39, 95% CI 1.61, 25.38) CONCLUSION: A hypertensive patient with spontaneous hypokalemia and screening findings of PAC > 20 ng/dL and suppressed PRA of < 0.6 ng/ml/hr, may be classified as "overt primary aldosteronism confirmed" and may not need to proceed with dynamic confirmatory testing. PROTOCOL REGISTRATION NUMBER: SRCTN34186253.

Comparison of four confirmatory tests for the diagnosis of primary aldosteronism: Bayesian analysis in the absence of a gold standard.

BACKGROUND: Captopril challenge test (CCT), seated saline infusion test (SSIT), oral sodium loading test (OSLT) and fludrocortisone suppression test (FST) are widely used diagnostic tests for primary aldosteronism (PA). These tests differ in terms of safety and complexity. Whether the simpler tests (CCT and SSIT) are comparable in diagnostic performance to the more complex ones (FST and OSLT) is unclear. PURPOSE: To compare the diagnostic accuracy of the four tests. METHODS: This is a retrospective study of hypertensive patients who were screened for PA and completed at least one confirmatory test. The patients were divided into two cohorts: one including those who completed one to three tests was used for the estimation of sensitivity and specificity. The other including those who completed four tests was used for the comparison of accuracy. Bayesian method was used to obtain the sensitivity, specificity, and Youden index of each test. RESULTS: The study included 1011 hypertensive patients. Among them, 895 patients completed one to three tests (including 889 CCT, 605 FST, 611 SSIT and 69 OSLT), and 116 patients completed four tests. SSIT had the highest sensitivity of 0.82(95% CI 0.78-0.86) but the lowest specificity of 0.76(0.70-0.80). OSLT had the lowest sensitivity of 0.65(0.56-0.75) but the highest specificity of 0.91(0.82-0.96). The sensitivity and specificity were 0.78 (95% CI, 0.75-0.82), 0.82 (95% CI, 0.78-0.85), for CCT, and 0.77 (95% CI, 0.73-0.81), 0.87 (95% CI, 0.82-0.91) for FST, respectively. The Youden index was not significantly different among the four tests[0.60(0.55-0.65) for CCT; 0.58(0.51-0.64) for SSIT; (0.64(0.57-0.69) for FST; 0.56(0.43-0.67) for OSLT]. CONCLUSION: The accuracy of simpler tests is comparable to the more complex ones. Considering the safety and simplicity of CCT, it may be a reasonable first choice when confirming the diagnosis of PA.

Assessment of CSF Dynamics Using Infusion Study: Tips and Tricks.

Idiopathic normal pressure hydrocephalus, secondary chronic hydrocephalus, and other cerebrospinal fluid (CSF) disorders are often challenging to diagnose. Since shunt surgery is usually the only therapeutic option and carries significant morbidity, optimal patient selection is crucial. The tap test is the most commonly used prognostic test to confirm the diagnosis but lacks sensitivity. The lumbar infusion study (LIS) appears to be a better option, offering additional information on brain dynamics without increasing morbidity. However, this technique remains underused. In this narrative review, supported by the extensive experience of several European expert centers, we detail the physiological basis, indications, and CSF dynamics parameters that can be measured. We also discuss technical modalities and variations, including one versus 2 needles, patient positioning, and the site of CSF measurement, as well as in vivo shunt testing. Finally, we discuss the limitations and morbidity associated with the LIS. This review aims to assist teams wishing to incorporate LIS into their screening tools for chronic hydrocephalus and other CSF disorders.

Comparison of saline infusion test and captopril challenge test in the diagnosis of Chinese with primary aldosteronism in different age groups.

Background: To explore the diagnostic accuracy and the optimal cutoff value between the saline infusion test (SIT) and captopril challenge test (CCT) [including the value and suppression of plasma aldosterone concentration (PAC)] for primary aldosteronism (PA) diagnosing. Methods: A total of 318 patients with hypertension were consecutively enrolled, including 126 patients with PA and 192 patients with essential hypertension (EH), in this observational study. The characteristics of patients and laboratory examinations were collected and compared. The comparison between SIT and CCT was carried by drawing the receiver operator characteristic curve (ROC) and calculating the area under the curve (AUC) to explore the diagnostic accuracy and the optimal cutoff value. Results: The average age was 51.59 ± 10.43 in the PA group and 45.72 ± 12.44 in the EH group (p<0.05). The optimal cutoff value was 10.7 ng/dL for post-CCT PAC, 6.8 ng/dL for post-SIT PAC, and 26.9% for suppression of post-CCT PAC. The diagnostic value of post-CCT PAC was the highest with 0.831 for the AUC and 0.552 for the Youden index. The optimal cutoff value for patients who were <50 years old was 11.5 ng/dL for post-CCT PAC and 8.4 ng/dL for post-SIT PAC. The suppression of post-CCT PAC turned to 18.2% for those of age 50 or older. Conclusion: Compared with SIT, CCT had a higher diagnostic value when post-CCT PAC was used as the diagnostic criterion in Chinese people, while the selection of diagnostic thresholds depended on patient age.

Observational study of intracranial pressure instability in patients with pseudotumour cerebri syndrome.

Introduction: A fixed CSF pressure (CSFp) of 25 cmH2O (18 mmHg) has been utilised to date to define and classify pseudotumour cerebri syndrome (PTCS). Furthermore, ICP monitoring, and CSF infusion tests have not been frequently performed in this group of patients. Research question: We aimed to report typical, unusual and unstable patterns of ICP in patients with PTCS. Material and methods: We reviewed the recordings of CSF infusion tests and overnight ICP monitoring of patients with suspected or confirmed IIH between January 2003-December 2020.We excluded all patients with a shunt in situ and selected recordings that represented unstable patterns of ICP changes in PTCS. Results: 463 CSF infusion tests and 26 ICP monitorings of PTCS patients had been performed in this timeframe. We divided results of observed pattern into two group: those with known venous sinus measurements (Group A) and those without (Group B). Observed recordings formed a total of 5 and 4 different patterns respectively, based on the behaviour of ICP and slow waves at rest, overnight, and during infusion as well as in relationship to the clinical presentation of each patient. Discussion and conclusion: Accurate monitoring of ICP in PTCS is quintessential. Full understanding of each element of its pathophysiology and their interaction would be essential and include quantification of the CSF pressure not only as a number, but also with consideration of its dynamic contents. Cerebral venous pressure measurements and/or monitoring may be useful. Consideration of the presence or absence of papilloedema in the context of disturbed CSF dynamics could reveal further diagnostic and therapeutic insights.

A 120-Minute Saline Infusion Test for the Confirmation of Primary Aldosteronism: A Pilot Study.

BACKGROUND: The saline infusion test (SIT) to confirm primary aldosteronism requires infusing 2 L of normal saline over 240 minutes. Previous studies raised concerns regarding increased blood pressure and worsening hypokalemia during SIT. We aimed to evaluate the diagnostic applicability of a SIT that requires 1 L of saline infusion over 120 minutes. METHODS: A cross-sectional study, including all patients in a large medical center who underwent SIT from 1 January 2015 to 30 April 2023. Blood samples were drawn for baseline renin and aldosterone (t = 0) after 2 hours (t = 120 min) and after 4 hours (t = 240 min) of saline infusion. We used ROC analysis to evaluate the sensitivity and specificity of various aldosterone cut-off values at t = 120 to confirm primary aldosteronism. RESULTS: The final analysis included 62 patients. A ROC analysis yielded 97% specificity and 90% sensitivity for a plasma aldosterone concentration (PAC) of 397 pmol/L (14 ng/dL) at t = 120 to confirm primary aldosteronism, and an area under the curve of 0.97 (95% CI [0.93, 1.00], P < 0.001). Almost half (44%) of the patients did not suppress PAC below 397 pmol/L (14 ng/dL) at t = 120. Of them, only one (4%) patient suppressed PAC below 276 pmol/L (10 ng/dL) at t = 240. Mean systolic blood pressure increased from 140.1 ±â€…21.3 mm Hg at t = 0 to 147.6 ±â€…14.5 mm Hg at t = 240 (P = 0.011). CONCLUSIONS: A PAC of 397 pmol/L (14 ng/dL) at t = 120 has high sensitivity and specificity for primary aldosteronism confirmation.

The role of confirmatory tests in the diagnosis of primary aldosteronism.

Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.

Idiopathic Normal Pressure Hydrocephalus: The Real Social and Economic Burden of a Possibly Enormous Underdiagnosis Problem.

Normal Pressure Hydrocephalus (iNPH) typically affects the elderly and can cause cognitive decline, resulting in its differential diagnosis with other neurodegenerative conditions. Moreover, it is probably underdiagnosed; such under- and misdiagnosis prevents the patient from receiving the right treatment and significantly affects the quality of life and life expectancy. This investigation is an in-depth analysis of the actual incidence of iNPH in the population of the province served by our hospital (circa 580,000 individuals). The first phase of this study was conducted by visualizing a total of 1232 brain CT scans performed in the Emergency Departments of the four hospitals of our network on patients who were admitted for different complaints yet screened as suspicious for iNPH. Subsequently, corresponding Emergency Department medical records were investigated to understand the medical history of each patient in search of elements attributable to an alteration of CSF dynamics. The cohort of positive CT scans, according to the radiological and clinical inclusion criteria, included 192 patients. Among the reasons to require acute medical care, "Fall" was the most common. The cumulative incidence of CT scans suggestive of iNPH among the patients undergoing CT scans was as high as 15.58%, and the period prevalence calculated for the total amount of patients accessing the Emergency Departments was 1.084%. The real incidence of iNPH in the population may be underestimated, and the social burden linked to the assistance of patients suffering from such untreated conditions could be significantly relieved.

Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals. METHODS: The CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001). CONCLUSIONS: The findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.

Prediction of shunt response in idiopathic normal pressure hydrocephalus by combined lumbar infusion test and preoperative imaging scoring.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a potentially treatable disorder, but prognostic tests or biomarkers are lacking. The aim was to study the predictive power of clinical, neuroimaging and lumbar infusion test parameters (resistance to outflow Rout , cardiac-related pulse amplitude PA and the PA to intracranial pressure ICP ratio). METHODS: In all, 127 patients diagnosed with iNPH who had a lumbar infusion test, a subsequent ventriculo-peritoneal shunt operation and at least 2 months of postoperative follow-up were retrospectively included. Preoperative magnetic resonance images were visually scored for NPH features using the iNPH Radscale. Preoperative and postoperative assessment was performed using cognitive testing, as well as gait and incontinence scales. RESULTS: At follow-up (7.4 months, range 2-20 months), an overall positive response was seen in 82% of the patients. Gait was more severely impaired at baseline in responders compared to non-responders. The iNPH Radscale score was borderline significantly higher in responders compared with non-responders, whereas no significant differences in infusion test parameters were seen between responders and non-responders. Infusion test parameters performed modestly with high positive (75%-92%) but low negative (17%-23%) predictive values. Although not significant, PA and PA/ICP seemed to perform better than Rout , and the odds ratio for shunt response seemed to increase in patients with higher PA/ICP, especially in patients with lower iNPH Radscale scores. CONCLUSION: Although only indicative, lumbar infusion test results increased the likelihood of a positive shunt outcome. Pulse amplitude measures showed promising results that should be further explored in prospective studies.

Slope until reaching the plateau: a new predictor of valve response obtained by lumbar infusion test for idiopathic normal pressure hydrocephalus.

BACKGROUND: Diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is based on clinical, radiological, and hydrodynamic data of cerebrospinal fluid (CSF) obtained by invasive methods such as lumbar infusion test, which is used to determine the resistance to CSF outflow (Rout). However, Rout has limitations, and its value as predictor of valve response is questioned. Other variables can be obtained by lumbar infusion test, such as the time to reach the plateau (TRP) and the slope until reaching the plateau (SRP). The objectives were to determine if SRP could be a predictor of response to ventriculoperitoneal shunt (VPS) and what variable (Rout versus SRP) would have greater predictive value. METHOD: Patients with probable iNPH who underwent a lumbar infusion test and were indicated for a VPS were retrospectively studied. Two groups were established, responders and non-responders. Rout, TRP (period between the start of infusion until reaching the plateau measured in seconds) and SRP ((plateau pressure-opening pressure)/TRP) were obtained. For Rout and SRP, the receiver operating curves (ROC) with its areas under the curve (AUC) were calculated. RESULTS: One hundred ten patients were included, being 86 responders (78.20%). Shunt responders had a significantly greater Rout (17.02 (14.45-20.23) versus 13.34 (12.10-16.28) mmHg/ml/min, p = 0.002) and SRP (0.049 (0.043-0.054) versus 0.031 (0.026-0.036) mmHg/sec, p < 0.001) and smaller TRP (641.28 (584.83-697.73) versus 777.65 (654.03-901.27) sec, p = 0.028) than non-responders. The AUC for SRP was greater than the AUC for Rout (0.763 (95 % CI 0.655-0.871, p < 0.001) versus 0.673 (95 % CI 0.595-0.801, p = 0.008), respectively), but the differences were not significant (p = 0.180). CONCLUSIONS: SRP could be considered predictor of response to VPS, and its accuracy tends to be better than Rout. So, this variable may be a useful tool to select shunt candidates among patients with probable iNPH.

Changes of cardiac output and velocity time integral in blood return at the end of renal replacement therapy predict fluid responsiveness in critically Ill patients with acute circulatory failure.

OBJECTIVES: To observe if blood return, also defined as the blood infusion test (BIT) could predict fluid responsiveness in critically ill patients with acute circulatory failure and renal replacement therapy (RRT). METHODS: This was a single-center, prospective, diagnostic accuracy study. Before BIT, the passive leg raise test (PLRT) was performed to record the change of cardiac output (ΔCO) by pulse contour analysis, and ΔCO > = 10% was defined as the fluid responder. Meanwhile, the change in velocity time integral (ΔVTI) was recorded by ultrasound. Later, the ΔCO and ΔVTI during BIT were recorded 5-10 min after PLRT. The receiver-operating characteristic curves of ΔCO and ΔVTI of BIT were performed in predicting the fluid responder defined by PLRT. RESULTS: A total of 43 patients with acute circulatory failure undergoing RRT were enrolled in the present study, and 25 patients (58.1%) were recognized as responders during PLRT. According to the receiver-operating characteristic curves, the cutoff value of ΔCO was 10% and ΔVTI was 9% during BIT with the area under curve of 0.96 and 0.94, respectively. CONCLUSIONS: BIT in RRT could identify fluid responsiveness in critically ill patients with shock. TRIAL REGISTRATION: ChiCTR-DDD-17010534. Registered on 30/01/2017 (retrospective registration).

A new machine learning-based prediction model for subtype diagnosis in primary aldosteronism.

Introduction: Unilateral primary aldosteronism (UPA) and bilateral primary aldosteronism (BPA) are the two subtypes of PA. Discriminating UPA from BPA is of great significance. Although adrenal venous sampling (AVS) is the gold standard for diagnosis, it has shortcomings. Thus, improved methods are needed. Methods: The original data were extracted from the public database "Dryad". Ten parameters were included to develop prediction models for PA subtype diagnosis using machine learning technology. Moreover, the optimal model was chose and validated in an external dataset. Results: In the modeling dataset, 165 patients (71 UPA, 94 BPA) were included, while in the external dataset, 43 consecutive patients (20 UPA, 23 BPA) were included. The ten parameters utilized in the prediction model include age, sex, systolic and diastolic blood pressure, aldosterone to renin ratio (ARR), serum potassium, ARR after 50 mg captopril challenge test (CCT), primary aldosterone concentration (PAC) after saline infusion test (SIT), PAC reduction rate after SIT, and number of types of antihypertensive agents at diagnosis. The accuracy, sensitivity, specificity, F1 score, and AUC for the optimal model using the random forest classifier were 90.0%, 81.8%, 96.4%, 0.878, and 0.938, respectively, in the testing dataset and 81.4%, 90.0%, 73.9%, 0.818 and 0.887, respectively, in the validating external dataset. The most important variables contributing to the prediction model were PAC after SIT, ARR, and ARR after CCT. Discussion: We developed a machine learning-based predictive model for PA subtype diagnosis based on ten clinical parameters without CT imaging. In the future, artificial intelligence-based prediction models might become a robust prediction tool for PA subtype diagnosis, thereby, might reducing at least some of the requests for CT or AVS and assisting clinical decision-making.

Validation of Existing Clinical Prediction Tools for Primary Aldosteronism Subtyping.

The new clinical prediction score (SCORE) has been recently proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). This study aimed to compare that SCORE with previously published scores and their validation using a cohort of patients at our center who had had positive SIT confirming PA and had been diagnosed with either bilateral PA according to AVS or unilateral PA if biochemically cured after an adrenalectomy. Final diagnoses were used to evaluate the diagnostic performance of the proposed clinical prediction tools. Only Kamemura's model (with a maximum score of 4 points) and Kobayashi's score (with a maximum score of 12 points) reached 100% reliability for prediction of bilateral PA; however, with sensitivity of only 3%. On the other hand, the values of SCORE = 3 (with sensitivity of 48%), the SPACE score ≥18 (with sensitivity of 35%), the Kobayashi's score ≤2 (with sensitivity of 28%), and the Kocjan's score = 3 (with sensitivity of 28%) were able to predict unilateral PA with 100% probability. Furthermore, Umakoshi's and Young's models both reached 100% reliability for a unilateral PA with score = 4 and both predictive factors together respectively; however, the sensitivity was lower compared with previous models; 4% and 14%, respectively. None of the clinical prediction tools applied to our cohort predicted unilateral and bilateral subtypes together with the expected high diagnostic performance, and therefore can only be used for precisely defined cases.

Adrenal Venous Sampling Could Be Omitted before Surgery in Patients with Conn's Adenoma Confirmed by Computed Tomography and Higher Normal Aldosterone Concentration after Saline Infusion Test.

PURPOSE: Adrenal venous sampling (AVS) performed to distinguish unilateral and bilateral primary aldosteronism (PA) is invasive and poorly standardized. This study aimed to identify non-invasive characteristics that can select the patients with unilateral PA who could bypass AVS before surgery. METHODS: A single-center study collected a total of 450 patients with PA. Development and validation cohorts included 242 and 208 patients. The AVS was successful in 150 and 138 patients from the cohorts, and the unilateral PA was found in 96 and 94 patients, respectively. Clinical factors independently associated with lateralized AVS in multivariable logistic regression were used to construct a unilateral PA prediction score (SCORE). RESULTS: The proposed SCORE was calculated as a sum of the prevalence of adrenal nodule on computed tomography (2 points) and plasma/serum aldosterone concentration ≥ 165 ng/L after the saline infusion test (SIT) (1 point). Importantly, the SCORE = 3 points identified 48% of unilateral PA patients with a specificity of 100% in the development cohort. The zero rate of false-positive classifications was preserved with the same cut-off value in the validation cohort. CONCLUSIONS: AVS could be omitted before surgery in patients with typical Conn´s adenoma provided the aldosterone concentration ≥ 165 ng/L after the SIT.

The Value of the Correlation Coefficient Between the ICP Wave Amplitude and the Mean ICP Level (RAP) Combined With the Resistance to CSF Outflow (Rout) for Early Prediction of the Outcome Before Shunting in Posttraumatic Hydrocephalus.

Objective: To evaluate the value of the correlation coefficient between the ICP wave amplitude and the mean ICP level (RAP) and the resistance to CSF outflow (Rout) in predicting the outcome of patients with post-traumatic hydrocephalus (PTH) selected for shunting. Materials and Methods: As a training set, a total of 191 patients with PTH treated with VP shunting were retrospectively analyzed to evaluate the potential predictive value of Rout, collected from pre-therapeutic CSF infusion test, for a desirable recovery level (dRL), standing for the modified rankin scale (mRS) of 0-2. Eventually, there were 70 patients with PTH prospectively included as a validation set to evaluate the value of Rout-combined RAP as a predictor of dRL. We calculated Rout from a CSF infusion test and collected RAP during continuous external lumbar drainage (ELD). Maximum RAP (RAPmax) and its changes relative to the baseline (ΔRAPmax%) served as specific parameters of evaluation. Results: In the training set, Rout was proved to be a significant predictor of dRL to shunting, with the area under the curve (AUC) of 0.686 (p < 0.001) in receiver-operating characteristic (ROC) analysis. In the validation set, Rout alone did not present a significant value in the prediction of desirable recovery level (dRL). ΔRAPmax% after 1st or 2nd day of ELD both showed significance in predicting of dRL to shunting with the AUC of 0.773 (p < 0.001) and 0.786 (p < 0.001), respectively. Significantly, Rout increased the value of ΔRAPmax% in the prediction of dRL with the AUC of 0.879 (p < 0.001), combining with ΔRAPmax% after the 1st and 2nd days of ELD. RAPmax after the 1st and 2nd days of ELD showed a remarkable predictive value for non-dRL (Levels 3-6 in Modified Rankin Scale) with the AUC of 0.891 (p < 0.001) and 0.746 (p < 0.001). Conclusion: Both RAP and Rout can predict desirable recovery level (dRL) to shunting in patients with PTH in the early phases of treatment. A RAP-combined Rout is a better dRL predictor for a good outcome to shunting. These findings help the neurosurgeon predict the probability of dRL and facilitate the optimization of the individual treatment plan in the event of ineffective or unessential shunting.

Are We Only Detecting the Tip of the Iceberg? A Nationwide Study on Primary Aldosteronism with up to 8-Year Follow-up.

BACKGROUND: Long-term follow-up studies on primary aldosteronism (PA) are lacking. OBJECTIVE: We aim to review results of diagnostic procedures and histopathology for patients diagnosed during 2012-2016 in Iceland, compare unilateral (UD) and bilateral disease (BD) and assess treatment response. METHODS: Thirty-two patients aged 28-88 were diagnosed and treated according to guidelines. RESULTS: The majority had BD. Everyone needed potassium supplementation at case detection. We saw a reduction in systolic blood pressure (p < .001, both groups), antihypertensive agents (p = .002 UD and p = .04 BD) and potassium supplementation (p < .001, both groups). CONCLUSION: Similar treatment response was seen in both subgroups. Ratio of hypokalemia and number of cases indicates severe PA underdiagnosis in Iceland.

Parathyroid hormone and calcitonin response during the calcium infusion test in patients with primary hyperparathyroidism.

OBJECTIVE: While activation of the calcium (Ca) sensing receptor (CaSR) suppresses parathyroid hormone (PTH) secretion, calcitonin (CT) secretion is stimulated via CaSR. The aim of this study was to evaluate PTH and CT responses during a calcium infusion test (CIT) in patients with primary hyperparathyroidism (PHPT). METHODS: This pivotal prospective study included 64 patients (44 PHPT patients vs. 20 healthy controls [HCs], median age 57 [25-79] vs. 56 [39-74] years). All PHPT patients underwent parathyroidectomy (PTX). A week before and 1 month after PTX, the CIT was performed (bolus infusion of Ca gluconate 0.2 ml/kg body weight), followed by plasma sampling for Ca2+, PTH, and CT at 0, 1, 2, 3, 5, 8, and 10 min. RESULTS: PTH suppression was lower in PHPT patients compared to HCs (49.82 vs. 64.06%, p = 0.006), but after PTX suppression, it was higher (76.3%, p < 0.001). PHPT patients had attenuated CT response vs. HCs during the CIT (3.1- vs. 8.0-fold increase, p < 0.001), but after PTX, it improved (5.8-fold increase). The PTHmin > 19.3 ng/l and CTmax ≤ 27.5 ng/l cut-off values predict diagnosis of PHPT (sensitivity 90.9%, 97.7%, and specificity 100%, 75%, respectively). Patients with adenoma had lower basal CT levels vs. hyperplasia both before and after PTX (4.5 vs. 6.8 and 5.4 vs. 7.9 ng/l, respectively, p = 0.008, p = 0.018). CONCLUSION: PTH and CT responses during the CIT in PHPT patients may be an additional diagnostic tool. The CIT could play a role in both the diagnosis of PHPT and in the differential diagnosis between adenoma and hyperplasia.

Prognostic value of the pulse pressure amplitudes, time to reach the plateau and the slope obtained in the lumbar infusion test for the study of idiophatic normal pressure hydrocephalus.

BACKGROUND AND OBJECTIVE: To study the prognostic value of the resistance to the cerebrospinal fluid outflow (Rout) obtained in the lumbar infusion test in idiopathic normal pressure hydrocephalus (iNPH), as well as the pulse pressure amplitudes in the different periods of the test and other new variables extracted by Neuropicture® software. MATERIAL AND METHODS: Patients with 'probable iNPH' who underwent a lumbar infusion test were retrospectively revised. The positive predictive values (PPV) of the cutoff point of the best prognostic accuracy of the Rout, the basal pulse pressure amplitude (AMPo), the pulse pressure amplitude during the first 10 min (AMP10min), the plateau pulse pressure amplitude (AMPmes), the Rout pulse pressure amplitude (AMPRout), the time to reach the plateau (T), and the slope until reaching the plateau were determined. Patients were categorized either as responders or non-responders. RESULTS: The study included 64 responders patients and 16 non-responders patients. The PPV of Rout > 15 mmHg/mL/min was 91.7%; AMPo > 2.34 mmHg: 91.3%; AMP10 min > 4.34 mmHg: 83.3%; AMPmes > 12.44 mmHg: 84.6%; AMPRout > 6.34 mmHg: 85%; T < 634 s: 86.7%; p > 0.040 mmHg/s: 96.3%. CONCLUSIONS: Rout is a valid criterion to indicate a ventricular shunt. Pulse pressure amplitudes in the different periods of the lumbar infusion test, in addition to T and P, are other variables whose positivity is indicative of shunt response and should be considered in the diagnostic protocol of the iNPH.

Long-Standing Overt Ventriculomegaly in Adults (LOVA): Diagnostic Aspects, CSF Dynamics with Lumbar Infusion Test and Treatment Options in a Consecutive Series with Long-Term Follow-Up.

BACKGROUND: Long-standing overt ventriculomegaly in adults is a chronic form of hydrocephalus without a clear pathophysiological description and a consensus about the treatment. We present the results of endoscopic third ventriculostomy (ETV) in a consecutive series with a mean follow-up of 79 ± 23 months, highlighting how the preoperative lumbar infusion test could facilitate understanding the pathophysiology of the disease. METHODS: We retrospectively collected data regarding clinical assessment, neuroradiological findings, and preoperative lumbar infusion tests in 22 symptomatic patients. RESULTS: In the majority of cases, patients reported imbalance and gait disorders, and 8 subjects had headaches. The preoperative lumbar infusion test demonstrated a mean opening pressure of 13.95 ± 2.88 mm Hg, with plateau values ranging from 22 to 39 mm Hg. The resistance to outflow was 11.21 ± 2.00 mm Hg/mL/min. After the procedure, all patients reported improvement or halted progression in their presenting symptoms, whereas no significant reduction was demonstrated in Evans' index. One subject underwent a second ETV procedure after more than 2 years because of the failure of the endoscopic approach. CONCLUSIONS: A progressive exhaustion of brain compliance plays an important role in explaining the dichotomy between severe ventriculomegaly and mild clinical symptoms in patients with long-standing overt ventriculomegaly in adults. The role of the aqueductal stenosis as a diagnostic criterion might be reconsidered. The preoperative infusion test data support this observation. Preoperative assessment should include not only clinical and neuroradiological evaluation but also the study of cerebrospinal fluid dynamics. ETV should be considered the treatment of choice because of its safety and efficacy. Long-term follow-up is mandatory.