Venoarterial extracorporeal membrane oxygenation for vasoplegic shock after treprostinil refill of an implanted intravenous pump: a case report.

Introduction: Venoarterial extracorporeal membrane oxygenation (ECMO) is a rescue therapy that can stabilize patients with hemodynamic compromise. Indications continue to evolve, including drug overdose. However, the indication merely for vasoplegic shock following drug overdose is controversial. Case summary: We report a case of a 57-year-old male with high-risk idiopathic pulmonary arterial hypertension treated with upfront triple combination therapy (sildenafil, bosentan, and intravenous treprostinil infusion via subcutaneous abdominal implantable pump). In one of the refills of the drug reservoir, accidental administration of 1 months's supply of treprostinil (200 mg) into the subcutaneous tissue occurred, causing refractory vasoplegic shock. He required urgent VA-ECMO for 96 h, surviving to discharge 28 days later. Discussion: Treprostinil poisoning is rare due to its less frequent use but is life-threatening. ECMO may be considered in vasoplegic shock due to overdose of vasodilatory medication. It allows organ perfusion to be maintained, with the knowledge that recovery is as rapid as drug elimination.

Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial.

BACKGROUND: It is uncertain whether individualisation of the perioperative open-lung approach (OLA) to ventilation reduces postoperative pulmonary complications in patients undergoing lung resection. We compared a perioperative individualised OLA (iOLA) ventilation strategy with standard lung-protective ventilation in patients undergoing thoracic surgery with one-lung ventilation. METHODS: This multicentre, randomised controlled trial enrolled patients scheduled for open or video-assisted thoracic surgery using one-lung ventilation in 25 participating hospitals in Spain, Italy, Turkey, Egypt, and Ecuador. Eligible adult patients (age ≥18 years) were randomly assigned to receive iOLA or standard lung-protective ventilation. Eligible patients (stratified by centre) were randomly assigned online by local principal investigators, with an allocation ratio of 1:1. Treatment with iOLA included an alveolar recruitment manoeuvre to 40 cm H2O of end-inspiratory pressure followed by individualised positive end-expiratory pressure (PEEP) titrated to best respiratory system compliance, and individualised postoperative respiratory support with high-flow oxygen therapy. Participants allocated to standard lung-protective ventilation received combined intraoperative 4 cm H2O of PEEP and postoperative conventional oxygen therapy. The primary outcome was a composite of severe postoperative pulmonary complications within the first 7 postoperative days, including atelectasis requiring bronchoscopy, severe respiratory failure, contralateral pneumothorax, early extubation failure (rescue with continuous positive airway pressure, non-invasive ventilation, invasive mechanical ventilation, or reintubation), acute respiratory distress syndrome, pulmonary infection, bronchopleural fistula, and pleural empyema. Due to trial setting, data obtained in the operating and postoperative rooms for routine monitoring were not blinded. At 24 h, data were acquired by an investigator blinded to group allocation. All analyses were performed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT03182062, and is complete. FINDINGS: Between Sept 11, 2018, and June 14, 2022, we enrolled 1380 patients, of whom 1308 eligible patients (670 [434 male, 233 female, and three with missing data] assigned to iOLA and 638 [395 male, 237 female, and six with missing data] to standard lung-protective ventilation) were included in the final analysis. The proportion of patients with the composite outcome of severe postoperative pulmonary complications within the first 7 postoperative days was lower in the iOLA group compared with the standard lung-protective ventilation group (40 [6%] vs 97 [15%], relative risk 0·39 [95% CI 0·28 to 0·56]), with an absolute risk difference of -9·23 (95% CI -12·55 to -5·92). Recruitment manoeuvre-related adverse events were reported in five patients. INTERPRETATION: Among patients subjected to lung resection under one-lung ventilation, iOLA was associated with a reduced risk of severe postoperative pulmonary complications when compared with conventional lung-protective ventilation. FUNDING: Instituto de Salud Carlos III and the European Regional Development Funds.

Pain Prevalence and Satisfaction with Pain Management in Inpatients: A Cross-Sectional Study.

BACKGROUND: Pain in hospitalized adults is underestimated and undervalued. The aim of this study was to evaluate pain prevalence and satisfaction with the hospital's pain management among patients attending a tertiary university hospital. Predictor factors of pain were also studied. METHODS: A prospective, cross-sectional study was carried out through a structured questionnaire given on one day to all hospitalized patients in a university hospital. Clinical data, such as personal history and analgesic treatment, were collected from medical records. Other variables related to pain (including intensity rated by the visual analogue scale as well as location and patient satisfaction measured by the numerical rating scale) were also obtained. RESULTS: Of the 274 surveyed patients, pain prevalence was 52.9%, with an average intensity of 5.3 ± 2.8 according to VAS. The overall satisfaction was 87.2%, and 72.6% had already been prescribed at least one analgesic. Patients receiving analgesics showed higher pain intensity (VAS 3.6 ± 3.4) than those without treatment (VAS 1.1 ± 2.1) (p < 0.001). However, patients with treatment showed more satisfaction (NRS 7.8 ± 2 vs. 5.3 ± 1.4, p < 0.001). CONCLUSIONS: The prevalence of pain in hospitalized patients was high, despite the fact that patient satisfaction was also very high.

Pain in High-Dose-Rate Brachytherapy for Cervical Cancer: A Retrospective Cohort Study.

High-dose-rate brachytherapy (HDR) is part of the main treatment for locally advanced uterine cervical cancer. Our aim was to evaluate the incidence and intensity of pain and patients' satisfaction during HDR. Risk factors for suffering pain were also analyzed. A retrospective study was carried out by extracting data from patients who had received HDR treatment for five years. Postoperative analgesia had been administered using pre-established analgesic protocols for 48 h. Pain assessment was collected according to a protocol by the acute pain unit. Analgesic assessment was compared according to analgesic protocol administered, number of needles implanted, and type of anesthesia performed during the procedure. From 172 patients treated, data from 247 treatments were analyzed. Pain was considered moderate in 18.2% of the patients, and 43.3% of the patients required at least one analgesic rescue. Patients receiving major opioids reported worse pain control. No differences were found regarding the analgesic management according to the intraprocedural anesthesia used or the patients' characteristics. The number of inserted needles did not influence the postoperative analgesic assessment. Continuous intravenous infusion of tramadol and metamizole made peri-procedural pain during HDR mild in most cases. Many patients still suffered from moderate pain.

Perioperative Management of Antisynthetase Syndrome: A Case Report.

Antisynthetase syndrome is a rare idiopathic inflammatory multisystem disorder, which can lead to serious postoperative complications. Due to its low incidence, there is little literature on its anesthetic management. However, patients with this disease can suffer from serious complications secondary to muscle weakness and respiratory complications. Although the intraoperative and the immediate postoperative periods may be uneventful, complications may appear later. The characteristics of the disease can lead to a misdiagnosis in the case of respiratory acute failure. The objective of this clinical report is to discuss the perioperative management of patients suffering from antisynthetase syndrome, assess the usefulness of postoperative monitoring, and evaluate alternatives that could have been carried out to prevent the fatal outcome reported in this narrative.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

Effect of Preoperative Anxiety on Postoperative Pain after Craniotomy.

Pain following craniotomy is challenging. Preoperative anxiety can be one of the controllable factors for prevention of post-craniotomy pain. The main objective of this prospective observational study is to determine this relationship in patients undergoing scheduled craniotomy from February to June 2021. After excluding patients with Mini-Mental State Examination (MMSE) ≤ 24 points, we administered a preoperative State Trait Anxiety Inventory (STAI) questionnaire. We recorded the patient's analgesic assessment using the Numerical Rating Score (NRS) at 1, 8, 24, and 48 h after surgery. A total of 73 patients were included in the study. Twelve others were excluded due to a MMSE ≤ 24 points. The main predictors for NRS postoperatively at 1, 8, 24, and 48 h were STAI A/E score, male gender, youth, and depression. We identified a cut-off point of 24.5 in STAI A/E for predicting a NRS > 3 (sensitivity 82% and specificity 65%) at 24 h postoperative and a cut-off of 31.5 in STAI A/R (sensitivity 64% and specificity 77%). In conclusion, preoperative STAI scores could be a useful tool for predicting which patient will experience at least moderate pain after craniotomy. The identification of these patients may allow us to highlight psychological preparation and adjuvant analgesia.

Clinical and biological markers for predicting ARDS and outcome in septic patients.

Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO2/FiO2, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.

Effect of prewarming on body temperature in short-term bladder or prostatic transurethral resection under general anesthesia: A randomized, double-blind, controlled trial.

Perioperative hypothermia causes postoperative complications. Prewarming reduces body temperature decrease in long-term surgeries. We aimed to assess the effect of different time-periods of prewarming on perioperative temperature in short-term transurethral resection under general anesthesia. Randomized, double-blind, controlled trial in patients scheduled for bladder or prostatic transurethral resection under general anesthesia. Eligible patients were randomly assigned to receive no-prewarming or prewarming during 15, 30, or 45 min using a forced-air blanket in the pre-anesthesia period. Tympanic temperature was used prior to induction of anesthesia and esophageal temperature intraoperatively. Primary outcome was the difference in core temperature among groups from the induction of general anesthesia until the end of surgery. Repeated measures multivariate analysis of covariance modeled the temperature response at each observation time according to prewarming. We examined modeled contrasts between temperature variables in subjects according to prophylaxis. We enrolled 297 patients and randomly assigned 76 patients to control group, 74 patients to 15-min group, 73 patients to 30-min group, and 74 patients to the 45-min group. Temperature in the control group before induction was 36.5 ± 0.5 °C. After prewarming, core temperature was significantly higher in 15- and 30-min groups (36.8 ± 0.5 °C, p = 0.004; 36.7 ± 0.5 °C, p = 0.041, respectively). Body temperature at the end of surgery was significantly lower in the control group (35.8 ± 0.6 °C) than in the three prewarmed groups (36.3 ± 0.6 °C in 15-min, 36.3 ± 0.5 °C in 30-min, and 36.3 ± 0.6 °C in 45-min group) (p < 0.001). Prewarming prior to short-term transurethral resection under general anesthesia reduced the body temperature drop during the perioperative period. These time-periods of prewarming also reduced the rate of postoperative complications.Study Registration Registered at ClinicalTrials.gov (Identifier: NCT03630887).

Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis.

Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39-9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.

Short-Periods of Pre-Warming in Laparoscopic Surgery. A Non-Randomized Clinical Trial Evaluating Current Clinical Practice.

BACKGROUND: Pre-warming prevents perioperative hypothermia. We evaluated the current clinical practice of pre-warming and its effects on temperature drop and postoperative complications; Methods: This prospective, observational pilot study examines clinical practice in a tertiary hospital on 99 patients undergoing laparoscopic urological surgery. Pre-warming was performed in the pre-anesthesia room. Patients were classified into three groups: P 0 (non-prewarmed), P 5-15 (pre-warming 5-15 min) and P > 15 (pre-warming 15-30 min). Tympanic temperature was recorded in the pre-anesthesia room, prior to anesthesia induction, and in the PACU. Esophageal temperature was recorded intraoperatively. The occurrence of shivering, pain intensity, length of stay in PACU, and postoperative complications during hospital stay were also recorded; Results: After pre-warming, between-group difference in body temperature was higher in P > 15 than in P 0 (0.4 °C, 95% CI 0.14-0.69, p = 0.004). Between P 5-15 and P 0 difference was 0.2 °C (95% CI 0.04-0.55, p = 0.093). Temperature at the end of surgery was higher in pre-warmed groups [mean between-group difference 0.5 °C (95% CI 0.13-0.81, p = 0.007) for P 5-15; 0.9 °C (95% CI 0.55-1.19, p < 0.001) for P > 15]. Pain and shivering was less common in pre-warmed groups. Postoperative transfusions and surgical site infections were lower in P > 15; Conclusion: Short-term pre-warming prior to laparoscopic urological surgery decreased temperature perioperative drop and postoperative complications.

Reanimación cardiopulmonar básica en decúbito prono: ¿una revolución necesaria? / Basic cardiopulmonary resuscitation in prone position: a necessary revolution?

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Cardiopulmonary Resuscitation in the Prone Position in the Operating Room or in the Intensive Care Unit: A Systematic Review.

The prone position is commonly used in certain surgical procedures and to improve oxygenation in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). Cardiorespiratory arrest (CRA) in this position may be more challenging to treat because care providers trained in conventional cardiopulmonary resuscitation (CPR) may not be familiar with CPR in the prone position. The aim of this systematic review is to provide an overview of current evidence regarding the methodology, efficacy, and experience of CPR in the prone position, in patients with the airway already secured. The search strategy included PubMed, Scopus, and Google Scholar. All studies published up to April 2020 including CRA or CPR in the prone position were included. Of the 268 articles located, 52 articles were included: 5 review articles, 8 clinical guidelines in which prone CPR was mentioned, 4 originals, 27 case reports, and 8 editorials or correspondences. Data from reviewed clinical studies confirm that CPR in the prone position is a reasonable alternative to supine CPR when the latter cannot be immediately implemented, and the airway is already secured. Defibrillation in the prone position is also possible. Familiarizing clinicians with CPR and defibrillation in the prone position may improve CPR performance in the prone position.

Association between red blood cell distribution width and mortality of COVID-19 patients.

PURPOSE: We have previously reported an association between high red blood cell distribution width (RDW) and mortality in septic and brain infarction patients. However, no association between RDW and mortality in coronavirus disease 2019 (COVID-19) patients has been reported so far; thus, the objective of this study was to determine if that association exists. METHODS: Prospective and observational study carried out in 8 Intensive Care Units from 6 hospitals of Canary Islands (Spain) including COVID-19 patients. We recorded RDW at ICU admission and 30-day survival. RESULTS: We found that patients who did not survive (n=25) compared to surviving patients (n=118) were older (p=0.004), showed higher RDW (p=0.001), urea (p<0.001), APACHE-II (p<0.001) and SOFA (p<0.001), and lower platelet count (p=0.007) and pH (p=0.008). Multiple binomial logistic regression analysis showed that RDW was associated with 30-day mortality after controlling for: SOFA and age (OR=1.659; 95% CI=1.130-2.434; p=0.01); APACHE-II and platelet count (OR=2.062; 95% CI=1.359-3.129; p=0.001); and pH and urea (OR=1.797; 95% CI=1.250-2.582; p=0.002). The area under the curve (AUC) of RDW for mortality prediction was of 71% (95% CI=63-78%; p<0.001). We did not find significant differences in the predictive capacity between RDW and SOFA (p=0.66) or between RDW and APACHE-II (p=0.12). CONCLUSIONS: Our study provides new information regarding the ability to predict mortality in patients with COVID-19. There is an association between high RDW and mortality. RDW has a good performance to predict 30-day mortality, similar to other severity scores (such as APACHE II and SOFA) but easier and faster to obtain.

Prospective observational study of the effectiveness of prewarming on perioperative hypothermia in surgical patients submitted to spinal anesthesia.

Prewarming has been shown to prevent intraoperative inadvertent hypothermia. Nevertheless, data about optimal prewarming-time from published clinical trials report contradictory results. We conducted this pilot study to evaluate routine clinical practice regarding prewarming and its effect on the prevalence of perioperative hypothermia in patients undergoing transurethral resection (TUR) under spinal anesthesia. This was a prospective, observational, pilot study to examine clinical practice in a tertiary hospital regarding prewarming in 140 consecutive patients. When prewarming (pw) was performed, forced-air warming was provided in the pre-anesthesia room for 15 (pw15), 30 (pw30), or 45 (pw45) min. Tympanic temperature was recorded upon entering the pre-anesthesia room, at the time of initiating surgery, and every 15 min intra-operatively. We also recorded duration of the surgical procedure and length of stay in the Post-Anesthesia Care Unit (PACU). Pw15 was performed in 34 patients, pw30 in 29 patients, and pw45 in 21 patients. Fifty-six patients did not receive pw and 96% of them developed hypothermia at the end of the surgical procedure, compared to 73% of patients in pw15 (p = 0.002), 75% in pw30 (p = 0.006) and 90% in pw45 (p = 0.3). Length of stay in the PACU was markedly shorter in pw15 (131 ± 69 min) and pw30 (123 ± 60 min) than in the non-pw group (197 ± 105 min) (p = 0.015 and p = 0.011, respectively). This difference was not significant in pw45 (129 ± 56 min) compared to non-pw patients. In conclusion, prewarming for 15 or 30 min before TUR under spinal anesthesia prevents development of hypothermia at the end of the surgical procedure.

Looking for the reason of hemodynamic instability: a case report of the role of intraoperative ultrasound / Buscando o motivo da instabilidade hemodinâmica: relato de caso sobre o papel do ultrassom intraoperatório

Abstract Background and objectives: A prompt and effective management of trauma patient is necessary. The aim of this case report is to highlight the importance of intraoperative echocardiography as a useful tool in patients suffering from refractory hemodynamic instability no otherwise explained. Case report: A 41 year-old woman suffered a car accident. At the emergency department, no abnormalities were found in ECG or chest X-ray. Abdominal ultrasound revealed the presence of abdominal free liquid and the patient was submitted to urgent exploratory laparotomy. Nevertheless, she persisted suffering arterial hypotension and metabolic acidosis. Looking for the reason of her hemodynamic instability, intraoperative transthoracic echocardiography was performed, finding out the presence of pericardial effusion. Once the cardiac surgeon extracted pericardial clots, patient's situation improved clinically and analytically. Conclusion: Every anesthesiologist should be able to use the intraoperative echocardiography as an effective tool in order to establish the appropriate measures to promote the survival of patients suffering severe trauma.

Resumo Justificativa e objetivos: O atendimento rápido e eficaz do paciente de trauma é necessário. O objetivo deste relato de caso foi destacar a importância do ecocardiograma intraoperatório como uma ferramenta útil em pacientes que sofrem de instabilidade hemodinâmica refratária sem explicação aparente. Relato de caso: Uma mulher de 41 anos sofreu um acidente de automóvel. No departamento de emergência, nenhuma anormalidade foi encontrada no ECG ou na radiografia de tórax. Uma ultrassonografia abdominal revelou a presença de líquido livre no abdome, e a paciente foi submetida à laparotomia exploradora de urgência. No entanto, a paciente continuou apresentando hipotensão arterial e acidose metabólica. Na busca pelo motivo de sua instabilidade hemodinâmica, um ecocardiograma transtorácico foi realizado no período intraoperatório e constatou a presenc¸a de derrame pericárdico. Após a remoção dos coágulos pericárdicos pelo cirurgião cardíaco, a condição da paciente melhorou clínica e analiticamente. Conclusão: Todo anestesiologista deve saber utilizar o ecocardiograma intraoperatório como ferramenta eficaz para estabelecer as medidas adequadas para promover a sobrevida de pacientes com traumatismos graves.

[Looking for the reason of hemodynamic instability: a case report of the role of intraoperative ultrasound]. / Buscando o motivo da instabilidade hemodinâmica: relato de caso sobre o papel do ultrassom intraoperatório.

BACKGROUND AND OBJECTIVES: A prompt and effective management of trauma patient is necessary. The aim of this case report is to highlight the importance of intraoperative echocardiography as a useful tool in patients suffering from refractory hemodynamic instability no otherwise explained. CASE REPORT: A 41 year-old woman suffered a car accident. At the emergency department, no abnormalities were found in ECG or chest X-ray. Abdominal ultrasound revealed the presence of abdominal free liquid and the patient was submitted to urgent exploratory laparotomy. Nevertheless, she persisted suffering arterial hypotension and metabolic acidosis. Looking for the reason of her hemodynamic instability, intraoperative transthoracic echocardiography was performed, finding out the presence of pericardial effusion. Once the cardiac surgeon extracted pericardial clots, patient's situation improved clinically and analytically. CONCLUSION: Every anesthesiologist should be able to use the intraoperative echocardiography as an effective tool in order to establish the appropriate measures to promote the survival of patients suffering severe trauma.

In-Out-Test: A New Paradigm for Sorting the Wheat from the Chaff in Prodromal Alzheimer's Disease.

BACKGROUND: Assessment of hippocampal amnesia is helpful to distinguish between normal cognition and mild cognitive impairment (MCI), but not for identifying converters to dementia. Here biomarkers are useful but novel neuropsychological approaches are needed in their absence. The In-out-test assesses episodic memory using a new paradigm hypothesized to avoid reliance on executive function, which may compensate for damaged memory networks. OBJECTIVE: To assess the validity of the In-out-test in identifying prodromal Alzheimer's disease (PAD) in a clinical setting, by comparing this to the Free and Cued Selective Reminding Test (FCSRT) and cerebrospinal fluid biomarkers. METHODS: A cross-sectional study of 32 cognitively healthy, 32 MCI, and 30 progressive dementia subjects. All participants were given both the In-out-test and the FCSRT; 40 of them also received a lumbar puncture. RESULTS: Internal consistency was demonstrated using Cronbach Alpha (r = 0.81) and Inter-rater reliability with Kappa (k = 0.94). Intraclass correlation (ICC) for test-retest reliability: r = 0.57 (p = 0.57). ICC between the In-out-test and FCSRT r = 0.87 (p = 0.001). ICC between the In-out-test and Aß42 and P-tau/Aß42 for controls: 0.73 and 0.75, respectively; P-tau for MCI: 0.77 and total sample: 0.70; Aß42 for dementia: 0.71. All ICC measures between FCSRT and biomarkers were ≤0.264. AD diagnosis: In-out-test k = 0.71; FCSRT k = 0.49. PAD diagnosis (N = 35): In-out-test k = 0.69; FCSRT k = 0.44. CONCLUSIONS: The In-out-test detected prodromal AD with a higher degree of accuracy than a conventional hippocampal-based memory test. These results suggest that this new paradigm could be of value in clinical settings, predicting which patients with MCI will go on to develop AD.