The effectiveness of a brief intervention for intensive care unit patients with hazardous alcohol use: a randomized controlled trial.

BACKGROUND: Screening for hazardous alcohol use and performing brief interventions (BIs) are recommended to reduce alcohol-related negative health consequences. We aimed to compare the effectiveness (defined as an at least 10% absolute difference) of BI with usual care in reducing alcohol intake in intensive care unit survivors with history of hazardous alcohol use. METHODS: We used Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) score to assess history of alcohol use. PATIENTS: Emergency admitted adult ICU patients in three Finnish university hospitals, with an AUDIT-C score > 5 (women), or > 6 (men). We randomized consenting eligible patients to receive a BI or treatment as usual (TAU). INTERVENTION: BI was delivered by the time of ICU discharge or shortly thereafter in the hospital ward. CONTROLS: Control patients received TAU. OUTCOME: The primary outcome was self-reported alcohol consumption during the preceding week 6 and 12 months after randomization. Secondary outcomes were the change in AUDIT-C scores from baseline to 6 and 12 months, health-related quality of life, and mortality. The trial was terminated early due to slow recruitment during the pandemic. RESULTS: We randomized 234 patients to receive BI (N = 117) or TAU (N = 117). At 6 months, the median alcohol intake in the BI and TAU groups were 6.5 g (interquartile range [IQR] 0-141) and 0 g (0-72), respectively (p = 0.544). At 12 months, it was 24 g (0-146) and 0 g (0-96) in the BI and TAU groups, respectively (p = 0.157). Median change in AUDIT-C from baseline to 6 months was - 1 (- 4 to 0) and 2 (- 6 to 0), (p = 0.144) in the BI and TAU groups, and to 12 months - 3 (- 5 to - 1) and - 4 (- 7 to - 1), respectively (p = 0.187). In total, 4% (n = 5) of patients in the BI group and 11% (n = 13) of patients in the TAU group were abstinent at 6 months, and 10% (n = 12) and 15% (n = 17), respectively, at 12 months. No between-groups difference in mortality emerged. CONCLUSION: As underpowered, our study cannot reject or confirm the hypothesis that a single BI early after critical illness is effective in reducing the amount of alcohol consumed compared to TAU. However, a considerable number in both groups reduced their alcohol consumption. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03047577).

Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial.

BACKGROUND: Activation of the triggering receptor expressed on myeloid cells-1 (TREM-1) pathway is associated with septic shock outcomes. Data suggest that modulation of this pathway in patients with activated TREM-1 might improve survival. Soluble TREM-1 (sTREM-1), a potential mechanism-based biomarker, might facilitate enrichment of patient selection in clinical trials of nangibotide, a TREM-1 modulator. In this phase 2b trial, we aimed to confirm the hypothesis that TREM1 inhibition might improve outcomes in patients with septic shock. METHODS: This double-blind, randomised, placebo-controlled, phase 2b trial assessed the efficacy and safety of two different doses of nangibotide compared with placebo, and aimed to identify the optimum treatment population, in patients across 42 hospitals with medical, surgical, or mixed intensive care units (ICUs) in seven countries. Non-COVID-19 patients (18-85 years) meeting the standard definition of septic shock, with documented or suspected infection (lung, abdominal, or urinary [in patients ≥65 years]), were eligible within 24 h of vasopressor initiation for the treatment of septic shock. Patients were randomly assigned in a 1:1:1 ratio to intravenous nangibotide 0·3 mg/kg per h (low-dose group), nangibotide 1·0 mg/kg per h (high-dose group), or matched placebo, using a computer-generated block randomisation scheme (block size 3). Patients and investigators were masked to treatment allocation. Patients were grouped according to sTREM-1 concentrations at baseline (established from sepsis observational studies and from phase 2a change to data) into high sTREM-1 (≥ 400 pg/mL). The primary outcome was the mean difference in total Sequential Organ Failure Assessment (SOFA) score from baseline to day 5 in the low-dose and high-dose groups compared with placebo, measured in the predefined high sTREM-1 (≥ 400 pg/mL) population and in the overall modified intention-to-treat population. Secondary endpoints included all-cause 28-day mortality, safety, pharmacokinetics, and evaluation of the relationship between TREM-1 activation and treatment response. This study is registered with EudraCT, 2018-004827-36, and Clinicaltrials.gov, NCT04055909. FINDINGS: Between Nov 14, 2019, and April 11, 2022, of 402 patients screened, 355 were included in the main analysis (116 in the placebo group, 118 in the low-dose group, and 121 in the high-dose group). In the preliminary high sTREM-1 population (total 253 [71%] of 355; placebo 75 [65%] of 116; low-dose 90 [76%] of 118; high-dose 88 [73%] of 121), the mean difference in SOFA score from baseline to day 5 was 0·21 (95% CI -1·45 to 1·87, p=0·80) in the low-dose group and 1·39 (-0·28 to 3·06, p=0·104) in the high-dose group versus placebo. In the overall population, the difference in SOFA score from baseline to day 5 between the placebo group and low-dose group was 0·20 (-1·09 to 1·50; p=0·76),and between the placebo group and the high-dose group was 1·06 (-0·23 to 2·35, p=0·108). In the predefined high sTREM-1 cutoff population, 23 (31%) patients in the placebo group, 35 (39%) in the low-dose group, and 25 (28%) in the high-dose group had died by day 28. In the overall population, 29 (25%) patients in the placebo, 38 (32%) in the low-dose, and 30 (25%) in the high-dose group had died by day 28. The number of treatment-emergent adverse events (111 [96%] patients in the placebo group, 113 [96%] in the low-dose group, and 115 [95%] in the high-dose group) and serious treatment-emergent adverse events (28 [24%], 26 [22%], and 31 [26%]) was similar between all three groups. High-dose nangibotide led to a clinically relevant improvement in SOFA score (of two points or more) from baseline to day 5 over placebo in those with higher cutoff concentrations (≥532 pg/mL) of sTREM-1 at baseline. Low dose nangibotide displayed a similar pattern with lower magnitude of effect across all cutoff values. INTERPRETATION: This trial did not achieve the primary outcome of improvement in SOFA score at the predefined sTREM-1 value. Future studies are needed to confirm the benefit of nangibotide at higher concentrations of TREM-1 activation. FUNDING: Inotrem.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Prevalence of risk-drinking in critically ill patients, screened with carbohydrate-deficient transferrin and AUDIT-C score: A retrospective study.

Background Studies demonstrate that up to one-third of intensive care unit (ICU) admissions are directly or indirectly related to alcohol. Screening for alcohol use is not routine. This study examined the prevalence of elevated %CDT (carbohydrate-deficient transferrin) and above risk-level AUDIT-C (Alcohol Use Disorders Identification Test, Consumption) in patients admitted to ICU. Methods We conducted a retrospective analysis of clinical and laboratory data from a single ICU where %CDT and AUDIT-C were included in routine assessment. After excluding readmissions, 2532 adult patients from a 21-month period were included. Admission values of %CDT were available for 2049 patients, and AUDIT-C was available for 1617 patients. The association of %CDT and AUDIT-C with short- and long-term outcome was studied by using univariate and multivariate logistic regression analysis. Results %CDT was above the reference value in 23.7% (486/2048) of patients with available %CDT. Of patients with available AUDIT-C, 33% (544/1617) had a risk-level AUDIT-C score. Patients with a risk-level AUDIT-C score were significantly younger than those with a lower score (51 vs 64 years, P < .0001). Increased %CDT was associated with higher severity of illness. AUDIT-C was associated independently with increased risk of long-term mortality in multivariate analysis (P = .007). Conclusion One in three of ICU patients are risk-level alcohol users as measured with AUDIT-C score, and one in four are analysed with %CDT. The prevalence varies according to the method used and any method alone may be insufficient to detect risk-level consumption reliably. Editorial Comment Alcohol overconsumption is associated with need for ICU admission and with less favorable outcomes. Diagnosis of alcohol overconsumption though is problematic due to low sensitivity in screening. In a pilot study, a biomarker and a screening tool are compared. The finding is that multiple tools are needed to achieve an adequate sensitivity for detection.

Prostate Cancer Detection with a Tactile Resonance Sensor-Measurement Considerations and Clinical Setup.

Tumors in the human prostate are usually stiffer compared to surrounding non-malignant glandular tissue, and tactile resonance sensors measuring stiffness can be used to detect prostate cancer. To explore this further, we used a tactile resonance sensor system combined with a rotatable sample holder where whole surgically removed prostates could be attached to detect tumors on, and beneath, the surface ex vivo. Model studies on tissue phantoms made of silicone and porcine tissue were performed. Finally, two resected human prostate glands were studied. Embedded stiff silicone inclusions placed 4 mm under the surface could be detected in both the silicone and biological tissue models, with a sensor indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa) could be distinguished from normal tissue (p < 0.05), when the tumor was located in the anterior part, whereas small tumors located in the dorsal aspect were undetected. The study indicates that PCa may be detected in a whole resected prostate with an uneven surface and through its capsule. This is promising for the development of a clinically useful instrument to detect prostate cancer during surgery.

Plasma Soluble Urokinase-Type Plasminogen Activator Receptor Is Not Associated with Neurological Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECT: Aneurysmal subarachnoid hemorrhage (aSAH) is a common cause of death or long-term disability. Despite advances in neurocritical care, there is still only a very limited ability to monitor the development of secondary brain injury or to predict neurological outcome after aSAH. Soluble urokinase-type plasminogen activator receptor (suPAR) has shown potential as a prognostic and as an inflammatory biomarker in a wide range of critical illnesses since it displays an association with overall immune system activation. This is the first time that suPAR has been evaluated as a prognostic biomarker in aSAH. METHODS: In this prospective population-based study, plasma suPAR levels were measured in aSAH patients (n = 47) for up to 5 days. suPAR was measured at 0, 12, and 24 h after patient admission to the intensive care unit (ICU) and daily thereafter until he/she was transferred from the ICU. The patients' neurological outcome was evaluated with the modified Rankin Scale (mRS) at 6 months after aSAH. RESULTS: suPAR levels (n = 47) during the first 24 h after aSAH were comparable in groups with a favorable (mRS 0-2) or an unfavorable (mRS 3-6) outcome. suPAR levels during the first 24 h were not associated with the findings in the primary brain CT, with acute hydrocephalus, or with antimicrobial medication use during 5-days' follow-up. suPAR levels were associated with generally accepted inflammatory biomarkers (C-reactive protein, leukocyte count). CONCLUSION: Plasma suPAR level was not associated with either neurological outcome or selected clinical conditions. While suPAR is a promising biomarker for prognostication in several conditions requiring intensive care, it did not reveal any value as a prognostic biomarker after aSAH.

Case report: Two severe cases of suicide attempts using nicotine containing e-cigarette liquid.

The use of electronic cigarettes and nicotine-containing liquids is getting more common, thus increasing the risk for intentional or unintentional nicotine poisoning. The results of ingestion of nicotine can be severe, even fatal. We describe two different cases of severe poisonings caused by nicotine-containing electronic cigarette liquids.

The predictive value of soluble urokinase plasminogen activator receptor (SuPAR) regarding 90-day mortality and 12-month neurological outcome in critically ill patients after out-of-hospital cardiac arrest. Data from the prospective FINNRESUSCI study.

AIM: The whole body ischaemia-reperfusion after cardiac arrest (CA) induces a systemic inflammation-reperfusion response. The expression of urokinase plasminogen activator receptor (uPAR) is known to be induced after hypoxia and increased levels of soluble form suPAR have been measured after hypoxia and ischaemia. Our aim was to evaluate, whether ischaemia/reperfusion injury after out-of-hospital cardiac arrest (OHCA) increases suPAR concentrations in serum and to evaluate the prognostic value of suPAR regarding 90-day mortality and 12-month neurological outcome. METHODS: This is a pre-determined substudy of prospective FINNRESUSCI study. Total of 287 patients treated in the intensive care units after OHCA and with consent from the next-of-kin and serum samples between baseline and day 4 were included. Outcome and neurological outcome were evaluated according the Pittsburgh Cerebral Performance Categories (CPC). Kaplan-Meier survival curves, areas under receiver operational characteristics curves and positive likelihood ratios for mortality and poor neurological outcome were calculated. RESULTS: Non-survivors had higher levels of suPAR after OHCA. Kaplan-Meier survival curves indicated high 90-day mortality in the highest concentration quintiles. LR+ for 1-year CPC 3-5 was 1.8-2.7 for the whole patient cohort and in shockable rhythms 2.0-2.4. In therapeutic hypothermia prognostic value remained. CONCLUSIONS: We found that high SuPAR concentrations were associated with poor outcome in patients with OHCA admitted to critical care. However, suPAR alone had inadequate predictive value for poor outcome and did not associate with 12-month neurological outcome.

Indentation loading response of a resonance sensor--discriminating prostate cancer and normal tissue.

Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R(2 )= 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.

Contact angle and indentation velocity dependency for a resonance sensor--evaluation on soft tissue silicone models.

Human tissue stiffness can vary due to different tissue conditions such as cancer tumours. Earlier studies show that stiffness may be detected with a resonance sensor that measures frequency shift and contact force at application. Through the frequency shift and the contact force, a tissue stiffness parameter can be derived. This study evaluated how the probe application angle and indentation velocity affected the results and determined the maximum parameter errors. The evaluation was made on flat silicone discs with specified hardness. The frequency shift, the force and the stiffness parameter all varied with contact angle and indentation velocity. A contact angle of ≤10° was acceptable for reliable measurements. A low indentation velocity was recommended. The maximum errors for the system were <1.1% of the measured values. It was concluded that contact angle and indentation velocity have to be considered in the clinical setting. The angular dependency is especially important in clinical use for studying stiffness of human soft tissue, e.g. in prostate cancer diagnosis.

SuPAR and PAI-1 in critically ill, mechanically ventilated patients.

PURPOSE: SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients. METHODS: We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan-Meier analysis were performed. RESULTS: Baseline suPAR was 11.6 ng/ml (quartiles Q1-Q3, 9.6-14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5-11.0). PAI-1 concentrations were 2.67 ng/ml (1.53-4.69) and 0.3 ng/ml (0.3-0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55-0.67), sepsis 0.68 (0.61-0.76), ALI/ARDS 0.64 (0.56-0.73) and RRT 0.65 (0.56-0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37-4.64, p = 0.003) for 90-day mortality and 3.16 (1.19-8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC's for suPAR were 90-day mortality 0.61 (0.54-0.68), RRT 0.73 (0.64-0.83), sepsis 0.70 (0.60-0.80), ALI/ARDS 0.61 (0.51-0.71). Predictive value of PAI-1 was negligible. CONCLUSIONS: In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.

Explanatory models for a tactile resonance sensor system-elastic and density-related variations of prostate tissue in vitro.

Tactile sensors based on piezoelectric resonance have been adopted for medical applications. The sensor consists of an oscillating piezoelectric sensor-circuit system, and a change in resonance frequency is observed when the sensor tip contacts a measured object such as tissue. The frequency change at a constant applied force or mass load is used as a stiffness-sensitive parameter in many applications. Differential relations between force and frequency have also been used for monitoring intraocular pressure and stiffness variations in prostate tissue in vitro. The aim of this study was to relate the frequency change (Deltaf), measured force (F) and the material properties, density and elasticity to an explanatory model for the resonance sensor measurement principle and thereby to give explanatory models for the stiffness parameters used previously. Simulations of theoretical equations were performed to investigate the relation between frequency change and contact impedance. Measurements with a resonance sensor system on prostate tissue in vitro were used for experimental validation of the theory. Tissue content was quantified with a microscopic-based morphometrical method. Simulation results showed that the frequency change was dependent upon density (rho) and contact area (S) according to Deltaf proportional, variant rhoS(3/2). The experiments followed the simulated theory at small impression depths. The measured contact force followed a theoretical model with the dependence of the elastic modulus (E) and contact area, F proportional, variant ES(3/2). Measured density variations related to histological variations were statistically weak or non-significant. Elastic variations were statistically significant with contributions from stroma and cancer relative to normal glandular tissue. The theoretical models of frequency change and force were related through the contact area, and a material-dependent explanatory model was found as Deltaf proportional, variant rhoE(-1)F. It explains the measurement principle and the previously established stiffness parameters from the material properties point of view.

Spatial variations in prostate tissue histology as measured by a tactile resonance sensor.

In recent years, tactile sensors based on piezoelectric resonance sensor technology have been used for medical diagnosis where the sensor's stiffness-measuring properties can reflect tissue pathology. The change in the frequency of the resonating system and the change in force when contact is made with tissue are used as a stiffness parameter. Earlier stiffness measurements of prostate tissue in vitro demonstrate variations related to tissue composition. In this study, measured stiffness from two human prostate specimens was compared to histological composition of prostate tissue below and around the measurement points. Tissue stiffness was measured with the resonance sensor system. Tissue composition was measured at four different depths in the tissue specimen using a microscopic-image-based morphometrical method. With this method, the proportion of tissue types was determined at the points of intersections in a circular grid on the images representing each measurement point. Numerical values were used for weighting the tissue proportions at different depths in the tissue specimen. For an impression depth of 1.0 mm, the sensing depth in this study was estimated to be 3.5-5.5 mm. Stiffness variations due to horizontal tissue variations were investigated by studying the dependence of the size of the circular grid area relative to the contact area of the sensor tip. The sensing area (grid radius) was estimated to be larger than the contact area (contact radius) between the sensor tip and the tissue. Thus, the sensor tip registers spatial variations in prostate tissue histology, both directly below and lateral to the tip itself. These findings indicate that tumours around the sensor tip could be detected, which in turn supports the idea of a future resonance-sensor-based clinical device for detecting tumours and for guiding biopsies.

Resonance sensor measurements of stiffness variations in prostate tissue in vitro--a weighted tissue proportion model.

Prostate cancer is the most common type of cancer in men in Europe and the US. The methods to detect prostate cancer are still precarious and new techniques are needed. A piezoelectric transducer element in a feedback system is set to vibrate with its resonance frequency. When the sensor element contacts an object a change in the resonance frequency is observed, and this feature has been utilized in sensor systems to describe physical properties of different objects. For medical applications it has been used to measure stiffness variations due to various patho-physiological conditions. In this study the sensor's ability to measure the stiffness of prostate tissue, from two excised prostatectomy specimens in vitro, was analysed. The specimens were also subjected to morphometric measurements, and the sensor parameter was compared with the morphology of the tissue with linear regression. In the probe impression interval 0.5-1.7 mm, the maximum R(2) > or = 0.60 (p < 0.05, n = 75). An increase in the proportion of prostate stones (corpora amylacea), stroma, or cancer in relation to healthy glandular tissue increased the measured stiffness. Cancer and stroma had the greatest effect on the measured stiffness. The deeper the sensor was pressed, the greater, i.e., deeper, volume it sensed. Tissue sections deeper in the tissue were assigned a lower mathematical weighting than sections closer to the sensor probe. It is concluded that cancer increases the measured stiffness as compared with healthy glandular tissue, but areas with predominantly stroma or many stones could be more difficult to differ from cancer.

Prostate tissue stiffness as measured with a resonance sensor system: a study on silicone and human prostate tissue in vitro.

Prostate cancer is the most common form of cancer in men in Europe and in the USA. Some prostate tumours are stiffer than the surrounding normal tissue, and it could therefore be of interest to measure prostate tissue stiffness. Resonance sensor technology based on piezoelectric resonance detects variations in tissue stiffness due to a change in the resonance frequency. An impression-controlled resonance sensor system was used to detect stiffness in silicone rubber and in human prostate tissue in vitro using two parameters, both combinations of frequency change and force. Variations in silicone rubber stiffness due to the mixing ratio of the two components could be detected (p<0.05) using both parameters. Measurements on prostate tissue showed that there existed a statistically significant (MANOVA test, p<0.001) reproducible difference between tumour tissue (n=13) and normal healthy tissue (n=98) when studying a multivariate parameter set. Both the tumour tissue and normal tissue groups had variations within them, which were assumed to be related to differences in tissue composition. Other sources of error could be uneven surfaces and different levels of dehydration for the prostates. Our results indicated that the resonance sensor could be used to detect stiffness variations in silicone and in human prostate tissue in vitro. This is promising for the development of a future diagnostic tool for prostate cancer.

Encoding of novel picture pairs activates the perirhinal cortex: an fMRI study.

It is well established in nonhuman primates that the medial temporal lobe (MTL) structures, the hippocampus and the entorhinal and perirhinal cortices, are necessary for declarative memory encoding. In humans, the neuropathological and neuropsychological changes in early Alzheimer's disease (AD) further support a role for the rhinal cortex in the consolidation of new events into long-term memory. Little is known, however, regarding the function of the rhinal cortex in humans in vivo. To examine the participation of the interconnected MTL structures as well as the whole-brain network of activated brain areas in visual associative long-term memory, functional magnetic resonance imaging (fMRI) was used to determine the brain regions that are activated during encoding and retrieval of paired pictures in 12 young control subjects. The most striking finding in the MTL activation pattern was the consistent activation of the perirhinal cortex in the encoding-baseline and encoding-retrieval comparisons with a strict statistical threshold (P < 0.00001). In contrast, no perirhinal cortex activation was detected in the retrieval-baseline or retrieval-encoding comparisons even with a low statistical threshold (P < 0.05). The location of the perirhinal activation area was in the transentorhinal part of the perirhinal cortex, in the medial bank of the collateral sulcus. The hippocampus and the more posterior parahippocampal gyrus were activated in both encoding and retrieval conditions. During the encoding processing, MTL activations were more consistent and the hippocampal activation area located more anteriorly than during retrieval. The frontal, parietal, temporal, and occipital association cortices were also activated in the encoding-baseline and retrieval-baseline comparisons. The data suggest that encoding, but not retrieval, of novel picture pairs activates the perirhinal cortex. To our knowledge, this is the first fMRI study reporting encoding activation in this transentorhinal part of the perirhinal cortex, the site of the very earliest neuropathological changes in AD.