How Common Are Chronic Residual Limb Pain, Phantom Pain, and Back Pain More Than 20 Years After Lower Limb Amputation for Malignant Tumors?

BACKGROUND: After major lower limb amputation, persistent pain is common, with up to 85% of patients reporting recurring phantom or residual-limb pain. Although pain management is an important factor of quality of life in patients with lower limb amputations, there are few long-term data regarding the frequency of persistent pain and how it impacts prosthesis use. QUESTIONS/PURPOSES: (1) How prevalent are different types of pain at long-term follow-up after amputation for malignant tumors? (2) What association do different pain types have with daily prosthesis use? METHODS: Between 1961 and 1995, 124 major amputations for malignant tumors were performed at one center in Austria in patients (1) who spoke German and (2) whose surgical date resulted in the possibility of a minimum follow-up time of 20 years at the time of this survey; those patients were considered potentially eligible for this retrospective study. The indications for major amputation were to achieve local tumor control in limbs that the surgeon deemed unsalvageable without amputation. Of those 124 patients, 71% (88) had died, 9% (11) could not be reached, and 3% (4) declined to participate. Thus, 58% (21 of 36) of those living at the time of this study and who underwent lower limb amputation between 1961 and 1993 with a median (range) follow-up duration of 41 years (23 to 55) completed a standardized questionnaire, including an assessment of pain and daily prosthesis use during the year before the survey. Phantom pain, residual limb pain, and back pain were each further subclassified into pain frequency, intensity, and restrictions in activities of daily living (ADL) due to the specific pain form and rated on a 5- (pain frequency) and 10-point (pain intensity, restrictions in ADL) numerical rating scale. Before multivariate regression analysis, daily prosthesis use was correlated with pain parameters using Spearman correlation testing. RESULTS: Seventeen of 21 patients reported phantom limb and back pain, and 15 patients reported residual limb pain in the past year. Median (range) phantom pain intensity was 7 (1 to 10) points, median residual limb pain intensity was 4 (1 to 9) points, and median back pain intensity was 5 (1 to 10) points. After controlling for relevant confounding variables such as age at amputation, age at survey, and stump length, we found that less intense residual limb pain (defined on a 10-point scale with 1 representing no pain at all and 10 representing extremely strong pain [95% CI 0.3 to 1.0]; r = 0.8; p = 0.003) was associated with greater daily prosthesis use. Higher amputation levels showed a decreased daily prosthesis use compared with patients with lower amputation levels (defined as transfemoral amputation versus knee disarticulation versus transtibial amputation [95% CI 0.3 to 5.1]; r = 0.5; p = 0.03). CONCLUSION: Decades after surgery, many patients with lower limb amputations experience pain that restricts them in terms of ADLs and decreases their daily prosthesis use. This information supports the need for regular residual limb inspections and careful prosthesis fitting even at long-term follow-up, as effective prosthesis fitting is a modifiable cause of residual limb pain. Future studies evaluating long-term treatment effects of pain relief surgery and therapeutic alternatives to conservative pain treatments should be performed, as these approaches may help alleviate pain in patients with refractory postamputation pain. LEVEL OF EVIDENCE: Level IV, therapeutic study.

High-resolution remote thermometry and thermography using luminescent low-dimensional tin-halide perovskites.

Although metal-halide perovskites have recently revolutionized research in optoelectronics through a unique combination of performance and synthetic simplicity, their low-dimensional counterparts can further expand the field with hitherto unknown and practically useful optical functionalities. In this context, we present the strong temperature dependence of the photoluminescence lifetime of low-dimensional, perovskite-like tin-halides and apply this property to thermal imaging. The photoluminescence lifetimes are governed by the heat-assisted de-trapping of self-trapped excitons, and their values can be varied over several orders of magnitude by adjusting the temperature (up to 20 ns °C-1). Typically, this sensitive range spans up to 100 °C, and it is both compound-specific and shown to be compositionally and structurally tunable from -100 to 110 °C going from [C(NH2)3]2SnBr4 to Cs4SnBr6 and (C4N2H14I)4SnI6. Finally, through the implementation of cost-effective hardware for fluorescence lifetime imaging, based on time-of-flight technology, these thermoluminophores have been used to record thermographic videos with high spatial and thermal resolution.

Prediction of fluid responsiveness in mechanically ventilated cardiac surgical patients: the performance of seven different functional hemodynamic parameters.

BACKGROUND: Functional hemodynamic parameters such as stroke volume and pulse pressure variation (SVV and PPV) have been shown to be reliable predictors of fluid responsiveness in mechanically ventilated patients. Today, different minimally- and non-invasive hemodynamic monitoring systems measure functional hemodynamic parameters. Although some of these parameters are described by the same name, they differ in their measurement technique and thus may provide different results. We aimed to test the performance of seven functional hemodynamic parameters simultaneously in the same clinical setting. METHODS: Hemodynamic measurements were done in 30 cardiac surgery patients that were mechanically ventilated. Before and after a standardized intravenous fluid bolus, hemodynamics were measured by the following monitoring systems: PiCCOplus (SVVPiCCO, PPVPiCCO), LiDCOrapid (SVVLiDCO, PPVLiDCO), FloTrac (SVVFloTrac), Philips Intellivue (PPVPhilips) and Masimo pulse oximeter (pleth variability index, PVI). Prediction of fluid responsiveness was tested by calculation of receiver operating characteristic (ROC) curves including a gray zone approach and compared using Fisher's Z-Test. RESULTS: Fluid administration resulted in an increase in cardiac output, while all functional hemodynamic parameters decreased. A wide range of areas under the ROC-curve (AUC's) was observed: AUC-SVVPiCCO = 0.91, AUC-PPVPiCCO = 0.88, AUC-SVVLiDCO = 0.78, AUC-PPVLiDCO = 0.89, AUC-SVVFloTrac = 0.87, AUC-PPVPhilips = 0.92 and AUC-PVI = 0.68. Optimal threshold values for prediction of fluid responsiveness ranged between 9.5 and 17.5%. Lowest threshold values were observed for SVVLiDCO, highest for PVI. CONCLUSION: All functional hemodynamic parameters tested except for PVI showed that their use allows a reliable identification of potential fluid responders. PVI however, may not be suitable after cardiac surgery to predict fluid responsiveness. TRIAL REGISTRATION: NCT02571465 , registered on October 7th, 2015 (retrospectively registered).

Accuracy, Precision, and Trending of 4 Pulse Wave Analysis Techniques in the Postoperative Period.

OBJECTIVE: The aim of this study was to analyze the accuracy, precision, and trending ability of the following 4 pulse wave analysis devices to measure continuous cardiac output: PiCCO2 ([PCCO]; Pulsion Medical System, Munich, Germany); LiDCORapid ([LCCO]; LiDCO Ltd, London, UK); FloTrac/Vigileo ([FCCO]; Edwards Lifesciences, Irvine, CA); and Nexfin ([NCCO]; BMEYE, Amsterdam, The Netherlands). DESIGN: Prospective, observational clinical study. SETTING: Intensive care unit of a single-center, teaching hospital. PARTICIPANTS: The study comprised 22 adult patients after elective coronary artery bypass surgery. INTERVENTIONS: Three measurement cycles were performed in all patient durings their immediate postoperative intensive care stay before and after fluid loading. Hemodynamic measurements were performed 5 minutes before and immediately after the administration of 500 mL colloidal fluid over 20 minutes. MEASUREMENTS AND MAIN RESULTS: PCCO, LCCO, FCCO, and NCCO were assessed and compared with cardiac output derived from intermittent transpulmonary thermodilution (ICO). One hundred thirty-two matched sets of data were available for analysis. Bland-Altman analysis using linear mixed effects models with random effects for patient and trial revealed a mean bias ±2 standard deviation (%error) of -0.86 ± 1.41 L/min (34.9%) for PCCO-ICO, -0.26 ± 2.81 L/min (46.3%) for LCCO-ICO, -0.28 ± 2.39 L/min (43.7%) for FCCO-ICO, and -0.93 ± 2.25 L/min (34.6%) for NCCO-ICO. Bland-Altman plots without adjustment for repeated measurements and replicates yielded considerably larger limits of agreement. Trend analysis for all techniques did not meet criteria for acceptable performance. CONCLUSIONS: All 4 tested devices using pulse wave analysis for measuring cardiac output failed to meet current criteria for meaningful and adequate accuracy, precision, and trending ability in cardiac output monitoring.

Lipoarabinomannan-Responsive Polycytotoxic T Cells Are Associated with Protection in Human Tuberculosis.

RATIONALE: The development of host-targeted, prophylactic, and therapeutic interventions against tuberculosis requires a better understanding of the immune mechanisms that determine the outcome of infection with Mycobacterium tuberculosis. OBJECTIVES: To identify T-cell-dependent mechanisms that are protective in tuberculosis. METHODS: Multicolor flow cytometry, cell sorting and growth inhibition assays were employed to compare the frequency, phenotype and function of T lymphocytes from bronchoalveolar lavage or the peripheral blood. MEASUREMENTS AND MAIN RESULTS: At two independent study sites, bronchoalveolar lavage cells from donors with latent tuberculosis infection limited the growth of virulent Mycobacterium tuberculosis more efficiently than those in patients who developed disease. Unconventional, glycolipid-responsive T cells contributed to reduced mycobacterial growth because antibodies to CD1b inhibited this effect by 55%. Lipoarabinomannan was the most potent mycobacterial lipid antigen (activation of 1.3% T lymphocytes) and activated CD1b-restricted T cells that limited bacterial growth. A subset of IFN-γ-producing lipoarabinomannan-responsive T cells coexpressed the cytotoxic molecules perforin, granulysin, and granzyme B, which we termed polycytotoxic T cells. Taking advantage of two well-defined cohorts of subjects latently infected with Mycobacterium tuberculosis or patients who developed active disease after infection, we found a correlation between the frequency of polycytotoxic T cells and the ability to control infection (latent tuberculosis infection, 62%; posttuberculosis patients, 26%). CONCLUSIONS: Our data define an unconventional CD8(+) T-cell subset (polycytotoxic T cells) that is based on antigen recognition and function. The results link clinical and mechanistic evidence that glycolipid-responsive, polycytotoxic T cells contribute to protection against tuberculosis.

Automated Image Acquisition for Low-Dose STEM at Atomic Resolution.

Beam damage is a major limitation in electron microscopy that becomes increasingly severe at higher resolution. One possible route to circumvent radiation damage, which forms the basis for single-particle electron microscopy and related techniques, is to distribute the dose over many identical copies of an object. For the acquisition of low-dose data, ideally no dose should be applied to the region of interest before the acquisition of data. We present an automated approach that can collect large amounts of data efficiently by acquiring images in a user-defined area-of-interest with atomic resolution. We demonstrate that the stage mechanics of the Nion UltraSTEM, combined with an intelligent algorithm to move the sample, allow the automated acquisition of atomically resolved images from micron-sized areas of a graphene substrate. Moving the sample stage automatically in a regular pattern over the area-of-interest enables the collection of data from pristine sample regions without exposing them to the electron beam before recording an image. Therefore, it is possible to obtain data with minimal dose (no prior exposure during focusing), which is only limited by the minimum signal needed for data processing. This enables us to minimize beam-induced damage in the sample and to acquire large data sets within a reasonable amount of time.

Continuous cardiac output measurement by un-calibrated pulse wave analysis and pulmonary artery catheter in patients with septic shock.

Septic shock is a serious medical condition. With increased concerns about invasive techniques, a number of non-invasive and semi-invasive devices measuring cardiac output (CO) have become commercially available. The aim of the present study was to determine the accuracy, precision and trending abilities of the FloTrac and the continuous pulmonary artery catheter thermodilution technique determining CO in septic shock patients. Consecutive septic shock patients were included in two centres and CO was measured every 4 h up to 48 h by FloTrac (APCO) and by pulmonary artery catheter (PAC) using the continuous (CCO) and intermittent (ICO) technique. Forty-seven septic shock patients with 326 matched sets of APCO, CCO and ICO data were available for analysis. Bland and Altman analysis revealed a mean bias ±2 SD of 0.0 ± 2.14 L min(-1) for APCO-ICO (%error = 34.5 %) and 0.23 ± 2.55 L min(-1) for CCO-ICO (%error = 40.4 %). Trend analysis showed a concordance of 85 and 81 % for APCO and CCO, respectively. In contrast to CCO, APCO was influenced by systemic vascular resistance and by mean arterial pressure. In septic shock patients, APCO measurements assessed by FloTrac but also the established CCO measurements using the PAC did not meet the currently accepted statistical criteria indicating acceptable clinical performance.

The influence of acute pulmonary hypertension on cardiac output measurements: calibrated pulse contour analysis, transpulmonary and pulmonary artery thermodilution against a modified Fick method in an animal model.

BACKGROUND: In critically ill patients with significant pulmonary hypertension (PH), close perioperative cardiovascular monitoring is mandatory, considering the increased morbidity and mortality in this patient group. Although the pulmonary artery catheter is still the standard for the diagnosis of PH, its use to monitor cardiac output (CO) in patients with PH is decreasing as a result of increased morbidity and possible influence of tricuspid regurgitation on the measurements. However, continuous CO measurement methods have never been evaluated under PH regarding their agreement and trending ability. In this study, we evaluated the influence of acute PH and different CO states on transpulmonary thermodilution (TPTD) and calibrated pulse contour analysis (PiCCO; both assessed with PiCCO plus™), intermittent pulmonary artery thermodilution (PATD), and continuous thermodilution (CCO) compared with a modified Fick method (FICK) in an animal model. METHODS: Nine healthy pigs were studied under anesthesia. PH of 25 and 40 mm Hg (by administration of the thromboxane analog U46619), CO decreases, and CO increases were induced to test the different CO measurement techniques over a broad range of hemodynamic situations. Before each step, a new baseline data set was collected. CO values were compared using Bland-Altman analysis; trending abilities were assessed via concordance and polar plot analysis. The influence of pulmonary pressure on CO measurements was analyzed using linear mixed models. RESULTS: A mean bias of -0.26 L/min with prediction intervals of -0.88 to 1.4 L/min was measured between TPTD and FICK. Their concordance rate was 100% (94%-100% confidence interval), and the mean polar angle -3° with radial limits of agreement of ±28° indicated good trending abilities. PATD compared with FICK also showed good trending ability. Comparisons of PiCCO and CCO versus FICK revealed low agreement and poor trending results with concordance rates of 84% (71%-93%) and 88% (74%-95%), mean polar angles from -17° and -19°, and radial limits of agreement of ±45° and 40°. Pulmonary pressures influenced only the difference between FICK and PiCCO, as assessed by linear mixed models. CONCLUSIONS: TPTD compared with FICK was able to track all changes induced during the study period, including those by PH. It yielded better agreement than PATD both compared with FICK. PiCCO and CCO were not mapping all changes correctly, and when used clinically in unstable patients, regular controls with intermittent techniques are required. Acute pharmacologically induced PH did influence the difference between FICK and PiCCO.

Viscoelastic blood coagulation measurement with Sonoclot predicts postoperative bleeding in cardiac surgery after heparin reversal.

OBJECTIVES: The aim of the study was to determine if Sonoclot with its sensitive glass bead-activated, viscoelastic test can predict postoperative bleeding in patients undergoing cardiac surgery at predefined time points. DESIGN: A prospective, observational clinical study. SETTING: A teaching hospital, single center. PARTICIPANTS: Consecutive patients undergoing cardiac surgery (N = 300). INTERVENTIONS: Besides routine laboratory coagulation studies and heparin management with standard (kaolin) activated clotting time, additional native blood samples were analyzed on a Sonoclot using glass bead-activated tests. Glass bead-activated clotting time, clot rate, and platelet function were recorded immediately before anesthesia induction and at the end of surgery after heparin reversal but before chest closure. MEASUREMENTS AND MAIN RESULTS: Primary outcome was postoperative blood loss (chest tube drainage at 4, 8, and 12 hours postoperatively). Secondary outcome parameters were transfusion requirements, need for surgical re-exploration, time of mechanical ventilation, length of intensive care unit and hospital stay, and hospital morbidity and mortality. Patients were categorized into "bleeders" and "nonbleeders." Patient characteristics, operations, preoperative standard laboratory parameters, and procedural times were comparable between bleeders and nonbleeders except for sex and age. Bleeders had higher rates of transfusions, surgical re-explorations, and complications. Only glass bead measurements by Sonoclot after heparin reversal before chest closure but not preoperatively were predictive for increased postoperative bleeding. CONCLUSIONS: Sonoclot with its glass bead-activated tests may predict the risk for postoperative bleeding in patients undergoing cardiac surgery at the end of surgery after heparin reversal but before chest closure.

Trending ability and limitations of transpulmonary thermodilution and pulse contour cardiac output measurement in cats as a model for pediatric patients.

The present study evaluated transpulmonary thermodilution (TPTD) and pulse contour cardiac output (PCCO) both measured by the PiCCO Plus™ monitor (Pulsion Medical Systems, Munich, Germany) against pulmonary artery thermodilution (PATD) in cats as a hemodynamic model for small children. A wide range of cardiac outputs (CO) was simultaneously measured. Accuracy and trending abilities were critically evaluated. Three cats were studied under isoflurane anesthesia and 160 CO measurements were performed with 3 mL ice-cold 5 % dextrose with PATD and TPTD. The results were compared with the PCCO measurement before the bolus measurement. Cardiac output was manipulated from 32 to 224 mL/kg/min by dobutamine, dopamine, phenylephrine, medetomidine and increased concentrations of isoflurane. Bland-Altman analysis, concordance and polar plot analysis were performed to assess accuracy and trending ability. TPTD was measuring constantly higher than PATD with a mean bias of 73 mL/kg/min and limits of agreement of 34-112 mL/kg/min, a concordance rate of 94 % and a mean polar angle of -5° with radial limits of agreement (RLOA) of 33°. Concordance rate of the PCCO versus PATD was 82 % with a mean polar angle of -10° and RLOA of 46° and versus TPTD 90 % with a mean polar angle of -6° and RLOA of 46°. Both tested methods constantly overestimated simultaneous PATD measurements. The small size, low flows and the relative short catheter not reaching the abdominal aorta may explain that. However TPTD tracked changes accurately opposed to a poor trending ability of the PCCO measurement.

Update on minimally invasive hemodynamic monitoring in thoracic anesthesia.

PURPOSE OF REVIEW: Advanced hemodynamic monitoring is indispensable for adequate management of patients undergoing major surgery. This article will summarize minimally invasive hemodynamic monitoring technologies and their potential use in thoracic anesthesia. RECENT FINDINGS: According to their inherent principle, currently available technologies can be classified into four groups: bioimpedance and bioreactance, applied Fick's principle, pulse wave analysis and Doppler. All devices measure stroke volume and cardiac output. Functional hemodynamic variables and volumetric parameters have been integrated in some devices. Two major indications can be identified: the 'hemodynamically unstable' patient and the patient 'at risk' for hemodynamic instability. Although there is evidence for the first indication, pre-emptive hemodynamic therapy or perioperative hemodynamic optimization for the patient 'at risk' is still an issue of ongoing debate. There is a growing body of evidence that this approach can positively influence patients' outcome with less postoperative complications in selected patient groups. SUMMARY: Many different minimally invasive hemodynamic monitoring devices have been developed and clinically introduced in the last years. They offer the advantage of being less invasive and easier to use. However, these techniques have several limitations and data are scarce in patients undergoing thoracic anesthesia, preventing their widespread use so far.

Whole-Body Electrostatic Pain Treatment in Adults with Chronic Pain: A Prospective Multicentric Observational Clinical Trial.

INTRODUCTION: In the treatment of patients with chronic pain, whole-body electrostatic therapy using the Elosan Cabin C1 has been proposed as an adjunctive therapy. So far, data on the use of this cabin are limited. Promising results with a significant reduction in pain scores have been obtained in a small group of patients. However, treatment with Elosan Cabin C1 has not been the subject of evaluation in a larger patient population. The aim of this study was to investigate the efficacy and adverse effects of electrostatic treatment in such a population. METHODS: Prospective, multi-center, observational clinical trial conducted in daily practice in a large adult ambulatory population with chronic pain. Each patient received eight weekly Elosan C1 treatment sessions for up to 9 weeks. Treatment was added to an established conservative pain management. Pain scores (visual analog scale (VAS) 0-100, primary outcome) and sleep quality (seven-point Likert scale, secondary outcome) were assessed before, during, and at the end of the treatment period; quality of life (SF-12: Physical Component Summary = PCS, Mental Component Summary = MCS; secondary outcome) was assessed before and at the end of the treatment period. Subgroup analyses were performed for sex, age, duration of pain, initial pain location, pain entity, and pain medication at the start of treatment. RESULTS: A total of 192 patients were enrolled, 143 patients (74.5%) had a complete set of 8 treatment sessions. A reduction in pain scores from 68 ± 14 points to 47 ± 22 points was observed (p < 0.001), 65% of patients (responders) had a reduction of > 15 points. Female patients had a significantly better response than male patients with a higher number of responders (76% vs. 38%; p < 0.001). Patients with a pain history < 1 year had a significantly better response than patients with a pain history > 1 year. The Physical Component Summary (PCS) increased from 36 ± 11 to 41 ± 11 (+ 18%, p < 0.001) and the Mental Component Summary (MCS) from 41 ± 7 to 43 ± 7 (+ 6%, p = 0.3). Overall sleep quality improved significantly from 4.6 ± 1.7 to 3.73 ± 1.7 points (p < 0.001), with a higher proportion of responders in the female group (37 vs. 18%; p < 0.034). No serious adverse events were observed during treatment. CONCLUSIONS: Electrostatic therapy with Elosan Cabin C1 may be a useful and effective adjunct therapy for patients with chronic pain. The results suggest that female patients and those with a recent history of pain experience the greatest benefit. TRIAL REGISTRATION: NCT04818294 (clinicaltrials.gov).

Electrostatic treatment with the Elosan Cabin C1 is a form of pain therapy that works by applying an electrical charge to the outside of the whole body without a corresponding current flowing inside. The treatment is painless and lasts 8 min per session. The study investigated the effect of the Elosan treatment in 143 patients over a period of 8 weeks with sessions once per week. Investigated outcomes were changes in pain, quality of life, sleep quality, and side effects of the treatment. 65% of the patients had a relevant improvement in pain levels, the average pain reduction in all patients was 30.9%. Quality of life and sleep quality also improved significantly. There were no relevant side effects of the treatment. The best effect was seen in female patients and if the duration of pain was less than 1 year. It was found that by applying the electrostatic field once a week, various types of pain can be reduced with a long-lasting effect. The treatment is ideally combined with physiotherapy and other complementary pain therapies.

Phase offset method of ptychographic contrast reversal correction.

The contrast transfer function of direct ptychography methods such as the single side band (SSB) method are single signed, yet these methods still sometimes exhibit contrast reversals, most often where the projected potentials are strong. In thicker samples central focusing often provides the best ptychographic contrast as this leads to defocus variations within the sample canceling out. However focusing away from the entrance surface is often undesirable as this degrades the annular dark field (ADF) signal. Here we discuss how phase wrap asymptotes in the frequency response of SSB ptychography give rise to contrast reversals, without the need for dynamical scattering, and how these can be counteracted by manipulating the phases such that the asymptotes are either shifted to higher frequencies or damped via amplitude modulation. This is what enables post collection defocus correction of contrast reversals. However, the phase offset method of counteracting contrast reversals we introduce here is generally found to be superior to post collection application of defocus, with greater reliability and generally stronger contrast. Importantly, the phase offset method also works for thin and thick samples where central focusing does not. Finally, the independence of the method from focus is useful for optical sectioning involving ptychography, improving interpretability by better disentangling the effects of strong potentials and focus.

Endothelial receptor proteins in acute venous thrombosis and delayed thrombus resolution in cerebral sinus vein thrombosis.

BACKGROUND AND PURPOSE: Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. METHODS: In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. RESULTS: Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer (p < 0.001) and sPECAM-1 (p < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). CONCLUSION: sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.

Reliable phase quantification in focused probe electron ptychography of thin materials.

Electron ptychography provides highly sensitive, dose efficient phase images which can be corrected for aberrations after the data has been acquired. This is crucial when very precise quantification is required, such as with sensitivity to charge transfer due to bonding. Drift can now be essentially eliminated as a major impediment to focused probe ptychography, which benefits from the availability of easily interpretable simultaneous Z-contrast imaging. However challenges have remained when quantifying the ptychographic phases of atomic sites. The phase response of a single atom has a negative halo which can cause atoms to reduce in phase when brought closer together. When unaccounted for, as in integrating methods of quantification, this effect can completely obscure the effects of charge transfer. Here we provide a new method of quantification that overcomes this challenge, at least for 2D materials, and is robust to experimental parameters such as noise, sample tilt.

Can changes in arterial pressure be used to detect changes in cardiac output during volume expansion in the perioperative period?

BACKGROUND: Cardiac output (CO) is rarely monitored during surgery, and arterial pressure remains the only hemodynamic parameter for assessing the effects of volume expansion (VE). However, whether VE-induced changes in arterial pressure accurately reflect changes in CO has not been demonstrated. The authors studied the ability of VE-induced changes in arterial pressure and in pulse pressure variation to detect changes in CO induced by VE in the perioperative period. METHODS: The authors studied 402 patients in four centers. Hemodynamic variables were recorded before and after VE. Response to VE was defined as more than 15% increase in CO. The ability of VE-induced changes in arterial pressure to detect changes in CO was assessed using a gray zone approach. RESULTS: VE increased CO of more than 15% in 205 patients (51%). Areas under the receiver operating characteristic curves for VE-induced changes in systolic, diastolic, means, and pulse pressure ranged between 0.64 and 0.70, and sensitivity and specificity ranged between 52 and 79%. For these four arterial pressure-derived parameters, large gray zones were found, and more than 60% of the patients lay within this inconclusive zone. A VE-induced decrease in pulse pressure variation of 3% or more allowed detecting a fluid-induced increase in CO of more than 15% with a sensitivity of 90% and a specificity of 77% and a gray zone between 2.2 and 4.7% decrease in pulse pressure variation including 14% of the patients. CONCLUSION: Only changes in pulse pressure variation accurately detect VE-induced changes in CO and have a potential clinical applicability.

Obese trauma patients are at increased risk of early hypovolemic shock: a retrospective cohort analysis of 1,084 severely injured patients.

INTRODUCTION: Morbid obesity and its consequences are considered risk factors for adverse outcome in trauma, although the pathophysiologic mechanisms are incompletely understood. The aim of this study was to compare initial resuscitation, treatment, and short-term outcome of severely injured patients by body mass index (BMI). METHODS: A total of 1,084 severely injured patients with an injury severity score of 16 or greater were enrolled between 1996 and 2009 and grouped according to BMI. Their course of treatment and in-hospital outcome were analyzed by univariate and multivariate comparison. RESULTS: Of these patients, 603 (55.6%) were of normal weight with a BMI between 18.5 and 24.9, 361 (33.3%) had BMI values between 25 and 29.9, and 90 patients (8.3%) were obese (BMI ≥ 30). Thirty patients (2.8%) had BMI levels below 18.5. All groups were comparable with respect to injury severity, initial resuscitation, and time to ICU admission. There was a tendency towards higher mortality in obese patients (mortality 24.4%) and also overweight patients (mortality 18.8%) when compared with patients with a normal BMI (mortality 16.6%). Obese patients showed the highest mortality on day 0 (8.9% vs. 2.8% in the normal-weight group, P = 0.023), mostly due to persistent shock (6.7%). When corrected for BMI, obese patients are provided significantly lower volumes of intravenous fluids during the initial resuscitation period. CONCLUSION: In contrast to the mostly American literature, only a low percentage of trauma patients at a European trauma center are obese. These patients are at risk of higher mortality from persistent hemorrhagic shock in the initial phase after trauma, which may potentially be related to relative hypovolemia during the resuscitation period. In the later course of treatment, no significant differences exist with respect to specific complications, hospital stay, or in-hospital mortality.

Clinical validation of a new thermodilution system for the assessment of cardiac output and volumetric parameters.

INTRODUCTION: Transpulmonary thermodilution is used to measure cardiac output (CO), global end-diastolic volume (GEDV) and extravascular lung water (EVLW). A system has been introduced (VolumeView/EV1000™ system, Edwards Lifesciences, Irvine CA, USA) that employs a novel algorithm for the mathematical analysis of the thermodilution curve. Our aim was to evaluate the agreement of this method with the established PiCCO™ method (Pulsion Medical Systems SE, Munich, Germany, clinicaltrials.gov identifier: NCT01405040) METHODS: Seventy-two critically ill patients with clinical indication for advanced hemodynamic monitoring were included in this prospective, multicenter, observational study. During a 72-hour observation period, 443 sets of thermodilution measurements were performed with the new system. These measurements were electronically recorded, converted into an analog resistance signal and then re-analyzed by a PiCCO2™ device (Pulsion Medical Systems SE). RESULTS: For CO, GEDV, and EVLW, the systems showed a high correlation (r(2) = 0.981, 0.926 and 0.971, respectively), minimal bias (0.2 L/minute, 29.4 ml and 36.8 ml), and a low percentage error (9.7%, 11.5% and 12.2%). Changes in CO, GEDV and EVLW were tracked with a high concordance between the two systems, with a traditional concordance for CO, GEDV, and EVLW of 98.5%, 95.1%, and 97.7% and a polar plot concordance of 100%, 99.8% and 99.8% for CO, GEDV, and EVLW, respectively. Radial limits of agreement for CO, GEDV and EVLW were 0.31 ml/minute, 81 ml and 40 ml, respectively. The precision of GEDV measurements was significantly better using the VolumeView™ algorithm compared to the PiCCO™ algorithm (0.033 (0.03) versus 0.040 (0.03; median (interquartile range), P = 0.000049). CONCLUSIONS: For CO, GEDV, and EVLW, the agreement of both the individual measurements as well as measurements of change showed the interchangeability of the two methods. For the VolumeView method, the higher precision may indicate a more robust GEDV algorithm. TRIAL REGISTRATION: clinicaltrials.gov NCT01405040.

[New aspects of minimally invasive cardiac output monitoring]. / Hämodynamisches Monitoring - Neue Aspekte des minimalinvasiven Herzzeitvolumen-Monitorings.

The variety of minimally invasive cardiac output (CO) monitoring devices is growing rendering it difficult to keep track of new developments. In this article technical principles, limitations and validation procedures considering new aspects are reviewed. An integrated approach for their use is proposed since no single device can comply with all clinical needs. CO should be interpreted in combination with clinical information and other hemodynamic parameters. It's evident that not the monitor per se, but only the protocol / therapy based on the hemodynamic data can improve patients outcome.

Aligned Stacking of Nanopatterned 2D Materials for High-Resolution 3D Device Fabrication.

Two-dimensional materials can be combined by placing individual layers on top of each other, so that they are bound only by their van der Waals interaction. The sequence of layers can be chosen arbitrarily, enabling an essentially atomic-level control of the material and thereby a wide choice of properties along one dimension. However, simultaneous control over the structure in the in-plane directions is so far still rather limited. Here, we combine spatially controlled modifications of 2D materials, using focused electron irradiation or electron beam induced etching, with the layer-by-layer assembly of van der Waals heterostructures. The presented assembly process makes it possible to structure each layer with an arbitrary pattern prior to the assembly into the heterostructure. Moreover, it enables a stacking of the layers with accurate lateral alignment, with an accuracy of currently 10 nm, under observation in an electron microscope. Together, this enables the fabrication of almost arbitrary 3D structures with highest spatial resolution.