Regional lung derecruitment after endotracheal suction during volume- or pressure-controlled ventilation: a study using electric impedance tomography

Objective

To assess lung volume and compliance changes during open- and closed-system suctioning using electric impedance tomography (EIT) during volume- or pressure-controlled ventilation.

Design and setting

Experimental study in a university research laboratory.

Subjects

Nine bronchoalveolar saline-lavaged pigs.

Interventions

Open and closed suctioning using a 14-F catheter in volume- or pressure-controlled ventilation at tidal volume 10?ml/kg, respiratory rate 20?breaths/min, and positive end-expiratory pressure 10?cmH₂O.

Measurements and results

Lung volume was monitored by EIT and a modified N₂ washout/-in technique. Airway pressure was measured via a pressure line in the endotracheal tube. In four ventral-to-dorsal regions of interest regional ventilation and compliance were calculated at baseline and 30?s and 1, 2, and 10?min after suctioning. Blood gases were followed. At disconnection functional residual capacity (FRC) decreased by 58?±?24% of baseline and by a further 22?±?10% during open suctioning. Arterial oxygen tension decreased to 59?±?14% of baseline value 1?min after open suctioning. Regional compliance deteriorated most in the dorsal parts of the lung. Restitution of lung volume and compliance was significantly slower during pressure-controlled than volume-controlled ventilation.

Conclusions

EIT can be used to monitor rapid lung volume changes. The two dorsal regions of the lavaged lungs are most affected by disconnection and suctioning with marked decreases in compliance. Volume-controlled ventilation can be used to rapidly restitute lung aeration and oxygenation after lung collapse induced by open suctioning.

     

Prone equals prone? Impact of positioning techniques on respiratory function in anesthetized and paralyzed healthy children

Objectives

Although the prone position is effectively used to improve oxygenation, its impact on functional residual capacity is controversial. Different techniques of body positioning might be an important confounding factor. The aim of this study was to determine the impact of two different prone positioning techniques on functional residual capacity and ventilation distribution in anesthetized, preschool-aged children.

Design

Functional residual capacity and lung clearance index, a measure of ventilation homogeneity, were calculated using a sulfur-hexafluoride multibreath washout technique. After intubation, measurements were taken in the supine position and, in random order, in the flat prone position and the augmented prone position (gel pads supporting the pelvis and the upper thorax).

Setting

Pediatric anesthesia unit of university hospital.

Patients and participants

Thirty preschool children without cardiopulmonary disease undergoing elective surgery.

Measurements and results

Mean (range) age was 48.5 (24–80) months, weight 17.2 (10.5–26.9)?kg, functional residual capacity (mean ±?SD) 22.9?±?6.2?ml.kg ^?1 in the supine position and 23.3?±?5.6?ml.kg ^?1 in the flat prone position, while lung clearance indices were 8.1?±?2.3 vs. 7.9?±?2.3, respectively. In contrast, functional residual capacity increased to 27.6 ± 6.5 ml.kg ^?1 (pp

Conclusions

Functional residual capacity and ventilation distribution were similar in the supine and flat prone positions, while these parameters improved significantly in the augmented prone position, suggesting that the technique of prone positioning has major implications for pulmonary function.

     

Imaging in acute respiratory distress syndrome

Purpose

Imaging has become increasingly important across medical specialties for diagnostic, monitoring, and investigative purposes in acute respiratory distress syndrome (ARDS).

Methods

This review addresses the use of imaging techniques for the diagnosis and management of ARDS as well as gaining knowledge about its pathogenesis and pathophysiology. The techniques described in this article are computed tomography, positron emission tomography, and two easily accessible imaging techniques available at the bedside—ultrasound and electrical impedance tomography (EIT).

Results

The use of computed tomography has provided new insights into ARDS pathophysiology, demonstrating that ARDS does not homogeneously affect the lung parenchyma and that lung injury severity is widely distributed in the ARDS population. Positron emission tomography is a functional imaging technique whose value resides in adding incremental insights to morphological imaging. It can quantify regional perfusion, ventilation, aeration, lung vascular permeability, edema, and inflammation. Lung ultrasound and EIT are radiation-free, noninvasive tools available at the bedside. Lung ultrasound can provide useful information on ARDS diagnosis when x-rays or CT scan are not available. EIT is a useful tool to monitor lung ventilation and to assess the regional distribution of perfusion.

Conclusions

The future of imaging in critical care will probably develop in two main directions: easily accessible imaging techniques that can be used at the bedside and sophisticated imaging methods that will be used to aid in difficult diagnostic cases or to advance our understanding of the pathogenesis and pathophysiology of an array of critical illnesses.

     

Nasal continuous positive airway pressure decreases respiratory muscles overload in young infants with severe acute viral bronchiolitis

Objective

To determine the efficacy of nasal continuous positive airway pressure (nCPAP) on respiratory distress symptoms and respiratory effort in young infants with acute respiratory syncytial virus bronchiolitis.

Design

Prospective study.

Setting

The paediatric intensive care unit of a university hospital.

Patients

Twelve infants less than 3 months of age, with severe respiratory distress.

Interventions

Respiratory distress was quantified with a specific scoring system. Oesophageal pressure (Pes) was measured during spontaneous ventilation before and after nCPAP, delivered through an infant-adapted ventilator. Simultaneous recording of gastric pressure (Pgas) was performed in the five oldest patients.

Measurements and results

The respiratory distress score decreased after nCPAP, particularly accessory muscles’ use and expiratory wheezing. The breathing pattern was modified, with shorter inspiratory and longer expiratory time. Pes swings and PTPes_insp, two indices of inspiratory effort, were reduced by 54 (±4)% and 59 (±5)%. PTPgas_exp, an indicator of expiratory muscles activity, was completely abolished. A significant correlation was observed between the respiratory distress score and Pes swings at baseline and after nCPAP.

Conclusions

In young infants with severe acute respiratory syncytial virus bronchiolitis, nCPAP rapidly unloads respiratory muscles and improves respiratory distress symptoms.

     

Determination of functional residual capacity by oxygen washin-washout: a validation study

Objective

To validate a new system for functional residual capacity (FRC) measurements using oxygen washin/washout in spontaneously breathing humans. The system (LUFU, Drägerwerk AG, Lübeck, Germany) consists of an unmodified EVITA 4 ventilator, a side-stream paramagnetic oxygen sensor and a dedicated software.

Design

Laboratory study and measurements in spontaneously breathing volunteers.

Setting

Pulmonary function laboratory of a university hospital.

Participants

20 healthy and 15 lung diseased volunteers.

Interventions

FRC was measured by LUFU (LUFU-FRC) and by helium dilution (He-FRC); intra-thoracic gas volume (ITGV) was determined by body plethysmography. Each measurement cycle consisted of four independent LUFU-FRC determinations (step change of FiO₂ from 0.21 to 0.5 and back and from 0.21 to 1.0 and back), two helium-dilution runs and two body box measurements. Repeatability and agreement between methods were determined by comparing different measurements of one technique and by comparing different techniques among each other.

Measurements and results

Repeatability of LUFU-FRC was estimated by comparing washin to washout and the different FiO₂steps. The difference of the means was 3.7% at the most. Agreement between methods resulted in the following differences (mean?±?standard deviation of differences) for healthy and lung-diseased volunteers, respectively: LUFU-FRC vs. He-FRC –0.40?±?0.50?L (0.02?±?0.95?L), LUFU-FRC vs. ITGV –0.43?±?0.54?L (–0.18?±?0.61?L) and He-FRC vs. ITGV –0.03?±?0.43?L (–0.20?±?0.98?L).

Conclusions

LUFU is a non-invasive method for the determination of FRC that requires only minor additional equipment and no modification to the ventilator. It can be used in difficult conditions such as breathing patterns with variations from breath to breath. The results of this study show that LUFU is sufficiently reliable and repeatable to warrant its clinical application.

     

Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study

Objective

To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.

Design and setting

Prospective crossover interventional study in an intensive care unit of a university hospital.

Patients

Twenty patients.

Interventions

After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.

Measurements and results

During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO₂ decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.

Conclusions

The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.

     

Pooled Aquablation Results for American Men with Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia in Large Prostates (60–150 cc)

Introduction

To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.

Methods

Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).

Results

One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Q_max increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.

Conclusion

Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.

Trial Registration

ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.

Funding

PROCEPT BioRobotics.

     

Terbutaline lessens protein fluxes across the alveolo-capillary barrier during high-volume ventilation

Objective

To evaluate whether a β₂-adrenergic agonist may reduce acute alveolo-capillary barrier alterations during high-volume ventilation.

Design

Experimental study.

Setting

Animal research laboratory.

Subjects

A total of 48 male Wistar rats.

Interventions

A zone of alveolar flooding was produced by liquid instillation in a distal airway. Proteins in the instilled solution were traced with ^99mTc-albumin. ¹¹¹In, which binds to transferrin, was injected into the systemic circulation. Terbutaline was administered in the instilled solution or intra-peritoneally. Conventional ventilation was applied for 30?min followed by different ventilation strategies for 90?min: conventional ventilation, high-volume ventilation with or without 6?cmH₂O PEEP.

Measurements and main results

Protein fluxes across the alveolar and microvascular barriers were evaluated by scintigraphy. High-volume ventilation resulted in immediate leakage of ^99mTc-albumin from alveolar spaces and increased pulmonary uptake of systemic ¹¹¹In-transferrin. Terbutaline in the instilled solution and PEEP lessened alveolar ^99mTc-albumin leakage and pulmonary ¹¹¹In-transferrin uptake due to high-volume ventilation, whereas terbutaline given intra-peritoneally only lessened ¹¹¹In-transferrin uptake. Terbutaline in the instilled solution also lessened the increase in lung wet-to-dry weight ratio due to high-volume ventilation.

Conclusions

Terbutaline reduces protein fluxes across the alveolar epithelial and pulmonary microvascular barriers during high-volume ventilation in vivo. The route of administration may be important.

     

Outcomes Following Implantation of Two Second-Generation Trabecular Micro-Bypass Stents in Patients with Open-Angle Glaucoma on One Medication: 18-Month Follow-Up

Introduction

The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication.

Methods

Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18–30 mmHg, and preoperative unmedicated (post-washout) IOP of 22–38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing.

Results

At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed.

Conclusion

In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety.

Trial Registration

ClinicalTrials.gov identifier, NCT02868190.

Funding

Glaukos Corporation, San Clemente, CA.

     

Biodistribution Study of Intravenously Injected Cetuximab-IRDye700DX in Cynomolgus Macaques

Purpose

The use of receptor-targeted antibodies conjugated to photosensitizers is actively being explored to enhance treatment efficacy. To facilitate clinical testing, we evaluated cetuximab conjugated to IRDye700DX (IR700) in cynomolgus macaques.

Procedures

Total IR700 and intact cetuximab-IR700 were measured in 51 tissues at 2 and 14 days after intravenous injection of 40 and 80 mg/kg cetuximab-IR700, respectively, and compared with an unlabeled cetuximab-dosed control group (two each per sex per time point per group).

Results

The IR700 retrieved from all tissues at 2 and 14 days after dosing was estimated at 34.9?±?1.8 and 2.53?±?0.67 % of the total dose, respectively. The tissues with the highest levels of intact cetuximab-IR700 at 2 days after dosing were the blood, lung, and skin. Formalin-fixed paraffin-embedded tissue sections at 2 days after dosing showed the highest IR700 signals in the axillary lymph node, mammary gland, and gall bladder.

Conclusions

Both IR700 and intact cetuximab-IR700 biodistributions were consistent with known epidermal growth factor receptor (EGFR) expression, and changes between 2 and 14 days were consistent with rapid metabolism and excretion of the cetuximab-IR700.

     

Combination of texture and shape features to detect pulmonary abnormalities in digital chest X-rays

Purpose

To improve detection of pulmonary and pleural abnormalities caused by pneumonia or tuberculosis (TB) in digital chest X-rays (CXRs).

Methods

A method was developed and tested by combining shape and texture features to classify CXRs into two categories: TB and non-TB cases. Based on observation that radiologist interpretation is typically comparative: between left and right lung fields, the algorithm uses shape features to describe the overall geometrical characteristics of the lung fields and texture features to represent image characteristics inside them.

Results

Our algorithm was evaluated on two different datasets containing tuberculosis and pneumonia cases.

Conclusions

Using our proposed algorithm, we were able to increase the overall performance, measured as area under the (ROC) curve (AUC) by 2.4 % over our previous work.

     

Lack of agreement between thermodilution and electrical velocimetry cardiac output measurements

Objective

The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance—electrical velocimetry (EV^®)—has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV^®-CO measurements reflect intraindividual changes in CO during cardiac surgery.

Design

Prospective, observational study.

Setting

Operating room (OR) and intensive care unit (ICU) of a university hospital.

Patients

Twenty-nine patients undergoing elective cardiac surgery.

Interventions

None.

Measurements

CO was determined simultaneously by PA-TD and EV^® after induction of anesthesia (t1) and 4.9?±?3.5?h after ICU admission (t2).

Results

TD-CO was 3.9?±?1.4 and 5.4?±?1.1 l/min at t1 and t2 (?p?®-CO was 4.3?±?1.1 and 4.9?±?1.5 l/min at t1 and t2 (?p?=?0.013). Bland–Altman analysis showed a bias of ?0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n?=?12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n?=?9 and n?=?8 patients, respectively.

Conclusions

The disagreement between PA-TD and EV^®-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV^®-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.

     

Effet des extraits de quelques plantes sur les bactéries pathogènes responsables de gastroentérites

Background

Phytochemicals are natural bioactive compounds that protect plants against the stress. These phytochemicals may also have other biological activities like, antibacterial activity.

Objective

The objective of this work is to study the antibacterial effect of aqueous and hydro-alcoholic extracts prepared from Thymus vulgaris, Aloysia triphylla, Pistacia lentiscus, Olea europaea leaves and Trigonella foenum-graecum seeds on some pathogenic bacteria responsible for gastroenteritis.

Result

The results obtained from the antibacterial effect showed a moderate activity against the strains studied with a diameters of inhibition zones ranging from 07.00 ± 0.8 to 16.00 ± 1.0 mm for aqueous extracts and vary between 07.00 ± 0.9 and 13.00 ± 1.0 mm for hydro-alcoholic extracts.

Conclusion

This study confirms the possibility of using these plants or components in the prevention of several diseases like, gastroenteritis.

     

Baseline [<Superscript>18</Superscript>F]FMISO μPET as a Predictive Biomarker for Response to HIF-1α Inhibition Combined with 5-FU Chemotherapy in a Human Colorectal Cancer Xenograft Model

Purpose

The purpose of this study was to characterize imaging biomarkers for the potential benefit of hypoxia-inducible factor-1 (HIF-1)α inhibition (by PX-12) during 5-fluorouracil (5-FU) chemotherapy in the treatment of colorectal cancer (CRC).

Procedures

Therapy response to 5-FU?±?PX-12 was assessed with baseline [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) and longitudinal 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) positron emission computed tomography (μPET/CT) in CRC xenograft model (n?=?36) during breathing of a hypoxic (10 % O₂) or normoxic (21 % O₂) atmosphere. Ex vivo, immunohistochemistry was performed.

Results

Baseline [¹⁸F]FMISO uptake and relative tumor volume (RTV) 2 days after 5-FU or 5-FU?+?PX-12 administration correlated significantly (p?≤?0.01). Under hypoxic breathing conditions, [¹⁸F]FDG uptake (?53.1?±?8.4 %) and Ki67 expression (?16 %) decreased and RTV stagnated in the 5-FU?+?PX-12 treatment group, but not in 5-FU alone-treated tumors. Under normoxic breathing, [¹⁸F]FDG uptake (?23.5?±?15.2 % and ?72.8?±?7.1 %) and Ki67 expression (?5 % and ?19 %) decreased and RTV stagnated in both the 5-FU and the combination treatment group, respectively.

Conclusion

Baseline [¹⁸F]FMISO μPET may predict the beneficial effect of HIF-1α inhibition during 5-FU chemotherapy in CRC.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

Purpose

The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer.

Procedures

CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated in a xenograft breast cancer mouse model using ductal carcinoma in situ cells (DCIS).

Results

Specific anti-CAIX nanobodies were obtained. Administration of a CAIX-specific nanobody into mice with DCIS xenografts overexpressing CAIX showed after 2 h a mean tumor-to-normal tissue ratio (TNR) of 4.3?±?0.6, compared to a TNR of 1.4?±?0.2 in mice injected with the negative control nanobody R2-IR. In DCIS mice, a TNR of 1.8?±?0.1 was obtained. Biodistribution studies demonstrated an uptake of 14.0?±?1.1 %I.D./g in DCIS?+?CAIX tumors, 4.6?±?0.8 %I.D./g in DCIS tumors, while 2.0?±?0.2 %I.D./g was obtained with R2-IR.

Conclusions

These results demonstrate the successful generation of a CAIX-specific nanobody-IRDye800CW conjugate that can be used for rapid imaging of (pre-)invasive breast cancer.

     

The Effectiveness of Trimetazidine Treatment in Patients with Stable Angina Pectoris of Various Durations: Results from the CHOICE-2 Study

Introduction

Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease.

Methods

CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina.

Results

A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration.

Conclusion

TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life.

Funding

Servier.

Trial Registration

ISRCTN identifier ISRCTN65209863.

Plain Language Summary

Plain language summary available for this article.

     

Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

Purpose

During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.

Procedures

Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.

Results

The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30 % of mice with positive margins. Molecular imaging identified an additional 50 % of residual tumor deposits (p?<?0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.

Conclusions

Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

     

Lung ultrasonography for assessment of oxygenation response to prone position ventilation in ARDS

Purpose

Prone position (PP) improves oxygenation and outcome of acute respiratory distress syndrome (ARDS) patients with a PaO₂/FiO₂ ratio <150 mmHg. Regional changes in lung aeration can be assessed by lung ultrasound (LUS). Our aim was to predict the magnitude of oxygenation response after PP using bedside LUS.

Methods

We conducted a prospective multicenter study that included adult patients with severe and moderate ARDS. LUS data were collected at four time points: 1 h before (baseline) and 1 h after turning the patient to PP, 1 h before and 1 h after turning the patient back to the supine position. Regional lung aeration changes and ultrasound reaeration scores were assessed at each time. Overdistension was not assessed.

Results

Fifty-one patients were included. Oxygenation response after PP was not correlated with a specific LUS pattern. The patients with focal and non-focal ARDS showed no difference in global reaeration score. With regard to the entire PP session, the patients with non-focal ARDS had an improved aeration gain in the anterior areas. Oxygenation response was not associated with aeration changes. No difference in PaCO₂ change was found according to oxygenation response or lung morphology.

Conclusions

In ARDS patients with a PaO₂/FiO₂ ratio ≤150 mmHg, bedside LUS cannot predict oxygenation response after the first PP session. At the bedside, LUS enables monitoring of aeration changes during PP.

     

Incidence,treatment, and outcome of severe sepsis in ICU-treated adults in Finland: the Finnsepsis study

Objective

To determine the incidence and outcome of severe sepsis in the adult Finnish population and to evaluate how treatment guidelines in severe sepsis are applied in clinical practice.

Study design

A prospective study in 24 closed multidisciplinary ICUs in 21 hospitals (4 university and 17 tertiary hospitals) in Finland.

Patients

All 4,500 consecutive ICU admission episodes were screened for severe sepsis during a 4-month period (1 November 2004 – 28 February 2005). The referral population was 3,743,225.

Results

The severe sepsis criteria were fulfilled in 470 patients, who had472 septic episodes. The incidence of severe sepsis in the ICUs in Finland was 0.38/1000 in the adult population (95% confidence interval 0.34–0.41). The mean ICU length of stay was 8.2?±?8.1?days. ICU, hospital, and 1-year mortality rates were 15.5%, 28.3%, and 40.9%, respectively. Respiratory failure requiring ventilation support was the most common organ failure (86.2%); septic shock was present in 77% and acute renal failure in 20.6% of cases. Activated protein C was given to only 15 of the 55 patients with indication (27%) and low-dose corticosteroids to 150 of 366 (41%) patients with septic shock.

Conclusions

This prospective study found the incidence of ICU-treated severe sepsis in Finland to be 0.38 per 1,000 of the population. The ICU and hospital mortalities were also lower than earlier reported in United States or Australia. Evidence-based sepsis therapies were not used as often as recommended.