Characteristics and patient-reported outcomes of long-term lung cancer survivors.

Background: Due to advances in screening and treatment of lung cancer, there has been increased interest in long-term lung cancer survivors (LTLCS). The aim of this study was to evaluate the prevalence of LTLCS, their characteristics and patient-reported outcomes (PROs) of LTLCS. Methods: Cross-sectional study that included patients diagnosed with primary lung cancer between Jan 2012 and Dec 2016 whose overall survival (OS) was greater than 5 years. A self-administered questionnaire was applied, including European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30), Patient Health Questionnaire-4 (PHQ-4) and two open questions regarding quality of life (QoL) and suggestions for improvements. Factors potentially related to QoL were analysed. Results: Of 767 lung cancer patients, 158 (20.6%) were LTLCS and LTLCS' proportion increased yearly. Most patients were male (70.9%) with median age of 65 [interquartile range (IQR), 56-71] years. Fifty-seven percent had adenocarcinoma, 66.2% were diagnosed at early stages but 8.9% were at stage IV. During follow-up, 77.1% quitted smoking, 31.8% had disease progression/relapse and 15.2% developed other tumours. Of all living LTLCS, 100 (85%) patients answered the PROs questionnaire. The median Global Health score was 66.67 (IQR, 50-83), social functioning had the best score and emotional functioning the worst. Pain and fatigue were the symptoms with the worst impact on QoL. PHQ-4 identified mental distress in 36% and patients with a lower QoL were more likely to present anxiety (35.3% vs. 9.4%, P=0.007) or depression (27.9% vs. 3%, P=0.006). In the open questions, patients reported pain (17%), lack of familiar/financial support (16%), dyspnoea (14%), depression (8%), concern for the future (8%) and limitations performing daily activities (8%) as the aspects with most impact in QoL. The most suggested measures were improvement of care provided by health institutions (25%) and better social support (16%). Conclusions: Prevalence of LTLCS is increasing and survivors may experience a high prevalence of anxiety and depression as well as a high disease burden affecting QoL. Therefore, it's important to provide multidisciplinary continuous patient-centred care and a careful follow-up for all lung cancer patients, including LTLCS.

Dexmedetomidine compared to low-dose ketamine better protected not only the brain but also the lungs in acute ischemic stroke.

BACKGROUND: Dexmedetomidine (DEX) and low-dose ketamine (KET) present neuroprotective effects in acute ischemic stroke (AIS); however, to date, no studies have evaluated which has better protective effects not only on the brain but also lungs in AIS. METHODS: AIS-induced Wistar rats (390 ± 30 g) were randomized after 24-h, receiving dexmedetomidine (STROKE-DEX, n = 10) or low-dose S(+)-ketamine (STROKE-KET, n = 10). After 1-h protective ventilation, perilesional brain tissue and lungs were removed for histologic and molecular biology analysis. STROKE animals (n = 5), receiving sodium thiopental but not ventilated, had brain and lungs removed for molecular biology analysis. Effects of DEX and KET mean plasma concentrations on alveolar macrophages, neutrophils, and lung endothelial cells, extracted primarily 24-h after AIS, were evaluated. RESULTS: In perilesional brain tissue, apoptosis did not differ between groups. In STROKE-DEX, compared to STROKE-KET, tumor necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1) expressions were reduced, but no changes in nuclear factor erythroid 2-related factor-2 (Nrf2) and super oxide dismutase (SOD)-1 were observed. In lungs, TNF-α and VCAM-1 were reduced, whereas Nrf2 and SOD-1 were increased in STROKE-DEX. In alveolar macrophages, TNF-α and inducible nitric oxide synthase (M1 macrophage phenotype) were lower and arginase and transforming growth factor-ß (M2 macrophage phenotype) higher in STROKE-DEX. In lung neutrophils, CXC chemokine receptors (CXCR2 and CXCR4) were higher in STROKE-DEX. In lung endothelial cells, E-selectin and VCAM-1 were lower in STROKE-DEX. CONCLUSIONS: In the current AIS model, dexmedetomidine compared to low-dose ketamine reduced inflammation and endothelial cell damage in both brain and lung, suggesting greater protection.

Clinical Approaches to Nestorone Subdermal Implant Therapy in Women's Health.

Segesterone acetate (SA) or Nestorone, a fourth-generation progestogen, is a synthetic compound with high progestational activity and no androgenic, glucocorticoid, or anabolic effects. However, due to its oral inactivity, SA must be used by other routes, such as subcutaneous. Thus, considering its peculiar properties, the SA subdermal implant is successfully used in female contraception and postmenopausal hormone replacement therapy (HRT). In recent years, its potential uses in endometriosis, polycystic ovaries syndrome (PCOS), and a new therapeutic possibility for neuroprotection have made this treatment extremely interesting. However, the absence of a standardized dose and the long-term safety of SA implant therapy in women is still controversial. Here, we present the possible indications, doses, limitations, and side effects of SA implant therapy.

Extracellular Vesicles from Different Sources of Mesenchymal Stromal Cells Have Distinct Effects on Lung and Distal Organs in Experimental Sepsis.

The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 106 MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome.

Development of nintedanib nanosuspension for inhaled treatment of experimental silicosis.

Silicosis is an irreversible and progressive fibrotic lung disease caused by massive inhalation of crystalline silica dust at workplaces, affecting millions of industrial workers worldwide. A tyrosine kinase inhibitor, nintedanib (NTB), has emerged as a potential silicosis treatment due to its inhibitory effects on key signaling pathways that promote silica-induced pulmonary fibrosis. However, chronic and frequent use of the oral NTB formulation clinically approved for treating other fibrotic lung diseases often results in significant side effects. To this end, we engineered a nanocrystal-based suspension formulation of NTB (NTB-NS) possessing specific physicochemical properties to enhance drug retention in the lung for localized treatment of silicosis via inhalation. Our NTB-NS formulation was prepared using a wet-milling procedure in presence of Pluronic F127 to endow the formulation with nonadhesive surface coatings to minimize interactions with therapy-inactivating delivery barriers in the lung. We found that NTB-NS, following intratracheal administration, provided robust anti-fibrotic effects and mechanical lung function recovery in a mouse model of silicosis, whereas a 100-fold greater oral NTB dose given with a triple dosing frequency failed to do so. Importantly, several key pathological phenotypes were fully normalized by NTB-NS without displaying notable local or systemic adverse effects. Overall, NTB-NS may open a new avenue for localized treatment of silicosis and potentially other fibrotic lung diseases.

Incidental giant thymoma-a reminder of the importance of a global look of the imaging scans.

A 49-year-old female patient, without previous medical history, underwent a thoracic CT due to SARS-CoV2 infection. This exam revealed a heterogeneous mass in the anterior mediastinum with 11 × 8.8 cm in close contact with main thoracic vessels and pericardium. Surgical biopsy documented a B2 thymoma. This clinical case reminds the importance of a systematic and global look of the imaging scans. Years before the thymoma diagnosis, the patient underwent a shoulder X-ray due to musculoskeletal pain, where an irregular shape of the aortic arch was visible, probably related to the growing mediastinal mass. An earlier diagnosis would allow a complete mass resection without such extensive surgery and less morbidity.

Male reproductive system of the freshwater prawn Macrobrachium brasiliense (Decapoda: Palaemonidae): Notes on spermatophore formation and sperm count.

Studies on the morphology of the reproductive system are essential for understanding the reproduction processes of species or even within genera or families. The present study aimed to describe the functional morphology of the male reproductive system, spermatophore formation, and sperm count of Macrobrachium brasiliense. The anatomy of the reproductive system consists of a pair of testes from which the vasa deferentia (VD) starts, extending to the fifth pair of pereopods. The VD is divided into three regions: proximal (PVD), middle (MVD), and distal (DVD). In the PVD, there is a prominent fold, the typhlosole, formed by columnar cells. The typhlosole disappears in the MVD, being incorporated into one of the faces of the VD wall, identified by its simple columnar epithelium while the remainder of the vessel wall is formed by squamous or simple cubic epithelium. Columnar cells produce type-II and III secretion. The epithelium in the DVD is made up only of cubic cells. Low sperm concentration was observed when compared to other species of the genus Macrobrachium. In conclusion, the typhlosole and columnar epithelium are responsible for the asymmetric spermatophore, which seems the pattern of Macrobrachium that is probably shared with other caridean shrimps.

Innovative 3d-Printed Prosthesis In A Rare Case Of A Huge Mass Of Anterior Thoracic Wall - Low Grade Fibromyxoid Sarcoma (Lgfms).

The need for complete resection of chest wall tumors creates a huge challenge in terms of reconstructing the complex dynamics of the thorax. We are reporting a case of a low-grade fibromyxoid sarcoma (LGFMS) diagnosed in a young male, where the complete resection of the mass, sternum and parcially the pericardium was performed. Subsequently, a composite porous high-density polyethylene StarPore® prosthesis of the sternum and costal arches was used and the latissimus dorsi muscle free flap with skin graft was implanted over the sternum.

An Unusual Location for a Lymph Node.

We report a case of a 67-years old non-smoking female diagnosed with hypertension when 24-years-old and complicated with chronic kidney and hypertensive heart diseases. On CT-Chest an incidental discovery of a lesion (16x14x23mm) adjacent to the abdominal aorta was made. Initially suspected to be paraganglioma, a hypothesis which the subsequent MRI did not exclude. Urine analysis showed normal Metanephrine with slightly elevated Chromogranin-A levels. During VATs-procedure "bulging" below the adventitial layer of the descending aorta at the level of the diaphragmatic gutter was identified. By opening the adventitia, a lipomatous lesion with a nodular, consistent center was identified and excised. Final histopathological report confirmed the diagnosis of lymph node not suggestive of neoplasia. Currently, 12 months after the surgery, the patient's condition is good being under surveillance in the Thoracosurgical Outpatient Clinic. Despite not having identified any neuroendocrine component, the patient had clinical signs of clear improvement of arterial hypertension.

Mild hypothermia combined with dexmedetomidine reduced brain, lung, and kidney damage in experimental acute focal ischemic stroke.

BACKGROUND: Sedatives and mild hypothermia alone may yield neuroprotective effects in acute ischemic stroke (AIS). However, the impact of this combination is still under investigation. We compared the effects of the combination of mild hypothermia or normothermia with propofol or dexmedetomidine on brain, lung, and kidney in experimental AIS. AIS-induced Wistar rats (n = 30) were randomly assigned, after 24 h, to normothermia or mild hypothermia (32-35 °C) with propofol or dexmedetomidine. Histologic injury score and molecular biomarkers were evaluated not only in brain, but also in lung and kidney. Hemodynamics, ventilatory parameters, and carotid Doppler ultrasonography were analyzed for 60 min. RESULTS: In brain: (1) hypothermia compared to normothermia, regardless of sedative, decreased tumor necrosis factor (TNF)-α expression and histologic injury score; (2) normothermia + dexmedetomidine reduced TNF-α and histologic injury score compared to normothermia + propofol; (3) hypothermia + dexmedetomidine increased zonula occludens-1 expression compared to normothermia + dexmedetomidine. In lungs: (1) hypothermia + propofol compared to normothermia + propofol reduced TNF-α and histologic injury score; (2) hypothermia + dexmedetomidine compared to normothermia + dexmedetomidine reduced histologic injury score. In kidneys: (1) hypothermia + dexmedetomidine compared to normothermia + dexmedetomidine decreased syndecan expression and histologic injury score; (2) hypothermia + dexmedetomidine compared to hypothermia + propofol decreased histologic injury score. CONCLUSIONS: In experimental AIS, the combination of mild hypothermia with dexmedetomidine reduced brain, lung, and kidney damage.

Ontogenetic niche specialization of the spider crab Libinia ferreirae associated with the medusa Lychnorhiza lucerna.

Symbiotic relationships in marine environments are not fixed and can change throughout the animal's life. This study investigated the ontogeny of symbiosis of the spider crab Libinia ferreirae with the host medusa Lychnorhiza lucerna. We described the type of relationship, the temporal correlation among species, and food habits. More than 50% of the sampled crabs were symbionts, most in early life stages. The highest number of crabs found in a single medusa was 11. Symbiosis was observed throughout most of the year but was more evident in warm periods. The crab has many benefits in this relationship with a medusa. One is the use of food resources captured by the medusa, primarily copepods. Because the crab steals the medusa's food, it is a kleptoparasitic relationship. There is a niche partition between symbiont and the free-living crabs as they occupy different habitats and use nonoverlapping food resources. Previous research reported that symbiosis first developed during the crab's last larval phase (megalopa) when crab and medusa are in the same habitat. Observation of the crab's behavior shows that symbiosis occurs when the crab can grab to the medusa when the host touches the sea bottom. The crab also took advantage of water currents, releasing itself from the substrate and then drifting toward the medusa. The symbiotic relationship that crabs have with the medusa provides then with a nursery, food resources, shelter, dispersion, and decreased competition with free-living adult crabs, all essential for the crab's survival.

Effects of different fluid management on lung and kidney during pressure-controlled and pressure-support ventilation in experimental acute lung injury.

Optimal fluid management is critical during mechanical ventilation to mitigate lung damage. Under normovolemia and protective ventilation, pulmonary tensile stress during pressure-support ventilation (PSV) results in comparable lung protection to compressive stress during pressure-controlled ventilation (PCV) in experimental acute lung injury (ALI). It is not yet known whether tensile stress can lead to comparable protection to compressive stress in ALI under a liberal fluid strategy (LF). A conservative fluid strategy (CF) was compared with LF during PSV and PCV on lungs and kidneys in an established model of ALI. Twenty-eight male Wistar rats received endotoxin intratracheally. After 24 h, they were treated with CF (minimum volume of Ringer's lactate to maintain normovolemia and mean arterial pressure ≥70 mmHg) or LF (~4 times higher than CF) combined with PSV or PCV (VT  = 6 ml/kg, PEEP = 3 cmH2 O) for 1 h. Nonventilated animals (n = 4) were used for molecular biology analyses. CF-PSV compared with LF-PSV: (1) decreased the diffuse alveolar damage score (10 [7.8-12] vs. 25 [23-31.5], p = 0.006), mainly due to edema in axial and alveolar parenchyma; (2) increased birefringence for occludin and claudin-4 in lung tissue and expression of zonula-occludens-1 and metalloproteinase-9 in lung. LF compared with CF reduced neutrophil gelatinase-associated lipocalin and interleukin-6 expression in the kidneys in PSV and PCV. In conclusion, CF compared with LF combined with PSV yielded less lung epithelial cell damage in the current model of ALI. However, LF compared with CF resulted in less kidney injury markers, regardless of the ventilatory strategy.

LUNG RESECTION FOR NON-SMALL-CELL LUNG CANCER - A NEW RISK SCORE TO PREDICT MAJOR PERIOPERATIVE COMPLICATIONS.

OBJECTIVES: Identify risk factors for major perioperative complications (MPC) after anatomical lung resection for NonSmall-Cell Lung Cancer (NSCLC) and establish a scoring system. METHODS: Single center retrospective study of all consecutive patients diagnosed with NSCLC submitted to anatomical lung resection from 2015 to 2019 (N=564). EXCLUSION CRITERIA: previous lung surgery, concomitant non-lung cancer related procedures, urgency surgery. STUDY POPULATION: 520 patients. PRIMARY END-POINT: MPC defined as a composite endpoint including at least one of the in-hospital complications. Univariable and Multivariable analyses were developed to identify predictors of perioperative complications and create a risk score. Discrimination was assessed using the C-statistic. Calibration was evaluated by Hosmer and Lemeshow test and internal validation was obtained by means of bootstrap replication. RESULTS: Mean age of 65 years and 327 (62.9%) were males. Mean hospital stay of 9 days after surgery. Overall MPC rate was 23.3%. Male gender, hypertension, FEV1<75%, thoracotomy, bilobectomy/pneumectomy and additional resection were independent predictors of MPC. A risk score based on the odds ratios was developed - Major Perioperative Complications of Lung Resection (MPCLR) scoring system - and ranged between 0 and 14 points. It was divided in 5 groups: 1-2 points (positive preditive value 15%); 3-4 (PPV 25%); 5-7 (PPV 35%); 8-9 (PPV 60%); >10 points (PPV 88%). The score showed rea- sonable discrimination (C-statistic=0.70), good calibration (P=.643) and it was internally validated (C-statistic=0,70 BCa95% CI,0.65-0.79). CONCLUSIONS: This study proposes a simple and daily-life risk score system that was able to predict the incidence of perioperative complications.

LYMPH NODE UPSTAGING AFTER SURGERY IN PATIENTS WITH NEGATIVE MEDIASTINAL STAGING BY EBUS.

INTRODUCTION: Mediastinal staging is a hot topic in thoracic oncology. According to the guidelines, and besides other criteria, in the presence of a primary lung cancer with increased mediastinal lymph node uptake on PET-CT, a negative result after lymph node sampling by Endobronchial Ultrasound (EBUS) is not enough to rule out mediastinal lymph node involve- ment, demanding a cervical mediastinoscopy to vouch for the results. METHODS AND OBJECTIVES: In order to study the percentage of lymph node surgical upstaging in patients with neg- ative mediastinal node staging by EBUS and evaluate the role of mediastinoscopy in these patients, we conducted a search in our department's database using the key-word EBUS in the period concerned between January 2014 and August 2020. A total of 302 patients were found. After applying defined criteria, we obtained 42 cases. RESULTS: Lymph node surgical upstaging occurred in 11 (26%) patients, of which 8 were upstaged to N2 and 3 to N1. Most of the cases were single station. Only in 5 (12% of the total) of the 11 patients, the upstaging was related to lymph node stations previously sampled by EBUS. Upstaging was more frequent among males and lower lobe tumours. DISCUSSION AND CONCLUSIONS: Regarding the 8 upstage cases for N2, 5 were single station. Of these 8 cases, only 5 would be approachable by cervical mediastinoscopy. Furthermore, 2 of them were single station, eligible for upfront surgery. Then, only in 3 (7%) of the 42 cases cervical mediastinoscopy would be of foremost importance.

Effects of time-controlled adaptive ventilation on cardiorespiratory parameters and inflammatory response in experimental emphysema.

The time-controlled adaptive ventilation (TCAV) method attenuates lung damage in acute respiratory distress syndrome. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury (VILI) and cardiac function in emphysema. We hypothesized that the use of the TCAV method to achieve an expiratory flow termination/expiratory peak flow (EFT/EPF) of 25% could reduce VILI and improve right ventricular function in elastase-induced lung emphysema in rats. Five weeks after the last intratracheal instillation of elastase, animals were anesthetized and mechanically ventilated for 1 h using TCAV adjusted to either EFT/EPF 25% or EFT/EPF 75%, the latter often applied in acute respiratory distress syndrome (ARDS). Pressure-controlled ventilation (PCV) groups with positive end-expiratory pressure levels similar to positive end-release pressure in TCAV with EFT/EPF 25% and EFT/EPF 75% were also analyzed. Echocardiography and lung ultrasonography were monitored. Lung morphometry, alveolar heterogeneity, and biological markers related to inflammation [interleukin 6 (IL-6), CINC-1], alveolar pulmonary stretch (amphiregulin), lung matrix damage [metalloproteinase 9 (MMP-9)] were assessed. EFT/EPF 25% reduced respiratory system peak pressure, mean linear intercept, B lines at lung ultrasonography, and increased pulmonary acceleration time/pulmonary ejection time ratio compared with EFT/EPF 75%. The volume fraction of mononuclear cells, neutrophils, and expression of IL-6, CINC-1, amphiregulin, and MMP-9 were lower with EFT/EPF 25% than with EFT/EPF 75%. In conclusion, TCAV with EFT/EPF 25%, compared with EFT/EPF 75%, led to less lung inflammation, hyperinflation, and pulmonary arterial hypertension, which may be a promising strategy for patients with emphysema.NEW & NOTEWORTHY The TCAV method reduces lung damage in ARDS. However, so far, no study has evaluated the impact of the TCAV method on ventilator-induced lung injury and cardiac function in experimental emphysema. The TCAV method at EFT/EPF ratio of 25%, compared with EFT/EPF of 75% (frequently used in ARDS), reduced lung inflammation, alveolar heterogeneity and hyperinflation, and pulmonary arterial hypertension in elastase-induced emphysema. TCAV may be a promising and personalized ventilation strategy for patients with emphysema.

Juvenile morphology of the ornamental crab Mithraculus forceps A. Milne-Edwards, 1875 (Crustacea, Brachyura).

The morphology of juveniles of Mithraculus forceps A. Milne-Edwards, 1875, raised in the laboratory, is described. The larvae were obtained from ovigerous females collected in the wild, maintained in the rearing system for culture of crabs (400 L). A total of 229 larvae (zoea I), from 7 females were distributed in lots of 20 larvae kept in glass flasks (500 ml), with seawater circulation and temperature and salinity constants, which were checked daily for molts or deaths. After the larvae reached the juvenile stage, exuviae and dead specimens were deposited in a scientific collection. We analyzed the external morphology (N = 10 ind.) of each size class (total = 8). We determined the number of size classes, based on carapace width CW vs. carapace length CL (mm) and its dispersion points, in which we can observe non-hierarchical groupings with no size classes overlapping. We analyzed the relative growth of the juveniles using the technique "Standard Major Axis'' (Type II regression). The relationships CW vs. CL and CW vs. AW showed negative allometry (b < 1; p < 0.05). The relationships CW vs. CPH and CW vs. CPL are isometric (b = 1; p > 0.05). The most remarkable morphological characters of the juveniles (first size class) are the following: spines at the anterior margin of the carapace, inner marginal teeth in the propodus and dactylus of the chelipeds, number of articles in the antennular endopod and the maxillular endopod, absence of setae on the maxillar endopod, and absence of rudimentary pleopods.

Comparative effects of dexmedetomidine and propofol on brain and lung damage in experimental acute ischemic stroke.

Acute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8-15.3) vs. 19.5(18-24), p = 0.007)], bronchoconstriction index [2.28(2.08-2.36) vs. 2.64(2.53-2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1ß compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1ß compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.

Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals.

We hypothesized whether propofol or active propofol component (2,6-diisopropylphenol [DIPPH] and lipid excipient [LIP-EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receive a standard (lean) or obesity-inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6-DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL-6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL-6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95-5.20]; p = .04) and its active component (2,6-DIPPH) (4.09[1.67-5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6-DIPPH increased IL-10 expression (7.59[6.28-12.95]; p = .001) in adipose tissue-derived macrophages. Additionally, 2,6-DIPPH increased C-X-C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23-29.01]; p = .02; 1.55[1.49-3.43]; p = .02) and adipose tissues (8.78[4.15-11.57]; p = .03; 2.86[2.17-3.71]; p = .01), as well as improved lung-derived neutrophil migration (28.00[-3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.

Impact of different frequencies of controlled breath and pressure-support levels during biphasic positive airway pressure ventilation on the lung and diaphragm in experimental mild acute respiratory distress syndrome.

BACKGROUND: We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. RESULTS: BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure-time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. CONCLUSION: In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI.

The impact of fluid status and decremental PEEP strategy on cardiac function and lung and kidney damage in mild-moderate experimental acute respiratory distress syndrome.

BACKGROUND: We evaluated the effects of abrupt versus gradual PEEP decrease, combined with standard versus high-volume fluid administration, on cardiac function, as well as lung and kidney damage in an established model of mild-moderate acute respiratory distress syndrome (ARDS). METHODS: Wistar rats received endotoxin intratracheally. After 24 h, they were treated with Ringer's lactate at standard (10 mL/kg/h) or high (30 mL/kg/h) dose. For 30 min, all animals were mechanically ventilated with tidal volume = 6 mL/kg and PEEP = 9 cmH2O (to keep alveoli open), then randomized to undergo abrupt or gradual (0.2 cmH2O/min for 30 min) PEEP decrease from 9 to 3 cmH2O. Animals were then further ventilated for 10 min at PEEP = 3 cmH2O, euthanized, and their lungs and kidneys removed for molecular biology analysis. RESULTS: At the end of the experiment, left and right ventricular end-diastolic areas were greater in animals treated with high compared to standard fluid administration, regardless of PEEP decrease rate. However, pulmonary arterial pressure, indicated by the pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio, was higher in abrupt compared to gradual PEEP decrease, independent of fluid status. Animals treated with high fluids and abrupt PEEP decrease exhibited greater diffuse alveolar damage and higher expression of interleukin-6 (a pro-inflammatory marker) and vascular endothelial growth factor (a marker of endothelial cell damage) compared to the other groups. The combination of standard fluid administration and gradual PEEP decrease increased zonula occludens-1 expression, suggesting epithelial cell preservation. Expression of club cell-16 protein, an alveolar epithelial cell damage marker, was higher in abrupt compared to gradual PEEP decrease groups, regardless of fluid status. Acute kidney injury score and gene expression of kidney injury molecule-1 were higher in the high versus standard fluid administration groups, regardless of PEEP decrease rate. CONCLUSION: In the ARDS model used herein, decreasing PEEP abruptly increased pulmonary arterial hypertension, independent of fluid status. The combination of abrupt PEEP decrease and high fluid administration led to greater lung and kidney damage. This information adds to the growing body of evidence that supports gradual transitioning of ventilatory patterns and warrants directing additional investigative effort into vascular and deflation issues that impact lung protection.