Outcome of Emergency Pulmonary Lobectomy under ECMO Support in Patients with COVID-19.

BACKGROUND: Not much is known about the results of nonelective anatomical lung resections in coronavirus disease 2019 (COVID-19) patients put on extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyze the outcome of lobectomy under ECMO support in patients with acute respiratory failure due to severe COVID-19. METHODS: All COVID-19 patients undergoing anatomical lung resection with ECMO support at a German university hospital were included into a prospective database. Study period was April 1, 2020, to April 30, 2021 (first, second, and third waves in Germany). RESULTS: A total of nine patients (median age 61 years, interquartile range 10 years) were included. There was virtually no preexisting comorbidity (median Charlson score of comorbidity 0.2). The mean interval between first positive COVID-19 test and surgery was 21.9 days. Clinical symptoms at the time of surgery were sepsis (nine of nine), respiratory failure (nine of nine), acute renal failure (five of nine), pleural empyema (five of nine), lung artery embolism (four of nine), and pneumothorax (two of nine). Mean intensive care unit (ICU) and ECMO days before surgery were 15.4 and 6, respectively. Indications for surgery were bacterial superinfection with lung abscess formation and progressive septic shock (seven of nine) and abscess formation with massive pulmonary hemorrhage into the abscess cavity (two of nine). All patients were under venovenous ECMO with femoral-jugular configuration. Operative procedures were lobectomy (eight) and pneumonectomy (one). Weaning from ECMO was successful in four of nine. In-hospital mortality was five of nine. Mean total ECMO days were 10.3 ± 6.2 and mean total ICU days were 27.7 ± 9.9. Mean length of stay was 28.7 ± 8.8 days. CONCLUSION: Emergency surgery under ECMO support seems to open up a perspective for surgical source control in COVID-19 patients with bacterial superinfection and localized pulmonary abscess.

Impact of self-coiling catheters for continuous popliteal sciatic block on postoperative pain level and dislocation rate: a randomized controlled trial.

BACKGROUND: Dislocation of catheters within the tissue is a challenge in continuous regional anesthesia. A novel self-coiling catheter design is available and has demonstrated a lower dislocation rate in a cadaver model. The dislocation rate and effect on postoperative pain of these catheters in vivo has yet to be determined and were the subjects of this investigation. METHODS: After ethics committee approval 140 patients undergoing elective distal lower limb surgery were enrolled in this prospective randomized controlled trial. Preoperatively, patients were randomly assigned and received either the conventional (n = 70) or self-coiling catheter (n = 70) for ultrasound-guided popliteal sciatic nerve block in short axis view and by the in-plane approach from lateral to medial. The primary outcome was pain intensity after surgery and on the following three postoperative days. Secondary outcomes investigated were dislocation rate in situ determined by sonography, catheter movement visible from outside, opioid consumption as well as leakage at the puncture site. RESULTS: All catheters were successfully inserted. The study population of self-coiling catheters had significantly lower mean numeric rating scale values than the reference cohort on the first (p = 0.01) and second postoperative days (p < 0.01). Sonographic evaluation demonstrated, 42 standard catheters (60%) and 10 self-coiling catheters (14.3%) were dislocated in situ within the first three postoperative days. The externally visible movement of the catheters at insertion site did not differ significantly between groups through the third postoperative day. The opioid consumption was significantly lower in the self-coiling catheter group on the day of surgery and on the second and third postoperative days (p = 0.04, p = 0.03 and p = 0.04, respectively). CONCLUSION: The self-coiling catheter offers a better postoperative pain control and a lower dislocation rate within the tissue when blocking the popliteal sciatic nerve compared to a conventional catheter. Further trials in large patient cohorts are warranted to investigate the potential beneficial effects of self-coiling catheters for other localisations and other application techniques. TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (DRKS) on 08/04/2020 ( DRKS00020938 , retrospectively registered).

Effects of regional anesthesia techniques on local anesthetic plasma levels and complications in carotid surgery: a randomized controlled pilot trial.

BACKGROUND: The ultrasound guided intermediate cervical plexus block with perivascular infiltration of the internal carotid artery (PVB) is a new technique for regional anesthesia in carotid endarterectomy (CEA). We conducted a pilot study investigating the effects of deep cervical block (DCB), intermediate cervical block alone (ICB) and PVB on perioperative complications in patients undergoing elective CEA. We hypothesized, that the ropivacaine plasma concentration is higher in patients receiving DCB compared to PVB and ICB. METHODS: In a randomized controlled pilot study thirty patients scheduled for elective CEA were randomly assigned into three groups: DCB receiving 20 mL ropivacaine 0.5% (n = 10), ICB receiving 20 mL ropivacaine 0.5% (n = 10) and PVB receiving 20 mL ropivacaine 0.5% and 10 mL ropivacaine 0,3% (n = 10). As primary outcome, plasma levels of ropivacaine were measured with high performance liquid chromatography before, 5, 10, 20, 60, and 180 min after the injection of ropivacaine. Secondary outcomes were vascular and neurological complications as well as patients' and surgeons' satisfaction. All analyses were performed on an intention-to-treat basis. Statistical significance was accepted at p < 0.05. RESULTS: No conversion to general anesthesia was necessary and we observed no signs of local anesthetic intoxication or accidental vascular puncture. Plasma concentration of ropivacaine was significantly higher in the DCB group compared to PVB and ICB (p < 0.001) and in the PVB group compared to ICB (p = 0.008). Surgeons' satisfaction was higher in the PVB group compared to ICB (p = 0.003) and patients' satisfaction was higher in the PVB group compared to ICB (p = 0.010) and DCB group (p = 0.029). Phrenic nerve paralysis was observed frequently in the DCB group (p < 0.05). None of these patients with hemi-diaphragmatic paralysis showed signs of respiratory distress. CONCLUSION: The ultrasound guided PVB is a safe and effective technique for CEA which is associated with lower plasma levels of local anesthetic than the standard DCB. Considering the low rate of complications in all types of regional anesthesia for CEA, larger randomized controlled trials are warranted to assess potential side effects among the blocks. TRIAL REGISTRATION: The trial was registered at German Clinical Trials Register (DRKS) on 04/05/2019 (DRKS00016705, retrospectively registered).

Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

BACKGROUND: To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. METHODS: Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. RESULTS: The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. CONCLUSIONS: In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

Reduced pulmonary blood flow in regions of injury 2 hours after acid aspiration in rats.

BACKGROUND: Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following acid aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after acid aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). METHODS: Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after acid instillation by measuring the concentration of [(68)Ga]-radiolabeled microspheres using positron emission tomography. RESULTS: CT scans revealed increased lung density in areas of acid aspiration. Lung injury was accompanied by impaired gas exchange. Acid aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). CONCLUSIONS: The PBF pattern 2 hours after aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation. Please see related article: http://dx.doi.org/10.1186/s12871-015-0014-z.

Higher levels of spontaneous breathing reduce lung injury in experimental moderate acute respiratory distress syndrome.

OBJECTIVES: To assess the effects of different levels of spontaneous breathing during biphasic positive airway pressure/airway pressure release ventilation on lung function and injury in an experimental model of moderate acute respiratory distress syndrome. DESIGN: Multiple-arm randomized experimental study. SETTING: University hospital research facility. SUBJECTS: Thirty-six juvenile pigs. INTERVENTIONS: Pigs were anesthetized, intubated, and mechanically ventilated. Moderate acute respiratory distress syndrome was induced by repetitive saline lung lavage. Biphasic positive airway pressure/airway pressure release ventilation was conducted using the airway pressure release ventilation mode with an inspiratory/expiratory ratio of 1:1. Animals were randomly assigned to one of four levels of spontaneous breath in total minute ventilation (n = 9 per group, 6 hr each): 1) biphasic positive airway pressure/airway pressure release ventilation, 0%; 2) biphasic positive airway pressure/airway pressure release ventilation, > 0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation, > 30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation, > 60%. MEASUREMENTS AND MAIN RESULTS: The inspiratory effort measured by the esophageal pressure time product increased proportionally to the amount of spontaneous breath and was accompanied by improvements in oxygenation and respiratory system elastance. Compared with biphasic positive airway pressure/airway pressure release ventilation of 0%, biphasic positive airway pressure/airway pressure release ventilation more than 60% resulted in lowest venous admixture, as well as peak and mean airway and transpulmonary pressures, redistributed ventilation to dependent lung regions, reduced the cumulative diffuse alveolar damage score across lungs (median [interquartile range], 11 [3-40] vs 18 [2-69]; p < 0.05), and decreased the level of tumor necrosis factor-α in ventral lung tissue (median [interquartile range], 17.7 pg/mg [8.4-19.8] vs 34.5 pg/mg [29.9-42.7]; p < 0.05). Biphasic positive airway pressure/airway pressure release ventilation more than 0-30% and more than 30-60% showed a less consistent pattern of improvement in lung function, inflammation, and damage compared with biphasic positive airway pressure/airway pressure release ventilation more than 60%. CONCLUSIONS: In this model of moderate acute respiratory distress syndrome in pigs, biphasic positive airway pressure/airway pressure release ventilation with levels of spontaneous breath higher than usually seen in clinical practice, that is, more than 30% of total minute ventilation, reduced lung injury with improved respiratory function, as compared with protective controlled mechanical ventilation.

Acute abdominal compartment syndrome as a complication of Holmium laser enucleation of the prostate: a case report.

BACKGROUND: In 1996, Holmium laser enucleation of the prostate was introduced and has been shown to be safe and highly effective. CASE PRESENTATION: We report a case of a rare complication that resulted in intra-abdominal compartment syndrome with prolonged intubation and intensive care, involving an 74-year-old male after holmium laser enucleation of prostate, with a massive irrigant fluid leakage into the retroperitoneal space. The elevated abdominal pressure was reduced by forced diuresis. The tracheal tube was removed 18 hours after the patient's transfer to the ICU. The patient was discharged to home one week after the operation. CONCLUSION: In rare cases when no obvious ruptures of the prostate capsule or the bladder occur during laser enucleation of prostate, knowledge regarding possible emersion of massive amounts of irrigant fluid into the retroperitoneal space leading to intra-abdominal compartment syndrome aids in the diagnosis and subsequent successful therapy of intra-abdominal hypertension.

[Influence of anesthesia on surgical site infections]. / Einfluss der Anästhesie auf chirurgische Wundinfektionen.

Surgical site infections (SSI) are the most frequent cause of impaired perioperative wound healing, lead to increased postoperative morbidity, mortality and length of hospital stay and are therefore a relevant perioperative complication. In addition to numerous measures taken by the surgical departments, there are anesthesiological options that can help to reduce the risk of SSI. In addition to heat, volume and transfusion management these include, for example, the use of antibiotics and the choice of the anesthesia procedure. This article is intended to provide fundamental knowledge on SSI, shows various options for reducing them in the context of anesthesia and evaluates their effectiveness and evidence based on the current state of knowledge.

Case of functional paraganglioma with intraoperative hypertensive crisis during robot-assisted thoracoscopic resection.

BACKGROUND: Mediastinal paragangliomas are rare. Their dangerousness may unfold during surgery, especially if hormonal activity was previously unknown. We report our experience with this case in context to the incidence and localization of atypically located mediastinal paragangliomas in the literature. CASE PRESENTATION: A 69-year-old female patient who was scheduled for thoracoscopic resection due to a posterior mediastinal tumor that had been progressing in size for several years and increasing symptoms. The induction of anesthesia, the ventilation of the lungs and the gas exchange after lung separation was uneventful. After initially stable circulatory conditions, there was a sudden increase in blood pressure up to 300/130 mmHg and tachycardia up to 130/min. This hypertensive phase was difficult to influence and required a rapid and consistent use of antihypertensive medication to bring down the blood pressure to reasonable values. The patient stabilized after tumor resection. The postoperative course was unremarkable. During the intraoperative blood pressure crisis, blood was drawn for analysis. These samples showed elevated concentrations of normetanephrine and metanephrine. The tumor subsequently presented as a catecholamine-secreting paraganglioma. CONCLUSION: In order to avoid life-threatening blood pressure crises, hormone activity should be ruled out preoperatively in the case of mediastinal tumor, in which a paraganglioma could be considered in the differential diagnosis, especially if there are indications of hypertension in the medical history. Robotic-assisted thoracoscopic resection of the posterior mediastinal tumor was a feasible surgical method, even in the case of unexpected functional paraganglioma.

Scalable Non-Volatile Tuning of Photonic Computational Memories by Automated Silicon Ion Implantation.

Photonic integrated circuits (PICs) are revolutionizing the realm of information technology, promising unprecedented speeds and efficiency in data processing and optical communication. However, the nanoscale precision required to fabricate these circuits at scale presents significant challenges, due to the need to maintain consistency across wavelength-selective components, which necessitates individualized adjustments after fabrication. Harnessing spectral alignment by automated silicon ion implantation, in this work scalable and non-volatile photonic computational memories are demonstrated in high-quality resonant devices. Precise spectral trimming of large-scale photonic ensembles from a few picometers to several nanometres is achieved with long-term stability and marginal loss penalty. Based on this approach, spectrally aligned photonic memory and computing systems for general matrix multiplication are demonstrated, enabling wavelength multiplexed integrated architectures at large scales.

Comparative effects of variable versus conventional volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in thoracic surgery patients: A randomized controlled clinical trial.

BACKGROUND: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV). METHODS: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H2O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H2O and an inspiratory oxygen fraction of 1.0. RESULTS: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO2) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups. CONCLUSIONS: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019. TRIAL REGISTRATION: at the German Clinical Trials Register: DRKS00022202 (16.06.2020).

Pulmonary blood flow increases in damaged regions directly after acid aspiration in rats.

BACKGROUND: After gastric aspiration events, patients are at risk of pulmonary dysfunction and the development of severe acute lung injury and acute respiratory distress syndrome, which may contribute to the development of an inflammatory reaction. The authors' aim in the current study was to investigate the role of the spatial distribution of pulmonary blood flow in the pathogenesis of pulmonary dysfunction during the early stages after acid aspiration. METHODS: The authors analyzed the pulmonary distribution of radiolabeled microspheres in normal (n = 6) and injured (n = 12) anesthetized rat lungs using positron emission tomography, computed tomography, and histological examination. RESULTS: Injured regions demonstrate increased pulmonary blood flow in association with reduced arterial pressure and the deterioration of arterial oxygenation. After acid aspiration, computed tomography scans revealed that lung density had increased in the injured regions and that these regions colocalized with areas of increased blood flow. The acid was instilled into the middle and basal regions of the lungs. The blood flow was significantly increased to these regions compared with the blood flow to uninjured lungs in the control animals (middle region: 1.23 [1.1; 1.4] (median [25%; 75%]) vs. 1.04 [1.0; 1.1] and basal region: 1.25 [1.2; 1.3] vs. 1.02 [1.0; 1.05], respectively). The increase in blood flow did not seem to be due to vascular leakage into these injured areas. CONCLUSIONS: The data suggest that 10 min after acid aspiration, damaged areas are characterized by increased pulmonary blood flow. The results may impact further treatment strategies, such as drug targeting.

Significance of Pulmonary Endothelial Injury and the Role of Cyclooxygenase-2 and Prostanoid Signaling.

The endothelium plays a key role in the dynamic balance of hemodynamic, humoral and inflammatory processes in the human body. Its central importance and the resulting therapeutic concepts are the subject of ongoing research efforts and form the basis for the treatment of numerous diseases. The pulmonary endothelium is an essential component for the gas exchange in humans. Pulmonary endothelial dysfunction has serious consequences for the oxygenation and the gas exchange in humans with the potential of consecutive multiple organ failure. Therefore, in this review, the dysfunction of the pulmonary endothel due to viral, bacterial, and fungal infections, ventilator-related injury, and aspiration is presented in a medical context. Selected aspects of the interaction of endothelial cells with primarily alveolar macrophages are reviewed in more detail. Elucidation of underlying causes and mechanisms of damage and repair may lead to new therapeutic approaches. Specific emphasis is placed on the processes leading to the induction of cyclooxygenase-2 and downstream prostanoid-based signaling pathways associated with this enzyme.

Hemodynamics and cutaneous microcirculation during induction of general anesthesia with and without esketamine.

OBJECTIVE: Currently, there are limited data on the effect of macrocirculatory hemodynamic changes on human microcirculation, especially during the induction of general anesthesia (GA). METHODS: We performed a non-randomized observational trial on patients receiving GA for elective surgery. In the control group (CG), for GA induction sufentanil, propofol, and rocuronium was administered. Patients assigned to the esketamine group (EG) received additional esketamine for GA induction. Invasive blood pressure (IBP) and pulse contour cardiac output (CO) measurement were performed continuously. Microcirculation was assessed using cutaneous Laser Doppler Flowmetry (forehead and sternum LDF), peripheral and central Capillary Refill Time (pCRT, cCRT), as well as brachial temperature gradient (Tskin-diff) at baseline, 5, 10 and 15 minutes after induction of GA. RESULTS: 42 patients were included in the analysis (CG n = 22, EG n = 20). pCRT, cCRT, Tskin-diff, forehead and sternum LDF decreased following GA induction in both groups. IBP and CO were significantly more stable in esketamine group. However, the changes in the microcirculatory parameters were not significantly different between the groups. CONCLUSIONS: The addition of esketamine for GA induction warranted better hemodynamic stability for the first five minutes, but had no significant effect on any of the cutaneous microcirculatory parameters measured.

Spinal anesthesia for cesarean section in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disorder of the peripheral nervous system with progressive or relapsing signs in more than one limb, ending in prolonged periods of disability. There are no guidelines for anesthesia in this uncommon paralyzing disease. This report features a 19-year-old woman with CIDP scheduled for an elective cesarean section who had prolonged recovery of motor function after the administration of spinal anesthesia. Although a partial neural block in both feet persisted for 1 day, we conclude that spinal anesthesia is acceptable for cesarean delivery in CIDP-patients when reasonable precautions have been taken.

Use of extracorporeal membrane oxygenation in non-elective major thoracic surgery for infectious lung abscess.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) support for elective cardiothoracic surgery is well established. In contrast, there are not much data regarding the usefulness and outcome of ECMO in non-elective major lung resections for infectious lung abscess. METHODS: All patients undergoing non-elective major lung surgery for infectious lung abscess at 5 centres in Germany, UK and Spain were enrolled in a prospective database. Malignant disorders and intrathoracic complications of other procedures were excluded. RESULTS: There were 127 patients. The median age was 59 years (interquartile range 18.75). The mean Charlson index of comorbidity was 2.83 (standard deviation 2.57). Surgical procedures were lobectomy (89), pneumectomy (20) and segmentectomy (18). ECMO was used for 10 patients (pneumectomy 2, lobectomy 8) and several more received pre-ECMO treatment. Mortality was 17/127. Intraoperatively no ECMO-associated complications were encountered. EMCO [1/10 vs 16/117; odds ratio (OR): 0.70, 95% confidence interval (CI) 0.08-5.91, P = 0.74] and the extent of pulmonary resection were not associated with higher mortality. Preoperative sepsis (OR: 17.84, 95% CI 2.29-139.28, P < 0.01), preoperative air leak (OR: 13.12, 95% CI 4.10-42.07, P < 0.001), acute renal failure (OR: 7.00, 95% CI 2.19-22.43, P < 0.01) and Charlson index of comorbidity ≥3 (OR: 10.83, 95% CI 2.36-49.71, P < 0.01) were associated with significantly higher mortality. CONCLUSIONS: The application of ECMO is widening the possibilities for successful surgical management of infectious, non-malignant lung abscesses. Particularly, patients with marginal functional operability benefit from the availability and readiness to use ECMO. Mortality is determined by the burden of pre-existent comorbidity, severe sepsis and septic shock.

Feedback between p21 and reactive oxygen production is necessary for cell senescence.

Cellular senescence--the permanent arrest of cycling in normally proliferating cells such as fibroblasts--contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of 'deep' cellular senescence. The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype.

Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence.

Aging is an inherently stochastic process, and its hallmark is heterogeneity between organisms, cell types, and clonal populations, even in identical environments. The replicative lifespan of primary human cells is telomere dependent; however, its heterogeneity is not understood. We show that mitochondrial superoxide production increases with replicative age in human fibroblasts despite an adaptive UCP-2-dependent mitochondrial uncoupling. This mitochondrial dysfunction is accompanied by compromised [Ca(2+)]i homeostasis and other indicators of a retrograde response in senescent cells. Replicative senescence of human fibroblasts is delayed by mild mitochondrial uncoupling. Uncoupling reduces mitochondrial superoxide generation, slows down telomere shortening, and delays formation of telomeric gamma-H2A.X foci. This indicates mitochondrial production of reactive oxygen species (ROS) as one of the causes of replicative senescence. By sorting early senescent (SES) cells from young proliferating fibroblast cultures, we show that SES cells have higher ROS levels, dysfunctional mitochondria, shorter telomeres, and telomeric gamma-H2A.X foci. We propose that mitochondrial ROS is a major determinant of telomere-dependent senescence at the single-cell level that is responsible for cell-to-cell variation in replicative lifespan.

Causative treatment of acid aspiration induced acute lung injury - Recent trends from animal experiments and critical perspective.

Aspiration of low-pH gastric fluid leads to an initial pneumonitis, which may become complicated by subsequent pneumonia or acute respiratory distress syndrome. Current treatment is at best supportive, but there is growing experimental evidence on the significant contribution of both neutrophils and platelets in the development of this inflammatory pulmonary reaction, a condition that can be attenuated by several medicinal products. This review aims to summarize novel findings in experimental models on pathomechanisms after an acid-aspiration event. Given the clinical relevance, specific emphasis is put on deduced potential experimental therapeutic approaches, which make use of the characteristic alteration of microcirculation in the injured lung.