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Electrical stimulation of peripheral nerves has been used in various pathological contexts for rehabilitation purposes or to alleviate the symptoms of neuropathologies, thus improving the overall quality of life of patients. However, the development of novel therapeutic strategies is still a challenging issue requiring extensive in vivo experimental campaigns and technical development. To facilitate the design of new stimulation strategies, we provide a fully open source and self-contained software framework for the in silico evaluation of peripheral nerve electrical stimulation. Our modeling approach, developed in the popular and well-established Python language, uses an object-oriented paradigm to map the physiological and electrical context. The framework is designed to facilitate multi-scale analysis, from single fiber stimulation to whole multifascicular nerves. It also allows the simulation of complex strategies such as multiple electrode combinations and waveforms ranging from conventional biphasic pulses to more complex modulated kHz stimuli. In addition, we provide automated support for stimulation strategy optimization and handle the computational backend transparently to the user. Our framework has been extensively tested and validated with several existing results in the literature., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Couppey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Out-of-hospital cardiac arrest (OHCA) is a leading cause of mortality. Despite decades of intensive research and several technological advancements, survival rates remain low. The integration of extracorporeal cardiopulmonary resuscitation (ECPR) has been recognized as a promising approach in refractory OHCA. However, evidence from recent randomized controlled trials yielded contradictory results, and the criteria for selecting eligible patients are still a subject of debate., Methods: This study is a retrospective analysis of refractory OHCA patients treated with ECPR. All adult patients who received ECPR, according to the hospital algorithm, from 2013 to 2021 were included. Two different algorithms were used during this period. A "permissive" algorithm was used from 2013 to mid-2016. Subsequently, a revised algorithm, more "restrictive", based on international guidelines, was implemented from mid-2016 to 2021. Key differences between the two algorithms included reducing the no-flow time from less than three minutes to zero minutes (implying that the cardiac arrests must occur in the presence of a witness with immediate CPR initiation), reducing low-flow duration from 100 to 60 min, and lowering the age limit from 65 to 55 years. The aim of this study is to compare these two algorithms (permissive (1) and restrictive (2)) to determine if the use of a restrictive algorithm was associated with higher survival rates., Results: A total of 48 patients were included in this study, with 23 treated under Algorithm 1 and 25 under Algorithm 2. A significant difference in survival rate was observed in favor of the restrictive algorithm (9% vs. 68%, p < 0.05). Moreover, significant differences emerged between algorithms regarding the no-flow time (0 (0-5) vs. 0 (0-0) minutes, p < 0.05). Survivors had a significantly shorter no-flow and low-flow time (0 (0-0) vs. 0 (0-3) minutes, p < 0.01 and 40 (31-53) vs. 60 (45-80) minutes, p < 0.05), respectively., Conclusion: The present study emphasizes that a stricter selection of OHCA patients improves survival rates in ECPR.

Collision-induced dissociation (CID) is the most wildly used fragmentation technique for qualitative and quantitative determination of low molecular weight compounds (LMWC). Ultraviolet photodissociation (UVPD) has been mainly investigated for the analysis of peptides and lipids while only in a limited way for LMWC. A triple quadrupole linear ion trap instrument has been modified to allow ultraviolet photodissociation (UVPD) in the end of the q2 region enabling various workflows with and without data-dependent acquisition (DDA) combining CID and UVPD in the same LC-MS analysis. The performance of UVPD, with a 266-nm laser, is compared to CID for a mix of 90 molecules from different classes of LMWC including peptides, pesticides, pharmaceuticals, metabolites, and drugs of abuse. These two activation methods offer complementary fragments as well as common fragments with similar sensitivities for most analytes investigated. The versatility of UVPD and CID is also demonstrated for quantitative analysis in human plasma of bosentan and its desmethyl metabolite, used as model analytes. Different background signals are observed for both fragmentation methods as well as unique fragments which opens the possibility of developing a selective quantitative assay with improved sample throughput, in particular for analytes present in different matrices., (© 2023. The Author(s).)

SGLT2i are now recommended in a wide spectrum of indications including type 2 diabetes (T2DM), heart failure, and chronic kidney disease. This medication class is now available in combination with metformin, which is still a fundamental treatment in patients with T2DM. Despite excellent proven safety profile for both drugs, the expanding use of these agents in clinical practice may lead to an increased incidence of rare side effects, like metformin-associated lactic acidosis (MALA) and euglycemic diabetic ketoacidosis (EDKA), which can be life-threatening. A 58-year-old woman with T2DM and severe heart failure treated by metformin and empagliflozin developed progressive EDKA triggered by fasting that was also complicated by severe acute renal failure and MALA. She was successfully treated with intermittent hemodialysis. This case report highlights the importance of the recognition of rare, but very serious adverse effects due to combined metformin and SGLT2i therapy., Competing Interests: There are no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Extracorporeal membrane oxygenation (ECMO) is an effective cardiorespiratory support technique in refractory cardiac arrest (CA). In patients under veno-arterial ECMO, the use of an Impella device, a microaxial pump inserted percutaneously, is a valuable strategy through a left ventricular unloading approach. ECMELLA, a combination of ECMO with Impella, seems to be a promising method to support end-organ perfusion while unloading the left ventricle., Case Summary: The present case report describes the clinical course of a patient with ischemic and dilated cardiomyopathy who presented with refractory ventricular fibrillation (VF) leading to CA in the late postmyocardial infarction (MI) period, and who was successfully treated with ECMO and IMPELLA as a bridge to heart transplantation., Discussion: In the case of CA on VF refractory to conventional resuscitation maneuvers, early extracorporeal cardiopulmonary resuscitation (ECPR) associated with an Impella seems to be the best strategy. It provides organ perfusion, left ventricular unloading, and ability for neurological evaluation and VF catheter ablation before allowing heart transplantation. It is the treatment of choice in cases of end-stage ischaemic cardiomyopathy and recurrent malignant arrhythmias., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Giraud, Assouline, Burri, Shah, Meyer, Degrauwe, Kirsch and Bendjelid.)

The SARS-CoV-2 pandemic has overwhelmed health care systems worldwide since its first wave. Intensive care units have been under a significant amount of pressure as patients with the most severe form of the disease presented with acute respiratory distress syndrome (ARDS). A proportion of them experienced refractory acute respiratory failure and had to be supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO). The present retrospective study reports the experiences of our ECMO center in the management of COVID-19 patients with refractory ARDS. Patient characteristics and outcomes are presented through the different waves of the pandemic. A cohort study was conducted on patients with refractory ARDS due to COVID-19 infection who were admitted to the intensive care unit (ICU) at the Geneva University Hospital and supported with VV-ECMO between 14 March 2020 and January 2022. The VV-ECMO implementation criteria were defined according to an institutional algorithm validated by the local crisis unit of the hospital and the Swiss Society of Intensive Care Medicine. Among the 500 ARDS patients admitted to our ICU, 41 patients with a median age of 57 (52−63) years, a body mass index (BMI) of 28 (26−32) kg/m2, and a SAPS II score of 57 (47−67), and 27 (66%) of whom were men required VV-ECMO. None of the patients were vaccinated. The time of ventilation, including noninvasive ventilation (NIV) and mechanical ventilation (MV), and the time of MV before ECMO were 7 (4−11) days and 4 (1−7) days, respectively. The time under ECMO was 20 (10−27) days. The ICU and hospital lengths of stay were 36 (21−45) days and 45 (33−69) days, respectively. The survival rate for patients on ECMO was 59%. Comparative analysis between survivors and non-survivors highlighted that survivors had a significantly shorter ventilation duration before ECMO (NIV + MV: 5.5 (1.3−9) vs. 9 (6.5−13.5) days, p = 0.0026 and MV alone: 1.6 (0.4−5.5) vs. 5.8 (5−8) days, p < 0.0001). The management of patients on ECMO by an experienced ECMO team dedicated to this activity was associated with improved survival (78% vs. 28%, p = 0.0012). Between the first wave and the following waves, patients presented with a higher incidence of ventilator-associated pneumonia (100% vs. 82%, p = 0.0325) but had better survival rates (74% vs. 35%, p = 0.024). The present study suggests that both the prompt insertion of VV-ECMO to control refractory hypoxemia and the involvement of an ECMO team improve the survival of COVID-19 patients.

Previous studies suggested that ongoing treatment with renin-angiotensin-aldosterone system (RAAS) inhibitor drugs may alter the course of SARS-CoV-2 infection and promote the development of more severe forms of the disease. The authors conducted a comparative, observational study to retrospectively analyze data collected from 394 patients admitted to ICU due to SARS-CoV-2 pneumonia. The primary aim of the study was to establish an association between the use of RAAS inhibitor drugs and mortality in the ICU. The secondary aims of the study were to establish an association between the use of RAAS inhibitor drugs and clinical severity at ICU admission, the need for tracheal intubation, total days of mechanical ventilation, and the ICU length of stay. The authors found no statistically significant difference in ICU mortality between patients on RAAS inhibitor drugs at admission and those who were not (31.3% versus 26.2% mortality, p-value 0.3). However, the group of patients taking RAAS inhibitor drugs appeared to be more critical at ICU admission, and this difference became statistically significant in the subgroup of non-hypertensive patients. ICU mortality in the subgroup of non-hypertensive patients treated with RAAS inhibitor drugs also tended to be higher. Overexpression of the angiotensin-converting enzyme 2 (ACE2) in human cells, induced by RAAS inhibitor drugs, promotes viral entry-replication of SARS-CoV-2 and alters the basal balance of the RAAS, which may explain the findings observed in the present study. These phenomena may be amplified in non-hypertensive patients treated with RAAS inhibitor therapy., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Pulmonary embolism (PE) is a common disease with an annual incidence rate ranging from 39-115 per 100,000 inhabitants. It is one of the leading causes of cardiovascular mortality in the USA and Europe. While the clinical presentation and severity may vary, it is a life-threatening condition in its most severe form, defined as high-risk or massive PE. Therapeutic options in high-risk PE are limited. Current guidelines recommend the use of systemic thrombolytic therapy as first-line therapy (Level Ib). However, this treatment has important drawbacks including bleeding complications, limited efficacy in patients with recurrent PE or cardiac arrest, and formal contraindications. In this context, the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in the management of high-risk PE has increased worldwide in the last decade. Strategies, including VA-ECMO as a stand-alone therapy or as a bridge to alternative reperfusion therapies, are associated with acceptable outcomes, especially if implemented before cardiac arrest. Nonetheless, the level of evidence supporting ECMO and alternative reperfusion therapies is low. The optimal management of high-risk PE patients will remain controversial until the realization of a prospective randomized trial comparing those cited strategies to systemic thrombolysis.

Introduction: Plasma free hemoglobin is the gold standard for monitoring hemolysis in extracorporeal membrane oxygenation (ECMO) but its routine use has some limitations. Carboxyhemoglobin (HbCO) is also a marker of intravascular hemolysis. We aimed to investigate HbCO as a marker of both hemolysis and oxygenator dysfunction in patients supported by ECMO., Methods: Retrospective analysis of patients on ECMO in an adult ICU in a tertiary hospital. HbCO was recorded every 6 h in the 48 h before and after oxygenator change in adult patients on ECMO support with an oxygenator dysfunction and replacement., Results: The investigation of 27 oxygenators replacements in 19 patients demonstrated that HbCO values progressively increased over time and then significantly decreased after oxygenator change. Median oxygenator lifespan was 14 days [interquartile range (IQR) 8-21] and there was no correlation between HbCO and oxygenator lifespan [Spearman coefficient 0.23 ( p = 0.23)]. HbCO values at oxygenator change [HbCO median 2.7 (IQR 2.5-3.5)] were significantly higher than the HbCO values 1 week before [HbCO median 2.07 (IQR 1.86-2.8)] ( p value < 0.001)., Conclusion: Our data highlight the potential role of HbCO as a novel marker for ECMO oxygenator dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cousin, Giraud, Assouline, Silva and Bendjelid.)

Background: Intensive Care Unit (ICU) patients are known to lose muscle mass and function during ICU stay. Ultrasonography (US) application for the assessment of the skeletal muscle is a promising tool and might help detecting muscle changes and thus several dysfunctions during early stages of ICU stay. MUSiShock is a research project aiming to investigate structure and function of diaphragm and peripheral muscles using ultrasound techniques in septic shock patients, and to assess their relevance in several clinical outcomes such as the weaning process., Methods and Design: This is a research protocol from an observational prospective cohort study. We plan to assess eighty-four septic shock patients during their ICU stay at the following time-points: at 24 hours of ICU admission, then daily until day 5, then weekly, at extubation time and at ICU discharge. At each time-point, we will measure the quadriceps rectus femoris and diaphragm muscles, using innovative US muscle markers such as Shear-Wave Elastography (SWE). In parallel, the Medical Research Council (MRC) sum score for muscle testing and the Airway occlusion pressure (P0.1) will also be collected. We will describe the association between SWE assessment and other US markers for each muscle. The association between the changes in both diaphragm and rectus femoris US markers over time will be explored as well; finally, the analysis of a combined model of one diaphragm US marker and one limb muscle US marker to predict weaning success/failure will be tested., Discussion: By using muscle ultrasound at both diaphragm and limb levels, MUSiShock aims to improve knowledge in the early detection of muscle dysfunction and weakness, and their relationship with muscle strength and MV weaning, in critically ill patients. A better anticipation of these short-term muscle structure and function outcomes may allow clinicians to rapidly implement measures to counteract it., Trial Registration: ClinicalTrials.gov, NCT04550143. Registered on 16 September 2020., Competing Interests: The authors have declared that no competing interests exist.

Microvesicles, so-called endothelial large extracellular vesicles (LEVs), are of great interest as biological markers and cell-free biotherapies in cardiovascular and oncologic diseases. However, their therapeutic perspectives remain limited due to the lack of reliable data regarding their systemic biodistribution after intravenous administration., Methods: Applied to a mouse model of peripheral ischemia, radiolabeled endothelial LEVs were tracked and their in vivo whole-body distribution was quantified by microSPECT/CT imaging. Hindlimb perfusion was followed by LASER Doppler and motility impairment function was evaluated up to day 28 post-ischemia., Results: Early and specific homing of LEVs to ischemic hind limbs was quantified on the day of ischemia and positively correlated with reperfusion intensity at a later stage on day 28 after ischemia, associated with an improved motility function., Conclusions: This concept is a major asset for investigating the biodistribution of LEVs issued from other cell types, including cancer, thus partly contributing to better knowledge and understanding of their fate after injection.

Background: Recombinant factor VIII Fc fusion protein (rFVIIIFc) is the first extended half-life (EHL) recombinant clotting factor with marketing authorization; it has been available in France since October 2016. However, data and literature about rFVIIIFc in clinical practice are scarce., Objective: We propose a 1-year clinical and economic outcome evaluation in patients with hemophilia A taking into consideration treatment adherence., Patients and Methods: We reviewed the diaries of all patients treated with rFVIIIFc at Marseille Hemophilia Center for 1 year. All the data were related to the patients' infusion (i.e., annual number of infusions, weekly dose/kg, and annual consumption) and bleeding reports. The clotting factor costs were considered, whereas additional costs (e.g., infusion devices and nurse intervention) were neglected., Results: A total of 34 patients were evaluated. Their median age was 18 years (IQR = 18). Treatment adherence was observed in 62% for FVIII and 66% for rFVIIIFc. The analysis revealed a negligible decrease in the annual clotting factor consumption following the switch (- 2%, p = 0.7339). These data were combined with a significant reduction in the annual number of infusion (- 22.5%, median = 138.5, IQR = 65.8 for FVIII; median = 105, IQR = 24 for rFVIIIFc, p < 0.0001) and bleeding (- 50%, median = 5, IQR = 7.5 for FVIII; median = 1, IQR = 4 for rFVIIIFc, p < 0.0001). With regard to the cost, a decreasing trend was observed (- 8%, p = 0.1300)., Conclusion: The analysis in a real-life setting revealed that the input of switches toward rFVIIIFc in different treatment (age of patients and regimen) patterns seems to corroborate previous studies. The results suggest that switches have a beneficial effect in terms of efficacy, clotting factor consumption, and cost., (© 2021. The Author(s).)

ECMO is the most frequently used mechanical support for patients suffering from low cardiac output syndrome. Combining IABP with ECMO is believed to increase coronary artery blood flow, decrease high afterload, and restore systemic pulsatile flow conditions. This study evaluates that combined effect on coronary artery flow during various load conditions using an in vitro circuit. In doing so, different clinical scenarios were simulated, such as normal cardiac output and moderate-to-severe heart failure. In the heart failure scenarios, we used peripheral ECMO support to compensate for the lowered cardiac output value and reach a default normal value. The increase in coronary blood flow using the combined IABP-ECMO setup was more noticeable in low heart rate conditions. At baseline, intermediate and severe LV failure levels, adding IABP increased coronary mean flow by 16%, 7.5%, and 3.4% (HR 60 bpm) and by 6%, 4.5%, and 2.5% (HR 100 bpm) respectively. Based on our in vitro study results, combining ECMO and IABP in a heart failure setup further improves coronary blood flow. This effect was more pronounced at a lower heart rate and decreased with heart failure, which might positively impact recovery from cardiac failure.

Objective: The present study investigates whether ScvO 2 variations induced by passive leg raising (PLR) are able to predict fluid responsiveness (FR) in mechanically ventilated patients., Design: A monocentric prospective clinical study., Setting: An intensive care division in a tertiary hospital., Patients: The inclusion criteria were elective postoperative cardiac surgery patients who were over 18 years old, deeply sedated, mechanically ventilated and needed volume expansion (VE). Fluid responders (R) were defined as patients who increased their left ventricular outflow tract velocity time integral (VTI) ≥15% after VE., Intervention: In patients included in this study, continuous ScvO 2  monitoring (CeVOX device, Pulsion Medical Systems) and VTI (transthoracic echocardiography) were measured simultaneously before and during a PLR test and before and after VE (with 500 ml of saline)., Measurements and Main Results: Thirty-three consecutive patients were included in this study. In 15 patients with a positive PLR test (increase in VTI ≥15%), ScvO 2 increased during PLR by 9 ± 4%. In the 18 patients with a negative PLR test, ScvO 2 did not significantly change during PLR. VE increased ScvO 2 by 9 ± 6% and 2 ± 4% in responders and nonresponders, respectively. If ScvO 2 increased by >4% during the PLR test, then a positive VTI response (≥15%) was diagnosed with a sensitivity of 93% (68-99%) and a specificity of 94% (63-99%) (Area under the receiver operating characteristic curve 0.92 ± 0.58, p < 0.05). Moreover, ScvO 2 variations were able to distinguish responders to VE from nonresponders to VE with a sensitivity of 87% (68-99%) and a specificity of 89% (63-99%) (Area under the receiver operating characteristic curve 0.89 ± 0.07, p < 0.05)., Conclusions: ScvO 2 variation induced by PLR is a reliable, minimally invasive parameter for predicting FR at the postoperative cardiac surgery bedside of mechanically ventilated, critically ill patients., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Angiotensin converting enzyme 2 (ACE 2 ) seems to be a central actor in the pathophysiology of SARS-Cov-2 infection. First, it acts as the receptor for the virus and permits its attachment to cells expressing ACE 2 . Second, the relative deficiency of ACE 2 during infection could be linked to several clinical features encountered during the disease, like ARDS and coagulation abnormalities. This study explores the strong link between ACE 2 and the majority of risk factors for the severe evolution of COVID-19. It seems that all these risks factors are linked to an increased level of ACE 2 and/or imbalance in ACE/ACE 2 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cousin, Giraud and Bendjelid.)

Introduction: Massive acute pulmonary embolism (MAPE) with obstructive cardiogenic shock is associated with a mortality rate of more than 50%. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used in refractory cardiogenic shock with very good results. In MAPE, although it is currently recommended as part of initial resuscitation, it is not yet considered a stand-alone therapy., Material and Methods: All patients with MAPE requiring the establishment of VA-ECMO and admitted to our tertiary intensive care unit were analysed over a period of 10 years. The characteristics of these patients, before, during and after ECMO were extracted and analysed., Results: A total of 36 patients were included in the present retrospective study. Overall survival was 64%. In the majority of cases, the haemodynamic and respiratory status of the patient improved significantly within the first 24 h on ECMO. The 30-day survival significantly increased when ECMO was used as stand-alone therapy (odds ratio (OR) 15.58, 95% confidence interval (CI) 2.65-91.57, p = 0.002). Nevertheless, when ECMO was implanted following the failure of thrombolysis, the bleeding complications were major (17 (100%) vs. 1 (5.3%) patients, p < 0.001) and the 30-day mortality increased significantly (OR 0.11, 95% CI 0.022-0.520, p = 0.006)., Conclusions: The present retrospective study is certainly one of the most important in terms of the number of patients with MAPE and shock treated with VA-ECMO. This short-term mechanical circulatory support, used as a stand-alone therapy in MAPE, allows for the optimal stabilisation of patients.

The biological mechanisms underlying emotional distress in HIV infection are likely to be complex but remain understudied. We investigated whether dysbiotic signatures in the gut microbiome of persons living with HIV (PLWH) are associated with their emotional status. We retrospectively examined the gut microbiome and clinical evaluation of 129 adults (94 PLWH and 35 HIV-) enrolled at UC San Diego's HIV Neurobehavioral Research Program. A subset of participants (32 PLWH vs. 13 HIV-) underwent an emotional assessment using the NIH Toolbox Emotion Battery summarized by three composite scores (negative affect, social satisfaction, and psychological well-being). We then sequenced the 16S rDNA V3-V4 regions from stool and performed taxonomic assignment using CLC Microbial Genomics Module. The gut microbiota profiles were evaluated in relation to participants' emotional assessment. All analyses were done in R statistical software. We found that the relative abundance of aerotolerant bacteria was significantly higher in PLWH (p < 0.01) and was associated with a lifetime major depression diagnosis independently of HIV status (p = 0.05). Moreover, PLWH experienced significantly worse psychological well-being (p = 0.02), less social satisfaction (p = 0.03), and more negative affect (p = 0.02). Higher levels of aerotolerant bacteria were associated with worse psychological well-being (rho = -0.35, p = 0.02), less social satisfaction (r = - 0.42, p < 0.01), and more negative affect (rho = 0.46, p < 0.01). The association of aerotolerant bacteria with social satisfaction and negative affect was independent of HIV status (p < 0.05, for both). The over-representation of aerotolerant bacteria in the gut may reflect worse oxidative stress and barrier defects and may contribute to emotional distress during HIV infection.

Background: Chronic obstructive pulmonary disease (COPD) exacerbation and protective mechanical ventilation of acute respiratory distress syndrome (ARDS) patients induce hypercapnic respiratory acidosis., Main Text: Extracorporeal carbon dioxide removal (ECCO 2 R) aims to eliminate blood CO 2 to fight against the adverse effects of hypercapnia and related acidosis. Hypercapnia has deleterious extrapulmonary consequences, particularly for the brain. In addition, in the lung, hypercapnia leads to: lower pH, pulmonary vasoconstriction, increases in right ventricular afterload, acute cor pulmonale. Moreover, hypercapnic acidosis may further damage the lungs by increasing both nitric oxide production and inflammation and altering alveolar epithelial cells. During an exacerbation of COPD, relieving the native lungs of at least a portion of the CO 2 could potentially reduce the patient's respiratory work, Instead of mechanically increasing alveolar ventilation with MV in an already hyperinflated lung to increase CO 2 removal, the use of ECCO 2 R may allow a decrease in respiratory volume and respiratory rate, resulting in improvement of lung mechanic. Thus, the use of ECCO 2 R may prevent noninvasive ventilation failure and allow intubated patients to be weaned off mechanical ventilation. In ARDS patients, ECCO 2 R may be used to promote an ultraprotective ventilation in allowing to lower tidal volume, plateau (Pplat) and driving pressures, parameters that have identified as a major risk factors for mortality. However, although ECCO 2 R appears to be effective in improving gas exchange and possibly in reducing the rate of endotracheal intubation and allowing more protective ventilation, its use may have pulmonary and hemodynamic consequences and may be associated with complications., Conclusion: In selected patients, ECCO 2 R may be a promising adjunctive therapeutic strategy for the management of patients with severe COPD exacerbation and for the establishment of protective or ultraprotective ventilation in patients with ARDS without prognosis-threatening hypoxemia.

Cardiac arrest (CA) is a frequent cause of death and a major public health issue. To date, conventional cardiopulmonary resuscitation (CPR) is the only efficient method of resuscitation available that positively impacts prognosis. Extracorporeal membrane oxygenation (ECMO) is a complex and costly technique that requires technical expertise. It is not considered standard of care in all hospitals and should be applied only in high-volume facilities. ECMO combined with CPR is known as ECPR (extracorporeal cardiopulmonary resuscitation) and permits hemodynamic and respiratory stabilization of patients with CA refractory to conventional CPR. This technique allows the parallel treatment of the underlying etiology of CA while maintaining organ perfusion. However, current evidence does not support the routine use of ECPR in all patients with refractory CA. Therefore, an appropriate selection of patients who may benefit from this procedure is key. Reducing the duration of low blood flow by means of performing high-quality CPR and promoting access to ECPR, may improve the survival rate of the patients presenting with refractory CA. Indeed, patients who benefit from ECPR seem to carry better neurological outcomes. The aim of this present narrative review is to present the most recent literature available on ECPR and to clarify its potential therapeutic role, as well as to provide an in-depth explanation of equipment and its set up, the patient selection process, and the patient management post-ECPR.

Type A lactic acidosis is a potentially life-threatening complication in critically ill patients and is the hallmark of a shock state as a result of tissue hypoperfusion and dysoxia. Type B lactic acidosis results from mechanisms other than dysoxia and is a rare condition in patients with solid tumors or hematological malignancies. We present a case of a 60-year-old man with lactic acidosis who was found to have a Burkitt lymphoma related to a posttransplant lymphoproliferative disorder. Lactagenic cancers are characterized by increased aerobic glycolysis and excessive lactate formation, a phenomenon described by Warburg in 1923 that is correlated with cancer aggressiveness and poor survival. There is increased glucose utilization with the purpose of lactagenesis under fully oxygenated conditions, as lactate seems to be a potent signaling molecule for angiogenesis, immune escape, cell migration, metastasis and self-sufficient metabolism, which are five essential steps of carcinogenesis. Type B lactic acidosis in association with malignancies carries an extremely poor prognosis. Currently, effective chemotherapy seems to be the only hope for survival., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Current knowledge on the use of extracorporeal membrane oxygenation (ECMO) in COVID-19 remains limited to small series and registry data. In the present retrospective monocentric study, we report on our experience, our basic principles, and our results in establishing and managing ECMO in critically ill COVID-19 patients., Methods: A cohort study was conducted in patients with severe acute respiratory distress syndrome (ARDS) related to COVID-19 pneumonia admitted to the ICU of the Geneva University Hospitals and supported by VV-ECMO from March 14 to May 31. The VV-ECMO implementation criteria were defined according to an institutional algorithm validated by the local crisis unit and the Swiss Society of Intensive Care Medicine., Results: Out of 137 ARDS patients admitted to our ICU, 10 patients (age 57 ± 4 years, BMI 31.5 ± 5 kg/m 2 , and SAPS II score 56 ± 3) were put on VV-ECMO. The mean duration of mechanical ventilation before ECMO and mean time under ECMO were 7 ± 3 days and 19 ± 11 days, respectively. The ICU and hospital length of stay were 26 ± 11 and 35 ± 10 days, respectively. The survival rate for patients on ECMO was 40%. The comparative analysis between survivors and non-survivors highlighted that survivors had a significantly shorter mechanical ventilation duration before ECMO (4 ± 2 days vs. 9 ± 2 days, p = 0.01). All the patients who had more than 150 h of mechanical ventilation before the application of ECMO ultimately died., Conclusion: The present results suggest that VV-ECMO can be safely utilized in appropriately selected COVID-19 patients with refractory hypoxemia. The main information for clinicians is that late VV-ECMO therapy (i.e., beyond the seventh day of mechanical ventilation) seems futile., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)