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This study describes the case of an 18-years-old male affected by severe COVID-19, who was receiving bilateral lung transplantation (LT), after 71 days of mechanical ventilation and 55 days of veno-venous extracorporeal membrane oxygenation. From post-operative day 2, early mobilization and physiotherapy treatments were performed. Weaning from mechanical ventilation, the use of non-invasive ventilation and tracheostomy management were included in the treatment. Forty-five days after LT the patient was discharged at home, showing improvements in terms of functional and respiratory parameters, quality of life and mood. While evidences about physiotherapy treatments in lung transplantation post severe COVID-19 remain limited, early approach and a multidisciplinary team may be considered key elements for functional recovery of these subjects.

Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation (LuTX) exposes the patients to a high risk of perioperative bleeding secondary to systemic anticoagulation and coagulation factors deficiency. With this case series, we propose innovative "no-heparin" management of ECMO-bridge support during LuTX, based upon 1) control heparin resistance with antithrombin III in the preoperative period; 2) relying upon a fully functional, brand new heparinized ECMO circuit; 3) completely avoiding perioperative heparin; 4) hampering fibrinolysis with tranexamic acid; and 5) limiting venoarterial (VA) ECMO escalation, and the following need for full anticoagulation. Following the application of this new approach, we carried out three challenging clinical cases of bilateral ECMO-bridged LuTX effectively, with limited intraoperative blood requirement and no major postoperative bleeding or thromboembolic events. Of note, two of them had an extremely high risk for hemorrhage due to complete right lung anatomic derangement in case number 2 and surgical adhesion following first LuTX in case number 3, while for the case number 1, no blood products were administered during surgery. Despite the limited patient population, such an approach relies on a strong rationale and may be beneficial for managing ECMO bridging to LuTX. Prospective studies are necessary to confirm the validity of our strategy.

Objectives Severe cases of coronavirus disease 2019 develop the acute respiratory distress syndrome, requiring admission to the ICU. This study aimed to describe specific pathophysiological characteristics of acute respiratory distress syndrome from coronavirus disease 2019. Design Prospective crossover physiologic study. Setting ICU of a university-affiliated hospital from northern Italy dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. Patients Ten intubated patients with acute respiratory distress syndrome and confirmed diagnosis of coronavirus disease 2019. Interventions We performed a two-step positive end-expiratory pressure trial with change of 10 cm H2O in random order. Measurements and main results At each positive end-expiratory pressure level, we assessed arterial blood gases, respiratory mechanics, ventilation inhomogeneity, and potential for lung recruitment by electrical impedance tomography. Potential for lung recruitment was assessed by the recently described recruitment to inflation ratio. In a subgroup of seven paralyzed patients, we also measured ventilation-perfusion mismatch at lower positive end-expiratory pressure by electrical impedance tomography. At higher positive end-expiratory pressure, respiratory mechanics did not change significantly: compliance remained relatively high with low driving pressure. Oxygenation and ventilation inhomogeneity improved but arterial CO2 increased despite unchanged respiratory rate and tidal volume. The recruitment to inflation ratio presented median value higher than previously reported in acute respiratory distress syndrome patients but with large variability (median, 0.79 [0.53-1.08]; range, 0.16-1.40). The FIO2 needed to obtain viable oxygenation at lower positive end-expiratory pressure was significantly correlated with the recruitment to inflation ratio (r = 0.603; p = 0.05). The ventilation-perfusion mismatch was elevated (median, 34% [32-45%] of lung units) and, in six out of seven patients, ventilated nonperfused units represented a much larger proportion than perfused nonventilated ones. Conclusions In patients with acute respiratory distress syndrome from coronavirus disease 2019, potential for lung recruitment presents large variability, while elevated dead space fraction may be a specific pathophysiological trait. These findings may guide selection of personalized mechanical ventilation settings.

BACKGROUND: Switching patients affected by early severe ARDS and undergoing extracorporeal membrane oxygenation (ECMO) from controlled ventilation to spontaneous breathing can be either beneficial or harmful, depending on how effectively the breathing pattern is controlled with ECMO. Identifying the factors associated with ineffective control of spontaneous breathing with ECMO may advance our pathophysiologic understanding of this syndrome. METHODS: We conducted a prospective study in subjects with severe ARDS who were on ECMO support ≤ 7 d. Subjects were switched to minimal sedation and pressure-support ventilation while extracorporeal CO2 removal was increased to approximate the subject’s total CO2 production ( V ˙ C O 2 ). We calculated the rapid shallow breathing index (RSBI) as breathing frequency divided by tidal volume. We explored the correlation between certain characteristics recorded during pretest controlled ventilation and the development of apnea (ie, expiratory pause lasting > 10 s; n= 3), normal breathing pattern (ie, apnea to RSBI ≤ 105 breaths/min/L; n= 6), and rapid shallow breathing (RSBI > 105 breaths/min/L; n= 6) that occurred during the test study. RESULTS: The ratio of extracorporeal CO2 removal to the subjects’ V ˙ C O 2 was >90% in all 15 subjects, and arterial blood gases remained within normal ranges. Baseline pretest Sequential Organ Failure Assessment score, total V ˙ C O 2 and ventilatory ratio increased steadily, whereas P aO 2 / F IO 2 was higher in subjects with apnea compared to intermediate RSBI ≤105 breaths/min/L and elevated RSBI >105 breaths/min/L. In subjects with rapid shallow breathing, baseline lung weight measured with quantitative computed tomography scored higher, as well. CONCLUSIONS: In early severe ARDS, the factors associated with rapid shallow breathing despite maximum extracorporeal CO2 extraction include less efficient CO2 and O2 exchange by the natural lung, higher severity of organ failure, and greater magnitude of lung edema.

Association of thoracic and abdominal injuries in patients with major trauma is common. Under emergency conditions, it is often difficult to promptly perform a certain diagnosis and identify treatment priorities of life-threatening lesions. We present the case of a young man with combined thoracic and abdominal injuries after a motorcycle accident. Primary evaluation through echography and X-ray showed fluid within the hepatorenal recess and an enlarged mediastinum. Volume load, blood transfusions, and vasoactive agents were initiated to sustain circulation. Despite hemodynamic instability, we decided to perform computed tomographic angiography (CTA) scan that revealed a high-grade traumatic aortic pseudoaneurysm, multiple and severe areas of liver contusion, and a small amount of hemoperitoneum, without active bleeding spots. The patient was successfully submitted to thoracic endovascular aortic repair (TEVAR). Immediately after the end of the successful TEVAR, signs of massive abdominal bleeding revealed. Immediate explorative laparotomy was performed showing massive hepatic hemorrhage. After liver packing and Pringle's maneuver, control of bleeding was lastly obtained with hemostatic devices and selective cross-clamping of the right hepatic artery. The patient was then transferred to intensive care unit where, despite absence of further hemorrhage, hemodynamic instability, anuria, severe lactic acidosis together with liver necrosis indices appeared. A new CTA demonstrated massive parenchymal disruption within the right lobe of the liver and multiple hematomas in the left lobe. Considering the high-grade lesions of the hepatic vascular tree and liver failure, patient was listed for emergency liver transplantation (LT). LT occurred few hours later, and patient's clinical conditions rapidly improved even if the subsequent clinical course was characterized by a severe fungal infection because of immunosuppression. Evaluation of life-threatening lesions and treatment priorities, availability of different excellence skills, and multidisciplinary collaboration have a key role to achieve clinical success in such severe cases.

Human adenoviruses (HAdVs) cause a wide spectrum of clinical syndromes, depending on species and types, from mild respiratory infections to deadly pneumonia: in particular, severe infections occur in immunocompromised patients. In this report, we describe the case of a 36 years-old woman admitted to our intensive care unit (ICU) with severe respiratory distress syndrome caused by adenovirus pneumonia, that required invasive respiratory support (mechanical ventilation and extracorporeal membrane oxygenation). Molecular assays detected the virus in respiratory and plasma specimen and sequencing procedure identified HAdV type 4. Patient improved after cidofovir administration. Leukopenia and subsequent bacterial infection occurred, but the patient recovered completely and was discharged from the hospital after 54days.

Abortion in dairy cattle may be caused by infectious (viruses, fungi and protozoa) and non-infectious causes mostly related to bad management practices and genetic factors. Recently, the significant contribution of mycotic infection to bovine abortion has been recognized. This report describes an abortion case in a Chianina cow due to Aspergillus nidulans, Aspergillus luchuensis and Lichtheimia sp. diagnosed by histology, cytology, culture and molecular assays. A mixed infection due to more than one fungus in abortion is rarely demonstrated. To our knowledge, this is the first case of bovine abortion caused by co-infection with three different moulds.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has started to be applied in awake spontaneously breathing patients as an alternative to invasive mechanical ventilation. As the physiologic cardiorespiratory variability is increased in this condition, the dynamic interaction between patient respiratory activity and extracorporeal system function affects the clinical management. The effect of extracorporeal CO2 removal on patient respiratory drive is variable and not always predictable, with some patients responding to CO2 removal with a decrease in respiratory rate and effort and other patients demonstrating a persistently high work of breathing independent on CO2 unload. While the pathophysiological mechanisms of this different interactions are still to be clarified, improved monitoring ability is needed both to titrate the support in responders and to avoid the risk of ventilation injury in non-responders. Acute changes in patient respiratory patterns may also occur during spontaneous breathing, making it difficult to maintain constant levels of extracorporeal respiratory support, also because changes in the distribution of venous blood volume due to lung-heart interactions affect extracorporeal blood flow. Assessment of native lung function and of its evolution over time is challenging while respiratory gas exchanges are provided by the extracorporeal system, since both oxygenation and decarboxylation capabilities can be fully evaluated only when alveolar ventilation is restored reducing extracorporeal CO2 removal. The rationale for using "awake ECMO" varies across different types of acute respiratory failure: the pathophysiological mechanisms of the underlying disease affect the patient-ECMO interaction and the goal of support. In this review we discuss the pathophysiology, technical challenges and monitoring issues of the use of ECMO in awake spontaneously breathing patients with acute respiratory failure of different etiologies.

BACKGROUND: Different lifestyle and dietetic factors have been linked with the onset and severity of acne. OBJECTIVE: To assess the complex interconnection between dietetic variables and acne. METHODS: This was a reanalysis of data from a case-control study by using a semantic connectivity map approach. 563 subjects, aged 10-24 years, involved in a case-control study of acne between March 2009 and February 2010, were considered in this study. The analysis evaluated the link between a moderate to severe acne and anthropometric variables, family history and dietetic factors. Analyses were conducted by relying on an artificial adaptive system, the Auto Semantic Connectivity Map (AutoCM). RESULTS: The AutoCM map showed that moderate-severe acne was closely associated with family history of acne in first degree relatives, obesity (BMI ≥ 30), and high consumption of milk, in particular skim milk, cheese/yogurt, sweets/cakes, chocolate, and a low consumption of fish, and limited intake of fruits/vegetables. CONCLUSION: Our analyses confirm the link between several dietetic items and acne. When providing care, dermatologists should also be aware of the complex interconnection between dietetic factors and acne.

Background We evaluate the clinical feasibility of spontaneous breathing on extracorporeal membrane oxygenation and the interactions between artificial and native lungs in patients bridged to lung transplant or with acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome. Methods The clinical course of a total of 48 patients was analyzed. Twenty-three of 48 patients were enrolled in the prospective study (nine bridged to lung transplant, six COPD, and eight acute respiratory distress syndrome). The response to the carbon dioxide removal was evaluated in terms of respiratory rate and esophageal pressure swings by increasing (“relief” threshold) and decreasing (“distress” threshold) the extracorporeal membrane oxygenation gas flow, starting from baseline condition. Results Considering all 48 patients, spontaneous breathing extracorporeal membrane oxygenation was performed in 100% bridge to lung transplant (9 of 9 extubated), 86% COPD (5 of 6 extubated), but 27% acute respiratory distress syndrome patients (6 of 8 extubated; P < 0.001) and was maintained for 92, 69, and 38% of the extracorporeal membrane oxygenation days (P = 0.021), respectively. In all the 23 patients enrolled in the study, gas flow increase (from 2.3 ± 2.2 to 9.2 ± 3.2 l/min) determined a decrease of both respiratory rate (from 29 ± 6 to 8 ± 9 breaths/min) and esophageal pressure swings (from 20 ± 9 to 4 ± 4 cm H2O; P < 0.001 for all). All COPD and bridge to lung transplant patients were responders (reached the relief threshold), while 50% of acute respiratory distress syndrome patients were nonresponders. Conclusions Carbon dioxide removal through extracorporeal membrane oxygenation relieves work of breathing and permits extubation in many patients, mainly bridge to lung transplant and COPD. Only few patients with acute respiratory distress syndrome were able to perform the spontaneous breathing trial, and in about 50% of these, removal of large amount of patient’s carbon dioxide production was not sufficient to prevent potentially harmful spontaneous respiratory effort.

Background The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTX) is still being debated. Methods We performed a retrospective two-center analysis of the relationship between ECMO bridging duration and survival in 25 patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early group) or longer (Late group). We also analyzed the impact of the ventilation strategy during ECMO bridging (ie, spontaneous breathing and noninvasive ventilation [NIV] or intubation and invasive mechanical ventilation [IMV]). Results Seventeen of 25 patients underwent a transplant (with a 76% 1-year survival), whereas eight patients died during bridging. In the 17 patients who underwent a transplant, mortality was positively related to waiting days until LTX (hazard ratio [HR], 1.12 per day; 95% CI, 1.02-1.23; P = .02), and the Early group showed better Kaplan-Meier curves (P = .02), higher 1-year survival rates (100% vs 50%, P = .03), and lower morbidity (days on IMV and length of stay in ICU and hospital). During the bridge to transplant, mortality increased steadily with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR, 1.06 per day; 95% CI, 1.01-1.11; P = .015) and 1-year survival (Early, 82% vs Late, 29%; P = .015). Morbidity indexes were lower in patients treated with NIV during the bridge. Conclusions The duration of the ECMO bridge is a relevant cofactor in the mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX.

Venovenous extracorporeal membrane oxygenation (vv-ECMO) has been classically employed as a rescue therapy for patients with respiratory failure not treatable with conventional mechanical ventilation alone. In recent years, however, the timing of ECMO initiation has been readdressed and ECMO is often started earlier in the time course of respiratory failure. Furthermore, some centers are starting to use ECMO as a first line of treatment, i.e., as an alternative to invasive mechanical ventilation in awake, non-intubated, spontaneously breathing patients with respiratory failure (“awake” ECMO). There is a strong rationale for this type of respiratory support as it avoids several side effects related to sedation, intubation, and mechanical ventilation. However, the complexity of the patient–ECMO interactions, the difficulties related to respiratory monitoring, and the management of an awake patient on extracorporeal support together pose a major challenge for the intensive care unit staff. Here, we review the use of vv-ECMO in awake, spontaneously breathing patients with respiratory failure, highlighting the pros and cons of this approach, analyzing the pathophysiology of patient–ECMO interactions, detailing some of the technical aspects, and summarizing the initial clinical experience gained over the past years.

To the Editors: Acute exacerbation of chronic obstructive pulmonary disease (COPD) is commonly treated with different kinds of noninvasive positive pressure devices, ranging from helmet or face-mask continuous positive airway pressure (CPAP) to noninvasive pressure support ventilation (NPPV), or Bi-PAP [1]. The use of positive end-expiratory pressure (PEEP) and NPPV often results in the successful treatment of COPD patients with respiratory distress [1, 2]. If, despite maximal medical management, respiratory distress and gas exchange deteriorate with increasing tachypnoea and acidosis, and with altered level of consciousness, then tracheal intubation and mechanical ventilation (MV) become mandatory [3]. However, tracheal intubation and MV have several detrimental side-effects that may concur to determine the high morbidity and mortality reported in COPD patients requiring them [3, 4]. Indeed, the increase in airway resistance, the prolonged time required for lung emptying and the resulting dynamic hyperinflation, named auto-PEEP [4], are the most important physiological alterations during COPD exacerbation. In this condition, the application of MV could increase lung hyperinflation and lead to barotrauma and circulatory failure [4, 5]. Furthermore, tracheal intubation is usually associated with the need for sedation. The side-effects of intubation, sedation and MV may initiate a vicious circle, often resulting in a very difficult or impossible weaning. In this report, we describe a patient with severe exacerbation of COPD, in whom after failure of noninvasive ventilation, we decided to treat the respiratory acidosis, tachypnoea and ventilatory fatigue by removing CO2 with an artificial lung. This avoided the need for tracheal intubation and MV, leaving the patient in spontaneous breathing. In September 2010, a 72-yr-old, female heavy …

Primary graft dysfunction (PGD) is a severe acute lung injury syndrome following lung transplantation. Previous studies of clinical risk factors, including a multicenter prospective cohort trial, have identified a number of recipient, donor, and operative variables related to Grade 3 PGD. The aim of this study was to validate these risk factors in a lung transplantation center with a low volume of procedures. We conducted a retrospective cohort study of 45 consecutive lung transplantations performed between January 2011 and September 2013. PGD was defined according to the International Society for Heart and Lung Transplantation grading scale. Risk factors were evaluated independently and the significant confounders entered into multivariable logistic regression models. The overall incidence of Grade 3 PGD was 35.5% at T24, 17.7% at T48, and 15.5% at T72. The following risk factors were associated with Grade 3 PGD at the indicated time points: recipient female gender at T24 (P=.034), mixed diagnoses at T72 (P=.047), ECMO bridge-to-lung transplantation at T24 (P=.0004) and at T48 (P=.038), donor causes of death different from stroke and trauma at T24 (P=.019) and T72 (P=.014), blood transfusions during surgery at T24 (P=.001), intraoperative venoarterial ECMO T24 (P.0001). Multivariate analysis at T24 identified recipient female gender and intraoperative venoarterial ECMO as risk factors (P=.010 and P=.018, respectively). This study demonstrated that risk factors for severe PGD in a low-volume center were similar to international reports in prevalence and type. ECMO bridge-to-lung transplantation emerged as a risk factor previously underestimated.

Cutaneous reactions represent in many surveillance systems, the most frequent adverse events attributable to drugs. The spectrum of clinical manifestations is wide and virtually encompasses any known dermatological disease. The introduction of biological agents and so-called targeted therapies has further enlarged the number of reaction patterns especially linked with cytokine release or in balance. The frequency and clinical patterns of cutaneous reactions are influenced by drug use, prevalence of specific conditions (e.g., HIV infection) and pharmacogenetic traits of a population, and they may vary greatly among the different populations around the world. Studies of reaction rates in cohorts of hospitalized patients revealed incidence rates ranging from, 1 out 1000 to 2 out 100 of all hospitalized patients. For drugs such as aminopenicillines and sulfamides the incidence of skin reactions is in the order of 3-5 cases out of 100 exposed people. Although the majority of cutaneous reactions are mild and self-limiting, there are reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) which are associated with significant morbidity and mortality. Surveillance systems routed on sound epidemiologic methodology, are needed to raise signals and to assess risks associated with specific reactions and drug exposures. Identification of risk factors for adverse reactions and appropriate genetic screening of groups at higher risk may improve the outcomes of skin reactions.

The different mass spectrometric approaches employed in the LC–MS coupling are described. The mechanisms of the ionization methods mostly employed (electrospray, atmospheric pressure chemical ionization, atmospheric pressure photoionization) are discussed. To increase the specificity of the MS data, accurate mass measurements and tandem mass spectrometry are particularly effective and their basic aspects are described. Finally, an overview of the most recent approaches (micro- and nano-LC–MS, capillary electrochromatography) is given.

OBJECTIVES: A large number of transplantation centres consider extracorporeal membrane oxygenation as an inappropriate option for bridging critical patients to lung transplantation. Technical improvements such as the introduction of a polymethylpentene membrane, new centrifugal pumps and heparin-coated circuits have led to a safer application of extracorporeal membrane oxygenation, and an increasing number of centres are reporting their positive experiences. The aim of this study was to review our practice in bridging critical candidates to lung transplantation with extracorporeal membrane oxygenation, by comparing patients with invasive mechanical ventilation with patients with spontaneous breathing. METHODS: The records of candidates for lung transplantation treated with extracorporeal membrane oxygenation have been revised. RESULTS: From February 2008 to 2012, 11 patients who experienced an abrupt worsening of their respiratory conditions were treated with extracorporeal membrane oxygenation; mean age: 33.9 ± 13.2 years, male/female ratio: 5/6, 6 patients were affected by cystic fibrosis, 2 had chronic rejection after transplantation, 2 had pulmonary fibrosis and 1 had systemic sclerosis. Seven patients were awake, while 4 patients received invasive mechanical ventilation. The sequential organ failure assessment score significantly increased during bridging time and this increase was significantly higher in the intubated patients. All the patients had bilateral lung transplantation. Spontaneously breathing patients showed a tendency to require a shorter duration of invasive mechanical ventilation, intensive care unit stay and hospital stay after transplantation. One-year survival rate was 85.7% in patients with spontaneous breathing vs 50% in patients with invasive mechanical ventilation. CONCLUSIONS: Extracorporeal membrane oxygenation in spontaneously breathing patients is a feasible, effective and safe bridge to lung transplantation.

Extracorporeal membrane oxygenation (ECMO) has now been used by an expanding number of centres for bridging to lung transplant (LTx) in patients with advanced cardiac and respiratory failure [1]. ECMO has been used for bridging to LTx almost exclusively in patients receiving mechanical ventilation. In order to avoid the drawbacks and complications associated with intubation and prolonged mechanical ventilation we hypothesized that the use of venovenous ECMO (VV-ECMO) in awake and spontaneously breathing patients might be an option for respiratory support in those patients who are severely deteriorating while waiting for lung transplant.

In the history of art, artists have used many different organic compounds to dissolve pigments and apply them onto a support to obtain a paint layer. Proteins were used with success from the Middle Ages up to the Renaissance, and the traditional protein sources were animal parts (skins, tendons and bones) or milk and eggs. Moreover, some of these materials are commonly used as adhesive. In this paper, the first application of the metallomic analytical technique to the identification of proteins in artworks is reported. Samples were derivatized with DTPA/Eu and the derivatization procedure was evaluated by matrix-assisted laser desorption/ionization time-of-flight before high performance liquid chromatography inductively coupled plasma MS analysis. This study has been carried out on laboratory models prepared in-house for method development, resulting in the correct identification of the different classes of proteinaceous binders typically used. In addition, some unknown paint layer samples have been analyzed demonstrating that the method is applicable to very small sample amounts (0.6 mg), which are compatible with the amount normally available for this kind of analysis. The results obtained demonstrate the effectiveness of the method, suggesting the potential future use as novel diagnostic tool in the scientific study of artworks.

Lung retransplantation is the only therapeutic option for acute and chronic graft failure, but only a few cases have been described to have been performed with extracorporeal membrane oxygenation (ECMO) support. We describe the successful case of a 46-year-old man treated with right lung transplantation and left lung retransplantation supported by venovenous ECMO. Lung retransplantation is the only therapeutic option to treat severe primary graft dysfunction, major technical problems, and refractory chronic rejection following pulmonary transplantation. Despite a number of comprehensive studies on lung retransplantation, only a few works have addressed the use of extracorporeal membrane oxygenation (ECMO) as a bridge to the surgical reoperation. Herein we have presented a patient treated with pulmonary bilateral retransplantation subsequent to ECMO therapy for progressive deterioration of pulmonary function in single lung transplantation.

Extracorporeal membrane oxygenation (ECMO) is the only therapeutic option for patients with ventilation-refractory hypercapnia while awaiting lung transplantation. Moreover, there is increasing success using ECMO for definitive respiratory failure in formerly healthy patients. This report describes the use of membrane oxygenation as a bridge to lung transplantation in 2 patients on the waiting list and in 2 previously healthy patients. Our experience showed that coagulation management, critical illness myopathy, and psychological disorders were the most critical problems. One patient died at 2 days after transplantation, 1 at 3 months, and 2 returned to their pretransplantation activities. We concluded that ECMO is an adequate bridge to lung transplantation but, especially in formerly healthy patients, an awake procedure is advisable for a successful outcome.

In a model of acute lung injury, we showed that positive end-expiratory pressure (PEEP) and tidal volume (VT) are interactive variables that determine the extent of lung recruitment, that recruitment occurs across the entire range of total lung capacity, and that superimposed pressure is a key determinant of lung collapse. Aiming to verify if the same rules apply in a clinical setting, we randomly ventilated five ALI/ARDS patients with 10, 15, 20, 30, 35, and 45 cm H2O plateau pressure and 5, 10, 15, and 20 cm H2O of PEEP. For each PEEP-VT condition, we obtained computed tomography at end inspiration and end expiration. We found that recruitment occurred along the entire volume-pressure curve, independent of lower and upper inflection points, and that estimated threshold opening pressures were normally distributed (mode = 20 cm H2O). Recruitment occurred progressively from nondependent to dependent lung regions. Overstretching was not associated with hyperinflation. Derecruitment did not parallel deflation, and estimated threshold closing pressures were normally distributed (mode = 5 cm H2O). End-inspiratory and end-expiratory collapse were correlated, suggesting a plateau-PEEP interaction. When superimposed gravitational pressure exceeded PEEP, end-expiratory collapse increased. We concluded that the rules governing recruitment and derecruitment equally apply in an oleic acid model and in human ALI/ARDS.

A novel pressure gated tidal flow extracorporeal circulation (TF ECC) device was developed, and it was hypothesized that it could provide total respiratory support in apneic adult sheep without adverse hemodynamic or cardiac effects. The circuit consisted of a single lumen cannula, computer driven tubing occluders gated by circuit pressure, a nonocclusive peristaltic blood pump, a spiral coiled membrane lung, and a heat exchanger. Six paralyzed, anesthetized adult sheep were instrumented and TF ECC was instituted via cannulation of the right atrium. Total respiratory support was provided by the circuit during an apneic period of 6 hours. Echocardiography was performed with the animal instrumented (baseline) and after 2 hours of TF ECC. Circuit blood tidal volume was 172.6 +/- 18.0 cc, resulting in a TF ECC flow of 71.1 +/- 10.1 cc/kg/min. At the end of the study period, PaCO2 was 35.5 +/- 7.6 mmHg, paO2) was 91.2 +/- 30.6 mmHg, and pulmonary artery oxygen saturation (SPAO2) was 95 +/- 5%. Hemodynamic stability was maintained with no significant differences at baseline and after 6 hours in mean arterial pressure, mean pulmonary artery pressure, or heart rate noted. Echocardiographic evaluation showed preserved fractional shortening of the left ventricular (LV) septal-lateral dimension (baseline 32.4 +/- 11.4%; 2 hours 34.8 +/- 8.4%). This study demonstrates TF ECC provides total respiratory support without adverse hemodynamic effects, and preserved LV function.

During severe exacerbation of chronic obstructive pulmonary disease (COPD) tachypnea, as a consequence of respiratory acidosis, and airflow limitation, due to small airway obstruction, lead to lung hyperinflation, respiratory distress and gas exchange impairment. Invasive mechanical ventilation could worsen lung hyperinflation and produce a vicious circle. We investigated whether increasing extracorporeal carbon dioxide removal (ECCO2 Cl) could reduce the respiratory rate (RR), so prolonging time for lung emptying and allowing resolution of hyperinflation.

Computed tomography (CT) has played an important role in improving our knowledge of the pathophysiology of the adult respiratory distress syndrome (ARDS), and in determining the morphological and functional relationships of different manoeuvres commonly used in the therapeutic management of this syndrome (changes in body position, application of positive end-expiratory pressure (PEEP) and mechanical ventilation). During the early phase of the disease, the ARDS lung is characterized by a homogenous alteration of the vascular permeability. Thus, oedema accumulates evenly in all lung regions with a nongravitational distribution (homogenous lung). The increased lung weight, due to increased oedema, causes a collapse of the lung regions along the vertical axis, through the transmission of hydrostatic forces (compression atelectasis). Thus, the lesions appear mainly in the dependent lung regions (dishomogeneous lung). During inspiration, at plateau pressure, the pulmonary units reopen and, if the PEEP applied is adequate, they stay open during the following expiration. Adequate PEEP is equal to or higher than the hydrostatic forces compressing that unit. Prone position is another manoeuvre which allows previously collapsed lung regions to reopen and, conversely, compresses previously aerated regions, reversing the distribution of gravitational forces. During late ARDS, there is less compression atelectasis and the lung undergoes structural changes, due to the reduced amount of oedema. This is usually associated with CO2 retention and the development of emphysema-like lesions. In conclusion, computed tomography is not only a research tool, but a useful technique which allows a better understanding of the progressive change in strategy needed to ventilate the adult respiratory distress syndrome lung at different stages of the disease.

The distribution of tidal volume (VT) and recruitment was investigated by chest computed tomography (CT) in eight sedated-paralyzed patients with the adult respiratory distress syndrome (ARDS). A CT section was obtained in the supine position at 0, 5, 10, 15, and 20 cm H2O positive end-expiratory pressure (PEEP) and at the corresponding inspiratory plateau pressure (21 +/- 1.8, 26 +/- 1.4, 31 +/- 1.8, 38 +/- 2.1, and 46 +/- 3.2 cm H2O [mean +/- SE]), keeping VT constant. Each CT section was divided along its ventral-dorsal height into 10 equally spaced intervals (levels). Vi(insp) and Vi(exp) were defined as the gas volume for level i (i = 1 to 10) at end-inspiration and at end-expiration, respectively. The following variables were computed at each lung level: (1) distribution of CT section tidal volume (VTct), i.e., the fraction of VT that inflates a given lung level; (2) the plateau-induced and PEEP-induced recruitment, i.e., the amount of lung tissue previously collapsed that inflates at plateau pressure and at PEEP, respectively; (3) the reopening-collapsing tissue, i.e., the amount of lung tissue that regains inflation at plateau pressure and collapses at PEEP. With increasing PEEP from 0 to 20 cm H2O, the VTct distribution decreased significantly (p0.01) in the upper levels, did not change in the middle levels, and increased significantly (p0.01) in the lower levels.(ABSTRACT TRUNCATED AT 250 WORDS)

A novel pressure gated tidal flow extracorporeal circulation (TF ECC) device was developed, and it was hypothesized that it could provide total respiratory support in apneic adult sheep without adverse hemodynamic or cardiac effects. The circuit consisted of a single lumen cannula, computer driven tubing occluders gated by circuit pressure, a nonocclusive peristaltic blood pump, a spiral coiled membrane lung, and a heat exchanger. Six paralyzed, anesthetized adult sheep were instrumented and TF ECC was instituted via cannulation of the right atrium. Total respiratory support was provided by the circuit during an apneic period of 6 hours. Echocardiography was performed with the animal instrumented (baseline) and after 2 hours of TF ECC. Circuit blood tidal volume was 172.6 +/- 18.0 cc, resulting in a TF ECC flow of 71.1 +/- 10.1 cc/kg/min. At the end of the study period, PaCO2 was 35.5 +/- 7.6 mmHg, paO2) was 91.2 +/- 30.6 mmHg, and pulmonary artery oxygen saturation (SPAO2) was 95 +/- 5%. Hemodynamic stability was maintained with no significant differences at baseline and after 6 hours in mean arterial pressure, mean pulmonary artery pressure, or heart rate noted. Echocardiographic evaluation showed preserved fractional shortening of the left ventricular (LV) septal-lateral dimension (baseline 32.4 +/- 11.4%; 2 hours 34.8 +/- 8.4%). This study demonstrates TF ECC provides total respiratory support without adverse hemodynamic effects, and preserved LV function.

In a previous preliminary study, HMG (Pergonal 500 -Serono Italy) was favourably used to induce superovulation in heifers. In the present work, the results of further clinical and endocrinological investigations using another treatment schedule are reported. Both friesian heifers and lactating friesian cows, starting from the 9th–11th day of the cycle, received i.m. two ampoules of Pergonal 500 (75 i.u. FSH and 75 i.u. LH per ampoule) at 0, 12, 24, 36 hours and one ampoule at 48, 60, 72, 84, 96 and 108 hours. At the 72nd hour, all donors received 2 ml of Estrumate (I.C.I.) and, at estrus, 1000 i.u. of HCG (Profasi, Serono) 24 hours apart. Both clinical and endocrinological results showed that all animals responded well to the superovulatory stimulus. No donor gave less than two transferable embryos. The mean number of ovulations (11.66 and 10.36 for heifers and cows respectively), the low individual variability, the low number of persistent follicles, the rate of transferable embryos (67%) and the rapid spontaneous restoration of estrous cycles show that the schedule adopted induced satisfactory superovulation of both heifers and cows in embryo transfer practice.

We studied 16 patients with acute lung injury receiving volume-controlled ventilation to assess the relationships between gas exchange and respiratory mechanics before, during, and after 2 h in the prone position. We measured the end-expiratory lung volume (EELV, helium dilution), the total respiratory system (Cst,rs), the lung (Cst,L) and the thoracoabdominal cage (Cst,w) compliances (end-inspiratory occlusion technique and esophageal balloon), the hemodynamics, and gas exchange. In the prone position, PaO2 increased from 103.2 +/- 23.8 to 129.3 +/- 32.9 mm Hg (p < 0.05) without significant changes of Cst,rs and EELV. However, Cst,w decreased from 204.8 +/- 97.4 to 135.9 +/- 52.5 ml/cm H2O (p < 0.01) and the decrease was correlated with the oxygenation increase (r = 0.62, p < 0.05). Furthermore, the greater the baseline supine Cst,w, the greater its decrease in the prone position (r = 0.82, p < 0.01). Consequently, the oxygenation changes in the prone position were predictable from baseline supine Cst,w (r = 0.80, p < 0.01). Returning to the supine position, Cst,rs increased compared with baseline (42.3 +/- 14.4 versus 38.4 +/- 13.7 ml/cm H2O; p < 0.01), mainly because of the lung component (57.5 +/- 25.1 versus 52.4 +/- 23.3 ml/cm H2O; p < 0.01). Thus, (1) baseline Cst,w and its changes may play a role in determining the oxygenation response in the prone position; (2) the prone position improves Cst,rs and Cst,L when the supine position is resumed.

I modelli di assegnazione stocastica si sono ampiamenti consolidati come strumenti applicativi ampiamente diffusi nel campo della pianificazione dei trasporti. Nel'utilizzo di tali modelli alcini aspetti devono essere attentamente valutati. Ad esempio, i costi di riferimento utilizzati per il calcolo della distribuzione dei costi percepiti d'arco dovrebbero essere tenuti fissi all'interno di un algoritmo MSA-probit. In secondo luogo, i test di arresto utilizzati per gli algoritmi MSA dovrebbero essere attentamente specificati e dovrebbero essere tesi a verificare (probabilisticamente) il soddisfacimento della definizione di equilibrio e non la mera stabilizzazione dell'algoritmo di calcolo dei flussi. La pubblicazione è finalizzata a dimostrare i più opportuni metodi per raggiungere buoni risultati in termioni di efficienza con riferimento alle predette esigenze e ad altre, quali ad esempi l'estrazione di costi percepiti su rete non negativi e la messa a punto di opportune routine di caricamento dei minimi percorsi iterativamente trovati da un algoritmo MSA.