The increase in cardiac output induced by a decrease in positive end-expiratory pressure reliably detects volume responsiveness: the PEEP-test study.

BACKGROUND: In patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness. METHODS: Mechanically ventilated patients with PEEP ≥ 10 cmH2O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test. RESULTS: We enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p < 0.0001) in comparison with volume unresponsive patients. In volume unresponsive patients, PLR and the PEEP-test increased CI by 2% (1-5%) and 6% (3-8%), respectively. Volume responsiveness was predicted by an increase in CI > 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p < 0.0001 vs. 0.5). Spearman's correlation coefficient between the changes in CI induced by PLR and the PEEP-test was 0.76 (95%CI 0.63-0.85, p < 0.0001). CONCLUSIONS: A CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

Environmental Impact of Bronchoscopy: Analysis of Waste Mass and Recyclability of Bronchoscopic Equipment and Consumables.

BACKGROUND: Greenhouse gases (GHGs) are significant contributors to climate change, and CO2 equivalent (CO2-e) is measured to compare emissions from GHGs. The healthcare sector contributes 4.4% of global CO2-e emissions, mainly with energy consumption and, in lesser extent, waste production. In this regard, bronchoscopy procedures produce a large amount of waste and are responsible for a significant consumption of energy. OBJECTIVE: We aimed at quantifying the impact on waste mass production, energy consumption, and recyclability of bronchoscopic procedures. METHODS: We conducted a prospective single-centre observational study; for each type of procedure (performed with either reusable or single-use instruments), the number of items used, their weight, and recyclability were evaluated, as well as the material of which recyclable waste was made of. We then calculated the total amount of waste produced, its recyclability, energy consumption, and CO2-e produced over 10 days of activity in our Interventional Pulmonology Unit. RESULTS: Sixty procedures generated 61,928 g of waste, of which only 15.8% was potentially recyclable. Single-use instruments generated nearly twofold more recyclable waste than reusable ones, 80% during the procedure phase. Reusable instruments generated 45% of waste during the reprocessing phase, of which 50% was recyclable. The recyclable material was totally composed of paper and plastic. During 10 days of activity, we consumed 64 kWh and produced more than 67 kg of CO2-e due to non-recyclable waste and energy consumption. CONCLUSIONS: Our results confirm the compelling need to recycle as many materials as possible, even if the amount of recyclable waste is limited. In this respect, official documents issued by international societies are urgently needed to align our activity with climate requirements and improve the sustainability of our work.

COVID-19 Biomarkers at the Crossroad between Patient Stratification and Targeted Therapy: The Role of Validated and Proposed Parameters.

Clinical knowledge about SARS-CoV-2 infection mechanisms and COVID-19 pathophysiology have enormously increased during the pandemic. Nevertheless, because of the great heterogeneity of disease manifestations, a precise patient stratification at admission is still difficult, thus rendering a rational allocation of limited medical resources as well as a tailored therapeutic approach challenging. To date, many hematologic biomarkers have been validated to support the early triage of SARS-CoV-2-positive patients and to monitor their disease progression. Among them, some indices have proven to be not only predictive parameters, but also direct or indirect pharmacological targets, thus allowing for a more tailored approach to single-patient symptoms, especially in those with severe progressive disease. While many blood test-derived parameters quickly entered routine clinical practice, other circulating biomarkers have been proposed by several researchers who have investigated their reliability in specific patient cohorts. Despite their usefulness in specific contexts as well as their potential interest as therapeutic targets, such experimental markers have not been implemented in routine clinical practice, mainly due to their higher costs and low availability in general hospital settings. This narrative review will present an overview of the most commonly adopted biomarkers in clinical practice and of the most promising ones emerging from specific population studies. Considering that each of the validated markers reflects a specific aspect of COVID-19 evolution, embedding new highly informative markers into routine clinical testing could help not only in early patient stratification, but also in guiding a timely and tailored method of therapeutic intervention.

Tidal volume challenge to predict preload responsiveness in patients with acute respiratory distress syndrome under prone position.

BACKGROUND: Prone position is frequently used in patients with acute respiratory distress syndrome (ARDS), especially during the Coronavirus disease 2019 pandemic. Our study investigated the ability of pulse pressure variation (PPV) and its changes during a tidal volume challenge (TVC) to assess preload responsiveness in ARDS patients under prone position. METHODS: This was a prospective study conducted in a 25-bed intensive care unit at a university hospital. We included patients with ARDS under prone position, ventilated with 6 mL/kg tidal volume and monitored by a transpulmonary thermodilution device. We measured PPV and its changes during a TVC (ΔPPV TVC6-8) after increasing the tidal volume from 6 to 8 mL/kg for one minute. Changes in cardiac index (CI) during a Trendelenburg maneuver (ΔCITREND) and during end-expiratory occlusion (EEO) at 8 mL/kg tidal volume (ΔCI EEO8) were recorded. Preload responsiveness was defined by both ΔCITREND ≥ 8% and ΔCI EEO8 ≥ 5%. Preload unresponsiveness was defined by both ΔCITREND < 8% and ΔCI EEO8 < 5%. RESULTS: Eighty-four sets of measurements were analyzed in 58 patients. Before prone positioning, the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen was 104 ± 27 mmHg. At the inclusion time, patients were under prone position for 11 (2-14) hours. Norepinephrine was administered in 83% of cases with a dose of 0.25 (0.15-0.42) µg/kg/min. The positive end-expiratory pressure was 14 (11-16) cmH2O. The driving pressure was 12 (10-17) cmH2O, and the respiratory system compliance was 32 (22-40) mL/cmH2O. Preload responsiveness was detected in 42 cases. An absolute change in PPV ≥ 3.5% during a TVC assessed preload responsiveness with an area under the receiver operating characteristics (AUROC) curve of 0.94 ± 0.03 (sensitivity: 98%, specificity: 86%) better than that of baseline PPV (0.85 ± 0.05; p = 0.047). In the 56 cases where baseline PPV was inconclusive (≥ 4% and < 11%), ΔPPV TVC6-8 ≥ 3.5% still enabled to reliably assess preload responsiveness (AUROC: 0.91 ± 0.05, sensitivity: 97%, specificity: 81%; p < 0.01 vs. baseline PPV). CONCLUSION: In patients with ARDS under low tidal volume ventilation during prone position, the changes in PPV during a TVC can reliably assess preload responsiveness without the need for cardiac output measurements. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04457739). Registered 30 June 2020 -Retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT04457739.

Extravascular lung water levels are associated with mortality: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of extravascular lung water (EVLW) measured by transpulmonary thermodilution (TPTD) in critically ill patients is debated. We performed a systematic review and meta-analysis of studies assessing the effects of TPTD-estimated EVLW on mortality in critically ill patients. METHODS: Cohort studies published in English from Embase, MEDLINE, and the Cochrane Database of Systematic Reviews from 1960 to 1 June 2021 were systematically searched. From eligible studies, the values of the odds ratio (OR) of EVLW as a risk factor for mortality, and the value of EVLW in survivors and non-survivors were extracted. Pooled OR were calculated from available studies. Mean differences and standard deviation of the EVLW between survivors and non-survivors were calculated. A random effects model was computed on the weighted mean differences across the two groups to estimate the pooled size effect. Subgroup analyses were performed to explore the possible sources of heterogeneity. RESULTS: Of the 18 studies included (1296 patients), OR could be extracted from 11 studies including 905 patients (464 survivors vs. 441 non-survivors), and 17 studies reported EVLW values of survivors and non-survivors, including 1246 patients (680 survivors vs. 566 non-survivors). The pooled OR of EVLW for mortality from eleven studies was 1.69 (95% confidence interval (CI) [1.22; 2.34], p < 0.0015). EVLW was significantly lower in survivors than non-survivors, with a mean difference of -4.97 mL/kg (95% CI [-6.54; -3.41], p < 0.001). The results regarding OR and mean differences were consistent in subgroup analyses. CONCLUSIONS: The value of EVLW measured by TPTD is associated with mortality in critically ill patients and is significantly higher in non-survivors than in survivors. This finding may also be interpreted as an indirect confirmation of the reliability of TPTD for estimating EVLW at the bedside. Nevertheless, our results should be considered cautiously due to the high risk of bias of many studies included in the meta-analysis and the low rating of certainty of evidence. Trial registration the study protocol was prospectively registered on PROSPERO: CRD42019126985.

COVID-19 Diagnosis in Case of Two Negative Nasopharyngeal Swabs: Association between Chest CT and Bronchoalveolar Lavage Results.

See also the editorial by Little in this issue.

Changes in the Plethysmographic Perfusion Index During an End-Expiratory Occlusion Detect a Positive Passive Leg Raising Test.

OBJECTIVES: The end-expiratory occlusion test for assessing preload responsiveness consists in interrupting mechanical ventilation for 15 seconds at end-expiration and measuring the cardiac index changes. The perfusion index is the ratio between the pulsatile and the nonpulsatile portions of the plethysmography signal and is, in part, determined by stroke volume. We tested whether the end-expiratory occlusion-induced changes in perfusion index could detect a positive passive leg raising test, suggesting preload responsiveness. DESIGN: Observational study. SETTING: Medical ICU. PATIENTS: Thirty-one ventilated patients without atrial fibrillation. INTERVENTIONS: We measured perfusion index (Radical-7 device; Masimo Corp., Irvine, CA) and cardiac index (PiCCO2; Pulsion Medical Systems, Feldkirchen, Germany) before and during a passive leg raising test and a 15-second end-expiratory occlusion. MEASUREMENTS AND MAIN RESULTS: In 19 patients with a positive passive leg raising test (increase in cardiac index ≥ 10%), compared to the baseline value and expressed as a relative change, passive leg raising increased cardiac index and perfusion index by 17% ± 7% and 49% ± 23%, respectively, In these patients, end-expiratory occlusion increased cardiac index and perfusion index by 6% ± 2% and 11% ± 8%, respectively. In the 12 patients with a negative passive leg raising test, perfusion index did not significantly change during passive leg raising and end-expiratory occlusion. Relative changes in perfusion index and cardiac index observed during all interventions were significantly correlated (r = 0.83). An end-expiratory occlusion-induced relative increase in perfusion index greater than or equal to 2.5% ([perfusion index during end-expiratory occlusion-perfusion index at baseline]/perfusion index at baseline × 100) detected a positive passive leg raising test with an area under the receiver operating characteristic curve of 0.95 ± 0.03. This threshold is larger than the least significant change observed for perfusion index (1.62% ± 0.80%). CONCLUSIONS: Perfusion index could be used as a reliable surrogate of cardiac index for performing the end-expiratory occlusion test. Confirming previous results, the relative changes in perfusion index also reliably detected a positive passive leg raising test.

Effects of Prone Positioning on Venous Return in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine the effects of prone positioning on venous return and its determinants such as mean systemic pressure and venous return resistance in patients with acute respiratory distress syndrome. DESIGN: Prospective monocentric study. SETTINGS: A 25-bed medical ICU. PATIENTS: About 22 patients with mild-to-severe acute respiratory distress syndrome in whom prone positioning was decided. INTERVENTIONS: We obtained cardiac index, mean systemic pressure, and venous return resistance (the latter two estimated through the heart-lung interactions method) before and during prone positioning. Preload responsiveness was assessed at baseline using an end-expiratory occlusion test. MEASUREMENTS AND MAIN RESULTS: Prone positioning significantly increased mean systemic pressure (from 24 mm Hg [19-34 mm Hg] to 35 mm Hg [32-46 mm Hg]). This was partly due to the trunk lowering performed before prone positioning. In seven patients, prone positioning increased cardiac index greater than or equal to 15%. All were preload responsive. In these patients, prone positioning increased mean systemic pressure by 82% (76-95%), central venous pressure by 33% (21-59%), (mean systemic pressure - central venous pressure) gradient by 144% (83-215)%, while it increased venous return resistance by 71% (60-154%). In 15 patients, prone positioning did not increase cardiac index greater than or equal to 15%. In these patients, prone positioning increased mean systemic pressure by 28% (18-56%) (p < 0.05 vs. patients with significant increase in cardiac index), central venous pressure by 21% (7-54%), (mean systemic pressure - central venous pressure) gradient by 28% (23-86%), and venous return resistance by 37% (17-77%). Eleven of these 15 patients were preload unresponsive. CONCLUSIONS: Prone positioning increased mean systemic pressure in all patients. The resulting change in cardiac index depended on the extent of increase in (mean systemic pressure - central venous pressure) gradient, of preload responsiveness, and of the increase in venous return resistance. Cardiac index increased only in preload-responsive patients if the increase in venous return resistance was lower than the increase in the (mean systemic pressure -central venous pressure) gradient.

Do changes in pulse pressure variation and inferior vena cava distensibility during passive leg raising and tidal volume challenge detect preload responsiveness in case of low tidal volume ventilation?

BACKGROUND: In patients ventilated with tidal volume (Vt) < 8 mL/kg, pulse pressure variation (PPV) and, likely, the variation of distensibility of the inferior vena cava diameter (IVCDV) are unable to detect preload responsiveness. In this condition, passive leg raising (PLR) could be used, but it requires a measurement of cardiac output. The tidal volume (Vt) challenge (PPV changes induced by a 1-min increase in Vt from 6 to 8 mL/kg) is another alternative, but it requires an arterial line. We tested whether, in case of Vt = 6 mL/kg, the effects of PLR could be assessed through changes in PPV (ΔPPVPLR) or in IVCDV (ΔIVCDVPLR) rather than changes in cardiac output, and whether the effects of the Vt challenge could be assessed by changes in IVCDV (ΔIVCDVVt) rather than changes in PPV (ΔPPVVt). METHODS: In 30 critically ill patients without spontaneous breathing and cardiac arrhythmias, ventilated with Vt = 6 mL/kg, we measured cardiac index (CI) (PiCCO2), IVCDV and PPV before/during a PLR test and before/during a Vt challenge. A PLR-induced increase in CI ≥ 10% defined preload responsiveness. RESULTS: At baseline, IVCDV was not different between preload responders (n = 15) and non-responders. Compared to non-responders, PPV and IVCDV decreased more during PLR (by - 38 ± 16% and - 26 ± 28%, respectively) and increased more during the Vt challenge (by 64 ± 42% and 91 ± 72%, respectively) in responders. ∆PPVPLR, expressed either as absolute or as percent relative changes, detected preload responsiveness (area under the receiver operating curve, AUROC: 0.98 ± 0.02 for both). ∆IVCDVPLR detected preload responsiveness only when expressed in absolute changes (AUROC: 0.76 ± 0.10), not in relative changes. ∆PPVVt, expressed as absolute or percent relative changes, detected preload responsiveness (AUROC: 0.98 ± 0.02 and 0.94 ± 0.04, respectively). This was also the case for ∆IVCDVVt, but the diagnostic threshold (1 point or 4%) was below the least significant change of IVCDV (9[3-18]%). CONCLUSIONS: During mechanical ventilation with Vt = 6 mL/kg, the effects of PLR can be assessed by changes in PPV. If IVCDV is used, it should be expressed in percent and not absolute changes. The effects of the Vt challenge can be assessed on PPV, but not on IVCDV, since the diagnostic threshold is too small compared to the reproducibility of this variable. TRIAL REGISTRATION: Agence Nationale de Sécurité du Médicament et des Produits de santé: ID-RCB: 2016-A00893-48.

Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock.

BACKGROUND: Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR). METHODS: In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%. RESULTS: Norepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose. CONCLUSIONS: Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.

4D Electromagnetic Navigation Bronchoscopy for the Sampling of Pulmonary Lesions: First European Real-Life Experience.

PURPOSE: The use of Electromagnetic navigation bronchoscopy (ENB) for the diagnosis of pulmonary peripheral lesions is still debated due to its variable diagnostic yield; a new 4D ENB system, acquiring inspiratory and expiratory computed tomography (CT) scans, overcomes respiratory motion and uses tracked sampling instruments, reaching higher diagnostic yields. We aimed at evaluating diagnostic yield and accuracy of a 4D ENB system in sampling pulmonary lesions and at describing their influencing factors. METHODS: We conducted a three-year retrospective observational study including all patients with pulmonary lesions who underwent 4D ENB with diagnostic purposes; all the factors potentially influencing diagnosis were recorded. RESULTS: 103 ENB procedures were included; diagnostic yield and accuracy were, respectively, 55.3% and 66.3%. We reported a navigation success rate of 80.6% and a diagnosis with ENB was achieved in 68.3% of cases; sensitivity for malignancy was 61.8%. The majority of lesions had a bronchus sign on CT, but only the size of lesions influenced ENB diagnosis (p < 0.05). Transbronchial needle aspiration biopsy was the most used tool (93.2% of times) with the higher diagnostic rate (70.2%). We reported only one case of pneumothorax. CONCLUSION: The diagnostic performance of a 4D ENB system is lower than other previous navigation systems used in research settings. Several factors still influence the reachability of the lesion and therefore diagnostic yield. Patient selection, as well as the multimodality approach of the lesion, is strongly recommended to obtain higher diagnostic yield and accuracy, with a low rate of complications.

SARS-CoV-2 Detection on Bronchoalveolar Lavage: An Italian Multicenter experience.

BACKGROUND: Bronchoscopy with bronchoalveolar lavage (BAL) during the SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic should be reserved to a limited number of clinical indications. The yield of BAL for the diagnosis of suspected or confirmed pulmonary SARS-CoV-2 infection is still unknown. OBJECTIVES: We aimed to evaluate the diagnostic ratio of BAL in detecting SARS-CoV-2 pulmonary infection in patients undergoing bronchoscopy for different indications as well as describe the clinical, radiological, and endoscopic characteristics of patients with SARS-CoV-2 on BAL. METHOD: We conducted a multicenter retrospective study including all patients who underwent bronchoscopy for the detection of SARS-CoV-2 on BAL. Clinical, computed tomography (CT), endoscopic, and microbiologic data were gathered from March 16th to May 27th, 2020. RESULTS: 131 patients were included. Bronchoscopy was performed for suspected SARS-CoV-2 infection (65.5%), alternative diagnosis (12.9%), suspected superinfections (19.8%), and lung atelectasis (1.5%). SARS-CoV-2 was isolated on BAL 43 times (32.8%) and the highest isolation rate was in patients with suspected SARS-CoV-2 infection (74.4%); 76% of positive patients had a double-negative nasopharyngeal swab. Peripheral, posterior and multilobar CT opacities were more frequent in SARS-CoV-2 patients, and the number of CT findings was higher in positive patients, particularly those with suspected SARS-CoV-2 infection. We recorded a progressive reduction of SARS-CoV-2 isolation during the observation period. CONCLUSIONS: In our centers, the rate of detection of SARS-CoV-2 on BAL in patients with suspected infection was 37.2%. The agreement of BAL with nasopharyngeal swabs was high; CT alterations could predict the pretest probability of SARS-CoV-2 infection, but suspicion of viral infection should be always considered.

Overlapping polyclonal lymphoproliferative disorders.

Multicentric Castleman disease (MCD) is a rare clinical entity characterized by a polyclonal lymphoid proliferation, leading to generalized lymphadenopathy, organomegaly and systemic symptoms. It has been reported in association with either other monoclonal or polyclonal lymphoid disorders, such as POEMS syndrome and immunoglobulin (Ig)G4-related disease. We present a patient showing a variant of MCD, sharing common features with POEMS syndrome and associated with the proliferation of IgG4-producing plasma cells.

The effects of passive leg raising may be detected by the plethysmographic oxygen saturation signal in critically ill patients.

BACKGROUND: A passive leg raising (PLR) test is positive if the cardiac index (CI) increased by > 10%, but it requires a direct measurement of CI. On the oxygen saturation plethysmographic signal, the perfusion index (PI) is the ratio between the pulsatile and the non-pulsatile portions. We hypothesised that the changes in PI could predict a positive PLR test and thus preload responsiveness in a totally non-invasive way. METHODS: In patients with acute circulatory failure, we measured PI (Radical-7) and CI (PiCCO2) before and during a PLR test and, if decided, before and after volume expansion (500-mL saline). RESULTS: Three patients were excluded because the plethysmography signal was absent and 3 other ones because it was unstable. Eventually, 72 patients were analysed. In 34 patients with a positive PLR test (increase in CI ≥ 10%), CI and PI increased during PLR by 21 ± 10% and 54 ± 53%, respectively. In the 38 patients with a negative PLR test, PI did not significantly change during PLR. In 26 patients in whom volume expansion was performed, CI and PI increased by 28 ± 14% and 53 ± 63%, respectively. The correlation between the PI and CI changes for all interventions was significant (r = 0.64, p < 0.001). During the PLR test, if PI increased by > 9%, a positive response of CI (≥ 10%) was diagnosed with a sensitivity of 91 (76-98%) and a specificity of 79 (63-90%) (area under the receiver operating characteristics curve 0.89 (0.80-0.95), p < 0.0001). CONCLUSION: An increase in PI during PLR by 9% accurately detects a positive response of the PLR test. TRIAL REGISTRATION: ID RCB 2016-A00959-42. Registered 27 June 2016.

Gas6/TAM System: A Key Modulator of the Interplay between Inflammation and Fibrosis.

Fibrosis is the result of an overly abundant deposition of extracellular matrix (ECM) due to the fact of repetitive tissue injuries and/or dysregulation of the repair process. Fibrogenesis is a pathogenetic phenomenon which is involved in different chronic human diseases, accounting for a high burden of morbidity and mortality. Despite being triggered by different causative factors, fibrogenesis follows common pathways, the knowledge of which is, however, still unsatisfactory. This represents a significant limit for the development of effective antifibrotic drugs. In the present paper, we aimed to review the current evidence regarding the potential role played in fibrogenesis by growth arrest-specific 6 (Gas6) and its receptors Tyro3 protein tyrosine kinase (Tyro3), Axl receptor tyrosine kinase (Axl), and Mer tyrosine kinase protooncogene (MerTK) (TAM). Moreover, we aimed to review data about the pathogenetic role of this system in the development of different human diseases characterized by fibrosis. Finally, we aimed to explore the potential implications of these findings in diagnosis and treatment.

Electromagnetic Navigation Bronchoscopy: Where Are We Now? Five Years of a Single-Center Experience.

INTRODUCTION: Electromagnetic navigation (ENB) is a guidance tool used in the diagnosis of solitary pulmonary nodules (SPNs) and masses. Its diagnostic yield is highly variable (38-71%) and a recent study has put in doubt the role of ENB in sampling SPNs in a real-life setting. The aim of this study is to describe the 5-year experience of our center with ENB, analyzing the population, possible confounding factors, and the diagnostic yield and accuracy of this technique. METHODS: We conducted a retrospective observational study including all consecutive patients who underwent ENB for SPNs and masses from January 2011 to December 2015. RESULTS: We included 113 patients; 79% had SPNs, 21% masses. The majority were localized in the upper and middle lobes (80%) and 61% presented a bronchus sign. 54% of the patients had a previous negative fluoroscopy-guided bronchoscopy. ENB achieved the diagnosis in 78 patients (69%) with 64 malignant and 14 were benign lesions. The diagnostic yield and accuracy of ENB were respectively 0.69 and 0.76. The only factor influencing the ability to reach a diagnosis was the presence of bronchus sign (p = 0.002). No procedural complications were reported. CONCLUSION: ENB is a safe procedure with a similar diagnostic yield in the real-life and research setting. Bronchus sign is an important factor in determining the diagnostic yield. ENB efficacy can be maximized by expertise and by a careful selection of each case.

Decrease of haemoconcentration reliably detects hydrostatic pulmonary oedema in dyspnoeic patients in the emergency department - a machine learning approach.

BACKGROUND: Haemoglobin variation (ΔHb) induced by fluid transfer through the intestitium has been proposed as a useful tool for detecting hydrostatic pulmonary oedema (HPO). However, its use in the emergency department (ED) setting still needs to be determined. METHODS: In this observational retrospective monocentric study, ED patients admitted for acute dyspnoea were enrolled. Hb values were recorded both at ED presentation (T0) and after 4 to 8 h (T1). ΔHb between T1 and T0 (ΔHbT1-T0) was calculated as absolute and relative value. Two investigators, unaware of Hb values, defined the cause of dyspnoea as HPO and non-HPO. ΔHbT1-T0 ability to detect HPO was evaluated. A machine learning approach was used to develop a predictive tool for HPO, by considering the ability of ΔHb as covariate, together with baseline patient characteristics. RESULTS: Seven-hundred-and-six dyspnoeic patients (203 HPO and 503 non-HPO) were enrolled over 19 months. Hb levels were significantly different between HPO and non-HPO patients both at T0 and T1 (p < 0.001). ΔHbT1-T0 were more pronounced in HPO than non-HPO patients, both as relative (-8.2 [-11.2 to -5.6] vs. 0.6 [-2.1 to 3.3] %) and absolute (-1.0 [-1.4 to -0.8] vs. 0.1 [-0.3 to 0.4] g/dL) values (p < 0.001). A relative ΔHbT1-T0 of -5% detected HPO with an area under the receiver operating characteristic curve (AUROC) of 0.901 [0.896-0.906]. Among the considered models, Gradient Boosting Machine showed excellent predictive ability in identifying HPO patients and was used to create a web-based application. ΔHbT1-T0 was confirmed as the most important covariate for HPO prediction. CONCLUSIONS: ΔHbT1-T0 in patients admitted for acute dyspnoea reliably identifies HPO in the ED setting. The machine learning predictive tool may represent a performing and clinically handy tool for confirming HPO.

Idiopathic Pulmonary Fibrosis and Post-COVID-19 Lung Fibrosis: Links and Risks.

Idiopathic pulmonary fibrosis (IPF) is considered the paradigmatic example of chronic progressive fibrosing disease; IPF does not result from a primary immunopathogenic mechanism, but immune cells play a complex role in orchestrating the fibrosing response. These cells are activated by pathogen-associated or danger-associated molecular patterns generating pro-fibrotic pathways or downregulating anti-fibrotic agents. Post-COVID pulmonary fibrosis (PCPF) is an emerging clinical entity, following SARS-CoV-2 infection; it shares many clinical, pathological, and immune features with IPF. Similarities between IPF and PCPF can be found in intra- and extracellular physiopathological pro-fibrotic processes, genetic signatures, as well as in the response to antifibrotic treatments. Moreover, SARS-CoV-2 infection can be a cause of acute exacerbation of IPF (AE-IPF), which can negatively impact on IPF patients' prognosis. In this narrative review, we explore the pathophysiological aspects of IPF, with particular attention given to the intracellular signaling involved in the generation of fibrosis in IPF and during the SARS-CoV-2 infection, and the similarities between IPF and PCPF. Finally, we focus on COVID-19 and IPF in clinical practice.

Measure of lung dielectric proprieties in patients with Idiopathic Pulmonary Fibrosis: correlation with clinical, radiological and pulmonary functional parameters.

BACKGROUND: Dielectric properties of biological tissues are biophysical parameters; in lung they change with amount of air, blood and parenchyma. Remote Dielectric Sensing (ReDS™) technology measures dielectric properties of lung tissues quantifying the content of fluids inside the scan volume. We aimed to evaluate the reliability of ReDS™ measure in Idiopathic Pulmonary Fibrosis (IPF) patients and in healthy volunteers, and to investigate the correlation of ReDS™ score with clinical, radiological and functional parameters. METHODS: We conducted a prospective observational study, including 52 patients with diagnosis of IPF and 17 healthy volunteers; for each patient we recorded: complete functional evaluation, dyspnoea score (mMRC scale), Usual Interstitial Pneumonia (UIP) Computed Tomography (CT) pattern (UIP definite or probable) and ReDS™ measure (expressed in %). RESULTS: ReDS™ measure was reported as correct both in patients and controls, the firsts with higher scores (33.8% vs 29.1%, p = 0.003). In IPF patients we observed a significant inverse correlation with ReDS™ score and Forced Vital Capacity (FVC), Vital Capacity (VC) and Total Lung Capacity (TLC) measures and, when we considered only patients with UIP definite CT pattern, the correlation was inverse with FVC, VC, TLC, DLCO. In IPF patients the higher was mMRC dyspnoea index, the higher was ReDS™ score. No significant correlations were observed between ReDS™ score and functional parameters in healthy controls. DISCUSSION: We demonstrated a correlation of ReDS™ scores with some functional (mainly indicative or diagnostic for restriction) and clinical parameters in IPF patients; the score was correlated with density of tissues possibly quantifying tissue fibrosis in IPF patients.