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Objective: Sniff nasal inspiratory pressure (SNIP), a useful tool for the assessment of diaphragm function in patients with Amyotrophic Lateral Sclerosis (ALS), is usually performed together with l...

We reported the case of a 55-year-old man with a large tracheal lobular capillary haemangioma attached to posterior tracheal wall and successfully managed with arterial embolization followed by endoscopic resection using Harmonic™ ACE Plus. Because of the high risk of bleeding, Harmonic™ was used in this case due to its ability to cut and cauterize simultaneously. The instrument jaw repeatedly grasped the attachment point of tumor, and then the cavitation effect, created by the longitudinal vibration of the blade tip, separated it from the posterior tracheal wall, reducing the risk of perforation. Yet, the ultrasonic energy denatured proteins and coagulated the vessels, preventing the bleeding during resection. No complications occurred during and after the procedure. Twelve-month follow-up showed no recurrence.

Background: Noninvasive mechanical ventilation (NIV) is an effective treatment in patients with neuromuscular diseases (NMD) to improve symptoms, quality of life, and survival. Summary: NIV should be used early in the course of respiratory muscle involvement in NMD patients and its requirements may increase over time. Therefore, training on technical equipment at home and advice on problem solving are warranted. Remote monitoring of ventilator parameters using built-in ventilator software is recommended. Telemedicine may be helpful in reducing hospital admissions. Anticipatory planning and palliative care should be carried out to lessen the burden of care, to maintain or withdraw from NIV, and to guarantee the most respectful management in the last days of NMD patients’ life. Key Message: Long-term NIV is effective but challenging in NMD patients. Efforts should be made by health care providers in arranging a planned transition to home and end-of-life discussions for ventilator-assisted individuals and their families.

COVID-19 survivors are associated with acute respiratory failure (ARF) and show a high prevalence of impairment in physical performance. The present studied aimed to assess whether we may cluster these individuals according to an exercise test. The presented study is a retrospective analysis of 154 survivors who were admitted to two hospitals of Istituti Clinici Scientifici Maugeri network, Italy. Clinical characteristics, walked distance, heart rate (HR), pulse oximetry (SpO2), dyspnoea, and leg fatigue (Borg scale: Borg-D and Borg-F, respectively) while performing the six-minute walking test (6MWT) were entered into unsupervised clustering analysis. Multivariate linear regression identified variables that were informative for the set of variables used for cluster definition. Cluster 1 (C1: 86.4% of participants) and Cluster 2 (C2: 13.6%) were identified. Compared to C1, the individuals in C2 were significantly older, showed significantly higher increase in fatigue and in dyspnoea, greater reduction in SpO2, and a lower HRpeak during the test. The need of walking aids, time from admission to acute care hospitals, age, body mass index, endotracheal intubation, baseline HR and baseline Borg-D, and exercise-induced SpO2 change were significantly associated with the variables that were used for cluster definition. Different characteristics and physiological parameters during the 6MWT characterise survivors of COVID-19-associated ARF. These results may help in the management of the long-term effects of the disease.

Introduction Les patients atteints d’une infection grave par la COVID-19 sont susceptibles de recevoir une assistance respiratoire par pression positive continue (PPC) ou ventilation non invasive (VNI). L’utilisation de ces traitements est associee a une aerosolisation du virus qui peut mettre en danger le personnel soignant et contre laquelle diverses strategies ont ete proposees par les experts, notamment l’utilisation de masques non ventiles avec ajout d’un filtre bacterien sur les circuits inspiratoire et expiratoire. Methodes Etude sur banc d’essai, nous avons utilise une tete en 3D realiste reliee a un poumon mecanique actif (ASL 5000), sur laquelle un masque naso-buccal non ventile (Quattro FX, ResMed) etait applique. Un ventilateur (Astral 150) etait connecte au masque via 8 configurations de circuits rapportees par les experts de la VNI associees a 2 types de filtre antibacterien (basse pression: Iso-Gard, et echangeur de chaleur et d’humidite: Inter-Therm). Les montages etaient (1) masque, filtre et connecteur a angle droit perce d’un orifice de o4 mm; (2) masque, filtre et valve Whisper Swivel II; (3) masque, connecteur en T et valve Whisper Swivel II; (4) masque, piece imprimee en 3D avec orifice de o4 mm, filtre; (5) masque, circuit double branche avec filtre sur les circuits inspiratoire et expiratoire; (6) masque, valve expiratoire active deportee et filtre; (7) masque, filtre et valve expiratoire active droite; (8) masque Helmet, filtre sur les branches inspiratoire et expiratoire ( Fig. 1 ). Resultats L’ajout d’un filtre etait associe a un travail inspiratoire accru (p = 0,001), une pression inspiratoire delivree diminuee (p Fig. 1 ). Les asynchronismes patient-ventilateur (PVA) ainsi que le travail ventilateur n’etaient pas affectes. Le type de montage impactait l’effort requis pour declencher le ventilateur (p Conclusion Les performances des ventilateurs sont influencees par les differentes configurations de circuits proposees pour minimiser l’aerosolisation des particules virales. L’utilisation d’un adaptateur presentant une fuite intentionnelle sur lequel un filtre bacterien peut etre ajuste semble etre la meilleure approche.

Soluble major histocompatibility complex class I polypeptide-related sequence A (sMICA) is a useful marker in surveillance of lung cancer. High serum sMICA level in patients with non-small-cell lung cancer (NSCLC) seems to be a poor prognostic factor being correlated with poor differentiation and advanced stage. However, the low specificity limits its role as a single prognostic marker of NSCLC, but its evaluation, in addition to standard serum markers, could improve the staging of NSCLC. Despite promising, all current studies are insufficient to assess the real efficiency of sMICA as a prognostic marker of NSCLC, and hence, future studies are required to validate it.

ALS patients should discuss the issue of tracheostomy before the onset of terminal respiratory failure. While the process of shared decision-making is desirable, there are few data on the practical application of this real-life situation.To determine how a decision-making process is actually carried out, we analysed the episodes of acute respiratory failure preceding tracheostomy.We studied the charts of a group of ALS patients after tracheostomy. An interview focusing on the existence of anticipated directives was carried out. Tracheostomies were classified as planned or unplanned according to the presence of a decision plan.A total of 209 ALS patients were cared for during a three-year period. Of these patients, 34 (16%) were tracheotomised. In 38% of cases, tracheostomy was planned, 41% were unplanned, and 21% remained undiagnosed.A minority of ALS patients make a voluntary decision for tracheostomy before the procedure is conducted. The advising process of care still presents limits that have been thus far poorly addressed. In the future, we will need to develop guidelines for the timing and content of the shared-decision making process.

Objective The study aimed to evaluate whether high-flow oxygen therapy (HFOT) during training was more effective than oxygen in improving exercise capacity in hypoxemic chronic obstructive pulmonary disease (COPD). Methods A total of 171 patients with COPD and chronic hypoxemia were consecutively recruited in 8 rehabilitation hospitals in a randomized controlled trial. Cycle-ergometer exercise training was used in 20 supervised sessions at iso inspiratory oxygen fraction in both groups. Pre- and post-training endurance time (Tlim), 6-minute walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel Index, Barthel Dyspnea Index, COPD Assessment Test, Maugeri Respiratory Failure questionnaire, and patient satisfaction were evaluated. Results Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in HFOT and Venturi mask (V-mask) groups, respectively. Exercise capacity significantly improved after training in both groups with similar patient satisfaction. Between-group difference in post-training improvement in 6MWD (mean: 17.14 m; 95% CI = 0.87 to 33.43 m) but not in Tlim (mean: 141.85 seconds; 95% CI = −18.72 to 302.42 seconds) was significantly higher in HFOT. The minimal clinically important difference of Tlim was reached by 47% of patients in the V-mask group and 56% of patients in the HFOT group, whereas the minimal clinically important difference of 6MWD was reached by 51% of patients in the V-mask group and 69% of patients in the HFOT group, respectively. Conclusion In patients with hypoxemic COPD, exercise training is effective in improving exercise capacity. Impact Statement The addition of HFOT during exercise training is not more effective than oxygen through V-mask in improving endurance time, the primary outcome, whereas it is more effective in improving walking distance.

Introduction The Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU. Methods In this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analysed. Data were collected including medication, mode and usage of the NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths. Results Forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean age was 68 (sd 13) years. The PaO2/FiO2 ratio at baseline was 152±79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression. Conclusions The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination., In patients with Coronavirus 2 infection and Acute Respiratory Failure, we demonstrated that the utilization of noninvasive respiratory support delivered outside the ICU, was feasible and effective, but associated with a risk of staff contamination

Herein, we report a new technique of middle lobe fixation using Hemopatch after thoracoscopic right upper lobectomy. A 3–0 atraumatic polypropylene suture is passed first through the Hemopatch, then two not-inflated lobes, and then again patch. The lung is half-inflated, and the Hemopatch is placed onto the surface of the two half-inflated lobes in a bridging manner over the fissure. The suture is then tied by a clip. This procedure was successfully applied in five consecutive patients after thoracoscopic right upper lobectomy for cancer. No complications occurred during and after operation.

Background: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. Methods: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. Results: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P

We compared in COPD with CRF undergoing training, HFOT (AIRVO2® FisherP all used the same high-intensity exercise program (1 session/day for ≥ 20 sessions) with different oxygen device. BMI, spirometry and co morbidities have been collected. Baseline and after training exercise tolerance (Constant Work Rate Exercise Test, CWERT + 6-min walk test, 6MWT), respiratory (MIP/MEP) and biceps/quadriceps muscle strength, blood gases, Barthel Index and Barthel Dyspnoea Index, CAT and MRF-26 were measured. Patients’ satisfaction has been evaluated. 71 and 66 patients were analysed for HFOT and V-mask respectively being 15% and 24% the rate of drop-out. All variables improved after training in both groups with similar satisfaction. Comparing the two groups, only meters at 6MWT resulted statistically higher in HFOT group (p=0.029). HFOT group performed 153 seconds more than V-mask at CWERT, without statistical significance (p=0.057). Improvers (gain > 150 sec at CWERT) were 44% and 56% for V-mask and HFOT, respectively. FEV1% prd higher than 30% (OR 2.44, p=0.025) and higher baseline endurance time (OR 1.15, p=0.024) predicted improvers. Low BMI (OR 0.9298, p=0.038) predicted drop-outs. CWERT improvement was positively related to comorbidities (p=0.025) and CAT (p=0.031), while negatively to PaO2/FiO2 (p=0.04). We have confirmed the strong indication to training program in advanced COPD with CRF; HFOT used during training may further increase exercise tolerance.

Background and objective: Non invasive ventilation (NIV) is currently employed for weaning from invasive ventilation (IMV) in the acute setting but its use for weaning from prolonged ventilation is still occasional and not standardized. We wanted to evaluate whether a combined protocol of NIV and decannulation in tracheostomized patients needing prolonged mechanical ventilation was feasible and what would be the one-year outcome. Methods: We studied patients still dependent from invasive mechanical ventilation with the following inclusion criteria: a) tolerance of at least 8 h of unsupported breathing, b) progressive hypercapnia/acidosis after invasive ventilation discontinuation, c) good adaptation to NIV, d) favorable criteria for decannulation. These patients were switched from IMV to NIV and decannulated; then they were discharged on home NIV and followed-up for one year in order to evaluate survival and complications rate. Results: Data from patients consecutively admitted to a weaning unit were prospectively collected between 2005 and 2018. Out of 587 patients admitted over that period, 341 were liberated from prolonged mechanical ventilation. Fifty-one out of 147 unweaned patients (35%) were eligible for the protocol but only 46 were enrolled. After a mean length of stay of 35 days they were decannulated and discharged on domiciliary NIV. After one year, 38 patients were still alive (survival rate 82%) and 37 were using NIV with good adherence (only one patient was switched again to invasive ventilation). Conclusions: NIV applied to patients with failed weaning from prolonged IMV is feasible and can facilitate the decannulation process. Patients successfully completing this process show good survival rates and few complications. Keywords: Prolonged weaning, Non invasive ventilation, Tracheostomy decannulation, Survival, Respiratory mechanics, Rehabilitation

High flow nasal cannula (HFNC) was shown to washout the anatomical dead space, permitting a higher fraction of minute ventilation to participate in gas pulmonary exchanges. Moreover, it is able to guarantee the desired inhaled oxygen fraction (FiO2) even at high level of patient's minute ventilation by minimizing the room air entrainment. The effect of HFNC has never been investigated on stable severe COPD patients in term of endurance capacity with standardised laboratory tests.We performed, in a randomized crossover study, two constant load exercise tests at the 75% of maximum workload achieved at a previous incremental exercise test on cycle-ergometer: with (HFNC-test) and without HFNC (Control-test). Both constant load tests were fulfilled at the same inhaled oxygen fraction (isoFiO2).The endurance time significantly increased in the HFNC-test compared to the Control-test (the mean difference between the two groups was 109 ± 104 s, p 0.015). At iso-time, HFNC-test showed a better oxygen saturation (95 ± 3% vs 89 ± 3%, respectively, p 0.005) either in the subgroup of patients who used supplemental oxygen and in the subgroup who did not. Moreover, a significantly lower dyspnea (median of 5.5 vs 10, respectively, p = 0.002) and leg fatigue score (median of 5 vs 9.5, p = 0.002) was recorded at iso-time during HFNC-test.HFNC may improve the exercise performance in severe COPD patients with ventilatory limitation. This effect is associated to an improvement of SaO2 and perceived symptoms at iso-time. In a Pulmonary Rehabilitation program HFNC may allow a given high intensity load to be sustained for a longer time with less symptoms.

Discussion about patients' end-of-life (E-o-L) preferences should be part of the routine practice. Using a semi-structured interview with a scenario-based decision, we performed a prospective multicentre study to elicit the patients' E-o-L preferences in very severe chronic obstructive pulmonary disease (COPD). We also checked their ability to retain this information and the respect of their decisions when they die. Forty-three out of ninety-one of the eligible patients completed the study. The choice of E-o-L practice was equally distributed among the three proposed options: endotracheal intubation (ETI), 'ceiling' non-invasive ventilation (NIV), and palliation of symptoms with oxygen and morphine. NIV and ETI were more frequently chosen by patients who already experienced them. ETI preference was also associated with the use of anti-depressant drugs and a low educational level, while a higher educational level and a previous discussion with a pneumologist significantly correlated with the preference for oxygen and morphine. Less than 50% of the patients retained a full comprehension of the options at 24 hours. About half of the patients who died in the follow-up period were not treated according to their wishes. In conclusion, in end-stage COPD more efforts are needed to improve communication, patients' knowledge of the disease and E-o-L practice.

Background: We report short and long-term results with the dedicated Synthes ® titanium plates system, introduced 5 years ago, for chest wall stabilization and reconstruction. Methods: We retrospectively analyzed (January 2010 to December 2014) 27 consecutive patients (22 males, 5 females; range 16–83 years, median age 60 years), treated with this system: primary [3] and secondary [8] chest wall tumor; flail chest [5]; multiple ribs fractures [5]; sternal dehiscence-diastasis [3]; sternal fracture [1]; sternoclavicular joint dislocation [1]; Poland syndrome [1]. Short-term results were evaluated as: operating time, post-operative morbidity, mortality, hospital stay; long-term results as: survival, plates-related morbidity, spirometric values, chest pain [measured with Verbal Rating Scale (VRS) and SF12 standard V1 questionnaire]. Results: Each patient received from 1 to 10 (median 2) titanium plates/splints; median operating time was 150 min (range: 115–430 min). Post-operative course: 15 patients (55.6%) uneventful, 10 (37%) minor complications, 2 (7.4%) major complications; no post-operative mortality. Median post-operative hospital stay was 13 days (range: 5–129 days). At a median follow-up of 20 months (range: 1–59 months), 21 patients (78%) were alive, 6 (22%) died. Three patients presented long-term plates-related morbidity: plates rupture [2], pin plate dislodgment [1]; two required a second surgical look. One-year from surgery median spirometric values were: FVC 3.31 L (90%), FEV1 2.46 L (78%), DLCO 20.9 mL/mmHg/min (76%). On 21 alive patients, 7 (33.3%) reported no pain (VRS score 0), 10 (47.6%) mild (score 2), 4 (19.1%) moderate (score 4), no-one severe (score >4); 15 (71.5%) reported none or mild, 6 (28.5%) moderate pain influencing quality of life. Conclusions: An optimal chest wall stabilization and reconstruction was achieved with the Synthes ® titanium plates system, with minimal morbidity, no post-operative mortality, acceptable operating time and post-operative hospital stay. Long-term restoration of a normal respiratory function was achieved, with minimal plates-related morbidity and chest pain.

Vascular injury is the most dreadful complication during a video-assisted thoracoscopic surgery (VATS) lobectomy and often lead to conversion to thoracotomy. While the rate of this event considerably drops with the progression on surgical team’s learning curve, however, it is always useful to have an emergency plan to deal with it. The repairing approaches described in literature are mostly based on suction-compression angiorrhaphy technique (SCAT), involving a suture on the damaged vessels. In our case-report we display a good alternative to SCAT when we are dealing with small size lesions, without resorting to conversion. A 63-year-old with lung adenocarcinoma underwent a right upper VATS lobectomy: during the procedure, an iatrogenic lesion to intrascissural upper lobe artery occurred. We made use of suction and compression but, instead of performing a suture on the vessel, we applied hemostatic matrix sealant agent. The bleeding was effectively stopped and the wound sealed, allowing us to safely carry out the lobectomy without conversion to thoracotomy. No post-operative complications were highlighted and the patient was still alive after 6 months since the procedure. Our approach could be a useful addition to techniques already described and could be easily executed by surgeons still in learning curve. This is the first case of vascular injury managed specifically with only hemostatic matrix sealant agent described in literature and it has proven effective as well as the angiorrhaphy technique when it comes to small size artery lesions. Thanks to the easiness of sealant application, execution time of our method is shorter than a more complex repair in VATS, allowing inexperienced surgeons to fix the injury with little effort.

BackgroundWhile the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients.Materials and methodsThe European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients.ResultsThe task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode.ConclusionsManaging hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.

Non-small-cell lung carcinomas (NSCLC) is the most common type of lung cancer and it has a poor prognosis, because overall survival after 5 years is 20-25% for all stages. Thus, it is extremely important to increase the survival rate in the early stages NSCLC by focusing on novel screening tests of cancer identifying specific biomarkers expression associated with a more accurate tumor staging and patient prognosis. In this study, we focused our attention on quantitative proteomics of three heavily glycosylated serum proteins: AMBP,α2 macroglobulin, and SERPINA1. In particular, we analyzed serum samples from 20 NSCLC lung adenocarcinoma cancer patients in early and advanced stages, and 10 healthy donors to obtain a relative quantification through the MRM analysis of these proteins that have shown to be markers of cancer development and progression. AMBP, α2 macroglobulin, and SERPINA1 were chosen because all of them possess endopeptidase inhibitor activity and play key roles in cancer. We observe a variation in the expression of these proteins linked to the stage of the disease. Therefore, we believe that proteins like α2 macroglobulin, αmicroglobulin/bikunin, and SERPINA1 could be useful biomarkers for early detection of lung cancer and in monitoring its evolution.

BACKGROUND: Humidification is a standard of care during invasive mechanical ventilation. Two types of devices are used for this purpose: heated humidifiers and heat-and-moisture exchangers (HME). AIM: To compare the short-term physiologic effects of an active HME, with those of heated humidifiers and HMEs in terms of respiratory effort, ventilatory pattern, and arterial blood gases during invasive mechanical ventilation. METHODS: We conducted a randomized crossover study with 3 different devices in 15 stable subjects who had a tracheostomy and were ventilator-dependent. Transdiaphragmatic pressure, ventilatory pattern, arterial blood gases, and dyspnea scale were recorded at baseline and at the end of a 20-min period with each device. RESULTS: Compared with heated humidifiers, the active HME was associated with higher diaphragmatic pressure-time product per minute (117.10 [interquartile range {IQR} 34.58–298.60]) versus 80.86 (IQR, 25.46–110.55) cm H2O×s/min, P = .01), higher PaCO2 (48.50 [IQR, 40.65–53.70] vs 39.60 [IQR, 37.50–49.95]) mm Hg, P = .02) and lower pH (7.41 [IQR, 7.36–7.49] vs 7.45 [IQR, 7.40–7.51], P = .030) without any significant difference in ventilatory pattern. A significantly worse dyspnea scale score (active HME, 3 (2–4) vs heated humidifiers: 4 (3–5); P = .009) was also observed. No significant differences were seen between active HME and HME. CONCLUSIONS: This study indicated that, compared with the heated humidifiers, the use of the active HME or the HME increased inspiratory effort, PaCO2, pH, and dyspnea in stable subjects who were tracheostomized and ventilator-dependent.

Background: The management of lung abscess may be a challenge in elderly patients undergoing chemotherapy and/or radiotherapy for previous malignancy. Herein, we reported a case series of elderly patients with previous lymphoma undergoing endoscopic treatment followed by pulmonary rehabilitation for lung abscess. Methods: Our study population included a consecutive series of elderly patients with previous lymphoma and lung abscess. Suppurative infection was refractory with specific antibiotic therapy. In all cases, drainage was endoscopically inserted in lung abscess via video-bronchoscopy. This strategy allowed performing daily therapy with the installation of gentamicin directly into the abscess cavity. All patients underwent a respiratory rehabilitation program to speed up convalescence and allow early discharge. Results: After positioning the catheter through a bronchoscopic route and subsequent washing with gentamicin, all the patients in our study showed an improvement in clinical conditions with resolution of fever within a few days of starting the procedure with normalization of blood tests (mean hospital length 7 &plusmn, 0.73 days). A follow-up chest computed tomography scan showed a resolution of lung abscess within a mean of 27 &plusmn, 1.53 days. Conclusions: Endoscopic treatment with a rehabilitation program may be a valuable strategy for the management of lung abscess that is refractory to standard antibiotic therapy. Further and larger studiesshould be done to confirm our results.

The aim of our study was to evaluate the prevalence and predictors of obstructive sleep apnea (OSA) in patients with chronic obstructive pulmonary disease (COPD) undergoing inpatient pulmonary rehabilitation programs (PRPs). A retrospective data review of consecutive stable patients with a known diagnosis of COPD, admitted for PRP between January 2007 and December 2013. Full overnight polysomnography (PSG) and Epworth Sleepiness Scale (ESS) were assessed in all patients. Out of 422 evaluated patients, 190 (45%) showed an Apnea Hypopnea Index (AHI) ≥ 15 events/hour and underwent OSA treatment. Patients with OSA were significantly younger and had a less severe airway obstruction as compared to patients without OSA. There were no significant differences in cardiac comorbidities nor in arterial blood gases. As expected, patients with OSA showed significantly more severe diurnal symptoms, as assessed by the ESS and higher body mass index (BMI). However, only 69 out of 190 patients with OSA (36.3%) showed an ESS10, whereas 25% of them had BMI ≤25 and 41% of them had a BMI30. In all, 68% of patients with OSA were discharged with continuous positive airway pressure (CPAP), 15% with Bilevel ventilation, and 17% without any ventilatory treatment. In conclusion, in the population studied, the combination of OSA and COPD was frequent. BMI and ESS values commonly considered cutoff values for the prediction of OSA in the general population may not be accurate in a subgroup of patients with COPD.

Exercise tolerance may be significantly impaired in severe COPD. NIV increases the walking distance; however a 35% of patients do not tolerate it (Walker DJ et al. COPD 2015;1:546-51). Recently, it has been demonstrated that high flow nasal cannula (HFNC) improves the endurance time in severe COPD patients (Cirio S et al. Respir Med. 2016 Sep;118:128-132). However, the lack of an internal battery has limited its use for moving. Our study aimed to investigate if HFNC powered by an external battery increases the walking distance in COPD patients with exercise limitation. Thirteen stable COPD patients with a walking distance lower than 70% of predicted value associated to a modified Borg dyspnea SB ≥5 at 6-minute walk test (6MWT), were included. They performed two consecutive 6MWTs, in a randomised cross-over design: with and without HFNC at the same oxygen inhaled fraction. Twelve patients (one dropped-out) (mean ±SD age 69.5 ±10.3 yrs, forced expiratory volume in 1 second 25±5.6% predicted) were analysed. Walking distance was significantly higher using HFNC (median 306m (IQR 246-342) compare to no-HFNC (267m (IQR 228-294) (p In conclusion, HFNC may be safely used also during walking. In severe COPD with exercise limitation it improves the walking distance without worsening of dynamic hyperinflation.

BACKGROUND: Until recently, it has been considered essential to maintain the use of a double-limb circuit in patients with amyotrophic lateral sclerosis (ALS) to avoid rebreathing expired air during invasive mechanical ventilation. Currently, life-sustaining home ventilators can work with a single, lighter circuit that is easier to manage. Our aim was to evaluate the effectiveness and safety of a single-limb circuit with intentional leaks (passive circuit) in comparison with a circuit with an expiratory valve (active circuit), in subjects with ALS who use invasive home ventilation. METHODS: We conducted a retrospective single-center study. The enrolled subjects were divided into 2 groups according to the type of exhalation port. The aim of the study was to compare arterial blood gases; nocturnal oxygen saturation recordings; and the occurrence of adverse events, both clinical and technical events. In addition, we compared the rate of mortality and unplanned hospital admissions that occurred within a year after discharge from the hospital. RESULTS: Forty-three subjects were included in our study: 23 who used a passive circuit and 20 who used an active circuit. No significant difference in nocturnal and diurnal gas exchanges was detected. The incidence of adverse events was significantly higher in the active circuit group (85% in active circuit vs 30% in passive circuit, P CONCLUSIONS: The passive circuit was shown to be as effective and safe as the active circuit during home invasive ventilation in the subjects with amyotrophic lateral sclerosis. A future randomized controlled study is necessary to confirm these results and to extend indications to other pathologies.

BACKGROUND: A recent study found that activation of disconnection and low-pressure alarms is common during mouthpiece ventilation and may represent a major limitation to its use. The aim of this bench study was: (1) to investigate the technical aspects that can influence the setting of the ventilator during mouthpiece ventilation and (2) to provide a practical setting strategy to avoid the alarm activation. METHODS: Eight life-support ventilators able to deliver volume controlled ventilation were tested in a bench study using a single-limb non-vented circuit configuration connected to a standard mouthpiece. Disconnection and apnea alarm were turned off or set at the least sensitive setting. The backup frequency was set at the lowest available level. Different tidal volumes (VT) (from 500 to 1,200 mL) were tested with the rectangular and descending flow shape. For each VT, we reported the maximum set inspiratory time (TI) that allowed preventing activation of the low-pressure alarm. The presence of auto-triggering was also surveyed. RESULTS: We found that a correct combination of VT and TI avoided the activation of disconnection and low-pressure alarms in all but 3 ventilators. One ventilator did not allow mouthpiece ventilation independently from the settings used. The inability to turn off the apnea alarm in two other ventilators led to the alarm going off in any tested conditions after 120 s without triggered breaths. Auto-triggering was seldom found and easily worked out, except for in one ventilator. CONCLUSIONS: An appropriate alarm setting and combination of VT and TI would allow the majority of the tested ventilators to be used for mouthpiece ventilation without alarm activation.

PURPOSE: Over the last two decades, noninvasive ventilation (NIV) has been proposed in various causes of acute respiratory failure (ARF) but some indications are debated. Current trends in NIV use are unknown. METHODS: Comparison of three multicenter prospective audits including all patients receiving mechanical ventilation and conducted in 1997, 2002, and 2011 in francophone countries. RESULTS: Among the 4132 patients enrolled, 2094 (51%) required ventilatory support for ARF and 2038 (49 %) for non-respiratory conditions. Overall NIV use was markedly increased in 2010/11 compared to 1997 and 2002 (37% of mechanically ventilated patients vs. 16% and 28%, P < 0.05). In 2010/11, the use of first-line NIV for ARF had reached a plateau (24% vs. 16% and 23%, P < 0.05) whereas pre-ICU and post-extubation NIV had substantially increased (11% vs. 4% and 11% vs. 7%, respectively, P < 0.05). First-line NIV remained stable in acute-on-chronic RF, continued to increase in cardiogenic pulmonary edema, but decreased in de novo ARF (16% in 2010/11 vs. 23% in 2002, P < 0.05). The NIV success rate increased from 56% in 2002 to 70% in 2010/11 and remained the lowest in de novo ARF. NIV failure in de novo ARF was associated with increased mortality in 2002 but not in 2010/11. Mortality decreased over time, and overall, NIV use was associated with a lower mortality. CONCLUSION: Increases in NIV use and success rate, an overall decrease in mortality, and a decrease of the adverse impact NIV failure has in de novo ARF suggest better patient selection and greater proficiency of staff in administering NIV. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT01449331.

Ventilation with continuous positive airway pressure (CPAP) is the gold standard therapy for obstructive sleep apnea (OSA). However, it was recently suggested that a novel mode of ventilation, Bilevel-auto, could be equally effective in treating patients unable to tolerate CPAP. The aim of this study was to investigate the ability of Bilevel-auto to treat OSA patients whose nocturnal ventilatory disturbances are not completely corrected by CPAP.We enrolled 66 consecutive OSA patients, not responsive to (group A) or intolerant of (group B) CPAP treatment, after a full night of manual CPAP titration in a laboratory. Full polysomnography data and daytime sleepiness score were compared for each group in the three different conditions: basal, during CPAP, and during Bilevel-auto.The apnea-hypopnea index decreased significantly during CPAP in both groups; however, in the group A, there was a further significant improvement during Bilevel-auto. The same trend was observed for oxygenation indices, while the distribution and the efficiency of sleep did not differ following the switch from CPAP to Bilevel-auto.This study confirmed the role of Bilevel-auto as an effective therapeutic alternative to CPAP in patients intolerant of this latter mode of ventilation. Moreover, extending the use of Bilevel-auto to those OSA patients not responsive to CPAP, we showed a significantly better correction of nocturnal respiratory disturbances.

Objectives The aim of this study is to compare the accuracy of the standard visual scoring of computed tomography (CT) scans with a cloud-based quantitative CT analysis that uses the StratX software, to measure collateral ventilation and, thus, predict lobar atelectasis after valve treatment. Methods This is a retrospective, multicentre study of patients who had previously undergone valve treatment for severe heterogeneous emphysema and whose required fissure integrity ≥90% had been qualitatively scored by visual assessment of CT scans. For this study, all preprocedural CT scans were retrospectively analysed using the StratX software to provide quantitative scores of fissure integrity. The diagnostic accuracies of the visual and quantitative scores for predicting a target lobe volume reduction (TLVR) of ≥350 ml were calculated and statistically compared, as this level of volume reduction can be achieved only with sound fissure integrity. The clinical outcome of TLVR was also evaluated according to the minimal clinically important difference criteria. Results Eighty-three patients were included in the analysis. Of them, 65 of 83 (78%) patients presented with TLVR ≥350 ml. Visual scoring correctly identified the absence of collateral ventilation in 65 of 83 (78%) cases but failed in 18 of 83 (22%) cases. Of these 18 patients, quantitative analysis showed that 16 of 18 (89%) patients did not present completeness of the fissure. The diagnostic accuracy of the quantitative analysis was better than that of the visual analysis (96.4% vs 78.3%; P = 0.0003). Only patients having TLVR ≥350 ml met or exceeded the minimal clinically important difference criteria. Conclusions The quantitative analysis using the StratX software contributed a more objective and efficient evaluation of collateral ventilation that would have improved the selection of emphysematous patients for endobronchial valve treatment in the study population.

Background The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), also referred to as overlap syndrome (OS), is associated with a high rate of morbidity, COPD exacerbations and mortality. Treatment with continuous positive airway pressure (CPAP) has proven to significantly decrease the rate of these complications. However, data concerning the effect of CPAP on pulmonary function are scarce and conflicting. The aim of our study was to evaluate the effect of 1 year of CPAP treatment on arterial blood gases (ABGs) and pulmonary function tests in patients with OS and its potential relationship with the baseline severity of airway obstruction. A secondary aim was to search for predictors of changes in the evaluated parameters. Methods A retrospective study on a cohort of 92 patients (74 males) discharged from the Pulmonary Rehabilitation Unit of the Istituti Clinici Scientifici Maugeri in Pavia (Italy) from January 2013 to January 2016, with a diagnosis of OS and a prescription of CPAP, was conducted. Collected data at discharge were compared with 1-year follow-up data. Results After 1 year of CPAP, we observed the following: (I) a significant improvement in ABGs in all patients [median pO2 65.0 (59.0-70.0) vs. 71 (64.8-77.1) mmHg, pCO2 39.8 (36.2-43.5) vs. 38.3 (32.3-44.2) at baseline and after 1 year respectively, P

Lung cancer is considered one of the major causes of cancer-related mortality. Our case report wishes to highlight the confusion one may have when faced with a lesion that could be a synchronous lesion or metastasis from an index lesion, and its management including whether re-do VATS is a good option. We report our case of a 68 years old male who came to our attention in March 2018 with history of weight loss and repeated chest infections. He was smoking until he was reviewed in our clinic, with a 40- pack year history. PET scan revealed an intense uptake of left lower nodule of size 3.5 cm (cT2aN0M0). He underwent uniportal VATS left basal segmentectomy and lymphadenectomy with the histopathology confirming a squamous cell carcinoma (SCC) (pT2aN0M0R0). During his follow-up, a new left upper lobe lesion was noticed in February 2019. PET scan showed increased uptake in the lesion and CT guided biopsy showed poorly differentiated SCC (cT1cN0M0). The patient underwent uniportal VATS left upper trisegmentectomy and lymphadenectomy with histopathology revealing the presence of two different lesions this time around: the larger one being a SCC with a staging of pT1cN0M0R0 and the smaller being a basaloid type of SCC with a staging of pT1aN0M0. In our opinion, the three cancerous nodules the patient developed represented multiple primary tumours arising on a background of field change rather than intrapulmonary metastasis from an index lesion (differentiating this was important from management point of view). Moreover, we managed to safely perform a redo surgery via uniportal VATS for the same sided lung lesion. This is feasible as long as the patient has an adequate cardiorespiratory function. We wish to take this opportunity to add to the literature our experience with this case of multiple primary lung cancer (MPLC).

Educational aims To discuss the basic principles of ventilator function To help the reader to recognise the different features of a home care ventilator To outline the advantages and drawbacks of the different home care ventilators To provide some recommendations to facilitate the clinical management of patients on home care ventilator Summary Mechanical ventilation, applied either invasively through a tracheotomy tube or noninvasively via a mask, is increasingly used for long-term management of many forms of severe chronic respiratory failure in the home setting. In recent years, the quality of the ventilators for long-term home mechanical ventilation has improved considerably and, concomitantly, the number of machines available has also increased. This broader range of commercially available machines is clearly an advantage; however, it makes the choice of the optimal device for a specific patient more difficult. The aim of the present article is to provide useful information to help and guide the choice of device for long-term mechanical ventilation in the home setting.

Background Noninvasive ventilation is used worldwide in many settings. Its effectiveness has been proven for common clinical conditions in critical care such as cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbations. Since the first pioneering studies of noninvasive ventilation in critical care in the late 1980s, thousands of studies and articles have been published on this topic. Interestingly, some aspects remain controversial (e.g. its use in de-novo hypoxemic respiratory failure, role of sedation, self-induced lung injury). Moreover, the role of NIV has recently been questioned and reconsidered in light of the recent reports of new techniques such as high-flow oxygen nasal therapy. Methods We conducted a survey among leading experts on NIV aiming to 1) identify a selection of 10 important articles on NIV in the critical care setting 2) summarize the reasons for the selection of each study 3) offer insights on the future for both clinical application and research on NIV. Results The experts selected articles over a span of 26 years, more clustered in the last 15 years. The most voted article studied the role of NIV in acute exacerbation chronic pulmonary disease. Concerning the future of clinical applications for and research on NIV, most of the experts forecast the development of innovative new interfaces more adaptable to patients characteristics, the need for good well-designed large randomized controlled trials of NIV in acute “de novo” hypoxemic respiratory failure (including its comparison with high-flow oxygen nasal therapy) and the development of software-based NIV settings to enhance patient-ventilator synchrony. Conclusions The selection made by the experts suggests that some applications of NIV in critical care are supported by solid data (e.g. COPD exacerbation) while others are still waiting for confirmation. Moreover, the identified insights for the future would lead to improved clinical effectiveness, new comparisons and evaluation of its role in still “lack of full evidence” clinical settings. Electronic supplementary material The online version of this article (10.1186/s12871-017-0409-0) contains supplementary material, which is available to authorized users.

Background: Bronchoscopic lung volume reduction (BLVR) with implant of one-way endobronchial valves (EBV) is a feasible treatment for management of heterogeneous emphysema (HE) with clinical benefits in the early follow-up. We aimed to evaluate the long-terms results and safety of this procedure in a consecutive series of patients with HE. Methods: It was a retrospective single center study including all consecutive patients with HE undergoing EBV treatment and completing at least 5 years of long-term follow-up. Patients were splitted into Collapse and No-Collapse Group if a lobar collapse or not were obtained after valves implant. The difference of functional data and quality of life (QoL) before and after the procedure (measured at 3, 6, 9, 12 months from the valve implantation, and then annually up to a maximum of 5 years) were statistically evaluated to show the long-term benefits of the procedure (primary endpoint). Yet, morbidity, mortality and survival rates were also recorded to show the safe of the treatment (secondary endpoint). Results: Thirty-three patients were included in the study. Of these, three patients underwent a bilateral treatment. Collapse Group patients (n=27) presented a significant improvement in FEV1% (+17%; P=0.001); in FVC% (+18%; P=0.002); in RV% (−39%; P=0.003); in 6MWT (P=0.001) and in SGRQ (P=0.001) in the early 12 months of follow-up and no significant decline was seen later. Conversely, No-Collapse Group (n=9) did not have significant benefits. No major complications and death related to the procedure were observed. The 1-,2-,3-,4- and 5-year survival rates were 100%, 90%, 78%, 71% and 71%, respectively. Collapse Group had a better survival than No-Collapse Group (45 vs . 24 months; P=0.001). Conclusions: Our study confirmed that the lobar collapse is the key success of EBV treatment and the early improvements of respiratory function could be maintained up to five years from the valves implant.

Symptoms, clinical course, functional and biological data during an exacerbation of chronic obstructive pulmonary disease (EXCOPD) have been investigated, but data on physiological changes of respiratory mechanics during a severe exacerbation with respiratory acidosis requiring noninvasive mechanical ventilation (NIMV) are scant. The aim of this study was to evaluate changes of respiratory mechanics in COPD patients comparing data observed during EXCOPD with those observed during stable state in the recovery phase. In 18 COPD patients having severe EXCOPD requiring NIMV for global respiratory failure, we measured respiratory mechanics during both EXCOPD (T0) and once the patients achieved a stable state (T1). The diaphragm and inspiratory muscles effort was significantly increased under relapse, as well as the pressure-time product of the diaphragm and the inspiratory muscle (PTPdi and PTPes). The resistive loads to breathe (i.e., PEEPi,dyn, compliance and inspiratory resistances) were also markedly increased, while the maximal pressures generated by the diaphragm and the inspiratory muscles, together with forced expired volumes were decreased. All these indices statistically improved but with a great intrasubject variability in stable condition. Moreover, tension-time index (TTdi) significantly improved from the EXCOPD state to the condition of clinical stability (0.156 ± 0.04 at T0 vs. 0.082 ± 0.02 at T1 p < 0.001). During an EXCOPD, the load/capacity of the respiratory pump is impaired, and although the patients exhibit a rapid shallow breathing pattern, this does not necessarily correlate with a TTdi ≥ 0.15. These changes are reverted once they recover from the EXCOPD, despite a large variability between patients.

Background LOPD is a metabolic, autosomal recessive disease due to a reduced functionality of protein α-glucosidase (GAA), which leads to an accumulation of glycogen in skeletal muscle tissue and in other organs. 70% of LOPD patients develops progressive respiratory failure (RF) with vital capacity reduction and risk of mechanical ventilation. Recent data suggest the importance of an early LOPD diagnosis. Aims Prevalence of LOPD suspect in patients with RF. Optimizing the diagnostic process encouraging early diagnosis. Methods 12 months real-life study, conducted in 18 Pulmonology Italian Centers, aimed to enroll 500 adult patients with unexplained RF and follow the diagnostic algorithm for suspected LOPD. For each patient, clinicians collected a drop of blood on Dried Blood Spot (DBS) for the measurement of GAA. Muscular disability was assessed with Walton Gardner Medwin Scale (WGMS). Results 38 patients enrolled: characteristics and preliminary data in Figure 1. 68% acceded for respiratory reasons, 32% for other causes. 42% was hospitalized and 24% needed mechanical ventilation. Hyperckemia was reported in 34% of patients. The majority of cases (76%) presented a WGMS between 0 and 5. 1 case resulted positive for LOPD suspect (GAA = 0,48 micromol/L/h). Conclusions PneumoLoped could provide original data to focus the role of pulmonologists in LOPD early diagnosis in patients with unexplained RF.

Weaning failure has been defined as failure to discontinue mechanical ventilation, as assessed by the spontaneous breathing trial, or need for re-intubation after extubation, so-called extubation failure. Both events represent major clinical and economic burdens, and are associated with high morbidity and mortality. The most important mechanism leading to discontinuation failure is an unfavourable balance between respiratory muscle capacity and the load they must face. Beyond specific diseases leading to loss of muscle force-generating capacity, other factors may impair respiratory muscle function, including prolonged mechanical ventilation, sedation, and ICU-acquired neuromuscular dysfunction, potentially consequent to multiple factors. The load depends on the mechanical properties of the respiratory system. An increased load is consequent to any condition leading to increased resistance, reduced compliance, and/or occurrence of intrinsic positive-end-expiratory pressure. Noteworthy, the load can significantly increase throughout the spontaneous breathing trial. Cardiac, cerebral, and neuropsychiatric disorders are also causes of discontinuation failure. Extubation failure may depend, on the one hand, on a deteriorated force-load balance occurring after removal of the endotracheal tube and, on the other hand, on specific problems. Careful patient evaluation, avoidance and treatment of all the potential determinants of failure are crucial to achieve successful discontinuation and extubation.

Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.

Summary Synchrony refers to the agreement between the patient9s own (neural) and the ventilator9s (mechanical) inspiratory and expiratory time. Noninvasive ventilation (NIV) is a semi-open system, which means air leaks are common. This greatly affects patient synchrony. In addition to air leaks, there are other factors that affect patient–ventilator mismatching. This review will focus on NIV and on the main forms of asynchrony and mismatching, their causes and methods to eventually identify these problems from the flow and pressure signals.

Mitochondria are highly specialized organelles and major players in fundamental aspects of cell physiology. In yeast, energy metabolism and coupling of mitochondrial activity to growth and survival is controlled by the protein kinase A pathway. In higher eukaryotes, modulation of the so-called A-kinase anchor protein (AKAP) complex regulates mitochondrial dynamics and activity, adapting the oxidative machinery and the metabolic pathway to changes in physiological demand. Protein kinases and phosphatases are assembled by AKAPs within transduction units, providing a mechanism to control signaling events at mitochondria and other target organelles. Ubiquitin-mediated proteolysis of signal transducers and effectors provides an additional layer of complexity in the regulation of mitochondria homeostasis. Genetic evidence indicates that alteration of one or more components of these biochemical pathways leads to mitochondrial dysfunction and human diseases. In this review, we focus on the emerging role of AKAP scaffolds and the proteasome pathway in the control of oxidative metabolism, organelle dynamics and the mitochondrial signaling network. These aspects are crucial elements for maintaining a proper energy balance and cellular lifespan.

PTPD1 is a cytosolic nonreceptor tyrosine phosphatase and a positive regulator of the Src-epidermal growth factor transduction pathway. We show that PTPD1 localizes along actin filaments and at adhesion plaques. PTPD1 forms a stable complex via distinct molecular modules with actin, Src tyrosine kinase, and focal adhesion kinase (FAK), a scaffold protein kinase enriched at adhesion plaques. Overexpression of PTPD1 promoted cell scattering and migration, short hairpin RNA-mediated silencing of endogenous PTPD1, or expression of PTPD1 mutants lacking either catalytic activity (PTPD1(C1108S)) or the FERM domain (PTPD1(Delta1-325)) significantly reduced cell motility. PTPD1 and Src catalytic activities were both required for epidermal growth factor-induced FAK autophosphorylation at its active site and for downstream propagation of ERK1/2 signaling. Our findings demonstrate that PTPD1 is a component of a multivalent scaffold complex nucleated by FAK at specific intracellular sites. By modulating Src-FAK signaling at adhesion sites, PTPD1 promotes the cytoskeleton events that induce cell adhesion and migration.