nnU-Net-based deep-learning for pulmonary embolism: detection, clot volume quantification, and severity correlation in the RSPECT dataset.

OBJECTIVES: CT pulmonary angiography is the gold standard for diagnosing pulmonary embolism, and DL algorithms are being developed to manage the increase in demand. The nnU-Net is a new auto-adaptive DL framework that minimizes manual tuning, making it easier to develop effective algorithms for medical imaging even without specific expertise. This study assesses the performance of a locally developed nnU-Net algorithm on the RSPECT dataset for PE detection, clot volume measurement, and correlation with right ventricle overload. MATERIALS & METHODS: User input was limited to segmentation using 3DSlicer. We worked with the RSPECT dataset and trained an algorithm from 205 PE and 340 negatives. The test dataset comprised 6573 exams. Performance was tested against PE characteristics, such as central, non-central, and RV overload. Blood clot volume (BCV) was extracted from each exam. We employed ROC curves and logistic regression for statistical validation. RESULTS: Negative studies had a median BCV of 1 µL, which increased to 345 µL in PE-positive cases and 7,378 µL in central PEs. Statistical analysis confirmed a significant BCV correlation with PE presence, central PE, and increased RV/LV ratio (p < 0.0001). The model's AUC for PE detection was 0.865, with an 83 % accuracy at a 55 µL threshold. Central PE detection AUC was 0.937 with 91 % accuracy at 850 µL. The RV overload AUC stood at 0.848 with 79 % accuracy. CONCLUSION: The nnU-Net algorithm demonstrated accurate PE detection, particularly for central PE. BCV is an accurate metric for automated severity stratification and case prioritization. CLINICAL RELEVANCE STATEMENT: The nnU-Net framework can be utilized to create a dependable DL for detecting PE. It offers a user-friendly approach to those lacking expertise in AI and rapidly extracts the Blood Clot Volume, a metric that can evaluate the PE's severity.

The Smokers Health Multiple ACtions (SMAC-1) Trial: Study Design and Results of the Baseline Round.

BACKGROUND: Lung cancer screening with low-dose helical computed tomography (LDCT) reduces mortality in high-risk subjects. Cigarette smoking is linked to up to 90% of lung cancer deaths. Even more so, it is a key risk factor for many other cancers and cardiovascular and pulmonary diseases. The Smokers health Multiple ACtions (SMAC-1) trial aimed to demonstrate the feasibility and effectiveness of an integrated program based on the early detection of smoking-related thoraco-cardiovascular diseases in high-risk subjects, combined with primary prevention. A new multi-component screening design was utilized to strengthen the framework on conventional lung cancer screening programs. We report here the study design and the results from our baseline round, focusing on oncological findings. METHODS: High-risk subjects were defined as being >55 years of age and active smokers or formers who had quit within 15 years (>30 pack/y). A PLCOm2012 threshold >2% was chosen. Subject outreach was streamlined through media campaign and general practitioners' engagement. Eligible subjects, upon written informed consent, underwent a psychology consultation, blood sample collection, self-evaluation questionnaire, spirometry, and LDCT scan. Blood samples were analyzed for pentraxin-3 protein levels, interleukins, microRNA, and circulating tumor cells. Cardiovascular risk assessment and coronary artery calcium (CAC) scoring were performed. Direct and indirect costs were analyzed focusing on the incremental cost-effectiveness ratio per quality-adjusted life years gained in different scenarios. Personalized screening time-intervals were determined using the "Maisonneuve risk re-calculation model", and a threshold <0.6% was chosen for the biennial round. RESULTS: In total, 3228 subjects were willing to be enrolled. Out of 1654 eligible subjects, 1112 participated. The mean age was 64 years (M/F 62/38%), with a mean PLCOm2012 of 5.6%. Former and active smokers represented 23% and 77% of the subjects, respectively. At least one nodule was identified in 348 subjects. LDCTs showed no clinically significant findings in 762 subjects (69%); thus, they were referred for annual/biennial LDCTs based on the Maisonneuve risk (mean value = 0.44%). Lung nodule active surveillance was indicated for 122 subjects (11%). Forty-four subjects with baseline suspicious nodules underwent a PET-FDG and twenty-seven a CT-guided lung biopsy. Finally, a total of 32 cancers were diagnosed, of which 30 were lung cancers (2.7%) and 2 were extrapulmonary cancers (malignant pleural mesothelioma and thymoma). Finally, 25 subjects underwent lung surgery (2.25%). Importantly, there were zero false positives and two false negatives with CT-guided biopsy, of which the patients were operated on with no stage shift. The final pathology included lung adenocarcinomas (69%), squamous cell carcinomas (10%), and others (21%). Pathological staging showed 14 stage I (47%) and 16 stage II-IV (53%) cancers. CONCLUSIONS: LDCTs continue to confirm their efficacy in safely detecting early-stage lung cancer in high-risk subjects, with a negligible risk of false-positive results. Re-calculating the risk of developing lung cancer after baseline LDCTs with the Maisonneuve model allows us to optimize time intervals to subsequent screening. The Smokers health Multiple ACtions (SMAC-1) trial offers solid support for policy assessments by policymakers. We trust that this will help in developing guidelines for the large-scale implementation of lung cancer screening, paving the way for better outcomes for lung cancer patients.

Percutaneous Computed Tomography (CT)-Guided Localization with Indocyanine Green for the Thoracoscopic Resection of Small Pulmonary Nodules.

BACKGROUND: The identification of small lung nodules is challenging during mini-invasive thoracic surgery. Unable to palpate them directly, surgeons have developed several methods to preoperatively localize pulmonary nodules, including the computed tomography-guided positioning of coils or metallic landmarks (hook wire) or bronchoscopic marking. METHODS: We present a series of patients scheduled for the video-assisted thoracoscopic sublobar resection of small pulmonary nodules, in which we performed preoperative percutaneous computed tomography (CT)-guided nodule localization through the injection of a mixture of indocyanine green and human albumin. RESULTS: A total of 40 patients underwent a preoperative CT-guided injection of indocyanine green followed by VATS resection within 24 h. Patients tolerated the procedure well, no pain medication was administrated, and no complications were observed during the marking procedure. All pulmonary nodules were easily detected and successfully resected. CONCLUSION: the near-infrared dye marking solution of indocyanine green (ICG) with diluted human albumin was safe, effective, and easy to perform. The ICG solution has the potential to facilitate the accurate localization and resection of pulmonary nodules during VATS surgery, avoiding the risk of marker displacement/migration.

Shear-wave elastography of the plantar fascia: a systematic review and meta-analysis.

PURPOSE: To assess the efficacy of shear-wave elastography (SWE) of the plantar fascia (PF) in identifying plantar fasciitis. METHODS: A literature search was conducted on the PubMed and Medline databases for articles published up to August 2022. The Newcastle-Ottawa scale was used to assess the risk of bias. We included original research studies in English dealing with the evaluation of patients with plantar fasciitis by means of SWE and including shear modulus (KPa) and/or shear-wave velocity (m/s). We compared healthy and pathologic PF stiffness using the standardised mean difference (SMD) in a random-effects model (95% CI). RESULTS: Five studies were included with a total of 158 pathologic PFs and 134 healthy PFs. No significant publication bias was detected. Studies were highly heterogeneous (p < 0.00001; I2 = 97%). Pathologic PFs showed significantly lower stiffness, with an SMD of - 3.00 m/s (95% confidence interval: - 4.95 to - 1.06, p = 0.002), compared to healthy PF. CONCLUSION: Pathologic PFs present significantly lower stiffness than healthy PFs. However, the analysed studies are highly heterogeneous.

Endosonography-Guided Versus Percutaneous Gallbladder Drainage Versus Cholecystectomy in Fragile Patients with Acute Cholecystitis-A High-Volume Center Study.

Background and Objectives: Acute cholecystitis is a frequent cause of admission to the emergency department, especially in old and frail patients. Percutaneous drainage (PT-GBD) and endosonographic guided drainage (EUS-GBD) could be an alternative option for relieving symptoms or act as a definitive treatment instead of a laparoscopic or open cholecystectomy (LC, OC). The aim of the present study was to compare different treatment groups. Materials and Methods: This is a five-year monocentric retrospective study including patients ≥65 years old who underwent an urgent operative procedure. A descriptive analysis was conducted comparing all treatment groups. A propensity score was estimated based on the ACS score, incorporated into a predictive model, and tested by recursive partitioning analysis. Results: 163 patients were included: 106 underwent a cholecystectomy (81 laparoscopic (LC) and 25 Open (OC)), 33 a PT-GBD and 21 EUS-GBD. The sample was categorized into three prognostic groups according to the adverse event occurrence rate. All patients treated with EUS-GBD or LC resulted in the low risk group, and the adverse event rate (AE) was 10/96 (10.4%). The AE was 4/28 (14.2%) and 21/36 (58.3%) in the middle- and high-risk groups respectively (p < 0.001). These groups included all the patients who underwent an OC or a PT-GBD. The PT-GBD group had a lower clinical success rate (55.5%) and higher RR (16,6%) when compared with other groups. Conclusions: Surgery still represents the gold standard for AC treatment. Nevertheless, EUS-GBD is a good alternative to PT-GBD in terms of clinical success, RR and AEs in all kinds of patients.

Quantitative Chest CT Analysis to Measure Short-Term Sequelae of COVID-19 Pneumonia: A Monocentric Prospective Study.

(1) Background: Quantitative CT analysis (QCT) has demonstrated promising results in the prognosis prediction of patients affected by COVID-19. We implemented QCT not only at diagnosis but also at short-term follow-up, pairing it with a clinical examination in search of a correlation between residual respiratory symptoms and abnormal QCT results. (2) Methods: In this prospective monocentric trial performed during the "first wave" of the Italian pandemic, i.e., from March to May 2020, we aimed to test the relationship between %deltaCL (variation of %CL-compromised lung volume) and variations of symptoms-dyspnea, cough and chest pain-at follow-up clinical assessment after hospitalization. (3) Results: 282 patients (95 females, 34%) with a median age of 60 years (IQR, 51-69) were included. We reported a correlation between changing lung abnormalities measured by QCT, and residual symptoms at short-term follow up after COVID-19 pneumonia. Independently from age, a low percentage of surviving patients (1-4%) may present residual respiratory symptoms at approximately two months after discharge. QCT was able to quantify the extent of residual lung damage underlying such symptoms, as the reduction of both %PAL (poorly aerated lung) and %CL volumes was correlated to their disappearance. (4) Conclusions QCT may be used as an objective metric for the measurement of COVID-19 sequelae.

Lung response to prone positioning in mechanically-ventilated patients with COVID-19.

BACKGROUND: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population. METHODS: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity. RESULTS: By the time of the study, PEEP was 12 (10-14) cmH2O and the PaO2:FiO2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001). CONCLUSIONS: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.

A Multimodal Clinical Approach for the Treatment of Bone Metastases in Solid Tumors.

Context: Bone metastasis (BM) is a frequent complication of cancer, representing the third most common site of secondary spread in solid cancers behind the lung and liver. Bone metastasis is found in up to 90% of prostate and breast cancer patients. They can cause significant complications, such as pathological fractures and paralysis of the spine, which decrease daily functioning and quality of life (QoL) and worsen prognosis. The growing life expectancy of cancer patients due to improvements in systemic therapies may further increase BM's eventuality and clinical burden in cancer patients. Evidence Acquisition: Four physicians from five different specialties were interviewed and resumed the most relevant literature of the last 20 years focusing on pain treatment in BM patients. Results: Treatment for BM ideally involves various types of specialists and assessments. The disease status and patient background should be considered, requiring holistic care and expertise from various medical specialties. Conclusions: Interventional, nuclear medicine, radiotherapy, and mini-invasive techniques can be safe and effective for relieving pain and modifying health-related QoL in BM patients.

Lung Response to a Higher Positive End-Expiratory Pressure in Mechanically Ventilated Patients With COVID-19.

BACKGROUND: International guidelines suggest using a higher (> 10 cm H2O) positive end-expiratory pressure (PEEP) in patients with moderate-to-severe ARDS due to COVID-19. However, even if oxygenation generally improves with a higher PEEP, compliance, and Paco2 frequently do not, as if recruitment was small. RESEARCH QUESTION: Is the potential for lung recruitment small in patients with early ARDS due to COVID-19? STUDY DESIGN AND METHODS: Forty patients with ARDS due to COVID-19 were studied in the supine position within 3 days of endotracheal intubation. They all underwent a PEEP trial, in which oxygenation, compliance, and Paco2 were measured with 5, 10, and 15 cm H2O of PEEP, and all other ventilatory settings unchanged. Twenty underwent a whole-lung static CT scan at 5 and 45 cm H2O, and the other 20 at 5 and 15 cm H2O of airway pressure. Recruitment and hyperinflation were defined as a decrease in the volume of the non-aerated (density above -100 HU) and an increase in the volume of the over-aerated (density below -900 HU) lung compartments, respectively. RESULTS: From 5 to 15 cm H2O, oxygenation improved in 36 (90%) patients but compliance only in 11 (28%) and Paco2 only in 14 (35%). From 5 to 45 cm H2O, recruitment was 351 (161-462) mL and hyperinflation 465 (220-681) mL. From 5 to 15 cm H2O, recruitment was 168 (110-202) mL and hyperinflation 121 (63-270) mL. Hyperinflation variably developed in all patients and exceeded recruitment in more than half of them. INTERPRETATION: Patients with early ARDS due to COVID-19, ventilated in the supine position, present with a large potential for lung recruitment. Even so, their compliance and Paco2 do not generally improve with a higher PEEP, possibly because of hyperinflation.

Myosteatosis Is Not Associated with Complications or Survival in HCC Patients Undergoing Trans Arterial Embolization.

Alterations in nutritional status, in particular sarcopenia, have been extensively associated with a poor prognosis in cirrhotic patients regardless of the etiology of liver disease. Less is known about the predictive value of myosteatosis, defined as pathological fat infiltration into the skeletal muscle. We retrospectively analyzed a cohort of 151 cirrhotic patients with unresectable hepatocellular carcinoma (HCC) who underwent their first trans-arterial embolization (TAE) between 1 March 2011 and 1 July 2019 at our Institution. Clinical and biochemical data were collected. Sarcopenia was assessed using the L3-SMI method while myosteatosis with a dedicated segmentation suite (3D Slicer), using a single slice at an axial plane located at L3 and calculating the IMAC (Intramuscular Adipose Tissue Content Index). The sex-specific cut-off values for defining myosteatosis were IMAC > −0.44 in males and >−0.31 in females. In our cohort, 115 (76%) patients were included in the myosteatosis group; 128 (85%) patients had a coexistent diagnosis of sarcopenia. Patients with myosteatosis were significantly older and showed higher BMI than patients without myosteatosis. In addition, male gender and alcoholic- or metabolic-related cirrhosis were most represented in the myosteatosis group. Myosteatosis was not associated with a different HCC burden, length of hospitalization, complication rate, and readmission in the first 30 days after discharge. Overall survival was not influenced by the presence of myosteatosis.

Environmental triggers for connective tissue disease: the case of COVID-19 associated with dermatomyositis-specific autoantibodies.

PURPOSE OF REVIEW: The aim of the present review is to analyze the link between autoimmune diseases and environmental factors, in particular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) as it shares numerous features with the interstitial lung disease associated with connective tissue diseases positive for rare autoantibodies directed at highly specific autoantigens (i.e., MDA5 and RIG1) among the intracellular sensors of SARS-CoV-2 in the innate response against viruses. RECENT FINDINGS: As shown in recent publications and in our original data, specific autoantibodies may be functionally relevant to COVID-19 infection. We evaluated sera from 35 hospitalized patients with COVID-19 to identify antinuclear antibodies and autoantibodies directed against specific antigenic targets, and we identified anti-nuclear antibodies (ANA) in 20/35 of patients with COVID-19 (57%), in patients with need for supplemental oxygen (90% vs. 20% in ANA-negative cases; P < 0.0001). In 7/35 COVID-19 sera, we detected anti-MJ/NXP2 (n = 3), anti-RIG1 (n = 2), anti-Scl-70/TOPO1 (n = 1), and anti-MDA5 (n = 1), overall associated with a significantly worse pulmonary involvement at lung computerized tomography scans. Eleven (31%) patients were positive for antibodies against the E2/E3 subunits of mitochondrial pyruvate dehydrogenase complex. SUMMARY: Viral infections such as COVID-19 are associated with ANA and autoantibodies directed toward antiviral signaling antigens in particular in patients with worse pulmonary involvement.

Compromised Lung Volume and Hemostatic Abnormalities in COVID-19 Pneumonia: Results from an Observational Study on 510 Consecutive Patients.

BACKGROUND: Hemostatic abnormalities have been described in COVID-19, and pulmonary microthrombosis was consistently found at autopsy with concomitant severe lung damage. METHODS: This is a retrospective observational cross-sectional study including consecutive patients with COVID-19 pneumonia who underwent unenhanced chest CT upon admittance at the emergency room (ER) in one large academic hospital. QCT was used for the calculation of compromised lung volume (%CL). Clinical data were retrieved from patients' files. Laboratory data were obtained upon presentation at the ER. AIM: The aim of this study was to evaluate the correlation between hemostatic abnormalities and lung involvement in patients affected by COVID-19 pneumonia as described using computer-aided quantitative evaluation of chest CT (quantitative CT (QCT)). RESULTS: A total of 510 consecutive patients (68% males), aged 67 years in median, diagnosed with COVID-19 pneumonia, who underwent unenhanced CT scan upon admission to the ER, were included. In all, 115 patients had %CL > 23%; compared to those with %CL < 23%, they showed higher levels of D-dimer, fibrinogen, and CRP, greater platelet count, and longer PT ratio. Via multivariate regression analysis, BMI ≥ 30 kg/m2, D-dimer levels > 500 ng/mL, CRP > 5.0 ng/mL and PT ratio > 1.2 were found to be independent predictors of a %CL > 23% (adjusted odds ratios (95% confidence intervals): 2.1 (1.1-4.0), 3.1 (1.6-5.8), 2.4 (1.3-4.5), and 3.4 (1.4-8.5), respectively). CONCLUSIONS: Hemostatic abnormalities in patients affected by COVID-19 correlate with the severity of lung injury as measured by %CL. Our results underline the pathogenetic role of hemostasis in COVID-19 pneumonia beyond the presence of clinically evident thromboembolic complications.

Percutaneous Treatment of Bronchobiliary Fistula: Report of a Successful Transhepatic Embolization and a Decision-Making Strategy Driven by Systematic Literature Review.

Bronchobiliary fistula is a rare condition characterized by bile leaking into the bronchial tree causing biliptysis. It may arise from liver infection or as a consequence of resection and thermal ablation of cancer. Currently, there is no consensus about the treatment strategy. Surgery is considered the main therapy by most authors. However, this systematic literature review shows that the success rate of percutaneous treatments may reach 75%. Adding to such evidence, we also report the case of a woman affected by iatrogenic bronchobiliary fistula secondary to liver thermal ablation, successfully treated with percutaneous drainage plus embolization. Summarizing these results, we encourage the percutaneous management of bronchobiliary fistula by providing a 3-step decision-making algorithm, aimed at reducing the need for major surgery.

Prognostic Value of Metabolic Imaging Data of 11C-choline PET/CT in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

11C-choline positron emission tomography/computed tomography (PET/CT) has been used for patients with some types of tumors, but few data are available for hepatocellular carcinoma (HCC). We queried our prospective database for patients with HCC staged with 11C-choline PET/CT to assess the clinical impact of this imaging modality. Seven parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), liver standardized uptake value (SUVliver), metabolic tumor volume (MTV), photopenic area, metabolic tumor burden (MTB = MTVxSUVmean), and SUVratio (SUVmax/SUVliver). Analysis was performed to identify parameters that could be predictors of overall survival (OS). Sixty patients were analyzed: fourteen (23%) were in stage 0-A, 37 (62%) in stage B, and 9 (15%) in stage C of the Barcelona classification. The Cox regression for OS showed that Barcelona stages (HR = 2.94; 95%CI = 1.41-4.51; p = 0.003) and MTV (HR = 2.11; 95%CI = 1.51-3.45; p = 0.026) were the only factors independently associated with OS. Receiver operating characteristics curve analysis revealed MTV ability in discriminating survival (area under the curve (AUC) = 0.77; 95%CI = 0.57-097; p < 0.001: patients with MTV ≥ 380 had worse OS (p = 0.015)). The use of 11C-choline PET/CT allows for better prognostic refinement in patients undergoing hepatectomy for HCC. Incorporation of such modality into HCC staging system should be considered.

US-guided percutaneous irrigation of calcific tendinopathy of the rotator cuff in patients with or without previous external shockwave therapy.

OBJECTIVES: To compare the outcome of US-guided percutaneous irrigation of calcific tendinopathy (US-PICT) of the rotator cuff in patients with or without previous external shockwave therapy (ESWT). METHODS: We analyzed all patients treated with US-PICT from March 1, 2016, to October 1, 2019, with shoulder pain refractory to conservative management for rotator cuff calcific tendinopathy, diagnosed with ultrasound. Each patient was examined using the Constant-Murley Score (CMS) questionnaire (score 0-100) before and after treatment. We tested CMS differences using the Mann-Whitney U (Wilcoxon rank-sum) test in the two groups. US-PICT was performed placing two or multiple 14G needles, according to the calcification size, inserted under US guidance to create a circuit of irrigation in the calcified tendon. NaCl solution at 38 °C was then injected from the entry needle in a variable amount to hydrate and fragment the calcification, finally allowing for its expulsion through the exit needle. All patients also received an intrabursal steroid injection. RESULTS: From 2016 to 2019, 72 US-PICT treatments were performed on 70 patients (females = 46; males = 26) with a mean age of 49.7 years (SD = 8.7. Thirty-three (47%) underwent previous ESWT, while thirty-seven (53%) had no previous treatments. No treatment-related complications were observed. Follow-up was averagely 14.4 months (median = 11.6, SD = 11.9, range 1-45); 37 patients had a follow-up shorter than 12 months (1-11.6); 35 patients were visited after more than 1 year (12.2-45.6, Table W). Before treatment, the mean CMS was 35 (SD = 21); after treatment, it reached 75.4, with an average CMS improvement of 40.3 points (SD = 23.7, p < 0.001). The comparison of improvement between the ESWT and non-ESWT group yielded no significant difference (p = 0.3). CONCLUSIONS: US-PICT of the rotator cuff is an effective procedure to reduce shoulder pain and increase mobility in patients with calcific tendinopathy, both in short- and long-term time intervals. Previous unsuccessful ESWT does not affect the outcome of US-PICT.

Correction: Sarcopenia as a predictor of survival in patients undergoing bland transarterial embolization for unresectable hepatocellular carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0232371.].

Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study.

BACKGROUND: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. METHODS: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. FINDINGS: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33-52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25-43]; p<0·0001). 17 (6%) of 297 patients with COVID-19-associated ARDS had compliances greater than the 95th percentile of the classical ARDS cohort. Total lung weight did not differ between the two cohorts. CT pulmonary angiograms (obtained in 23 [8%] patients with COVID-19-related ARDS) showed that 15 (94%) of 16 patients with D-dimer concentrations greater than the median had bilateral areas of hypoperfusion, consistent with thromboembolic disease. Patients with D-dimer concentrations equal to or less than the median had ventilatory ratios lower than those of patients with D-dimer concentrations greater than the median (1·66 [1·32-1·95] vs 1·90 [1·50-2·33]; p=0·0001). Patients with static compliance equal to or less than the median and D-dimer concentrations greater than the median had markedly increased 28-day mortality compared with other patient subgroups (40 [56%] of 71 with high D-dimers and low compliance vs 18 [27%] of 67 with low D-dimers and high compliance, 13 [22%] of 60 with low D-dimers and low compliance, and 22 [35%] of 63 with high D-dimers and high compliance, all p=0·0001). INTERPRETATION: Patients with COVID-19-associated ARDS have a form of injury that, in many aspects, is similar to that of those with ARDS unrelated to COVID-19. Notably, patients with COVID-19-related ARDS who have a reduction in respiratory system compliance together with increased D-dimer concentrations have high mortality rates. FUNDING: None.