Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition".

PURPOSE: Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." METHODS: Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. RESULTS: Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. CONCLUSIONS: One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.

Association of autoimmune pancreatitis and intraductal papillary mucinous neoplasm. A retrospective analysis from a tertiary care referral center.

BACKGROUND: Autoimmune Pancreatitis (AIP) is a rare chronic inflammatory disease affecting the pancreas. Chronic pancreatic inflammation represents a risk factor for pre-neoplastic conditions such as Intraductal Papillary Mucinous Neoplasia (IPMN). Due to the rarity of AIP, the incidence, and clinical features of IPMN occurring in AIP patients remains unknown. AIMS: In the present study we aimed to explore the relationship between AIP and IPMN and to characterize the clinical features and outcomes of IPMN occurring in the context of AIP. METHODS: We retrospectively (2008-2020) analyzed the clinical and radiological records of a large single center cohort of patients with AIP and investigated the prevalence of IPMN. We then compared the clinical, laboratory and radiological characteristics of patients with IPMN and AIP with a cohort of patients with isolated IPMN. RESULTS: Five hundred and nineteen patients were included in this retrospective study. Sixteen patients had concomitant IPMN and AIP(3%); 61 patients had isolated AIP (12%); 442 patients had isolated IPMN (85%). The prevalence of IPMN in patients with AIP was higher than that observed in the general population (21%vs8-10%). Worrisome Features and High-Risk Stigmata were more frequently observed in IPMN occurring together with AIP compared to isolated IPMN(p < 0.05). Based on radiological features IPMN in the context of AIP was more frequently of main-duct type compared to isolated IPMN(p < 0.05). CONCLUSION: Our data suggest that AIP represents a chronic inflammatory condition that might favor IPMN development with high-risk features. Prolonged surveillance of these patients and longitudinal studies are required to further test the association with AIP and malignant and pre-malignant conditions.

Preoperative MRI radiomic analysis for predicting local tumor progression in colorectal liver metastases before microwave ablation.

PURPOSE: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). METHODS: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. RESULTS: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. CONCLUSION: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.

Macklin Effect: From Pathophysiology to Clinical Implication.

Air leak syndromes (such as pneumomediastinum, pneumothorax, or subcutaneous emphysema) are frequent complications of acute respiratory distress syndrome (ARDS). Unfortunately, the development of air leaks is associated with worse outcomes. In addition, it has been hypothesized that the development of pneumomediastinum could be a marker of disease severity in patients with respiratory failure receiving noninvasive respiratory support or assisted ventilation. The so-called Macklin effect (or pulmonary interstitial emphysema) is the air dissection of the lung bronchovascular tree from peripheral to central airways following injury to distal alveoli. Ultimately, the progression of the Macklin effect leads to the development of pneumomediastinum, subcutaneous emphysema, or pneumothorax. The Macklin effect is identifiable on a chest computed tomography (CT) scan. The Macklin effect could be an accurate predictor of barotrauma in patients with ARDS (sensitivity = 89.2% [95% CI: 74.6-96.9]; specificity = 95.6% [95% CI: 90.6-98.4]), and may be a marker of disease severity. Accordingly, the detection of the Macklin effect on a chest CT scan could be used to select which patients with ARDS might benefit from different treatment algorithms, including advanced respiratory monitoring, early intubation, or, potentially, the institution of early extracorporeal support with or without invasive ventilation. In this video, the authors summarize the pathophysiology and potential clinical significance and applications of the Macklin effect in patients with acute respiratory failure.

Prognostic Significance and Predictors of Nodal Recurrence After Surgery for Non-Functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: The prognosis of nodal recurrence after surgery for non-functioning pancreatic neuroendocrine tumors (NF-PanNETs) and its predictors have been poorly investigated. This study aimed to compare clinicopathologic features and survival between patients with nodal relapse and those with distant relapse and to identify predictors of nodal relapse after surgery for NF-PanNETs. METHODS: All patients (n = 321) submitted to surgery for NF-PanNETs were included. Nodal recurrence was defined as the presence of one or more enlarged LNs at high-quality radiologic examinations and always confirmed by 68Ga-DOTA-PET or biopsy. RESULTS: Altogether, 21 patients (6 %) experienced nodal (± distant) relapse, and 35 patients (11 %) had distant recurrence alone. Isolated nodal recurrence occurred for 23 % of patients with recurrence. Overall, 11 patients died of disease, one of whom (pT3N1G3) had an isolated nodal relapse. The rate of LN metastases (81 % vs 54 %; p = 0.044) and median number of positive LNs (PLN) (3 vs 0; p = 0.019) both were significantly higher for the patients with nodal (± distant) relapse than for those with distant relapse alone. Microvascular invasion (p = 0.046), T stage (p = 0.004), N stage (N1 [p = 0.049]; N2 [p = 0.001]), M stage (p < 0.001), and necrosis (p = 0.011) independently predicted nodal relapse. After distal pancreatectomy (n = 182), 13 patients experienced nodal recurrence, 9 of whom had left paraortic LNs involvement. DISCUSSION: Lymph nodes are not rare sites of recurrence after surgery for NF-PanNETs. Lymph node involvement is a powerful determinant of nodal relapse. Nodal relapse frequently involves LNs that are not removed during standard lymphadenectomy.

Prediction of the characteristics of aggressiveness of pancreatic neuroendocrine neoplasms (PanNENs) based on CT radiomic features.

OBJECTIVES: To predict tumor grade (G1 vs. G2/3), presence of distant metastasis (M+), metastatic lymph nodes (N+), and microvascular invasion (VI) of pancreatic neuroendocrine neoplasms (PanNEN) based on preoperative CT radiomic features (RFs), by applying a machine learning approach aimed to limit overfit. METHODS: This retrospective study included 101 patients who underwent surgery for PanNEN; the entire population was split into training (n = 70) and validation cohort (n = 31). Based on a previously validated methodology, after tumor segmentation on contrast-enhanced CT, RFs were extracted from unenhanced CT images. In addition, conventional radiological and clinical features were combined with RFs into multivariate logistic regression models using minimum redundancy and a bootstrap-based machine learning approach. For each endpoint, models were trained and validated including only RFs (RF_model), and both (radiomic and clinicoradiological) features (COMB_model). RESULTS: Twenty-five patients had G2/G3 tumor, 37 N+, and 14 M+ and 38 were shown to have VI. From a total of 182 RFs initially extracted, few independent radiomic and clinicoradiological features were identified. For M+ and G, the resulting models showed moderate to high performances: areas under the curve (AUC) for training/validation cohorts were 0.85/0.77 (RF_model) and 0.81/0.81 (COMB_model) for M+ and 0.67/0.72 and 0.68/0.70 for G. Concerning N+ and VI, only the COMB_model could be built, with poorer performance for N+ (AUC = 0.72/0.61) compared to VI (0.82/0.75). For all endpoints, the negative predictive value was good (≥ 0.75). CONCLUSIONS: Combining few radiomic and clinicoradiological features resulted in presurgical prediction of histological characteristics of PanNENs. Despite the limited risk of overfit, external validations are warranted. KEY POINTS: • Histology is the only tool currently available allowing characterization of PanNEN biological characteristics important for prognostic assessment; significant limitations to this approach exist. • Based upon preoperative contrast-enhanced CT images, a machine learning approach optimized to favor models' generalizability was successfully applied to train predictive models for tumor grading (G1 vs. G2/3), microvascular invasion, metastatic lymph nodes, and distant metastatic spread. • Moderate to high discriminative models (AUC: 0.67-0.85) based on few parameters (≤ 3) showing high negative predictive value (0.75-0.98) were generated and then successfully validated.

Management of clinically relevant postoperative pancreatic fistula-related fluid collections after distal pancreatectomy.

BACKGROUND: Distal pancreatectomy is burdened by a high rate of clinically relevant postoperative pancreatic fistula (CR-POPF). The presence of a fistula-related abdominal collection often requires additional treatment such as antibiotics, percutaneous drainage, and endoscopic drainage thus prolonging patient recovery. Aim of this study was to describe the management of abdominal collections related to CR-POPF and identify variables associated with the need for invasive procedures. METHODS: A retrospective review of clinical data for patients who underwent distal pancreatectomy between 2015 and 2020 was conducted. All postoperative CT-scan imaging performed for clinical signs related to POPF was reviewed. The main outcome of the study was the need for procedural management (percutaneous or endoscopic) of CR-POPF-related fluid collections at 90 days after surgery. A multivariate regression analysis was adopted to analyze factors influencing procedural management of the collection. RESULTS: Five hundred sixteen patients were included in the study. Laparoscopic resection was performed in 290 patients (56%). At 90 days after surgery, CR-POPF occurred in 207 (40.1%) patients. A symptomatic collection related to fistula was observed in 130 patients (25.2%). Factors associated with fluid collections were increased body mass index (BMI) (25.5 versus 24, p = 0.001) and intraoperative blood loss (median of 250 versus 200 ml, p < 0.001). Procedural management was required in 70 patients (13.6%); 52 patients required interventional radiology and 18 endoscopic drainage. At multivariate analysis, risk factors for invasive procedures were the following CT-scan parameters: fluid collection diameter greater than 5 cm (OR 6.366, 95%CI 2.29-17.66, p = 0.001), presence of blood in the fluid collection (OR 10.618, 95%CI 1.94-58.09, p = 0.006), and enhancement of its walls (OR 4.073, 95%CI 1.22-13.57, p = 0.022). CONCLUSION: CR-POPF-related fluid collections affect about a quarter of patients undergoing distal pancreatectomy. CT-scan provides important information which can guide the management of the collection in a "step-up" fashion.

Limited impact of discretization/interpolation parameters on the predictive power of CT radiomic features in a surgical cohort of pancreatic cancer patients.

PURPOSE: To explore the variation of the discriminative power of CT (Computed Tomography) radiomic features (RF) against image discretization/interpolation in predicting early distant relapses (EDR) after upfront surgery. MATERIALS AND METHODS: Data of 144 patients with pre-surgical high contrast CT were processed consistently with IBSI (Image Biomarker Standardization Initiative) guidelines. Image interpolation/discretization parameters were intentionally changed, including cubic voxel size (0.21-27 mm3) and binning (32-128 grey levels) in a 15 parameter's sets. After excluding RF with poor inter-observer delineation agreement (ICC < 0.80) and not negligible inter-scanner variability, the variation of 80 RF against discretization/interpolation was first quantified. Then, their ability in classifying patients with early distant relapses (EDR, < 10 months, previously assessed at the first quartile value of time-to-relapse) was investigated in terms of AUC (Area Under Curve) variation for those RF significantly associated to EDR. RESULTS: Despite RF variability against discretization/interpolation parameters was large and only 30/80 RF showed %COV < 20 (%COV = 100*STDEV/MEAN), AUC changes were relatively limited: for 30 RF significantly associated with EDR (AUC values around 0.60-0.70), the mean values of SD of AUC variability and AUC range were 0.02 and 0.05 respectively. AUC ranges were between 0.00 and 0.11, with values ≤ 0.05 in 16/30 RF. These variations were further reduced when excluding the extreme values of 32 and 128 for grey levels (Average AUC range 0.04, with values between 0.00 and 0.08). CONCLUSIONS: The discriminative power of CT RF in the prediction of EDR after upfront surgery for pancreatic cancer is relatively invariant against image interpolation/discretization within a large range of voxel sizes and binning.

A Single-center Prospective Observational Study Investigating the Accuracy of Preoperative Diagnostic Procedures in the Assessment of Lymph Node Metastases in Nonfunctioning Pancreatic Neuroendocrine Tumors.

OBJECTIVE: To determine the accuracy of preoperative imaging, including contrast-enhanced computed tomography (CE-CT), endoscopic ultrasound (EUS), and 68 Gallium-DOTATOC positron emission tomography ( 68 Ga-DOTATOC PET), in identifying nodal metastases (N+) in sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). BACKGROUND: An accurate preoperative identification of N+ in NF-PanNETs is critical for surgical planning. The accuracy of different imaging techniques in detecting lymph node (LN) metastases in NF-PanNETs has been poorly investigated. METHODS: All consecutive patients undergoing surgery for sporadic NF-PanNETs (2018-2021) were enrolled in a prospective study (DETECTYON; NCT03918759). The accuracy of preoperative imaging techniques in detecting N+ was assessed through sensitivity, specificity positive and negative predictive values. RESULTS: Overall, 100 patients with NF-PanNETs underwent CE-CT, EUS, and 68 Ga-DOTATOC PET before pancreatic resection. LN metastases were found in 42 cases (42%). Sensitivity, specificity, positive predictive value, and negative predictive value of different imaging techniques were 26%, 95%, 79%, 64% for CE-CT, 19%, 98%, 89%, 63% for EUS, and 12%, 95%, 63%, 60% for 68 Ga-DOTATOC PET, respectively. Radiologic tumor size >4 cm and the presence of radiologic N+ at ≥1 imaging were independent predictors of N+ at pathology. The identification of N+ at ≥1 imaging technique was associated with a higher number of positive LNs compared with negative imaging (4 vs 2) ( P =0.012). CONCLUSIONS: CE-CT, EUS, and 68 Ga-DOTATOC PET are poorly sensitive in predicting nodal status in NF-PanNETs despite a high specificity.

Barotrauma in Coronavirus Disease 2019 Patients Undergoing Invasive Mechanical Ventilation: A Systematic Literature Review.

OBJECTIVE: There are concerns of a high barotrauma rate in coronavirus disease 2019 patients with acute respiratory distress syndrome receiving invasive mechanical ventilation. However, a few studies were published, and reported rates were highly variable. We performed a systematic literature review to identify rates of barotrauma, pneumothorax, and pneumomediastinum in coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation. DATA SOURCE: PubMed and Scopus were searched for studies reporting barotrauma event rate in adult coronavirus disease 2019 patients receiving invasive mechanical ventilation. STUDY SELECTION: We included all studies investigating adult patients with coronavirus disease 2019 acute respiratory distress syndrome requiring mechanical ventilation. Case reports, studies performed outside ICU setting, and pediatric studies were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of pneumothorax, pneumomediastinum and overall barotrauma events, and mortality. When available, data from noncoronavirus disease 2019 acute respiratory distress syndrome patients were also collected. Pooled estimates for barotrauma, pneumothorax, and pneumomediastinum were calculated. DATA SYNTHESIS: A total of 13 studies with 1,814 invasively ventilated coronavirus disease 2019 patients and 493 noncoronavirus disease 2019 patients were included. A total of 266/1,814 patients (14.7%) had at least one barotrauma event (pooled estimates, 16.1% [95% CI, 11.8-20.4%]). Pneumothorax occurred in 132/1,435 patients (pooled estimates, 10.7%; 95% CI, 6.7-14.7%), whereas pneumomediastinum occurred in 162/1,432 patients (pooled estimates, 11.2%; 95% CI, 8.0-14.3%). Mortality in coronavirus disease 2019 patients who developed barotrauma was 111/198 patients (pooled estimates, 61.6%; 95% CI, 50.2-73.0%). In noncoronavirus disease 2019 acute respiratory distress syndrome patients, barotrauma occurred in 31/493 patients (6.3%; pooled estimates, 5.7%; 95% CI, -2.1% to 13.5%). CONCLUSIONS: Barotrauma occurs in one out of six coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation and is associated with a mortality rate of about 60%. Barotrauma rate may be higher than noncoronavirus disease 2019 controls.

The Impact of CT-Assessed Liver Steatosis on Postoperative Complications After Pancreaticoduodenectomy for Cancer.

INTRODUCTION: Liver steatosis (LS) has been increasingly described in preoperative imaging of patients undergoing pancreaticoduodenectomy (PD). The aim of this study was to assess the impact of preoperative LS on complications after PD and identify possible contributors to LS development in this specific cohort. METHODS: Pancreatic head adenocarcinoma (PDAC) patients scheduled for PD, with preoperative CT-imaging available were included in the study. LS was defined as mean liver density lower than 45 Hounsfield units. Patients showing preoperative LS were matched for patient age, gender, BMI, ASA score, neoadjuvant treatment, and vascular and multivisceral resections, based on propensity scores in a 1:2 ratio to patients with no LS. The primary outcome was postoperative complication severity at 90 days as measured by the comprehensive complication index (CCI) RESULTS: Overall, 247 patients were included in the study. Forty-three (17%) patients presented with LS at preoperative CT-scan. After matching, the LS group included 37 patients, whereas the non-LS group had 74 patients. LS patients had a higher mean (SD) CCI, 29.7 (24.5) versus 19.5 (22.5), p = 0.035, and a longer length of hospital stay, median [IQR] 12 [8-26] versus 8 [7-13] days, p = 0.006 compared with non-LS patients. On multivariate analysis, variables independently associated with CCI were: LS (16% increase, p = 0.048), male sex (19% increase, p = 0.030), ASA score ≥ 3 (26% increase, p = 0.002), fistula risk score (FRS) (28% increase for each point of FRS, p = 0.001) and vascular resection (20% increase, p = 0.019). CONCLUSION: Preliminary evidence suggests that preoperative LS assessed by CT-scan influences complication severity in patients undergoing PD for PDAC.

Improving diagnostic accuracy and appropriate indications for surgery in pancreatic cystic neoplasms: the role of EUS.

BACKGROUND AND AIMS: Pancreatic cystic neoplasms (PCNs) represent a difficult preoperative diagnosis despite improvements in imaging. In this study, we compared preoperative and final pathologic diagnosis in a large cohort of resected PCNs, evaluating diagnostic accuracy with a specific focus on the value of EUS. METHODS: A retrospective analysis of patients undergoing resection between 2009 and 2019 for presumed PCNs was performed. Preoperative workup was reviewed by analyzing the role of imaging and EUS. Patients with a benign histology who did not show absolute indication were categorized as "delayable surgery." RESULTS: Of 585 patients who were retrospectively analyzed, in 108 (18.5%) final histology did not confirm preoperative diagnosis. EUS was associated with a lower rate of incorrect diagnosis (16%; P = .03), but the risk of overtreatment was similar regardless of instrumental diagnostic path (33/131 vs 68/328, P = .298). Dilatation of the main pancreatic duct and cytologic sampling were the only variables independently associated with a correct diagnosis (P < .001 and P = .041, respectively). Based on clinical presentation and final histology, pancreatic resection could have been spared or delayed in 101 of 459 patients (22%), and this was influenced by age (odds ratio [OR], .97; P = .002), cyst larger than 30 mm (OR, 1.89; P = .005), and type of operation (OR, 3.46 [P < .001] and 3.18 [P = .023] for distal pancreatectomies and other resections, respectively). CONCLUSIONS: The overall risk of unnecessary immediate surgery for PCNs is about 22% in a high-volume referral center. EUS with cytologic sampling is a useful procedure in the diagnostic management of PCNs, improving their diagnostic accuracy.

Combining Laparoscopic Liver Partitioning and Simultaneous Portohepatic Venous Deprivation for Rapid Liver Hypertrophy.

Future liver remnant (FLR) volume is an important indicator of the risk of posthepatectomy liver failure (PHLF) and limits the feasibility of major hepatectomies. A case series of 5 patients treated with a novel approach is presented. Laparoscopic liver partitioning was combined with subsequent liver venous deprivation (embolization of both the portal and the hepatic veins). Baseline average FLR was 28.8%. All procedures were successfully performed without major complications. Mean 1-, 2- and 4-week hypertrophy of the FLR were 35%, 40.3%, and 46.4%, respectively. Four patients underwent planned surgery after a mean interval of 28 days. Of these, 2 patients achieved sufficient FLR volume and function after 2 weeks and underwent surgery before the 4-week volumetric analysis. One patient did not undergo surgery because of intraoperative diagnosis of peritoneal metastases. No cases of PHLF were observed at 5-day follow-up.

Residual lung damage following ARDS in COVID-19 ICU survivors.

BACKGROUND: Coronavirus disease 2019 acute respiratory distress syndrome (COVID-19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID-19 ARDS sequelae. We assessed the mid-term lung status of COVID-19 survivors and investigated factors associated with pulmonary sequelae. METHODS: All adult COVID-19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. RESULTS: Forty-nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89-105) days, whilst PFT after 142 (133-160) days. The median age was 58 (52-65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6-16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71-7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO ) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9-93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. CONCLUSIONS: Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID-19.

Venovenous Extracorporeal Membrane Oxygenation in Awake Non-Intubated Patients With COVID-19 ARDS at High Risk for Barotrauma.

OBJECTIVES: To assess the efficacy of an awake venovenous extracorporeal membrane oxygenation (VV-ECMO) management strategy in preventing clinically relevant barotrauma in patients with coronavirus disease 2019 (COVID-19) with severe acute respiratory distress syndrome (ARDS) at high risk for pneumothorax (PNX)/pneumomediastinum (PMD), defined as the detection of the Macklin-like effect on chest computed tomography (CT) scan. DESIGN: A case series. SETTING: At the intensive care unit of a tertiary-care institution. PARTICIPANTS: Seven patients with COVID-19-associated severe ARDS and Macklin-like radiologic sign on baseline chest CT. INTERVENTIONS: Primary VV-ECMO under spontaneous breathing instead of invasive mechanical ventilation (IMV). All patients received noninvasive ventilation or oxygen through a high-flow nasal cannula before and during ECMO support. The study authors collected data on cannulation strategy, clinical management, and outcome. Failure of awake VV-ECMO strategy was defined as the need for IMV due to worsening respiratory failure or delirium/agitation. The primary outcome was the development of PNX/PMD. MEASUREMENTS AND MAIN RESULTS: No patient developed PNX/PMD. The awake VV-ECMO strategy failed in 1 patient (14.3%). Severe complications were observed in 4 (57.1%) patients and were noted as the following: intracranial bleeding in 1 patient (14.3%), septic shock in 2 patients (28.6%), and secondary pulmonary infections in 3 patients (42.8%). Two patients died (28.6%), whereas 5 were successfully weaned off VV-ECMO and were discharged home. CONCLUSIONS: VV-ECMO in awake and spontaneously breathing patients with severe COVID-19 ARDS may be a feasible and safe strategy to prevent the development of PNX/PMD in patients at high risk for this complication.

One-Year Multidisciplinary Follow-Up of Patients With COVID-19 Requiring Invasive Mechanical Ventilation.

OBJECTIVES: Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. The authors investigated 1-year survival, quality of life, and functional recovery of patients with COVID-19 ARDS requiring invasive mechanical ventilation. DESIGN: Prospective observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: All patients with COVID-19 ARDS receiving invasive mechanical ventilation and discharged alive from hospital. INTERVENTIONS: Patients were contacted by phone after 1 year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS: The study included all adult (age ≥18 years) patients with COVID-19-related ARDS admitted to an ICU of the authors' institution between February 25, 2020, and April 27, 2020, who received at least 1 day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed 1 year after discharge and 56 completed a battery of tests of cognition, activities of daily living, and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by 5 (8.9%) patients. Comparing 2-month and 1-year data, the authors observed the most significant improvements in the areas of working status and exertional dyspnea. One-year chest CT scans were available for 36 patients; fibrotic-like changes were present in 4 patients. CONCLUSIONS: All patients who survived the acute phase of COVID-19 and were discharged from the hospital were alive at the 1-year follow up, and the vast majority of them had good overall recovery and quality of life.

Before sentinel bleeding: early prediction of postpancreatectomy hemorrhage (PPH) with a CT-based scoring system.

OBJECTIVES: Clinically significant pancreatic fistula (POPF) has been established as a well-known risk factor for late and severe postpancreatectomy hemorrhage after pancreaticoduodenectomy (PD) (postpancreatectomy pancreatic fistula-associated hemorrhage [PPFH]). Our aim was to assess whether contrast-enhanced CT scan after PD is an effective tool for early prediction of PPFH. METHODS: From a prospectively acquired database, all consecutive patients who underwent PD between January 2013 and May 2019 were identified; within this database, all patients who were evaluated, for clinical suspicion of POPF, with at least one contrast-enhanced CT scan examination, were enrolled in this retrospective study. The selected CT findings included perianastomotic fluid collections and air bubbles; pancreaticojejunostomy (PJ) was analyzed in terms of dehiscence and defect. RESULTS: One hundred seventy-eight out of 953 PD patients (18.7%) suffered from clinically significant POPF; after exclusions, 166 patients were enrolled. Among this subset, 33 patients (19.9%) had at least one PPFH episode. In multivariable analysis, PPFH was associated with postoperative CT evidence of fluid collections (p = 0.046), air bubbles (p = 0.046), and posterior PJ defect (p < 0.001). Based on these findings, a practical 4-point prediction score was developed (AUC: 0.904, Se: 76%, Sp: 93.8%): patients with a score ≥ 3 demonstrated a significantly higher risk of PPFH development (OR = 45.6, 95% CI: 13.0-159.3). CONCLUSIONS: Postoperative CT scan permits early stratification of PPFH risk, thus providing an actual aid for patients' management. KEY POINTS: • Postpancreatectomy hemorrhage (PPH) is a dramatic, clinically unpredictable occurrence. • After pancreaticoduodenectomy (PD), early identification of posterior pancreaticojejunostomy defect, perianastomotic air bubbles, and retroperitoneal fluid collections enables effective PPH risk stratification by means of a practical CT-based 4-point scoring system. • CT scan after PD allows a paradigm shift in the management PPH, from a conventional "wait and see" approach, to a more proactive one that relies on early anticipation and timely prevention.

Initial chest radiographs and artificial intelligence (AI) predict clinical outcomes in COVID-19 patients: analysis of 697 Italian patients.

OBJECTIVE: To evaluate whether the initial chest X-ray (CXR) severity assessed by an AI system may have prognostic utility in patients with COVID-19. METHODS: This retrospective single-center study included adult patients presenting to the emergency department (ED) between February 25 and April 9, 2020, with SARS-CoV-2 infection confirmed on real-time reverse transcriptase polymerase chain reaction (RT-PCR). Initial CXRs obtained on ED presentation were evaluated by a deep learning artificial intelligence (AI) system and compared with the Radiographic Assessment of Lung Edema (RALE) score, calculated by two experienced radiologists. Death and critical COVID-19 (admission to intensive care unit (ICU) or deaths occurring before ICU admission) were identified as clinical outcomes. Independent predictors of adverse outcomes were evaluated by multivariate analyses. RESULTS: Six hundred ninety-seven 697 patients were included in the study: 465 males (66.7%), median age of 62 years (IQR 52-75). Multivariate analyses adjusting for demographics and comorbidities showed that an AI system-based score ≥ 30 on the initial CXR was an independent predictor both for mortality (HR 2.60 (95% CI 1.69 - 3.99; p < 0.001)) and critical COVID-19 (HR 3.40 (95% CI 2.35-4.94; p < 0.001)). Other independent predictors were RALE score, older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. CONCLUSION: AI- and radiologist-assessed disease severity scores on CXRs obtained on ED presentation were independent and comparable predictors of adverse outcomes in patients with COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366 ( https://clinicaltrials.gov/ct2/show/NCT04318366 ). KEY POINTS: • AI system-based score ≥ 30 and a RALE score ≥ 12 at CXRs performed at ED presentation are independent and comparable predictors of death and/or ICU admission in COVID-19 patients. • Other independent predictors are older age, male sex, coronary artery disease, COPD, and neurodegenerative disease. • The comparable performance of the AI system in relation to a radiologist-assessed score in predicting adverse outcomes may represent a game-changer in resource-constrained settings.

Predictors of Pneumothorax/Pneumomediastinum in Mechanically Ventilated COVID-19 Patients.

OBJECTIVE: To determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). DESIGN: Observational study. SETTING: Tertiary-care university hospital. PARTICIPANTS: One hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS. INTERVENTIONS: The authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD. MEASUREMENTS AND MAIN RESULTS: PNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04). CONCLUSION: PNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.

Pulmonary Vascular Thrombosis in COVID-19 Pneumonia.

OBJECTIVES: During severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, dramatic endothelial cell damage with pulmonary microvascular thrombosis have been was hypothesized to occur. The aim was to assess whether pulmonary vascular thrombosis (PVT) is due to recurrent thromboembolism from peripheral deep vein thrombosis or to local inflammatory endothelial damage, with a superimposed thrombotic late complication. DESIGN: Observational study. SETTING: Medical and intensive care unit wards of a teaching hospital. PARTICIPANTS: The authors report a subset of patients included in a prospective institutional study (CovidBiob study) with clinical suspicion of pulmonary vascular thromboembolism. INTERVENTIONS: Computed tomography pulmonary angiography and evaluation of laboratory markers and coagulation profile. MEASUREMENTS AND MAIN RESULTS: Twenty-eight of 55 (50.9%) patients showed PVT, with a median time interval from symptom onset of 17.5 days. Simultaneous multiple PVTs were identified in 22 patients, with bilateral involvement in 16, mostly affecting segmental/subsegmental pulmonary artery branches (67.8% and 96.4%). Patients with PVT had significantly higher ground glass opacity areas (31.7% [22.9-41] v 17.8% [10.8-22.1], p < 0.001) compared with those without PVT. Remarkably, in all 28 patients, ground glass opacities areas and PVT had an almost perfect spatial overlap. D-dimer level at hospital admission was predictive of PVT. CONCLUSIONS: The findings identified a specific radiologic pattern of coronavirus disease 2019 (COVID-19) pneumonia with a unique spatial distribution of PVT overlapping areas of ground-glass opacities. These findings supported the hypothesis of a pathogenetic relationship between COVID-19 lung inflammation and PVT and challenged the previous definition of pulmonary embolism associated with COVID-19 pneumonia.