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BACKGROUND: Necrotizing pneumonia is an uncommon but severe complication of bacterial pneumonia, associated with high morbidity and mortality. The availability of current data regarding the management of necrotizing pneumonia is limited to case reports and small retrospective observational cohort studies. Consequently, appropriate management for these patients remains unclear. OBJECTIVE: To describe five cases and review the available literature to help guide management of necrotizing pneumonia. METHODS: Cases involving five adults with respiratory failure due to necrotizing pneumonia admitted to a tertiary care centre and infected with Streptococcus pneumoniae (n=3), Klebsiella pneumoniae (n=1) and methicillin‐resistant Staphylococcus aureus (n=1) were reviewed. All available literature was reviewed and encompassed case reports and retrospective reviews dating from 1975 to the present. RESULTS: All five patients received aggressive medical management and consultation by thoracic surgery. Three patients underwent surgical procedures to debride necrotic lung parenchyma. Two of the five patients died in hospital. CONCLUSIONS: Necrotizing pneumonia often leads to pulmonary gangrene. Computed tomography of the thorax with contrast is recommended to evaluate the pulmonary vascular supply. Further study is necessary to determine whether surgical intervention, in the absence of pulmonary gangrene, results in better outcomes.

Background Our aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy. Methods We prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis. Results CTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p =0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p =0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65; p =0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p =0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p =0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p =0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p =0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p <0.001). Conclusion The presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

Abstract This case report outlines a 70-year-old female patient who presented with a concurrent mixed autoimmune hemolytic anemia (AIHA) and a gastric adenocarcinoma. Her treatment course of these two diseases is summarized, which included supportive care, neoadjuvant chemotherapy for her gastric adenocarcinoma, steroids, rituximab, and surgical resection of the tumor. This approach ultimately led to the stabilization of her AIHA and primary cure for her solid malignancy. We briefly review both AIHA and gastric adenocarcinoma as clinical entities, propose working causes of hemolytic anemia including gastric adenocarcinoma, and outline a successful treatment pathway for these two concurrent conditions.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are characterised by high-protein pulmonary edema and severe hypoxaemic respiratory failure due to increased permeability of pulmonary microvascular endothelial cells (PMVEC). Alveolar epithelial cells (AEC) contribute importantly to normal alveolar function, and AEC dysfunction in ALI/ARDS is associated with worse outcomes. We hypothesized that AEC can modulate human PMVEC barrier function, and investigated the effects of AEC presence on human PMVEC barrier under septic conditions in vitro. PMVEC isolated from human lung were treated in vitro with septic stimulation (lipopolysaccharide [LPS], a mixture of clinically-relevant cytokines [cytomix], or plasma from patients with severe sepsis), and the trans-PMVEC leak of Evans Blue dye-labeled albumin assessed. PMVEC septic responses were compared in the presence/absence of co-cultured A549 epithelial cell line or primary human AEC. Septic stimulation with LPS, cytomix, or septic plasma induced marked PMVEC hyper-permeability (10.2±1.8, 8.9±2.2, and 3.7±0.2 fold-increase vs. control, respectively, p<0.01 for all). The presence of A549 cells or primary human AEC in a non-contact co-culture model attenuated septic PMVEC hyper-permeability by 39±4% to 100±3%, depending on the septic stimulation (p<0.05). Septic PMVEC hyper-permeability was also attenuated following treatment with culture medium conditioned by previous incubation with either naïve or cytomix-treated A549 cells (p<0.05), and this protective effect of A549 cell-conditioned medium was both heat-stable and transferable following lipid extraction. Cytomix-stimulated PMN-dependent PMVEC hyper-permeability and trans-PMVEC PMN migration were also inhibited in the presence of A549 cells or A549 cell-conditioned medium (p<0.05). Human AEC appear to protect human PMVEC barrier function under septic conditions in vitro, through release of a soluble mediator(s), which are at least partly lipid in nature. This study suggests a scientific and potential clinical therapeutic importance of epithelial-endothelial cross talk in maintaining alveolar integrity in ALI/ARDS.

Surgical recovery after hospital discharge often presents challenges for patients and caregivers. Postoperative complications and poorly managed pain at home can lead to unexpected visits to the emergency department (ED) and readmission to the hospital. Digital home monitoring (DHM) may improve postoperative care compared to standard methods. We conducted a feasibility study for a randomized controlled trial (RCT) to assess DHM's effectiveness following thoracic surgical procedures compared to standard care. We conducted a 2-arm parallel-group pilot RCT at a single tertiary care center. Adult patients undergoing thoracic surgical procedures were randomized 1:1 into 2 groups: the DHM group and the standard of care (control group). We adhered to the intention-to-treat analysis principle. The primary outcome was predetermined RCT feasibility criteria. The trial would be feasible if more than 75% of trial recruitment, protocol adherence, and data collection were achieved. Secondary outcomes included 30-day ED visit rates, 30-day readmission rates, postoperative complications, length of stay, postdischarge 30-day opioid consumption, 30-day quality of recovery, patient-program satisfaction, caregiver satisfaction, health care provider satisfaction, and cost per case. All RCT feasibility criteria were met. The trial recruitment rate was 87.9% (95% CI 79.4%-93.8%). Protocol adherence and outcome data collection rates were 96.3% (95% CI 89.4%-99.2%) and 98.7% (95% CI 92.9%-99.9%), respectively. In total, 80 patients were randomized, with 40 (50%) in the DHM group and 40 (50%) in the control group. Baseline patient and clinical characteristics were comparable between the 2 groups. The DHM group had fewer unplanned ED visits (2.7% vs 20.5%; P=.02), fewer unplanned admission rates (0% vs 7.6%; P=.24), lower rates of postoperative complications (20% vs 47.5%, P=.01) shorter hospital stays (4.0 vs 6.9 days; P=.05), but more opioid consumption (111.6, SD 110.9) vs 74.3, SD 71.9 mg morphine equivalents; P=.08) compared to the control group. DHM also resulted in shorter ED visit times (130, SD 0 vs 1048, SD 1093 minutes; P=.48) and lower cost per case (CAD $12,145 [US $ 8436.34], SD CAD $8779 [US $ 6098.20] vs CAD $17,247 [US $11,980.37], SD CAD $15,313 [US $10,636.95]; P=.07). The quality of recovery scores was clinically significantly better than the controls (185.4, SD 2.6 vs 178.3, SD 3.3; P<.001). All 37 patients who completed the intervention answered the program satisfaction survey questionnaires (100%; 95% CI 90.5%-100%). Only 36 out of 80 caregivers responded to the caregiver satisfaction questionnaires at the end of the fourth week post hospital discharge (47.7%; 95% CI 35.7%-59.1%). Health care providers reported a 100% satisfaction rate. This pilot RCT demonstrates the feasibility of conducting a full-scale trial to assess DHM's efficacy in improving postoperative care following thoracic surgery. DHM shows promise for enhancing continuity of care and warrants further investigation. ClinicalTrials.gov NCT04340960; https://clinicaltrials.gov/study/NCT04340960.

Background Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [ 18 F]FDG-PET and CT Perfusion (CTP). Methods Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [ 18 F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [ 18 F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria. Results RPA identified three response groups based on tumour blood volume before SABR (BV pre-SABR ) and change in SUV max (ΔSUV max ), the thresholds being BV pre-SABR  = 9.3 mL/100 g and ΔSUV max  = − 48.9%. The highest true pCR rate of 92% was observed in the group with BV pre-SABR  < 9.3 mL/100 g and ΔSUV max  < − 48.9% after SABR while the worst was observed in the group with BV pre-SABR  ≥ 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P  = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively). Conclusions In this study, we developed a predictive model based on dynamic [ 18 F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BV pre-SABR and ΔSUV max which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies. Trial registration MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, https://clinicaltrials.gov/ct2/show/NCT02136355

Background The effect of surgical wait times on survival in patients with non–small cell lung cancer (NSCLC) remains largely unknown. Our objective was to determine the effect of surgical wait time on survival and incidence of upstaging in patients with stage I and II NSCLC. Methods All patients with clinical stage I and II NSCLC who underwent surgical resection in a single centre between January 2010 and December 2011 were reviewed. Analysis was stratified based on preoperative clinical stage. We assessed the effect of wait time on survival using a Cox proportional hazard model with wait time in months as a categorical variable. Incidence of upstaging at least 1 stage was assessed using logistic regression. Results We identified 222 patients: 180 were stage I and 42 were stage II. For stage I, wait times up to 4 months had no significant effect on survival or incidence of upstaging. For stage II, patients waiting between 2 and 3 months had significantly decreased survival (hazard ratio 3.6, p = 0.036) and increased incidence of upstaging (odds ratio 2.0, p = 0.020) than those waiting 0 to 1 month. For those waiting between 1 and 2 months, there was no significant difference in survival or upstaging. Conclusion We did not identify an effect of wait time up to 4 months on survival or upstaging for patients with stage I NSCLC. For patients with stage II disease, wait times greater than 2 months adversely affected survival and upstaging.

Background We compared the health‐related quality of life (HRQOL) in patients undergoing trimodality therapy for resectable stage I‐III esophageal cancer. Methods A total of 96 patients were randomized to standard neoadjuvant cisplatin and 5‐fluorouracil chemotherapy plus radiotherapy (neoadjuvant) followed by surgical resection or adjuvant cisplatin, 5‐fluorouracil, and epirubicin chemotherapy with concurrent extended volume radiotherapy (adjuvant) following surgical resection. Results There was no significant difference in the functional assessment of cancer therapy‐esophageal (FACT‐E) total scores between arms at 1 year (p = 0.759) with 36% versus 41% (neoadjuvant vs. adjuvant), respectively, showing an increase of ≥15 points compared to pre‐treatment (p = 0.638). The HRQOL was significantly inferior at 2 months in the neoadjuvant arm for FACT‐E, European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ‐OG25), and EuroQol 5‐D‐3 L in the dysphagia, reflux, pain, taste, and coughing domains (p < 0.05). Half of patients were able to complete the prescribed neoadjuvant arm chemotherapy without modification compared to only 14% in the adjuvant arm (p < 0.001). Chemotherapy related adverse events of grade ≥2 occurred significantly more frequently in the neoadjuvant arm (100% vs. 69%, p < 0.001). Surgery related adverse events of grade ≥2 were similar in both arms (72% vs. 86%, p = 0.107). There were no 30‐day mortalities and 2% vs. 10% 90‐day mortalities (p = 0.204). There were no significant differences in either overall survival (OS) (5‐year: 35% vs. 32%, p = 0.409) or disease‐free survival (DFS) (5‐year: 31% vs. 30%, p = 0.710). Conclusion Trimodality therapy is challenging for patients with resectable esophageal cancer regardless of whether it is given before or after surgery. Newer and less toxic protocols are needed. This randomized trial assessed the health related quality of life in esophageal cancer patients undergoing neoadjuvant versus adjuvant trimodality therapy. Every patient experienced at least one adverse event. The quality of life was worse for patients undergoing neoadjuvant compared to adjuvant chemoradiation with no significant difference in either overall survival or disease‐free survival. More effective therapy is needed.

COVID-19 puts health care providers at risk for infection with SARS-CoV-2. Personal protective equipment (PPE) can reduce viral transmission if used properly. We used simulation of an intraoperative crisis involving an infectious outbreak to assess PPE adherence and confidence in PPE use. Simulation of an intraoperative crisis with a patient with COVID-19 revealed gaps in PPE adherence; however, simulation training successfully increased confidence in PPE use and received positive feedback.

Background Stereotactic ablative radiation therapy (SABR) is effective in treating inoperable stage I non-small cell lung cancer (NSCLC), but imaging assessment of response after SABR is difficult. This prospective study aimed to develop a predictive model for true pathologic complete response (pCR) to SABR using imaging-based biomarkers from dynamic [.sup.18F]FDG-PET and CT Perfusion (CTP). Methods Twenty-six patients with early-stage NSCLC treated with SABR followed by surgical resection were included, as a pre-specified secondary analysis of a larger study. Dynamic [.sup.18F]FDG-PET and CTP were performed pre-SABR and 8-week post. Dynamic [.sup.18F]FDG-PET provided maximum and mean standardized uptake value (SUV) and kinetic parameters estimated using a previously developed flow-modified two-tissue compartment model while CTP measured blood flow, blood volume and vessel permeability surface product. Recursive partitioning analysis (RPA) was used to establish a predictive model with the measured PET and CTP imaging biomarkers for predicting pCR. The model was compared to current RECIST (Response Evaluation Criteria in Solid Tumours version 1.1) and PERCIST (PET Response Criteria in Solid Tumours version 1.0) criteria. Results RPA identified three response groups based on tumour blood volume before SABR (BV.sub.pre-SABR) and change in SUV.sub.max ([DELA]SUV.sub.max), the thresholds being BV.sub.pre-SABR = 9.3 mL/100 g and [DELA]SUV.sub.max = - 48.9%. The highest true pCR rate of 92% was observed in the group with BV.sub.pre-SABR < 9.3 mL/100 g and [DELA]SUV.sub.max < - 48.9% after SABR while the worst was observed in the group with BV.sub.pre-SABR [greater than or equai to] 9.3 mL/100 g (0%). RPA model achieved excellent pCR prediction (Concordance: 0.92; P = 0.03). RECIST and PERCIST showed poor pCR prediction (Concordance: 0.54 and 0.58, respectively). Conclusions In this study, we developed a predictive model based on dynamic [.sup.18F]FDG-PET and CT Perfusion imaging that was significantly better than RECIST and PERCIST criteria to predict pCR of NSCLC to SABR. The model used BV.sub.pre-SABR and [DELA]SUV.sub.max which correlates to tumour microvessel density and cell proliferation, respectively and warrants validation with larger sample size studies. Trial registration MISSILE-NSCLC, NCT02136355 (ClinicalTrials.gov). Registered May 8, 2014, Keywords: Stereotactic ablative radiation therapy (SABR), Non-small cell lung cancer (NSCLC), Pathologic complete response (pCR), Dynamic positron emission tomography (PET), [.sup.18F]FDG, CT perfusion, Kinetic analysis