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Pleural mesothelioma (PM) is a fatal disease with limited treatment options. Recently, PM management has improved with the development of immune checkpoint inhibitors (ICIs). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. Here, we evaluated the effect of Hyperthermic IntraThOracic Chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine PM model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of PM by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial.

The response to proteotoxic stresses such as heat shock allows organisms to maintain protein homeostasis under changing environmental conditions. We asked what happens if an organism can no longer react to cytosolic proteotoxic stress. To test this, we deleted or depleted, either individually or in combination, the stress-responsive transcription factors Msn2, Msn4, and Hsf1 in Saccharomyces cerevisiae. Our study reveals a combination of survival strategies, which together protect essential proteins. Msn2 and 4 broadly reprogram transcription, triggering the response to oxidative stress, as well as biosynthesis of the protective sugar trehalose and glycolytic enzymes, while Hsf1 mainly induces the synthesis of molecular chaperones and reverses the transcriptional response upon prolonged mild heat stress (adaptation)., (© 2024 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Since the late 1990s, and Henrik Kehlet's hypothesis that a reduction of the body's stress response to major surgeries could decrease postoperative morbidity, "Enhanced Recovery After Surgery" (ERAS) care pathways have been streamlined. They are now well accepted and considered standard in many surgical disciplines. Yet, to this day, there is no specific ERAS protocol for chest wall resections (CWRs), the removal of a full-thickness portion of the chest wall, including muscle, bone and possibly skin. This is most unfortunate because these are high-risk surgeries, which carry high morbidity rates. In this review, we propose an overview of the current key elements of the ERAS guidelines for thoracic surgery that might apply to CWRs. A successful ERAS pathway for CWR patients would entail, as is the standard approach, three parts: pre-, peri- and postoperative elements. Preoperative items would include specific information, targeted patient education, involvement of all members of the team, including the plastic surgeons, smoking cessation, dedicated nutrition and carbohydrate loading. Perioperative items would likely be standard for thoracotomy patients, namely carefully selective pre-anesthesia sedative medication only in some rare instances, low-molecular-weight heparin throughout, antibiotic prophylaxis, minimization of postoperative nausea and vomiting, avoidance of fluid overload and of urinary drainage. Postoperative elements would include early mobilization and feeding, swift discontinuation of intravenous fluid supply and chest tube removal as soon as safe. Optimal pain management throughout also appears to be critical to minimize the risk of respiratory complications. Together, all these items are achievable and may hold the key to successful introduction of ERAS pathways to the benefit of CWR patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-911/coif). The series “Chest Wall Resections and Reconstructions” was commissioned by the editorial office without any funding or sponsorship. M.G. serves as an unpaid editorial board member of Journal of Thoracic Disease from February 2023 to January 2025. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Objectives: The aim of this study was to compare short-term outcomes and local control in pT1c pN0 non-small-cell lung cancer that were intentionally treated by video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy., Methods: Multicentre retrospective study of consecutive patients undergoing VATS lobectomy (VL) or VATS segmentectomy (VS) for pT1c pN0 non-small-cell lung cancer from January 2014 to October 2021. Patients' characteristics, postoperative outcomes and survival were compared., Results: In total, 162 patients underwent VL (n = 81) or VS (n = 81). Except for age [median (interquartile range) 68 (60-73) vs 71 (65-76) years; P = 0.034] and past medical history of cancer (32% vs 48%; P = 0.038), there was no difference between VL and VS in terms of demographics and comorbidities. Overall 30-day postoperative morbidity was similar in both groups (34% vs 30%; P = 0.5). The median time for chest tube removal [3 (1-5) vs 2 (1-3) days; P = 0.002] and median postoperative length of stay [6 (4-9) vs 5 (3-7) days; P = 0.039] were in favour of the VS group. Significantly larger tumour size (mean ± standard deviation 25.1 ± 3.1 vs 23.6 ± 3.1 mm; P = 0.001) and an increased number of lymph nodes removal [median (interquartile range) 14 (9-23) vs 10 (6-15); P < 0.001] were found in the VL group. During the follow-up [median (interquartile range) 31 (14-48) months], no statistical difference was found for local and distant recurrence in VL groups (12.3%) and VS group (6.1%) (P = 0.183). Overall survival (80% vs 80%) was comparable between both groups (P = 0.166)., Conclusions: Despite a short follow-up, our preliminary data shows that local control is comparable for VL and VS., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

We aimed to evaluate whether computed tomography (CT)-derived preoperative sarcopenia measures were associated with postoperative outcomes and survival after video-assisted thoracoscopic (VATS) anatomical pulmonary resection in patients with early-stage non-small cell lung cancer (NSCLC). We retrospectively reviewed all consecutive patients that underwent VATS anatomical pulmonary resection for NSCLC between 2012 and 2019. Skeletal muscle mass was measured at L3 vertebral level on preoperative CT or PET/CT scans to identify sarcopenic patients according to established threshold values. We compared postoperative outcomes and survival of sarcopenic vs. non-sarcopenic patients. A total of 401 patients underwent VATS anatomical pulmonary resection for NSCLC. Sarcopenia was identified in 92 patients (23%). Sarcopenic patients were predominantly males (75% vs. 25%; p < 0.001) and had a lower BMI (21.4 vs. 26.5 kg/m 2 ; p < 0.001). The overall postoperative complication rate was significantly higher (53.2% vs. 39.2%; p = 0.017) in sarcopenic patients and the length of hospital stay was prolonged (8 vs. 6 days; p = 0.032). Two factors were associated with postoperative morbidity in multivariate analysis: BMI and American Society of Anesthesiologists score >2. Median overall survival was comparable between groups (41 vs. 46 months; p = 0.240). CT-derived sarcopenia appeared to have a small impact on early postoperative clinical outcomes, but no effect on overall survival after VATS anatomical lung resection for NSCLC., Competing Interests: The authors declare no conflicts of interest.

Objectives: A paucity of data supports the use of transesophageal echocardiography (TEE) for bedside extracorporeal membrane oxygenation (ECMO) cannulation. Concerns have been raised about performing TEEs in patients with COVID-19. The authors describe the use and safety of TEE guidance for ECMO cannulation for COVID-19., Design: Single-center retrospective cohort study., Setting: The study took place in the intensive care unit of an academic tertiary center., Participants: The authors included 107 patients with confirmed SARS-CoV-2 infection who underwent bedside venovenous ECMO (VV ECMO) cannulation under TEE guidance between May 2020 and June 2021., Interventions: TEE-guided bedside VV ECMO cannulation., Measurements: Patient characteristics, physiologic and ventilatory parameters, and echocardiographic findings were analyzed. The primary outcome was the number of successful TEE-guided bedside cannulations without complications. The secondary outcomes were cannulation complications, frequency of cannula repositioning, and TEE-related complications., Main Results: TEE-guided cannulation was successful in 99% of the patients. Initial cannula position was adequate in all but 1 patient. Fourteen patients (13%) required cannula repositioning during ECMO support. Forty-five patients (42%) had right ventricular systolic dysfunction, and 9 (8%) had left ventricular systolic dysfunction. Twelve patients (11%) had intracardiac thrombi. One superficial arterial injury and 1 pneumothorax occurred. No pericardial tamponade, hemothorax or intraabdominal bleeding occurred in the authors' cohort. No TEE-related complications or COVID-19 infection of healthcare providers were reported during this study., Conclusions: Bedside TEE guidance for VV ECMO cannulation is safe in patients with severe respiratory failure due to COVID-19. No tamponade or hemothorax, nor TEE-related complications were observed in the authors' cohort., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Our recent work has challenged 4°C as an optimal lung preservation temperature by showing storage at 10°C to allow for the extension of preservation periods. Despite these findings, the impact of 10°C storage has not been evaluated in the setting of injured donor lungs., Methods: Aspiration injury was created through bronchoscopic delivery of gastric juice (pH: 1.8). Injured donor lungs (n = 5/group) were then procured and blindly randomized to storage at 4°C (on ice) or at 10°C (in a thermoelectric cooler) for 12 hours. A third group included immediate transplantation. A left lung transplant was performed thereafter followed by 4 hours of graft evaluation., Results: After transplantation, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C group (343 ± 43 mm Hg vs 128 ± 76 mm Hg, p = 0.03). Active metabolism occurred during the 12 hours storage period at 10°C, producing cytoprotective metabolites within the graft. When compared to lungs undergoing immediate transplant, lungs preserved at 10°C tended to have lower peak airway pressures (p = 0.15) and higher dynamic lung compliances (p = 0.09). Circulating cell-free mitochondrial DNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those underwent immediate transplant (p = 0.048), alongside a tendency of lower levels of tissue apoptotic cell death (p = 0.075)., Conclusions: We demonstrate 10°C as a potentially superior storage temperature for injured donor lungs in a pig model when compared to the current clinical standard (4°C) and immediate transplantation. Continuing protective metabolism at 10°C for donor lungs may result in better transplant outcomes., Competing Interests: Disclosure statement MC, TW, SK are shareholders of Traferox Technologies Inc, Traferox devices were not used in any part of the study. MC, TW and SK are consultants for Lung Bioengineering Inc. None of the other authors have conflict of interest to disclose. This work was supported by the UHN Foundation #5790-6833-0776 (MC). We thank Paul Chartrand (Latner Thoracic Surgery Laboratories) for supplies and logistics management throughout the study., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Persistent pain and disability following rib fractures result in a large psycho-socio-economic impact for health-care system. Benefits of rib osteosynthesis are well documented in patients with flail chest that necessitates invasive ventilation. In patients with uncomplicated and simple rib fractures, indication for rib osteosynthesis is not clear. The aim of this trial is to compare pain at 2 months after rib osteosynthesis versus medical therapy., Methods: This trial is a pragmatic multicenter, randomized, superiority, controlled, two-arm, not-blinded, trial that compares pain evolution between rib fixation and standard pain medication versus standard pain medication alone in patients with uncomplicated rib fractures. The study takes place in three hospitals of Thoracic Surgery of Western Switzerland. Primary outcome is pain measured by the brief pain inventory (BPI) questionnaire at 2 months post-surgery. The study includes follow-up assessments at 1, 2, 3, 6, and 12 months after discharge. To be able to detect at least 2 point-difference on the BPI between both groups (standard deviation 2) with 90% power and two-sided 5% type I error, 46 patients per group are required. Adjusting for 10% drop-outs leads to 51 patients per group., Discussion: Uncomplicated rib fractures have a significant medico-economic impact. Surgical treatment with rib fixation could result in better clinical recovery of patients with uncomplicated rib fractures. These improved outcomes could include less acute and chronic pain, improved pulmonary function and quality of life, and shorter return to work. Finally, surgical treatment could then result in less financial costs., Trial Registration: ClinicalTrials.gov NCT04745520 . Registered on 8 February 2021., (© 2022. The Author(s).)

Introduction: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) and decompensated right heart failure (DRHF) have worse outcomes after pulmonary endarterectomy (PEA). We reviewed the role of central veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a bridge to recovery after PEA in these patients., Methods: Of 388 consecutive patients undergoing PEA, 40 (10.3%) were admitted with DRHF before PEA. This group was compared to the remaining 348 patients undergoing PEA (elective group). We also compared 2 periods: 2005-2013 (n = 120) and 2014-2019 (n = 268) after which early central VA-ECMO was introduced as a strategy to manage difficulty weaning from cardiopulmonary bypass (CPB)., Results: The proportion of patients with DRHF remained similar between the first and second period (13% vs 9%, p = .2). The number of VA-ECMO bridge to recovery increased from 0.8% in 2005-2013 to 6.3% in 2014-2019 (p = .02). In the second period, 29% of DRHF patients were transitioned intraoperatively from CPB to central VA-ECMO for a median duration of 3 (2-7) days. After the introduction of central VA-ECMO as a bridge to recovery, the hospital mortality in patients with DRHF dropped from 31% in 2005-2013 to 4% in 2014-2019 (p = .03). In the long-term, the functional recovery and survival after discharged from hospital was similar between the DRHF group and the elective group. However, at 5 years, DRHF patients more frequently required PH targeted medical therapy (45% vs 20% in the elective group, p = .002)., Conclusions: Central VA-ECMO as a bridge to recovery is an important treatment strategy that can decrease hospital mortality in patients with DRHF and lead to excellent long-term outcome., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Video-assisted thoracic surgery (VATS) is now the preferred approach for standard anatomical pulmonary resections. This study evaluates the impact of operative time (OT) on post-operative outcomes after VATS anatomical pulmonary resection for non-small cell lung cancer (NSCLC)., Methods: We retrospectively reviewed all consecutive patients undergoing VATS lobectomy or segmentectomy for NSCLC between November 2010 and December 2019. Postoperative outcomes were compared between short (<150 minutes) and long (≥150 minutes) OT groups. A multivariable analysis was performed to identify predictors of long OT and overall post-operative complications., Results: A total of 670 patients underwent lobectomy (n=496, 74%) or segmentectomy (n=174, 26%) for NSCLC. Mediastinal lymph node dissection was performed in 621 patients (92.7%). The median OT was 141 minutes (SD: 47 minutes) and 387 patients (57.8%) were operated within 150 minutes. Neoadjuvant chemotherapy was given in 25 patients (3.7%). Conversion thoracotomy was realized in 40 patients (6%). Shorter OT was significantly associated with decreased post-operative overall complication rate (30% vs. 41%; P=0.003), shorter median length of drainage (3 vs. 4 days; P<0.001) and shorter median length of hospital stay (6 vs. 7 days; P<0.001). On multivariable analysis, long OT (≥150 minutes) (OR 1.64, P=0.006), ASA score >2 (OR 1.87, P=0.001), FEV 1 <80% (OR 1.47, P=0.046) and DLCO <80% (OR 1.5, P=0.045) were significantly associated with postoperative complications. Two predictors of long OT were identified: neoadjuvant chemotherapy (OR 3.11, P=0.01) and lobectomy (OR 1.5, P=0.032)., Conclusions: A prolonged OT is significantly associated with postoperative complications in our collective of patients undergoing VATS anatomical pulmonary resection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1774/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background: Chest wall resections/reconstructions are a validated approach to manage tumors invading the thorax. However, how resection characteristics affect postoperative morbidity and mortality is unknown. We determined the impact of chest wall resection size and location on patient short and long-term postoperative outcomes., Methods: We reviewed all consecutive patients who underwent resections/reconstructions for chest wall tumors between 2003 and 2018. The impact of chest wall resection size and location and reconstruction on perioperative morbidity/mortality and oncological outcome were evaluated for each patient., Results: Ninety-three chest wall resections were performed in 88 patients for primary (sarcoma, breast cancer, n=66, 71%) and metastatic (n=27, 29%) chest wall tumors. The mean chest bony resection size was 107 (range, 15-375) cm 2 and involved ribs only in 57% (n=53) or ribs combined to sternal/clavicular resections in 43% of patients (n=40). Chest defect reconstruction methods included muscle flaps alone (14%) prosthetic material alone (25%) or a combination of both (61%). Early systemic postoperative complications included pneumonia (n=15, 16%), atelectasis (n=6, 6%), pleural effusion (n=15, 16%) and arrhythmia (n=6, 6%). The most frequent long-term reconstructive complications included wound dehiscence (n=4), mesh infection (n=5) and seroma (n=4). Uni- and multivariable analyses indicated that chest wall resection size (>114 cm 2 ) and location (sternum) were significantly associated with the occurrence of pneumonia and atelectasis [odds ratio (OR) =3.67, P=0.05; OR =78.92, P=0.02, respectively]. Disease-free and overall survival were 37±43 and 48±42 months for primary malignancy and of 24±33 and 48±53 months for metastatic chest wall tumors respectively with a mean follow-up of 46±44 months., Conclusions: Chest wall resections present good long-term oncological outcomes. A resection size above 114 cm 2 and the involvement of the sternum are significantly associated with higher rates of postoperative pneumonia/atelectasis. This subgroup of patients should have reinforced perioperative physical therapy protocols., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-2143/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Background: Pulmonary endarterectomy (PEA) in severe chronic thromboembolic pulmonary hypertension (CTEPH) is associated with higher risks. However, recent evidence suggests that these risks may be mitigated with the use of extracorporeal membrane oxygenation (ECMO)., Methods: We performed a retrospective analysis of 401 consecutive patients undergoing PEA at the Toronto General Hospital between August 2005 and March 2020. Patients with severe CTEPH defined by pulmonary vascular resistance (PVR) >1,000 dynes.s.cm -5 at the time of diagnosis were compared to those with PVR <1,000 dynes.s.cm -5 ., Results: The New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and 6-minute walk distance were worse in patients with PVR >1,000 dynes.s.cm -5 . A greater proportion of patients with PVR >1,000 dynes.s.cm -5 was treated with targeted pulmonary hypertension (PH) medical therapy (38% vs. 18%, P<0.001) and initiated on inotropic support (7% vs. 0.3%, P<0.001) before PEA. Since 2014, the ECMO utilization rate increased in patients with PVR >1,000 dynes.s.cm -5 compared to those with PVR <1,000 dynes.s.cm -5 (18% vs. 3.1%, P<0.001). The hospital mortality in patients with PVR >1,000 dynes.s.cm -5 decreased from 10.3% in 2005-2013 to 1.6% in 2014-2020 (P=0.05), while the hospital mortality in patients with PVR <1,000 dynes.s.cm -5 remained stable (1.2% in 2005-2013 vs. 2.7% in 2014-2020, P=0.4). The overall survival reached 84% at 10 years in patients with PVR >1,000 dynes.s.cm -5 compared to 78% in patients with PVR <1,000 dynes.s.cm -5 (P=0.7)., Conclusions: The early and long-term results of PEA in patients with severe CTEPH are excellent despite greater postoperative risks. ECMO as a bridge to recovery after PEA can be useful in patients with severe CTEPH., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2022 Annals of Cardiothoracic Surgery. All rights reserved.)

Donor organ allocation is dependent on ABO matching, restricting the opportunity for some patients to receive a life-saving transplant. The enzymes FpGalNAc deacetylase and FpGalactosaminidase, used in combination, have been described to effectively convert group A (ABO-A) red blood cells (RBCs) to group O (ABO-O). Here, we study the safety and preclinical efficacy of using these enzymes to remove A antigen (A-Ag) from human donor lungs using ex vivo lung perfusion (EVLP). First, the ability of these enzymes to remove A-Ag in organ perfusate solutions was examined on five human ABO-A1 RBC samples and three human aortae after static incubation. The enzymes removed greater than 99 and 90% A-Ag from RBCs and aortae, respectively, at concentrations as low as 1 μg/ml. Eight ABO-A1 human lungs were then treated by EVLP. Baseline analyses of A-Ag in lungs revealed expression predominantly in the endothelial and epithelial cells. EVLP of lungs with enzyme-containing perfusate removed over 97% of endothelial A-Ag within 4 hours. No treatment-related acute lung toxicity was observed. An ABO-incompatible transplant was then simulated with an ex vivo model of antibody-mediated rejection using ABO-O plasma as the surrogate for the recipient circulation using three donor lungs. The treatment of donor lungs minimized antibody binding, complement deposition, and antibody-mediated injury as compared with control lungs. These results show that depletion of donor lung A-Ag can be achieved with EVLP treatment. This strategy has the potential to expand ABO-incompatible lung transplantation and lead to improvements in fairness of organ allocation.

Background: Identification of the prognostic factors of recurrence and survival after single pulmonary metastasectomy (PM)., Methods: Retrospective analysis of all consecutive patients who underwent PM for a single lung metastasis between 2003 and 2018., Results: A total of 162 patients with a median age of 64 years underwent single PM. Video-Assisted Thoracic Surgery (VATS) was performed in 83.9% of cases. Surgical resection was achieved by wedge in 73.5%, segmentectomy in 7.4%, lobectomy in 17.9% and pneumonectomy in 1.2% of cases. The median durations of hospital stay and of drainage were 4 days (IQR 3-7) and 1 day (IQR 1-2), respectively. During the follow-up (median 31 months; IQR 15-58), 93 patients (57.4%) presented recurrences and repeated PM could be realized in 35 patients (21.6%) achieved by VATS in 77.1%. Non-colorectal tumour (HR 1.84), age < 70 years (HR 1.77) and previous extra-thoracic metastases (HR 1.61) were identified as prognostic factors of recurrence. Overall survival at 5-year was estimated at 67%. Non-colorectal tumour (HR 2.40) and mediastinal lymph nodes involvement (HR 3.42) were significantly associated with an increased risk of death., Conclusions: Despite high recurrence rates after PM, surgical resection shows low morbidity rate and acceptable long-term survival, thus should remain the standard treatment for single pulmonary metastases., Trial Registration: The Local Ethics Committee approved the study (No. 2019-02,474) and individual consent was waived., (© 2021. The Author(s).)

Objectives: Although video-assisted thoracic surgery (VATS) has shortened hospitalization duration for non-small-cell lung cancer (NSCLC) patients, the factors associated with early discharge remain unclear. This study aimed to identify patients eligible for a 72-h stay after VATS anatomical resection., Methods: Monocentric retrospective study including all consecutive patients undergoing VATS anatomical resection for NSCLC between February 2010 and December 2019. Two groups were defined according to the discharge: 'early discharge' (within 72 postoperative hours) and 'routine discharge' (at >72 postoperative hours)., Results: A total of 660 patients with a median age of 66.5 years (interquartile range 60-73 years) (female/male: 321/339) underwent VATS anatomical pulmonary resection for NSCLC [segmentectomy in 169 (25.6%), lobectomy in 481 (72.9%), bilobectomy in 8 (1.2%) and pneumonectomy in 2 (0.3%) patients]. The cardiopulmonary and Clavien-Dindo III-IV postoperative complication rates were 32.6% and 7.7%, respectively. The median postoperative length of stay was 6 days (interquartile range 4-10 days). In total, 119 patients (18%) could be discharged within 72 h of surgery. On multivariable analysis, the factors significantly associated with an increased likelihood of early discharge were: body mass index >20 kg/m2 [odds ratio (OR) 2.37], absence of prior cardiopathy (OR 2), diffusing capacity of the lung for carbon monoxide >60% (OR 1.82), inclusion in an enhanced recovery after surgery protocol (OR 2.23), use of a single chest tube (OR 5.73) and postoperative transfer to the ward (OR 4.84). Factors significantly associated with a decreased likelihood of early discharge were: age >60 years (OR 0.53), American Society of Anaesthesiologists score >2 (OR 0.46) and use of an epidural catheter (OR 0.41). Readmission rates were not statistically different between both groups (5.9% vs 3.1%; P = 0.17)., Conclusions: Age, pulmonary functions and comorbidities may influence discharge after VATS anatomical resection. The early discharge does not increase readmission rates., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Cold static preservation on ice (~4°C) remains the clinical standard of donor organ preservation. However, mitochondrial injury develops during prolonged storage, which limits the extent of time that organs can maintain viability. We explored the feasibility of prolonged donor lung storage at 10°C using a large animal model and investigated mechanisms related to mitochondrial protection. Functional assessments performed during ex vivo lung perfusion demonstrated that porcine lungs stored for 36 hours at 10°C had lower airway pressures, higher lung compliances, and better oxygenation capabilities, indicative of better pulmonary physiology, as compared to lungs stored conventionally at 4°C. Mitochondrial protective metabolites including itaconate, glutamine, and N -acetylglutamine were present in greater intensities in lungs stored at 10°C than at 4°C. Analysis of mitochondrial injury markers further confirmed that 10°C storage resulted in greater protection of mitochondrial health. We applied this strategy clinically to prolong preservation of human donor lungs beyond the currently accepted clinical preservation limit of about 6 to 8 hours. Five patients received donor lung transplants after a median preservation time of 10.4 hours (9.92 to 14.8 hours) for the first implanted lung and 12.1 hours (10.9 to 16.5 hours) for the second. All have survived the first 30 days after transplantation. There was no grade 3 primary graft dysfunction at 72 hours after transplantation, and median post-transplant mechanical ventilation time was 1.73 days (0.24 to 6.71 days). Preservation at 10°C could become the standard of care for prolonged pulmonary preservation, providing benefits to both patients and health care teams.

Background: Lung transplantation (LTx) is associated with sterile inflammation, possibly related to the release of damage associated molecular patterns (DAMPs) by injured allograft cells. We have measured cellular damage and the release of DAMPs and cytokines in an experimental model of LTx after cold or warm ischemia and examined the effect of pretreatment with ex-vivo lung perfusion (EVLP)., Methods: Rat lungs were exposed to cold ischemia alone (CI group) or with 3h EVLP (CI-E group), warm ischemia alone (WI group) or with 3 hour EVLP (WI-E group), followed by LTx (2 hour). Bronchoalveolar lavage (BAL) was performed before (right lung) or after (left lung) LTx to measure LDH (marker of cellular injury), the DAMPs HMGB1, IL-33, HSP-70 and S100A8, and the cytokines IL-1β, IL-6, TNFα, and CXCL-1. Graft oxygenation capacity and static compliance after LTx were also determined., Results: Compared to CI, WI displayed cellular damage and inflammation without any increase of DAMPs after ischemia alone, but with a significant increase of HMGB1 and functional impairment after LTx. EVLP promoted significant inflammation in both cold (CI-E) and warm (WI-E) groups, which was not associated with cell death or DAMP release at the end of EVLP, but with the release of S100A8 after LTx. EVLP reduced graft damage and dysfunction in warm ischemic, but not cold ischemic, lungs., Conclusions: The pathomechanisms of sterile lung inflammation during LTx are significantly dependent on the conditions. The release of HMGB1 (in the absence of EVLP) and S100A8 (following EVLP) may be important factors in the pathogenesis of LTx., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The shortage of organ donors remains the major limiting factor in lung transplant, with the number of patients on the waiting list largely exceeding the number of available organ donors. Another issue is the low utilization rate seen in some types of donors. Therefore, novel strategies are continuously being explored to increase the donor pool. Advanced age, smoking history, positive serologies, and size mismatch are common criteria that decrease the rate of use when it comes to organ utilization. Questioning these limitations is one of the purposes of this review. Challenging these limitations by adapting novel donor management strategies could help to increase the rate of suitable lungs for transplantation while still maintaining good outcomes. A second goal is to present the latest advances in organ donation after controlled and uncontrolled cardiac death, and also on how to improve these lungs on ex vivo platforms for assessment and future specific therapies. Finally, pushing the limit of the donor envelope also means reviewing some of the recent improvements made in lung preservation itself, as well as upcoming experimental research fields. In summary, donor lung optimization refers to a global care strategy to increase the total numbers of available allografts, and preserve or improve organ quality without paying the price of early-, mid-, or long-term negative outcomes after transplantation., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: This study evaluates the effect of enhanced recovery after surgery (ERAS) pathways on postoperative outcomes of non-small cell lung cancer (NSCLC) patients undergoing video-assisted thoracic surgery (VATS) lobectomy., Methods: We retrospectively reviewed all consecutive patients undergoing VATS lobectomy for NSCLC between January 2014 and October 2019 and assigned them to the relevant group ("pre-ERAS" or "ERAS"). Length of stay, readmissions and complications within 30 days were compared between both groups. A propensity score-matched analysis was performed based on sex, age, type of operation, comorbidities, American Society of Anesthesiologists (ASA) score and preoperative pulmonary functions., Results: A total of 307 records (164 male/143 female; 140 ERAS/167 pre-ERAS; median age: 67) were reviewed. There was no statistical difference in patient's characteristics. Overall ERAS compliance was 81%. The ERAS group presented significantly shorter length of stay (median 5 vs. 7 days; P=0.004) without significant difference in cardiopulmonary complication rate (27.1% vs. 35.9%; P=0.1). Readmission (3.6% vs. 5.4%; P=0.75) and duration of drainage (median 2 vs. 3 days; P=0.14) were similar between groups. The propensity score-matched analysis showed that the length of hospital stay was reduced by 1.4 days (P=0.034) and the postoperative cardiopulmonary complication rate by 13% (P=0.044) in the ERAS group., Conclusions: Adoption of an ERAS pathway for VATS lobectomies in NSCLC patients has decreased the length of hospital stay and the cardiopulmonary complication rate without affecting the readmission rate., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-891). The authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Recurrence after pulmonary metastasectomy (PM) is frequent, but it is unclear to whom repeated pulmonary metastasectomy (RPM) offers highest benefits. Retrospective analysis of oncological and post-operative outcomes of consecutive patients who underwent PM from 2003 to 2018. Overall survival (OS) and disease-free interval (DFI) were calculated. Cox regression was used to identify variables influencing OS and DFI. In total, 264 patients (female/male: 114/150; median age: 62 years) underwent PM for colorectal cancer (32%), sarcoma (19%), melanoma (16%) and other primary tumors (33%). Pulmonary metastasectomy was approached by video-assisted thoracic surgery (VATS) in 73% and pulmonary resection was realized by non-anatomical resection in 76% of cases. The overall median follow-up time was 33 months (IQR 16-56 months) and overall 5-year survival rate was 62%. Local or distant recurrences were observed in 172 patients (65%) and RPM could be performed in 66 patients (25%) for a total of 116 procedures. RPM was realized by VATS in 49% and pulmonary resection by wedge in 77% of cases. In RPM patients, the 5-year survival rate after first PM was 79%. Post-operative cardio-pulmonary complication rate (13% vs. 12%; p = 0.8) and median length of stay (4 vs. 5 days; p = 0.2) were not statistically different between first PM and RPM. Colorectal cancer (HR 0.56), metachronous metastasis (HR 0.48) and RPM (HR 0.5) were associated with better survival. In conclusion, our results suggest that RPM offers favorable survival rates without increasing post-operative morbidity.

Objectives: Implementation of an Enhanced Recovery After Surgery (ERAS) program is associated with better postoperative outcomes. The aim of this study was to evaluate the impact of ERAS compliance (overall and to specific elements of the program) on them., Design: Retrospective analysis of prospectively collected data., Setting: University hospital, monocentric., Participants: All adult (≥18 years old) patients undergoing video-assisted thoracic surgery (VATS) anatomic pulmonary resection., Interventions: ERAS-governed VATS anatomic pulmonary resection., Measurements and Main Results: Demographics, surgical characteristics and pre-, peri-, and postoperative compliance with 16 elements of the ERAS program were assessed. Postoperative outcomes and length of stay were compared between low- (<75% of adherence) and high-compliance (≥75%) groups. From April 2017 to November 2018, 192 ERAS patients (female/male: 98/94) of median age of 66 years (interquartile range 58-71) underwent VATS resection (109 lobectomies, 83 segmentectomies). There was no 30-day mortality and resurgery rate was 5.7%. Overall ERAS compliance was 76%. High compliance was associated with fewer complications (18% v 48%, p < 0.0001) and lower rate of delayed discharge (37% v 60%, p = 0.0013). Early removal of chest tubes (odds ratio [OR]: 0.26, p < 0.002), use of electronic drainage (OR: 0.39, p = 0.036), opioid cessation on day 3 (OR: 0.28, p = 0.016), and early feeding (OR: 0.12, p = 0.014) were associated with reduced rates of postoperative complications. Shorter hospital stay was correlated with early removal of chest tubes (OR: 0.12, p < 0.0001) and opioid cessation on day 3 (OR: 0.23, p = 0.001)., Conclusions: High ERAS compliance is associated with better postoperative outcomes in patients undergoing anatomic pulmonary VATS resections., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ex vivo lung perfusion (EVLP) with pharmacological reconditioning may increase donor lung utilization for transplantation (LTx). 3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) polymerase (PARP), reduces ex vivo lung injury in rat lungs damaged by warm ischemia (WI). Here we determined the effects of 3-AB reconditioning on graft outcome after LTx. Three groups of donor lungs were studied: Control (Ctrl): 1 hour WI + 3 hours cold ischemia (CI) + LTx; EVLP: 1 hour WI + 3 hours EVLP + LTx; EVLP + 3-AB: 1 hour WI + 3 hours EVLP + 3-AB (1 mg . mL -1 ) + LTx. Two hours after LTx, we determined lung graft compliance, edema, histology, neutrophil counts in bronchoalveolar lavage (BAL), mRNA levels of adhesion molecules within the graft, as well as concentrations of interleukin-6 and 10 (IL-6, IL-10) in BAL and plasma. 3-AB reconditioning during EVLP improved compliance and reduced lung edema, neutrophil infiltration, and the expression of adhesion molecules within the transplanted lungs. 3-AB also attenuated the IL-6/IL-10 ratio in BAL and plasma, supporting an improved balance between pro- and anti-inflammatory mediators. Thus, 3-AB reconditioning during EVLP of rat lung grafts damaged by WI markedly reduces inflammation, edema, and physiological deterioration after LTx, supporting the use of PARP inhibitors for the rehabilitation of damaged lungs during EVLP., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Life is resilient because living systems are able to respond to elevated temperatures with an ancient gene expression program called the heat shock response (HSR). In yeast, the transcription of hundreds of genes is upregulated at stress temperatures. Besides stress protection conferred by chaperones, the function of the majority of the upregulated genes under stress has remained enigmatic. We show that those genes are required to directly counterbalance increased protein turnover at stress temperatures and to maintain the metabolism. This anaplerotic reaction together with molecular chaperones allows yeast to efficiently buffer proteotoxic stress. When the capacity of this system is exhausted at extreme temperatures, aggregation processes stop translation and growth pauses. The emerging concept is that the HSR is modular with distinct programs dependent on the severity of the stress., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Compared to lobectomy by video-assisted thoracic surgery (VATS), segmentectomy by VATS has a potential higher risk of postoperative atelectasis and air leakage. We compared postoperative complications between these two procedures, and analyzed their risk factors., Methods: We reviewed the records of all patients who underwent anatomical pulmonary resections by VATS from January 2014 to March 2018 in two Swiss university hospitals. All complications were reported. A logistic regression model was used to compare the risks of complications for the two interventions. Adjustment for patient characteristics was performed using a propensity score, and by including risk factors separately., Results: Among 690 patients reviewed, the major indication for lung resection was primary lung cancer (86.4%) followed by metastasis resection (5.8%), benign lesion (3.9%), infection (3.2%) and emphysema (0.7%). Postoperatively, there were 80 instances (33.3%) of complications in 240 segmentectomies, and 171 instances (38.0%) of complications in 450 lobectomies (P = 0.73). After adjustment for the patient's propensity to be treated by segmentectomy rather than lobectomy, the risks of a complication remained comparable for the two techniques (odds ratio for segmentectomy 0.91 (0.61-1.30), p = 0.59). Length of hospital stay and drainage duration were shorter after segmentectomy. On multivariate analysis, an American Society of Anesthesiologists score above 2 and a forced expiratory volume in one second below 80% of predicted value were significantly associated with the occurrence of complications., Conclusions: The rate of complications and their grade were similar between segmentectomy and lobectomy by VATS.

Background: Pulmonary segmentectomies are generally classified into simple (tri-segmentectomy or lingulectomy as well as apical or basilar segmentectomy) and complex (individual or bi-segmentectomy of the upper, middle and lower lobes). Complex segmentectomies are technically feasible by video-assisted thoracic surgery (VATS) but remain challenging, and reports on post-operative outcomes are scarce. This study analyzes the differences between simple and complex VATS segmentectomy in terms of peri- and post-operative outcomes., Methods: We retrospectively reviewed records of all patients who underwent anatomical pulmonary segmentectomy by VATS from 2014 to 2018 in two university hospitals., Results: A total of 232 patients (114 men; median age 67 years; range, 29-87 years) underwent VATS segmentectomy for primary lung cancer (n=177), metastases (n=26) and benign lesions (n=29). The overall 30-day mortality and morbidity rates were 0.8% and 29.7%, respectively. The re-operation rate was 4.7%. Complex segmentectomy was realized in 111 patients including 86 (77.5%) upper lobe segmentectomies and 44 (39.6%) bi-segmentectomies. There was no statistical difference between complex and simple segmentectomy in terms of operative time (145 vs. 143 min, respectively; P=0.79) and chest tube duration [median: 1 (range, 0-33) vs. 2 (range, 1-19) days, respectively; P=0.95]. Post-operative overall complication rates were similar for both groups (30% vs. 30%, respectively; P=0.99) and were not correlated with the type of segmentectomy. However, complex segmentectomy patients had a shorter length of hospitalization compared to simple segmentectomy patients [median: 5 (range, 1-36) vs. 7 (range, 2-31) days; P=0.026]. Interestingly, complex segmentectomies were realized most frequently 2 years after implementation of VATS segmentectomy (23% vs. 77%; P=0.01)., Conclusions: In comparison with simple segmentectomy, complex segmentectomy by VATS seems to present similar post-operative complication rates. Learning curve and progressive increase in acceptance by surgeons seem to be key elements for successful implementation of complex segmentectomies and could explain the shorter length of stay we observed., Competing Interests: Conflicts of Interest: Presented as poster at the 27th Annual Meeting of the European Society of Thoracic Surgery, Dublin, Slovenia, 9-12 June 2019., (2019 Journal of Thoracic Disease. All rights reserved.)

Motivation: Several gene expression-based risk scores and subtype classifiers for breast cancer were developed to distinguish high- and low-risk patients. Evaluating the performance of these classifiers helps to decide which classifiers should be used in clinical practice for personal therapeutic recommendations. So far, studies that compared multiple classifiers in large independent patient cohorts mostly used microarray measurements. qPCR-based classifiers were not included in the comparison or had to be adapted to the different experimental platforms., Results: We used a prospective study of 726 early breast cancer patients from seven certified German breast cancer centers. Patients were treated according to national guidelines and the expressions of 94 selected genes were measured by the mid-throughput qPCR platform Fluidigm. Clinical and pathological data including outcome over five years is available. Using these data, we could compare the performance of six classifiers (scmgene and research versions of PAM50, ROR-S, recurrence score, EndoPredict and GGI). Similar to other studies, we found a similar or even higher concordance between most of the classifiers and most were also able to differentiate high- and low-risk patients. The classifiers that were originally developed for microarray data still performed similarly using the Fluidigm data. Therefore, Fluidigm can be used to measure the gene expressions needed by several classifiers for a large cohort with little effort. In addition, we provide an interactive report of the results, which enables a transparent, in-depth comparison of classifiers and their prediction of individual patients., Availability and Implementation: https://services.bio.ifi.lmu.de/pia/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The lung is the second site of metastasis after the liver, affecting 30 to 40 % of all patients with a malignant tumor. Chemotherapy seems to be ineffective for some types of tumor. Although there are no prospective randomized studies that confirm the benefit of surgical pulmonary metastasectomy, many studies have shown the existence of a group of patients with pulmonary metastases who benefit from a complete resection for curative purposes in case of complete resection of lung metastases. Different approaches are known to achieve a complete resection with maximum lung parenchyma sparing. Minimal invasive approaches appear to offer a better quality of life and have equivalent oncologic outcomes compared to the open approach., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objectives: A lung retransplant has been shown to be a valid option in selected patients with chronic lung allograft dysfunction (CLAD). However, a subgroup of patients may require, in addition to invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) as a bridge to a retransplant. Overall and CLAD-free survival after ECMO-bridged retransplants are compared to first transplants with and without bridging ECMO and to retransplants without bridging ECMO., Methods: We reported a retrospective, single-institution experience based on a prospective data set of all patients undergoing lung transplants between January 2004 and December 2016 with a mean follow-up of 51 ± 41 months., Results: A total of 230 patients (96 men, 134 women, mean age 47.3 years) had lung transplants: 200 had first transplants without bridging ECMO; 13 had first transplants with bridging ECMO; 11 had retransplants without bridging ECMO; and 6 had retransplants with bridging ECMO. The 3- and 5-year survival rates were 81%/76%, 68%/68%, 69%/46% and 50%/25%, respectively. There was no significant difference in overall survival between those who had first transplants with and without bridging ECMO or retransplants without bridging ECMO. In contrast, patients undergoing ECMO-bridged retransplants had a significantly lower overall survival rate than those with a first transplant without bridging ECMO (P = 0.007). In addition, the post-transplant CLAD-free survival curves varied significantly among the 4 treatment groups (P = 0.041), paralleling overall survival., Conclusions: Patients requiring ECMO as a bridge to a retransplant had lower overall and CLAD-free survival rates compared to those who had a first transplant with and without bridging ECMO and a retransplant without bridging ECMO., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Spectral libraries play a central role in the analysis of data-independent-acquisition (DIA) proteomics experiments. A main assumption in current spectral library tools is that a single characteristic intensity pattern (CIP) suffices to describe the fragmentation of a peptide in a particular charge state (peptide charge pair). However, we find that this is often not the case. We carry out a systematic evaluation of spectral variability over public repositories and in-house data sets. We show that spectral variability is widespread and partly occurs under fixed experimental conditions. Using clustering of preprocessed spectra, we derive a limited number of multiple characteristic intensity patterns (MCIPs) for each peptide charge pair, which allow almost complete coverage of our heterogeneous data set without affecting the false discovery rate. We show that a MCIP library derived from public repositories performs in most cases similar to a "custom-made" spectral library, which has been acquired under identical experimental conditions as the query spectra. We apply the MCIP approach to a DIA data set and observe a significant increase in peptide recognition. We propose the MCIP approach as an easy-to-implement addition to current spectral library search engines and as a new way to utilize the data stored in spectral repositories.

The stress response in the model organisms Saccharomyces cerevisiae is a well-studied system for which many data sets are available. Already in 2000, it was discovered that yeast cells trigger a similar transcriptional response when different types of stress are applied. However, the exact regulatory mechanisms and differences between the different types of stress are still not understood. Here, we present the Yeast Environmental Stress database (YESdb), a database containing all high-throughput experiments measuring various kinds of stress in yeast. The goal of the database is to allow the user to execute complex, integrative analyses of selected data sets, e.g. the comparison of measurements of the same stress using different platforms or differences between strains, stress strengths or types of stress. The analyses can be visualized in various ways and can be compiled into interactive reports to summarize and communicate the results. The data sets are available as differential conditions (typically stressed vs control), which are grouped to time or concentration series when multiple measurements over time or concentrations are done in one experiment. An annotation ontology has been constructed to annotate the data sets with the type, duration and strength of the applied stress, the used strain and experimental platform as well as the publication date. These annotations can easily be combined to select all relevant data sets for an analysis. YESdb allows to construct and execute Petri net-based workflows to perform predefined and custom analyses. E.g. to compare two types of stress (e.g. salt vs oxidative stress), the corresponding data sets are selected from the database, the consistently changed genes are defined and combined and the shared genes are characterized by enrichment analysis. A broad collection of visualizations is available most of which are also interactive. The results of all analyses can be summarized in an interactive report. Visualizations of individual steps (transitions) of YESdb workflows can be automatically added to this report or customized visualizations as well as interpretive text can manually be added to the report. Overall, YESdb aims at making all published data sets on yeast stress immediately available and comparable for integrated analysis of data sets and sets of genes in order to identify and assess hypotheses and mechanisms., (© The Author(s) 2019. Published by Oxford University Press.)

Enhanced recovery after surgery is well established in specialties such as colorectal surgery. It is achieved through the introduction of multiple evidence-based perioperative measures that aim to diminish postoperative organ dysfunction while facilitating recovery. This review aims to present consensus recommendations for the optimal perioperative management of patients undergoing thoracic surgery (principally lung resection). A systematic review of meta-analyses, randomized controlled trials, large non-randomized studies and reviews was conducted for each protocol element. Smaller prospective and retrospective cohort studies were considered only when higher-level evidence was unavailable. The quality of the evidence base was graded by the authors and used to form consensus recommendations for each topic. Development of these recommendations was endorsed by the Enhanced Recovery after Surgery Society and the European Society for Thoracic Surgery. Recommendations were developed for a total of 45 enhanced recovery items covering topics related to preadmission, admission, intraoperative care and postoperative care. Most are based on good-quality studies. In some instances, good-quality data were not available, and subsequent recommendations are generic or based on data extrapolated from other specialties. In other cases, no recommendation can currently be made because either equipoise exists or there is a lack of available evidence. Recommendations are based not only on the quality of the evidence but also on the balance between desirable and undesirable effects. Key recommendations include preoperative counselling, nutritional screening, smoking cessation, prehabilitation for high-risk patients, avoidance of fasting, carbohydrate loading, avoidance of preoperative sedatives, venous thromboembolism prophylaxis, prevention of hypothermia, short-acting anaesthetics to facilitate early emergence, regional anaesthesia, nausea and vomiting control, opioid-sparing analgesia, euvolemic fluid management, minimally invasive surgery, early chest drain removal, avoidance of urinary catheters and early mobilization after surgery. These guidelines outline recommendations for the perioperative management of patients undergoing lung surgery based on the best available evidence. As the recommendation grade for most of the elements is strong, the use of a systematic perioperative care pathway has the potential to improve outcomes after surgery.

Chest tube management represents a major issue after lung surgery as no protocol is widely accepted and tube management is generally based on local or personal habits. Aim of this study is to evaluate the impact of a standardized protocol for chest tube management after pulmonary resections on the post-operative outcomes. We performed a single center retrospective analysis of all adult patients undergoing thoracoscopic pulmonary resection from January 2020 to December 2021. Starting from January 2021 a standardized protocol of chest tube management was applied after all procedures. Patients were divided into two groups according to the chest tube management strategy. he two groups had similar pre-operative characteristics and the extent of lung resection was comparable. Intervention group had significantly shorter time to chest tube removal (median 1 vs 3 days, p < 0.001) and post-operative length of stay (median 3 vs 4 days, p < 0.001). Despite earlier chest tube removal, there was not an increased incidence of post-removal complications. On multivariable analysis, the new chest drain management strategy was an independent predictor of earlier chest tube removal. A standardized protocol of chest tube management allows for an earlier chest tube removal and a shorter hospital stay, without an increase in post-operative complications., (© 2023. Italian Society of Surgery (SIC).)

Background: Enhanced recovery after surgery (ERAS) programs have been reported to decrease complications and shorten hospital stays after lung resections, but their implementation requires time and financial investment with dedicated staff. The aim of this study was to evaluate the clinical and economic outcomes of video-assisted thoracoscopic surgery (VATS) anatomical pulmonary resections before and after implementation of an ERAS program., Methods: The first 50 consecutive patients undergoing VATS lobectomy or segmentectomy for malignancy after implementation of an ERAS program were compared with 50 consecutive patients treated before its introduction. The ERAS protocol included preoperative counseling, reduced preoperative fasting with concomitant carbohydrate loading, avoidance of premedication, standardized surgery, anesthesia and postoperative analgesia, early removal of chest tube, nutrition and mobilization. Length of stay, readmissions and cardio-pulmonary complications within 30 days were compared. Total costs were collected for each patient and a cost-minimization analysis integrating ERAS-specific costs was performed., Results: Both groups were similar in terms of demographics and surgical characteristics. The ERAS group had significantly shorter postoperative length of stay (median: 4 vs . 7 days, P<0.0001), decreased pulmonary complications (16% vs. 38%; P=0.01) and decreased overall post-operative complications (24% vs . 48%, P=0.03). One patient in each group was readmitted and there was no 30-day mortality. ERAS-specific costs were calculated at €729 per patient including the clinical nurse and database costs. Average total hospitalization costs were significantly lower in ERAS group (€15,945 vs . €20,360, P<0.0001), mainly due to lower costs during the post-operative period (€7,449 vs. €11,454, P<0.0001) in comparison with the intra-operative period (€8,496 vs . €8,906, P=0.303). Cost-minimization analysis showed a mean saving in the ERAS group of €3,686 per patient., Conclusions: An ERAS program for VATS anatomical lung resection is cost-effective and is associated with a lower complication rate and a shorter postoperative hospitalization., Competing Interests: Conflicts of Interest: This work was presented at the 26th Annual Meeting of the European Society of Thoracic Surgery, Ljubljana, Slovenia, 26-29 May 2018.

Background: Pulmonary anatomical segmentectomies are increasingly being done via video-assisted thoracoscopic surgery (VATS). We analyzed clinical outcomes and risk factors for post-operative complications after pulmonary segmentectomy by VATS was introduced in two institutions., Methods: We retrospectively reviewed records of all patients who underwent anatomical pulmonary segmentectomy by VATS from 2014 to 2016 at the university hospitals of Geneva and Lausanne in Switzerland., Results: One hundred twenty-nine patients (64 men; median age 68 years, range, 29-85 years) underwent anatomical VATS segmentectomy for primary lung tumors (n=100), metastases (n=16) and benign lesions (n=13). The overall 30-day mortality and morbidity rates were 0.8% and 31%, respectively. The reoperation rate was 4.7% [indications: hemothorax 2, prolonged air leak (PAL) 2, segmental torsion 1, empyema 1]. Chest drainage lasted for a median of 2 days (range, 1-33 days) and patients were discharged from the hospital after a median of 6 days (range, 2-37 days). Postoperative complications were mainly associated with chronic obstructive pulmonary disease (COPD) [odds ratio (OR) 2.54 and 95% confidence interval (95% CI), 1.18-5.47], and smoking pack-years >50 units (OR 5.27; 95% CI, 1.68-16.55). Nine patients (9%) presented with distant recurrences. Nodule size >2 cm was associated with decreased disease-free survival (DFS) (P=0.04). There was no association between surgical experience in VATS segmentectomy and DFS or postoperative complications., Conclusions: Segmentectomies can be safely performed by VATS in an initial experience and result in favorable clinical outcome. COPD and smoking pack-years are associated with an increased risk of complications., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Colorectal cancer (CRC) is a frequently occurring disease, yet diagnosed at a local stage in only 40% of cases. Lung metastases (LM) appear in 5-15% of patients and, left untreated, carry a very poor prognosis. Some CRC patients may benefit from a potentially curative LM resection, but success and benefit are difficult to predict. We discuss prognostic factors of survival after lung metastasectomy in CRC patients under several scenarios (with/ without prior liver metastases; repetitive pulmonary resections). We reviewed all studies (2005-2015) about pulmonary metastases surgical management with curative intent in CRC patients, with a minimum threshold on the number of patients reported (without prior liver metastases: n ≥ 100; with prior resection of liver metastases: n ≥ 50; repetitive thoracic surgery: n ≥ 30). The picture of the prognostic factors of survival is nuanced: surgical management demonstrates clear successes and steady progress, yet there is no single success criterion; stratification of patients and selection bias impact the conclusions. Surgical management of liver and lung metastases may prolong life or cure CRC patients, provided the lesions are fully resected and patients carefully selected. Repeat lung metastasectomy is a safe approach to treat patients in selected cases. In conclusion, there is no standard for surgical management in CRC patients with pulmonary metastases. Patients with isolated unilateral lung metastasis with normal CEA level and no lymph node involvement benefit the most from surgery. Most series report good results in highly selected patients, but instances of long-term disease-free survival remain exceptional., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Solitary pulmonary nodules (SPN) are frequently detected in cancer patients. These lesions are often considered as pulmonary metastases and increasingly treated by non-surgical techniques without histological confirmation. The aim of this study is to determine the histological nature of SPN resected by thoracoscopy and to identify risk factors of malignancy., Methods: Single-institution retrospective analysis of all consecutive patients with previously known malignancies who underwent thoracoscopic resection of SPN with unknown diagnosis between 2001 and 2014., Results: One hundred and forty cancer patients underwent thoracoscopic resection of a SPN. The resected SPN was benign in 34 patients (24.3%) and malignant in 106 patients. The latter were metastasis in 70 patients (50%) and a primary lung cancer in 36 patients (25.7%). Upon univariate analysis, malignancy was significantly associated with age >60 years, disease-free interval ≥24 months, SPN size >8 mm, upper lobe localization and SUV max  > 2.5 on PET-CT. Upon multivariate analysis, upper lobe localization and SUV max  > 2.5 were associated with malignancy. Smoking was significantly associated with SPN containing primary lung cancer., Conclusion: In this series, only 50% of SPN in patients with known malignant disease were pulmonary metastases and 25% had a newly diagnosed NSCLC. Smoking was associated with primary lung cancer but no other predictor was found to allow the distinction between pulmonary metastasis and lung cancer. These results endorse the need of histological confirmation of SPN in patients with previous malignancies to avoid diagnostic uncertainty and suboptimal treatments.

Motivation: The goal of many genome-wide experiments is to explain the changes between the analyzed conditions. Typically, the analysis is started with a set of differential genes DG and the first step is to identify the set of relevant biological processes BP . Current enrichment methods identify the involved biological process via statistically significant overrepresentation of differential genes in predefined sets, but do not further explain how the differential genes interact with each other or which other genes might be important for the enriched process. Other network-based methods determine subnetworks of interacting genes containing many differential genes, but do not employ process knowledge for a more focused analysis., Results: RelExplain is a method to analyze a given biological process bp (e.g. identified by enrichment) in more detail by computing an explanation using the measured DG and a given network. An explanation is a subnetwork that contains the differential genes in the process bp and connects them in the best way given the experimental data using also genes that are not differential or not in bp . RelExplain takes into account the functional annotations of nodes and the edge consistency of the measurements. Explanations are compact networks of the relevant part of the bp and additional nodes that might be important for the bp . Our evaluation showed that RelExplain is better suited to retrieve manually curated subnetworks from unspecific networks than other algorithms. The interactive RelExplain tool allows to compute and inspect sub-optimal and alternative optimal explanations., Availability and Implementation: A webserver is available at https://services.bio.ifi.lmu.de/relexplain ., Contact: berchtold@bio.ifi.lmu.de., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

In a double-blind placebo-controlled trial on 52 patients with bee venom allergy we studied the effect of a pretreatment with terfenadine 120 mg twice daily on the occurrence of local and systemic allergic side effects from rush-immunotherapy. Large local reactions were significantly reduced by terfenadine pretreatment (P < 0.01), while systemic side effects were observed with similar frequencies in both groups. Analysis of individual systemic allergic manifestations showed that cutaneous symptoms like itching (P < 0.025) and urticaria/angioedema (P < 0.05) were significantly reduced, while respiratory or cardiovascular symptoms were not influenced, A lower consumption of additional anti-allergic medication was found during terfenadine pretreatment (P < 0.05). Pretreatment with antihistamines during immunotherapy may thus be helpful in the management of patients with cutaneous side effects. [ABSTRACT FROM AUTHOR]

To identify the allergenic components of honey we studied 22 patients with a history of systemic allergic symptoms following honey ingestion. The group of honey-allergic patients was compared with three control groups: 10 subjects sensitized to artemisia, 10 with honey bee venom allergy and 10 without a history of atopy or bee sting reactions. The allergological tests included skin tests and RAST with three different kinds of Swiss honey (dandelion, forest and rape), pollen of compositae species, celery tuber, extract of bee pharyngeal glands, honey bee venom and bee whole body extract. The results show that ¾ of honey-allergies are sensitive to dandelion honey and 13 of 22 also to compositae pollen. Nine of the honey allergic patients were sensitized to honey bee venom, 3 also to bee pharyngeal glands and to bee whole body extract. Analysis of diagnostic tests and RAST inhibition studies suggest that besides compositae pollen other allergens, most likely of bee origin are important. In honey allergies primary sensitization may be due either to the honey itself, to airborne compositae pollen or even to cross-reacting bee venom components. [ABSTRACT FROM AUTHOR]