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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.

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).)

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.)

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.)

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.)

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.)

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.)

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.

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.)

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)

Several methods predict activity changes of transcription factors (TFs) from a given regulatory network and measured expression data. But available gene regulatory networks are incomplete and contain many condition-dependent regulations that are not relevant for the specific expression measurement. It is not known which combination of active TFs is needed to cause a change in the expression of a target gene. A method to systematically evaluate the inferred activity changes is missing. We present such an evaluation strategy that indicates for how many target genes the observed expression changes can be explained by a given set of active TFs. To overcome the problem that the exact combination of active TFs needed to activate a gene is typically not known, we assume a gene to be explained if there exists any combination for which the predicted active TFs can possibly explain the observed change of the gene. We introduce the i-score (inconsistency score), which quantifies how many genes could not be explained by the set of activity changes of TFs. We observe that, even for these minimal requirements, published methods yield many unexplained target genes, i.e. large i-scores. This holds for all methods and all expression datasets we evaluated. We provide new optimization methods to calculate the best possible (minimal) i-score given the network and measured expression data. The evaluation of this optimized i-score on a large data compendium yields many unexplained target genes for almost every case. This indicates that currently available regulatory networks are still far from being complete. Both the presented Act-SAT and Act-A* methods produce optimal sets of TF activity changes, which can be used to investigate the difficult interplay of expression and network data. A web server and a command line tool to calculate our i-score and to find the active TFs associated with the minimal i-score is available from https://services.bio.ifi.lmu.de/i-score., Competing Interests: The authors have declared that no competing interests exist.

Background: Infected postpneumonectomy chest cavities may be related to chronic postpneumonectomy empyema or arise in rare situations of necrotizing pneumonia with complete lung destruction where pneumonectomy and pleural debridement are required. We evaluated the safety and efficacy of an intrathoracic vacuum-assisted closure device (VAC) for the treatment of infected postpneumonectomy chest cavities., Method: A retrospective single institution review of all patients with infected postpneumonectomy chest cavities treated by VAC between 2005 and 2013. Patients underwent surgical debridement of the thoracic cavity, muscle flap closure of the bronchial stump when a fistula was present, and repeated intrathoracic VAC dressings until granulation tissue covered the entire chest cavity. After this, the cavity was obliterated by a Clagett procedure and closed., Results: Twenty-one patients (14 men and 7 women) underwent VAC treatment of their infected postpneumonectomy chest cavity. Twelve patients presented with a chronic postpneumonectomy empyema (10 of them with a bronchopleural fistula) and 9 patients with an empyema occurring in the context of necrotizing pneumonia treated by pneumonectomy. In-hospital mortality was 23%. The median duration of VAC therapy was 23 days (range, 4-61 days) and the median number of VAC changes per patient was 6 (range, 2-14 days). Infection control and successful chest cavity closure was achieved in all surviving patients. One adverse VAC treatment-related event was identified (5%)., Conclusions: The intrathoracic VAC application is a safe and efficient treatment of infected postpneumonectomy chest cavities and allows the preservation of chest wall integrity., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: Evidence-based studies optimizing chest tube management have been conducted to accelerate the recovery process for lung cancer patients after video-assisted thoracoscopic surgery (VATS). This study is to evaluate whether using the multi-lateral pores chest tube can achieve better drainage performance than conventional-lateral-pore drainage. Methods: Data from patients undergoing VATS were consecutively collected from September 2023 to June 2024. The groups were randomized into two subgroups, which were multi-lateral-pores drainage group (MDG) and conventional-lateral-pore drainage group (CDG). The primary outcomes included chest drainage performance, and the secondary outcomes included postoperative complications (PPCs). Results: After screening, 228 patients were randomized into two groups, in which 116 patients in MDG and 112 patients in CDG. The daily drainage volume [199.70 (95%CI: 165.19~234.99) mL/d vs 149.43 (95%CI: 120.70~179.21) mL/d, P<0.01] and total drainage volume [342.79 (95%CI: 291.91~392.63) mL vs 272.68 (95%CI: 225.87~322.11) mL, P = 0.04] in the MDG was significantly higher that that in the CDG. The drainage duration in the MDG was also less than that in the CDG [36.41 (95%CI: 32.23~40.72) h vs 51.02 (95%CI: 46.03~56.38) h, P < 0.01]. The incidence of pleural effusion was lower in the MDG when compared with that in CDG (1.7% vs 9.0%, P = 0.04). No differences were found in the other incidences of chest tube—related PPCs, including pneumothorax (12.0% vs 15.2%, P = 0.15) and subcutaneous emphysema (17.2% vs 17.9%, P = 0.35), however. Conclusions: Based on this single-center analysis, multi-lateral pores chest tube provided better drainage performance after VATS. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to evaluate the postoperative short-term outcomes of patients undergoing video-assisted thoracoscopic surgery (VATS) for lung resection with the enhanced recovery after surgery (ERAS) protocol. Methods: A single-institution, prospective randomized controlled study was conducted. The primary outcome measures were postoperative pulmonary complications (PPCs) and postoperative short-term effects. Results: Among the 611 patients, 305 were assigned to the ERAS group, and 306 were assigned to the routine group. The ERAS group achieved earlier oral feeding, earlier mobilization, a shorter duration of drainage (2.0 vs. 5.0 days, P<0.001), and a shorter hospital stay (3.0 vs. 7.0 days, P<0.001). The biological impacts were confirmed to be significantly better for the ERAS group. Furthermore, the ERAS group also had a lower incidence of PPCs (11.5% vs. 22.9%, P<0.001) than did the routine group. Multivariate logistic regression analysis revealed the following predictors of drainage tube removal on the 1st day after surgery without pneumonia during hospitalization: comorbidity (P=0.029), surgical procedure (P=0.001), and operation time (P=0.039). Conclusions: Implementation of the ERAS protocol led to a decreased incidence of PPCs, suggesting that the ERAS protocol has a better biological impact on patients undergoing VATS for lung resection. Multigradient individual ERAS protocols are recommended at different institutions according to the individual conditions of patients. Clinical Trial Registration: https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009ZT9&selectaction=Edit&uid=U0002ZGN&ts=3&cx=ks7hrg , identifier NCT04451473. [ABSTRACT FROM AUTHOR]

Background: With growing concerns about opioid-related risks, efforts to reduce opioid use throughout the perioperative period have increased. This study aimed to compare postoperative recovery outcomes between opioid-free anesthesia (OFA) and opioid-sparing anesthesia (OSA) under a multimodal analgesic protocol in video-assisted thoracoscopic surgery (VATS). Methods: A retrospective cohort study was conducted on 196 patients undergoing VATS from August 2019 to December 2021. Patients received either dexmedetomidine-based OFA or remifentanil-based OSA. Postoperative recovery was assessed using the Quality of Recovery-15 (QoR-15) score, opioid consumption, and pain intensity. Additionally, opioid-related complications and intraoperative hemodynamic changes were evaluated. Results: Both groups showed similar QoR-15 scores 24 h postoperatively (124.2 ± 7.0 vs. 123.0 ± 6.9, p = 0.227). Opioid consumption and pain intensity were comparable, and the incidence of opioid-related adverse events did not significantly differ between the groups. Intraoperative hypotension and bradycardia were more frequent in the OFA group, but the differences were not statistically significant. Conclusions: The study concluded that both OFA and OSA, when used under a multimodal analgesic protocol, provided effective postoperative recovery in patients undergoing VATS with no significant differences in outcomes. [ABSTRACT FROM AUTHOR]

Among survivors of acute pulmonary embolism (PE), roughly half report persistent dyspnea, impaired functional status, and decreased quality of life. Post-pulmonary embolism syndrome (PPES) is a broad condition which has been increasingly recognized in recent years and may be due to post-pulmonary embolism functional impairment, chronic thromboembolic disease, or the most severe long-term complication of PE, chronic thromboembolic pulmonary hypertension. Despite guideline recommendations for appropriate follow-up for post-pulmonary embolism patients, PPES remains underrecognized and diagnostic testing underutilized. Patients with symptoms suggestive of PPES at follow-up should undergo a transthoracic echocardiogram to screen for the presence of pulmonary hypertension; additional testing, such as a ventilation/perfusion scan, right heart catheterization, and cardiopulmonary exercise testing may be indicated. The pathophysiology of post-pulmonary embolism syndrome is complex and heterogeneous. In chronic thromboembolic pulmonary hypertension, the pathophysiology reflects persistent pulmonary arterial thrombi and a progressive small vessel vasculopathy. In patients with chronic thromboembolic disease or chronic thromboembolic pulmonary hypertension, medical therapy, balloon pulmonary angioplasty, or pulmonary thromboendarterectomy should be considered, and in cases of chronic thromboembolic pulmonary hypertension, pulmonary thromboendarterectomy significantly improves mortality. In all causes of post-pulmonary embolism syndrome, rehabilitation is a safe treatment option that may improve quality of life. [ABSTRACT FROM AUTHOR]

The field of organ transplantation is experiencing a transformative shift with the rise of Advanced Therapy Medicinal Products (ATMPs), which include gene therapies, somatic cell therapies, and tissue-engineered products. These therapies offer new, potentially curative treatments for longstanding medical challenges, impacting numerous patients. However, their adoption is hindered by complex regulatory frameworks, high production costs, and inconsistent access across Europe. The ESOT ATMP Task Force's position paper analyzes these challenges from research to clinical application, advocating for a coordinated strategy to position Europe as a leader in ATMP development. It proposes specific actions such as streamlining regulatory pathways to accelerate approvals, boosting funding for ATMP research, and creating specialized facilities for development and implementation. The paper also highlights the critical roles of patient engagement and real-world evidence in optimizing clinical and regulatory practices. [ABSTRACT FROM AUTHOR]

Background: Despite the implementation of enhanced recovery programs, the reported average postoperative length of stay after robotic lobectomy remains as 4 days. In this prospective study, we present the outcomes of early discharge (on day 2) with telehealth home monitoring device after robotic lobectomy for lung cancer in selected patients. Methods: All patients with a caregiver were discharged on postoperative day 2 (POD 2) with a telemonitoring device provided they met the specific discharge criteria. Inclusion criteria: <75 years old, stage I-II NSCLC, with caregiver, ECOG 0–2, scheduled for lobectomy, logistic proximity to hospital (<60 km); intra-postoperative exclusion criteria: conversion to open surgery, early complications needing hospital monitoring or redo-operation, difficult pain management, <92 HbO2% saturation on room air or need for O2 supplementation, altered vital or laboratory parameters. Teleconsultations were scheduled as follows: the first one in afternoon of POD2, two on POD3, then once a day until chest tube removal. After discharge, patients recorded their vital signs at least four times a day using the device, which allowed two surgeons to monitor them via a mobile application. In the event of sudden changes in vital signs or the occurrence of adverse events, patients had access to a direct phone line and a dedicated re-hospitalization pathway. The primary outcome was safety, assessed by the occurrence of post-discharge complications or readmissions, as well as feasibility. Secondary outcomes: comparison of safety profile with a matched control group in which the standard of care and the evaluation of resource optimization were maintained and economic evaluation. Results: Between July 2022 and February 2024, 48 patients were enrolled in the present study. Six patients (12.5%) dropped out due to unsatisfied discharge criteria on POD2. Exclusion causes were: significant air leaks (n:2) requiring monitoring and the use of suction device, uncontrolled pain (n:2), atrial fibrillation, and occurrence of cerebral ischemia (n:1 each). The adherence rate to vital signs monitoring by patients was 100%. A mean number of four measurements per day was performed by each patient. During telehealth home monitoring, a total of 71/2163 (1.4%) vital sign measurements violated the established acceptable threshold in 22 (52%) patients. All critical violations were managed at home. During the surveillance period (defined as the time from POD 2 to the day of chest tube removal), a persistent air leak was recorded in one patient requiring readmission to the hospital (on POD 13) and re-intervention with placement of a second thoracic drainage due to unsatisfactory lung expansion. No other postoperative complication occurred nor was there any readmission needed. Compared to the control group, the discharge gain was 2.5 days, with an economic benefit of 528 €/day (55.440 € on the total enrolled population). Conclusions: Our results confirm that the adoption of telehealth home monitoring is feasible and allows a safe discharge on postoperative day two after robotic surgery for stage I-II NSCLC in selected patients. A potential economic benefit (141 days of hospitalizations avoided) for the healthcare system could result from the adoption of this protocol. [ABSTRACT FROM AUTHOR]

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Renal tubular epithelial cells (TECs) undergo an energy‐related metabolic shift from fatty acid oxidation to glycolysis during chronic kidney disease (CKD) progression. However, the mechanisms underlying this burst of glycolysis remain unclear. Herein, a new critical glycolysis regulator, the transcription factor forkhead box protein K1 (FOXK1) that is expressed in TECs during renal fibrosis and exhibits fibrogenic and metabolism‐rewiring capacities is reported. Genetic modification of the Foxk1 locus in TECs alters glycolytic metabolism and fibrotic lesions. A surge in the expression of a set of glycolysis‐related genes following FOXK1 protein activation contributes to the energy‐related metabolic shift. Nuclear‐translocated FOXK1 forms condensate through liquid‐liquid phase separation (LLPS) to drive the transcription of target genes. Core intrinsically disordered regions within FOXK1 protein are mapped and validated. A therapeutic strategy is explored by targeting the Foxk1 locus in a murine model of CKD by the renal subcapsular injection of a recombinant adeno‐associated virus 9 vector encoding Foxk1‐short hairpin RNA. In summary, the mechanism of a FOXK1‐mediated glycolytic burst in TECs, which involves the LLPS to enhance FOXK1 transcriptional activity is elucidated. [ABSTRACT FROM AUTHOR]

Background: Intraoperative fluid management based on pulse pressure variation has shown potential to reduce postoperative pulmonary complications (PPCs) and improve clinical outcomes in various surgical settings. However, its efficacy and safety have not been assessed in patients undergoing thoracic surgery with one-lung ventilation. Methods: Patients scheduled for pulmonary lobectomy using uniportal video-assisted thoracic surgery approach were randomly assigned to two groups. In the PPV group, fluid administration was guided by the pulse pressure variation parameter, while in the near-zero group, it was guided by conventional hemodynamic parameters. The primary outcome was the partial pressure of oxygen (PaO2)/ fraction of inspired oxygen (FiO2) ratio 15 min after extubation. The secondary outcomes included extubation time, the incidence of postoperative pulmonary complications in the first three postoperative days, and the length of hospital stay. Results: The PaO2/FiO2 ratio did not differ between the two groups (364.48 ± 38.06 vs. 359.21 ± 36.95; p = 0.51), although patients in the PPV group (n = 44) received a larger amount of both crystalloids (1145 ± 470.21 vs. 890 ± 459.31, p = 0.01) and colloids (162.5 ± 278.31 vs 18.18 ± 94.68, p = 0.002) compared to the near-zero group (n = 44). No differences were found in extubation time, type and number of PPCs, and length of hospital stay. Conclusions: PPV-guided fluid management in thoracic surgery requiring one-lung ventilation does not improve pulmonary gas exchange as measured by the PaO2/FiO2 ratio and does not seem to offer clinical benefits. Additionally, it results in increased fluid administration compared to fluid management based on conventional hemodynamic parameters. [ABSTRACT FROM AUTHOR]

Background: Early postoperative mobilization is important for enhanced recovery but can be hindered by orthostatic intolerance. However, study on postoperative orthostatic intolerance in thoracoscopic lung resection is limited. Thus, this investigation aims to examine the prevalence and variables contributing to orthostatic intolerance on the first day following thoracoscopic lung cancer resection. Methods: A prospective observational study was conducted from February 01 to May 05, 2023, at the First Affiliated Hospital of Chongqing Medical University. Typically, 215 subjects subjected to thoracoscopic lung resection were enrolled in this study. Their general information, disease, and treatment information were collected, and the occurrence of orthostatic intolerance was recorded. Results: Typically, 64 patients (29.77%) demonstrated orthostatic intolerance during early mobilization, and 43.75% failed to walk. The prevalence of nausea, dizziness, and impaired vision was 60.94%, 92.19%, and 25.00%, respectively, and no patient experienced syncope. The factors shown to be independently linked with orthostatic intolerance were being female (OR = 2.98, 1.53 to 5.82) and high pain level during sitting (OR = 2.69, 1.79 to 4.04). Individuals with orthostatic intolerance had a longer postoperative hospital stay with a mean of 5.42 days against 4.25 days (p = 0.003). Conclusions: Orthostatic intolerance was prevalent following thoracoscopic lung cancer resection and affected patients' capability to mobilize and prolonged postoperative hospitalization. Being female and having high pain levels during sitting were identified as independent factors for orthostatic intolerance. This suggests that more emphasis should be given to risky patients, and for these groups, we may optimize pain management to adjust the risk of emerging orthostatic intolerance, facilitating early mobilization and early postoperative rehabilitation. [ABSTRACT FROM AUTHOR]

Respiratory failure is a common perioperative complication. The risk of respiratory failure can be reduced with effective preoperative evaluation, preventative measures, and knowledge of evidence-based management techniques. Effective preoperative screening methods include ARISCAT scoring, OSA screening, and the LAS VEGAS score (including the ASA physical status score). Evaluation by the six-minute walk test and a routine pulmonary physical exam has been shown to be effective at predicting postoperative pulmonary complications, whereas evidence on the predictive power of pulmonary function tests and chest radiography has been inconclusive. Preoperative smoking cessation and lung expansion maneuvers have been shown to decrease the risk of pulmonary complications postoperatively. Intraoperative management techniques that decrease the pulmonary complication risk include neuromuscular blockade reversal with sugammadex, limiting surgical times to less than 3 h when possible, lung-protective ventilation techniques, and multimodal analgesia to decrease opioid usage. In the immediate postoperative period, providers should be prepared to quickly treat bronchospasm, hypoventilation, and upper airway obstruction. For post-surgical patients who remain in the hospital, the risk of pulmonary complications can be decreased with lung expansion techniques, adequate analgesia, automated continuous postoperative ward monitoring, non-invasive ventilatory support, and early mobilization. This article was written to analyze the available literature on this topic in order to learn and practice the prevention of perioperative respiratory failure when caring for patients on a daily basis. [ABSTRACT FROM AUTHOR]

Introduction: Chronic post-surgical pain (CPSP) remains a prevalent issue following video-assisted thoracic surgery (VATS), despite advancements in surgical techniques. Various regional anesthesia techniques, including thoracic paravertebral block (PVB), intercostal nerve block (ICNB), serratus anterior plane block (SAPB), erector spinae plane block (ESPB), and thoracic epidural anesthesia (TEA), have been employed in VATS procedures to mitigate this issue. This study aims to compare the efficacy of these analgesia methods in reducing the incidence of CPSP in VATS patients through a network meta-analysis. Methods: A systematic search was conducted in PubMed, the Cochrane Library, and EMBASE for randomized controlled trials (RCTs) comparing the incidence of CPSP associated with PVB, ICNB, SAPB, ESPB, and TEA. The occurrence of CPSP was evaluated at both 2–3 months and 6 months post-surgery. Results: Six RCTs, involving 652 patients, were included in the analysis of CPSP incidence at 2–3 months, while seven RCTs, involving 715 patients, were included for 6 months analysis. PVB, ICNB, or TEA reduced CPSP incidence compared with control group (without regional anesthesia techniques) at both 2–3 months and 6 months post-surgery. However, SAPB was found less effective in reducing CPSP incidence at 2–3 months post-VATS compared to PVB, ICNB, or TEA. Conclusions: PVB, ICNB, and TEA exhibit significant effects on reducing CPSP incidence following VATS. Conversely, SAPB is not recommended for reducing CPSP incidence post-VATS. Nonetheless, considering the limitation of a small sample size in this network meta-analysis, additional RCTs are necessary to validate these conclusions and enhance the management of CPSP after VATS. [ABSTRACT FROM AUTHOR]

Background: A recent large-scale analysis of Gene Expression Omnibus (GEO) data found frequent evidence for spatial defects in a substantial fraction of Affymetrix microarrays in the GEO. Nevertheless, in contrast to quality assessment, artefact detection is not widely used in standard gene expression analysis pipelines. Furthermore, although approaches have been proposed to detect diverse types of spatial noise on arrays, the correction of these artefacts is mostly left to either summarization methods or the corresponding arrays are completely discarded., Results: We show that state-of-the-art robust summarization procedures are vulnerable to artefacts on arrays and cannot appropriately correct for these. To address this problem, we present a simple approach to detect artefacts with high recall and precision, which we further improve by taking into account the spatial layout of arrays. Finally, we propose two correction methods for these artefacts that either substitute values of defective probes using probeset information or filter corrupted probes. We show that our approach can identify and correct defective probe measurements appropriately and outperforms existing tools., Conclusions: While summarization is insufficient to correct for defective probes, this problem can be addressed in a straightforward way by the methods we present for identification and correction of defective probes. As these methods output CEL files with corrected probe values that serve as input to standard normalization and summarization procedures, they can be easily integrated into existing microarray analysis pipelines as an additional pre-processing step. An R package is freely available from http://www.bio.ifi.lmu.de/artefact-correction.

In Firmicutes bacteria, ATP-binding cassette (ABC) transporters have been recognized as important resistance determinants against antimicrobial peptides. Together with neighboring two-component systems (TCSs), which regulate their expression, they form specific detoxification modules. Both the transport permease and sensor kinase components show unusual domain architecture: the permeases contain a large extracellular domain, while the sensor kinases lack an obvious input domain. One of the best-characterized examples is the bacitracin resistance module BceRS-BceAB of Bacillus subtilis. Strikingly, in this system, the ABC transporter and TCS have an absolute mutual requirement for each other in both sensing of and resistance to bacitracin, suggesting a novel mode of signal transduction in which the transporter constitutes the actual sensor. We identified over 250 such BceAB-like ABC transporters in the current databases. They occurred almost exclusively in Firmicutes bacteria, and 80% of the transporters were associated with a BceRS-like TCS. Phylogenetic analyses of the permease and sensor kinase components revealed a tight evolutionary correlation. Our findings suggest a direct regulatory interaction between the ABC transporters and TCSs, mediating communication between both components. Based on their observed coclustering and conservation of response regulator binding sites, we could identify putative corresponding two-component systems for transporters lacking a regulatory system in their immediate neighborhood. Taken together, our results show that these types of ABC transporters and TCSs have coevolved to form self-sufficient detoxification modules against antimicrobial peptides, widely distributed among Firmicutes bacteria.

Background: Mammalian target of rapamycin (mTOR) inhibitors such as rapamycin have shown modest effects in cancer therapy due in part to the removal of a negative feedback loop leading to the activation of the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathway. In this report, we have investigated the role of FOXO1, a downstream substrate of the PI3K/Akt pathway in the anticancer efficacy of rapamycin., Materials and Methods: Colon cancer cells were treated with rapamycin and FOXO1 phosphorylation was determined by Western blot. Colon cancer cells transfected with a constitutively active mutant of FOXO1 or a control plasmid were treated with rapamycin and the antiproliferative efficacy of rapamycin was monitored., Results: Rapamycin induced the phosphorylation of FOXO1 as well as its translocation from the nucleus to the cytoplasm, leading to FOXO1 inactivation. The expression of an active mutant of FOXO1 in colon cancer cells potentiated the antiproliferative efficacy of rapamycin in vitro and its antitumor efficacy in vivo., Conclusion: Taken together these results show that rapamycin-induced FOXO1 inactivation reduces the antitumor efficacy of rapamycin.