Preoperative Anemia is Associated With Worse Long-Term Survival After Lung Cancer Resection: A Multicenter Cohort Study of 5,029 Patients.

OBJECTIVES: Although some evidence to suggest an association between preoperative anemia and reduced overall survival exists, contemporary studies investigating the impact of preoperative anemia on outcomes after resection for primary lung cancer are lacking. DESIGN: A multicenter retrospective review. SETTING: Two tertiary cardiothoracic surgery centers in the Northwest of England. PARTICIPANTS: A total of 5,029 patients between 2012 and 2018. INTERVENTIONS: All patients underwent lung resection for primary lung cancer. Patients were classified as anemic based on the World Health Organization definition. Men with hemoglobin <130 g/L and women with hemoglobin <120 g/L were considered to be anemic. MEASUREMENTS AND MAIN RESULTS: Outcomes assessed included perioperative mortality, 90-day mortality, and overall survival. Multivariate logistic and Cox regression analyses were used to assess the impact of preoperative anemia on 90-day mortality and overall survival, respectively. Overall, preoperatively, 24.0% (n = 1207) of patients were anemic. The 90-day mortality for anemic and nonanemic patients was 5.6% and 3.1%, respectively (p < 0.001). After multivariate adjustment, preoperative anemia was not associated with increased 90-day mortality. However, a log-rank analysis demonstrated reduced overall survival for anemic patients (p < 0.001). After multivariate adjustment, preoperative anemia was found to be independently associated with reduced overall survival (hazard ratio 1.287, 95% confidence interval 1.141-1.451, p < 0.001). CONCLUSIONS: Although anemia was not an independent predictor of short-term outcomes, it was independently associated with significantly reduced survival for patients undergoing resection for lung cancer. Further work is required to understand why anemia reduces long-term survival and whether pathways for anemic patients can be adapted to improve long-term outcomes.

Patients with left ventricle assist devices presenting for thoracic surgery and lung resection: tips, tricks and evidence.

PURPOSE OF REVIEW: Over a thousand left ventricular-assist device (LVAD) implants were performed for heart failure destination therapy in 2017. With increasing survival, we are seeing increasing numbers of patients present for noncardiac surgery, including resections for cancer. This article will review the relevant literature and guidelines for patients with LVADs undergoing thoracic surgery, including lung resection. RECENT FINDINGS: The International Society for Heart and Lung Transplant Mechanically Assisted Circulatory Support Registry has received data on more than 16 000 patients with LVADs. Four-year survival is more than 60% for centrifugal devices. There are increasing case reports, summaries and recommendations for patients with LVADs undergoing noncardiac surgery. However, data on thoracic surgery is restricted to case reports. SUMMARY: Successful thoracic surgery requires understanding of the LVAD physiology. Modern devices are preload dependent and afterload sensitive. The effects of one-lung ventilation, including hypoxia and hypercapnia, may increase pulmonary vascular resistance and impair the right ventricle. Successful surgery necessitates a multidisciplinary approach, including thorough preoperative assessment; optimization and planning of intraoperative management strategies; and approaches to anticoagulation, right ventricular failure and LVAD flow optimization. This article discusses recent evidence on these topics.

Comparison of Blood and Blood Product Transfusion in COVID-19 and Non-COVID-19 Patients Requiring Extracorporeal Membrane Oxygenation for Severe Respiratory Failure.

COVID-19 has resulted in an exponential increase in patients with severe respiratory failure requiring extracorporeal membrane oxygenation (ECMO). Patients on ECMO regularly require high volumes of blood and blood products but, so far, there has been no comparison of transfusion requirements between COVID-19 and non-COVID-19. Using electronic patient records at two major UK ECMO centres, Royal Papworth Hospital and University Hospital South Manchester, we reviewed the transfusion requirements of patients requiring ECMO between January 2019 to December 2021. A total of 271 patients, including 168 COVID-19 patients were available for analysis. Since COVID-19 patients spent almost twice as long on ECMO (27.1 vs. 14.16 days, p ≤ 0.0001) we indexed transfusion in both groups to days on ECMO to allow comparison. COVID-19 patients required less red blood cells (RBC) per day (0.408 vs. 0.996, p = 0.0005) but more cryoprecipitate transfusions (0.117 vs. 0.106, p = 0.022) compared to non-COVID-19 patients. COVID-19 patients had more than double the mortality of non-COVID-19 patients (47% vs. 20.4%, p = 0.0001) and those who died during the study period had higher platelet transfusion requirements (p = 0.007) than their non-COVID-19 counterparts. Transfusion requirements and coagulopathy differ between COVID-19 and non-COVID-19 patients. The distinctly different transfusion patterns between the two groups remain difficult to interpret, but further investigations may help explain the haematological aspects of severe COVID-19 infection.

Preoperative validation of edema-corrected tractography in neurosurgical practice: translating surgeon insights into novel software implementation.

Background: Peritumoral edema alters diffusion anisotropy, resulting in false negatives in tractography reconstructions negatively impacting surgical decision-making. With supratotal resections tied to survival benefit in glioma patients, advanced diffusion modeling is critical to visualize fibers within the peritumoral zone to prevent eloquent fiber transection thereafter. A preoperative assessment paradigm is therefore warranted to systematically evaluate multi-subject tractograms along clinically meaningful parameters. We propose a novel noninvasive surgically-focused survey to evaluate the benefits of a tractography algorithm for preoperative planning, subsequently applied to Synaptive Medical's free-water correction algorithm developed for clinically feasible single-shell DTI data. Methods: Ten neurosurgeons participated in the study and were presented with patient datasets containing histological lesions of varying degrees of edema. They were asked to compare standard (uncorrected) tractography reconstructions overlaid onto anatomical images with enhanced (corrected) reconstructions. The raters assessed the datasets in terms of overall data quality, tract alteration patterns, and the impact of the correction on lesion definition, brain-tumor interface, and optimal surgical pathway. Inter-rater reliability coefficients were calculated, and statistical comparisons were made. Results: Standard tractography was perceived as problematic in areas proximal to the lesion, presenting with significant tract reduction that challenged assessment of the brain-tumor interface and of tract infiltration. With correction applied, significant reduction in false negatives were reported along with additional insight into tract infiltration. Significant positive correlations were shown between favorable responses to the correction algorithm and the lesion-to-edema ratio, such that the correction offered further clarification in increasingly edematous and malignant lesions. Lastly, the correction was perceived to introduce false tracts in CSF spaces and - to a lesser degree - the grey-white matter interface, highlighting the need for noise mitigation. As a result, the algorithm was modified by free-water-parameterizing the tractography dataset and introducing a novel adaptive thresholding tool for customizable correction guided by the surgeon's discretion. Conclusion: Here we translate surgeon insights into a clinically deployable software implementation capable of recovering peritumoral tracts in edematous zones while mitigating artifacts through the introduction of a novel and adaptive case-specific correction tool. Together, these advances maximize tractography's clinical potential to personalize surgical decisions when faced with complex pathologies.

The effect of veno-venous ECMO on the pharmacokinetics of Ritonavir, Darunavir, Tenofovir and Lamivudine.

INTRODUCTION: To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV ECMO). METHODS: Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments. Published population PK models were used to simulate plasma concentration profiles for the drugs. The population prediction and the observed plasma concentrations were then overlaid with the expected drug profiles using the individual Bayesian post-hoc parameter estimates. RESULTS: Following dose adjustments, the PK profiles of Ritonavir, Darunavir and Tenofovir fell within the expected range and appeared similar to the population prediction, although slightly different for Ritonavir. The observed data for Lamivudine and its PK profile were completely different from the data available in the literature. CONCLUSIONS: To our knowledge, this is the first study reporting the PK profile of ART drugs during ECMO therapy. Based on our results, dose adjustment of ART drugs while on VV ECMO may be advisable. Further study of the PK profile of Lamivudine is required.

Extracorporeal Membrane Oxygenation Assisted Segmentectomy for Metachronous Lung Cancer After Pneumonectomy.

Advances in extracorporeal membrane oxygenation have enabled the facilitation of surgical intervention in patients who may otherwise be considered inoperable using conventional ventilation-for example, the resection of an early stage metachronous lung cancer in a patient who has previously undergone a pneumonectomy for a prior lung cancer. We present one such case: a 52-year-old man who underwent right lower lobe segmentectomy for a second primary lung cancer, 3 years after left pneumonectomy, using extracorporeal membrane oxygenation. To our knowledge, there are no published case reports describing the use of extracorporeal membrane oxygenation in resection of metachronous lung cancer after pneumonectomy.

Chronic mould exposure as a risk factor for severe community acquired pneumonia in a patient requiring extra corporeal membrane oxygenation.

A previously fit and well man developed acute respiratory failure due to environmental mould exposure from living in damp rental accommodation. Despite aggressive intensive care management he rapidly deteriorated and required respiratory and cardiac Extracorporeal Membrane Oxygenation. We hypothesize that poor domiciliary conditions may make an underestimated contribution to community respiratory disease. These conditions may present as acute and severe illness with non-typical pathogens identified.

A new approach for the detection and identification of protein impurities using combinatorial solid phase ligand libraries.

We propose a novel method for detection of protein impurities present in plasma-derived and recombinant purified injectable biopharmaceuticals by enhancing the concentration of protein impurities, in essence "amplifying" their presence to detectable levels. The method is based on the capture of proteins using a combinatorial solid-phase hexapeptides ligand library previously described for the reduction of protein concentration difference in biological fluids. Three proteins have been investigated: Staphylococcus aureus Protein A, expressed in Escherichia coli and supplied as 99% pure, recombinant human albumin, expressed in Pichia pastoris and certified as 95% pure, and therapeutic albumin supplied as 96-98% pure injectable solution. In all cases, after treatment with the ligand libraries, a number of additional polypeptide chains, not visible in the control, could be detected and obtained in sufficient amounts for MS analysis. In the cases of the two recombinant proteins, it could be demonstrated that a number of these polypeptide chains were host cell proteins still present in the purified product. In addition, a substantial number of these spots were found to be cleavage products of the original recombinant DNA species. Such cleavage products were particularly abundant in the recombinant human albumin preparation. From pure injectable serum albumin, a number of human plasma protein impurities were also identified by LC-MS/MS analysis. Treatment with ligand libraries of purified proteins is thus seen as a very powerful method of capture and concentration of host proteins and cleaved products for further analysis to control better the quality of industrial biotechnology products.

Pancreatic arteriovenous malformation.

We report a case of a 57-year-old male with a pancreatic arteriovenous malformation (AVM). The diagnosis was made by CT scan and angiography. In the reported case, bleeding from AVM into the biliary tract caused haemobilia and bleeding into the pancreatic head caused abdominal pain. Pancreatic AVM has been only rarely reported as a cause of haemobilia.