Increased minute ventilation-to-carbon dioxide slope during cardiopulmonary exercise test is associated with poor postoperative outcome following lung cancer resection.

OBJECTIVES: Ventilatory efficiency [minute ventilation-to-carbon dioxide output slope (VE/VCO2 slope)] can be measured at sub-maximal workload during cardiopulmonary exercise test. The aim of this study is to assess the association between VE/VCO2 slope and outcome after lung cancer resections. METHODS: Retrospective, single-centre analysis on all patients undergoing lung resection for cancer (April 2014-August 2022) and with a preoperative cardiopulmonary exercise test. VE/VCO2 slope >40 was chosen as high-risk threshold. Logistic regression analysis was used to test the association of VE/VCO2 slope and several patient- and surgery-related factors with 90-day mortality. RESULTS: A total of 552 patients were included (374 lobectomies, 81 segmentectomies, 55 pneumonectomies and 42 wedge resections). Seventy-four percent were minimally invasive procedures. Cardiopulmonary morbidity was 32%, in-hospital/30-day mortality 6.9% and 90-day mortality 8.9%. A total of 137 patients (25%) had a slope of >40. These patients were older (72 vs 70 years, P = 0.012), had more frequently coronary artery disease (17% vs 10%, P = 0.028), lower carbon monoxide lung diffusion capacity (57% vs 68%, P < 0.001), lower body mass index (25.4 vs 27.0 kg/m2, P = 0.001) and lower peak VO2 (14.9 vs 17.0 ml/kg/min, P < 0.001) than those with a lower slope. The cardiopulmonary morbidity among patients with a slope of >40 was 40% vs 29% in those with lower slope (P = 0.019). Ninety-day mortality was 15% vs 6.7% (P = 0.002). The 90-day mortality of elderly patients with slope >40 was 21% vs 7.8% (P = 0.001). After adjusting for peak VO2 value, extent of operation and other patient-related variables in a logistic regression analysis, VE/VCO2 slope retained a significant association with 90-day mortality. CONCLUSIONS: VE/VCO2 slope was strongly associated with morbidity and mortality following lung resection and should be included in the functional algorithm to assess fitness for surgery.

Minimally invasive segmentectomy and lobectomy for peripheral stage IA1-2 non-small-cell lung cancer: a case-matched cohort study from a UK Centre.

OBJECTIVES: The objective of this study is to compare in a real-world series the short- and long-term results of segmentectomy and lobectomy for peripheral clinical stage IA non-small-cell lung cancer (NSCLC). METHODS: Single-centre cohort study including a series of consecutive patients undergoing minimally invasive segmentectomy or lobectomy for peripheral (outer third of the lung) clinical stage IA NSCLC (January 2017-August 2022). Propensity score case matching analysis generated 2 matched groups of patients undergoing segmentectomy or lobectomy. Short-term (morbidity and mortality) and long-term [overall survival and event-free survival (EFS)] outcomes were compared between the 2 matched groups. EFS was calculated by including death resulting from any cause and any recurrence as events. RESULTS: Propensity score generated 118 pairs of patients undergoing minimally invasive segmentectomy or lobectomy. The median follow-up was 30 months (95% confidence limits (CL) 4-64). The median postoperative length of stay was 4 days in both groups. Ninety-day mortality was similar (segmentectomy 2.5% versus lobectomy 1.7%, P = 1). Three-year overall survival [segmentectomy 87% (76-93) versus lobectomy 81% (72-88), P = 0.73] and EFS [segmentectomy 82% (72-90) versus lobectomy 78% (68-84), P = 0.52] did not differ between the groups. Loco-regional recurrence rate [segmentectomy 4.2% (5/118) versus lobectomy 9.3% (11/118), P = 0.19] was similar despite a lower nodal upstaging [segmentectomy 3.4% (4/118) versus lobectomy 14% (17/118), P = 0.005]. The occurrence of compromised resection margins (pR1 or pR uncertain) was similar between the groups [segmentectomy 7.6% (9/118) versus lobectomy 9.3% (11/118), P = 0.81]. CONCLUSIONS: This observational series confirms the non-inferiority of segmentectomy compared to lobectomy in treating peripherally located stage IA NSCLC.

TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary Atherosclerosis?

BACKGROUND: Inflammatory mechanisms are key to the pathogenesis of atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14 promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in subjects with Coronary Artery Disease (CAD). METHODS: DNA was obtained from 100 human paraffin-embedded aortic specimens, from cadavers with known coronary atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control group consisted of 100 healthy individuals (Group C). Genotyping was performed by Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR). Plasma levels of sCD14 were measured with ELISA. RESULTS: For TLR-4 Asp299Gly and Thr399Ile polymorphisms, no statistically significant differences were observed. Regarding the C260T polymorphism, frequencies of T allele were significantly higher in the control group compared to the case group (p = 0.05). The Odds Ratio (OR) showed statistically significant association of TT genotype with healthy individuals (OR 0.25, 95% Confidence Interval CI 0.10-0.62, p = 0.0017). Plasma levels of sCD14 in patients with CAD (mean value = 1.35 µg/mL) were reduced when compared to reference value. CONCLUSIONS: The studied polymorphisms ofTLR-4 showed no association with CAD. Conversely, the functional polymorphism of CD14 has a statistically significant difference in expression between healthy and affected by CAD individuals.

Management of malignant middle cerebral artery infarction following a cardiac stab wound--the role of early decompressive craniectomy.

We report the presentation, investigation and management of a 22-year-old male who developed a right malignant middle cerebral artery infarct following a cardiac stab wound. This case exemplifies that early identification and timely decompression of young patients with embolic infarcts as a result of penetrating trauma can lead to a favourable clinical outcome.

Role of thoracotomy and metastatectomy in gestational trophoblastic neoplasia: a single center experience.

Gestational trophoblastic neoplasia (GTN) is a rare collection of malignancies which are usually curable with modern chemotherapy. Lung metastasis is a relatively common feature of these malignancies and is not considered an adverse prognostic feature. Occasionally, however, the management of these patients necessitates adjuvant thoracic surgery, either to establish the diagnosis or to potentially provide a curative resection of drug-resistant foci of disease. This case series highlights 5 such cases in which thoracic surgery has significantly contributed to the management and outcome of complicated GTN patients, and suggests when thoracic surgery should be considered in this rare group of patients.

The association between preoperative pain catastrophizing and postoperative pain intensity in cardiac surgery patients.

OBJECTIVE: Postoperative pain is associated with delayed discharged and recovery, reduced patient satisfaction, and increased costs. The aim of this study was to investigate the short-term association between preoperative psychological variables (pain catastrophizing, anxiety, and depression) and postoperative pain in a sample of cardiac surgery patients. DESIGN: This is a prospective epidemiological study. SETTING: This study was carried out at two Imperial College Healthcare National Health Service Trust Hospitals (St. Mary's Hospital and Hammersmith Hospital, London, UK). SUBJECTS: Sixty-four cardiac surgery patients completed the "pain catastrophizing scale (PCS)," the "hospital anxiety and depression scale," and the "verbal rating scale" (VRS) for pain intensity preoperatively and at 48 hours postoperatively. Analgesia consumption was recorded. Data on demographic, operative, and clinical characteristics were obtained from medical records. OUTCOME MEASURES: Pain intensity at 48 hours postoperatively. RESULTS: Scores on the anxiety, depression, and PCSs were not significantly different between the pre- and postoperative period. In contrast, patients reported a higher level of pain intensity postoperatively (P < 0.001). In the fully adjusted multiple regression analysis, postoperative pain intensity was predicted by a higher level of preoperative pain intensity (dichotomized above median; ß = 2.00, 95% confidence interval [CI]: 0.28-3.72) and a higher score on the preoperative PCS (dichotomized above median; ß = 1.87, 95% CI: 0.53-3.21). CONCLUSIONS: Pain catastrophizing can predict postoperative pain intensity in cardiac surgery patients, independently of the presence of anxiety, depression, or preoperative level of pain. Future studies should aim to establish the role of pain catastrophizing in longer-term outcomes in cardiac surgery.

Simple surface sulfonation retards plasticiser migration and impacts upon blood/material contact activation processes.

BACKGROUND: The use of Di-2-ethylhexyl phthalate (DEHP) plasticised polyvinyl chloride (DEHPPPVC) in medical devices persists despite evidence suggesting that DEHP migration can be harmful. Researchers have shown that a simple surface sulfonation process can retard the migration of DEHP, which may reduce the associated inflammatory response. The present study is designed to investigate the effects of surface sulfonation on DEHP migration and blood contact activation using in vitro and rodent models. METHODS: The study was carried out in two phases: phase 1, in which the migration rate of DEHP from DEHPPPVC and sulfonated DEHP plasticised PVC (SDEHPPPVC) was measured; phase 2 of the study, in which the materials were incorporated into a rat recirculation biomaterial test model and blood samples taken to assess CD11b expression on neutrophils, IL-6 and Factor XIIa. RESULTS: The initial DEHP concentration washed from the surface after storage was 37.19 +/- 1.17 mg/l in the PPVC group and 5.89 +/- 0.81 mg/l in the SPPVC group (p<0.0001). The post-wash migration rate was 3.07 +/- 0.32 mg/l/hour in the PPVC group compared to 0.46 +/- 0.038 mg/l/hour in the SPPVC group (p<0.0001). In phase 2 of the study, CD11b expression increased by 228.9% +/- 37% over the test period in the PPVC group compared to 118.3% +/- 46% in the SPPVC group (p<0.01). IL-6 levels rose from 3.1 +/- 1.4 pg/ml to 263 +/- 26 pg/ml in the PPVC group and 2.2 +/- 1.6 pg/ml to 161 +/- 29 pg/ml in the SPPVC group (p<0.01). Factor XIIa levels rose from 0.22 +/- 0.13 g/ml to 3.7 +/- 0.32 microg/ml and 0.28 +/- 0.09 to 2.71 +/- 0.21 microg/ml in the PPVC and SPPVC groups, respectively (p<0.05 at 90 minutes). CONCLUSIONS: The simple sulfonation process significantly retards the migration of DEHP and is associated with the moderation of contact activation processes.

Pericardial abscess mimicking intracardiac neoplasm causing right heart failure.

Purulent pericarditis involves the whole pericardium and usually presents as an acute illness with high mortality without prompt diagnosis and treatment. Presentation as a mediastinal mass causing compression of the right ventricle (RV) and symptoms of heart failure in patients without previous cardiac surgery is very rare and only three cases have been reported up to now (English language medical literature). Clinicians should be aware of this unusual condition for prompt diagnosis and treatment to be instituted.

Monocyte Fc gamma receptor expression in patients undergoing coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass is associated with an inflammatory response with potential deleterious effects. The white cell subpopulation mostly investigated so far is the neutrophil. To date very little has been investigated regarding the role of the monocyte/macrophage. This study focuses on the expression of Fc gamma receptors I, II, and III by monocytes in patients undergoing cardiopulmonary bypass. METHODS: We studied the surface expression of Fc gamma receptors I, II, and III by flow cytometry on gated monocyte subpopulations in the whole blood of adult patients undergoing elective coronary artery bypass grafting. Blood samples were drawn preoperatively and at 15 minutes, 1, 2, 4, 24, 48, and 72 hours, and 6 days postoperatively. A second group of patients undergoing lung resection surgery were studied in a similar fashion. RESULTS: Neither Fc receptor I nor receptor II expression were significantly changed throughout the time points studied. Fc receptor III expression was reduced at 2 and 4 hours (p = 0.016 and 0.002) and increased at 24, 48, and 72 hours after commencement of CPB on a selected subpopulation (15%-35%) of monocytes (p = 0.004, < 0.001, and < 0.001, respectively). This expression returned to preoperative levels by the sixth postoperative day. There were no statistically significant changes in the lung resection group. CONCLUSIONS: Our study demonstrated that cardiopulmonary bypass is associated with a biphasic Fc gamma receptor III expression on a subpopulation of peripheral blood monocytes up to 3 days postoperatively.

Leucocyte depletion in cardiopulmonary bypass: a comparison of four strategies.

Leucocytes have been shown to play a fundamental role in the pathophysiology of inflammation. This prospective, randomized, controlled study was designed to identify the most advantageous leucocyte depletion technique in terms of reduction in systemic inflammatory response syndrome and myocardial ischaemia reperfusion injury associated with cardiopulmonary bypass (CPB). Forty consecutive patients undergoing elective coronary artery bypass graft (CABG) surgery were randomly allocated to one of four groups. The four groups consisted of a control group, a systemic leucocyte depletion (SLD) group, a cardioplegic leucocyte depletion (CLD) group and a total leucocyte depletion (TLD) group. There were 10 patients in each group. Lactoferrin (marker of neutrophil activation) and troponin-I (marker of myocardial ischaemia reperfusion injury) were measured at six time points: post induction, 5 min on CPB, 5 min before releasing the aortic crossclamp, 15 min after releasing the clamp and 1 and 24 hours after the discontinuation of CPB. Plasma lactoferrin levels increased rapidly in every group after the commencement of CPB, subsequently reached a peak after releasing the aortic crossclamp and gradually declined after the discontinuation of CPB. The lowest lactoferrin concentration was observed in the TLD (range 2.15-141.9 ng/mL) and CLD groups (7.469-114.6 ng/mL). Regarding myocardial injury, plasma cardiac troponin-I levels did not differ significantly between groups; but troponin-I concentrations rose dramatically after releasing the aortic crossclamp in all groups. Nevertheless, the CLD group had the lowest troponin-I level (1.37-5.55 ng/mL). In conclusion, it is believed that myocardial ischaemia is probably a major contributor to the inflammatory response. Although there is no clear statistical significance shown in this pilot study, the data tend to support the cardioplegic leucocyte depletion strategy as the optimal method for attenuating neutrophil activation and myocardial ischaemia reperfusion injury.

Inflammatory response of rat and human neutrophils exposed to di-(2-ethyl-hexyl)-phthalate-plasticized polyvinyl chloride.

A series of in vitro studies were designed to determine whether di-(2-ethyl-hexyl)-phthalate (DEHP)-plasticized polyvinyl chloride (PVC) and DEHP itself initiated an inflammatory response in both human and rat blood. Additionally, the effect of methanol washing of the PVC on the inflammatory response was studied in both blood types. Blood from both species was exposed to first, no material; second, ground DEHP-plasticized PVC; third, methanol-washed ground DEHP-plasticized PVC; and fourth, known concentrations of DEHP. The expression of the integrin CD11b was employed as a marker of the inflammatory response. After 20 minutes' exposure to PVC, CD11b expression increased to 210 +/- 32% of baseline in human blood and to 238 +/- 21.7% in rodent blood. Both blood types showed an increase in CD11b expression with increasing concentrations of DEHP (214 +/- 40.8% of baseline levels in human blood and 237 +/- 14.5% in rodent blood at the highest concentration). Methanol washing resulted in a significant moderation in CD11b upregulation in both blood types; 117 +/- 27% of baseline in human and 150 +/- 14.7% in rodent. These results support the hypothesis that DEHP-plasticized PVC and DEHP itself are proinflammatory in blood from both species, and suggest that the rodent is an appropriate model for studies of this nature.

The effect of methanol washing of plasticized polyvinyl chloride on biomaterial-contact-mediated CD11b (mac-1) expression in a rat recirculation model.

Our objective was to assess whether using a methanol wash to reduce the level of plasticizer present on the surface of medical-grade polyvinyl chloride (PVC) has a moderating effect on the expression of CD11b (mac-1) on neutrophils in rats undergoing recirculation. The study was carried out on 3 groups of 10 adult male Sprague-Dawley rats weighing between 350 and 450 g. In the 2 test groups, the animals were exposed to 48 cm(2) of di-(2-ethyl-hexyl)-phthalate (DEHP)-plasticized PVC in a parallel plate recirculating test cell through which blood was recirculated at 1.5 ml/min. In the first test group, the PVC was untreated; in the second test group, the PVC was washed in methanol to reduce the level of plasticizer on the surface. The test cell was connected to the right femoral circulation, and recirculation was established for a period of 60 min. Blood samples were taken at 0, 30, and 60 min for assessment of CD11b expression on neutrophils using flow cytometric analysis. In a third group of 10 control experiments, rats underwent the entire surgical procedure, but without recirculation through the test cell. There was statistically significant (p < 0.001) lower Cd11b expression on neutrophils in the blood of rats perfused through the cell containing methanol-washed PVC after 30 min and at 60 min. CD11b expression was significantly (p < 0.001) lower in the control group than in both test groups at both the 30 and 60 min time points and at the 60 min time point on comparison with the group where blood was perfused through methanol-washed PVC. These results demonstrate that the biomaterial-contact-mediated upregulation of CD11b may be significantly reduced by employing a methanol-washing technique on the plasticized PVC. Although this technique does not entirely eliminate the expression of CD11b on neutrophils, the difference is significant and suggests the role of the plasticizer in the development of this inappropriate inflammatory response.