Study protocol for IMPRoVE: a multicentre prospective observational cohort study of the incidence, impact and mechanisms of perioperative right ventricular dysfunction in non-cardiac surgery.

INTRODUCTION: Perioperative myocardial injury evidenced by elevated cardiac biomarkers (both natriuretic peptides and troponin) is common after major non-cardiac surgery. However, it is unclear if the rise in cardiac biomarkers represents global or more localised cardiac injury. We have previously shown isolated right ventricular (RV) dysfunction in patients following lung resection surgery, with no change in left ventricular (LV) function. Given that perioperative RV dysfunction (RVD) can manifest insidiously, we hypothesise there may be a substantial burden of covert yet clinically important perioperative RVD in other major non-cardiac surgical groups. The Incidence, impact and Mechanisms of Perioperative Right VEntricular dysfunction (IMPRoVE) study has been designed to address this knowledge gap. METHODS AND ANALYSIS: A multicentre prospective observational cohort study across four centres in the West of Scotland and London. One hundred and seventy-five patients will be recruited from five surgical specialties: thoracic, upper gastrointestinal, vascular, colorectal and orthopaedic surgery (35 patients from each group). All patients will undergo preoperative and postoperative (day 2-4) echocardiography, with contemporaneous cardiac biomarker testing. Ten patients from each surgical specialty (50 patients in total) will undergo T1-cardiovascular magnetic resonance (CMR) imaging preoperatively and postoperatively. The coprimary outcomes are the incidence of perioperative RVD (diagnosed by RV speckle tracking echocardiography) and the effect that RVD has on days alive and at home at 30 days postoperatively. Secondary outcomes include LV dysfunction and clinical outcomes informed by Standardised Endpoints in Perioperative Medicine consensus definitions. T1 CMR will be used to investigate for imaging correlates of myocardial inflammation as a possible mechanism driving perioperative RVD. ETHICS AND DISSEMINATION: Approval was gained from Oxford C Research Ethics Committee (REC reference 22/SC/0442). Findings will be disseminated by various methods including social media, international presentations and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05827315.

Perioperative cardiovascular pathophysiology in patients undergoing lung resection surgery: a narrative review.

Although thoracic surgery is understood to confer a high risk of postoperative respiratory complications, the substantial haemodynamic challenges posed are less well appreciated. This review highlights the influence of cardiovascular comorbidity on outcome, reviews the complex pathophysiological changes inherent in one-lung ventilation and lung resection, and examines their influence on cardiovascular complications and postoperative functional limitation. There is now good evidence for the presence of right ventricular dysfunction postoperatively, a finding that persists to at least 3 months. This dysfunction results from increased right ventricular afterload occurring both intraoperatively and persisting postoperatively. Although many patients adapt well, those with reduced right ventricular contractile reserve and reduced pulmonary vascular flow reserve might struggle. Postoperative right ventricular dysfunction has been implicated in the aetiology of postoperative atrial fibrillation and perioperative myocardial injury, both common cardiovascular complications which are increasingly being appreciated to have impact long into the postoperative period. In response to the physiological demands of critical illness or exercise, contractile reserve, flow reserve, or both can be overwhelmed resulting in acute decompensation or impaired long-term functional capacity. Aiding adaptation to the unique perioperative physiology seen in patients undergoing thoracic surgery could provide a novel therapeutic avenue to prevent cardiovascular complications and improve long-term functional capacity after surgery.

A new bronchoscopic catheter for the transbronchial ablation of pulmonary nodules.

OBJECTIVES: With the objective of simultaneous bronchoscopic biopsy and ablation of malignant solitary pulmonary nodules, we have developed a flexible monopolar radiofrequency (RF) catheter that can be deployed through the working channel of most bronchoscopes. MATERIALS AND METHODS: Fresh tumor specimens were heated in a water bath to 37 °C, and the RF catheter was inserted into the tumors within the specimen. Temperature sensors were positioned 3 mm, 5 mm and 7 mm from the electrode to measure the temperature of the surrounding tissue every 1 s. The ablation was conducted by applying RF energy for 8 min. The ablated specimens were evaluated by cutting the tissue samples along the top of the device and measuring the ablation zones. RESULTS: Five ablations were performed in 3 specimens. All of the ablation zones had a major axis length (along the electrode axis) between 18.9 mm and 22.8 mm and a minor axis length (perpendicular to the major axis) between 13.3 mm and 18.0 mm. The temperature data showed that all of the temperature sensors detected 60 °C or higher. These results demonstrate that the RF catheter was capable of generating ablation zones that were locally contained in ex vivo human cancerous lung specimens and that incorporated the tumor tissues. CONCLUSION: We present the results of a benchtop study demonstrating the local control of ablation achieved using the RF device. This study suggests that the ex vivo ablation of lung malignancy with a new bronchoscopic RF catheter is feasible and that in vivo tumor ablation with this method in humans merits further study.

High yield of bronchoscopic transparenchymal nodule access real-time image-guided sampling in a novel model of small pulmonary nodules in canines.

BACKGROUND: Bronchoscopic transparenchymal nodule access (BTPNA) is a novel approach to accessing pulmonary nodules. This real-time, image-guided approach was evaluated for safety, accuracy, and yield in the healthy canine model. METHODS: A novel, inorganic model of subcentimeter pulmonary nodules was developed, consisting of 0.25-cc aliquots of calcium hydroxylapatite (Radiesse) implanted via transbronchial access in airways seven generations beyond the main bronchi to represent targets for evaluation of accuracy and yield. Thoracic CT scans were acquired for each subject, and from these CT scans LungPoint Virtual Bronchoscopic Navigation software provided guidance to the region of interest. Novel transparenchymal nodule access software algorithms automatically generated point-of-entry recommendations, registered CT images, and real-time fluoroscopic images and overlaid guidance onto live bronchoscopic and fluoroscopic video to achieve a vessel-free, straight-line path from a central airway through parenchymal tissue for access to peripheral lesions. RESULTS: In a nine-canine cohort, the BTPNA procedure was performed to sample 31 implanted Radiesse targets, implanted to simulate pulmonary nodules, via biopsy forceps through a specially designed sheath. The mean length of the 31 tunnels was 35 mm (20.5-50.3-mm range). Mean tunnel creation time was 16:52 min, and diagnostic yield was 90.3% (28 of 31). No significant adverse events were noted in the status of any of the canine subjects post BTPNA, with no pneumothoraces and minimal bleeding (all bleeding events < 2 mL in volume). CONCLUSIONS: These canine studies demonstrate that BTPNA has the potential to achieve the high yield of transthoracic needle aspiration with the low complication profile associated with traditional bronchoscopy. These results merit further study in humans.

Feasibility and safety of bronchoscopic transparenchymal nodule access in canines: a new real-time image-guided approach to lung lesions.

BACKGROUND: The current approaches for tissue diagnosis of a solitary pulmonary nodule are transthoracic needle aspiration, guided bronchoscopy, or surgical resection. The choice of procedure is driven by patient and radiographic factors, risks, and benefits. We describe a new approach to the diagnosis of a solitary pulmonary nodule, namely bronchoscopic transparenchymal nodule access (BTPNA). METHODS: In anesthetized dogs, fiducial markers were placed and thoracic CT images acquired. From the CT scan, the BTPNA software provided automatic point-of-entry prescribing of a bronchoscopic path (tunnel) through parenchymal tissue directly to the lesion. The preplanned procedure was uploaded to a virtual bronchoscopic navigation system. Bronchoscopic access was performed through the tunnels created. Proximity of the distal end of the tunnel sheath to the target was measured, and safety was recorded. RESULTS: In four canines, 13 tunnels were created. The average length of the tunnels was 32.3 mm (range, 24.7-46.7 mm). The average proximity measure was 5.7 mm (range, 0.1-12.9 mm). The distance from the pleura to the nearest point within the target was 7.4 mm (range, 0.1-15 mm). Estimated blood loss was <2 mL per case. There were no pneumothoraces. CONCLUSIONS: We describe a new approach to accessing lesions in the lung parenchyma. BTPNA allows bronchoscopic creation of a direct path with a sheath placed in proximity to the target, creating the potential to deliver biopsy tools within a lesion to acquire tissue. The technology appears safe. Further experiments are needed to assess the diagnostic yield of this procedure in animals and, if promising, to assess this technology in humans.

Pure white cell aplasia: report of first case associated with autoimmune hepatitis.

Pure white cell aplasia (PWCA) is a rare, immune-mediated condition that causes a profound inhibition of myelopoiesis. It has been seen in association with other autoimmune conditions, thymomas, chronic lymphocytic leukaemia and as an adverse drug reaction. We report what we believe to be the first case of PWCA associated with autoimmune hepatitis. An 18-year-old woman presented with jaundice and was found to be suffering from acute hepatitis. Later she became neutropenic and lymphopenic. Liver biopsy was indicative of autoimmune hepatitis. This was later confirmed by autoantibody results. Bone marrow aspirate found an absence of all myeloid progenitor cells, highly suggestive of PWCA. The low white cell count only improved after immunosuppression with corticosteroids. Her condition remains stable 1 year later with azathioprine therapy.

Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs.

We delivered controlled radio frequency energy to the airways of anesthetized, ventilated dogs to examine the effect of this treatment on reducing airway narrowing caused by a known airway constrictor. The airways of 11 dogs were treated with a specially designed bronchial catheter in three of four lung regions. Treatments in each of the three treated lung regions were controlled to a different temperature (55, 65, and 75 degrees C); the untreated lung region served as a control. We measured airway responsiveness to local methacholine chloride (MCh) challenge before and after treatment and examined posttreatment histology to 3 yr. Treatments controlled to 65 degrees C as well as 75 degrees C persistently and significantly reduced airway responsiveness to local MCh challenge (P < or = 0.022). Airway responsiveness (mean percent decrease in airway diameter after MCh challenge) averaged from 6 mo to 3 yr posttreatment was 79 +/- 2.2% in control airways vs. 39 +/- 2.6% (P < or = 0.001) for airways treated at 65 degrees C, and 26 +/- 2.7% (P < or = 0.001) for airways treated at 75 degrees C. Treatment effects were confined to the airway wall and the immediate peribronchial region on histological examination. Airway responsiveness to local MCh challenge was inversely correlated to the extent of altered airway smooth muscle observed in histology (r = -0.54, P < 0.001). We conclude that the temperature-controlled application of radio frequency energy to the airways can reduce airway responsiveness to MCh for at least 3 yr in dogs by reducing airway smooth muscle contractility.