Ashutosh Hardikar

Epithelial mesenchymal transition in smokers: large versus small airways and relation to airflow obstruction

Background Small airway fibrosis is the main contributor in airflow obstruction in chronic obstructive pulmonary disease. Epithelial mesenchymal transition (EMT) has been implicated in this process, and in large airways, is associated with angiogenesis, ie, Type-3, which is classically promalignant. Objective In this study we have investigated whether EMT biomarkers are expressed in small airways compared to large airways in subjects with chronic airflow limitation (CAL) and what type of EMT is present on the basis of vascularity. Methods We evaluated epithelial activation, reticular basement membrane fragmentation (core structural EMT marker) and EMT-related mesenchymal biomarkers in small and large airways from resected lung tissue from 18 lung cancer patients with CAL and 9 normal controls. Tissues were immunostained for epidermal growth factor receptor (EGFR; epithelial activation marker), vimentin (mesenchymal marker), and S100A4 (fibroblast epitope). Type-IV collagen was stained to demonstrate vessels. Results There was increased expression of EMT-related markers in CAL small airways compared to controls: EGFR (P<0.001), vimentin (P<0.001), S100A4 (P<0.001), and fragmentation (P<0.001), but this was less than that in large airways. Notably, there was no hypervascularity in small airway reticular basement membrane as in large airways. Epithelial activation and S100A4 expression were related to airflow obstruction. Conclusion EMT is active in small airways, but less so than in large airways in CAL, and may be relevant to the key pathologies of chronic obstructive pulmonary disease, small airway fibrosis, and airway cancers.

The natural history of guidelines: The case of aortopathy related to bicuspid aortic valves

Clinical guidelines represent statements that seek to synthesize the best evidence to guide a course of action to improve health outcomes and more cost-effective use of resources. However, even when the evidence is not definitive, comprehensive documents are still needed to guide clinical decision-making. In these circumstances, guidelines are inevitably affected by perceptions of the problem and their possible solutions. From 1998 to 2014, 10 different international guidelines have focused on the aortopathy related to bicuspid aortic valves. Recommended thresholds for intervention started at a cutoff level of 5.5cm in 1998, reached a nadir of 4 to 4.5cm in 2010, and returned to a 5.5cm cutoff level in 2014. During this time, no conclusive objective proof was published to support either an aggressive or conservative strategy. The consequence was that an undefined number of patients underwent surgery (and potential complications thereof) at an earlier disease stage than might have been necessary. This experience might provide a clue as to how guidelines evolve, and provide insight as to how to avoid a similar process in the future.

Bilateral Anterior Compartment Syndrome After Routine Coronary Artery Bypass Surgery and Severe Hypothyroidism

Compartment syndrome is a very rare complication of coronary artery bypass grafting and previously it has only been described unilaterally. We describe the development of compartment syndrome in bilateral anterior compartments of the lower leg after vein harvest for coronary artery bypass grafting. We describe a series of predisposing factors contributing to this condition and its delayed diagnosis, including severe undiagnosed hypothyroidism. We advise a high index of suspicion in patients postvein harvest and recommend thyroid function testing for all patients who have compartment syndrome develop.

Intracardiac lipoma arising from the papillary muscle.

Abstract  Cardiac lipoma is the commonest nonmyxomatous benign primary cardiac tumor. We report a case of lipoma arising from the anterolateral papillary muscle and presenting with a transient ischemic episode and a history of malignant melanoma. The lipoma was removed leaving the mitral apparatus intact. (J Card Surg 2011;26:65‐66)

Blunt cardiac rupture in the setting of previous sternotomy.

Most cases of blunt cardiac rupture (BCR) are associated with mortality at the scene of the injury. For the fortunate 13% to 17% of patients who survive the journey to the hospital, the treatment is definitive surgical repair. In the setting of previous sternotomy, the pericardial adhesions may limit the damage and protect against cardiac tamponade. We describe a patient who sustained 2 right ventricular tears from blunt trauma in a motor vehicle accident 18 years after coronary artery bypass graft surgery. He did not demonstrate hemodynamic compromise and was successfully managed conservatively.

Evaluation of hemolysis in microcatheter directed blood infusion at different flow rates for transarterial salvage reperfusion: In-vitro study

BACKGROUND Microcatheter directed blood reperfusion is an endovascular salvage option for acute cerebral artery occlusions. It has not been investigated whether this technique may be associated with hemolysis. OBJECTIVE Analysis of hemolysis during blood infusion through different microcatheters and infusion rates to assess related risks. METHODS Four microcatheters with different inner diameters were perfused with blood samples at three infusion rates. Hemolytic markers including lactate-dehydrogenase (LDH) and haptoglobin were analyzed. Samples before and after blood infusion were compared using Students t-test. Flow-related degree of hemolysis was analyzed with regression analysis. Resulting shear stress was calculated and correlated with LDH and haptoglobin. RESULTS Significant increase of LDH and decrease of haptoglobin was found after blood reperfusion through small microcatheters at progressive flow rates (p<0.05). No hemolysis was found with larger diameter microcatheters at all flow rates (p>0.05). Correlation between shear stress, LDH and haptoglobin was r=0.86 and r=0.75, respectively. CONCLUSIONS Progressive hemolysis occurs during blood perfusion of small lumen microcatheters at increasing flow rates. This phenomenon may be related to turbulent flow, exposure time and increased shear stress. Larger microcatheters did not induce hemolysis and may be the preferred choice for stroke reperfusion.

Answer to quiz on page 26 and Case Discussion: The ICD patient with chest pain

Chest discomfort has multiple causes. The timing of the symptoms after device implantation suggests a complication of the procedure. Pneumothorax and lead perforation need to be excluded, however an ECG should be performed first as this can be done with minimal delay and can exclude an acute coronary syndrome. Chest X-ray should also be performed and can show pneumothorax, lead dislodgement (however, it is non-specific in detecting perforation), and rib fractures (this patient had received chest compressions during his cardiac arrest). Device interrogation should be performed and can give information on lead dislocation or perforation (increased impedance and thresholds, decreased sensing, and stimulation of extracardiac tissue in the case of a perforation). An echocardiogram should be performed if perforation is suspected to evaluate the presence of pericardial effusion and tamponade. There should be a low threshold for performing a chest CT as this may show a pneumothorax that is not present on echocardiography or lead perforation that is not present on echocardiogram.

Recurrent Pericardial Effusion While Receiving Nivolumab for Metastatic Lung Adenocarcinoma: Case Report and Review of the Literature

Nivolumab is an immune checkpoint inhibitor used to treat various malignancies including metastatic non-small cell lung cancer. Immune checkpoint inhibitors have excellent efficacy, but are known to cause auto-immune inflammation, with four recent cases in the literature for Nivolumab causing pericardial effusion. We describe the clinical course of a patient in which this drug seems to have caused recurrence of pericardial effusion despite previous surgical interventions. Clinical Practice Points • In this manuscript, we build on four prior case reports in the literature of nivolumab and its potential association with pericardial effusion, especially in those with previous episodes of pericardial effusion. • Immune checkpoint inhibitors have the ability to cause immune related inflammation, but previous pericardial effusion is not currently considered a contraindication to nivolumab therapy. • This is the first case report of a patient on nivolumab with re-collection of pericardial effusion despite multiple surgical interventions. • This case also describes two presentations of pericardial effusion within eleven weeks on nivolumab, with then no further effusions in the ten months after nivolumab cessation. • The significance of this paper is to outline the possible contraindication of previous pericardial effusion for patients being considered for nivolumab.

Anomalous systemic arterial supply to the left lower lobe without evidence of pulmonary sequestration: Images for Surgeons

An 18‐year‐old male was referred to our department after developing episodes of haemoptysis following heavy contact during sport. He had no significant past medical history and clinical examination was unremarkable. A chest X‐ray revealed no abnormal shadow. Subsequent computed tomography (CT) of the chest with contrast showed an anomalous systemic artery measuring 14 mm in diameter arising from the anterior surface of the descending thoracic aorta passing into the left lung on the inferior aspect of the left hilum inferior to the left inferior pulmonary vein (Fig. 1). There was a small amount of blood seen within the left lower lobe peripherally. Radiologically guided percutaneous intervention with balloon occlusion or embolization was considered; however, the size of the anomalous artery was considered too big to achieve a satisfactory result. A transthoracic echocardiogram was performed, which showed normal left atrial size, normal biventricular size and function, and both inferior pulmonary veins were seen to drain in to the left atrium as expected. Without intervention, the patient would be at risk of ongoing haemoptysis and bleeding, as well as left heart volume overload and pulmonary hypertension secondary to significant aorto‐pulmonary shunt. At surgery, the patient initially underwent bronchoscopy which confirmed normal bronchial anatomy, and no evidence of bleeding to suggest a communication between the anomalous artery and the airways. A mini‐thoracotomy was then performed and the anomalous artery was found to feed the left lower lobe. The fissures were dissected and the normal pulmonary arterial branches were seen to enter the left lower lobe also. These vessels were not atresic or hypoplastic. On direct palpation, there was no thrill evident and so the presence of an arterial‐venous malformation was unlikely. The lung parenchyma appeared normal. The anomalous vessel was clamped and the left lower lobe remained well perfused. The findings were consistent with systemic arterialization of the lung without sequestration, and so the anomalous artery was divided with a stapler device and we did not perform lobectomy. The patient was discharged without any complication. At 6 weeks follow‐up, the patient reports no further symptoms. Systemic arterial supply from the descending thoracic aorta to the basal segment of the left lower lobe is a rare congenital anomaly within the spectrum of pulmonary sequestration. CT of the chest is the most useful diagnostic test as it demonstrates both the bronchial and vascular anatomy of the lung, and CT angiography can clearly demonstrate the origin of the aberrant systemic artery. Although angiographic interventions such as embolization have been described, surgery remains the gold standard of treatment and is always indicated in order to prevent the long‐term potential adverse effects associated with this anomaly.

Occam's Razor and Hickam's Dictum: A Rare Case of Synchronous Solid and Hematological Malignancies and Transformed EGFR-Mutated NSCLC.

Occam’s Razor and Hickam’s Dictum: A Rare Case of Synchronous Solid and Hematological Malignancies and Transformed EGFR-Mutated NSCLC Ciara Conduit, M.B.B.S.,* Ashutosh Hardikar, M.B.B.S., Ritam Prasad, M.B.B.S., Louise Nott, M.B.B.S. Department of Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia Department of Cardiothoracic Surgery, Royal Hobart Hospital, Hobart, Tasmania, Australia Department of Hematology, Royal Hobart Hospital, Hobart, Tasmania, Australia