Impaired DNA Double-Strand Break Repair in Irradiated Sheep Lung Fibroblasts: Late Effects of Previous Irradiation of the Spinal Thecal Sac.

Children with cancer previously treated with radiotherapy face the likelihood of side effects that can be debilitating or fatal. This study aimed to assess the long-term effect of medulloblastoma radiotherapy on the DNA double-strand break (DSB) repair capability of primary fibroblasts derived from lung biopsies of previously irradiated young sheep. This study included biopsies from three control and five irradiated sheep. The treated sheep had previously received spinal radiotherapy at a total dose of 28 Gy, which is equivalent to pediatric medulloblastoma treatment. Lung biopsies were taken 4 years post-irradiation from high-dose (HD, >18 Gy) and low-dose (LD, <2 Gy) regions. Fifteen cell lines were extracted (six control, four LD and five HD). The cells were irradiated, and DNA DSB repair was analyzed by immunofluorescence. Clonogenic, trypan blue and micronuclei assays were performed. Both the HD and LD cell lines had a significantly higher number of residual γH2AX foci 24 h and a significant decrease in pATM activity post-irradiation compared to the control. There was no statistically significant difference in the clonogenic assay, trypan blue and micronuclei results. Our study showed that a previous irradiation can impair the DNA DSB repair mechanism of ovine lung fibroblasts.

Tracheal Schwannoma Presenting as Subcutaneous Emphysema and Pneumomediastinum.

Primary tracheal schwannomas are rare benign tumours. This is a case report, and therefore, no specific methods or results are applicable. We here report a case of a tracheal schwannoma in an early adolescent girl presenting with subcutaneous emphysema and symptoms of airway obstruction. Tracheal resection and reconstruction by primary anastomosis were performed. Pathology confirmed the diagnosis of tracheal schwannoma. This is an unusual life-threatening presentation of a benign rare tracheal tumour with a challenging approach to management.

Paraganglioma arising from the liver and abutting the heart.

A paraganglioma is a rare extra-adrenal neuroendocrine tumour with a variable clinical presentation. A paraganglioma can arise anywhere along the sympathetic and parasympathetic chains, but it can occasionally emerge from unusual locations such as the liver and the thoracic cavity. We report a rare case of a woman in her 30s who presented to our emergency department with symptoms of chest discomfort, episodic hypertension, tachycardia and diaphoresis. A diagnostic approach including a chest X-ray, an MRI and a positron emission tomography-CT scan showed a large exophytic liver mass protruding into the thoracic cavity. For further characterisation of the mass, a biopsy of the lesion was performed, demonstrating that the tumour is of neuroendocrine origin. This was supported by a urine metanephrine test showing high levels of catecholamine breakdown products. Treatment consisted of a unique multidisciplinary approach involving hepatobiliary and cardiothoracic surgery allowing a safe and complete extermination of the hepatic tumour and its cardiac extension.

Lower limb amputation following venous cannulation for VA-ECMO: a case report.

Lower limb amputation following arterial cannulation for VA-ECMO has been described in the literature. Limb ischemia however following venous cannulation is very rare and not quite understood. We present a case of limb ischemia following venous cannulation. A combination of venous congestion, compartment syndrome and subsequent arterial insufficiency is the proposed pathophysiology. Shock and use of vasopressors are compounding factors. Limb ischemia can be transient and reversible if diagnosed immediately and treated by early removal of the cannula. Our patient was unstable and ECMO dependent, and removal of the cannula was not an option. This resulted in limb loss and eventual above knee amputation. Use of the smallest appropriate venous cannula and early fasciotomy, in addition to hemodynamic optimization are measures that could help in preventing major amputation.

Initiating a Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Endarterectomy Program Based on a Single Center Experience in Lebanon.

PURPOSE: In 2018, the American University of Beirut Medical Center established the first multidisciplinary Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Endarterectomy program in Lebanon. The study describes the challenges faced in establishing the program and in improving patient referral, evaluation, and perioperative care. METHODS: The program establishment including the preparation phase, clinical evaluation, and team education is discussed. The implementation of the flow of patients referred to the program was established. Education regarding diagnosis and referral were provided to physicians in the community. The initial experience is described in a retrospective analysis of 4 consecutive patients who were diagnosed with CTEPH and underwent PEA. RESULTS: Four patients were diagnosed with CTEPH had PEA performed. The mean age of patients was 64 years. The average CPB and total circulatory arrest times were 244 and 23.9 minutes per side, respectively. No mortalities were encountered perio-operatively. All patients reported significant improvement in functional capacity from NYHA III and IV to a NYHA class of I with an average PASP decrease of 59.5 ± 19.7 mmHg and mPAP drop by 30.2 ± 16.3 mmHg. CONCLUSION: The launch of the first CTEPH and PEA program in Lebanon, with a clear framework, coupled with good surgical outcomes is very encouraging. The program offers a curative solution for CTEPH patients in the region. A clear referral process and an increase in disease and treatment awareness in the community are crucial to the future success of the program, offering a definitive treatment, and avoiding delays to surgery.

Structural valve deterioration of the Labcor Dokimos aortic prosthesis: a single-centre experience.

OBJECTIVES: The goal of this study was to assess the performance and incidence of the deterioration of the Labcor Dokimos bioprosthetic aortic valve. METHODS: We performed a retrospective medical chart review of 116 patients who underwent surgical aortic valve replacement with the Labcor Dokimos aortic valve between 2010 and 2018. Abstracted data included patient demographic and echocardiographic data. Patients were divided into 2 groups: patients with structural valve deterioration (SVD) and patients without SVD. RESULTS: Among the patients with complete follow-up (n = 95), 10 patients were excluded because they died within a year; 85 patients were included in the final analysis. Of the 85 patients, 32 (38%) developed SVD; 22 (26%) had severe SVD, 15 (18%) of whom underwent reintervention. The most common aetiology of SVD was severe central aortic regurgitation, which was detected in 91% of the patients who had severe SVD. The average time from operation to severe SVD was 4.7 years with a minimum of 1.5 years and a maximum of 7.9 years. CONCLUSIONS: Bioprosthetic aortic valve deterioration due to severe aortic regurgitation is common and occurs early with the Labcor Dokimos valve. This occurrence needs to be furthered investigated in larger registries.

Management of a mechanical aortic valve during left ventricular assist device implantation in a previously replaced aortic root.

The use of left ventricular assist device (LVAD) in patients with mechanical aortic valves may result in thromboembolic events due to blood stasis around the valve and intermittent valve opening. Mechanical aortic valves encountered during LVAD implantation are managed by replacement with a tissue valve, or closure of the valve with a patch. Closure of the valve carries the risk of sudden death in cases of LVAD stoppage. Replacing the whole mechanical valve conduit is time consuming and carries a significant risk of bleeding and right ventricular (RV) failure. We describe an alternative technique of replacing a mechanical aortic valve by breaking its inner leaflets and sewing a tissue valve on top of the mechanical valve ring.

Stereotactic Radiosurgery for Atrioventricular Node Ablation in Swine: A Study on Efficacy and Dosimetric Evaluation of Organs at Risk.

Introduction Stereotactic radiosurgery (SRS) delivered to arrhythmogenic foci within the heart is a promising treatment modality. We dosimetrically evaluated the radiation dose to the organs at risk of four swine that were successfully treated with linear-accelerator-based SRS for atrioventricular (AV) node ablation. Materials and methods Single-chamber pacemakers were implanted in four large white breed swine. Cardiac computed tomography simulation scans were performed to localize the AV node and organs at risk. SRS (35-40 Gy) was delivered to the AV node, and the pigs were followed up with pacemaker interrogations. One-sample t-tests were used to evaluate Dmax of great vessels, esophagus, and chest wall as compared to known normal tissue constraints as per RTOG 0631 and AAPM Task Group 101. Results All pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic and microscopic evaluation showed fibrosis in the AV node but did not reveal any changes in non-nodal cardiac tissue or vessels. The mean Dmax±SD (p-value) of the chest wall (14.7±3.3 (0.02)), esophagus (10.7±1.1 (<0.01)) superior vena cava (3.3±4.1 (<0.01)), right pulmonary artery (16.1±6.4 (<0.01)), right pulmonary vein (15.7± 5 (<0.01)), left pulmonary artery (11.1±1.7 (<0.01)) and left pulmonary vein (14.1±2.6 (<0.01)), and the inferior vena cava (33.68±1.6 (0.026)) were significantly below the normal tissue constraint cutoffs. Mean±SD (p-value) of the ascending aorta (19.4±16.1 (0.12)) was not significantly different than normal tissue constraint cutoffs. One swine model treated at 40 Gy had small area of hotspot in the ascending aorta (40.65 (0.4 cc)). Conclusion We have demonstrated in our swine models that SRS using 35-40 Gy can be done without exceeding known human normal tissue constraints to the chest wall, esophagus, and great vessels.

Mesenteric Malperfusion Syndromes in Type A Aortic Dissection: Current Management Strategies.

Acute type A aortic dissection is a surgical emergency associated with high mortality and morbidity. When complicated with mesenteric malperfusion, its management carries a very high mortality. Many innovations in the field of vascular and cardiothoracic surgery in the last two decades have been tried in the continuous efforts to improve on the surgical outcomes. Although some reports have documented better mortality rates with reperfusion-first strategies, there is still room for improvement in the absence of a general consensus on its management.

Cytomegalovirus reactivation in left ventricular assist device patients: case series and literature review.

BACKGROUND: Cytomegalovirus (CMV) reactivation after placing left ventricular assist device (LVAD) is not a well-known entity with few cases reported in the literature. Here, we are presenting three cases of CMV reactivation after placing LVAD. A literature review of all reported cases in the literature was done. CASE SUMMARY: Three cases of advanced heart failure with reduced ejection fraction (Stage D9) had placed (LVAD) at the American University of Beirut Medical Center, a tertiary care centre in Lebanon. Within the first 2 weeks after LVAD implantation, the three patients spiked a high-grade fever for which sepsis workup was done, and antibiotics were initiated. Despite the escalating antibiotic regimens, the three patients had a persistent high-grade fever. The negative cultures and the continuous fever prompted an investigation for other causes of fever. Therefore, CMV polymerase chain reaction in blood was performed and revealed high titres. Patients received a full course of treatment with ganciclovir. The fever and the CMV titres declined after completing the antiviral therapy with better clinical outcomes. This raises the concern of CMV reactivation in LVAD patients. DISCUSSION: This case series and literature review highlight the epidemiology, incidence, and management of CMV reactivation among LVAD patients. Awareness about this clinical entity should be raised, especially with the increase of LVAD surgeries.

Neoadjuvant chemotherapy and Avelumab in early stage resectable nonsmall cell lung cancer.

Multiple randomized studies have shown that combination of chemotherapy and immune checkpoint inhibitors (ICIs) leads to better response rates and survival as compared to chemotherapy alone in the advanced stage of NSCLC. Data suggesting a benefit to using ICIs in the neoadjuvant therapy of patients with early stage NSCLC are emerging. Eligible subjects were treatment naïve patients with stage IB, II, and resectable IIIA NSCLC. Patients received three cycles of neoadjuvant chemotherapy with four doses of avelumab every 2 weeks. Patients with squamous cell cancer received cisplatin or carboplatin on day 1 and gemcitabine on days 1 and 8 of each cycle of chemotherapy. Patients with nonsquamous histology received cisplatin or carboplatin with pemetrexed on day 1 of each cycle. Patients then proceeded to their planned surgery. Out of 15 patients accrued as part of stage 1 of the study, four had a radiologic response (1 complete response), lower than the minimum of six responses needed to continue to phase 2 of the study. The study was therefore terminated. Majority had adenocarcinoma histology and stage IIIA disease. The treatment was well tolerated with no unexpected side effects. Four patients (26.7%) had grade III/IV CTCAE toxicity. This study confirms that the preoperative administration of chemotherapy and avelumab is safe. There was no indication of increased surgical complications. The benefit of adding immunotherapy to chemotherapy did not appear to enhance the overall response rate of patients in the neoadjuvant setting in patients with resectable NSCLC because this study failed to meet its primary endpoint.

Current status in decision making to treat acute type A dissection: limited versus extended repair.

Acute type A aortic dissection remains one of the most challenging conditions in aortic surgery. Despite the advancements in the field, the mortality rate still remains high. Though there is a general consensus that the ascending aorta should be replaced, the distal extension of the surgery still remains a controversy. Few surgeons argue for a conservative approach to reduce operative and postoperative morbidity while others considering the problems associated with "downstream problems" support an aggressive approach including a frozen elephant trunk. The cohort in the Indian subcontinent and APAC is far different from the western world. Many factors determine the decision for surgery apart from the pathology of the disease. Economy, availability of the suitable prosthesis, the experience of the surgeon, ease of access to the medical facility all contribute to the decision making to treat acute type A dissection.

Large esophageal schwannoma: En-bloc resection with primary closure by esophagoplasty.

BACKGROUND: Gastrointestinal schwannomas are submucosal tumors accounting for 2-7% of mesenchymal gastro-intestinal neoplasms; the stomach being the most common site. Esophageal schwannomas are more frequent in women, and are usually located in the upper to mid portion. Dysphagia is the main presenting symptom. A definitive diagnosis requires confirmation by histopathological and immunohistochemical studies. CASE PRESENTATION: A 50-year-old healthy lady, presented with gradual increasing onset of dyspnea, with minimal dysphagia to solid food, over a period of several years. Enhanced CT scan of the chest revealed a well-defined soft tissue mass arising from the proximal third of the esophagus, measuring 7.8 × 5.4 x 10.5 cm. Esophagogastric endoscopy with ultrasonography showed an elevated, smooth surface lesion, arising from the submucosal layer of the esophagus, with a hypervascular mucosa. Enucleation of this large tumor, with preservation of the overlying mucosa, was difficult to accomplish due to its large size. Making use of a dilated proximal esophageal segment, total en-bloc excision of the mass rendered a 15 cm esophagotomy gap, which was easily closed, in two layers, without affecting the overall caliber thus achieving a good esophagoplasty result. Histologically, abundance of spindle-shaped cells with positive S-100 proteins, confirmed the diagnosis of esophageal schwannoma. CONCLUSION: Variations in mesenchymal gastrointestinal tumors is vast, rendering diagnosis by radiology alone difficult. As such, characteristic histologic and immunostaining features are cornerstones in precise diagnosis of esophageal schwannomas. Despite being rare in incidence, symptomatic esophageal schwannoma lesions can be excised entirely, with low rate of recurrence and favorable overall outcomes.

Establishing an ECMO program in a developing country: challenges and lessons learned.

AIM: The ECMO (extracorporeal membrane oxygenation) Program at the American University of Beirut Medical Center was established in November 2015 as the first program serving adult and pediatric population in a low-resource setting. The aim of the study is to describe the challenges faced during the establishment of the program and factors leading to its success. METHODS: The program establishment is described. The preparation phase, included the strategic, financial, and clinical planning by administration, nursing, and a multidisciplinary team of physicians. The training and education phase included all the involved nurses, perfusionists, and physicians. Concerns were heard from various stakeholders, and the challenges were analyzed and discussed. RESULTS: The preparation committee chose the adequate equipment, responded to the concerns, defined roles and responsibilities through credentialing and privileging, wrote policies and protocols, and established a strategy to decide for the ECMO indication. Selected team of nurses, physicians, and perfusionists are identified and trained locally, and abroad. A full-time ECMO physician was recruited to launch the program. Twelve patients (6 adults, 3 children, and 3 neonates) were supported by ECMO, for cardiac and respiratory indications. Eleven patients were supported by veno-arterial ECMO, and 1 patient (a neonate) with veno-venous ECMO. Overall, 75% survived to decannulation and 41% survived to discharge. CONCLUSION: With limited human and financial resources, new ECMO centers need to carefully establish selection criteria that may differ from those used in developed countries. Indications should be discussed on a case by case basis, taking into account clinical, social, and financial issues. This experience might help other institutions in developing countries to build their own program despite financial and human limitations.

Penetrating shrapnel injury to the chest presenting as a delayed tracheoesophageal fistula (TEF). A case report.

Tracheo-esophageal fistulae (TEF) due to trauma are rare. We report a case of a delayed TEF caused by a shrapnel from a blast. A 25-year-old male was admitted to the hospital after sustaining a blast injury. A contrast CT scan of the chest and neck revealed the presence of metallic shrapnel in close proximity to the tracheo-esophageal groove at the level of the thoracic inlet. Bronchoscopy revealed 0.5 cm tear in the membranous trachea while esophagoscopy and contrast swallow were normal. Coughs after starting fluid intake triggered a repeat endoscopy that showed a large TEF at 22 cm from the incisors. He underwent surgical repair through a collar incision and limited sternotomy. The TEF extended for 2 cm. The esophagus was repaired in two layers, the membranous trachea was sutured primarily, and an interposition strap muscle flap was placed. A contrast swallow on postoperative day 7 revealed the presence of a small leak into the trachea that was treated conservatively. Traumatic TEF are rare and should be suspected in patients with injuries to proximal structures. Delay in diagnosis and appropriate management can conceivably lead to death.

Swine Atrioventricular Node Ablation Using Stereotactic Radiosurgery: Methods and In Vivo Feasibility Investigation for Catheter-Free Ablation of Cardiac Arrhythmias.

BACKGROUND: Linear accelerator-based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter-free ablation modality. We tested the feasibility of in vivo atrioventricular (AV) node ablation in swine using stereotactic radiosurgery. METHODS AND RESULTS: Five Large White breed swine (weight 40-75 kg; 4 females) were studied. Single-chamber St Jude pacemakers were implanted in each pig. The pigs were placed under general anesthesia, and coronary/cardiac computed tomography simulation scans were performed to localize the AV node. Cone beam computed tomography was used for target positioning. Stereotactic radiosurgery doses ranging from 35 to 40 Gy were delivered by a linear accelerator to the AV node, and the pigs were followed up with weekly pacemaker interrogations to observe for potential electrocardiographic changes. Once changes were observed, the pigs were euthanized, and pathology specimens of various tissues, including the AV node and tissues surrounding the AV node, were taken to study the effects of radiation. All 5 pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic inspection did not reveal damage to the myocardium, and pigs had preserved systolic function on echocardiography. Immunostaining revealed fibrosis in the target region of the AV node, whereas no fibrosis was detected in the nontargeted regions. CONCLUSIONS: Catheter-free radioablation using linear accelerator-based stereotactic radiosurgery is feasible in an intact swine model.

Preoperative Localization of Mediastinal Parathyroid Adenoma with Intra-arterial Methylene Blue.

Ectopic parathyroid is found in 16% of patients with hyperparathyroidism. 2% of ectopic parathyroid adenomas are not accessible to standard cervical excision. In such cases, video-assisted thoracoscopic resection is the recommended definitive treatment. We present a case of mediastinal parathyroid adenoma localized preoperatively by injecting methylene blue within a branch of the internal mammary artery that is supplying the adenoma. Intra-arterial methylene blue injection facilitated visualization and resection of the adenoma. The preoperative intra-arterial infusion of methylene blue appears to be an effective and safe method for localization of ectopic mediastinal parathyroid adenomas and allows rapid identification during thoracoscopic resection.

Hemorrhoids screening and treatment prior to LVAD: is it a necessity?

Continuous-flow left ventricle assist devices (CF-LVADs) has become an essential modality in the management of stage D heart failure (HF) with significant improvement in survival and quality of life. Due to the durability of such devices and long term support complications such as bleeding and aortic insufficiency has emerged. Bleeding accounts for more than 20 % with the majority being from the gastrointestinal tract. The increase of bleeding tendency are mainly attributed to the loss of large von Willebrand's Factor (vWF) multimers due to shear stress with the chronic intake of anticoagulants. We are reporting two cases of patients with Stage D HF and history of hemorrhoids presenting for LVAD implantation. Many efforts that decrease bleeding related to CF-LVADs will be discussed with focus on hemorrhoids.