Ibrahim Fawzy Hassan

Down-regulation of the canonical Wnt β-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD.

Background The Wnt pathway mediates differentiation of epithelial tissues; depending on the tissue types, Wnt can either drive or inhibit the differentiation process. We hypothesized that key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the epithelial differentiated state. Methodology/Principal Findings Microarrays were used to assess the expression of Wnt-related genes in the small airway epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers, healthy smokers, and smokers with COPD. Thirty-three of 56 known Wnt-related genes were expressed in the SAE. Wnt pathway downstream mediators β-catenin and the transcription factor 7-like 1 were down-regulated in healthy smokers and smokers with COPD, as were many Wnt target genes. Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers, an observation confirmed by TaqMan Real-time PCR, Western analysis and immunohistochemistry. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and down-regulation of Wnt target genes in airway epithelial cells in vitro. Conclusions/Significance Smoking down-regulates the Wnt pathway in the human airway epithelium. In the context that Wnt pathway plays an important role in differentiation of epithelial tissues, the down-regulation of Wnt pathway may contribute to the dysregulation of airway epithelium differentiation observed in smoking-related airway disorders.

Position paper for the organization of ECMO programs for cardiac failure in adults

Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory cardiogenic shock, refractory ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest, and acute or decompensated right heart failure. Evidence is emerging to guide the use of this therapy for some of these indications, but there remains a need for additional evidence to guide best practices. As a result, the use of ECMO may vary widely across centers. The purpose of this document is to highlight key aspects of care delivery, with the goal of codifying the current use of this rapidly growing technology. A major challenge in this field is the need to emergently deploy ECMO for cardiac failure, often with limited time to assess the appropriateness of patients for the intervention. For this reason, we advocate for a multidisciplinary team of experts to guide institutional use of this therapy and the care of patients receiving it. Rigorous patient selection and careful attention to potential complications are key factors in optimizing patient outcomes. Seamless patient transport and clearly defined pathways for transition of care to centers capable of providing heart replacement therapies (e.g., durable ventricular assist device or heart transplantation) are essential to providing the highest level of care for those patients stabilized by ECMO but unable to be weaned from the device. Ultimately, concentration of the most complex care at high-volume centers with advanced cardiac capabilities may be a way to significantly improve the care of this patient population.

Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease

The TLRs are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. On the basis of the knowledge that smokers are more susceptible to pulmonary infection and that the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th to 12th order) epithelium from healthy nonsmokers (n = 60), healthy smokers (n = 73), and smokers with COPD (n = 36). Using the criteria of detection call of present (P call) ≥50%, 6 of 10 TLRs (TLRs 1–5 and 8) were expressed. Compared with nonsmokers, the most striking change was for TLR5, which was downregulated in healthy smokers (1.4-fold, p < 10−10) and smokers with COPD (1.6-fold, p < 10−11). TaqMan RT-PCR confirmed these observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was expressed mainly on the apical side of the epithelium and was decreased in healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream genes, IL-6 and IL-8, was highly induced by flagellin in TLR5 high-expressing cells compared with TLR5 low-expressing cells. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced downregulation of TLR5 may contribute to smoking-related susceptibility to airway infection, at least for flagellated bacteria.

Building Qatar severe respiratory failure ECMO program

Introduction: The aim of the program was to establish a severe respiratory failure (SRF) service with mobile extracorporeal membrane oxygenation (ECMO) retrieval capability throughout Qatar. This was achieved through the collaboration of various Hamad Medical Corporation (HMC) entities (critical care, cardiothoracic surgery, vascular surgery, and ambulance services). The service was commissioned by the Ministry of Public Health in October 2013 in response to the emerging MERS-Corona outbreak and its associated high mortality. After extensive team building and training, the service treated its first patient in June 2014. The key result has been an improvement in survival rate from 19 to 68%. The service is ranked among the best in the Extracorporeal Life Support Organization (ELSO) outcomes benchmark of worldwide SRF services. The provision of the highest quality care to patients with high predicted mortality has given a new hope in improving clinical outcomes and their reintegration into community. Background: In 2013, a novel virus (MERS Corona virus) was identified in Saudi Arabia, with subsequent cases in other gulf states including Qatar.1 The MERS virus was associated with rapid onset of severe respiratory and renal failure, resulting in a very high mortality rate (>50%) in the early days of the infection.2 The need to establish a SRF center with mobile ECMO retrieval capabilities was identified by the HMC senior leadership in order to anticipate and proactively deal with the situation. The program became a matter of utmost importance due to the inevitable social, political, and geographical factors, which united the people of the GCC. Strategically speaking, regulating the travel norms or bringing in a quarantine on travelers arriving from the countries affected by the MERS Corona virus were not a feasible alternative.3 Furthermore, the high mortality rate, failure of conventional ICU care, and the high cost of transporting and hospitalizing these patients in other countries with advanced respiratory support capability highlighted the need for the development of a severe respiratory failure and extracorporeal membrane oxygenation (SRF-ECMO) service program in Qatar. Evidence: The value of a SRF-ECMO service had previously been demonstrated during the international outbreak of H1N1 virus, when survival of patients with significant respiratory failure would have been left to chance or luck if no such advanced program had been in place. The SRF-ECMO services were achieving global survival rates of 60–70% in patients with otherwise very high mortality rates.4 Additionally, treatment of SRF in the SRF-ECMO Center decreased mortality rates.5 The vision of the leadership in promoting interdepartmental collaboration along with the support from the management at various levels was the highlight in the development of this program which now is recognized internationally for its clinical excellence and well known for its best practices, teaching, and mentorship programs. Program implementation and team training: The idea of a SRF-ECMO service in the State of Qatar had to be planned immaculately due to the fact that this was the first project of its kind in the country and there is always a sense of anticipation and enigma surrounding such a cutting-edge technology being made available with the help of the government itself. As a result of various fruitful deliberations, a steering committee was created which identified all the potential services that would be involved in the program along with the identification of the potential stakeholders in its successful implementation. The Guys and St Thomas (GSTT) Hospital team in London (UK) was identified as the potential partner for the implementation of the SRF-ECMO in Qatar and hence an official mission consisting of leaders from various services involved went on a field visit to get a firsthand experience about the program. Various discussions with the GSTT team took place in order to understand the processes and the actual difficulties they faced when they started their own SRF-ECMO service. The clinical leaders realized that the only way this project could succeed – taking into consideration the relative inexperience of the team involved with regards to ECMO – was to provide hands-on experience to all HMC staff involved so they could become a fully functional and highly efficient team, which worked according to the best current evidence-based practices. The HMC senior leadership left no page unturned in the training of the team members, which is exemplified by the various international courses and workshops they were supported to attend to master the art of ECMO. Members of the team attended: ■ ECMO simulation course at GSTT ■ Cadaveric ECMO course in Charite Hospital (Berlin) ■ Residential hands-on training in London In addition, selected stakeholders spent a short period of time at GSTT to observe their service and obtain more technical information to effectively set up the program. This investment was highly fruitful in the sense that various members of the team which included physicians, nurses, perfusionists, respiratory therapists, pharmacists, physiotherapist, nutritionists, critical care paramedics, and educators were able to take part and bring the knowledge and skills back in Qatar for the benefit of a whole region. The training was intended to provide each member with the whole repertoire of knowledge so as to help in the smooth gelling and functioning of the team, which could produce optimum results within the minimal timeframe and with the resources then available. The physicians were provided with all the resources to master the relevant knowledge in quality and research, and were given the best training for cannulation. They were also provided with the knowledge of the anticipated problems that could arise during the procedure and during the retrieval and transport of ECMO patients. The most important part of the documentation and guidelines were mastered by the very skillful team that included consultants, specialists, and fellows from the MICU. The nurses in the team, who form an integral part in the success of the procedure and process, were trained as ECMO specialist nurses with the responsibility of ensuring that all were functioning well with the help of checklists, protocols, and guidelines. They also have an important role in training other nurses in the MICU about the techniques and processes involved in this complex lifesaving procedure. They were also provided with the Sheikh Khalifa Medical City (SKMC, Abu Dhabi) nurses training program to further enhance their clinical skills. The respiratory specialists in the team were given training in pre-ECMO management and positive end expiratory pressure (PEEP) optimization along with the other important procedures like positioning in ECMO, recruitment maneuvers, and ventilation in ECMO. The perfusionists were given training in all the technical aspects of the circuit and its interaction with the patient throughout the various phases of ECMO. The pharmacists were trained with all the potential drug interactions in the ECMO patient interface and were given the responsibility of reviewing all the protocols for the drugs used by the GSTT team. The physiotherapists were given training in the positioning of the patient (which can be tricky especially when they are prone) and were given the all-important jobs of resuming mobilization and exercise training of the patients while still on ECMO. Further, they were given special training in chest physiotherapy in patients who were on ECMO, which can be very challenging, given the technology involved. The nutritionists in the team were responsible for the total parenteral nutrition (TPN) and the interactions with the circuits. They further were given training in enteral feeding in ECMO, which reduces the complications and the morbidity in patients who undergo successful decannulation. The Critical Care Paramedics play an essential role in the mobile retrieval capabilities of the program, including the road map plan for activation and deployment of the team. In our case, they had crucial input into the design of the ECMO and ambulance trolley. The educator integrated all the knowledge and skills to maintain the competency of the team, from simple water drills all the way to advanced simulation-based competency assessment. Up-to-date cases: The first patient was admitted to the SRF-ECMO service in May 2014 with H1N1 pneumonia and successfully discharged from the hospital after 3 weeks of ECMO therapy. Since then, the SRF-ECMO service has treated 50 patients with a survival rate of 66% in total. Of these patients, 25% were trauma cases. Additionally, the SRF-ECMO service has also started its retrieval arm, moving patients from other hospitals in Qatar to the SRF-ECMO Center following cannulation and placing the patient on ECMO, 11 retrievals have been undertaken with one patient dying before transport. Additionally, two patients have been transferred with ECMO to the Heart Hospital for Cardiothoracic Surgery (severe PE and thoracic trauma with bronchial tear) and one patient has been successfully repatriated on ECMO to India using our own aeromedical ECMO transfer team. Summary: The Qatar SRF-ECMO program is one of the few programs worldwide that operates to the highest level and has been developed in less than 6 months. This has only been possible thanks to the enormous support of the leadership, dedication of the multidisciplinary team, and the partnership with an experienced center such as Guys and St Thomas’ NHS Foundation Trust.

Addressing the challenges of ECMO simulation

Introduction/Aim: The patient’s condition and high-risk nature of extracorporeal membrane oxygenation (ECMO) therapy force clinical services to ensure clinicians are properly trained and always ready to deal effectively with critical situations. Simulation-based education (SBE), from the simplest approaches to the most immersive modalities, helps promote optimum individual and team performance. The risks of SBE are negative learning, inauthenticity in learning and over-reliance on the participants’ suspension of disbelief. This is especially relevant to ECMO SBE as circuit/patient interactions are difficult to fully simulate without confusing circuit alterations. Methods: Our efforts concentrate on making ECMO simulation easier and more realistic in order to reduce the current gap there is between SBE and real ECMO patient care. Issues to be overcome include controlling the circuit pressures, system failures, patient issues, blood colour and cost factors. Key to our developments are the hospital-university collaboration and research funding. Results: A prototype ECMO simulator has been developed that allows for realistic ECMO SBE. The system emulates the ECMO machine interface with remotely controllable pressure parameters, haemorrhaging, line chattering, air bubble noise and simulated blood colour change. Conclusion: The prototype simulator allows the simulation of common ECMO emergencies through innovative solutions that enhance the fidelity of ECMO SBE and reduce the requirement for suspension of disbelief from participants. Future developments will encompass the patient cannulation aspect.

Qatar ECMO program: Past, present, and future

The clarion call for setting up a Qatar adult extracorporeal membrane oxygenation (ECMO) program came during the MERS-CoV outbreak in the Arabian Peninsula region. 1 This carried a high mortality rate in those presenting with severe respiratory failure, and recent data from the “CESAR Trial” showed that treatment in a severe respiratory failure center with ECMO capabilities improved severe respiratory failure (SRF) patient survival. 2 Owing to the regional novelty of the program, potential partners of external well-established ECMO programs were sought. The model of care hinged on medical versus surgical ECMO delivery. The balance tipped in favor of a medical model in view of the prevailing nature of the pandemic outbreak at the time. There is plenty of evidence demonstrating that the intensivist-led ECMO cannulation model is safe. 3 The commissioning body also favored the notion of a severe respiratory failure outreach and retrieval service, delivered round-the-clock with the provision of on-site cannula...

Acute respiratory failure: From intubation to ECMO

Introduction: Acute severe respiratory failure poses a major treatment challenge which stubbornly carries high mortality and morbidity rates. Here, we review PaO2/FiO2 (PF) ratio and disease severity, and discuss protective lung ventilation and the rescue therapies, and when to use what? PF ratio alone is not sufficient to determine disease severity: A recent study by Villar and colleagues demonstrated that only 38% of patients who were classified as severe acute respiratory disease syndrome (ARDS) patients based on the PF ratio met the actual severe ARDS criteria after a standardized ventilator setting. In a recent trial conducted by Caironi 1 and colleagues, alteration in the positive end-expiratory pressure (PEEP) level affected the PF ratio and disease severity. Using the PF ratio alone as the major determinant for disease severity will increase the risk of selecting the wrong therapy for the patient. Protective lung ventilation: Between 1998 and 2000, two prospective randomized controlled trials (RCT...

ECMO for a polytrauma patient without systemic anticoagulation

Background: ECMO has been successfully used to support patients with trauma-induced respiratory failure. Here, we present the successful application of ECMO in a patient with life-threatening polytrauma following a road traffic accident complicated by severe acute respiratory failure. 1 Methods: This is a retrospective case report, and approval for presentation has been obtained from the department and can be submitted upon request. The patient was 20 years old and found at the roadside after being hit by a vehicle. The patient was rushed into the ED by an ambulance, where the trachea was intubated due to the low Glasgow Coma Score. A trauma CT scan revealed severe head injury with possible diffuse axonal injury. The scan also confirmed fractures of the mandible, left transfers process of L3,4,5 and first sacral vertebrae, pelvis and comminuted fracture of the right tibia and fibula. The patient was admitted to the Trauma Intensive Care Unit (TICU). A subsequent head CT scan showed multiple hemorrhagic co...