Patterns and predictors of positive multiplex polymerase chain reaction respiratory panel among patients with acute respiratory infections in a single center in Lebanon.

BACKGROUND: Infectious agents associated with community-acquired acute respiratory infections (ARIs) remain understudied in Lebanon. We aim to assess the microbiological profiles of ARIs by employing polymerase chain reaction (PCR) and identifying predictors of positive PCR results among patients admitted for ARI. METHODS AND RESULTS: We conducted a retrospective single-center study at the American University of Beirut Medical Center, including all respiratory PCR panels performed on pediatric (< 18) and adult (≥ 18) patients presenting with an ARI from January 2015 to March 2018, prior to the onset of the COVID-19 pandemic. We aimed to identify the epidemiological patterns of ARIs and the factors associated with positive PCRs in both adult and pediatric patients. Among 281 respiratory PCRs, 168 (59.7%) were positive for at least one pathogen, with 54.1% positive PCR for viruses, 7.8% for bacteria species, and 3.9% with virus-bacteria codetection. Almost 60% of the patients received antibiotics prior to PCR testing. PCR panels yielded more positive results in pediatric patients than in adults (P = 0.005). Bacterial detection was more common in adults compared to pediatrics (P < 0.001). The most common organism recovered in the entire population was Human Rhinovirus (RhV) (18.5%). Patients with pleural effusion on chest CT were less likely to have a positive PCR (95% Cl: 0.22-0.99). On multivariate analysis, pediatric age group (P < 0.001), stem cell transplant (P = 0.006), fever (P = 0.03) and UTRI symptoms (P = 0.004) were all predictive of a positive viral PCR. CONCLUSION: Understanding the local epidemiology of ARI is crucial for proper antimicrobial stewardship. The identification of factors associated with positive respiratory PCR enhances our understanding of clinical characteristics and potential predictors of viral detection in our population.

A Framework for the Development of Living Practice Guidelines in Health Care.

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication. LIMITATION: This study does not provide detailed or practical guidance for how the described concepts would be best implemented. CONCLUSION: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines. PRIMARY FUNDING SOURCE: None.

Clinical and genetic characteristics of pulmonary arterial hypertension in Lebanon.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an incidence rate of 2-6 cases per million per year. Our knowledge of the disease in the Middle East and North Africa (MENA) region is limited by the small number of clinical studies and the complete absence of genetic studies. METHODS: Our aim was to shed light on the clinical and genetic characteristics of PAH in Lebanon and the region by using exome sequencing on PAH patients referred to the American University of Beirut Medical Center (AUBMC). Twenty-one idiopathic, hereditary and Congenital Heart Disease (CHD) PAH patients were prospectively recruited, their clinical data summarized, and sequencing performed. RESULTS: The mean age at diagnosis was 33 years with a female preponderance of 70%. The mean pulmonary artery pressure at the time of diagnosis was 55. Genetic testing showed that 5 out of 19 idiopathic and Congenital Heart Disease PAH patients had Bone Morphogenetic Protein Receptor 2 (BMPR2) mutations at 25% prevalence, with 2 of these patients exhibiting a novel mutation. It also showed the presence of 1 BMPR2 mutation with 100% penetrance in a heritable PAH family. In the remaining cases, the lack of a complete genotype/phenotype correlation entailed a multigenic inheritance; suspected interactions involved previously associated genes T-box transcription factor 4 (TBX4), Bone Morphogenic Protein 10 (BMP10) and Growth Differentiation Factor 2 (GDF2). CONCLUSIONS: This is the first study that looks into the genetic causes of PAH, including known and new BMPR2 mutations, in the MENA region. It is also the first study to characterize the clinical features of the disease in Lebanon.

Ventilator auto-cycling from cardiogenic oscillations: case report and review of literature.

BACKGROUND: Brain death is the total loss of all brain and brain stem functions, and its diagnosis is often confirmed by an apnoea test, which relies on disconnecting the patient from the ventilator. Auto-triggering or auto-cycling is defined as a ventilator being triggered in the absence of patient effort, intrinsic respiratory drive or inspiratory muscle activity. Ventilator auto-triggering could delay the diagnosis of brain death leading to unnecessary admission for the patient and false hopes of recovery for the family. METHODS: We report a case of ventilator auto-triggering associated with cardiogenic oscillations in a female patient. RESULTS: We confirmed the finding of ventilator auto-triggering by changing the patient's position and reassessing the triggering thresholds. Brain death was then confirmed by apnoea test. CONCLUSION: This case is presented to arouse the awareness of the medical staff and nurses to this phenomenon, which can mimic an intrinsic respiratory effort in patients allegedly diagnosed with brain death. Along with this case report, we review the English language publications for similar cases.

Weaning from mechanical ventilation.

PURPOSE OF REVIEW: Liberation from mechanical ventilation is a defining moment for intubated patients, and thus a critical clinical decision. Extubating the patient too early exposes the patient to extubation failure and reintubation. Waiting too long increases the complications of prolonged intubation. Tools to help the physician with this critical decision and to test readiness have been available for decades, and are continuously being improved. New methods to improve extubation outcomes are also being developed. This review covers the latest studies in order to help physicians take advantage of the latest developments in a rapidly evolving field. RECENT FINDINGS: This review highlights the recent advances in assessing and testing for readiness of weaning and liberation from mechanical ventilation, the cause of weaning failure, the value of weaning protocols, and the role of noninvasive positive pressure ventilation in liberating patients from invasive mechanical ventilation. SUMMARY: Recent findings are shedding more light on this topic, and transforming 'the artistic' aspect of weaning and liberation from mechanical ventilation into a more 'scientific' approach that will expedite liberation from mechanical ventilation yet without encountering high failure rates, and without exposing patients to unnecessary risks.

Black Urine and Methemoglobinemia in the Setting of Sepsis Due to Clostridium Perfringens.

Clostridium Perfringens is an anaerobic gram-positive bacillus able to produce different types of toxins and can cause septicemia. The mechanism is through translocation from a previously colonized gastrointestinal or genital tract. Massive intravascular hemolysis induced by this bacterium is a rare presentation reported in only 7% to 15% of cases of Clostridium Perfringens bacteremia with a mortality rate reaching 90%.We present the case of a middle-aged man with metastatic melanoma having black-colored urine as the first sign of massive hemolysis along with mild methemoglobinemia. Despite timely management, the patient progressed into septic shock with severe hypoxia and passed away. Postmortem, blood cultures grew clostridium perfringens. Black-colored urine and blood samples, sepsis-induced mild methemoglobinemia and acute massive hemolysis should raise concern for Clostridium Perfringens sepsis in the appropriate clinical settings.

Comparison of the Oxygenation Factor and the Oxygenation Ratio in Subjects With ARDS.

BACKGROUND: The oxygenation ratio (ie, [Formula: see text]/[Formula: see text]) remains the most commonly used index for assessing oxygenation and disease severity in patients with acute ARDS. However, the oxygenation ratio does not account for mechanical ventilation settings. We hypothesized that the oxygenation factor (ie, oxygenation ratio/mean airway pressure) is superior to the oxygenation ratio in reflecting oxygenation in patients with ARDS and results in a different classification of ARDS severity. METHODS: In 150 subjects with ARDS (50 severe, 50 moderate, and 50 mild), arterial blood gas, mean airway pressure, static lung compliance, driving pressure, and mechanical power were obtained. The oxygenation ratio and the oxygenation factor were then calculated. Receiver operating characteristic curves were constructed for oxygenation ratio and oxygenation factor at lung compliance > 40 mL/cm H2O, driving pressure < 15 cm H2O, and mechanical power < 17 J/min, thresholds that are known to predict survival in patients with ARDS. Subjects were reclassified for ARDS severity on the basis of the oxygenation factor and compared to classification on the basis of the oxygenation ratio. RESULTS: Areas under the receiver operating characteristic curves for the oxygenation factor were significantly higher than for the oxygenation ratio. Reclassification of ARDS severity using the oxygenation factor did not affect subjects classified as having severe ARDS per the oxygenation ratio. However, 52% of subjects with moderate ARDS per the oxygenation ratio criteria were reclassified as either severe (25 subjects) or mild ARDS (1 subject) on the basis of oxygenation factor criteria. Also, 54% of subjects with mild ARDS per the oxygenation ratio criteria were reclassified as severe (4 subjects), moderate (21 subjects), or non-ARDS (2 subjects) on the basis of oxygenation factor criteria. CONCLUSIONS: The oxygenation factor was a superior ARDS oxygenation index compared to the oxygenation ratio and should be considered as a substitute criteria for classification of the severity of ARDS. (ClinicalTrials.gov registration NCT03946189.).

Transfusion-related Plasmodium ovale malaria complicated by acute respiratory distress syndrome (ARDS) in a non-endemic country.

46year old female presented with a one week history of high grade fever, chills, cough, and severe nausea. The patient had been admitted a month earlier with severe lower gastrointestinal bleeding from hemorrhoids necessitating transfusion of 7 units of packed red blood cells. Initial work-up was unremarkable. Because of persistent symptoms, the patient was admitted 2 days later. Malaria smear was positive. Due to the severity of her symptoms, she was managed as falciparum malaria and was started on intravenous quinine and oral doxycycline. On the second day of treatment the patient developed respiratory failure, requiring intubation and ventilatory support with new bilateral pulmonary infiltrates. Antimalarial treatment was continued for a total of 7 days followed by primaquine for 14 days once the blood smear results revealed Plasmodium ovale infection. The patient remained intubated in the intensive care unit (ICU) for 16 days, and was later extubated successfully with a clear chest x-ray after a total of one month hospitalization. To our knowledge, this is the first case of acute respiratory distress syndrome (ARDS) secondary to blood transfusion related P. ovale malaria infection in a non-endemic country.

Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release.

Macrophage responses to Francisella infection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. Therefore, we studied the ability of fresh human blood monocytes to engulf and respond to Francisella by using the live vaccine strain variant and Francisella novicida. Because Francisella organisms have been reported to escape from the phagolysosome into the cytosol, we hypothesized that this escape may trigger the activation of caspase-1. Francisella tularensis variants were readily taken up by fresh human CD14(+) monocytes, inducing the release of IL-1beta, as well as IL-8, in a time- and dose-dependent fashion. Importantly, whereas live and dead Escherichia coli, F. novicida, and live vaccine strain, as well as the LPS of E. coli, were able to induce abundant IL-1beta mRNA synthesis and intracellular pro-IL-1beta production, only live Francisella induced enhanced IL-1beta processing and release (51 +/- 10 vs. 7.1 +/- 2.1 ng/ml, for F. novicida vs. E. coli LPS; P = 0.0032). Cytochalasin D blocked the Francisella internalization and the Francisella-induced monocyte IL-1beta processing and release but not that induced by the exogenous stimulus E. coli LPS. Also, killing bacteria did not block uptake but significantly diminished the IL-1beta processing and release that was induced by Francisella. Blocking bacterial escape from the phagosome into the cytosol also decreased IL-1beta but not IL-8 release. These findings demonstrate that Francisella organisms efficiently induce IL-1beta processing and release in fresh monocytes by means of a sensing system that requires the uptake of live bacteria capable of phagosome escape.