Legionella infections have a propensity for occurring in HIV-infected individuals, with immunosuppressed individuals tending to present with more severe disease. However, understanding regarding the Legionella host response in immune compromised individuals is lacking. This study investigated the inflammatory profiles associated with Legionella infection in patients hospitalized with HIV and pneumonia in Medellín, Colombia from February 2007 to April 2014, and correlated these profiles with clinical outcomes. Sample aliquots from the Colombian cohort were shipped to Canada where Legionella infections and systemic cytokine profiles were determined using real-time PCR and bead-based technology, respectively. To determine the effect of Legionella coinfection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella-positive and -negative individuals. Principal component analysis revealed higher plasma concentrations of eotaxin, IP-10 and MCP-1 (p = 0.0046) during Legionella infection. Individuals with this immune profile also had higher rates of intensive care unit admissions (adjusted relative risk 1.047 [95% confidence interval 1.027–1.066]). Results demonstrate that systemic markers of monocyte/macrophage activation and differentiation (eotaxin, MCP-1, and IP-10) are associated with Legionella infection and worse patient outcomes. Further investigations are warranted to determine how this cytokine profile may play a role in Legionella pneumonia pathogenesis or immunity.

Background:Ventilator-induced lung injury (VILI) can occur as a result of mechanical ventilation to two lungs. Thoracic surgery often requires one-lung ventilation (OLV). The potential for VILI is likely higher in OLV. The impact of OLV on development of post-operative pulmonary complications is not well understood. We aimed to perform a scoping review to determine reliable biomarkers of VILI after OLV. Methods:A scoping review was performed using Cochrane Collaboration methodology. We searched Medline, EMBASE and SCOPUS. Gray literature was searched. Studies of adult human or animal models without pre-existing lung damage exposed to OLV, with biomarker responses analyzed were included. Results:After screening 5,613 eligible papers, 89 papers were chosen for full text review, with 29 meeting inclusion. Approximately half (52%, n=15) of studies were conducted in humans in an intra-operative setting. Bronchoalveolar lavage (BAL) & serum analyses with enzyme-linked immunosorbent assay (ELISA)-based assays were most commonly used. The majority of analytes were investigated by a single study. Of the analytes that were investigated by two or more studies (n=31), only 16 were concordant in their findings. Across all sample types and studies 84% (n=66) of the 79 inflammatory markers and 75% (n=6) of the 8 anti-inflammatory markers tested were found to increase. Half (48%) of all studies showed an increase in TNF-α or IL-6. Conclusions:A scoping review of the state of the evidence demonstrated that candidate biomarkers with the most evidence and greatest reliability are general markers of inflammation, such as IL-6 and TNF-α assessed using ELISA assays. Studies were limited in the number of biomarkers measured concurrently, sample size, and studies using human participants. In conclusion these identified markers can potentially serve as outcome measures for studies on OLV.

BackgroundCongenital heart disease is the most common congenital birth defect and presents with differing degrees of complexity. Patients require lifelong specialized care. The transfer from paediatric to adult care is a time of risk that may result in lapses or loss of care. A successful transfer from paediatric to adult care is integral for improved patient outcomes.MethodsIn this retrospective study, we used the paediatric cardiology database and the electronic records at the adult congenital heart disease (ACHD) clinic to identify referrals and successful transfer between 2008 and 2017. Successful transfer was defined as a patient referred to the ACHD clinic who was seen in the clinic and has ongoing follow-up. We also sought to identify predictors of a successful transfer.ResultsA total of 555 patients were referred to the ACHD clinic (2008-2017). Of all patients referred, 62% had a successful transfer and an ongoing specialist care. The remaining 38% either did not show for first appointments or missed 3 consecutive visits. Independent predictors of a successful transfer were the presence of moderate or complex ACHD, residing within the city limits, older age at the time of referral, and a more recent year of referral.ConclusionsOver one-third of patients did not achieve successful transfer, namely attendance at first clinic visit plus early retention in care. We were able to identify several variables that predict successful transfer. Further research is required to identify interventions that can be implemented to reduce lapses in patient care.

A 62-year-old man with a history of stable ischemic heart disease presented to the emergency room with nausea, vomiting, and chest pain at rest. The chest pain was atypical in nature; it did not respond to nitroglycerin and did not worsen with exertion. He took only aspirin, metoprolol, and ramipril at home. The patient was normotensive and normoxemic. Serial high-sensitivity troponin test results were normal, and other bloodwork (including calcium and magnesium levels) was unremarkable, with the exception of a serum potassium level of 2.4 mmol/L. His presenting electrocardiogram (ECG; Fig. 1A ) showed sinus rhythm with a right bundle branch block and a mildly prolonged QTc interval (450 msec using Bazett’s formula1Bazett H. An analysis of the time-relations of electrocardiograms.Heart. 1920; 7: 353-370Google Scholar). However, conduction delays prolong the QRS interval, which affects the length of the QT interval without significant impact on the repolarization duration. Bogossian’s formula can correct the QTc interval in the presence of bundle branch blocks, and this yielded a normal QTc interval of 302 msec.2Bogossian H. Linz D. Heijman J. et al.QTc evaluation in patients with bundle branch block.Int J Cardiol Heart Vasc. 2020; 30: 100636PubMed Google ScholarFigure 1Electrocardiogram showing (A) sinus rhythm with a right bundle branch block (bbb) and mildly prolonged QTc interval; (B) ST changes with profound QTc interval prolongation; and (C) partial resolution of the ST changes.View Large Image Figure ViewerDownload Hi-res image Download (PPT) During his time in the emergency room, he experienced nausea and was given 4 mg of ondansetron intravenously. He was also given 40 mmol of KCl orally for his hypokalemia. Fifteen minutes later, the patient had a mild recurrence of atypical chest discomfort at rest, and another ECG Fig. 1B) was performed. This showed nonspecific ST changes with profound QTc interval prolongation, using both Bogossian’s formula (562 msec) and Bazett’s formula (628 msec). In addition to QTc interval prolongation, there was a dramatic difference in T wave morphology, including prolongation of the Tpeak–Tend interval. Ten minutes later, an ECG (Fig. 1C) and blood work were repeated, which showed a serum potassium level of 3 mmol/L, and partial resolution of the ST changes. The patient was not given any further QT-prolonging medication, and he was subsequently diagnosed with noncardiac chest pain after undergoing normal stress myocardial perfusion imaging. Severe hypokalemia is a known cause of QT interval prolongation.3Yelamanchi V.P. Molnar J. Ranade V. Somberg J.C. Influence of electrolyte abnormalities on interlead variability of ventricular repolarization times in 12-lead electrocardiography.Am J Ther. 2001; 8: 117-122Crossref PubMed Scopus (35) Google Scholar However, this patient’s initial ECG demonstrates a normal (by Bogossian’s formula) or only modestly prolonged (by Bazett’s formula) QTc interval. Subsequent administration of IV ondansetron resulted in profound transient QTc interval prolongation relative to this patient’s baseline, and marked changes in T wave morphology. It has been previously described that intravenous ondansetron administration can lead to QT interval prolongation and T wave changes. Our patient had a history of ischemic heart disease; the presence of structural heart disease increases the risk for acquired QT interval prolongation. Such prolongations of the QTc and Tpeak–Tend intervals are associated with increased risk of Torsades de Pointes and sudden cardiac death, with the risk increasing proportionally to QTc interval duration.4Thomas S. Behr E. Pharmacologic treatment of acquired QT prolongation and torsades de pointe.Br J Clin Pharmacol. 2016; 81: 420-427Crossref PubMed Scopus (67) Google Scholar, 5Hafermann M. Namdar R. Seibold G. et al.Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study.Drug Healthc Patient Saf. 2011; 3: 53-58PubMed Google Scholar, 6Tse G. Gong M. Meng L. et al.Predictive value of Tpeak-Tend indices for adverse outcomes on acquired QT prolongation: a meta-analysis.Front Physiol. 2018; 9: 1226Crossref PubMed Scopus (18) Google Scholar These images demonstrate the importance of cautious administration of QT interval–prolonging medications, particularly in the presence of other risk factors for QT interval prolongation such as hypokalemia and underlying structural heart disease, even if the baseline QTc interval is not markedly prolonged.Novel Teaching Points•Proper assessment of the QT interval is important in the setting of a bundle branch block, as widening of the QRS will cause subsequent QT interval prolongation without significant impact on the duration of repolarization.•Bogossian’s formula is an alternative method for calculating the QT interval in the setting of a bundle branch block. However, no single formula is perfect for QTc interval calculation in every situation.•Caution is needed when prescribing medications that prolong the QT interval, especially for patients with an underlying predilection for QT interval prolongation. The authors have no funding sources to declare.

We present the case of a 16-year-old patient with anomalous left coronary artery from the left pulmonary artery requiring percutaneous coronary intervention in infancy who presented with ventricular fibrillation arrest. A coronary angiogram revealed 40% narrowing of the stent relative to the remainder of the left main coronary artery. Optical coherence tomography was performed and revealed an area stenosis of 70% relative to the native left main coronary artery. The patient had outgrown the stent. (Level of Difficulty: Advanced.)

Prior studies have shown that HIV patients develop permanent pulmonary dysfunction following an episode of community-acquired pneumonia (CAP). However, the mechanism causing pulmonary dysfunction remains an enigma. HIV patients experience chronic inflammation. We hypothesized that CAP exacerbates inflammation in HIV patients resulting in an accelerated decline in lung function. A prospective cohort pilot study enrolled HIV patients hospitalized in Medellin, Colombia, with a diagnosis of CAP. Sixteen patients were eligible for the study; they were split into 2 groups: HIV and HIV+CAP. Plasma, sputum, and pulmonary function test (PFT) measurements were retrieved within 48h of hospital admission and at 1 month follow-up. The concentrations of 13 molecules and PFT values were compared between the 2 cohorts. The HIV+CAP group had lower lung function compared to the HIV group; forced vital capacity (FVC)% predicted and forced expiratory volume in 1s (FEV1)% predicted decreased, while FEV1/FVC remained constant. APRIL, BAFF, CCL3, and TIMP-1 correlated negatively with FVC% predicted and FEV1% predicted; the relationships however were moderate in strength. Furthermore, the concentrations of BAFF, CCL3, and TIMP-1 were statistically significant between the 2 groups (P <= 0.05). Our results indicate that HIV patients with CAP have a different inflammatory pattern and lower lung function compared to HIV patients without CAP. BAFF, CCL3, and TIMP-1 were abnormally elevated in HIV patients with CAP. Future studies with larger cohorts are required to verify these results. In addition, further investigation is required to determine if BAFF, CCL3, and TIMP-1 play a role in the process causing pulmonary dysfunction.

HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.

Abstract Background HIV patients face higher rates of morbidity compared with the general population, largely due to the earlier development of age related diseases (cardiovascular, kidney, and liver disease). While it is likely that chronic immune activation and inflammation are the main contributors to this process, it’s relation to lung injury in HIV remains unknown. Despite restoration of systemic immune function following Antiretroviral Therapy, the risk for lower respiratory tract infection remain elevated in the HIV population. The objective of the study was to assess the relationship between pulmonary inflammation and lung injury. Methods A prospective cohort study was performed, participants include patients hospitalized in Hospital Universitario San Vicente Fundación and Clínica SOMA, in Colombia. Patients were eligible if they were over the age of 18 and had a documented HIV infection or if they have HIV with newly diagnosed community acquired pneumonia (CAP). The main exclusion criteria were chronic lung disease and immunosuppression that is not due to HIV. Patients belonged to two groups: HIV and HIV + CAP. Plasma, sputum samples and pulmonary function test measurements (PFT) were retrieved within 48 hours of hospital admission and at one month follow-up. The concentrations of 13 biomarkers were measured and correlated with PFT values, followed by a comparison between the two groups. Results Principle Component Analysis revealed that CCL3, CCL4, BAFF, APRIL, and TIMP-1 accounts for the majority of the variation between the two groups. Furthermore, Kruskal–Wallis testing demonstrates that BAFF and CCL3 are elevated in the HIV + CAP group, compared with the HIV group (P < 0.005). Other markers of bacterial translocation and monocyte activation did not differ between these groups. FVC and FEV1 measurements are lower in the HIV + CAP group compared with the HIV group, while FEV1/FVC remain constant. Conclusion The results of this study identify a unique constellation of biomarkers in HIV patients with CAP, this constellation of biomarkers consists of pro-inflammatory cytokines and regulators of extracellular matrix remodeling, hinting at the occurrence of an inflammatory and tissue injuring process in the lungs. This is supported by the restrictive ventilation pattern seen in this group of patients. Disclosures All authors: No reported disclosures.