Igor Barjaktarevic

Organizing Pneumonia as a Side Effect of Ipilimumab Treatment of Melanoma

Ipilimumab is one of the newly developed human monoclonal antibodies used in the treatment of metastatic melanoma. Its primary mechanism of action is a specific blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a T-cell receptor responsible for inhibition of lymphocyte activation. By blocking CTLA-4, ipilimumab enhances immune responses against tumor cells, but also exposes normal tissues to an increased risk of autoimmune phenomena as a potential side effect. In this report, we describe the case of a 58-year-old woman with metastatic melanoma who was treated with ipilimumab in the weeks prior to the onset of severe nonresolving dyspnea and cough. Extensive workup revealed organizing pneumonia as the cause of her hypoxemic respiratory failure and treatment with steroids led to a resolution of her pulmonary disease. To our knowledge, this is the first report of pulmonary toxicity caused by ipilimumab, which manifested on pathology as organizing pneumonia.

Bronchoscopic Intubation During Continuous Nasal Positive Pressure Ventilation in the Treatment of Hypoxemic Respiratory Failure

Endotracheal intubation is difficult in patients with hypoxemic respiratory failure who deteriorate despite treatment with noninvasive positive pressure ventilation (NIPPV). Maintaining NIPPV during intubation may prevent alveolar derecruitment and deterioration in gas exchange. We report a case series of 10 nonconsecutive patients with NIPPV failure who were intubated via a flexible bronchoscope during nasal mask positive pressure ventilation. All 10 patients were intubated in the first attempt. Hypotension was the most frequent complication (33%). Mean decrease in oxyhemoglobin saturation during the procedure was 4.7 ± 3.1. This method of intubation may extend the benefits of preoxygenation throughout the whole process of endotracheal intubation. It requires an experienced operator and partially cooperative patients. A prospective trial is necessary to determine the best intubation method for NIPPV failure.

Transition from Hepatopulmonary Syndrome to Portopulmonary Hypertension: A Case Series of 3 Patients

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are the two major pulmonary vascular complications of liver disease. While HPS is characterized by low pulmonary vascular resistance, PPHTN is defined by the presence of elevated pulmonary vascular resistance. Given these seemingly opposing pathophysiologic mechanisms, these conditions were traditionally felt to be mutually exclusive. In this series, we present three patients with severe hepatopulmonary syndrome who had spontaneous resolution of their HPS with the subsequent development of PPHTN. To our knowledge, this is the largest case series presented of this phenomenon in nontransplanted patients. One proposed mechanism for the occurrence of this phenomenon involves dysregulation of the same vascular signaling pathway, which may lead to both pulmonary vascular dilatations and pulmonary arterial remodeling in the same patient. Another theory involves the possible differential binding of endothelin-1, a vasoactive signaling peptide that induces vasoconstriction when bound to receptor A and vasodilation when bound to receptor B. Although the mechanisms for this phenomenon remain unclear, it is important to be vigilant of this phenomenon as it may change the patients overall treatment plan, especially in regard to appropriateness and timing of liver transplant.

Positioning new pharmacotherapies for COPD.

COPD imposes considerable worldwide burden in terms of morbidity and mortality. In recognition of this, there is now extensive focus on early diagnosis, secondary prevention, and optimizing medical management of the disease. While established guidelines recognize different grades of disease severity and offer a structured basis for disease management based on symptoms and risk, it is becoming increasingly evident that COPD is a condition characterized by many phenotypes and its control in a single patient may require clinicians to have access to a broader spectrum of pharmacotherapies. This review summarizes recent developments in COPD management and compares established pharmacotherapy with new and emerging pharmacotherapies including long-acting muscarinic antagonists, long-acting β-2 sympathomimetic agonists, and fixed-dose combinations of long-acting muscarinic antagonists and long-acting β-2 sympathomimetic agonists as well as inhaled cortiocosteroids, phosphodiesterase inhibitors, and targeted anti-inflammatory drugs. We also review the available oral medications and new agents with novel mechanisms of action in early stages of development. With several new pharmacological agents intended for the management of COPD, it is our goal to familiarize potential prescribers with evidence relating to the efficacy and safety of new medications and to suggest circumstances in which these therapies could be most useful.

Diffusing Capacity for Carbon Monoxide Correlates Best With Tissue Volume From Quantitative CT Scanning Analysis

BACKGROUND Quantitative analysis of high-resolution chest CT scan (QCT) is an established method for determining the severity and distribution of lung parenchymal destruction inpatients with emphysema. Diffusing capacity of the lung for carbon monoxide (D(LCO)) is a traditional physiologic measure of emphysema severity and is probably influenced more by destruction of the alveolar capillary bed than by membrane diffusion per se. We reasoned that D(LCO) should correlate with tissue volume from QCT. METHODS A total of 460 patients with upper-lobe-predominant emphysema were enrolled in the study. Th e mean (SD) of percent predicted values for FEV 1 , total lung capacity, and D(LCO) were 30.6% (8.0%), 129.5% (18.1%), and 6.7% (13.1%), respectively. QCT was performed using custom soft ware; the relationship between D(LCO) and various metrics from QCT were evaluated using Pearson correlation coefficients. RESULTS On average, whole-body plethysmography volumes were higher by 841 mL compared with QCT-calculated total lung volume. However, there was a strong correlation between these measurements (r=0.824, P < .0001). D(LCO) correlated with total lung volume (r=0.314, P<.0001), total tissue volume (r=0.498, P<.0001), and percentage of lung with low density (-950 Hounsfield units) (r=-0.337, P<.0001). CONCLUSIONS In patients with severe emphysema, D(LCO) correlates best with total tissue volume,supporting the hypothesis that pulmonary capillary blood volume is the main determinant of D(LCO) in the human lung. Th e relationships between D(LCO) and various anatomic metrics of lung parenchymal destruction from QCT inform our understanding of the relationship between structure and function of the human lung.

Reduced COPD Exacerbation Risk Correlates With Improved FEV1: A Meta-Regression Analysis

BACKGROUND: The mechanism by which various classes of medication reduce COPD exacerbation risk remains unknown. We hypothesized a correlation between reduced exacerbation risk and improvement in airway patency as measured according to FEV1. METHODS: By systematic review, COPD trials were identified that reported therapeutic changes in predose FEV1 (dFEV1) and occurrence of moderate to severe exacerbations. Using meta‐regression analysis, a model was generated with dFEV1 as the moderator variable and the absolute difference in exacerbation rate (RD), ratio of exacerbation rates (RRs), or hazard ratio (HR) as dependent variables. RESULTS: The analysis of RD and RR included 119,227 patients, and the HR analysis included 73,475 patients. For every 100‐mL change in predose FEV1, the HR decreased by 21% (95% CI, 17‐26; P < .001; R2 = 0.85) and the absolute exacerbation rate decreased by 0.06 per patient per year (95% CI, 0.02‐0.11; P = .009; R2 = 0.05), which corresponded to an RR of 0.86 (95% CI, 0.81‐0.91; P < .001; R2 = 0.20). The relationship with exacerbation risk remained statistically significant across multiple subgroup analyses. CONCLUSIONS: A significant correlation between increased FEV1 and lower COPD exacerbation risk suggests that airway patency is an important mechanism responsible for this effect.

Ultrasound-Guided Cannulation: Time to Bring Subclavian Central Lines Back.

Despite multiple advantages, subclavian vein (SCV) cannulation via the traditional landmark approach has become less used in comparison to ultrasound (US) guided internal jugular catheterization due to a higher rate of mechanical complications. A growing body of evidence indicates that SCV catheterization with real-time US guidance can be accomplished safely and efficiently. While several cannulation approaches with real-time US guidance have been described, available literature suggests that the infraclavicular, longitudinal “in-plane” technique may be preferred. This approach allows for direct visualization of needle advancement, which reduces risk of complications and improves successful placement. Infraclavicular SCV cannulation requires simultaneous use of US during needle advancement, but for an inexperienced operator, it is more easily learned compared to the traditional landmark approach. In this article, we review the evidence supporting the use of US guidance for SCV catheterization and discuss technical aspects of the procedure itself.

Bronchoscopic intubation is an effective airway strategy in critically ill patients.

Purpose: American Society of Anesthesiologists guidelines recommend the use of bronchoscopic intubation as a rescue technique in critically ill patients. We sought to assess the safety and efficacy of bronchoscopic intubation as an initial approach in critically ill patients. Methods: We performed a retrospective cohort study of patients who underwent endotracheal intubation in the medical intensive care unit of a tertiary urban referral center over 1 academic year. The primary outcome was first‐pass success rate. Measurements and main results: We identified 219 patients who underwent either bronchoscopic (n = 52) or laryngoscopic guided (n = 167) intubation as the initial attempt. There was a higher first‐pass success rate in the bronchoscopic intubation group than in the laryngoscopic group (96% vs 78%; P = .003). The bronchoscopic intubation group had a higher body mass index (28.4 vs 25.9; P = .027) and higher preintubation fraction of inspired oxygen requirement (0.73 ± 0.27 vs 0.63 ± 0.30; P = .044) than the laryngoscopic group. There were no cases of right mainstem intubation, esophageal intubation, or pneumothorax with bronchoscopic intubation. Rates of postintubation hypotension and hypoxemia were similar in both groups. The association with first‐pass success remained with multivariate and propensity matched analysis. Conclusions: Bronchoscopic intubation as an initial strategy in critically ill patients is associated with a higher first‐pass success rate than laryngoscopic intubation, and is not associated with an increase in complications.

Catheter-directed clot fragmentation using the Cleaner™ device in a patient presenting with massive pulmonary embolism

Massive pulmonary embolism not amenable to systemic thrombolysis is a therapeutic challenge. Catheter directed clot fragmentation and thrombolysis have been efficacious in this setting. We describe successfully treating a massive pulmonary embolism with catheter-directed thrombolysis and clot fragmentation using local tPA, aspiration, and the Cleaner™ device in a patient with an absolute contraindication to systemic thrombolysis.

Primary salivary duct carcinoma of the lung, mucin-rich variant.

Primary salivary gland-type lung cancer is a heterogeneous group of neoplasms arising from the seromucinous glands of the respiratory tract. Histopathologically, they are identical to salivary gland neoplasms of the head and neck. While mucoepidermoid carcinoma and adenoid cystic carcinoma are overwhelmingly the most common subtypes found in the lung, reports of uncommon subtypes can be found in the literature. We report a case of a 73-year-old woman with primary lung salivary duct carcinoma, mucin-rich variant--an exceedingly rare subtype of an already rare malignant salivary-type neoplasm. One case of primary lung salivary duct carcinoma has been reported in the literature; however, the mucin-rich variant has never been described in the lung. Furthermore, the tumor in our case bears a rare BRAF G464V mutation. To our knowledge, this is the first reported case of a BRAF G464V mutation detected in a salivary duct carcinoma or any other salivary-type neoplasm.