Point-of-Care Echocardiography Unveils Misclassification of Acute Kidney Injury as Hepatorenal Syndrome.

INTRODUCTION: Fulfillment of the diagnostic criteria for -hepatorenal syndrome type 1 (HRS-1) requires prior failure of 2 days of intravenous volume expansion and/or diuretic withdrawal. However, no parameter of volume status is used to guide the need for volume expansion in patients with suspected HRS-1. We hypothesized that point-of-care echocardiography (POCE) may better characterize the volume status in patients with acute kidney injury (AKI) and cirrhosis to ascertain or disprove the diagnosis of HRS-1. METHODS: A pilot observational study was conducted to determine the clinical utility of POCE-based examination of inferior vena cava diameter (IVCD) and collapsibility index (IVCCI) to assess intravascular volume status in patients with cirrhosis and AKI who had been deemed adequately volume-repleted and thereby assigned a clinical diagnosis of HRS-1. Early improvement in kidney function was defined as ≥20% decrease in serum creatinine (sCr) at 48-72 h. RESULTS: A total of 53 patients were included. The mean sCr at the time of volume assessment was 3.2 ± 1.5 mg/dL, and the mean Model for End-Stage Liver Disease score was 29 ± 8. Fifteen (23%) patients had an IVCD <1.3 cm and IVCCI >40% and were reclassified as fluid-depleted, 11 (21%) had an IVCD >2 cm and IVCCI <40% and were reclassified as fluid-expanded, and 8 (15%) had and IVCD <1.3 cm and IVCCI <40% and were reclassified as having intra-abdominal hypertension (IAH). Twelve (23%) patients exhibited early improvement in kidney function following a POCE-guided therapeutic maneuver, that is, volume expansion, diuresis, or paracentesis for those deemed fluid-depleted, fluid-expanded or having IAH, respectively. CONCLUSION: POCE-based assessment of volume status in cirrhotic individuals with AKI reveals marked heterogeneity. Unguided volume expansion in these patients may lead to premature or delayed diagnosis of HRS-1.

Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis.

We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1) in patients with idiopathic pulmonary fibrosis (IPF).This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day-1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602-2403 mg·day-1) and nintedanib (200-300 mg·day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither.89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs.Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.

Why do two procedures when one will do? Thoracic ultrasound guiding management of complex pleural space infections.

Complicated parapneumonic effusions and empyemas are associated with significant morbidity and mortality. When managing a potentially infected pleural space, current guidelines support performing diagnostic thoracentesis prior to consideration of chest tube insertion. We present a case demonstrating our clinical approach to the management of complicated parapneumonic effusions and empyemas, with patient presentation and initial point-of-care thoracic ultrasound assessment guiding consideration of immediate insertion of small-bore (14 F) chest tube.

Utility of point-of-care ultrasound for guidance of ultrafiltration goal in a patient with end stage renal disease and acute hypoxic respiratory failure following 2 weeks on mechanical ventilation.

Point-of-care ultrasound is a bedside tool that is increasingly being used as part of the physical examination to evaluate fluid status. Cardiac ultrasound for assessment of volume status focuses on evaluating left ventricular ejection fraction, presence of pericardial effusion, right ventricular size, inferior vena cava size and collapsibility, and stroke volume measurement at the left ventricular outflow tract. Another way in which POCUS can be used to assess for fluid overload is the use of mitral inflow doppler to measure early diastolic transmitral flow velocity (E) and tissue doppler to measure early diastolic mitral annular velocity (e'). The ratio of E/e' is then used as an estimation of left ventricular filling pressure. This is a case where a 54-year-old female with end stage renal disease presents with hypoxic respiratory failure and is found to have diffuse bilateral airspace opacities on chest radiograph. E/e' was used to determine the etiology of the patient's undifferentiated pulmonary infiltrates and guide fluid removal through ultrafiltration. Ultrafiltration was performed with subsequent improvement in E/e' and the patient was successfully weaned off mechanical ventilation.

Intrapleural therapy.

Numerous intrapleural therapies have been adopted to treat a vast array of pleural diseases. The first intrapleural therapies proposed focused on the use of fibrinolytics and DNase to promote fluid drainage in empyema. Numerous case series and five randomized controlled trials have been published to determine the outcomes of fibrinolytics in empyema treatment. In the largest randomized trial, the use of streptokinase had no reduction in mortality, decortication rates or hospital days compared with placebo in the treatment of empyema. Criticism over study design and patient selection may have potentially affected the outcomes in this study. The development of dyspnoea is common in the setting of malignant pleural effusions. Pleural fluid evacuation followed by pleurodesis is often attempted. Numerous sclerosing agents have been studied, with talc emerging as the most effective agent. Small particle size of talc should be avoided because of increased systemic absorption potentiating toxicity, such as acute lung injury. Over the past several years, the use of chronic indwelling pleural catheters have emerged as the preferred modality in the treating a symptomatic malignant pleural effusion. For patients with malignant-related lung entrapment, pleurodesis often fails due to the presence of visceral pleural restriction; however, chronic indwelling pleural catheters are effective in palliation of dyspnoea. Finally, the use of staphylococcal superantigens has been proposed as a therapeutic model for the treatment of non-small lung cancer. Intrapleural instillation of staphylococcal superantigens increased median survival by 5 months in patients with non-small cell lung cancer with a malignant pleural effusion.

Management of complex pleural disease in the critically ill patient.

Disorders of the pleural space are quite common in the critically ill patient. They are generally associated with the underlying illness. It is sometimes difficult to assess for pleural space disorders in the ICU given the instability of some patients. Although the portable chest X-ray remains the primary modality of diagnosis for pleural disorders in the ICU. It can be nonspecific and may miss subtle findings. Ultrasound has become a useful tool to the bedside clinician to aid in diagnosis and management of pleural disease. The majority of pleural space disorders resolve as the patient's illness improves. There remain a few pleural processes that need specific therapies. While uncomplicated parapneumonic effusions do not have their own treatments. Those that progress to become a complex infected pleural space can have its individual complexity in therapy. Chest tube drainage remains the cornerstone in therapy. The use of intrapleural fibrinolytics has decreased the need for surgical referral. A large hemothorax or pneumothorax in patients admitted to the ICU represent medical emergencies and require emergent action. In this review we focus on the management of commonly encountered complex pleural space disorders in critically ill patients such as complicated pleural space infections, hemothoraces and pneumothoraces.

Systemic sclerosis with associated interstitial lung disease: management considerations and future directions.

Systemic sclerosis (SSc), also referred to as scleroderma, is a rare autoimmune disease associated with vasculopathy, inflammation, and fibrosis of the skin and/or internal organs. Interstitial lung disease (ILD) is a frequent complication and is the leading cause of death in patients with SSc. Although economic data are limited, available data suggest that SSc-ILD is associated with significant cost implications. Treatment of SSc-ILD has historically been with immunosuppressive agents. In 2019, however, the treatment landscape expanded with the FDA approval of the tyrosine kinase inhibitor nintedanib. A lack of codified treatment guidelines for patients with SSc-ILD creates significant challenges in improving outcomes at the patient level and, more generally, in reducing disease burden to the health care system. As the treatment landscape continues to evolve, it is likely that to reduce lung volume loss in patients, a combination of immunosuppressive and antifibrotic approaches will need to be used. Additionally, a greater emphasis on risk-stratification strategies may allow for more efficient follow-up, monitoring, and assessment of treatment response.

Chylothorax and cholesterol pleural effusion.

A chylothorax and a cholesterol pleural effusion represent the two forms of lipid effusions encountered. Traditionally, a lipid pleural effusion is characterized by the presence of milky fluid. Although these two effusions often share a similar pleural fluid appearance due to the high lipid concentration, they have major differences in the pathogenesis, clinical presentation, diagnosis, predisposing conditions, and management of these effusions. A chylothorax is defined by the presence of chyle in the pleural space resulting from obstruction or disruption of the thoracic duct or one of its major tributaries. A triglyceride concentration > 110 mg/dL is virtually diagnostic, but the presence of chylomicrons confirms the diagnosis. However, a chylothorax defined by these criteria represents a heterogeneous group of clinical entities. The presence of chylomicrons or triglyceride levels > 110 mg/dL in a pleural effusion should be considered evidence of chyle leakage of indeterminate clinical significance. Many cases of a chylous effusion may be associated with other causes of pleural fluid formation. In the case of an acute or chronic chylothorax due to recent or remote thoracic duct injury, this assessment is essential, as surgical ligation of the thoracic duct is often entertained. In other cases, especially lymphoma or chylous ascites, treatment of the underlying condition is indicated regardless, and the assessment of the response to treatment is a reasonable initial approach. In contrast, a cholesterol effusion is typically the result of long-standing pleurisy with elevated cholesterol levels in the pleural space; however, this paradigm has been challenged. Lung entrapment with thickened parietal and visceral pleural membranes is the typical radiographic findings of a cholesterol effusion. Most cases of cholesterol pleural effusions are attributed to tuberculous or rheumatoid pleurisy. Decortication is the mainstay of treatment for a cholesterol effusion in symptomatic patients with restrictive lung function.

Serious adverse events in patients with idiopathic pulmonary fibrosis in the placebo arms of 6 clinical trials.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by irreversible loss of lung function and an unpredictable course of disease progression. METHODS: The safety data for patients with IPF who received placebo in 6 clinical trials were pooled to examine the categories and frequencies of serious adverse events (SAEs) in this population. RESULTS: In 1082 patients with IPF who received placebo, 673 SAEs were reported. Of these, 93 SAEs resulted in death (8.6% of patients). Respiratory-related conditions were the most frequently reported SAE (225 events, 16.33 per 100 patient-exposure years [PEY]), followed by infections and infestations (136 events, 9.87 per 100 PEY) and cardiac disorders (79 events, 5.73 per 100 PEY); these categories also had the most fatal outcomes (60, 10, and 10 deaths, respectively). The most frequently reported fatal respiratory-related SAEs were IPF and respiratory failure (38 and 11 patients, respectively), and the most frequently reported fatal infections and infestations and cardiac disorders were pneumonia (5 patients) and myocardial infarction (3 patients), respectively. CONCLUSIONS: This pooled analysis has value as a comparator for safety in future studies of IPF and provides insights in the natural evolution of both IPF and common comorbidities.

Management of pneumothorax in lymphangioleiomyomatosis: effects on recurrence and lung transplantation complications.

STUDY OBJECTIVES: Pneumothorax is a common complication of lymphangioleiomyomatosis (LAM), and the optimal approach to its treatment and prevention is unknown. Chemical or surgical pleurodesis are often required to prevent recurrence. However, their efficacy in LAM is unclear, and whether they contribute to perioperative complications during lung transplantation is uncertain. SETTING: The LAM Foundation database of registered patients. DESIGN: A questionnaire was sent to all registered patients who had at least one pneumothorax to determine rates and patterns of recurrence and efficacy of interventions. A second questionnaire was sent to registered LAM patients who received a lung transplant. PATIENTS OR PARTICIPANTS: Of 395 registered patients, 260 patients (66%) reported at least one pneumothorax during their lifetime, 193 of whom (74%) completed the questionnaire. Of the 85 lung transplant patients who were sent a separate questionnaire, 80 patients (94%) responded. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of the 193 respondents to the pneumothorax questionnaire, data on 676 episodes of pneumothorax were collected. Eighty-two percent (158 of 193 patients) had their first pneumothorax prior to a diagnosis of LAM. One hundred forty patients (73%) had at least one additional pneumothorax, either an ipsilateral recurrence (99 of 140 patients, 71%) or a contralateral pneumothorax (104 of 140 patients, 74%). Recurrence rates were 66% after conservative therapy, 27% after chemical pleurodesis, and 32% after surgery. In patients who had undergone lung transplantation, prior chemical or surgical pleurodesis was performed in 45 of 80 patients (56%). Fourteen of 80 patients (18%) reported pleural-related postoperative bleeding, 13 of whom (93%) had prior pleurodesis. CONCLUSIONS: Chemical pleurodesis or surgery are equally effective and better than conservative therapy in preventing recurrence of pneumothorax in LAM. Due to the high recurrence rate, either procedure should be considered for the initial pneumothorax in these patients. However, both contribute to increased perioperative bleeding following lung transplantation, with no effect on length of hospital stay.

Using endobronchial ultrasound features to predict lymph node metastasis in patients with lung cancer.

PURPOSES: Reliable staging of the mediastinum determines TNM classification and directs therapy for non-small cell lung cancer (NSCLC). Our aim was to evaluate predictors of mediastinal lymph node metastasis in patients undergoing endobronchial ultrasound (EBUS). METHODS: Patients with known or suspected lung cancer undergoing EBUS for staging were included. Lymph node radiographic characteristics on chest CT/PET scan and ultrasound characteristics of size, shape, border, echogenicity, and number were correlated with rapid on-site evaluation (ROSE) and final pathology. Logistic regression (estimated with generalized estimating equations to account for correlation across nodes within patients) was used with cancer (vs normal pathology) as the outcome. ORs compare risks across groups, and testing was performed with two-sided α of 0.05. RESULTS: Two hundred twenty-seven distinct lymph nodes (22.5% positive for malignancy) were evaluated in 100 patients. Lymph node size, by CT scan and EBUS measurements, and round and oval shape were predictive of mediastinal metastasis. Increasing size of lymph nodes on EBUS was associated with increasing malignancy risk (P = .0002). When adjusted for CT scan size, hypermetabolic lymph nodes on PET scan did not predict malignancy. Echogenicity and border contour on EBUS and site of biopsy were not significantly associated with cancer. In 94.8% of lymph nodes with a clear diagnosis, the ROSE of the first pass correlated with subsequent passes. CONCLUSIONS: Lymph node size on CT scan and EBUS and round or oval shape by EBUS are predictors of malignancy, but no single characteristic can exclude a visualized lymph node from biopsy. Further, increasing the number of samples taken is unlikely to significantly improve sensitivity.

Dasatinib-induced pleural effusions: a lymphatic network disorder?

Dasatanib, which has been approved for rescue therapy for patients with imatinib-resistant chronic myelogenous leukemia and Philadelphia chromosome positive acute lymphoblastic leukemia, is a novel, orally available multitargeted kinase inhibitor of BCR-ABL and SRC family kinases (Quintas-Cardama et al, J Clin Oncol 2007;25:3908-14). It binds to both active and inactive conformations of the ABL gene and is 325 times more potent than imatinib in inhibiting the growth of BCR/ABL cells in vitro (Morelock and Sahn, Chest 1999;116:212-21; Huggins and Sahn, Clin Chest Med 2004;25:141-53). Although dasatinib is a generally well-tolerated drug in the treatment of Philadelphia chromosome positive hematopoetic malignancies, pleural effusions have been frequently noted and have been reported in up to 35% of patients (Sahn SA. Drug-induced pleural disease. In: Camus P, Rosenow E, editors. Drug-induced iatrogenic lung disease. London: Hodder Arnold; 2009). Although there have been numerous reports of effusions, none have provided complete pleural fluid analysis; therefore, we report 2 patients with dasatinib-induced pleural effusion with complete pleural fluid analysis.

Successful real-time endobronchial ultrasound-guided transbronchial needle aspiration of a hilar lung mass obtained by traversing the pulmonary artery.

The utility and safety of transbronchial needle aspiration is well described. Serious complications from transbronchial needle aspiration are exceedingly rare. The addition of endoscopic ultrasonographic techniques in the form of endoscopic ultrasonography and, more recently, endobronchial ultrasonography has added valuable information regarding lymphatic anatomy of the hilum and mediastinum. In addition, the use of real-time ultrasound gives the operator visual feedback of needle placement and proximity to major surrounding structures such as the heart and great vessels. Here, the authors present the case of a 74-year-old man with a left hilar mass who underwent biopsy by means of intentional traverse of the pulmonary artery.