Jessica Cope

Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease

Background: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. Objectives: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. Methods: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. Results: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. Conclusion: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

Restoration of Patency to Central Airways Occluded by Malignant Endobronchial Tumors Using Intratumoral Injection of Cisplatin

RATIONALE Malignant airway obstruction is commonly found in patients with lung cancer and is associated with significant morbidity and mortality. Relieving malignant obstruction may improve symptoms, quality of life, and life expectancy. OBJECTIVES The objective of this study was to analyze our experience with bronchoscopic endobronchial intratumoral injection of cisplatin for malignant airway obstruction. METHODS We conducted a retrospective analysis of patients with malignant airway obstruction treated with bronchoscopic intratumoral injection of cisplatin. Patient characteristics, histology, degree of airway obstruction, procedural methods, treatment cycles, performance status, and therapeutic outcomes were evaluated. Tumor response was analyzed based on bronchoscopic measurements performed on completion the of final treatment session. Adverse events and overall survival were abstracted. MEASUREMENTS AND MAIN RESULTS Between January 2009 and September 2014, 22 patients (10 men, 12 women; mean age ± SD, 64.4 ± 9.5 yr) were treated with one to four injections of 40 mg of cisplatin mixed in 40 ml of 0.9% NaCl. Treatments were completed 1 week apart. The primary etiologies of airway obstruction included squamous cell carcinoma (n = 11), adenocarcinoma (n = 6), small cell carcinoma (n = 2), large cell undifferentiated carcinoma (n = 1), and metastatic endobronchial cancer (n = 2). Twenty-one of 22 patients were evaluable for response. The majority of patients (15/21, 71.4%) responded to therapy, defined as greater than 50% relative reduction in obstruction from baseline. Treatment response was obtained regardless of tumor histology, concurrent systemic therapy, number of treatment cycles administered, performance status, or use of additional ablative interventions. Responders had significantly improved overall survival as compared with nonresponders, although the difference was small. Severe treatment-related side effects or complications were not observed. CONCLUSIONS Subject to the limitations of a single-center retrospective study and a subjective primary outcome measure, we have demonstrated the feasibility of improving the patency of central airways that are largely or completely occluded by endobronchial malignant tumor using intraluminal injection of cisplatin. Additional longer-term, larger-scale safety and comparative effectiveness studies of this palliative treatment modality are warranted.

Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin

PURPOSE A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). METHODS Patients treated between Jan 2009-September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8-12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. RESULTS 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9±8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6-11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. CONCLUSION EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population.

Titanium exposure and yellow nail syndrome

Yellow nail syndrome is a rare disease of unclear etiology. We describe a patient who develops yellow nail syndrome, with primary nail and sinus manifestations, shortly after amalgam dental implants. A study of the patients nail shedding showed elevated nail titanium levels. The patient had her dental implants removed and had complete resolution of her sinus symptoms with no change in her nail findings. Since the patients nail findings did not resolve we do not believe titanium exposure is a cause of her yellow nail syndrome but perhaps a possible relationship exists between titanium exposure and yellow nail syndrome that requires further studies.

Pulmonary arterial hypertension and acute respiratory distress syndrome in a patient with adult-onset stills disease:

Adult-onset Still’s disease (AOSD) is an inflammatory disorder characterized by recurrent fevers, arthralgia, leukocytosis, and a salmon-colored rash. Diagnosis is made based on the Yamaguchi criteria. Various cardiac and pulmonary manifestations have been described in association with AOSD, including acute respiratory distress syndrome (ARDS) and pulmonary arterial hypertension (PAH). We describe the first case of both PAH and ARDS in a patient with AOSD who, despite aggressive therapy, declined rapidly and ultimately died. There was concern for pulmonary veno-occlusive disease given the rate of her decompensation, but this was found not to be the case on autopsy. Treatment of AOSD with cardiopulmonary involvement requires rapid identification of AOSD followed by aggressive immunosuppression.

A Review of Targeted Pulmonary Arterial Hypertension-Specific Pharmacotherapy

Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways.

Pulmonary arterial hypertension and associated conditions

Pulmonary hypertension (PH) refers to an increase in pulmonary arterial pressure, defined as mean pulmonary artery pressure (mPAP) Z25 mmHg at rest, that if left untreated may progress to right ventricle dysfunction and failure. Worldwide, pulmonary hypertension associated with schistosomiasis is considered the most common form of the disease. In the United States, postcapillary pulmonary hypertension due to left heart disease is the most prevalent form of PH. Pulmonary arterial hypertension (PAH) is a form of pre-capillary pulmonary hypertension that is defined based on cardiopulmonary hemodynamics as a mPAP Z 25 mmHg, pulmonary artery occlusion pressure (PAOP) r 15 mmHg, and pulmonary vascular resistance (PVR) Z 3 Wood units (WU) at rest. According to the latest classification by the World Symposium in Pulmonary Hypertension (WSPH), this group of pre-capillary pulmonary hypertension, termed Group 1 PAH, consists of idiopathic pulmonary arterial hypertension (IPAH) and heritable PAH (HPAH) that occur in the absence of any identifiable cause, and PAH associated with other conditions such as the use of anorexigens and other drugs, schistosomiasis infection, connective tissue diseases, congenital heart disease, HIV, or chronic liver disease. IPAH and HPAH are rare, with an estimated incidence of 1–2 cases per million in the general population according to the REVEAL registry. Historically, the first report of PAH dates back to 1891 by Ernst von Romberg who described findings of “pulmonary vascular stenosis” on autopsy. However, it was not until the 1970s with the recognition of fenfluramine/phentermine (also known as fen–phen)-associated PAH, that prompted the first WSPH meeting to address, describe, and classify PH. Since then, great strides have been made in the advancement of research and management of this disease.

Vasovagal response secondary to permanent contraception device in pulmonary arterial hypertension.

Adequate contraception is an essential component of managing pulmonary hypertension in women of childbearing age. Intrauterine devices are a popular contraceptive choice for many women but are associated with a risk of vagal response upon placement in certain patients with pulmonary hypertension, which may not be well tolerated. More recently, newer permanent contraception devices have emerged in the market, such as the Essure. We describe the first case, to our knowledge, of vagal-associated response due to an Essure device placement.

Impact of an Extended Infusion Beta-lactam Strategy on Outcomes in Critically Ill Patients with Pseudomonas Infections

Abstract Background Pseudomonas aeruginosa (PSA) is frequently associated with nosocomial infections resulting in significant morbidity and mortality. High MICs in MDR strains highlights the need to maximize antibiotic exposure with the goal of improving patient outcomes. For β-lactams, optimal efficacy is achieved when free drug concentrations are above the MIC for ~ 40–60% of the dosing interval. Unfortunately, due to significant pharmacokinetic variability in the critically ill, achieving this target with standard intermittent infusions (II) is challenging, resulting in preference for extended (EI) or continuous infusion strategies. Additional data in patients with PSA infections are needed to understand the association between infusion strategy and clinical outcome. Methods A single-center, retrospective chart review. Adult patients with positive respiratory or blood cultures for PSA treated with cefepime or piperacillin/tazobactam managed in an ICU from January 2012 to May 2016 were included. Primary endpoint was clinical cure (CC) at end of therapy (EOT) between patients receiving EI or II. Secondary endpoints included microbiologic eradication (ME), 28-day mortality, length of ICU and hospital stay, and effect of baseline kidney function on clinical cure. Results Eighty-three patients were included in the analysis. Patient characteristics were well matched except for a higher frequency of malignancy in the EI arm (P = 0.02). CC was achieved in an overwhelming majority of EI patients compared with II (89.2% vs. 69.6%, P = 0.031). Further, patients with normal renal function (CrCL ≥ 60; P = 0.02) or APACHE II ≥ 17 (P = 0.04) receiving II experienced higher failure rates. In multivariate analysis, use of II associated with 4-fold higher incidence of clinical failure (OR 4.5 [1.3–16.3]). For other secondary endpoints, ME was observed in 73% of EI vs. 65% of II (P = 0.44) and 28-day mortality was observed in 13% of patients in both arms (P = 0.94). No significant differences were observed with other secondary variables. Conclusion Use of an EI strategy in critically ill patients with PSA infections improves CC. Further, EI benefitted those patients with normal to augmented renal clearance suggesting that improved exposure may play a role in clinical outcomes. Disclosures K. Klinker, The Medicines Company: Scientific Advisor, Consulting fee.

In reply: Submassive pulmonary embolism

We thank Dr. Katyal for his thoughtful comments. Dr. Katyal points out that the grade of recommendation for thrombolysis in patients with massive pulmonary embolism was upgraded from 2C to 2B in the 2016 American College of Chest Physicians (ACCP) guidelines[1][1] compared with the 2012 guidelines[