David Horak

A Randomized, Controlled Trial of Prophylactic Ganciclovir for Cytomegalovirus Pulmonary Infection in Recipients of Allogeneic Bone Marrow Transplants

Abstract Background. Cytomegalovirus (CMV)-associated interstitial pneumonia is a major cause of death after allogeneic bone marrow transplantation. We conducted a controlled trial of ganciclovir in recipients of bone marrow transplants who had asymptomatic pulmonary CMV infection. We also sought to identify risk factors for the development of CMV interstitial pneumonia. Methods. After bone marrow transplantation, 104 patients who had no evidence of respiratory disease underwent routine bronchoalveolar lavage on day 35. The 40 patients who had positive cultures for CMV were randomly assigned to either prophylactic ganciclovir or observation alone. Ganciclovir (5 mg per kilogram of body weight intravenously) was given twice daily for two weeks and then five times per week until day 120. Results. Of the 20 culture-positive patients who received prophylactic ganciclovir, 5 (25 percent) died or had CMV pneumonia before day 120, as compared with 14 of the 20 culture-positive control patients (70 percent) who w...

The value of bronchoalveolar lavage and bronchial washings in the diagnosis of invasive pulmonary aspergillosis

The objective of this study was to clarify conflicting reports of the sensitivity and specificity of bronchoalveolar lavage or bronchial washings for diagnosing invasive pulmonary aspergillosis. The study was a retrospective review of 300 consecutive patients in a tertiary referral centre subjected to 343 fiberoptic bronchoscopic procedures for the evaluation of pulmonary infiltrates. Classification of paired fungal culture and cytologic examination of bronchoalveolar lavage or bronchial washing fluid according to clinical, radiographic, histological and autopsy evidence of invasive pulmonary aspergillosis. One-hundred and fifteen deaths occurred, with a 58% autopsy rate. A diagnosis of invasive pulmonary aspergillosis was made in 21 immunosuppressed patients with 16 deaths. Bronchoalveolar lavage cytology showed aspergillus in 19 specimens (invasive pulmonary aspergillosis in 16), cultures yielded aspergillus in 41 (invasive pulmonary aspergillosis in ten), with both tests positive in nine. Cytology sensitivity was 64.0%, specificity 99.1%, positive predictive value 84.2%, and negative predictive value 97.2%. Culture sensitivity was 40.0%, specificity 90.3%, positive predictive value 24.4%, and negative predictive value 95.0%. Concordant cytology and culture sensitivity was 32.0%, specificity 99.7%, positive predictive value 88.9%, and negative predictive value 94.9%. In conclusion, when characteristic hyphae are visualized in bronchoalveolar lavage specimens from immunosuppressed patients with compatible clinical data, it is advisable to treat for presumptive invasive pulmonary aspergillosis.

Fractional Flow Reserve–Guided Multivessel Angioplasty in Myocardial Infarction

BACKGROUND In patients with ST‐segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct‐related coronary artery improves outcomes. The use of PCI in non‐infarct‐related coronary arteries remains controversial. METHODS We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct‐related coronary artery in a 1:2 ratio to undergo complete revascularization of non‐infarct‐related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non‐infarct‐related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct‐related coronary artery only. RESULTS The primary outcome occurred in 23 patients in the complete‐revascularization group and in 121 patients in the infarct‐artery‐only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; P<0.001). Death occurred in 4 patients in the complete‐revascularization group and in 10 patients in the infarct‐artery‐only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR‐related serious adverse event occurred in 2 patients (both in the group receiving infarct‐related treatment only). CONCLUSIONS In patients with STEMI and multivessel disease who underwent primary PCI of an infarct‐related artery, the addition of FFR‐guided complete revascularization of non‐infarct‐related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct‐related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare‐Acute ClinicalTrials.gov number, NCT01399736.)

Spontaneous pneumothorax in patients irradiated for Hodgkin's disease and other malignant lymphomas

A retrospective review of patients treated for Hodgkins disease or other malignant lymphomas between 1953 and 1988 revealed 10 cases of spontaneous pneumothorax. Nine had Hodgkins disease whereas one had diffuse histiocytic lymphoma. Ages of the 10 patients ranged from 11 to 54 years, although nine were less than 30-years old. Spontaneous pneumothorax was observed only in patients who had received mantle or mini-mantle radiation therapy (RT). Five patients had concurrent severe parenchymal pulmonary disease including chemotherapy-induced interstitial fibrosis, Varicella pneumonia and severe radiation pneumonitis. Pneumothorax in these patients tended to be severe, bilateral and/or recurrent. All five required chest tube placement. Three of the five also required thoracotomy. RT dose ranged from 3000-7500 cGy, exceeding 4700 cGy in three patients who required a second course of RT which included the involved lung apex. In comparison, the five who did not have concurrent severe lung disease had milder episodes of pneumothorax. Only one required chest tube placement, whereas none required thoracotomy. Pulmonary apex RT dose ranged from 3672-4257 cGy. For Hodgkins disease patients treated by RT, the frequency of spontaneous pneumothorax in the absence of concurrent pulmonary disease was 2.2%. Limiting analysis to patients in the peak age population of 10-30 years raised the frequency to 3.0%. No RT dose-response effect could be demonstrated, although spontaneous pneumothorax was not observed in patients who received less than 3000 cGy. Spontaneous pneumothorax was not more frequent among patients who also received chemotherapy as compared to those treated only by RT. Exploratory thoracotomy in three cases with severe pulmonary disease revealed subpleural apical blebs and/or dense pleural fibrosis. Unusual aspects in the medical histories of other cases suggest the possibility that patients who develop pneumothorax may have unusually dense pulmonary and/or pleural fibrosis compared to the majority of patients who receive RT for Hodgkins disease or other malignant lymphomas.

LIDOCAINE FOR SEVERE HICCUPS

To the Editor: The pharmacologic approaches to the treatment of severe hiccups include the use of chlorpromazine, carbamazepine, nifedipine, baclofen, metoclopramide, haloperidol, ketamine, and phe...

Long-Term Pulmonary Function in Survivors of Childhood Cancer

PURPOSE This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. PATIENTS AND METHODS Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. RESULTS Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. CONCLUSION Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring.

CRITICAL CARE OF THE HEMATOPOIETIC STEM CELL PATIENT

Hematopoietic stem cell transplantation is evolving into a treatment modality with expanding indications and volume and with excellent outcomes, although it carries significant risk for morbidity and mortality affecting most major organ systems and often requires ICU care. With continuing improvements in supportive care and specific therapy of complications following HCT including the open-lung strategy of mechanical ventilation, use of nitric oxide, less toxic myeloablative regimens, newer classes of antibiotics, and improved immunosuppression strategies, it is hoped that mortality in this setting will continue to decline in coming years.

Oxygen for end-of-life lung cancer care: managing dyspnea and hypoxemia.

Oxygen is commonly prescribed for lung cancer patients with advancing disease. Indications include hypoxemia and dyspnea. Reversal of hypoxemia in some cases will alleviate dyspnea. Oxygen is sometimes prescribed for non-hypoxemic patients to relieve dyspnea. While some patients may derive symptomatic benefit, recent studies demonstrate that compressed room air is just as effective. This raises the question as to whether to continue their oxygen. The most efficacious treatment for dyspnea is pharmacotherapy–particularly opioids. Adjunctive therapies include pursed lips breathing and a fan blowing toward the patient. Some patients may come to require high-flow oxygen. High-flow delivery devices include masks, high-flow nasal oxygen and reservoir cannulas. Each device has advantages and drawbacks. Eventually, it may be impossible or impractical to maintain a SpO2 > 90%. The overall goal in these patients is comfort rather than a target SpO2. It may eventually be advisable to remove continuous oximetry and transition focus to pharmacological management to achieve patient comfort.