Relative Lung Perfusion on Ventilation-Perfusion Scans After Double Lung Transplant.

BACKGROUND: Pulmonary blood flow can be assessed on ventilation-perfusion (VQ) scan with relative lung perfusion, with a 55% to 45% (or 10%) right-to-left differential considered normal. We hypothesized that wide perfusion differential on routine VQ studies at 3 mo posttransplant would be associated with an increased risk of death or retransplantation, chronic lung allograft (CLAD), and baseline lung allograft dysfunction. METHODS: We conducted a retrospective cohort study on all patients who underwent double-lung transplant in our program between 2005 and 2016, identifying patients with a wide perfusion differential of >10% on a 3-mo VQ scan. We used Kaplan-Meier estimates and proportional hazards models to assess the association between perfusion differential and time to death or retransplant and time to CLAD onset. We used correlation and linear regression to assess the relationship with lung function at time of scan and with baseline lung allograft dysfunction. RESULTS: Of 340 patients who met inclusion criteria, 169 (49%) had a relative perfusion differential of ≥ 10% on a 3-mo VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation ( P = 0.011) and CLAD onset ( P = 0.012) after adjustment for other radiographic/endoscopic abnormalities. Increased perfusion differential was associated with lower lung function at time of scan. CONCLUSIONS: Wide lung perfusion differential was common after lung transplant in our cohort and associated with increased risk of death, poor lung function, and CLAD onset. The nature of this abnormality and its use as a predictor of future risk warrant further investigation.

Endobronchial hamartoma.

We present images of an endobronchial hamartoma visible by bronchoscopy in the left lower lobe. A 56-year-old woman with a late presentation of an acute anterior myocardial infarction requires urgent heart transplantation and subsequently has trouble weaning off the ventilator. Bronchoscopic evaluation reveals a 1 cm endobronchial hamartoma obstruction the left lower lobe bronchus. A polypectomy snare was effectively used with electrocautery to excise the lesion. The patient was successfully able to wean off the ventilator once the left lower lobe was free from obstruction.

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD.

An international survey of cytomegalovirus management practices in lung transplantation.

BACKGROUND: Cytomegalovirus (CMV) is an important infection in lung transplant recipients. Center-to-center variation in preventive and treatment strategies is unknown. METHODS: An electronic survey was sent to 102 lung transplant programs registered with the International Society of Heart and Lung Transplantation and United Network for Organ Sharing. RESULTS: Fifty-nine (58%) programs responded to the survey. For CMV prevention (D+/R-), 56 of the 59 (94.9%) programs used prophylaxis and two (3.4%) of them used preemptive therapy. For R+ patients, 86.4% used prophylaxis and 13.6% used preemptive strategy. Duration of prophylaxis was extremely variable ranging from 3 months to indefinite. Adjunctive prophylactic strategies included routine viral monitoring (51% D+/R-; 44% R+) and CMV immunoglobulin (32% D+/R-; 14% R+). The medication used for prophylaxis was valganciclovir with approximately half starting with intravenous ganciclovir. 9 of the 59 (15.2%) centers reported using specific CMV prophylaxis in D-/R- patients. Methods for viral monitoring included peripheral blood polymerase chain reaction, antigenemia, bronchoalveolar lavage viral culture, and bronchoalveolar lavage polymerase chain reaction. For treatment of CMV viremia, valganciclovir or intravenous ganciclovir were used. A total of 47.5% of centers routinely decreased immunosuppression at the time of viremia. Secondary antiviral prophylaxis was used routinely by 36 of the 59 (61%) centers. CONCLUSIONS: Although prophylaxis is the most commonly used preventive strategy, significant variation exists in the way it is implemented. Specifically, duration of prophylaxis is extremely variable. Uniform international guidelines would be of value in this population.

Successful bilateral lung transplantation in a patient with end-stage lung disease and positive novel influenza virus (H1N1).

In 2009, a pandemic novel influenza virus (H1N1) outbreak was declared by the World Health Organization and resulted in significant worldwide illness. This report describes a 50-year-old male with end-stage lung disease secondary to alpha(1)-anti-trypsin deficiency and chronic obstructive pulmonary disease. He was admitted for potential bilateral lung transplantation when suitable organs became available. Incidentally, he was found to have some non-specific symptoms, including malaise and myalgias. These findings were attributed to killed-virus H1N1 vaccine given 48 hours earlier. However, as a safety measure, a nasopharyngeal swab was taken, and anti-viral therapy with oseltamivir (Tamiflu) was started empirically. He underwent bilateral lung transplantation on the same day of admission. In the immediate post-operative period his nasopharyngeal swab came back positive for H1N1 influenza virus. Then, post-operatively, two consecutive bronchoalveolar lavage samples from the transplanted lungs were found to be positive for H1N1 virus. He received three-weeks of antiviral treatment post-operatively and he had uneventful procedure with favorable outcome.

An unusual case of spinal column metastasis after orthotopic transplantation for cardiac sarcoma.

The authors describe a patient who underwent orthotopic cardiac transplantation after an undifferentiated cardiac sarcoma was diagnosed. While receiving immunosuppressive therapy, the patient developed spinal column metastases and cauda equina syndrome requiring surgical decompression and stabilization. This occurred despite an exhaustive search for metastatic disease prior to the transplantation. To the authors' knowledge, this represents the first reported case of an undifferentiated cardiac sarcoma metastasis to the spine. This previously healthy 18-year-old woman presented with a myocardial infarction. Investigations revealed a left atrial tumor, which was resected. Following local recurrence, the patient underwent extensive studies to rule out systemic disease. Orthotopic heart-lung transplantation was then performed. While receiving postoperative immunosuppressive therapy the patient presented with cauda equina syndrome secondary to metastatic tumor compression at the L-5 level. Despite a comprehensive screening process to exclude metastatic disease prior to transplantation, spinal metastases occurred while this patient was receiving immunosuppressive therapy. This represents a previously unreported and clinically significant complication for undifferentiated cardiac sarcoma.

Transcutaneous electrical nerve stimulation for severe gastroparesis after lung transplantation.

Gastroparesis is a serious complication of lung transplantation that can lead to weight loss, gastroesophageal reflux disease, and recurrent aspiration pneumonia. We present 2 lung allograft recipients in whom gastroparesis resolved with the use of transcutaneous electrical nerve stimulation (TENS). In both patients, severe symptoms of gastroparesis refractory to medical therapy were completely ablated after 20 and 30 days of therapy. Both patients are currently asymptomatic with a normal diet, without the use of promotility agents. Lung transplant recipients with severe gastroparesis can derive significant benefit from TENS.

Why do some countries publish more than others? An international comparison of research funding, English proficiency and publication output in highly ranked general medical journals.

National factor(s) influencing publication output in the highest ranked medical journals are largely unknown. We sought to examine the relationship between national research funding and English proficiency on publication output. We identified all original research articles appearing in the five highest ranked general medical journals between 1997 and 2001. Using the country of the corresponding author as the source nation for each article, we determined a standardized publication rate across developed nations. We used multiple regression techniques to determine the influence of national expenditures on research and scores from the Test of English as a Foreign Language (TOEFL), a surrogate for English proficiency, on publication output. There was a significant relationship of national spending on research and TOEFL scores to publication output of developed countries (p = 0.04; p < 0.01, respectively). These two variables explained approximately 71.5% of the variation in publication rate across developed nations around the world (R = 0.85; p < 0.01). Normalized for population size, English-speaking nations and certain northern European countries such as Denmark, The Netherlands, Switzerland, and Sweden had the highest rate of publication in the five highest ranked general medical journals, while Asian countries had generally low rates of publication. Research spending and English proficiency were strongly associated with publication output in the highest ranked general medical journals. While these data cannot be considered definitive due to their observational nature, they do suggest that for English-language medical journals, research funding and English proficiency may be important determinants of publication.