Christian A. Merlo

Bio: Christian A. Merlo is an academic researcher from Johns Hopkins University School of Medicine. The author has contributed to research in topics: Lung transplantation & Transplantation. The author has an hindex of 34, co-authored 118 publications receiving 4007 citations. Previous affiliations of Christian A. Merlo include Johns Hopkins University.

HIV Infection Is Associated with an Increased Risk for Lung Cancer, Independent of Smoking

Abstract: Background Human immunodeficiency virus (HIV)–infected persons have an elevated risk for lung cancer, but whether the increase reflects solely their heavy tobacco use remains an open question.

Association between respiratory tract methicillin-resistant Staphylococcus aureus and survival in cystic fibrosis.

Abstract: Context The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the respiratory tract of individuals with cystic fibrosis (CF) has increased dramatically; however, its impact on outcomes in CF is unclear. Because the time between infection with bacteria in CF and death can be decades, observational studies with long periods of follow-up are well suited to address the current gap in knowledge. Objective To determine whether isolation of MRSA from the respiratory tract of CF patients is associated with worse survival compared with patients who never have a culture positive for MRSA. Design, Setting, and Participants Cohort study of 19 833 CF patients aged 6 to 45 years seen at centers accredited by the Cystic Fibrosis Foundation in the United States. Patients entered between January 1996 and December 2006 and were followed up through December 2008. Cox regression models with time-varying covariates were used to compare survival between CF patients with and without respiratory tract MRSA. Main Outcome Measure Time from age at entry until age at death from any cause. Results In 137 819 patient-years of observation (median, 7.3 years/patient), 2537 CF patients died and 5759 patients had MRSA detected. The mortality rate was 18.3 deaths (95% confidence interval [CI], 17.5-19.1) per 1000 patient-years in patients without MRSA and 27.7 deaths (95% CI, 25.3-30.4) per 1000 patient-years in those with MRSA. Among those with MRSA, the attributable risk percentage of death associated with MRSA was 34.0% (95% CI, 26.7%-40.4%). The unadjusted hazard ratio associated with MRSA was 1.47 (95% CI, 1.32-1.62). After adjustment for time-varying covariates associated with severity of illness, MRSA remained associated with a higher risk of death (1.27; 95% CI, 1.11-1.45). Conclusion Detection of MRSA in the respiratory tract of CF patients was associated with worse survival.

Persistent methicillin-resistant Staphylococcus aureus and rate of FEV1 decline in cystic fibrosis.

Abstract: Rationale: The prevalence in cystic fibrosis (CF) of respiratory cultures with methicillin-resistant Staphylococcus aureus (MRSA) has dramatically increased over the last 10 years, but the effect of MRSA on FEV1 decline in CF is unknown.Objectives: To determine the association between MRSA respiratory infection and FEV1 decline in children and adults with CF.Methods: This was a 10-year cohort study using the Cystic Fibrosis Foundation patient registry from 1996–2005. We studied individuals who developed new MRSA respiratory tract infection. Repeated-measures regression was used to assess the association between MRSA and FEV1 decline, adjusted for confounders, in individuals aged 8–21 years and adults (aged 22–45 yr). Two different statistical models were used to assess robustness of results.Measurements and Main Results: The study cohort included 17,357 patients with an average follow-up of 5.3 years. During the study period, 1,732 individuals developed new persistent MRSA infection (≥3 MRSA cultures; ave...

An epistaxis severity score for hereditary hemorrhagic telangiectasia

Abstract: Objectives/Hypothesis: Hereditary hemorrhagic telangiectasia (HHT)-related epistaxis leads to alterations in social functioning and quality of life. Although more than 95% experience epistaxis, there is considerable variability of severity. Because no standardized method exists to measure epistaxis severity, the purpose of this study was to determine factors associated with patient-reported severity to develop a severity score. Study Design: Prospective, survey-based study. Methods: HHT care providers and a focus group of patients were interviewed to determine epistaxis-associated factors. From this, an electronic survey was developed and administered to patients with HHT. Descriptive analyses were performed with calculations of means and medians for continuous and proportions for categorical variables. Multiple ordinal logistic and linear regression models were developed to determine risk factors for epistaxis severity. Results: Nine hundred respondents from 21 countries were included. Eight hundred fifty-five (95%) subjects reported epistaxis. The mean (standard deviation) age was 52.1 (13.9) years, and 61.4% were female. Independently associated risk factors for self-reported epistaxis severity included epistaxis frequency (odds ratio [OR] 1.57), duration (OR 2.17), intensity (OR 2.45), need for transfusion (OR 2.74), anemia (OR 1.44), and aggressiveness of treatment required (OR 1.53, P < .001 for all). Conclusions: Risk factors for increasing epistaxis severity in patients with HHT include frequency, duration, and intensity of episodes; invasiveness of prior therapy required to stop epistaxis; anemia; and the need for blood transfusion. From these factors, an epistaxis severity score will be presented. Laryngoscope, 2010

Impact of U.S. Lung Allocation Score on Survival After Lung Transplantation

Abstract: Background The Lung Allocation Score (LAS) dramatically changed organ allocation in lung transplantation. The impact of this change on patient outcomes is unknown. The purpose of the study was to examine early mortality after lung transplantation under the LAS system. Methods All patients undergoing first-time lung transplantation during the period from May 1, 2005 through April 30, 2008 were included in the study. The cohort was divided into quintiles by LAS. A high-risk group (LAS >46) was comprised of the highest quintile, Quintile 5, and a low-risk group (LAS ≤46) included the lower quintiles, Quintiles 1 through 4. A time-to-event analysis was performed for risk of death after transplantation using Kaplan–Meier survival and Cox proportional hazards models. Results There were 4,346 patients who underwent lung transplantation during the study period. Patients in the high-risk group (LAS >46) were more likely to have idiopathic pulmonary fibrosis (IPF; 52.9% vs 23.8%, p p p p Conclusions Overall 1-year survival under the new LAS system appears to be similar to that in historic reports. However, risk of death was significantly increased among patients with LAS >46.

Cystic Fibrosis

Abstract: Cystic fibrosis is the most common autosomal recessive disorder in white people, with a frequency of about 1 in 2500 livebirths. Discovery of the mutated gene encoding a defective chloride channel in epithelial cells--named cystic fibrosis transmembrane conductance regulator (CFTR)--has improved our understanding of the disorder's pathophysiology and has aided diagnosis, but has shown the disease's complexity. Gene replacement therapy is still far from being used in patients with cystic fibrosis, mostly because of difficulties of targeting the appropriate cells. Life expectancy of patients with the disorder has been greatly increased over past decades because of better notions of symptomatic treatment strategies. Here, we summarise advances in understanding and treatment of cystic fibrosis, focusing on pulmonary disease, which accounts for most morbidity and deaths.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

Abstract: Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic.

Abstract: Summary: Staphylococcus aureus is an important cause of skin and soft-tissue infections (SSTIs), endovascular infections, pneumonia, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis. Methicillin-resistant S. aureus (MRSA) isolates were once confined largely to hospitals, other health care environments, and patients frequenting these facilities. Since the mid-1990s, however, there has been an explosion in the number of MRSA infections reported in populations lacking risk factors for exposure to the health care system. This increase in the incidence of MRSA infection has been associated with the recognition of new MRSA clones known as community-associated MRSA (CA-MRSA). CA-MRSA strains differ from the older, health care-associated MRSA strains; they infect a different group of patients, they cause different clinical syndromes, they differ in antimicrobial susceptibility patterns, they spread rapidly among healthy people in the community, and they frequently cause infections in health care environments as well. This review details what is known about the epidemiology of CA-MRSA strains and the clinical spectrum of infectious syndromes associated with them that ranges from a commensal state to severe, overwhelming infection. It also addresses the therapy of these infections and strategies for their prevention.

Natural Innate and Adaptive Immunity to Cancer

Abstract: The immune system can identify and destroy nascent tumor cells in a process termed cancer immunosurveillance, which functions as an important defense against cancer. Recently, data obtained from numerous investigations in mouse models of cancer and in humans with cancer offer compelling evidence that particular innate and adaptive immune cell types, effector molecules, and pathways can sometimes collectively function as extrinsic tumor-suppressor mechanisms. However, the immune system can also promote tumor progression. Together, the dual host-protective and tumor-promoting actions of immunity are referred to as cancer immunoediting. In this review, we discuss the current experimental and human clinical data supporting a cancer immunoediting process that provide the fundamental basis for further study of immunity to cancer and for the rational design of immunotherapies against cancer.