Vaidehi Kaza

Successful liver transplantation following medical management of portopulmonary hypertension: a single-center series.

Severe portopulmonary hypertension (POPH) is an absolute contraindication to orthotopic liver transplantation (OLT). Vasodilators have been used, but the safety of subsequent transplantation and the reversibility of pulmonary hypertension after transplantation are uncertain. This study examined the feasibility and post‐transplant effects of liver transplantation following medical control of POPH. Eight consecutive patients (three females and five males, ages 39–51) with POPH as their only contraindication to transplantation were treated with continuous intravenous epoprostenol. Liver transplantation was considered if the mean pulmonary artery pressure (PAM) was lowered to <35 mmHg. Epoprostenol 2–8 ng/kg/min successfully improved hemodynamics in seven of eight patients, usually within 6.5 months of initiating therapy. PAM declined from an average of 43–33 mmHg (p = 0.03); mean pulmonary vascular resistance declined from 410 to 192 dyn s cm−5 (p = 0.01) and cardiac output increased from 6.6 to 10 L/min (p = 0.02). Six of the seven responders were actively listed for liver transplantation. Two died on the waiting list; the remaining four were transplanted and remain alive and well 9–18 months post‐OLT—two without vasodilators, and two on oral medication. We conclude that pulmonary vasodilators permit safe liver transplantation in some cases, and that POPH may be reversible after transplantation.

Effect of telomere length on survival in patients with idiopathic pulmonary fibrosis: an observational cohort study with independent validation

BACKGROUND Short telomere lengths are found in a subset of patients with idiopathic pulmonary fibrosis, but their clinical significance is unknown. Our aim was to investigate whether patients with various blood leucocyte telomere lengths had different overall survival. METHODS In this observational cohort study, we enrolled patients with interstitial lung disease from Dallas, TX (primary cohort), and from Chicago, IL, and San Francisco, CA (replication cohorts). We obtained genomic DNA samples from unrelated healthy controls in Dallas, TX, and spouses of patients were also enrolled as an independent control group. Telomere lengths were measured in genomic DNA samples isolated from peripheral blood obtained at the time of the initial enrolment assessment. The primary endpoint was transplant-free survival (ie, time to death or lung transplantation) in the Dallas cohort. Findings were validated in the two independent idiopathic pulmonary fibrosis cohorts (Chicago and San Francisco). FINDINGS 370 patients were enrolled into the Dallas cohort between June 17, 2003, and Aug 25, 2011. The 149 patients with idiopathic pulmonary fibrosis had shorter telomere lengths than did the 195 healthy controls (mean age-adjusted log-transformed ratio of telomere to single copy gene was -0.16 [SD 0.23] vs 0.00 [0.18]; p<0.0001); however, telomere lengths of the Dallas patients with idiopathic pulmonary fibrosis (1.33 [SD 0.25]) were similar to the 221 patients with other interstitial lung disease diagnoses (1.46 [0.24]) after adjusting for age, sex, and ethnicity (p=0.47). Telomere length was independently associated with transplant-free survival time for patients with idiopathic pulmonary fibrosis (HR 0.22 [95% CI 0.08-0.63]; p=0.0048), but not for patients with interstitial lung disease diagnoses other than idiopathic pulmonary fibrosis (HR 0.73 [0.16-3.41]; p=0.69). The association between telomere length and survival in patients with idiopathic pulmonary fibrosis was independent of age, sex, forced vital capacity, or diffusing capacity of carbon monoxide, and was replicated in the two independent idiopathic pulmonary fibrosis replication cohorts (Chicago cohort, HR 0.11 [0.03-0.39], p=0.00066; San Francisco cohort, HR 0.25 [0.07-0.87], p=0.029). INTERPRETATION Shorter leucocyte telomere lengths are associated with worse survival in idiopathic pulmonary fibrosis. Additional studies will be needed to establish clinically relevant thresholds for telomere length and how this biomarker might affect risk stratification of patients with idiopathic pulmonary fibrosis. FUNDING US National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, Harroun Family Foundation, and Nina Ireland Lung Disease Program.

Acute severe asthma: recent advances.

Purpose of review Acute severe asthma is challenging to the clinician both in terms of recognition and appropriate treatment. About 30% of these episodes need admission to the medical intensive care unit with a mortality of 8%. Relapse rates vary from 7 to 15% depending on how well the patient is managed. The purpose of this review is to discuss recent advances in identification of risk factors, pathophysiology and management of acute severe asthma. Recent findings Although the exact mechanism for acute severe asthma is unclear, some that are implicated include inflammation, airway remodeling and downregulation of β-receptors. None of the environmental factors have been clearly related to the development of near fatal attacks. Genetic polymorphisms have been associated with severe asthma. Lack of steroid responsiveness has been linked to severe asthma attacks. Chemokines and basement membrane changes characteristic of severe asthma are reported in a few studies. Lack of symptom perception in a certain group of patients with acute severe asthma leads to delayed interventions. Specific treatment modalities and ventilator management is reviewed. Summary Severe asthma is a phenotype of asthma with variable pathology and clinical presentation. Early recognition and timely intervention is needed to prevent significant mortality and morbidity.

Hospital length of stay after lung transplantation: Independent predictors and association with early and late survival

BACKGROUND Duration of index hospitalization after lung transplantation (LTx) is an important variable that has not received much attention. We sought to determine independent predictors of prolonged hospital length of stay (LOS) and its association with early and late outcomes. METHODS The United Network of Organ Sharing database was queried for adult patients undergoing LTx between 2006 and 2014 (N = 14,320). Patients with dual organ or previous transplantation and patients who died during the first 25 days after LTx were excluded (n = 12,647, mean age 55.2 years ± 13.1). Primary outcome was prolonged LOS (>25 days) (3,251/12,647; 25.7%). Donor, recipient, and procedure-related variables were analyzed as potential predictors of prolonged LOS. Association of prolonged LOS with 1-year and 5-year survival was evaluated using Cox proportional hazards analysis. RESULTS Independent predictors of prolonged LOS included serum albumin, lung allocation score, functional status, and need of extracorporeal membrane oxygenation or ventilator support at the time of transplant; donor age >40 years; gender mismatch (female donor to male recipient); donor body mass index; African American ethnicity; ischemic time >6 hours; and double LTx. Prolonged LOS was independently associated with increased mortality at 1 year (hazard ratio, 3.96; 95% confidence interval, 3.48-4.50; p < 0.001) and 5 years (hazard ratio, 2.00; 95% confidence interval, 1.79-2.25; p < 0.001). CONCLUSIONS A significant proportion of patients have a prolonged LOS after LTx, and several recipient, donor, and procedure-related variables are independent predictors of this outcome. Patients with prolonged LOS after LTx have significantly increased risk of death at 1 year and 5 years.

Contemporary analysis of incidence of post-operative atrial fibrillation, its predictors, and association with clinical outcomes in lung transplantation

BACKGROUND Atrial fibrillation (AF) is a common complication after lung transplantation (LT). Since the lung allocation score (LAS) was implemented in 2005, there has been significant evolution in the practice of LT, necessitating re-evaluation of this arrhythmia. METHODS One hundred thirty-one patients undergoing LT between January 2011 and April 2013 were reviewed retrospectively to assess the occurrence of AF and its outcomes (mortality, morbidity measures, treatment strategies). Uni- and multivariate logistic regression models were constructed to ascertain predictors of AF. RESULTS Forty-six patients (35.1%) developed post-operative AF at 4.65 ± 3.68 days post-LT. The AF group was older (60.07 vs 54.48 years, p = 0.01), and had higher rates of cardiopulmonary bypass (CPB) (73.33% vs 43.53%, p = 0.001). There was no difference in mortality, ICU length of stay (LOS) and ventilator days; however, the AF group had a significantly higher mean hospital LOS by 8.43 days (17.09 vs 25.52, p = 0.04). Age (OR = 1.04, p = 0.03) and CPB (OR = 3.68, p = 0.002) were identified as predictors of AF by stepwise logistic regression after adjusting for gender, history of AF, type of LT, pulmonary hypertension and LT indication. In the AF group, 78.26% of patients required combination therapy. Anti-arrhythmics were used in 52.17% of patients. Dofetilide/ibutilide use was not associated with increased mortality. A total of 97.82% were in sinus rhythm at discharge. CONCLUSIONS To our knowledge, this is the first study to examine post-operative AF exclusively in the post-LAS era. Incidence of AF after LT is 35%. It increases hospital LOS, but not mortality. Management of AF is challenging and dofetilide/ibutilide serve as effective adjuncts to current therapy.

Telomere length in patients with pulmonary fibrosis associated with chronic lung allograft dysfunction and post–lung transplantation survival

BACKGROUND Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes based on leukocyte telomere length. METHODS We conducted an observational cohort study of all patients with pulmonary fibrosis who underwent lung transplantation at a single center between January 1, 2007, and December 31, 2014. Leukocyte telomere length was measured from a blood sample collected before lung transplantation, and subjects were stratified into 2 groups (telomere length <10th percentile vs ≥10th percentile). Primary outcome was post-lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction, and infection. RESULTS Approximately 32% of subjects had a telomere length <10th percentile. Telomere length <10th percentile was independently associated with worse survival (hazard ratio 10.9, 95% confidence interval 2.7-44.8, p = 0.001). Telomere length <10th percentile was also independently associated with a shorter time to onset of chronic lung allograft dysfunction (hazard ratio 6.3, 95% confidence interval 2.0-20.0, p = 0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared with the ≥10th percentile group (28% vs 7%; p = 0.034). There was no difference between the 2 groups in incidence of acute cellular rejection, cytopenias, infection, or renal dysfunction. CONCLUSIONS Telomere length <10th percentile was associated with worse survival and shorter time to onset of chronic lung allograft dysfunction and thus represents a biomarker that may aid in risk stratification of patients with pulmonary fibrosis before lung transplantation.

Predictors of outcome among patients on extracorporeal membrane oxygenation as a bridge to lung transplantation

There is a lack of data regarding clinical variables associated with successful bridge to lung transplantation (LT) using extracorporeal membrane oxygenation (ECMO) support.

Association of pretransplant kidney function with outcomes after lung transplantation

There is a lack of data regarding the independent association of pretransplant kidney function with early and late outcomes among lung transplant (LT) recipients.

Left Ventricular Dysfunction After Lung Transplantation for Pulmonary Arterial Hypertension

BACKGROUND Lung transplantation (LT) is the final treatment option for patients with pulmonary arterial hypertension (PAH). Perioperative challenges after LT are unique and commonly include excessive bleeding, arrhythmias, and primary graft dysfunction. Transient left ventricular dysfunction (LVD) is a known postoperative complication, but not fully explored. We describe our experiences at a single institution. METHODS We reviewed our database for patients with PAH who underwent LT from July 2008 to July 2012. The data were analyzed for preoperative inotrope use, intravenous prostacyclin, cardiac catheterization, and imaging. Also measured were perioperative ischemic time, bypass time, primary graft dysfunction, ventilator days, length of stay, and mortality. LVD is defined as acute cardiopulmonary compromise (acute worsening of hypoxia with new bilateral infiltrates on imaging) with a drop in LV systolic function of 15% from baseline. We compared data between patients with LVD and without LVD. RESULTS Sixteen patients met the criteria, the majority of patients (10) with World Health Organization (WHO) group 1 PAH. Thirteen received intravenous prostacyclin therapy, and 6 required inotropes before surgery. Five patients (31%) developed LVD after transplantation. Average time to onset of LVD was 4.2 days. Preoperative vasopressors were required in 60% of those developing LVD. Patients with LVD had lower right and left ventricular ejection fraction with higher left ventricular end diastolic volume before surgery. All patients recovered from LVD within 4 months after LT. CONCLUSIONS LVD is a phenomenon observed mostly in patients with WHO group 1 PAH receiving LT. Prompt recognition and treatment of this condition reduced morbidity.

Characteristics and outcomes among patients with need for early dialysis after lung transplantation surgery

With the introduction of lung allocation score (LAS), increasingly sicker patients are undergoing lung transplantation (LT). This study was conducted to determine the time trends in need for dialysis after LT, identify variables independently associated with need for dialysis, and evaluate its association with 1‐ and 5‐year mortality.