Atrial Arrhythmias in Patients With Pulmonary Hypertension.

TOPIC IMPORTANCE: Atrial arrhythmia (AA) are common in patients with pulmonary hypertension (PH) and contribute to morbidity and mortality. Given the growing PH population, understanding the pathophysiology, clinical impact, and management of AA in PH is important. REVIEW FINDINGS: AA occurs in PH with a 5-year incidence of 10% to 25%. AA confers a higher morbidity and mortality, and restoration of normal sinus rhythm improves survival and functionality. AA is thought to develop because of structural alterations of the right atrium caused by changes to the right ventricle (RV) due to elevated pulmonary artery pressures. AA can subsequently worsen RV function. Current guidelines do not provide comprehensive recommendations for the management of AA in PH. Robust evidence to favor a specific treatment approach is lacking. Although the role of medical rate or rhythm control, and the use of cardioversion and ablation, can be inferred from other populations, evidence is lacking in the PH population. Much remains to be determined regarding the optimal management strategy. We present here our institutional approach and discuss areas for future research. SUMMARY: This review highlights the epidemiology and pathophysiology of AA in patients with PH, describes the relationship between AA and RV dysfunction, and discusses current management practices. We outline our institutional approach and offer directions for future investigation.

Cardiopulmonary Exercise Testing in Pulmonary Arterial Hypertension.

Cardiopulmonary exercise testing (CPET) is a comprehensive methodology well studied in pulmonary arterial hypertension (PAH) with roles in diagnosis, treatment response, and prognosis. Submaximal and maximal exercise data is a valuable tool in detecting abnormal hemodynamics associated with exercise-induced and resting pulmonary hypertension as well as right ventricular dysfunction. The increased granularity of CPET may help further risk stratify patients to inform prognosis and better individualize treatment decisions. This article reviews the most commonly implicated variables from CPET in PAH literature and summarizes the latest developments in CPET and exercise testing.

A Prospective Trial of an In-house Overnight Fellow Rotation in the Intensive Care Unit.

Background: Although previous studies in academic intensive care units (ICUs) have found no improvement in patient care outcomes with in-house overnight attending physician coverage compared with home call coverage, the effect of in-house supervision on trainee education and well-being is less clear. In addition, no studies have examined the effect of in-house coverage by fellow physicians overnight. Objective: What is the impact of an in-house overnight critical care fellow on resident, fellow, and attending perception of patient safety, house staff education, and house staff well-being? Methods: A prospective trial alternating 2-week periods of in-house overnight critical care fellow coverage with 2-week periods of home call coverage was performed in our tertiary medical ICU. Residents, fellows, and attendings were surveyed to evaluate perceptions of the night fellows' impact on patient care, communication, supervision, educational experience, autonomy, well-being, and job satisfaction. Results: Over the 6-month study period, surveys were sent to 83 residents, 22 fellows, and 23 attendings, with completion by 56 (67%), 22 (100%), and 16 (70%), respectively. Overall, 89% of residents, 68% of fellows, and 81% of attendings reported perceived improvements in patient care with an in-house fellow. The in-house fellow was also associated with improved well-being in 79% of residents and 73% of fellows, and 82% of residents felt that it positively impacted education. Conclusion: As compared with the traditional home call system, an in-house night critical care fellow can improve the perception of patient care, trainee well-being, and education in a tertiary ICU at an academic hospital.

Right Side of the Heart Pulmonary Circulation Unit Involvement in Left-Sided Heart Failure: Diagnostic, Prognostic, and Therapeutic Implications.

Although long neglected, the right side of the heart (RH) is now widely accepted as a pivotal player in heart failure (HF) either with reduced or preserved ejection fraction. The chronic overload of the pulmonary microcirculation results in an initial phase characterized by right ventricular (RV) hypertrophy, right atrial dilation, and diastolic dysfunction. This progresses to overt RH failure when RV dilation and systolic dysfunction lead to RV-pulmonary arterial (RV-PA) uncoupling with low RV output. In the context of its established relevance to progression of HF, clinicians should consider assessment of the RH with information from clinical assessment, biomarkers, and imaging. Notably, no single parameter can predict prognosis alone in HF. Assessments simultaneously should encompass RV systolic function, pulmonary pressures, an estimation of RV-PA coupling, and RH morphologic features. Despite a large volume of evidence indicating the relevance of RH function to the clinical syndrome of HF, evidence-based management strategies are lacking. Targeting RH dysfunction in HF should be an objective of future investigations, being an unmet need in the current management of HF.

Update on Medical Management of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension is a rare disease characterized by pulmonary microvasculature remodeling leading to right ventricular failure and death. Medical management of pulmonary hypertension has grown increasingly complex as more therapeutic agents have been developed. Evolving treatment strategies leveraging the endothelin, nitric oxide, and prostacyclin pathways lead to improved exercise capacity and outcomes in patients; however, significant opportunities for advancement remain.

Significance of autoimmune disease in severe pulmonary hypertension complicating extensive pulmonary fibrosis: a prospective cohort study.

The association of autoimmune disease (AI) with transplant-free survival in the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis remains unclear. We report cases of severe pulmonary hypertension (mean pulmonary artery pressure ≥35 mmHg and right ventricular dysfunction) and extensive pulmonary fibrosis after pulmonary arterial hypertension-specific therapy. We used multivariate regression to determine the clinical variables associated with transplant-free survival. Of 286 screened patients, 55 demonstrated severe pulmonary hypertension and extensive pulmonary fibrosis and were treated with parenteral prostacyclin therapy. The (+)AI subgroup (n = 34), when compared to the (-)AI subgroup (n = 21), was more likely to be female (77% versus 19%) and younger (58.7 ± 12.1 versus 66.0 ± 10.7 years), and revealed lower forced vital capacity (absolute) (1.9 ± 0.7 versus 2.9 ± 1.1 L), higher DLCO (% predicted) (31.1 ± 15.2 versus 23.2 ± 8.0), and increased unadjusted transplant-free survival (1 year (84.6 ± 6.3% versus 45 ± 11.1%)), 3 years (71 ± 8.2% versus 28.6 ± 11.9%), and 5 years (47.6 ± 9.6% versus 6.4 ± 8.2%); (p = 0.01)). Transplant-free survival was unchanged after adjusting for age and gender. The pulmonary hemodynamic profiles improved after parenteral prostacyclin therapy, independent of AI status. The baseline variables associated with mortality included age at pulmonary hypertension diagnosis (heart rate (HR) 1.23 (confidence interval (CI) 1.03-1.47); p = 0.02) and presence of AI (HR 0.26 (confidence interval (CI) 0.10-0.70); p < 0.01). Gas exchange was not adversely affected by parenteral prostacyclin therapy. In the setting of severe Group 3 pulmonary hypertension and extensive pulmonary fibrosis treated with pulmonary arterial hypertension-specific therapy, AI is independently associated with increased transplant-free survival. Pulmonary hypertension/pulmonary fibrosis associated with AI should be considered in future clinical trials of pulmonary arterial hypertension-specific therapy in Group 3 pulmonary hypertension.

Non-hematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults.

OBJECTIVES: The International Prognostic Scoring System (IPSS) is commonly used to predict survival and assign treatment for the myelodysplastic syndromes (MDS). We explored whether self-reported and readily available non-hematologic predictors of survival add independent prognostic information to the IPSS. MATERIALS AND METHODS: Retrospective cohort study of consecutive MDS patients ≥age 65 who presented to Dana-Farber Cancer Institute between 2006 and 2011 and completed a baseline quality of life questionnaire. Questions corresponding to functional status and symptoms and extracted clinical-pathologic data from medical records. Kaplan-Meier and Cox proportional hazards models were used to estimate survival. RESULTS: One hundred fourteen patients consented and were available for analysis. Median age was 73 years, and the majority of patients were White, were male, and had a Charlson comorbidity score of <2. Few patients (24%) had an IPSS score consistent with lower-risk disease and the majority received chemotherapy. In addition to IPSS score and history of prior chemotherapy or radiation, significant univariate predictors of survival included low serum albumin, Charlson score, performance status, ability to take a long walk, and interference of physical symptoms in family life. The multivariate model that best predicted mortality included low serum albumin (HR=2.3; 95% CI: 1.06-5.14), therapy-related MDS (HR=2.1; 95% CI: 1.16-4.24), IPSS score (HR=1.7; 95% CI: 1.14-2.49), and ease taking a long walk (HR=0.44; 95% CI: 0.23-0.90). CONCLUSIONS: In this study of older adults with MDS, we found that low serum albumin and physical function added important prognostic information to the IPSS score. Self-reported physical function was more predictive than physician-assigned performance status.

Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes.

We explored whether geriatric assessment variables predicted mortality in addition to known prognostic factors in 101 patients aged ≥ 65 with newly diagnosed AML. Baseline comorbidity score (HR=1.92; 95%CI 1.18-3.11), difficulty with strenuous activity (HR=2.18; 95%CI 1.19-4.00), and pain (HR=2.17; 95%CI 1.19-3.97) were independent prognostic factors for greater risk of death in a multivariable model that included cytogenetic risk group. They remained independent predictors in the subset of patients with baseline ECOG PS 0-1. Our results support the use of geriatric assessment to better predict prognosis in older patients with AML, even among those with excellent functional status.

Factors associated with publication of plenary presentations at the Society of Gynecologic Oncologists annual meeting.

OBJECTIVE: To determine the rate and factors associated with publication of plenary abstract presentations from the Society of Gynecologic Oncologists annual meeting. METHODS: Plenary presentations were reviewed from 2000 to 2005. A PubMed search was performed to identify subsequent peer-reviewed publication of these presentations. Chi-squared test and logistic regression were used for statistical analyses. RESULTS: Of 378 main, focused or express plenary presentations, 173 (45.8%) involved multiple and 205 (54.2%) single institutions. The types of study include: chart review (29.4%), cohort study (28.0%), translational (23.5%), and randomized clinical trial (6.9%). 309 (81.7%) of presentations were subsequently published. The median time from presentation to publication was 14months (range: 1-85). Studies from multiple vs. single institutions were more likely to be published (87.9% vs. 76.6%; p=0.005). In addition, randomized controlled trials were more likely to be published compared with chart review, cohort, and translation research (92.3% vs. 83.8%, 77.4%, and 74.2%; p<0.01). On multivariate analysis, multi-institutional studies (OR=2.28, 95% CI=1.28-4.04; p=0.005) and type of study (OR=1.64, 95% CI=1.19-2.26; p=0.002) were independent factors associated with publication. In addition, multi-institutional studies had longer times from presentation to publication compared with their counterparts. CONCLUSIONS: A high percentage of plenary presentations at the Society of Gynecologic Oncologists annual meeting resulted in subsequent publication. Multi-institutional studies and randomized clinical trials were more likely to be published.

Characteristics of success in mentoring and research productivity - a case-control study of academic centers.

OBJECTIVES: While mentoring has been associated with research productivity, the specific characteristics of successful mentoring have not been well studied. Thus, we performed a case-control study to identify characteristics of successful mentoring programs. METHODS: Institutions were divided based on number of plenary research presentations at an annual society meeting over 6years. Case institutions (Group A) had more presentations vs. controls (Group B). A survey of professors and research fellows assessed characteristics of their mentoring program. Chi-square and logistic regression analyses were performed. RESULTS: Of 159 surveyed, response rates were 46% for professors and 51% for fellows. Compared to Group B, Group A was more likely to have: an additional year of protected fellowship research training (62% vs. 24%; p=0.003), an established program to connect a mentor and mentee with similar research interests (52% vs. 27%; p=0.049), methods to provide feedback to mentors (62% vs. 29%; p=0.01), require mentee research progress reports (45% vs. 21%; p=0.047), and report ease of identifying a mentor (90% vs. 69%; p=0.046). On multivariate analyses, the additional year of research training (OR=7.53, 95% CI: 2.10-27.09; p=0.002) and ease at identifying a research mentor (OR=7.45, 95% CI: 1.44-38.6; p=0.017) remained as independent factors associated with higher research productivity. CONCLUSIONS: Our data suggest that programs can enhance research productivity with the incorporation of accountability features including formalized reports of progress and mentorship feedback in fellowship training. Facilitating the identification of a mentor and providing an additional year of research may be independent factors associated with research productivity.

Role of Sonic Hedgehog signaling during progression from inflammation to cancer in the stomach.

Despite advances in treatment and the declining incidence, gastric cancer remains the second leading cause of cancer-related deaths in the world. Understanding the progression from inflammation to cancer in the stomach is crucial in the development of novel therapies and strategies for treating this disease. Chronic inflammation of the stomach is typically caused by Helicobacter pylori (H. pylori) and resulting lesions may lead to gastric cancer. During the progression from inflammation to cancer, the stomach epithelium changes with evidence of the disruption of normal epithelial cell differentiation and infiltrating inflammatory cells. Coincident with the development of atrophic gastritis and metaplasia, is the loss of the gastric morphogen Sonic Hedgehog (Shh). Given its critical role as a regulator of gastric tissue homeostasis, the disruption of Shh expression during inflammation correlates with the loss of normal epithelial cell differentiation, but this has only recently been rigorously tested in vivo using a unique mouse model of targeted gastric Shh deletion. While pre-neoplastic lesions such as atrophic gastritis and intestinal metaplasia are associated with the loss of Shh within the acid-secreting glands of the stomach, there is a clear link between elevated Shh and signaling to gastric cancers. The current review focuses on the effects of aberrant Shh expression and its role in the development of gastric cancer, specifically in response to H. pylori infection.

Predictors of intensive care unit utilization in gynecologic oncology surgery.

OBJECTIVES: The objectives of the study were to examine factors predicting intensive care unit (ICU) admission after surgery for gynecologic cancer and to determine the impact of ICU admission on survival. METHODS: This was a retrospective study of women undergoing laparotomy for staging and debulking of gynecologic cancer at an academic hospital with tertiary ICU facilities from July 2000 through June 2003. Data on clinicopathologic factors, comorbidities, operative outcomes, and survival were obtained from medical records and institutional cancer registry. The χ analysis, Kaplan-Meier analysis, and Cox regression methods were used for analyses. RESULTS: Two hundred fifty-five patients met our inclusion criteria, 43 of whom had a postoperative admission to the ICU. Factors predicting ICU admission on univariate analysis included age 60 years or older, hematocrit of 30% or less, albumin of 3.5 g/dL or less, and Charlson Comorbidity Index (CCI) score greater than 8; after multivariate analysis, CCI score of greater than 8 (hazard ratio, 2.5; confidence interval, 1.11-5.69) and albumin of 3.5 or less (hazard ratio, 3.8; confidence interval, 1.66-8.85) were associated with an increased risk of ICU admission. After adjusting for albumin and CCI score, ICU admission did not have a significant effect on survival. CONCLUSIONS: The ability to predict ICU admission helps in appropriate counseling of patients and identification of institutional resource utilization.

Influence of gynecologic oncologists on the survival of patients with endometrial cancer.

PURPOSE: Despite a lack of evidence for survival benefit, the American College of Obstetrics and Gynecology has recommendations for referral to gynecologic oncologists for the treatment of endometrial cancer. Therefore, we propose to determine the influence of gynecologic oncologists on the treatment and survival of patients with endometrial cancer. PATIENTS AND METHODS: Data were obtained from Medicare and Surveillance, Epidemiology, and End Results (SEER) databases from 1988 to 2005. Kaplan-Meier and Cox proportional hazard methods were used for analyses. RESULTS: Of 18,338 women, 21.4% received care from gynecologic oncologists (group A) while 78.6% were treated by others (group B). Women in group A were older (age > 71 years: 49.6% v 44%; P < .001), had more lymph nodes (> 16) removed (22% v 17%; P < .001), presented with more advanced (stages III to IV) cancers (21.9% v 14.6%; P < .001), had higher-grade tumors (P < .001), and were more likely to receive chemotherapy for advanced disease (22.6% v 12.4%; P < .001). In those with stages II to IV disease, the 5-year disease-specific survival (DSS) of group A was 79% versus 73% in group B (P = .001). Moreover, in advanced-stage (III to IV) disease, group A had 5-year DSS of 72% versus 64% in group B (P < .001). However, no association with DSS was identified in stage I cancers. On multivariable analysis, younger age, early stage, lower grade, and treatment by gynecologic oncologists were independent prognostic factors for improved survival. CONCLUSION: Patients with endometrial cancer treated by gynecologic oncologists were more likely to undergo staging surgery and receive adjuvant chemotherapy for advanced disease. Care provided by gynecologic oncologists improved the survival of those with high-risk cancers.

Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients.

OBJECTIVE: To determine the clinicopathologic factors associated with survival in neuroendocrine small cell cervical cancer patients. STUDY DESIGN: Patients were identified from a review of literature with an additional 52 patients from four hospitals. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: Of 188 patients, 135 had stages I-IIA, 45 stages IIB-IVA, and 8 stage IVB disease. A total of 55.3% underwent surgery, 16.0% had chemoradiation, 12.8% radiation, and 3.2% chemotherapy alone. The 5-year disease-specific survival in stage I-IIA, IIB-IVA, and IVB disease was 36.8%, 9.8%, and 0%, respectively (P < .001). Adjuvant chemotherapy or chemoradiation was associated with improved survival in patients with stages IIB-IVA disease compared with those who did not receive chemotherapy (17.8% vs 6.0%; P = .04). On multivariable analysis, early-stage disease and use of chemotherapy or chemoradiation were independent prognostic factors for improved survival. CONCLUSION: Use of adjuvant chemotherapy or chemoradiation was associated with higher survival in small cell cervical cancer patients.

Adjuvant radiation therapy in stage III node-positive uterine cancer.

OBJECTIVES: To determine the association of adjuvant radiotherapy and outcomes of women with stage III node-positive uterine cancer. METHODS: All patients with surgically-staged stage III node-positive uterine cancer from the Surveillance Epidemiology and End Results database of the US National Cancer Institute from 1988 to 2001 were identified. Data were analyzed using Kaplan-Meier and logistic regression methods. RESULTS: Of 943 women, the median age was 64 years (range: 28-93). 82.1%, 8.6%, and 6.8% were White, Black, and Asian respectively. The median number of removed nodes was 11. 54.9% had a single positive node and 45.1% had 2-5 positive nodes. Endometrioid, papillary serous, sarcomas, and clear cell carcinomas comprised of 69.7%, 16.3%, 9.9%, and 4.1% of histologies, respectively. 67.3% of the women underwent adjuvant radiotherapy with a 5-year disease-specific survival of 67.9% compared to 53.4% in those without radiotherapy (p<0.001). Adjuvant radiotherapy improved the survival from 54.4% to 74.3% (p<0.001) in those with a single positive node and from 52.4% to 59.7% (p=0.089) in those with 2-5 positive nodes. On multivariate analysis, older age, non-endometrioid histology, and lack of adjuvant radiotherapy remained as significant independent prognostic factors for worsened survival. CONCLUSIONS: Our data suggest that adjuvant radiotherapy is associated with a significant survival benefit in women with single-positive node endometrioid uterine cancers. Prospective clinical trials are warranted to confirm these findings.