Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders.

BACKGROUND: Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease. METHODS: Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita. RESULTS: Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed. CONCLUSIONS: This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.

Risk factors for conversion from laparoscopic to open surgery: analysis of 2138 converted operations in the American College of Surgeons National Surgical Quality Improvement Program.

Minimal access procedures have influenced surgical practice and patient expectations. Risk of laparoscopic conversion to open surgery is frequently cited but vaguely quantified. The present study examines three common procedures to identify risk factors for laparoscopic conversion to open (LCO) events. Cross-sectional analysis using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP; 2005 to 2009) identified cases with laparoscopic procedure codes for appendectomy, cholecystectomy, and bariatric procedures. The primary outcome was conversion of a laparoscopic procedure to its open equivalent. Summary statistics for laparoscopic and LCO groups were compared and logistic regression analysis was used to estimate patient and operative risk factors for conversion. Of 176,014 selected laparoscopic operations, 2,138 (1.2%) were converted. Most patients were female (68%) and white (71.2%); mean age was 45.1 years. LCO cholecystectomy was significantly more likely (n = 1526 [1.9%]) and LCO bariatric procedures were less likely (n = 121 [0.3%]); appendectomy was intermediate (n = 491 [1.0%], P < 0.001). Patient factors associated with LCO included male sex (P < 0.001), age 30 years or older (P < 0.025), American Society of Anesthesiologists Class 2 to 4 (P < 0.001), obesity (P < 0.01), history of bleeding disorder (P = 0.036), or preoperative systemic inflammatory response syndrome or sepsis (P < 0.001). LCO was associated with greater incidence of postoperative complications, including death, organ space surgical site infection, sepsis, wound dehiscence, and return to the operating room (P < 0.001). Overall LCO incidence is low in hospitals participating in ACS-NSQIP. Conversion risk factors include patient age, sex, obesity, and preoperative comorbidity as well as the procedure performed. This information should be valuable to clinicians in discussing conversion risk with patients.

Risk of perforation increases with delay in recognition and surgery for acute appendicitis.

BACKGROUND: Appendicitis remains a common indication for urgent surgical intervention in the United States, and early appendectomy has long been advocated to mitigate the risk of appendiceal perforation. To better quantify the risk of perforation associated with delayed operative timing, this study examines the impact of length of inpatient stay preceding surgery on rates of perforated appendicitis in both adults and children. METHODS: This study was a cross-sectional analysis using the National Inpatient Sample and Kids' Inpatient Database from 1988-2008. We selected patients with a discharge diagnosis of acute appendicitis (perforated or nonperforated) and receiving appendectomy within 7 d after admission. Patients electively admitted or receiving drainage procedures before appendectomy were excluded. We analyzed perforation rates as a function of both age and length of inpatient hospitalization before appendectomy. RESULTS: Of 683,590 patients with a discharge diagnosis of appendicitis, 30.3% were recorded as perforated. Over 80% of patients underwent appendectomy on the day of admission, approximately 18% of operations were performed on hospital days 2-4, and later operations accounted for <1% of cases. During appendectomy on the day of admission, the perforation rate was 28.8%; this increased to 33.3% for surgeries on hospital day 2 and 78.8% by hospital day 8 (P<0.001). Adjusted for patient, procedure, and hospital characteristics, odds of perforation increased from 1.20 for adults and 1.08 for children on hospital day 2 to 4.76 for adults and 15.42 for children by hospital day 8 (P<0.001). CONCLUSIONS: Greater inpatient delay before appendectomy is associated with increased perforation rates for children and adults within this population-based study. These findings align with previous studies and with the conventional progressive pathophysiologic appendicitis model. Randomized prospective studies are needed to determine which patients benefit from nonoperative versus surgically aggressive management strategies for acute appendicitis.

Assessing trainee impact on operative time for common general surgical procedures in ACS-NSQIP.

OBJECTIVE: To examine the effect of surgical trainee involvement on operative time for common surgical procedures. Laparoscopic appendectomy, laparoscopic cholecystectomy, and open inguinal hernia repair comprise 17.7% of the total cases sampled in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. These cases are commonly performed by residents at varying levels of surgical training. STUDY DESIGN: A cross-sectional study was performed using American College of Surgeons National Surgical Quality Improvement Program data from 2005 through 2008 selecting patients undergoing laparoscopic appendectomy, laparoscopic cholecystectomy, and open inguinal hernia repair. The primary outcome was operative time and predictive variables were resident involvement and training level. Linear regression analysis was used to compare operative times between cases performed by an attending alone and those assisted by junior (postgraduate year 1-2) or senior (postgraduate year 3-5) trainees, adjusting for patient and operative factors. RESULTS: A total of 115,535 surgical cases were included, with 65,364 (59%) performed with junior or senior surgical residents. Resident participation was associated with higher operative times with no significant differences between the junior and senior cohorts; this effect persisted after controlling for potential confounding factors. Operative time increased by 16.6 minutes (95% confidence interval, 16.2-17.0) for junior residents and also by 16.6 minutes (95% confidence interval, 16.2-16.9) for senior residents. CONCLUSIONS: Surgical trainees' participation in common surgical procedures is associated with an increase in total operative time, with no difference between trainee seniority levels. This finding may be significant in assessing the impact of residency training programs on hospital efficiency.

Telomere length is a determinant of emphysema susceptibility.

RATIONALE: Germline mutations in the enzyme telomerase cause telomere shortening, and have their most common clinical manifestation in age-related lung disease that manifests as idiopathic pulmonary fibrosis. Short telomeres are also a unique heritable trait that is acquired with age. OBJECTIVES: We sought to understand the mechanisms by which telomerase deficiency contributes to lung disease. METHODS: We studied telomerase null mice with short telomeres. MEASUREMENTS AND MAIN RESULTS: Although they have no baseline histologic defects, when mice with short telomeres are exposed to chronic cigarette smoke, in contrast with controls, they develop emphysematous air space enlargement. The emphysema susceptibility did not depend on circulating cell genotype, because mice with short telomeres developed emphysema even when transplanted with wild-type bone marrow. In lung epithelium, cigarette smoke exposure caused additive DNA damage to telomere dysfunction, which limited their proliferative recovery, and coincided with a failure to down-regulate p21, a mediator of cellular senescence, and we show here, a determinant of alveolar epithelial cell cycle progression. We also report early onset of emphysema, in addition to pulmonary fibrosis, in a family with a germline deletion in the Box H domain of the RNA component of telomerase. CONCLUSIONS: Our data indicate that short telomeres lower the threshold of cigarette smoke-induced damage, and implicate telomere length as a genetic susceptibility factor in emphysema, potentially contributing to its age-related onset in humans.