Sex and genetic differences in postoperative cognitive dysfunction: a longitudinal cohort analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common postoperative complication experienced by patients aged 65 years and older, and these older adults comprise more than one third of the surgical patients in the USA. Because not everyone with a history of exposure to surgery and anesthesia develops POCD, there are likely major biological risk factors involved. There are important gaps in our knowledge regarding whether genetic makeup, biological sex, or other Alzheimer's disease risk factors predispose older adults to developing POCD. We set out to determine whether biological sex and Apolipoprotein E-ε4 (APOE4) carrier status increase the risk of developing POCD in older adults. METHODS: We performed a cohort analysis of 1033 participants of prospective longitudinal aging studies. Participants underwent regular cognitive test batteries and we compared the annual rate of change over time in various cognitive measures in the women exposed to surgery and general anesthesia compared to the men exposed to surgery and general anesthesia. Mixed-effects statistical models were used to assess the relationship between biological sex, APOE4 carrier status, surgery and anesthesia exposure, and the rate of change in cognitive test scores. RESULTS: When comparing all men (n = 89) and women (n = 164) who had surgery, there were no significant sex differences in postoperative cognitive outcomes. However, men with an APOE4 allele performed significantly worse on cognitive testing following surgery and anesthesia than women APOE4 carriers, even after adjusting for age, education level, and comorbidities. CONCLUSIONS: Older men with APOE4 allele may be more vulnerable to postoperative cognitive dysfunction than older women with APOE4 allele.

Surgery is associated with ventricular enlargement as well as cognitive and functional decline.

INTRODUCTION: In preclinical studies, surgery/anesthesia contribute to cognitive decline and enhance neuropathologic changes underlying Alzheimer's disease (AD). Nevertheless, the link between surgery, anesthesia, apolipoprotein E ε4 (APOE ε4), and AD remains unclear. METHODS: We performed a retrospective cohort analysis of two prospective longitudinal aging studies. Mixed-effects statistical models were used to assess the relationship between surgical/anesthetic exposure, the APOE genotype, and rate of change in measures of cognition, function, and brain volumes. RESULTS: The surgical group (n = 182) experienced a more rapid rate of deterioration compared with the nonsurgical group (n = 345) in several cognitive, functional, and brain magnetic resonance imaging measures. Furthermore, there was a significant synergistic effect of anesthesia/surgery exposure and presence of the APOE ε4 allele in the decline of multiple cognitive and functional measures. DISCUSSION: These data provide insight into the role of surgical exposure as a risk factor for cognitive and functional decline in older adults.

Prevalence of complicated gastroesophageal reflux disease and Barrett's esophagus among racial groups in a multi-center consortium.

AIMS: The Clinical Outcomes Research Initiative database was used to evaluate ethnic trends in complicated reflux disease and suspected Barrett's esophagus among various racial groups. METHODS: Endoscopic findings for procedures performed January 2000-December 2005 for any indication and for reflux-related indications were reviewed by racial group. RESULTS: Of 280,075 procedures examined, Hispanics were the most likely to have esophagitis (Hispanic 19.6%, white 17.3%, black 15.8%, Asian/Pacific Islander 9.5%, P-value<0.0001), and white subjects were most likely to have suspected BE (white 5.0%, Hispanic 2.9%, Asian/Pacific Islander 1.8%, black 1.5%, P-value<0.0001). Endoscopies performed for reflux-related indications had similar trends for esophagitis and esophageal stricture. Among reflux/Barrett's screening procedures adjusted for age and gender, Hispanics were most likely to have esophagitis (OR=1.28, P-value<0.0001) compared to Caucasians. CONCLUSION: Our results demonstrate an association of suspected Barrett's esophagus and stricture with white patients and esophagitis with Hispanic patients. These findings need to be followed-up with further study.

The value of traditional upper endoscopy as a diagnostic test for Barrett's esophagus.

BACKGROUND: The standard test for diagnosing Barrett's esophagus (BE) is a conventional upper endoscopy. However, studies have shown that confirmation of BE by endoscopy with histologic intestinal metaplasia can be difficult. OBJECTIVE: To determine the overall accuracy, as well as factors that influence the accuracy of a conventional upper endoscopy in diagnosing BE. SETTING: Thirteen academic, community, and Veterans Affairs sites. DESIGN: A retrospective data review. PATIENTS: Patients who underwent an upper endoscopy with a finding of "suspected Barrett's esophagus" and esophageal biopsies. Pathology reports were examined to identify cases with intestinal metaplasia. MAIN OUTCOME MEASUREMENTS: Percentage of pathology-confirmed BE among suspected cases. RESULTS: A total of 2511 procedures were examined; the frequency of biopsy-confirmed BE was 48.4%. Multivariate logistic regression identified the following factors to be independently associated with biopsy-confirmed BE: long-segment BE that measured > or = 3 cm (odds ratio [OR] 4.61 [95% CI, 3.73-5.69]), male sex (OR 1.82 [95% CI, 1.49-2.22]), increasing age (age interval 70-79 years with OR 2.33 compared with age <50 years [95% CI, 1.75-3.10]), the presence of a hiatal hernia (OR 1.46 [95% CI, 1.22-1.84]), and white race (OR 1.90 [95% CI, 1.49-2.22]). LIMITATIONS: Biopsy specimens were assumed to sample the tubular esophagus; the actual pathology slides were not reevaluated by the investigators. CONCLUSIONS: Endoscopic evaluation has limitations for the diagnosis of BE. Specific patient and endoscopic characteristics may be associated with the confirmation of BE on biopsy specimens. Further study is needed to determine if new endoscopic imaging technologies improve the ability to correctly identify BE.

Colonic biopsy practice for evaluation of diarrhea in patients with normal endoscopic findings: results from a national endoscopic database.

BACKGROUND: The colonic biopsy is the only reliable method for identification of microscopic colitis in patients with chronic diarrhea and normal endoscopic findings. METHODS: The Clinical Outcomes Research Initiative national endoscopic database was analyzed to determine the rate at which colonic biopsy specimens were obtained in patients undergoing colonoscopy for the evaluation of diarrhea with no visible mucosal abnormality. RESULTS: Between January 2000 and December 2003, 5565 unique adult patients underwent colonoscopy for evaluation of diarrhea without detection of any mucosal abnormality. Colonic mucosal biopsy specimens were obtained in 4410 (79.2%) of these patients. The rates at which biopsy specimens were obtained differed among the sites where colonoscopy was performed; biopsy specimens were obtained from more patients undergoing colonoscopy in university-affiliated settings (86.8%) compared with Veterans Affairs Medical Centers (VAMC) (78.5%) or community sites (78.6%) ( p < 0.001). On multivariate analysis, biopsy specimens were more likely to be obtained in younger patients (OR 0.7: 95%CI[0.6, 0.8] for age >50 years vs. <50 years), women patients (OR 1.4: 95% CI[1.2, 1.6] in community setting; OR 4.1: 95% CI[1.6, 10.5] in VAMC setting), and patients seen in university-affiliated medical centers (university center OR 2.1: 95% CI[1.5, 3.0] vs. community setting). CONCLUSIONS: Biopsy specimens are obtained in four fifths of patients with diarrhea and normal colonoscopy findings to exclude microscopic colitis. Variation in biopsy practice exists among endoscopy site types and by gender. Clear guidelines are needed for the endoscopic approach to these patients.

A phase I study of 5-fluorouracil, leucovorin, and celecoxib in patients with incurable colorectal cancer.

A phase I study of fixed-dose 5-fluorouracil (FU) and leucovorin (LCV), with excalating doses of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib, was conducted in 16 patients with advanced colorectal adenocarcinoma. At doses typically used to treat arthritis patients (100-200 mg po BID), celecoxib did not increase toxicities expected from the chemotherapy alone. 5-FU and leucovorin did not affect COX-2 inhibition by celecoxib. Preliminary data suggest it is safe to combine celecoxib with standard chemotherapeutic agents, in treatment of patients with colorectal cancer.