Consequences of being phenotypically mismatched with the environment: rapid muscle ultrastructural changes in cold-shocked black-capped chickadees (Poecile atricapillus).

Phenotypic flexibility has received considerable attention in the last decade; however, whereas many studies have reported amplitude of variation in phenotypic traits, much less attention has focused on the rate at which traits can adjust in response to sudden changes in the environment. We investigated whole animal and muscle phenotypic changes occurring in black-capped chickadees (Poecile atricapillus) acclimated to cold (-5°C) and warm (20°C) temperatures in the first 3 h following a 15°C temperature drop (over 3 h). Before the temperature change, cold-acclimated birds were consuming 95% more food, were carrying twice as much body fat, and had 23% larger pectoralis muscle fiber diameters than individuals kept at 20°C. In the 3 h following the temperature drop, these same birds altered their pectoralis muscle ultrastructure by increasing the number of capillaries per fiber area and the number of nuclei per millimeter of fiber by 22%, consequently leading to a 22% decrease in myonuclear domain (amount of cytoplasm serviced per nucleus), whereas no such changes were observed in the warm-acclimated birds. To our knowledge, this is the first demonstration of such a rapid adjustment in muscle fiber ultrastructure in vertebrates. These results support the hypothesis that chickadees maintaining a cold phenotype are better prepared than warm-phenotype individuals to respond to a sudden decline in temperature, such as what may be experienced in their natural wintering environment.

Muscle myonuclear domain, but not oxidative stress, decreases with age in a long-lived seabird with high activity costs.

In birds, many physiological parameters appear to remain constant with increasing age, showing no deterioration until 'catastrophic' mortality sets in. Given their high whole-organism metabolic rate and the importance of flight in foraging and predator avoidance, flight muscle deterioration and accumulated oxidative stress and tissue deterioration may be an important contributor to physiological senescence in wild birds. As a by-product of aerobic respiration, reactive oxygen species are produced and can cause structural damage within cells. The anti-oxidant system deters oxidative damage to macromolecules. We examined oxidative stress and muscle ultrastructure in thick-billed murres aged 8 to 37 years (N=50) in pectoralis muscle biopsies. When considered in general linear models with body mass, body size and sex, no oxidative stress parameter varied with age. In contrast, there was a decrease in myonuclear domain similar to that seen in human muscle aging. We conclude that for wild birds with very high flight activity levels, muscle ultrastructural changes may be an important contributor to demographic senescence. Such gradual, linear declines in muscle morphology may eventually contribute to 'catastrophic' failure in foraging or predator avoidance abilities, leading to demographic senescence.

Seasonal muscle ultrastructure plasticity and resistance of muscle structural changes during temperature increases in resident black-capped chickadees and rock pigeons.

Resident birds in temperate zones respond to seasonally fluctuating temperatures by adjusting their physiology, such as changes in basal metabolic rate or peak metabolic rate during cold exposure, or altering their organ sizes, so as to match the thermogenic requirements of their current environment. Climate change is predicted to cause increases in the frequency of heat and cold wave events, which could increase the likelihood that birds will face an environmental mismatch. Here, we examined seasonality and the effects of acute and chronic heat shock to 33°C and subsequent recovery from heat shock on the ultrastructure of the superficial pectoralis muscle fiber diameter, myonuclear domain (MND) and capillary density in two temperate bird species of differing body mass, the black-capped chickadee (Poecile atricapillus) and the rock pigeon (Columba livia). We found that muscle fiber ultrastructure did not change with heat treatment. However, in black-capped chickadees, there was a significant increase in fiber diameter in spring phenotype birds compared with summer phenotype birds. In rock pigeons, we saw no differences in fiber diameter across seasons. Capillary density did not change as a function of fiber diameter in black-capped chickadees, but did change seasonally, as did MND. Across seasons, as fiber diameter decreased, capillary density increased in the pectoralis muscle of rock pigeons. For both species in this study, we found that as fiber diameter increased, so did MND. Our findings imply that these two temperate birds employ different muscular growth strategies that may be metabolically beneficial to each.

Predictors of short-term postoperative survival after elective colectomy in colon cancer patients ≥ 80 years of age.

BACKGROUND: Individuals ≥ 80 years of age represent an increasing proportion of colon cancer diagnoses. Selecting these patients for elective surgery is challenging because of diminished overall health, functional decline, and limited data to guide decisions. The objective was to identify overall health measures that are predictive of poor survival after elective surgery in these oldest-old colon cancer patients. METHODS: Medicare beneficiaries ≥ 80 years who underwent elective colectomy for stage I-III colon cancer from 1992-2005 were identified from the Surveillance, Epidemiology and End Results(SEER)-Medicare database. Kaplan-Meier survival analysis determined 90-day and 1-year overall survival. Multivariable logistic regression assessed factors associated with short-term postoperative survival. RESULTS: Overall survival for the 12,979 oldest-old patients undergoing elective colectomy for colon cancer was 93.4 and 85.7 %, at 90 days and 1 year. Older age, male gender, frailty, increased hospitalizations in prior year, and dementia were most strongly associated with decreased survival. In addition, AJCC stage III (vs stage I) disease and widowed (vs married) were highly associated with decreased survival at 1 year. Although only 4.4 % of patients were considered frail, this had the strongest association with mortality, with an odds ratio of 8.4 (95 % confidence interval, 6.4-11.1). CONCLUSIONS: Although most oldest-old colon cancer patients do well after elective colectomy, a significant proportion (6.6 %) die by postoperative day 90 and frailty is the strongest predictor. The ability to identify frailty through billing claims is intriguing and suggests the potential to prospectively identify, through the electronic medical record, patients at highest risk of decreased survival.

Surgical treatment of colon cancer in patients aged 80 years and older : analysis of 31,574 patients in the SEER-Medicare database.

BACKGROUND: Age-related disparities in colon cancer treatment exist, with older patients being less likely to receive recommended therapy. However, to the authors' knowledge, few studies to date have focused on receipt of surgery. The objective of the current study was to describe patterns of surgery in patients aged ≥ 80 years with colon cancer and examine outcomes with and without colectomy. METHODS: Medicare beneficiaries aged ≥ 80 years with colon cancer who were diagnosed between 1992 and 2005 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Multivariable logistic regression analysis was used to assess factors associated with nonoperative management. Kaplan-Meier survival analysis determined 1-year overall and colon cancer-specific survival. RESULTS: Of 31,574 patients, 80% underwent colectomy. Approximately 46% were diagnosed during an urgent/emergent hospital admission, with decreased 1-year overall survival (70% vs 86% for patients diagnosed during an elective admission) noted among these individuals. Factors found to be most predictive of nonoperative management included older age, black race, more hospital admissions, use of home oxygen, use of a wheelchair, being frail, and having dementia. For both operative and nonoperative patients, the 1-year overall survival rate was lower than the colon cancer-specific survival rate (operative patients: 78% vs 89%; nonoperative patients: 58% vs 78%). CONCLUSIONS: The majority of older patients with colon cancer undergo surgery, with improved outcomes noted compared with nonoperative management. However, many patients who are not selected for surgery die of unrelated causes, reflecting good surgical selection. Patients undergoing surgery during an urgent/emergent admission have an increased short-term mortality risk. Because the earlier detection of colon cancer may increase the percentage of older patients undergoing elective surgery, the findings of the current study may have policy implications for colon cancer screening and suggest that age should not be the only factor driving cancer screening recommendations.

Outpatient diverticulitis: mild or myth?

BACKGROUND: Diverticulitis is considered common in the outpatient population, with mild variants of described diagnostic criteria: left lower quadrant pain, fever, and leukocytosis. Here, expected criteria utilization among outpatients with a possible diagnosis of diverticulitis is assessed. STUDY DESIGN: Primary care acute clinic visits in 2008 for diverticulitis (ICD-9 562.11/562.13) or left lower quadrant pain (789.04) were identified among patients ≥ 40 years old. Encounters were reviewed through structured manual chart abstraction and evaluated for diagnostic accuracy compared to expected criteria. Analysis included inter-rater reliability (kappa tests) and descriptive frequencies by diagnosis code and diverticulitis rating (χ (2) tests). RESULTS: A total of 376 acute visits were identified with codes for diverticulitis (n=97) or left lower quadrant pain (n=279). High inter-rater reliability was demonstrated for key clinical variables (kappa=0.84-1.0). Left lower quadrant pain was reported in >75% of patients, while temperature and white blood cell count data were frequently unavailable. Lack of these expected criteria resulted in low diagnostic accuracy ratings ("No/unlikely"-53.6% diverticulitis, 88.2% left lower quadrant pain, p<0.001). CONCLUSIONS: This investigation raises concern for low accuracy in the outpatient diagnosis of diverticulitis due to inconsistent use of expected criteria, suggesting a smaller population with true diverticulitis than previously anticipated, or lack of criteria applicability in this setting.

Mortality by stage for right- versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data.

PURPOSE: Recent studies have reported increased mortality for right-sided colon cancers but had limited adjustment for patient characteristics and conflicting results by stage. We examined the relationship between colon cancer location (right- v left-side) and 5-year mortality by stage. PATIENTS AND METHODS: We identified Medicare beneficiaries from 1992 to 2005 with American Joint Commission on Cancer stages I to III primary adenocarcinoma of the colon who underwent surgery for curative intent through Surveillance, Epidemiology, and End Results (SEER) -Medicare data. Adjusted hazard ratios (HRs) and 95% CIs for predictors of all-cause 5-year mortality were obtained by using Cox proportional hazards regression. RESULTS: Of 53,801 patients, 67% had right-sided colon cancer. Patients with right-sided cancer were more likely to be older, to be women, to be diagnosed with a more advanced stage, and to have more poorly differentiated tumors. Adjusted Cox regression showed no significant difference in mortality between right- and left-sided cancers for all stages combined (HR, 1.01; 95% CI, 0.98 to 1.04; P = .598) or for stage I cancers (HR, 0.95; 95% CI, 0.88 to 1.03; P = .211). Stage II right-sided cancers had lower mortality than left-sided cancers (HR, 0.92; 95% CI, 0.87 to 0.97; P = .001), and stage III right-sided cancers had higher mortality (HR, 1.12; 95% CI, 1.06 to 1.18; P < .001). CONCLUSION: When analysis was adjusted for multiple patient, disease, comorbidity, and treatment variables, no overall difference in 5-year mortality was seen between right- and left-sided colon cancers. However, within stage II disease, right-sided cancers had lower mortality; within stage III, right-sided cancers had higher mortality.

Adjuvant chemotherapy for stage II colon cancer with poor prognostic features.

PURPOSE: Adjuvant chemotherapy is typically considered for patients with stage II colon cancer characterized by poor prognostic features, including obstruction, perforation, emergent admission, T4 stage, resection of fewer than 12 lymph nodes, and poor histology. Despite frequent use, the survival advantage conferred on patients with stage II disease by chemotherapy is yet unproven. We sought to determine the overall survival benefit of chemotherapy among patients with stage II colon cancer having poor prognostic features. PATIENTS AND METHODS: A total of 43,032 Medicare beneficiaries who underwent colectomy for stage II and III primary colon adenocarcinoma diagnosed from 1992 to 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) -Medicare database. χ(2) and two-way analysis of variance were used to assess differences in patient- and disease-related characteristics. Five-year overall survival was examined using Kaplan-Meier survival analysis and Cox proportional hazards regression with propensity score weighting. RESULTS: Of the 24,847 patients with stage II cancer, 75% had one or more poor prognostic features. Adjuvant chemotherapy was received by 20% of patients with stage II disease and 57% of patients with stage III disease. After adjustment, 5-year survival benefit from chemotherapy was observed only for patients with stage III disease (hazard ratio[HR], 0.64; 95% CI, 0.60 to 0.67). No survival benefit was observed for patients with stage II cancer with no poor prognostic features (HR, 1.02; 95% CI, 0.84 to 1.25) or stage II cancer with any poor prognostic features (HR, 1.03; 95% CI, 0.94 to 1.13). CONCLUSION: Among Medicare patients identified with stage II colon cancer, either with or without poor prognostic features, adjuvant chemotherapy did not substantially improve overall survival. This lack of benefit must be considered in treatment decisions for similar older adults with colon cancer.

Optimizing surgical care of colon cancer in the older adult population.

OBJECTIVE: We have undertaken the current study to evaluate factors that correlate with postoperative complications in older patients undergoing surgery for colon cancer. PATIENTS AND METHODS: The database of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) from years 2005 to 2008 was accessed. Patients age 65 and older were included according to Current Procedural Terminology and International Classification of Disease-9 codes. Preoperative and operative variables were examined and postoperative complications assessed using a combination of univariate and multivariate statistical models. Propensity score matching was used to control for nonrandomization of the database. RESULTS: We found that patients undergoing laparoscopic (n = 2113) and open (n = 3801) surgery for the diagnosis of colon cancer were similar in age and gender. However, patients undergoing laparoscopic surgery were generally at lower risk for developing postoperative complications (16.1% vs. 25.4%, P < 0.005). Statistical models controlling for preoperative and operative variables demonstrated patients with elevated body mass index (odds ratio [OR] = 1.26), a history of chronic obstructive pulmonary disease (OR = 1.63), over age 85 (OR = 1.35), a surgery lasting longer than 4 hours (OR = 1.48), or having undergone an open operation (OR = 1.53) to have increased risk for developing postoperative complications. Propensity score match analysis confirmed these results. CONCLUSIONS: Identification of preoperative factors that predispose patients to postoperative complications could allow for the institution of protocols that may decrease these events. Furthermore, expanding the role of laparoscopy in the treatment of older patients with colon cancer may decrease rates of postoperative complications.

Readmission after colectomy for cancer predicts one-year mortality.

OBJECTIVES: Early hospital readmission is a common and costly problem in the Medicare population. In 2009, the Centers for Medicaid and Medicare Services began mandating hospital reporting of disease-specific readmission rates. We sought to determine the rate and predictors of readmission after colectomy for cancer, as well as the association between readmission and mortality. METHODS: Medicare beneficiaries who underwent colectomy for stage I to III colon adenocarcinoma from 1992 to 2002 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Multivariate logistic regression identified predictors of early readmission and 1-year mortality. Odds ratios were adjusted for multiple factors, including measures of comorbidity, socioeconomic status, and disease severity. RESULTS: Of 42,348 patients who were discharged, 4662 (11.0%) were readmitted within 30 days. The most common causes of rehospitalization were ileus/obstruction and infection. Significant predictors of readmission included male gender, comorbidity, emergent admission, prolonged hospital stay, blood transfusion, ostomy, and discharge to nursing home. Readmission was inversely associated with hospital procedure volume, but not surgeon volume. After adjusting for potential confounding variables, the predicted probability of 1-year mortality was 16% for readmitted patients, compared with 7% for those not readmitted. This difference in mortality was significant for all stages of cancer. CONCLUSIONS: Early readmission after colectomy for cancer is common and due in part to modifiable factors. There is a remarkable association between readmission and 1-year mortality. Early readmission is therefore an important quality-of-care indicator for colon cancer surgery. These findings may facilitate the development of targeted interventions that will decrease readmissions and improve patient outcomes.

Developing a practice-based learning and improvement curriculum for an academic general surgery residency.

BACKGROUND: Program directors in surgery are now facing the challenge of incorporating the ACGME's practice-based learning and improvement (PBLI) competency into residency curriculum. We introduced a comprehensive PBLI experience for postgraduate year 2 (PGY2) residents designed to integrate specific competency goals (ie, quality improvement, clinical thinking, and self-directed learning) within the context of residents' clinical practice. STUDY DESIGN: Fourteen PGY2 residents participated in a 3-week PBLI curriculum consisting of 3 components: complex clinical decision making, individual learning plan, and quality improvement (QI). To assess how effectively the curriculum addressed these 3 competencies, residents rated their understanding of PBLI by answering a 12-question written survey given pre- and post-rotation. Resident satisfaction was assessed through standard post-rotation evaluations. RESULTS: Analysis of the pre- and post-rotation surveys from the 14 participants showed an increase in all measured elements, including knowledge of PBLI (p < 0.001), ability to assess learning needs (p < 0.001), set learning goals (p < 0.001), understanding of QI concepts (p = 0.001), and experience with QI projects (p < 0.001). Fourteen QI projects were developed. Although many residents found the creation of measurable learning goals to be challenging, the process of identifying strengths and weaknesses enhanced the resident's self-understanding and contributed to overall satisfaction with the rotation. CONCLUSIONS: The initial implementation of our PBLI curriculum demonstrated that residents report personal progress in their clinical decision making, self-directed learning, and familiarity with QI. This comprehensive PBLI curriculum was accepted by surgical residents as a valuable part of their training. We are encouraged to continue a clinically grounded PBLI experience for PGY2 residents.

The diagnosis of diverticulitis in outpatients: on what evidence?

PURPOSE: Diverticular disease is common in the outpatient setting; yet, rigorous study of diagnosis and management strategies is currently limited to hospitalized patients. Here, we characterize the clinical assessment generating the diagnostic label of diverticulitis in outpatients. METHODS: Encounters for diverticulitis were identified using ICD-9 diagnosis codes (562.11/562.13) from the electronic medical record system of a tertiary referral hospital and its regional clinics. The frequencies of various demographic and clinical variables were compared between patients presenting in the emergency room (ER) or outpatient Clinic. RESULTS: Between 2003 and 2008, 820 inpatients and 2,576 outpatients met inclusion criteria (328 [13%] ER, 2,248 [87%] Clinic). Compared to ER patients, Clinic patients were less likely to undergo urgent abdominal/pelvic computed tomography (CT) scan (14% vs. 85%, p<.0001) or have an abnormal WBC count (35% vs. 69%, p<.0001). Twenty-four hour , including inpatient admission (30% ER vs. 3.5% Clinic, p<.0001) and colectomy (1.2% ER vs. 0.4% Clinic, p=0.08) were rare in both groups. CONCLUSION: Diverticulitis in the outpatient setting is often characterized by infrequent use of CT scans, lack of leukocytosis, and rare need for urgent surgery or early admission. As this diagnostic label appears to be commonly applied without objective evidence, further study is needed to evaluate its validity.

Perceptual-learning evidence for separate processing of asynchrony and order tasks.

Normal perception depends, in part, on accurate judgments of the temporal relationships between sensory events. Two such relative-timing skills are the ability to detect stimulus asynchrony and to discriminate stimulus order. Here we investigated the neural processes contributing to the performance of auditory asynchrony and order tasks in humans, using a perceptual-learning paradigm. In each of two parallel experiments, we tested listeners on a pretest and a posttest consisting of auditory relative-timing conditions. Between these two tests, we trained a subset of listeners approximately 1 h/d for 6-8 d on a single relative-timing condition. The trained listeners practiced asynchrony detection in one experiment and order discrimination in the other. Both groups were trained at sound onset with tones at 0.25 and 4.0 kHz. The remaining listeners in each experiment, who served as controls, did not receive multihour training during the 8-10 d between the pretest and posttest. These controls improved even without intervening training, adding to evidence that a single session of exposure to perceptual tasks can yield learning. Most importantly, each of the two groups of trained listeners learned more on their respective trained conditions than controls, but this learning occurred only on the two trained conditions. Neither group of trained listeners generalized their learning to the other task (order or asynchrony), an untrained temporal position (sound offset), or untrained frequency pairs. Thus, it appears that multihour training on relative-timing skills affects task-specific neural circuits that are tuned to a given temporal position and combination of stimulus components.