26 research outputs found

    Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia.

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    BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. METHODS: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. RESULTS: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. CONCLUSIONS: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia

    Will Patients Benefit from Regionalization of Gynecologic Cancer Care?

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    OBJECTIVE: Patient chances for cure and palliation for a variety of malignancies may be greatly affected by the care provided by a treating hospital. We sought to determine the effect of volume and teaching status on patient outcomes for five gynecologic malignancies: endometrial, cervical, ovarian and vulvar carcinoma and uterine sarcoma. METHODS: The Florida Cancer Data System dataset was queried for all patients undergoing treatment for gynecologic cancers from 1990-2000. RESULTS: Overall, 48,981 patients with gynecologic malignancies were identified. Endometrial tumors were the most common, representing 43.2% of the entire cohort, followed by ovarian cancer (30.9%), cervical cancer (20.8%), vulvar cancer (4.6%), and uterine sarcoma (0.5%). By univariate analysis, although patients treated at high volume centers (HVC) were significantly younger, they benefited from an improved short-term (30-day and/or 90-day) survival for cervical, ovarian and endometrial cancers. Multivariate analysis (MVA), however, failed to demonstrate significant survival benefit for gynecologic cancer patients treated at teaching facilities (TF) or HVC. Significant prognostic factors at presentation by MVA were age over 65 (HR = 2.6, p<0.01), African-American race (HR = 1.36, p<0.01), and advanced stage (regional HR = 2.08, p<0.01; advanced HR = 3.82, p<0.01, respectively). Surgery and use of chemotherapy were each significantly associated with improved survival. CONCLUSION: No difference in patient survival was observed for any gynecologic malignancy based upon treating hospital teaching or volume status. Although instances of improved outcomes may occur, overall further regionalization would not appear to significantly improve patient survival

    Unique Aspects of the Elderly Surgical Population

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    Increasing life expectancies paired with age-related comorbidities have resulted in the continued growth of the elderly surgical population. In this group, age-associated changes and decreased physiological reserve impede the body’s ability to maintain homeostasis during times of physiological stress, with a subsequent decrease in physiological reserve. This can lead to age-related physiological and cognitive dysfunction resulting in perioperative complications. Changes in the cardiovascular, pulmonary, nervous, hepatorenal, endocrine, skin, and soft tissue systems are discussed as they are connected to the perioperative experience. Alterations affect both the pharmacodynamics and pharmacokinetics of administered drugs. Elderly patients with coexisting diseases are at a greater risk for polypharmacy that can further complicate anesthetic management. Consequently, the importance of conducting a focused preoperative evaluation and identifying potential risk factors is strongly emphasized. Efforts to maintain intraoperative normothermia have been shown to be of great importance. Procedures to maintain stable body temperature throughout the perioperative period are presented. The choice of anesthetic technique, in regard to a regional versus general anesthetic approach, is debated widely in the literature. The type of anesthesia to be administered should be assessed on a case-by-case basis, with special consideration given to the health status of the patient, the type of operation being conducted, and the expertise of the anesthesiologist. Specifically addressed in this article are age-related cognitive issues such as postoperative cognitive dysfunction and postoperative delirium. Strategies are suggested for avoiding these pitfalls

    A 3-dimensional ultrasound study of local anesthetic spread during lateral popliteal nerve block: what is the ideal end point for needle tip position?

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    Recent clinical trials suggest that subfascial (sometimes termed subepineural) injections result in faster block onset and success compared with conventional techniques. This prospective, randomized, observer-blinded study measured and compared the 3-dimensional spread pattern and volume of perineural local anesthetic (LA) in contact with the sciatic nerve after subfascial versus extrafascial lateral popliteal injections. Sixty patients were randomly assigned to either the subfascial or the extrafascial injection group. All patients received a single-injection, US-guided lateral popliteal sciatic nerve block for postoperative pain. Depending on group assignment, the needle tip was placed outside or beneath the sciatic fascial sheath for a single injection of 30 mL of ropivacaine 0.5%. Using 3-dimensional ultrasound imaging, postblock scans were acquired to quantify the volume and spread pattern of perineural LA around the sciatic nerve in each group. The mean LA perineural volume for the extrafascial group was 1.48 (SD, 0.50) mL versus a mean of 5.57 (SD, 1.68) mL for the subfascial group, P < 0.05. The mean distance of longitudinal perineural LA spread (along the length of the nerve) for the subfascial group was 66% greater than that observed using the conventional technique (9.3 vs 5.6 cm, P < 0.01). Complete sensory block to pinprick for the extrafascial group was 63% versus 90% (P < 0.05) for the subfascial group. Placement of the needle tip beneath the complex fascial sheath of the sciatic nerve resulted in significantly greater perineural local anesthetic volume following a single-injection lateral popliteal approach at the nerve bifurcation and was associated with greater sensory blockade and a characteristic laminar LA spread pattern

    Primary Solid Tumors of the Colon and Rectum in the Pediatric Patient: A Review of 270 Cases

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    To study the outcomes of solid tumors of the colon and rectum in pediatric patients. The Surveillance, Epidemiology, and End Results (SEER) database (1973–2005) was queried for patients less than 20 y of age. Overall, 270 patients with malignant tumors of the lower gastrointestinal tract were identified. The annual incidence was 1.04 cases per million in 2005. Overall, equal distribution between boys (50.7%) and girls (49.3%) was observed. The majority of tumors arose in adolescents (68.1% were older than 15 y). Tumors were more commonly seen in white (77.8%) and non-Hispanic (78.9%) patients. Tumors were identified in the right colon (45.9%), transverse colon (9.3%), left colon (20.4%), rectum (15.2%), and anal canal (1.1%). The most common histology of these tumors was adenocarcinoma (35.6%), followed by carcinoid (34.1%). Disease specific 5- and 10-y-survival for the entire cohort was 61.0% and 57.9%, respectively. Multivariate analysis of the cohort identified tumor stage (HR 8.39, P < 0.001 for distant disease), tumor type (signet ring HR 2.12, P = 0.025, and carcinoid HR = 0.14, P = 0.001), and surgical resection (no surgery HR 2.98, P = 0.010) as independent predictors of worse outcome. In the pediatric population, solid tumors of the colon and rectum occur more frequently in the right side of the colon in teenagers. Surgical resection significantly improves survival for most pediatric tumors of the lower gastrointestinal tract
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