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OBJECTIVES Most patients with pancreatic cancer have high symptom burden and poor outcomes. Palliative care (PC) can improve the quality of care through expert symptom management, although the optimal timing of PC referral is still poorly understood. We aimed to assess the association of early PC on health care utilization and charges of care for pancreatic cancer patients. MATERIALS AND METHODS We selected patients with pancreatic cancer diagnosed between 2000 and 2009 who received at least 1 PC encounter using the Surveillance, Epidemiology, and End Results (SEER)-Medicare. Patients who had unknown follow-up were excluded. We defined "early PC" if the patients received PC within 30 days of diagnosis. RESULTS A total of 3166 patients had a PC encounter; 28% had an early PC. Patients receiving early PC were more likely to be female and have older age compared with patients receiving late PC (P

Introduction: This study aimed to determine if gentamicin bladder instillations reduce the rate of symptomatic urinary tract infection (UTI) in neurogenic bladder (NGB) patients on intermittent self-catheterization (ISC) who have recurrent UTIs. Secondary aims were to examine the effects of intravesical gentamicin on the organism resistance patterns.Methods: We retrospectively reviewed our prospective NGB database. Inclusion criteria were NGB patients performing ISC exclusively for bladder drainage with clinical data available for six months before and six months after initiating prophylactic intravesical gentamicin instillations. Symptomatic UTIs were defined as symptoms consistent with UTI plus the need for antibiotic treatment.Results: Twenty-two patients met inclusion criteria; etiology of NGB was 63.6% spinal cord injury, 13.6% multiple sclerosis. Median time since injury/diagnosis was 14 years and 6/22 (27.3%) hadundergone urological reconstruction. Patients had fewer symptomatic UTI’s (median 4 vs. 1 episodes; p

Insulin and insulin-like growth factor 1 (IGF-1) receptor signaling pathways differentially modulate cardiac growth under resting conditions and following exercise training. These effects are mediated by insulin receptor substrate 1 (IRS1) and IRS2, which also differentially regulate resting cardiac mass. To determine the role of IRS isoforms in mediating the hypertrophic and metabolic adaptations of the heart to exercise training, we subjected mice with cardiomyocyte-specific deletion of either IRS1 (CIRS1 knockout [CIRS1KO] mice) or IRS2 (CIRS2KO mice) to swim training. CIRS1KO hearts were reduced in size under basal conditions, whereas CIRS2KO hearts exhibited hypertrophy. Following exercise swim training in CIRS1KO and CIRS2KO hearts, the hypertrophic response was equivalently attenuated, phosphoinositol 3-kinase (PI3K) activation was blunted, and prohypertrophic signaling intermediates, such as Akt and glycogen synthase kinase 3β (GSK3β), were dephosphorylated potentially on the basis of reduced Janus kinase-mediated inhibition of protein phosphatase 2a (PP2A). Exercise training increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein content, mitochondrial capacity, fatty acid oxidation, and glycogen synthesis in wild-type (WT) controls but not in IRS1- and IRS2-deficient hearts. PGC-1α protein content remained unchanged in CIRS1KO but decreased in CIRS2KO hearts. These results indicate that although IRS isoforms play divergent roles in the developmental regulation of cardiac size, these isoforms exhibit nonredundant roles in mediating the hypertrophic and metabolic response of the heart to exercise.

The induction of autophagy in the mammalian heart during the perinatal period is an essential adaptation required to survive early neonatal starvation; however, the mechanisms that mediate autophagy suppression once feeding is established are not known. Insulin signaling in the heart is transduced via insulin and IGF-1 receptors (IGF-1Rs). We disrupted insulin and IGF-1R signaling by generating mice with combined cardiomyocyte-specific deletion of Irs1 and Irs2. Here we show that loss of IRS signaling prevented the physiological suppression of autophagy that normally parallels the postnatal increase in circulating insulin. This resulted in unrestrained autophagy in cardiomyocytes, which contributed to myocyte loss, heart failure, and premature death. This process was ameliorated either by activation of mTOR with aa supplementation or by genetic suppression of autophagic activation. Loss of IRS1 and IRS2 signaling also increased apoptosis and precipitated mitochondrial dysfunction, which were not reduced when autophagic flux was normalized. Together, these data indicate that in addition to prosurvival signaling, insulin action in early life mediates the physiological postnatal suppression of autophagy, thereby linking nutrient sensing to postnatal cardiac development.

Phosphoinositide-dependent protein kinase-1 (PDPK1) is an important mediator of phosphatidylinositol 3-kinase (PI3K) signaling. We previously reported that PI3K but not Akt signaling mediates the increase of mitochondrial oxidative capacity to physiological cardiac hypertrophy. To determine if PDPK1 regulates these metabolic adaptations we examined mice with cardiomyocyte-specific heterozygous knockout of PDPK1 (cPDPK1+/−) after 5 wk. exercise swim training. Akt phosphorylation at Thr308 increased by 43% in wildtype (WT) mice but not in cPDPK1+/− mice following exercise training. Ventricular contractile function was not different between WT and cPDPK1+/− mice at baseline. In addition, exercise did not influence ventricular function in WT or cPDPK1+/− mice. Heart weight normalized to tibia length ratios increased by 13.8% in WT mice (6.2 ± 0.2 vs. 7.1 ± 0.2, P=0.001), but not in cPDPK1+/− (6.2 ± 0.3 vs. 6.5 ± 0.2, P=0.20) mice after swim training. Diastolic LV dimension increased in WT mice (3.7 ± 0.1 vs. 4.0 ± 0.1 mm, P=0.01) but not in cPDPK1+/− (3.8 ± 0.1 vs. 3.7 ± 0.1 mm, P=0.56) following swim training. Maximal mitochondrial oxygen consumption (VADP, nmol/min/mg) using palmitoyl carnitine as a substrate was significantly increased in mice of all genotypes following swim training (WT: 13.6 ± 0.6 vs.16.1 ± 0.9, P=0.04; cPDPK1+/−: 12.4 ± 0.6 vs.15.9 ± 1.2, P=0.04). These findings suggest that PDPK1 is required for exercise-induced cardiac hypertrophy but does not contribute to exercise-induced increases in mitochondrial function.

General surgery residents' exposure to cardiothoracic (CT) surgery rotations has decreased, which may affect resident satisfaction. We surveyed general surgery graduates to assess the relationships among rotation satisfaction, CT disease exposure, rotation length, mentorship, and mistreatment.A survey assessing CT curriculum, exposure, mentorship, and satisfaction was forwarded to general surgery graduates from 17 residency programs. A Wilcoxon rank-sum test was used to assess statistical significance of ordinal level data. Statistical significance was defined as p0.05.This study was conducted at the University of Michigan Health System in Ann Arbor, MI, a tertiary care center.The survey was sent to approximately 1300 graduates of general surgery residency programs who graduated between the years of 1999 to 2014. A total of 94 responses were completed and received.Receiving adequate exposure to CT procedures and disease management was significantly associated with higher satisfaction ratings for all procedures, particularly thoracotomy incisions (p0.001), empyemas and pleural effusions (p0.001), and lung cancer care (p0.001). The absence of mistreatment and good/very good mentorship were both positively associated with higher reported satisfaction (p = 0.018 and p0.001, respectively). Increased length of time on CT rotation was neither associated with improved levels of satisfaction nor with an improvement in the quality of mentorship.Rotation satisfaction is positively associated with procedure exposure, better mentorship, and the absence of mistreatment. Longer rotation length was not associated with satisfaction. Shorter rotations are not detrimental to training if they have focused clinical exposure and invested mentors to maximize resident satisfaction. These specific markers of rotation quality are useful in curricular design.