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Objectives: Patients with head and neck cancer (HNC) frequently present with weight loss secondary to dysphagia and malnutrition. We sought to determine the relationship between weight loss and in-hospital mortality, complications, length of hospitalization, and costs in HNC surgery. Methods: We analyzed discharge data from the Nationwide Inpatient Sample for 93,663 patients who underwent an ablative procedure for malignant oral cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasms between 2003 and 2008. Results: Weight loss was significantly associated with dysphagia (relative risk ratio [RRR] = 3.0; p < 0.001), alcohol abuse (RRR = 2.0; p < 0.001), advanced comorbidity (RRR = 1.8; p < 0.001), Medicaid payor status (RRR = 1.6; p = 0.002), urgent or emergent admission (RRR = 1.7; p = 0.015), and major surgical procedures (RRR = 2.3; p < 0.001). Patients with weight loss had increased risks of acute cardiac events, pneumonia, renal failure, sepsis, pulmonary failure (RRR = 2.6; p < 0.001), and postoperative wound healing complications, including fistula, dehiscence, and surgical site infection (RRR = 2.0; p < 0.001). After we controlled for all other variables, weight loss was associated with significantly increased length of hospitalization and hospital-related costs. Conclusions: Weight loss is associated with increases in medical complications, surgical complications, length of hospitalization, and hospital-related costs in HNC surgical patients. Aggressive preoperative identification and treatment of underlying dysphagia and malnutrition may reduce the medical and surgical morbidity in this high-risk population. [ABSTRACT FROM AUTHOR]

Some chemotherapeutic agents have been shown to lead to the severe wasting syndrome known as cachexia resulting in dramatic losses of both skeletal muscle and adipose tissue. Previous studies have shown that chemotherapy-induced cachexia is characterized by unique metabolic alterations. Recent results from our laboratory and others have shown that the use of ACVR2B/Fc, a soluble form of the activin receptor 2B (ACVR2B), can mitigate muscle wasting induced by chemotherapy, although the underlying mechanisms responsible for such protective effects are unclear. In order to understand the biochemical mechanisms through which ACVR2B/Fc functions, we employed a comprehensive, multi-platform metabolomics approach. Using both nuclear magnetic resonance (NMR) and mass-spectrometry (MS), we profiled the metabolome of both serum and muscle tissue from four groups of mice including (1) vehicle, (2) the chemotherapeutic agent, Folfiri, (3) ACVR2B/Fc alone, and (4) combined treatment with both Folfiri and ACVR2B/Fc. The metabolic profiles demonstrated large effects with Folfiri treatment and much weaker effects with ACVR2B/Fc treatment. Interestingly, a number of significant effects were observed in the co-treatment group, with the addition of ACVR2B/Fc providing some level of rescue to the perturbations induced by Folfiri alone. The most prominent of these were a normalization of systemic glucose and lipid metabolism. Identification of these pathways provides important insights into the mechanism by which ACVR2B/Fc protects against chemotherapy-induced cachexia. [ABSTRACT FROM AUTHOR]

Background An increasing number of women are pursuing a career in surgery. Concurrently, the percentage of surgeons in dual-profession partnerships is increasing. We sought to evaluate the gender differences in professional advancement, work-life balance, and satisfaction at a large academic center. Materials and methods All surgical trainees and faculty at a single academic medical center were surveyed. Collected variables included gender, academic rank, marital status, family size, division of household responsibilities, and career satisfaction. Student t -test, Fisher's exact test, and chi-square test were used to compare results. Results There were 127 faculty and 116 trainee respondents (>80% response rate). Respondents were mostly male (77% of faculty, 58% of trainees). Women were more likely than men to be married to a professional (90% versus 37%, for faculty; 82% versus 41% for trainees, P < 0.001 for both) who was working full time ( P < 0.001) and were less likely to be on tenure track ( P = 0.002). Women faculty were more likely to be primarily responsible for childcare planning ( P < 0.001), meal planning ( P < 0.001), grocery shopping ( P < 0.001), and vacation planning ( P = 0.003). Gender-neutral responsibilities included financial planning ( P = 0.04) and monthly bill payment ( P = 0.03). Gender differences in division of household responsibilities were similar in surgical trainees except for childcare planning, which was a shared responsibility. Conclusions Women surgeons are more likely to be partnered with a full-time working spouse and to be primarily responsible for managing their households. Additional consideration for improvement in recruitment and retention strategies for surgeons might address barriers to equalizing these gender disparities. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin. GDF11 exposure in mice induced whole body wasting and profound loss of function in cardiac and skeletal muscle over a 14-day period. Loss of cardiac mass preceded skeletal muscle loss. Cardiac histologic and echocardiographic evaluation demonstrated loss of ventricular muscle wall thickness, decreased cardiomyocyte size, and decreased cardiac function 10 days following initiation of GDF11 exposure. Changes in skeletal muscle after GDF11 exposure were manifest at day 13 and were associated with wasting, decreased fiber size, and reduced strength. Changes in cardiomyocytes and skeletal muscle fibers were associated with activation of SMAD2, the ubiquitin–proteasome pathway and autophagy. Thus, GDF11 over administration in vivo results in cardiac and skeletal muscle loss, dysfunction, and death. Here, serum levels of GDF11 by Western blotting were 1.5-fold increased over controls. Although GDF11 effects in vivo are likely dose, route, and duration dependent, its physiologic changes are similar to myostatin and other Activin receptors ligands. These data support that GDF11, like its other closely related TGF-beta family members, induces loss of cardiac and skeletal muscle mass and function. [ABSTRACT FROM AUTHOR]

Necrotizing fasciitis is a severe, rapidly progressive infection of the subcutaneous tissue that causes signiicant destruction. It is rarely encountered in the pediatric population. We describe the case of a 14-year-old boy who was diagnosed with Chromobacterium violaceum necrotizing fasciitis and subsequently found to have autosomal recessive chronic granulomatous disease. [ABSTRACT FROM AUTHOR]

Necrotizing fasciitis is a severe, rapidly progressive infection of the subcutaneous tissue that causes signiicant destruction. It is rarely encountered in the pediatric population. We describe the case of a 14-year-old boy who was diagnosed with Chromobacterium violaceum necrotizing fasciitis and subsequently found to have autosomal recessive chronic granulomatous disease. [ABSTRACT FROM AUTHOR]

Simple Summary: More than 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia, characterized by loss of muscle and fat. However, most cachexia studies were predominantly focused on muscle. Our clinical study showed adipose tissue loss as a prognosticator in PDAC cachexia. Our study aims to understand the concurrent muscle and adipose changes using transcriptome profiling. We identified tissue-specific gene expression profiles with changes in adipose being more dynamic. Pathway analysis suggests that muscle and adipose wasting may be mediated through independently targetable mechanisms which may have therapeutic implications. Many of the well-known and novel cachexia genes have been validated using an external muscle and adipose datasets. The study provides the groundwork for future studies to understand if fat wasting precedes muscle wasting in PDAC and if adipose can be targeted for therapeutic interventions. The study also shows that age related muscle loss has distinct mechanisms compared to cachexia. The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n = 11) and patients with PDAC (n = 24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia. [ABSTRACT FROM AUTHOR]

The article describes the case of a 43-year-old alcoholic man with oropharyngeal histoplasmosis. The patient showed hypernasal speech with a body mass index of 16.7. A previous in-clinic biopsy by the referring otolaryngologist showed squamous atypia and inflammatory infiltrate. He reported improvement of symptoms upon follow-up after two weeks.

Cachexia is frequently accompanied by severe metabolic derangements, although the mechanisms responsible for this debilitating condition remain unclear. Pyruvate dehydrogenase kinase (PDK)4, a critical regulator of cellular energetic metabolism, was found elevated in experimental models of cancer, starvation, diabetes, and sepsis. Here we aimed to investigate the link between PDK4 and the changes in muscle size in cancer cachexia. High PDK4 and abnormal energetic metabolism were found in the skeletal muscle of colon-26 tumor hosts, as well as in mice fed a diet enriched in Pirinixic acid, previously shown to increase PDK4 levels. Viral-mediated PDK4 overexpression in myotube cultures was sufficient to promote myofiber shrinkage, consistent with enhanced protein catabolism and mitochondrial abnormalities. On the contrary, blockade of PDK4 was sufficient to restore myotube size in C2C12 cultures exposed to tumor media. Our data support, for the first time, a direct role for PDK4 in promoting cancer-associated muscle metabolic alterations and skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]