Effects of testosterone on body composition of the aging male

The aging process is accompanied by significant changes in body composition characterized by decreased fat free mass and increased and redistributed fat mass. Muscle loss results from the atrophy of muscle fibers and decreased synthesis of muscle proteins. Increased number of adipocytes and fat accumulation in non-adipose tissue leads to adiposity. These changes can impose functional limitations and increase morbidity. In men, declining testosterone levels that occur with aging can be a contributing factor to these changes. Studies in hypogonadal men have shown that testosterone replacement is effective in increasing muscle mass and strength and decreasing fat mass. The molecular mechanisms of testosterone's influence on muscle and adipose are not fully elucidated. However, testosterone appears to stimulate IGF-1 expression directly and indirectly leading to increased muscle protein synthesis and growth. It may also counter the inhibitory effects of myostatin, cytokines, and glucocorticoids. The predominant effects of testosterone on fat mass are increased lipolysis and decreased adipogenesis. Current evidence suggests that testosterone replacement may be effective in reversing age-dependent body composition changes and associated morbidity. However, hypogonadism must be diagnosed carefully, and therapy should be monitored regularly in order to avoid the adverse effects associated with testosterone supplementation.     

Endogenous postmenopausal hormones and serum lipids: the atherosclerosis risk in communities study

Previous studies have revealed that exogenous estrogen has a beneficial effect on the lipid profile; however, studies examining the relation between endogenous hormones and lipid profiles in postmenopausal women have yielded conflicting results. We sought to characterize the cross-sectional relationship between endogenous hormones and lipid parameters in postmenopausal women with significant (cases, n = 156) and minimal (controls, n = 172) carotid atherosclerosis not taking hormone therapy in the Atherosclerosis Risk in Communities Study. Endogenous hormone status was assessed by measuring levels of estrone, total testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG. Free testosterone was estimated using the free androgen index (total testosterone/SHBG). Lipid parameters assessed included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. We found that SHBG was significantly associated with a more favorable lipid profile, including lower total and LDL cholesterol and triglycerides and higher HDL cholesterol among controls. This association was less prominent among cases where SHBG was only associated with higher triglycerides and lower HDL cholesterol. The free androgen index was associated with a more atherogenic lipid profile, including increased LDL cholesterol among controls and increased total and LDL cholesterol and triglycerides among cases. These relations were independent of demographic and metabolic factors and health behaviors. In contrast to controls, estrone was associated with higher total cholesterol and triglycerides among cases in multivariate analyses. Our data suggest that endogenous sex hormones may play a role in regulating lipid metabolism in postmenopausal women.     

Flow cytometric findings in hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) is an often fatal hyperinflammatory syndrome. HLH may be inherited, but it more commonly arises secondary to Epstein-Barr virus (EBV) or other infections, hematologic malignancies, or rheumatologic diseases. We identified 17 patients diagnosed with HLH who had flow cytometric analysis of peripheral blood or bone marrow performed at the time of diagnosis. Two patients had primary HLH, and the others had HLH secondary to EBV infection, hematologic malignancies, rheumatologic conditions, or tuberculosis. The marrow typically showed a reactive lymphocytosis and a marked left shift in myelopoiesis regardless of the etiology. Qualitative abnormalities were also found in several cases, including T-cell abnormalities in the majority of the EBV-associated HLH cases. While not specific, flow cytometric findings in HLH are different from the findings in uninvolved marrow samples, and care should be taken not to overinterpret immunophenotypic findings in these cases as indicative of a primary marrow disorder or lymphoma.     

Pneumoperitoneum in a patient with pneumothorax and blunt neck trauma

INTRODUCTION

Blunt trauma as a cause of pneumoperitoneum is less frequent and its occurrence without a ruptured viscus is rarely seen.

PRESENTATION OF CASE

We report a case of blunt neck trauma in which a motorcycle rider hit a fixed object causing severe laryngotracheal injury. The patient developed pneumothorax bilaterally and had pneumoperitoneum despite no injury to the internal viscus. Bilateral chest tube drainage and abdominal exploratory laparotomy was performed.

CONCLUSION

Free air in the abdomen after blunt traumatic neck injury is very rare. If pneumoperitoneum is suspected in the presence of pneumothorax, exploratory laparotomy should be performed to rule out intraabdominal injury. As, there is no consensus for this plan yet, further prospective studies are warrant. Conservative management for pneumoperitoneum in the absence of viscus perforation is still a safe option in carefully selected cases.     

Risk factors for ventilator-associated pneumonia in trauma patients: A descriptive analysis

BACKGROUND: We sought to evaluate the risk factors for developing ventilator-associated pneumonia (VAP) and whether the location of intubation posed a risk in trauma patients.METHODS: Data were retrospectively reviewed for adult trauma patients requiring intubation for > 48 hours, admitted between 2010 and 2013. Patients’ demographics, clinical presentations and outcomes were compared according to intubation location (prehospital intubation [PHI] vs. trauma room [TRI]) and presence vs. absence of VAP. Multivariate regression analysis was performed to identify predictors of VAP.RESULTS: Of 471 intubated patients, 332 patients met the inclusion criteria (124 had PHI and 208 had TRI) with a mean age of 30.7±14.8 years. PHI group had lower GCS (P=0.001), respiratory rate (P=0.001), and higher frequency of head (P=0.02) and chest injuries (P=0.04). The rate of VAP in PHI group was comparable to the TRI group (P=0.60). Patients who developed VAP were 6 years older, had significantly lower GCS and higher ISS, head AIS, and higher rates of polytrauma. The overall mortality was 7.5%, and was not associated with intubation location or pneumonia rates. In the early-VAP group, gram-positive pathogens were more common, while gram-negative microorganisms were more frequently encountered in the late VAP group. Logistic regression analysis and modeling showed that the impact of the location of intubation in predicting the risk of VAP appeared only when chest injury was included in the models.CONCLUSION: In trauma, the risk of developing VAP is multifactorial. However, the location of intubation and presence of chest injury could play an important role.     

Merkel cell carcinoma metastatic to the thyroid gland: Aspiration findings and differential diagnosis

Clinically diagnosed metastasis to the thyroid gland is exceptionally rare and may present diagnostic issues on fine needle aspiration. The most common primary sites of metastases to the thyroid are cancers of the lung, breast, skin (especially melanoma), colon, and kidney. Herein, we report a case of metastatic Merkel cell carcinoma to the thyroid presenting as a 2.1‐cm solid nodule in a 50‐year‐old male with a previous history of Merkel cell carcinoma of the upper extremity. The aspirates were moderately to highly cellular featuring small to intermediate sized cells with scant to no cytoplasm, round‐to‐oval nuclei with finely dispersed chromatin, and predominantly arranged as scattered single cells. There was focal nuclear molding, numerous mitoses, and karyorrhectic nuclei. The differential diagnosis centered on the “small round blue cell” tumor group such as medullary thyroid carcinoma and non‐Hodgkin lymphoma. However, in light of our patient's previous history, the FNA findings were most consistent with a metastasis of Merkel cell carcinoma. In patients with a known history of a primary neoplasm, the differential diagnosis of a thyroid nodule should always include potential metastasis. Diagn. Cytopathol. 2010;38:754–757. © 2010 Wiley‐Liss, Inc.     

Patterns of EphA2 protein expression in primary and metastatic pancreatic carcinoma and correlation with genetic status

EphA2 is a transmembrane receptor tyrosine kinase that functions in the regulation of cell growth, survival, angiogenesis, and migration and EphA2 targeting has been proposed as a novel therapeutic strategy for neoplasms that overexpress this protein. EphA2 overexpression has been correlated with increased invasive and metastatic ability in pancreatic cancer cell lines. However, the patterns of EphA2 expression in human pancreatic cancers and associated metastases is unknown, as are the genetics of EphA2 in this tumor type. We collected clinicopathologic data and paraffin-embedded materials from 98 patients with primary and/or metastatic pancreatic cancer and performed immunohistochemical labeling for EphA2 protein. EphA2 protein immunolabeling was found in 207 of 219 samples (95%). The expression was predominantly cytoplasmic, although predominant membranous staining was observed in a minority of cases. When evaluated specifically for labeling intensity, primary and metastatic carcinomas were more strongly positive compared to benign ducts and PanIN lesions (P < 0.00001 and P < 0.01, respectively) and poorly differentiated carcinomas were more strongly positive for EphA2 than well and moderately differentiated tumors (P < 0.005). When primary carcinomas without metastatic disease were specifically compared to carcinomas with associated metastatic disease, the advanced carcinomas showed relatively less strong positive labeling for EphA2 (P < 0.008). Moreover, decreased EphA2 labeling was more commonly found in liver (P < 0.002), lung (P < 0.004) or peritoneal metastases (P < 0.01) as compared to distant lymph node metastases (P < 0.01). Genetic sequencing of the tyrosine kinase domain of EPHA2 in 22 samples of xenograft enriched pancreatic cancer did not reveal any inactivating mutations. However, EPHA2 amplification was found in 1 of 33 pancreatic cancers corresponding to a lymph node metastasis, indicating EPHA2 genomic amplification may underlie EphA2 overexpression in a minority of patients. Our data confirms that EphA2 is overexpressed in pancreatic cancer, but suggests a relative loss of EphA2 in co-existent pancreatic cancer metastases as well as a role for EPHA2 in organ specific metastasis. Shiyama V. Mudali and Baojin Fu contributed equally to this work.