Evidence-based review: Screening body dysmorphic disorder in aesthetic clinical settings.

BACKGROUND: Body dysmorphic disorder (BDD) is a psychiatric disturbance with high incidence in aesthetic clinical settings. Early recognition may avoid unnecessary elective procedures with ethical and medicolegal consequences. AIMS: To identify validated BDD screening tools and critically appraise current literature regarding its implementation and efficacy in aesthetic medicine and surgery scenarios, with the purpose of transposing the findings to the broad clinical settings in the field. METHODS: Data was collected using advanced search from PubMed (MEDLINE). Having satisfied the search parameters, 12 studies referring BDD definition according to Diagnostic and Statistical Manual of Mental Disorder (DSM-5) criteria and including a BDD screening tool in clinical aesthetic settings were selected. RESULTS: While BDD screening enables the recognition of at-risk individuals, further work is required to uncover the best screening tool for general aesthetic clinical practice. Level III evidence favored BDD Questionnaire (BDDQ)/BDDQ-Dermatology Version (DV), and The Dysmorphic Concern Questionnaire (DCQ) among the limited available validated screening instruments to be used outside the psychiatric environment. Based on level II self-classification, one study selected BDDQ-Aesthetic Surgery (AS) version for rhinoplasty patients. The validation process of both BDDQ-AS and Cosmetic Procedure Screening Questionnaire (COPS) had limitations. For BDD screening potential in avoiding postoperative complications, the limited studies found evaluating the outcomes following aesthetic treatments using validated BDD screening measures showed a trend toward less satisfaction with aesthetic treatment outcome among positive screening population against non-BDD counterparts. CONCLUSION: Further research is necessary to establish more effective methods to identify BDD and evaluate the impact of positive findings on aesthetic intervention outcomes. Future studies may elucidate which BDD characteristics best predict a favorable outcome and provide high-quality evidence for standardized protocols in research and clinical practice.

Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy.

Hypertrophic osteoarthropathy (HOA) is a disabling condition that may occur secondarily to primary lung cancer. It is characterized by digital clubbing, arthralgia/arthritis, and periostosis of the tubular bones. The pain associated with HOA can be disabling and often refractory to conventional analgesics. We performed a comprehensive review of the literature using the PubMed database on treatment modalities available for HOA. We found 52 relevant articles-40 case reports, six case series, two review papers, and four combined case series and review papers. There were no randomized controlled trials reported. We then classified treatments used for HOA into two categories: (1) treatment of primary cause (i.e., resection of tumor, chemotherapy, radiotherapy, treatment of infection, etc.) and (2) symptomatic treatments (i.e., bisphosphonates, octreotide, NSAIDs, vagotomy, etc.). Subsequently, we summarized the main findings for each treatment. Although the clinical diagnosis of HOA has existed for over 100 years, the pathogenesis mechanism has not yet been elucidated, and treatment options for this condition remain experimental. Primary treatment is the most widely reported modality to be efficacious. In cases which primary therapy is not possible, several symptomatic treatment modalities are suggested, with various degree of success. Further research is needed to clarify the pathophysiological mechanism of HOA as to appropriately direct therapy.

Betaine prevents Mallory-Denk body formation in drug-primed mice by epigenetic mechanisms.

Previous studies showed that S-Adenosylmethionine (SAMe) prevented MDB formation and the hypomethylation of histones induced by DDC feeding. These results suggest that formation of MDBs is an epigenetic phenomenon. To further test this theory, drug-primed mice were fed the methyl donor, betaine, together with DDC, which was refed for 7 days. Betaine significantly reduced MDB formation, decreased the liver/body weight ratio and decreased the number of FAT10 positive liver cells when they proliferate in response to DDC refeeding. Betaine also significantly prevented the decreased expression of BHMT, AHCY, MAT1a and GNMT and the increased expression of MTHFR, caused by DDC refeeding. S-Adenosylhomocysteine (SAH) levels were reduced by DDC refeeding and this was prevented by betaine. The results support the concept that betaine donates methyl groups, increasing methionine available in the cell. SAMe metabolism was reduced by the decrease in GNMT expression, which prevented the conversion of SAMe to SAH. As a consequence, betaine prevented MDB formation and FAT10 positive cell proliferation by blocking the epigenetic memory expressed by hepatocytes. The results further support the concept that MDB formation is the result of an epigenetic phenomenon, where a change in methionine metabolism causes global gene expression changes in hepatocytes.

Safety of nab-paclitaxel plus sunitinib: analysis of three cases.

BACKGROUND: Second-line treatment options are limited in controlling advanced thoracic cancer in patients who have progressed following first-line chemotherapy. CASE REPORT: The safety of combination therapy with nab-paclitaxel, an albumin-bound paclitaxel, and sunitinib, a tyrosine kinase receptor inhibitor, was evaluated retrospectively in three patients with advanced, previously treated metastatic esophageal cancer, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC), respectively. RESULTS: Grade 3 and 4 toxicities were mainly hematological and manageable. A notable improvement in cancer symptoms and reduction in tumor size were seen in all three patients. CONCLUSION: Based on the easily managed toxicities and apparent efficacy of the regimen of weekly nab-paclitaxel and daily sunitinib, we conclude that further evaluation is warranted to assess the efficacy of this combination therapy in previously chemotherapy-treated patients with advanced thoracic cancer.

Neoadjuvant chemotherapy with reduced-dose carboplatin and gemcitabine for non-small cell lung cancer in a patient with Fanconi anemia.

Fanconi anemia (FA) is characterized by pancytopenia, congenital malformations, and susceptibility to malignancies. We describe a 31-year-old man with FA, who had undergone bone marrow transplantation and whole body irradiation at the age 17 years for FA. Fourteen years later, he presented with squamous cell carcinoma of the bronchus intermedius in the right lung. The tumor was located next to the main pulmonary artery and between the superior and inferior pulmonary veins. Two cycles of neoadjuvant therapy were given in an attempt to decrease tumor size and avoid a potential right pneumonectomy. Treatment consisted of a 21-day cycle with carboplatin (area under the curve 3) given on day 1 and gemcitabine (1250 mg/m) on day 1 and 8. Because FA cells are hypersensitive to DNA crosslinking agents, we reduced the carboplatin dose to minimize treatment-related toxicity. The tumor regressed sufficiently to permit performance of a right middle and lower lobectomy. In our case, neoadjuvant therapy with gemcitabine and low-dose carboplatin exhibited antitumor activity with manageable side-effects, suggesting that this chemotherapy regimen can be safely and effectively used in the treatment of NSCLC in FA patients who have achieved hematopoietic reconstitution after bone marrow transplantation.

Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed mouse model of tumorigenesis.

There is clinical evidence that chronic liver diseases in which MDBs (Mallory Denk Bodies) form progress to hepatocellular carcinoma. The present study provides evidence that links MDB formation induced by chronic drug injury, with preneoplasia and later to the formation of tumors, which develop long after drug withdrawal. Evidence indicated that this link was due to an epigenetic cellular memory induced by chronic drug ingestion. Microarray analysis showed that the expressions of many markers of preneoplasia (UBD, Alpha Fetoprotein, KLF6 and glutathione-S-transferase mu2) were increased together when the drug DDC was refed. These changes were suppressed by S-adenosylmethionine feeding, indicating that the drug was affecting DNA and histones methylation in an epigenetic manner. The link between MDB formation and neoplasia formation was likely due to the over expression of UBD (also called FAT10), which is up regulated in 90% of human hepatocellular carcinomas. Immunohistochemical staining of drug-primed mouse livers showed that FAT10 positive liver cells persisted up to 4 months after drug withdrawal and they were still found in the livers of mice, 14 months after drug withdrawal. The refeeding of DDC increased the percent of FAT10 hepatocytes.

Circumstances of patient falls and injuries in 9 hospitals in a midwestern healthcare system.

OBJECTIVE: Preventing hospital falls and injuries requires knowledge of fall and injury circumstances. Our objectives were to determine whether reported fall circumstances differ among hospitals and to identify predictors of fall-related injury. DESIGN: Retrospective cohort study. Adverse event data on falls were compared according to hospital characteristics. Logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for risk factors for fall-related injury. SETTING: Nine hospitals in a Midwestern healthcare system. PATIENTS: Inpatients who fell during 2001-2003. RESULTS: The 9 hospitals reported 8,974 falls that occurred in patient care areas, involving 7,082 patients; 7,082 falls were included in our analysis. Assisted falls (which accounted for 13.3% of falls in the academic hospital and 9.8% of falls in the nonacademic hospitals; P<.001) and serious fall-related injuries (which accounted for 3.7% of fall-related injuries in the academic hospital and 2.2% of fall-related injuries in the nonacademic hospitals; P<.001) differed by hospital type. In multivariate analysis for the academic hospital, increased age (aOR, 1.006 [95% CI, 1.000-1.012]), falls in locations other than patient rooms (aOR, 1.53 [95% CI, 1.03-2.27]), and unassisted falls (aOR, 1.70 [95% CI, 1.23-2.36]) were associated with increased injury risk. Altered mental status was associated with a decreased injury risk (aOR, 0.72 [95% CI, 0.58-0.89]). In multivariate analysis for the nonacademic hospitals, increased age (aOR, 1.007 [95% CI, 1.002-1.013]), falls in the bathroom (aOR, 1.46 [95% CI, 1.06-2.01]), and unassisted falls (aOR, 1.83 [95% CI, 1.37-2.43]) were associated with injury. Female sex (aOR, 0.83 [95% CI, 0.71-0.97]) was associated with a decreased risk of injury. CONCLUSION: Some fall characteristics differed by hospital type. Further research is necessary to determine whether differences reflect true differences or merely differences in reporting practices. Fall prevention programs should target falls involving older patients, unassisted falls, and falls that occur in the patient's bathroom and in patient care areas outside of the patient's room to reduce injuries.

CYP2E1 induced by ethanol causes oxidative stress, proteasome inhibition and cytokeratin aggresome (Mallory body-like) formation.

The role of oxidative stress in alcoholic liver disease and cytokeratin aggresome formation is the focus of this in vitro study. HepG2 cells transduced to over express CYP2E1 (E47) and control HepG2 cells (C34) were first treated with arachidonic acid, then Fe-NAT, and finally with ethanol. In the E47 ethanol-treated cells, CYP2E1 was induced and a higher level of reactive oxygen species and carbonyl proteins were generated. The proteasome activity decreased significantly in the E47 ethanol-treated cells. This inhibition was prevented when CYP2E1 was inhibited by DAS. Microarray analysis showed gene expression down regulation of the proteasome subunit, as well as ubiquitin pathway proteins in the E47 ethanol-treated cells. 4-Hydroxynonenal (4-HNE) adducts were increased in the E47 cells treated with ethanol. Furthermore, the immunoprecipitated 4-HNE modified proteins from these cells stained positive with antibodies to the proteasome subunit alpha 6. These results indicate that the ethanol induced CYP2E1 generates oxidative stress that is responsible for the decrease in proteasome activity. Cytokeratin 8 and 18 were induced by ethanol treatment of E47 cells and polyubiquitinated forms of these proteins were found in the polyubiquitin smear upon Western blots analysis. Cytokeratin aggresomes and Mallory body-like inclusions formed in the ethanol-treated E47 cells, indicating that the ubiquitinated cytokeratins accumulated as a result of the inhibition of the proteasome by ethanol treatment when oxidation of ethanol induced oxidative stress. This is the first report where ethanol caused Mallory body-like cytokeratin inclusions in transformed human liver cells in vitro.

RNA interference of VCP/p97 increases Mallory body formation.

In the present report, valosin-containing protein (VCP) was present in Mallory bodies (MBs). To determine if VCP plays a role in MB formation, primary cultured hepatocytes from drug-primed mice that spontaneously form MBs in vitro were studied. The results were compared with control normal hepatocytes. Gene-specific FITC-labeled gripNA (gVCP) was added to the medium of the primary cultures to inhibit the expression of VCP. gVCP increased MB formation by 230% in drug-primed mouse hepatocytes compared with primed liver cells where no VCP oligos were added. Blocking VCP expression induced both multiple small ubiquitin (Ub) and cytokeratin (CK) aggregates to form within the cytoplasm in normal mouse hepatocytes. Inhibition of VCP expression in both drug-primed and control hepatocytes caused a decrease in proteasome chymotrypsin-like (ChT-L) activity. Overexpression of VCP was achieved by transfecting the hepatocytes with a plasmid containing green fluorescent protein (GFP)-fused VCP (pVCP-GFP). Overexpressed VCP was located in both the cytoplasm and nucleus of pVCP-GFP overexpressing drug-primed hepatocytes. VCP was also concentrated within MBs. MB formation was not decreased by the overexpression of VCP in the cells. These results indicate that VCP plays an important role in inducing MB formation, probably through its molecular chaperone function in the ubiquitin-proteasome system (UPS).