Incidence,risk factors and causes of death in an HIV care programme with a large proportion of injecting drug users

Objectives To identify factors influencing mortality in an HIV programme providing care to large numbers of injecting drug users (IDUs) and patients co‐infected with hepatitis C (HCV). Methods A longitudinal analysis of monitoring data from HIV‐infected adults who started antiretroviral therapy (ART) between 2003 and 2009 was performed. Mortality and programme attrition rates within 2 years of ART initiation were estimated. Associations with individual‐level factors were assessed with multivariable Cox and piece‐wise Cox regression. Results A total of 1671 person‐years of follow‐up from 1014 individuals was analysed. Thirty‐four percent of patients were women and 33% were current or ex‐IDUs. 36.2% of patients (90.8% of IDUs) were co‐infected with HCV. Two‐year all‐cause mortality rate was 5.4 per 100 person‐years (95% CI, 4.4–6.7). Most HIV‐related deaths occurred within 6 months of ART start (36, 67.9%), but only 5 (25.0%) non‐HIV‐related deaths were recorded during this period. Mortality was higher in older patients (HR = 2.50; 95% CI, 1.42–4.40 for ≥40 compared to 15–29 years), and in those with initial BMI < 18.5 kg/m² (HR = 3.38; 95% CI, 1.82–5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47–10.65 during the second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54–13.41 for <100 compared to ≥100 cells/μl). Risk of death was not associated with IDU status (P = 0.38). Conclusion Increased mortality was associated with late presentation of patients. In this programme, death rates were similar regardless of injection drug exposure, supporting the notion that satisfactory treatment outcomes can be achieved when comprehensive care is provided to these patients.     

Attention‐deficit hyperactivity disorder reduces automatic attention in young adults

Previous ERP studies have provided mixed information about ADHD, especially in adults and when conscious attention to stimuli is not required. We used the auditory N1 to assess automatic attention in adults with and without ADHD. While participants watched a silent video, trains of 5 tones (400‐ms onset‐to‐onset time) were presented with intertrain intervals (ITIs) of 1 or 5 s. The P1, N1, P2, and N2 were analyzed. Compared to controls, participants with ADHD had relatively little N1 attenuation after the 5‐s ITI, which was driven by uniformly small N1s to all tones. However, after the 1‐s ITI, the ADHD group had relatively large N2s to all 5 tones in the train. The reduced N1 in adults with ADHD indicated reduced automatic attention to salient sound stimuli, which may be due to reduced function of brain‐stem arousal mechanisms. However, the increased N2 in these participants suggests they had developed certain compensatory mechanisms.     

Coexistence of Hodgkin lymphoma and cyst hydatic disease of the liver

Although both Hodgkin lymphoma and cyst hydatic disease in children have been seen with an increased frequency, there is no previously reported case of Hodgkin lymphoma associated with cyst hydatic disease from Turkey. The authors report such a case of Hodgkin lymphoma. Intrahepatic cystic masses were diagnosed during ultrasound examination for clinical staging on admission. The diagnosis of cyst hydatic of the liver was confirmed by surgery. Although there was no residual and/or new cyst formation on radiologic follow-up, elevated antibody titers (indirect hemagglutination test) persisted following surgical excision at least for 2 years of follow-up.     

Significance of orbital fatty tissue for exophthalmos in thyroid-associated ophthalmopathy

PURPOSE: To correlate exophthalmos with the volume of extraocular muscle and orbital fatty tissue in thyroid-associated ophthalmopathy (TAO), using MRI that enables the orbital soft tissues to be well defined. METHODS: Thirty-three orbits, 20 from 10 patients with TAO and 13 from 13 controls, were employed. T1-weighted orbital MR slices 2 or 3 mm thick were obtained in axial, coronal and sagittal planes. Tracing the outlines of each structure, we measured the total sectional areas. Volumes of the extraocular muscle, of the fatty tissue and of the bony orbital cavity were calculated by multiplying the slice thickness. Exophthalmos was also measured using axial MRI. RESULTS: In TAO the volume increment of orbital fatty tissue (6.19 cm(3)) was much greater than that of extraocular muscle (1.16 cm(3)). Increase of exophthalmos by 1 mm needed a total orbital volume increment of 0.92 cm(3). The total orbital fatty tissue volume (correlation coefficient 0.70, P=0.06%) and the anterior orbital fatty tissue volume (0.64, P=0.23%) were more closely correlated with the degree of exophthalmos than was extraocular muscle volume (0.58, P=0.8%). Moreover, the volume increment of extraocular muscle and orbital fatty tissue was not always proportional. CONCLUSION: The results show that the orbital fatty tissue involvement is closely related to the degree of exophthalmos. For studying exophthalmos in TAO, the volumetric change, not only in ocular muscles, but also in orbital fatty tissue, should be taken into consideration.     

MicroRNA-381 increases radiosensitivity in esophageal squamous cell carcinoma

Background: Radiation resistance poses a major clinical challenge in treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms of radioresistance has not been fully elucidated. Since accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer sensitivity to radiation, we aimed to identify miRNAs associated with radioresistance of ESCC. Methods: In this study, we used GeneChip miRNA Array to perform an comparison of miRNAs expression in tissues from primary ESCC and recurrent ESCC in situ after radiotherapy. Differential expressions of miRNAs were comfirmed by quantitative Real-Time PCR in tissues and six ESCC cell lines. Cell radiosensitivity were determined by colony formation assay. Functional analyses of miRNA-381 in ESCC cells growth and metastasis were performed by MTT and Transwell Assays. In vivo assays of the functions of miRNA-381 were performed in tumor xenografts. Results: One miRNA candidate, miRNA-381, was found to be downregulated in radiation resistance tissues and cells. Enforced expression of miRNA-381 increased radiosensitivity of ESCC cells and promoted nonaggressive phenotype including decreased cellular proliferation and migration. In contrast, inhibition of miRNA-381 in ESCC cells promoted radiation resistance and development of an aggressive phenotype. In vivo assays extended the significance of these results, showing that miRNA-381 overexpression decreased the tumor growth and the resistance to radiation treatment in tumor xenografts. Conclusions: Together, our work reveals miRNA-381 expression as a critical determinant of radiosensitivity in esophageal cancer cells.     

Hypermethylation of repetitive DNA elements in livers of mice fed an atherogenic diet

ObjectiveDNA methylation status was examined in C57BL/6J obese mice fed an atherogenic diet (AD) to establish the correlation between epigenetic alterations and obesity-related abnormalities.MethodsSix-week-old male C57BL/6J mice were fed a normal diet (ND) or AD for 8 wk. Methylation levels of global DNA and repetitive DNA elements in livers of ND-fed mice and AD-fed mice were examined.ResultsThe total amounts of 5-MeC genomic contents in livers of AD-fed mice were increased as compared with those of ND-fed mice. Hypermethylation of repetitive DNA elements was observed in livers of AD-fed mice.ConclusionHypermethylation of repetitive DNA elements in livers of AD-fed mice proposes epigenetic changes by nutritional intervention.     

A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: A meta‐analysis

Objective

To perform a meta‐analysis comparing the efficacy and safety of recommended dosages of nonsteroidal antiinflammatory drugs (NSAIDs), including cyclooxygenase 2 inhibitors, versus acetaminophen in the treatment of symptomatic hip and knee osteoarthritis.

Methods

Medline and EMBASE searches were performed for original clinical trials directly comparing NSAIDs with acetaminophen. A standardized form was used to abstract all data, including outcome measures of pain at rest, walking pain, and dropouts due to adverse effects. Inverse‐variance‐weighted mean differences (WMDs) and 95% confidence intervals (95% CI) for pain measures were determined for treatment groups. Odds ratios (ORs) and 95% CIs were calculated for withdrawals due to adverse events. Results were compared using a random effects model.

Results

Seven articles met inclusion criteria with sufficient data for analysis. Participants had a mean age of 61.1 years and 71.1% were women. Test of heterogeneity was not significant for either rest (P = 0.73) or walking (P = 0.76) pain. The scores for overall pain at rest (WMD ?6.33 mm on a 100‐mm visual analog scale [VAS], 95% CI ?9.24, ?3.41) and walking pain (WMD –5.76 mm on a 100‐mm VAS, 95% CI –8.99, –2.52) favored the NSAID‐treated group. Although NSAIDs elevated the risk of withdrawals due to adverse events, the difference was not statistically significant (OR 1.45, 95% CI 0.93, 2.27).

Conclusion

NSAIDs are statistically superior in reducing rest and walking pain compared with acetaminophen for symptomatic osteoarthritis. Safety, measured by discontinuation due to adverse events, was not statistically different between NSAID‐ and acetaminophen‐treated groups.

     

Promoter methylation and response to chemotherapy and radiation in esophageal cancer.

BACKGROUND & AIMS: Multiple studies have shown that promoter methylation of tumor suppressor genes underlies esophageal carcinogenesis. Hypothetically, methylation resulting in tumor suppressor gene inactivation might result in tumors that are unresponsive to chemotherapy and radiation. Accordingly, our aim was to find methylation markers that could be used to predict response to chemoradiation. METHODS: Tumor specimens were obtained before treatment from 35 patients enrolled in a uniform chemoradiation treatment protocol. Methylation-specific quantitative polymerase chain reaction was performed on all samples. Pathology reports from esophagectomy specimens were used to define response to treatment. RESULTS: Thirteen (37%) of 35 patients were responders, and 22 (63%) of 35 patients were nonresponders. The number of methylated genes per patient was significantly lower in responders than in nonresponders (1.4 vs 2.4 genes per patient; Student t test, P = .026). The combined mean level of promoter methylation of p16, Reprimo, p57, p73, RUNX-3, CHFR, MGMT, TIMP-3, and HPP1 was also lower in responders than in nonresponders (Student t test, P = .003; Mann-Whitney test, P = .001). The frequency (15% of responders vs 64% of nonresponders; Fisher exact test, P = .01) and level (0.078 in responders vs 0.313 in nonresponders; Mann-Whitney test, P = .037) of Reprimo methylation was significantly lower in responders than in nonresponders. CONCLUSIONS: Reprimo methylation occurred at significantly lower levels and less frequently in chemoradioresponsive than in nonresponsive esophageal cancer patients, suggesting potential clinical application of this single-gene biomarker in defining prognosis and management. In addition, increased methylation of a 9-gene panel correlated significantly with poor responsiveness to chemoradiation.