BackgroundIn the antibiotic era, tuberculosis (TB) still causes a substantial number of mortalities. We aimed to identify the causes and risks of death among TB patients.MethodsMedical records of mortality cases of culture-proven TB diagnosed during 2003–2007 were reviewed. All TB deaths were classified into 2 groups (TB-related and non-TB-related), based on the underlying cause of death.ResultsDuring the study period, 2016 cases (male: 71.1%) of culture-proven TB were identified. The mean age was 59.3 (range: 0.3–96) years. The overall mortality rate was 12.3% (249 cases) and the mean age at death was 74 years; 17.3% (43 cases) of all TB deaths were TB-related. Most of the TB-related deaths occurred early (median survival: 20 days), and the patient died of septic shock. Malignancy, liver cirrhosis, renal failure, and miliary and pneumonic radiographic patterns were all independent predictors for all TB deaths. Cavitary, miliary and pneumonic radiographic patterns were all significant predictive factors for TB-related death. Extrapulmonary involvement and liver cirrhosis were also factors contributing to TB-related death.ConclusionsThe majority of TB deaths were ascribed to non-TB-related causes. Managing TB as well as underlying comorbidities in a multidisciplinary approach is essential to improve the outcome of patients in an aging population. However, the clinical manifestations of patients with TB-related death vary; many progressed to fulminant septic shock requiring timely recognition with prompt treatment to prevent early death.

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BackgroundLung cancer in young patients (less or equal to 45 years) is uncommon and has clinical characteristics different from that in older patients. We investigated the outcomes and prognostic factors of young patients with advanced non-small cell lung cancer (NSCLC).MethodsFrom January 2000 to December 2009, we enrolled patients aged ≤45 years and diagnosed with stage IIIB or IV NSCLC. Their clinical data, including age, gender, performance status, histologic types, disease stages, laboratory data at diagnosis, treatment modalities, and survival were reviewed and analyzed. A Cox proportional hazard model was used to calculate the hazard ratio (HR) and its 95% confidence interval (CI).ResultsA total of 144 patients with advanced NSCLC were included. Female patients were more prevalent (n = 74, 51.4%). Adenocarcinoma was the most common histologic type (n = 119, 82.6%) in both genders (male, n = 54, 77.1%; female, n = 65, 87.8%). Epidermal growth factor receptor (EGFR) sequences were determined using tumor specimens from 58 patients, and 29 showed an EGFR mutation. No significant difference in median survival was found between patient groups with and without the EGFR mutation (798 vs. 708 days, p = 0.65). In multivariate analysis, male gender (HR, 1.70; 95% CI: 1.08-2.68), body mass index (BMI) less than 25 kg/m2 (HR, 2.72; 95% CI: 1.39-5.30), stage IV disease (HR, 2.62; 95% CI: 1.50-4.57), and anemia (HR, 2.08; 95% CI: 1.15-3.77) were associated with a short survival time.ConclusionsLow BMI, stage IV disease, anemia at diagnosis, and male gender were the negative prognostic factors for young patients with advanced NSCLC.

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10−14), rs9276370 (HLA-DQA2, P = 1.9×10−12), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10−11 and P = 6.66×10−15 respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10−10). The “T-T-G-G-T” haplotype of the five SNPs further signified their association with the disease (P = 1.48×10−12; OR = 1.49). The “T-T” haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The “G-C” haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.

The genetic predisposition to addiction to opioids and other substances is transmitted as a complex genetic trait, which investigators are attempting to characterize using genetic linkage and association. We now report a high-density genome-wide linkage study of opioid dependence. We ascertained 305 DSM-IV opioid dependent affected sibling pairs from an ethnically mixed population of methadone maintained subjects and genotyped their DNA using Affymetrix 10K v2 arrays. Analysis with MERLIN identified a region on chromosome 14q with a non-parametric lod (NPL) of 3.30. Secondary analyses indicated that this locus was relatively specific to the self-identified Puerto Rican subset, as the NPL increased from 3.30 to 5.00 (NPL(Caucasian) = 0.05 and NPL(African Amer.) = 0.15). The 14q peak encompasses the NRXN3 gene (neurexin 3), which was previously identified as a potential candidate gene for addiction. Secondary analyses also identified several regions with gender-specific NPL scores greater than 2.00. The most significant was a peak on (10q) that increased from 0.90 to 3.22 when only males were considered (NPL(female) = 0.05). Our linkage data suggest specific chromosomal loci for future fine-mapping genetic analysis and support the hypothesis that ethnic and gender specific genes underlie addiction susceptibility.