Background Human papillomavirus type 16 (HPV16) seropositivity and alcohol and tobacco use have been associated with risk of head and neck squamous cell carcinoma (HNSCC). However, it is less clear ...whether HPV16 influences HNSCC risk associated with alcohol and tobacco use. Methods Incident cases of HNSCC diagnosed between December 1999 and December 2003 were identified from nine medical facilities in Greater Boston, MA. Control subjects were frequency matched to case subjects on age, sex, and town of residence. A total of 485 case subjects and 549 control subjects reported information on lifetime smoking and alcohol consumption and provided sera, which was used to determine presence of HPV16 antibodies. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of HNSCC risk by alcohol consumption (drinks per week: <3, 3 to <8, 8 to <25, ≥25) and smoking (pack-years: none, >0 to <20, 20 to <45, ≥45), adjusting for age, sex, race, education, and HPV16 serology. Polytomous logistic regression was used to estimate odds ratios and 95% confidence intervals for the association of HPV16 serology, alcohol consumption, and tobacco use in site-specific analyses. All statistical tests were two-sided. Results The strongest risk factors by tumor site were smoking for laryngeal cancer, alcohol for cancer of the oral cavity, and HPV16 for pharyngeal cancer. For pharyngeal cancer, risk increased with increasing alcohol consumption (OR≥25 versus <3 drinks per week = 5.1, 95% CI = 2.4 to 11.0) and smoking (OR≥45 pack-years versus never smoker = 6.9, 95% CI = 3.1 to 15.1) among HPV16-seronegative subjects but not among HPV16-seropositive subjects (Pinteraction, HPV16 serology and alcohol = .002; Pinteraction, HPV16 serology and smoking = .007). Among light drinkers or never smokers, HPV16 seropositivity was associated with a 30-fold increased risk of pharyngeal cancer. Conclusions Alcohol or tobacco use does not further increase risk of HPV16-associated pharyngeal cancer. HNSCC risk associated with smoking, alcohol, and HPV16 differs by tumor site.
BACKGROUND:Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver ...complications among HIV/HBV-coinfected individuals remain unknown.
SETTING:North American AIDS Cohort Collaboration on Research and Design.
METHODS:We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios aHRs with 95% confidence interval (CIs) of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL).
RESULTS:Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 95% CI6.6 to 9.7 events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race aHR = 1.76 (1.13–2.74), diabetes mellitus aHR = 2.07 (1.20–3.57), lower time-updated CD4 cell count <200 cells/mmaHR = 2.59 (1.36–4.91); 201–499 cells/mmaHR = 1.75 (1.01–3.06) versus ≥500 cells/mm, heavy alcohol use aHR = 1.58 (1.04–2.39), and higher FIB-4 at start of follow-up >3.25aHR = 9.79 (5.73–16.74); 1.45–3.25aHR = 3.20 (1.87–5.47) versus FIB-4 <1.45. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV aHR = 0.56 (0.35–0.91).
CONCLUSIONS:Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.
Abstract
Background
Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.
Methods
To identify sex-specific genetic ...loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group.
Results
A male-specific region near the adenosine diphosphate–ribosylation factor–like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10−07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10−06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor.
Conclusions
These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.
Using sex-stratified genome-wide association analyses we identified a male-specific association of spontaneous clearance of hepatitis C virus and markers near adenosine diphosphate–ribosylation factor–like 5B gene in chromosome 10 and suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome with effects in both sexes.
Background: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer–preventive
agents. This has stimulated extensive laboratory and clinical ...research, as well as much commercial and public enthusiasm.
However, the epidemiologic evidence remains inconclusive.
Materials and Methods: We investigated the association between prediagnostic serum carotenoids (lycopene, α-carotene, β-carotene,
β-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer
Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study
included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with
regional or distant stage ( n = 90) or Gleason score ≥7 ( n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to
annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance
that is difficult to attain under non–trial conditions.
Results: No association was observed between serum lycopene and total prostate cancer odds ratios (OR), 1.14; 95% confidence
intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28 or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). β-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72
for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest
quintile; P for trend, 0.02); other carotenoids were not associated with risk.
Conclusion: In this large prospective study, high serum β-carotene concentrations were associated with increased risk for
aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent
with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate
cancer prevention. (Cancer Epidemiol Biomarkers Prev 2007;16(5):962–8)
In tissues and organs, the extracellular matrix (ECM) helps maintain inter- and intracellular architectures that sustain the structure–function relationships defining physiological homeostasis. ...Combining fiber scaffolds and cells to form engineered tissues is a means of replicating these relationships. Engineered tissues' fiber scaffolds are designed to mimic the topology and chemical composition of the ECM network. Here, we asked how cells found in the heart compare in their propensity to align their cytoskeleton and self-organize in response to topological cues in fibrous scaffolds. We studied cardiomyocytes, valvular interstitial cells, and vascular endothelial cells as they adapted their inter- and intracellular architectures to the extracellular space. We used focused rotary jet spinning to manufacture aligned fibrous scaffolds to mimic the length scale and three-dimensional (3D) nature of the native ECM in the muscular, valvular, and vascular tissues of the heart. The representative cardiovascular cell types were seeded onto fiber scaffolds and infiltrated the fibrous network. We measured different cell types' propensity for cytoskeletal alignment in response to fiber scaffolds with differing levels of anisotropy. The results indicated that valvular interstitial cells on moderately anisotropic substrates have a higher propensity for cytoskeletal alignment than cardiomyocytes and vascular endothelial cells. However, all cell types displayed similar levels of alignment on more extreme (isotropic and highly anisotropic) fiber scaffold organizations. These data suggest that in the hierarchy of signals that dictate the spatiotemporal organization of a tissue, geometric cues within the ECM and cellular networks may homogenize behaviors across cell populations and demographics.
This large randomized trial with a 2-by-2 factorial design compared a lower target range of oxygen saturation (85 to 89%) with a higher target range (91 to 95%) in extremely preterm infants. The ...lower target range did not significantly decrease the combined outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors.
A lower target range of oxygen saturation did not significantly decrease the combined outcome of severe retinopathy or death, but it resulted in an increase in mortality and a substantial decrease in severe retinopathy among survivors.
Retinopathy of prematurity is an important cause of blindness and other visual disabilities in preterm infants. The incidence of retinopathy of prematurity was increased with exposure to unrestricted oxygen supplementation in preterm infants in randomized, controlled trials performed in the 1950s.
1
In the 1960s, this increase resulted in the practice of restricting the fraction of inspired oxygen (FIO
2
) to no more than 0.50, which was estimated to result in an excess of 16 deaths per case of blindness prevented.
2
More recent data suggest that levels of oxygen saturation previously thought to be at the upper end of the . . .
Prostate cancer is the most frequent cancer in men and a leading cause of cancer death. Determining a patient's optimal therapy is a challenge, where oncologists must select a therapy with the ...highest likelihood of success and the lowest likelihood of toxicity. International standards for prognostication rely on non-specific and semi-quantitative tools, commonly leading to over- and under-treatment. Tissue-based molecular biomarkers have attempted to address this, but most have limited validation in prospective randomized trials and expensive processing costs, posing substantial barriers to widespread adoption. There remains a significant need for accurate and scalable tools to support therapy personalization. Here we demonstrate prostate cancer therapy personalization by predicting long-term, clinically relevant outcomes using a multimodal deep learning architecture and train models using clinical data and digital histopathology from prostate biopsies. We train and validate models using five phase III randomized trials conducted across hundreds of clinical centers. Histopathological data was available for 5654 of 7764 randomized patients (71%) with a median follow-up of 11.4 years. Compared to the most common risk-stratification tool-risk groups developed by the National Cancer Center Network (NCCN)-our models have superior discriminatory performance across all endpoints, ranging from 9.2% to 14.6% relative improvement in a held-out validation set. This artificial intelligence-based tool improves prognostication over standard tools and allows oncologists to computationally predict the likeliest outcomes of specific patients to determine optimal treatment. Outfitted with digital scanners and internet access, any clinic could offer such capabilities, enabling global access to therapy personalization.
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