Towards a combined prognostic index for survival in HIV infection: the role of ‘non‐HIV’ biomarkers

Background

As those with HIV infection live longer, ‘non‐AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non‐HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).

Methods

Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV‐infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS‐defining conditions); ‘non‐HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.

Results

Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle‐aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non‐HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30‐day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data.

Conclusions

When added to HIV biomarkers, ‘non‐HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.     

Advances in the field of nanooncology

Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important chapter of nanomedicine. Nanobiotechnology has refined and extended the limits of molecular diagnosis of cancer, for example, through the use of gold nanoparticles and quantum dots. Nanobiotechnology has also improved the discovery of cancer biomarkers, one such example being the sensitive detection of multiple protein biomarkers by nanobiosensors. Magnetic nanoparticles can capture circulating tumor cells in the bloodstream followed by rapid photoacoustic detection. Nanoparticles enable targeted drug delivery in cancer that increases efficacy and decreases adverse effects through reducing the dosage of anticancer drugs administered. Nanoparticulate anticancer drugs can cross some of the biological barriers and achieve therapeutic concentrations in tumor and spare the surrounding normal tissues from toxic effects. Nanoparticle constructs facilitate the delivery of various forms of energy for noninvasive thermal destruction of surgically inaccessible malignant tumors. Nanoparticle-based optical imaging of tumors as well as contrast agents to enhance detection of tumors by magnetic resonance imaging can be combined with delivery of therapeutic agents for cancer. Monoclonal antibody nanoparticle complexes are under investigation for diagnosis as well as targeted delivery of cancer therapy. Nanoparticle-based chemotherapeutic agents are already on the market, and several are in clinical trials. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level, which is facilitated by nanobiotechnology. Nanobiotechnology will facilitate the combination of diagnostics with therapeutics, which is an important feature of a personalized medicine approach to cancer.     

Antiviral activity and safety of aplaviroc,a CCR5 antagonist,in combination with lopinavir/ritonavir in HIV‐infected,therapy‐naïve patients: results of the EPIC study (CCR100136)*

Background

This phase IIb study explored the antiviral activity and safety of the investigational CC chemokine receptor 5 (CCR5) antagonist aplaviroc (APL) in antiretroviral‐naïve patients harbouring R5‐ or R5X4‐tropic virus.

Methods

A total of 191 patients were randomized 2:2:2:1 to one of three APL dosing regimens or to lamivudine (3TC)/zidovudine (ZDV) twice daily (bid), each in combination with lopinavir/ritonavir (LPV/r) 400 mg/100 mg bid. Efficacy, safety and pharmacokinetic parameters were assessed.

Results

This study was terminated prematurely because of APL‐associated idiosyncratic hepatotoxicity. A total of 141 patients initiated treatment early enough to have been able to complete 12 weeks on treatment [modified intent‐to‐treat (M‐ITT) population]; of these, 133 completed the 12‐week treatment phase. The proportion of subjects in the M‐ITT population with HIV‐1 RNA <400 copies/mL at week 12 was 50, 48, 54 and 75% in the APL 200 mg bid, APL 400 mg bid, APL 800 mg once a day (qd) and 3TC/ZDV arms, respectively. Similar responses were seen in the few subjects harbouring R5X4‐tropic virus (n=17). Common clinical adverse events (AEs) were diarrhoea, nausea, fatigue and headache. APL demonstrated nonlinear pharmacokinetics with high interpatient variability.

Conclusions

While target plasma concentrations of APL were achieved, the antiviral activity of APL+LPV/r did not appear to be comparable to that of 3TC/ZDV+LPV/r.     

Duplication of hemi mandible and oral cavity, presentation of an adult patient--a case report.

We are present a case of duplication of hemi mandible and oral cavity in an adult patient. This is a very rare condition and each and every case warrants publication. This patient is unique in that she would not have presented for surgery if she was married. She presented at 30 years of age. The patient underwent radiological investigations using CAT scan, orthopantogram and routine X-ray films. She was operated on with an elliptical incision around the swelling, excising the whole of the duplicated mandible along with other associated structures such as a salivary gland and the branchial cyst present along with it. Postoperatively the patient had mild marginal mandibular weakness which recovered with time.     

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Preoperative assessment of secondary intraocular lens implantation for aphakia: a comparison of 2 techniques

PURPOSE: To compare the preoperative evaluation of secondary intraocular lens (IOL) implantation in aphakic adults following cataract extraction in childhood using slitlamp examination and high-frequency ultrasound (HFU). METHODS: In a prospective case series, patients who had had lensectomies for congenital cataracts without primary implantation IOL were evaluated for secondary IOL insertion. Slitlamp examination and HFU were performed to study the degree of ciliary sulcus support and iridocapsular adhesions. The choice of IOL (posterior sulcus supported or anterior chamber) was compared using the 2 techniques. RESULTS: Nine eyes of 5 patients (3 men and 2 women aged 15 to 40 years) were assessed for secondary IOL insertion. Clinical slitlamp examination suggested that 3 of 9 eyes had inadequate sulcociliary support, but HFU of these eyes revealed more than adequate capsular remnants. In all 9 eyes, sulcus-supported posterior chamber IOLs were implanted. No postoperative complications were observed, and no patients required surgery for dislocated IOL. CONCLUSIONS: High-frequency ultrasound is a useful adjunct for the preoperative assessment of secondary ciliary sulcus-supported IOL implantation in aphakic patients who had congenital cataract extraction without IOL implantation. In patients in whom inadequate dilation precludes the detection of capsular support, posterior ciliary sulcus-supported secondary IOL implantation should be considered preoperatively. Although the technique enhances surgical planning and informed patient consent, the final decision occurs at the time of surgery with direct visualization of the ciliary sulcus support.