Clinical Assessment of a Novel Recombinant Simian Adenovirus ChAdOx1 as a Vectored Vaccine Expressing Conserved Influenza A Antigens

Adenoviruses are potent vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same drawbacks. We have constructed a replication-deficient chimpanzee adenovirus-vectored vaccine expressing the conserved influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1). Here, we report safety and T-cell immunogenicity following vaccination with this novel recombinant simian adenovirus, ChAdOx1 NP+M1, in a first in human dose-escalation study using a 3+3 study design, followed by boosting with modified vaccinia virus Ankara expressing the same antigens in some volunteers. We demonstrate ChAdOx1 NP+M1 to be safe and immunogenic. ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection.     

Coadministration of Seasonal Influenza Vaccine and MVA-NP+M1 Simultaneously Achieves Potent Humoral and Cell-Mediated Responses

Current seasonal influenza vaccines have reduced immunogenicity and are of suboptimal efficacy in older adults. We have previously shown that the novel candidate vaccine MVA-NP+M1 is able to boost memory T cell responses in adults aged 50–85 years. Preclinical studies have demonstrated that viral vectored vaccines can act as adjuvants when coadministered with protein-based vaccines. We have conducted a phase I clinical trial to compare the coadministration of seasonal influenza vaccine and MVA-NP+M1 with seasonal influenza vaccine alone in adults aged 50 years and above. This combination of vaccines was safe and well tolerated. T cell responses to internal influenza proteins were boosted to significantly higher levels in the group receiving MVA-NP+M1 compared with the group receiving seasonal influenza vaccine alone. Rates of seroprotection and seroconversion against the three vaccine strains were similar in both groups; however, there was a significant increase in the geometric mean titer ratio for the H3N2 component of seasonal influenza vaccine in the coadministration group. While some vaccine combinations result in immune interference, the coadministration of MVA-NP+M1 alongside seasonal influenza vaccine is shown here to increase some influenza strain-specific antibody responses and boost memory T cells capable of recognizing a range of influenza A subtypes.     

Surface roughness and translucency of resin composites after immersion in coffee and soft drink

The aim of this study was to evaluate the in vitro changes in color and surface roughness of different composite resins when subjected to cycles of immersion in three coloring solutions: coffee, soft drink, and coffee plus soft drink. Sixty test specimens were made of each material, all in shade A3. Translucency and initial roughness measurements were taken by spectrophotometer and roughness meter. Then the samples were submitted to three cycles per day of exposure to potentially coloring solutions for a period of 15 days. Final roughness and translucency measurements were taken, the mean and standard deviation calculated for each resin and each variable. Data were initially analyzed by the one away ANOVA test, which showed significant differences between groups (p<0.05). Subsequently the post hoc and Tukey tests were performed with level of significance of 0.05. The results showed that the coloring substances altered translucency and surface roughness. DURAFILL resin immersed in the soft drink (M3) was the least pigmented, while CONCEPT resin immersed in the coffee (M2) showed the the least loss of surface smoothness. The Spearman and Pearson coefficients were 0.38 and 0.04 respectively, signifying that there is no correlation between roughness and translucency.     

Massive pleural effusion due to metastasis of prostate cancer

We describe the case of a 72-year old male with pleural effusion associated with prostate cancer. There was a previous history of tobacco smoking (pack/year: 47) and of total prostatectomy followed by external beam radiation therapy seven years previously for prostate cancer. Furthermore, he was submitted to orchiectomy plus non-steroidal anti-androgen blockage, in addition to docetaxel-based chemotherapy and prednisone. After the beginning of chemotherapy, a progressive elevation in prostate specific antigen (PSA) levels was observed. On admission, he presented with fever, weight loss, and respiratory symptoms due to a massive right pleural effusion. Fluid samples obtained by needle aspiration showed haemorrhagic exudates without malignant cells. Pleural metastasis were detected by thorax imaging studies, and biopsy samples revealed prostate adenocarcinoma as the origin of his pleural effusion. Pleural fluid was drained and talc pleurodesis was performed. This report aims to describe the occurrence of massive pleural effusion due to metastasis of prostate cancer and emphasizes the role of pleural biopsy with immunohistochemical studies to characterize this diagnosis.     

The origins of a research community in the Majengo observational cohort study,Nairobi, Kenya

Background  

Since the 1980s the Majengo Observational Cohort Study (MOCS) has examined sexually transmitted infections, in particular HIV/AIDS, in a cohort of sex workers in Majengo, an impoverished urban village in Nairobi, Kenya. The MOCS investigators have faced criticism since the women have remained in the sex trade for the duration of their participation in the study, prompting concerns about exploitation. Yet despite these concerns, the cohort has survived for almost 30 years.     

Accelerated hypofractionated adjuvant whole breast radiation with simultaneous integrated boost using volumetric modulated arc therapy for early breast cancer: A phase I/II dosimetric and clinical feasibility study from a tertiary cancer care centre of India

Background

Hypofractionation has become standard of care after Breast Conserving Therapy (BCT) in many European and few others western countries. Though still debatable, tumor cavity boost is routinely practised in our centre. Hypofractionation is not yet the current standard of practice in Asian countries. Employing hypofractionation and simultaneous integrated boost to lumpectomy cavity with conformal technique is not the current practice in this region. Hence the study was performed to see whether accelerated hypofractionation and simultaneous boost can be combined using volumetric modulated arc therapy (VMAT) in treating early breast cancer (EBC) patients.

Delayed diagnosis of anorectal malformations: are current guidelines sufficient?

Aim: To determine the frequency and presenting features of infants with delayed diagnosis of anorectal malformations (ARM) referred to an Australian tertiary paediatric institution. Methods: Infants referred to our institution with a final diagnosis of ARM were retrospectively reviewed between 2001 and 2009. The first cohort consisted of patients that were referred between November 2001 and November 2006 with the diagnosis of an ARM that had been delayed for more than 48 h. The second cohort was those referred between December 2006 and May 2009 with whom the diagnosis of ARM had not been made within 24 h of birth. Results: Nineteen infants were referred with delayed diagnosis of an ARM over the 7.5 years of the study. Of 44 patients referred to our institution between December 2006 and May 2009, diagnosis of an ARM was delayed more than 24 h in 14 (32%). There was no difference in gender, birth weight, prematurity, type of malformation or presence of associated anomalies between those with timely and delayed diagnosis of their ARM. A significantly greater proportion of those with a delayed diagnosis presented with obstructive symptoms (86% vs. 27%, P < 0.001), including abdominal distension (57%) and delayed passage of meconium or stool (29%). Despite undergoing neonatal examination, the diagnosis of ARM was missed in 12 patients overall. Conclusion: Delayed diagnosis of an ARM appears to be common, occurring in approximately 32% of patients referred to our institution over the last 2.5 years. Current guidelines appear insufficient to ensure prompt diagnosis of ARM.     

A randomized controlled trial comparing a computer-assisted insulin infusion protocol with a strict and a conventional protocol for glucose control in critically ill patients

Purpose

The objective of this study is to evaluate blood glucose (BG) control efficacy and safety of 3 insulin protocols in medical intensive care unit (MICU) patients.

Methods

This was a multicenter randomized controlled trial involving 167 MICU patients with at least one BG measurement ≥150 mg/dL and one or more of the following: mechanical ventilation, systemic inflammatory response syndrome, trauma, or burns. The interventions were computer-assisted insulin protocol (CAIP), with insulin infusion maintaining BG between 100 and 130 mg/dL; Leuven protocol, with insulin maintaining BG between 80 and 110 mg/dL; or conventional treatment—subcutaneous insulin if glucose >150 mg/dL. The main efficacy outcome was the mean of patients' median BG, and the safety outcome was the incidence of hypoglycemia (≤40 mg/dL).

Results

The mean of patients' median BG was 125.0, 127.1, and 158.5 mg/dL for CAIP, Leuven, and conventional treatment, respectively (P = .34, CAIP vs Leuven; P < .001, CAIP vs conventional). In CAIP, 12 patients (21.4%) had at least one episode of hypoglycemia vs 24 (41.4%) in Leuven and 2 (3.8%) in conventional treatment (P = .02, CAIP vs Leuven; P = .006, CAIP vs conventional).

Conclusions

The CAIP is safer than and as effective as the standard strict protocol for controlling glucose in MICU patients. Hypoglycemia was rare under conventional treatment. However, BG levels were higher than with IV insulin protocols.