PET-CT as a predictor of outcome in resectable colorectal liver metastases

Introduction
PET-computed tomography (PET-CT) is a useful staging imaging modality in colorectal liver metastases (CRLM). This study aimed to determine whether PET-CT parameters, standardized uptake value (SUV) and reconstructed tumour volume (RTV), are predictors of prognosis and survival.

Methods
A study of all resectable CRLM patients in the regional HPB unit from 2007–2009 was performed. Preoperative PET-CT scans were retrospectively reviewed; SUV, diameter and RTV for each lesion was recorded. Correlation analysis was performed with other pathological and biochemical parameters, by Pearson’s correlation analysis. Survival analysis was performed using Cox regression hazard model. A P value of less than 0.05 was considered statistically significant.

Results
A total of 79 patients were included. SUV moderately correlated with tumour diameter, both PET-CT (r=0.4927; P<0.0001) and histology (r=0.4513; P=0.0003); RTV (r=0.4489; P<0.001), preoperative carcinoembryonic antigen (CEA) (r=0.4977; P=0.0001), and postoperative CEA (r=0.3727; P=0.004). Multivariate analysis found that an independent predictor of SUVmax was preoperative CEA (P=0.03). RTV strongly correlated with preoperative CEA (r=0.9389; P<0.0001). SUV and RTV had a negative effect on survival.

Conclusion
PET-CT, in the setting of CRLM, may have a prognostic role in assessing survival. Although no definite conclusions can be drawn regarding the prognostic role of SUV and RTV, it acts to reinforce the need for further prospective studies to validate these findings.

Three dimensional morphology and compressive behaviour of sintered biodegradable composite scaffolds

Porous poly-L-lactide acid (PLA) scaffolds are prepared using polymer sintering and porogen leaching method. Different weight fractions of the Hydroxyapatite (HA) are added to the PLA to control the acidity and degradation rate. The three dimensional morphology and surface porosity are tested using micro CT, optical microscopy and scanning electron microscopy (SEM). Results indicate that the surface porosity does not change by addition of HA. The micro Ct examinations show slight decrease in the pore size and increase in wall thickness accompanied with reduced anisotropy for the scaffolds containing HA. SEM micrographs show detectable interconnected pores for the scaffold with pure PLA. Addition of the HA results in agglomeration of the HA which blocks some of the pores. Compression tests of the scaffold identify three stages in the stress-strain curve. The addition of HA adversely affects the modulus of the scaffold at the first stage, but this was reversed for the second and third stages of the compression. The results of these tests are compared with the cellular material model. The manufactured scaffold have acceptable properties for a scaffold, however improvement to the mixing of the phases of PLA and HA is required to achieve better integrity of the composite scaffolds.

Will VEGF Trap-Eye reduce the treatment burden in neovascular age-related macular degeneration?

Evaluation of: Brown DM, Heier JS, Ciulla T et al. Primary end point results of a Phase II study of vascular endothelial growth factor trap-eye in wet age-related macular degeneration. Ophthalmology 118(6), 1089-1097 (2011); Heier JS, Boyer D, Nguyen QD et al. The 1-year results of CLEAR-IT 2, a Phase 2 study of vascular endothelial growth factor trap-eye dosed as-needed after 12-week fixed dosing. Ophthalmology 118(6), 1098-1106 (2011). Age-related macular degeneration is the most common cause of blindness in older adults in western countries, and is likely to become the largest cause of irreversible sight loss in the developing world. Treatments such as ranibizumab and bevacizumab that inhibit VEGF have improved visual outcomes markedly. Controlled trials and clinical experience have shown that the best outcomes are achieved when monthly treatment has been administered over 2 years. This poses a significant burden on health providers and patients. A novel inhibitor of VEGF, VEGF Trap-Eye, which allows less frequent dosing without loss of efficacy, has emerged as a potential treatment. CLEAR-IT 2 was a prospective randomized Phase II trial designed to assess the safety, tolerability and the anatomic and visual effects of repeated treatments with a range of doses of VEGF Trap-Eye. Impressive anatomic and visual improvements were noted with no safety concerns. © 2011 Expert Reviews Ltd.

Surveillance of Non melanoma Skin Cancer Incidence Rates in Kidney Transplant Recipients in Ireland

Background: The incidence of nonmelanomatous skin cancer (NMSC) is substantially higher among renal transplant recipients (RTRs) than in the general population. With a growing RTR population, a robust method for monitoring skin cancer rates in this population is required.
Methods: A modeling approach was used to estimate the trends in NMSC rates that adjusted for changes in the RTR population (sex and age), calendar time, the duration of posttransplant follow-up, and background population NMSC incidence rates. RTR databases in both Northern Ireland (NI) and the Republic of Ireland (ROI) were linked to their respective cancer registries for diagnosis of NMSC, mainly squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).
Results: RTRs in the ROI had three times the incidence (P<0.001) of NMSC compared with NI. There was a decline (P<0.001) in NMSC 10-year cumulative incidence rate in RTRs over the period 1994–2009, which was driven by reductions in both SCC and BCC incidence rates. Nevertheless, there was an increase in the incidence of NMSC with time since transplantation. The observed graft survival was higher in ROI than NI (P<0.05) from 1994–2004. The overall patient survival of RTRs was similar in NI and ROI.
Conclusion: Appropriate modeling of incidence trends in NMSC among RTRs is a valuable surveillance exercise for assessing the impact of change in clinical practices over time on the incidence rates of skin cancer in RTRs. It can form the basis of further research into unexplained regional variations in NMSC incidence.

Microneedle-Mediated Minimally Invasive Patient Monitoring

Background: The emerging field of microneedle-based minimally invasive patient monitoring and diagnosis is reviewed. Microneedle arrays consist of rows of micron-scale projections attached to a solid support. They have been widely investigated for transdermal drug and vaccine delivery applications since the late 1990s. However, researchers and clinicians have recently realized the great potential of microneedles for extraction of skin interstitial fluid and, less commonly, blood, for enhanced monitoring of patient health.

Methods: We reviewed the journal and patent literature, and summarized the findings and provided technical insights and critical analysis.

Results: We describe the basic concepts in detail and extensively review the work performed to date.

Conclusions: It is our view that microneedles will have an important role to play in clinical management of patients and will ultimately improve therapeutic outcomes for people worldwide.

Comparing a trauma focused and non trauma focused intervention with war affected Congolese youth: a preliminary randomised trial

While there is broad consensus about the need for interventions to help psychologically distressed, war affected youth, there is also limited research and even less agreement on which interventions work best. Therefore, this paper presents a randomised trial of trauma focused, and non trauma focused, interventions with war affected Congolese youth. Fifty war affected Congolese youth, who had been exposed to multiple adverse life events, were randomly assigned to either a Trauma Focused Cognitive Behavioural Therapy group or a non trauma based psychosocial intervention (Child Friendly Spaces). Non clinically trained, Congolese facilitators ran both groups. A convenience sample, waiting list group was also formed. Using blind assessors, participants were individually interviewed at pre intervention, post intervention and a 6-month follow-up using self-report posttraumatic stress and internalising symptoms, conduct problems and pro social behaviour. Both treatment groups made statistically significant improvements, compared to the control group. Large, within subject, effect sizes were reported at both post intervention and follow-up. At the 6-month follow-up, only the Child Friendly Spaces group showed a significant decrease in pro social behaviour. The paper concludes that both trauma focused and non trauma focused interventions led to reductions in psychological distress in war affected youth.

Reticular Pseudodrusen in Age-Related Macular Degeneration

Historically, drusen, which are recognized as the hallmark of age-related macular degeneration (AMD), have been described in terms of size, margins, and texture, and several studies have emphasized the importance of large soft drusen particularly when combined with focal pigmentary irregularities in determining the risk of progression to neovascular AMD. However, recent developments in imaging over the past decade have revealed a further distinct phenotype strongly associated with the development of late AMD, namely, reticular pseudodrusen (RPD) or reticular drusen. Reticular pseudodrusen appear as yellowish interlacing networks in the fundus and, although visible on color photography, are better visualized using infrared imaging or spectral domain optical coherence tomography. Studies correlating spectral domain optical coherence tomography and confocal scanning laser ophthalmoscopy have shown that RPD are subretinal deposits located internal to the retinal pigment epithelium in contrast to traditional drusen, which are located external to the retinal pigment epithelium. As multiple longitudinal studies have revealed RPD are strong predictors for progression to both neovascular AMD and geographic atrophy, the interest in understanding the role that RPD play in the pathogenesis of AMD has grown. This review focuses on the current literature concerning RPD and considers what is currently known regarding their epidemiology, risk factors, appearance in both retinal imaging and histology, impact on visual function, relationship to other AMD lesions, and association with the development of late AMD.

Psychosocial, educational and communicative interventions for patients with cachexia and their family carers

Purpose of review: Cancer cachexia has a substantial impact on both patients and their family carers. It has been acknowledged as one of the two most frequent and devastating problems of advanced cancer. The impact of cachexia spans biopsychosocial realms. Symptom management in cachexia is fraught with difficulties and globally, there remains no agreed standard care or treatment for this client group. There is a need to address the psychosocial impact of cachexia for both patients and their family carers.

Recent findings: Patients living at home and their family carers are often left to manage the distressing psychosocial impacts of cancer cachexia themselves. Successful symptom management requires healthcare professionals to address the holistic impact of cancer cachexia. High quality and rigorous research details the existential impact of cachexia on patients and their family carers. This information needs to inform psychosocial, educational and communicative supportive healthcare interventions to help both patients and their family carers better cope with the effects of cachexia.

Summary: Supportive interventions need to inform both patients and their family carers of the expected impacts of cachexia, and address how to cope with them to retain a functional, supported family unit who are informed about and equipped to care for a loved one with cachexia.

Human Parechovirus Infection in Neonatal Intensive Care

Background: Approximately 5-6% of all infective episodes in NICU are of viral origin. Previous studies suggest that human parechovirus (HPeV) infection presents most commonly in term infants, as a sepsis-like syndrome in which meningoencephalitis is prominent. Our aim was to study the infection rate and associated features of HPeV.

Methods: Blood samples were taken from NICU babies greater than 48 hours old, who were being investigated for late onset sepsis. Clinical and laboratory data were collected at the time of the suspected sepsis episode. Samples were tested using universal primers and probe directed at the 5'-untranslated region of the HPeV genome by reverse transcriptase PCR. Results were confirmed by electrophoresis and DNA sequencing.

Results: HPeV was detected in 11 of 84 samples (13%). These infants had a mean (interquartile range, IQR) gestational age of 28.9 (26.9 - 30.6) weeks and mean birth weight of 1.26 (SD = 0.72) kg. The median day of presentation was 16 (IQR: 11-27). These characteristics were similar to the infants without positive viral detection. Six infants presented with respiratory signs. One infant presented with signs of meningitis. Six of the 11 episodes of HPeV infection occurred during the winter months (December - February). No HPeV positive infants had abnormal findings on their 28-day cranial ultrasound examination.

Conclusions: We found a HPeV infection rate of 13% in infants being tested for late onset sepsis. HPeV should be considered as a possible cause of sepsis-like symptoms in preterm infants.

Genetic polymorphisms and kidney transplant outcomes

Purpose of review: Gene polymorphism studies are growing at a quasiexponential rate and aim to improve immediate and long-term outcomes in renal transplantation. This review highlights recent evidence and potential future directions for genetic research studies.

Recent findings: Studies are largely based on immunity, inflammation and pharmacogenetics, investigating mostly 'surrogate' outcomes with sometimes conflicting results. However, the last 12 months has also heralded the emergence of important genome-wide association studies on transplantation, more robust replicated multicentre analyses of candidate gene variants, meta-analyses, and an increasing interest in copy number variation and donor genetics.

Summary: These studies set the scene for further investigation, aiming to understand pathways of disease and biomarkers of risk, and are leading to a greater understanding of the biology of transplantation. Future studies will require focus on donor : recipient and gene : environment interactions, and an integrated approach of 'transplantomics' to evaluate long-term outcomes in multinational collaborations.

Cationicity-Enhanced Analogues of the Antimicrobial Peptides, AcrAP1 and AcrAP2, from the Venom of the Scorpion, Androctonus crassicauda, Display Potent Growth Modulation Effects on Human Cancer Cell Lines

The non disulphide-bridged peptides (NDBPs) of scorpion venoms are attracting increased interest due to their structural heterogeneity and broad spectrum of biological activities. Here, two novel peptides, named AcrAP1 and AcrAP2, have been identified in the lyophilised venom of the Arabian scorpion, Androctonus crassicauda, through “shotgun” molecular cloning of their biosynthetic precursor-encoding cDNAs. The respective mature peptides, predicted from these cloned cDNAs, were subsequently isolated from the same venom sample using reverse phase HPLC and their identities were confirmed by use of mass spectrometric techniques. Both were found to belong to a family of highly-conserved scorpion venom antimicrobial peptides - a finding confirmed through the biological investigation of synthetic replicates. Analogues of both peptides designed for enhanced cationicity, displayed enhanced potency and spectra of antimicrobial activity but, unlike the native peptides, these also displayed potent growth modulation effects on a range of human cancer cell lines. Thus natural peptide templates from venom peptidomes can provide the basis for rational analogue design to improve both biological potency and spectrum of action. The diversity of such templates from such natural sources undoubtedly provides the pharmaceutical industry with unique lead compounds for drug discovery.

The lip:A histologic and analytical approach of relevance to esthetic plastic surgery

This is a study done for the first time to understand the histologic features of the lip deeply, quantitatively, and analytically and identify the differences between the outer, intermediate, and inner parts of the lips. Previous researchers did not tackle the histologic features of the lip from this point of view. Half lip was obtained from different well-preserved cadavers where the upper lip, lower lip, and lip angle were evaluated by coronal histologic sections. A total of 43 slides were studied and photographed using light and digital microscopes (Nikon COOLSCOPE, Nikon Corporation, Tokyo, Japan), respectively. The cadavers (26 men and 17 women) were in the age group of 45 to 65 years old, and older than 65 years. Data were entered on a study pro forma and statistically analyzed. Normal histologic features of the upper lip, intermediate, and the inner lip sections were observed. Fibrous septations that sometimes had muscular components inserting into them could be identified. In between these septations, there were loose areas (chambers). The mean numbers of chambers identified in the upper and lower lips were higher in the red areas, and more septations and chambers were identified in the lower lip. New histologic observations were classified into types 1 to 7. Significant relations were identified between the total number of septations and chambers in relation to age group and sex. Higher means of septations and chambers were detected in the age group older than 65 years, and in women as a whole. In conclusion, the findings detected in this work could explain the congenital lip pits that are familial or syndromic and many post-lip augmentation complications. © 2009 Lippincott Williams & Wilkins, Inc.

Anatomic dissection of the arterial supply of the lips:an anatomical and analytical approach

Previous investigators have not described some of the new anatomic variations or provided quantitative and analytical data of the arterial anatomy of the lips in as much depth as in this study. Dissections of 14 different facial sides of cadavers were done. Through investigating the arterial supply of the upper and lower lips, measurements were performed and statistically analyzed. The main arterial supply of the upper lip was from the superior labial artery (SLA, mean external diameter, 1.8 mm [SD, 0.74 mm]); in addition, the subalar and septal branches contributed to its vascularization. The origin of the SLA was above the labial commissure in 78.6%. The subalar branch was not found but replaced by the alar artery that arose from the infraorbital artery in 1 specimen. The main arterial supply of the lower lip was derived from 3 branches of the facial artery, the inferior labial artery (mean external diameters, 1.4 mm [SD, 0.31 mm]) and the horizontal and vertical labiomental arteries. The inferior labial artery originated mostly below the labial commissure in 42.9% and formed a common trunk with the SLA in 28.6%. The horizontal labiomental artery was present in all, but vertical labiomental artery was absent in 21.4% of specimens. Overall, observed anatomic variations were classified into types I to VIII. Significant relations between the demographic variables and measured parameters were reported including the correlation coefficient among evaluated parameters. In conclusion, this study provides various information that aids in creating new flaps and supports the vascular base for clinical procedures in reconstructive surgery of the lip.