Jeremy W. Simcock

First and subsequent nonmelanoma skin cancers: incidence and predictors in a population of New Zealand renal transplant recipients

BACKGROUND Renal transplant recipients (RTRs) have an increased risk of developing nonmelanoma skin cancers (NMSCs). The aims of this study were to determine the incidence and subsequent history of NMSCs in RTRs, together with risk factors. METHODS All patients transplanted between July 1972 and March 2007, and followed up at Christchurch Hospital, New Zealand, were studied. Immunosuppression regimens were mostly prednisone, azathioprine, cyclosporine and prednisone, mycophenolate mofetil, cyclosporine since 1998. RESULTS Of 384 RTRs, 96 developed at least one NMSC. The median time to first NMSC was 18.3 years (95% CI 14.2, 22.9) from transplant, as estimated by survival analysis. Individual predictors of first NMSC in RTRs were older age at first transplant (P < 0.0001), male sex (P = 0.006) and initial immunosuppression regimen (P = 0.001); only age (P < 0.0001) and male gender (P = 0.003) were significant predictors in a joint model. The mean rate of subsequent NMSCs was 1.67 per year (95% CI = 1.32, 2.11). Older age at first renal transplant (P = 0.009) or at discovery of the first NMSC (P = 0.01) was associated with a higher annual rate of new NMSC following the discovery of the first NMSC. The median survival time to a second NMSC was 2.2 years (CI 1.4, 3.0). Fourteen patients died of metastatic squamous cell carcinoma (15% case fatality). CONCLUSIONS NMSCs are a major health issue for RTRs, especially in older males. Once RTRs have developed their first NMSC, ongoing surveillance and prompt treatment are essential.

Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations

Background: Vitamin C (ascorbate) is likely to be essential for skeletal muscle structure and function via its role as an enzyme cofactor for collagen and carnitine biosynthesis. Vitamin C may also protect these metabolically active cells from oxidative stress. Objective: We investigated the bioavailability of vitamin C to human skeletal muscle in relation to dietary intake and plasma concentrations and compared this relation with ascorbate uptake by leukocytes. Design: Thirty-six nonsmoking men were randomly assigned to receive 6 wk of 0.5 or 2 kiwifruit/d, an outstanding dietary source of vitamin C. Fasting blood samples were drawn weekly, and 24-h urine and leukocyte samples were collected before intervention, after intervention, and after washout. Needle biopsies of skeletal muscle (vastus lateralis) were carried out before and after intervention. Results: Baseline vastus lateralis ascorbate concentrations were ∼16 nmol/g tissue. After intervention with 0.5 or 2 kiwifruit/d, these concentrations increased ∼3.5-fold to 53 and 61 nmol/g, respectively. There was no significant difference between the responses of the 2 groups. Mononuclear cell and neutrophil ascorbate concentrations increased only ∼1.5- and ∼2-fold, respectively. Muscle ascorbate concentrations were highly correlated (P < 0.001) with dietary intake (R = 0.61) and plasma concentrations (R = 0.75) in the range from 5 to 80 μmol/L. Conclusions: Human skeletal muscle is highly responsive to vitamin C intake and plasma concentrations and exhibits a greater relative uptake of ascorbate than leukocytes. Thus, muscle appears to comprise a relatively labile pool of ascorbate and is likely to be prone to ascorbate depletion with inadequate dietary intake. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12611000162910.

Postdischarge clean wound infections: Incidence underestimated and risk factors overemphasized

Background:  Wound infections are a leading cause of postoperative morbidity and a cost to both the individual and community. The surgeon now has a reduced appreciation of wound‐infection rates because of shorter hospital stays and an increasing reliance on the primary care physicians. The incidence of wound infections which occurred following clean surgical procedures, as well as whether they could have been predicted by the known risk factors, were analysed in the present prospective study.

Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells

BACKGROUND Cancer, particularly cutaneous squamous cell carcinoma (SCC), is a major cause of mortality in renal transplant recipients (RTRs). Myeloid-derived suppressor cells (MDSC) play a central role in suppressing cancer immunosurveillance but their potential mobilisation in RTRs and levels relative to those of other immunoregulatory dendritic cell (DC) populations have not been analysed. METHODS The circulating frequencies of MDSC and DC were analysed by multicolour flow cytometry in immunocompetent patients without (n = 13) or with (ICI-SCC(Pos), n = 14) current SCC, normal donors (NDs, n = 34), chronic kidney disease patients (CKD patients, n = 22) and RTRs (n = 31). RESULTS Compared to NDs, RTRs had significantly elevated levels of both CD14(Neg) and CD14(Pos) MDSC subsets (P < 0.001), while CKD patients and ICI-SCC(Pos) had significantly elevated levels of only the CD14(Neg)-MDSC subset. DC frequencies were significantly decreased in RTRs and CKD patients but were at normal levels in ICI-SCC(Pos). The MDSC/DC ratio was significantly elevated (P < 0.05) in RTRs (median = 5.7), CKD patients (median = 3.2) and ICI-SCC(Pos) (median = 3.5) relative to NDs (median = 0.7). The use of immunosuppressive drugs in CKD patients and past/current occurrence of SCC in RTRs was associated with significantly increased CD14(Neg)-MDSC frequencies. MDSC enriched from RTRs, when co-cultured with activated NDs T cells significantly suppressed extracellular IL-10 levels and can, when activated with formyl-methionyl-leucyl-phenylalanine, inhibit T-cell proliferation. CONCLUSIONS RTRs, CKD patients and ICI-SCC(Pos) have increased MDSC frequencies and MDSC/DC ratios. These changes may impact on cancer immunosurveillance. Therefore, MDSC represent both a potential therapeutic target and prognostic marker in these patients, with respect to the development of SCC and other malignancies.

Endothelial precursor cells home to a vascularized tissue engineering chamber by application of the angiogenic chemokine CXCL12.

Tissue engineering of vascularized constructs has great utility in reconstructive surgery. While we have been successful in generating vascularized granulation-like tissue and adipose tissue in an in vivo tissue engineering chamber, production of other differentiated tissues in a stable construct remains a challenge. One approach is to utilize potent differentiation factors, which can influence the base tissue. Endothelial precursor cells (EPCs) have the ability to both carry differentiation factors and home to developing vasculature. In this study, proof-of-principle experiments demonstrate that such cells can be recruited from the circulation into an in vivo tissue engineering chamber. CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor 1 was infused into the chamber through Alzet osmotic pumps and chamber cannulation between days 0 and 7, and facilitated recruitment of systemically inoculated exogenous human EPCs injected on day 6. CXCL12 infusion resulted in an eightfold increase in EPC recruitment, 2 (p = 0.03) and 7 days postinfusion (p = 0.008). Delivery of chemotactic/proliferation and/or differentiation factors and appropriately timed introduction of effective cells may allow us to better exploit the regenerative potential of the established chamber construct.

A randomized steady-state bioavailability study of synthetic versus natural (kiwifruit-derived) vitamin C.

Whether vitamin C from wholefoods has equivalent bioavailability to a purified supplement remains unclear. We have previously showed that kiwifruit provided significantly higher serum and tissue ascorbate levels than synthetic vitamin C in a genetically vitamin C-deficient mouse model, suggesting a synergistic activity of the whole fruit. To determine if these results are translatable to humans, we carried out a randomized human study comparing the bioavailability of vitamin C from kiwifruit with that of a vitamin C tablet of equivalent dosage. Thirty-six young non-smoking adult males were randomized to receive either half a gold kiwifruit (Actinidia Chinensis var. Hort 16A) per day or a comparable vitamin C dose (50 mg) in a chewable tablet for six weeks. Ascorbate was monitored weekly in fasting venous blood and in urine, semen, leukocytes, and skeletal muscle (vastus lateralis) pre- and post-intervention. Dietary intake of vitamin C was monitored using seven day food and beverage records. Participant ascorbate levels increased in plasma (P < 0.001), urine (P < 0.05), mononuclear cells (P < 0.01), neutrophils (P < 0.01) and muscle tissue (P < 0.001) post intervention. There were no significant differences in vitamin C bioavailability between the two intervention groups in any of the fluid, cell or tissue samples tested. Overall, our study showed comparable bioavailability of synthetic and kiwifruit-derived vitamin C.

Angiogenesis and host immune response contribute to the aggressive character of non-melanoma skin cancers in renal transplant recipients

Mackenzie K A, Miller A P, Hock B D, Gardner J, Simcock J W, Roake J A, Dachs G U, Robinson B A & Currie M J
(2011) Histopathology 58, 875–885
Angiogenesis and host immune response contribute to the aggressive character of non‐melanoma skin cancers in renal transplant recipients

Keratin-based products for effective wound care management in superficial and partial thickness burns injuries

This n=40 cohort study on superficial and partial thickness burns compares novel keratin-based products with the standard products used at our facility. The keratin products are found to facilitate healing with minimal scarring, be well tolerated with minimal pain and itch, be easy to use for the health professional and be cost effective for the health care provider. For these reasons they are being adopted into use at our facility.

Tendon Transfer Surgery for People With Tetraplegia: An Overview

After cervical spinal cord injury, the loss of upper limb function is common. This affects an individuals ability to perform activities of daily living and participate in previous life roles. There are surgical procedures that can restore some of the upper limb function lost after cervical spinal cord injury. Tendon transfer surgery has been performed in the tetraplegic population since the early 1970s. The goals of surgery are to provide a person with tetraplegia with active elbow extension, wrist extension (if absent), and sufficient pinch and/or grip strength to perform activities of daily living without the need for adaptive equipment or orthoses. These procedures are suitable for a specific group, usually with spinal cord impairment of C4-8, with explicit components of motor and sensory loss. Comprehensive team assessments of current functioning, environment, and personal circumstances are important to ensure success of any procedure. Rehabilitation after tendon transfer surgery involves immobilization for tendon healing followed by specific, targeted therapy based on motor learning and goal-orientated training. Outcomes of tendon transfer surgery are not limited to the improvements in an individuals strength, function, and performance of activities but have much greater life affects, especially with regard to well-being, employment, and participation. This article will provide an overview of the aims of surgery, preoperative assessment, common procedures, postoperative rehabilitation strategies, and outcomes based on clinical experience and international published literature.

Myocardial Metastasis of Cutaneous Squamous Cell Carcinoma in a Renal Transplant Recipient

Myocardial metastasis from a cutaneous squamous cell carcinoma (SCC) is rare. Herein we have presented a case of metastasis from cutaneous SCC to the myocardium in a renal transplant recipient, which was confirmed by a cardiac fine-needle biopsy. Postmortem examination revealed disseminated metastatic disease involving myocardium, lungs, thyroid, skin, and peritoneum secondary to cutaneous SCC likely related to immunosuppression. At 46 years of age, he received a renal transplant for chronic renal failure caused by chronic glomerulonephritis. He started to develop multiple nonmelanoma skin cancers 4 years later. At least 23 invasive SCCs and 14 basal cell carcinomas were excised. His immunosuppressive regimen consisted of cyclosporine (150 mg), azathioprine (75 mg), and prednisone (10 mg daily), which was not modified despite multiple nonmelanoma skin cancers. Our case report further illustrates the potentially aggressive and fatal nature of cutaneous SCCs that can develop in organ transplant recipients. It argues for modification of the immunosuppressive regimen in such patients. The management of renal transplant patients with nonmelanoma skin cancers remains difficult and complex.