Risk of skin cancer and other malignancies in kidney,liver, heart and lung transplant recipients 1970 to 2008—A Swedish population‐based study

Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population‐based studies have quantified and compared cancer risks according to graft type and with long‐term follow‐up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow‐up of 93,432 person‐years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIR_{cancer excl SCC} 2.4 (95% CI, 2.2–2.5); SIR_SCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIR_{cancer excl SCC} 3.3 (95% CI, 2.8–4.0); SIR_SCC 198 (95% CI, 174–224), followed by kidney SIR_{cancer excl SCC} 2.3 (95% CI, 2.1–2.4); SIR_SCC 121 (95% CI, 116–127) and liver recipients SIR_{cancer excl SCC} 2.3 (95% CI, 1.9–2.8); SIR_SCC 32 (95% CI, 24–42). During follow‐up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post‐transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.     

Effect of phenytoin on interleukin-1β production in human gingival fibroblasts challenged to tumor necrosis factor αin vitro

Effects and interaction of tumor necrosis factor α (TNFα) and the antiepileptic drug phenytoin (PHT) on interleukin-1β (IL-1β) production as well as on prostaglandin E₂ (PGE₂) formation were studied in gingival fibroblasts in vitro. TNFα, in contrast to PHT, dose-dependently stimulated the production of cell-associated IL-1β. The stimulatory effect of TNFα on IL-1β production was accompanied by enhanced PGE₂ formation. When PHT and TNFα were added simultaneously, the drug potentiated the stimulatory effect of TNFα on both IL-Iβ production and PGE₂ formation. The major PHT metabolite, p-HPPH, did not affect IL-1β production, either alone or in combination with TNFα. The production of IL-1β induced by TNFα and the combination of TNFα and PHT was further enhanced in the presence of the prostaglandin endoperoxide (PGH) synthase inhibitors, indomethacin and flurbiprofen. The PHT-mediated enhancement of TNFα-induced IL-1β production and PGE₂ formation in gingival fibroblasts may be an important link in the pathogenesis of gingival overgrowth induced by PHT.     

Cadmium exposure from smoking cigarettes: variations with time and country where purchased

Cadmium has been determined in 26 brands of cigarettes purchased in eight different countries throughout the world and in 16 different samples of cigarettes produced in Sweden between 1918 and 1968. In addition the amount of cadmium released from smoking one cigarette to the particulate phase collected from a smoking simulation machine, corresponding to the amount actually inhaled by a smoker, has been determined. The cadmium concentration in different brands of cigarettes ranged from 0.19 to 3.0 micrograms Cd/g dry wt, with a general tendency toward lower values in cigarettes from developing countries. No systematic change in the cadmium concentration of cigarettes with time could be revealed. The amount of cadmium inhaled from smoking one cigarette containing about 1.7 microgram Cd was estimated to be 0.14 to 0.19 microgram, corresponding to about 10% of the total cadmium content in the cigarette.     

Thrombospondin-1: an islet endothelial cell signal of importance for β-cell function

OBJECTIVE

Loss of thrombospondin (TSP)-1 in pancreatic islets has been shown to cause islet hyperplasia. This study tested the hypothesis that endothelial-derived TSP-1 is important for β-cell function.

RESEARCH DESIGN AND METHODS

Islet function was evaluated both in vivo and in vitro. Messenger RNA and protein expression were measured by real-time PCR and Western blot, respectively. The role of endothelial-derived TSP-1 for β-cell function was determined using a transplantation design in which recipient blood vessels either were allowed to grow or not into the transplanted islets.

RESULTS

TSP-1–deficient mice were glucose intolerant, despite having an increased β-cell mass. Moreover, their islets had decreased glucose-stimulated insulin release, (pro)insulin biosynthesis, and glucose oxidation rate, as well as increased expression of uncoupling protein-2 and lactate dehydrogenase-A when compared with control islets. Almost all TSP-1 in normal islets were found to be derived from the endothelium. Transplantation of free and encapsulated neonatal wild-type and TSP-1–deficient islets was performed in order to selectively reconstitute with TSP-1–positive or –negative blood vessels in the islets and supported that the β-cell defects occurring in TSP-1–deficient islets reflected postnatal loss of the glycoprotein in the islet endothelial cells. Treatment of neonatal TSP-1–deficient mice with the transforming growth factor (TGF)β-1–activating sequence of TSP-1 showed that reconstitution of TGFβ-1 activation prevented the development of decreased glucose tolerance in these mice. Thus, endothelial-derived TSP-1 activates islet TGFβ-1 of importance for β-cells.

CONCLUSIONS

Our study indicates a novel role for endothelial cells as functional paracrine support for pancreatic β-cells.The vasculature traditionally has been regarded mainly as a transport system that mediates metabolic exchange between tissues and blood. However, aside from its transport functions, blood-vessel cells have, in recent years, been recognized to be able to interact with and differentiate adjacent parenchymal cells through paracrine signals during development (1–3). Moreover, they seem to be able to provide mitotic signals during adulthood (4).To date, there have been few studies (5–7) on whether endothelial cells may directly affect parenchymal function. Islets of Langerhans in the adult have a uniquely dense network of capillaries maintained by constant exposure to vascular endothelial growth factor (VEGF)-A secreted from adjacent β-cells (8,9). The high number of islet capillaries results in each β-cell being located directly adjacent to at least one endothelial cell (10), thereby enabling a direct interaction with endothelium-derived factors. The importance of islet endothelial factors in the control of β-cell proliferation recently has been studied, and both endothelium-derived hepatocyte growth factor (11) and the vascular membrane component laminin (7) seem to be important in this context.In the current study, we investigated products of purified and isolated islet endothelial cells and thereby found the glycoprotein thrombospondin (TSP)-1 to be highly expressed in the endothelium of islets. TSP-1 is mainly known for its antiangiogenic properties (12) but also may alter the morphology of pancreatic islets and functions as a major activator of transforming growth factor (TGF)β-1 (13). Because TGFβ-1 is known to modulate β-cell function (14,15), we tested the hypothesis that endothelial cell–derived TSP-1 is important to maintain β-cell function postnatally.     

Chronic kidney disease--a common and serious complication after intestinal transplantation

BACKGROUND: Chronic kidney disease after organ transplantation is a serious complication that negatively impacts on long-term patient survival. We describe long-term renal function after intestinal transplantation by serial measurements of glomerular filtration rates (GFR) with Chromium EDTA clearance. MATERIALS AND METHODS: Ten patients with at least 6 months survival form the basis of this report. Glomerular filtration rate measurements were performed at baseline, 3 months posttransplantation, and yearly thereafter. Median follow-up time for the cohort was 1.5 years (0.5-7.8 years). Tacrolimus (Prograf) was discontinued in four patients because of impaired renal function. These four patients were switched to sirolimus (Rapamune) at 11, 18, 24, and 40 months posttransplantation. RESULTS: Median baseline GFR was 67 (22-114) mL/min/1.73 m. In the adult patients, GFR 3 months posttransplantation had decreased to 50% of the baseline. At 1 year, median GFR in the adult patients was reduced by 72% (n=5). Two patients developed renal failure within the first year and required hemodialysis. One of the pediatric patients fully recovered her renal function, the second pediatric patient lost 20% of her baseline GFR at 6 months posttransplantation. Glomerular filtration rate calculated with the modified diet in renal disease formula consistently overestimated GFR by approximately 30% compared with measured GFR. CONCLUSION: Chronic kidney disease and renal failure are common after intestinal transplantation. These two factors significantly contribute to poor long-term survival rates. Measurements of GFR may help to identify those individuals at risk for developing chronic kidney disease to implement renal sparing strategies.     

Otitis media and feeding with breast milk of children with cleft palate.

The purpose of the present study was to analyse the incidence of acute and secretory otitis media (OM), and feeding with breast milk, and the use of a grommet in children with a cleft palate (CP/CLP) or cleft lip (CL), compared with controls. A total of 84 children between 6 and 10 years of age were studied. The CP/CLP group consisted of 48 children with an isolated cleft palate (n = 28), or a cleft lip and palate (n = 20). The CL group consisted of 15 children with an isolated cleft lip. The controls were 21 children without clefts. Children with CP/CLP had acute OM significantly more often than children without clefts (43/48 compared with 10/21), and secretory OM (40/48 compared with 4/21), despite the use of grommets. CP/CLP children were breast fed for a mean of 2.8 months (range 0-13), compared with 3.6 months (0-12) for CL, and 7.5 (0-24) months for controls. There was a significant correlation during the first 18 months of life between longer duration of feeding with breast milk and a lower incidence of acute and secretory OM in the three study groups combined. The incidence of otitis media was not affected by care in a day centre, having a sibling attending a day care centre, or by the family's medical history. Despite cleft repair and early treatment with grommets, both secretory and acute OM are common among children with cleft palate, presumably as a result of their eustachian tube dysfunction. The present study suggests that premature cessation of feeding with breast milk may contribute to an increased incidence of acute and secretory OM.     

Prophylactic incisional negative pressure wound therapy shows promising results in prevention of wound complications following inguinal lymph node dissection for Melanoma: A retrospective case-control series

BackgroundInguinal lymphadenectomy (ILND) for melanoma is associated with a number of complications including seroma, surgical site infection (SSI), and lymphedema. Incisional negative pressure wound therapy (iNPWT) has shown promising results in preventing postoperative morbidity across a wide variety of surgical procedures, but these results are yet to be investigated in patients undergoing ILND for melanoma.MethodsIn this study, we reviewed the data of 55 melanoma patients treated with ILND between January 2015 and January 2017 at Odense University Hospital. Patients were followed up until April 2018 for the occurrence of seroma, SSI, and lymphedema. We used prophylactic iNPWT after ILND in 14 patients and compared their morbidity outcomes with the 41 patients receiving standard postoperative wound care in the same period.ResultsThe iNPWT intervention significantly reduced seroma compared to the control group (28.6% vs. 90.3%, p < 0.001) and had a trending impact on wound infection (42.9% vs. 65.9%, p = 0.13). The effect was not significant for the prevention of lymphedema (35.7% vs. 51.2%, p = 0.33). Because the iNPWT group had relatively fewer incidences of seroma, SSI, and lymphedema, the iNPWT intervention was more cost-effective than conventional wound care (US$911.2 vs. US$2542.7, p < 0.05).ConclusionThe use of prophylactic iNPWT significantly reduced seroma formation following ILND. These promising results, however, need to be confirmed in a future prospective randomized trial.     

Epidemiology of adult ankle fractures in Sweden between 1987 and 2004: a population-based study of 91,410 Swedish inpatients

Background and purpose

Previous national epidemiological data on the characteristics and trends of patients with ankle fractures have been limited. We therefore analyzed data on Swedish inpatients with ankle fractures in this nationwide population study, based on data from 1987 through 2004.

Patients and methods

Data on all inpatients aged 15 years and older with ankle fracture were extracted from the Swedish National Patient Register for the period 1987–2004.

Results

We identified 91,410 hospital admissions with ankle fracture, corresponding to an annual incidence rate of 71 per 10⁵ person-years. During the study period, the number of hospital admissions increased by 0.2% annually, mainly from increase in fracture incidence in the elderly women. Mean age at admission was 45 (SD 19) years for men and 58 (18) for women. The major mechanism of injury was falling at the same level (64%).

Interpretation

This nationwide study of inpatients with ankle fractures showed an increase in fracture incidence, particularly in elderly women.Ankle fractures are among the most common fractures treated in orthopaedic surgery today. They are also a significant source of morbidity in both the young and the elderly (Donaldson et al. 1990, Jones et al. 1994, van Staa et al. 2001). Previous epidemiological studies have shown trends of increasing incidence over time, mainly in elderly women (Bengnér et al. 1986, Daly et al. 1987, Baron et al. 1996, Kannus et al. 1996, Court-Brown et al. 1998, van Staa et al. 2001, Kannus et al. 2002). However, most of these studies have included limited numbers of patients, and mostly originated from single hospitals or limited areas.Basic epidemiological data such as incidence, fracture type, age and sex distribution, mechanisms of injury, and surgical procedures can provide estimates when discussing disease burden and in the planning and provision of healthcare.The purpose of this study was to perform an epidemiological analysis of all adult ankle fractures requiring hospital admission in Sweden from 1997 through 2004, including incidence, causes of fracture, surgical procedures, patient characteristics, and trends over time.