Expression of hypoxia‐inducible factor‐1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

Late renal graft loss is associated with interstitial fibrosis. Hypoxia‐inducible factor‐1α (HIF‐1α) is thought to facilitate fibrosis through interaction with TGF‐β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF‐1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty‐nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF‐1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF‐1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF‐1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF‐1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1‐10‐72‐318‐13)     

Nasal-continuous positive airway pressure reduces pulmonary morbidity and length of hospital stay following thoracoabdominal aortic surgery

STUDY OBJECTIVES: Patients who undergo surgical repair of thoracoabdominal aortic aneurysms have a high risk for the development of respiratory complications, which cause significant postoperative morbidity and prolong hospitalization, compared to patients who undergo other types of surgery. We studied whether prophylactic noninvasive application of nasal continuous positive airway pressure (nCPAP) administered via a facemask immediately after extubation may reduce pulmonary morbidity and shorten the length of hospitalization. DESIGN: Prospective randomized clinical trial. SETTING: Surgical ICU of a university hospital. PATIENTS: Fifty-six patients following elective prosthetic replacement of the thoracoabdominal aorta, of whom 6 patients were excluded because they had received prolonged mechanical ventilation. INTERVENTIONS: Following extubation in the ICU, nCPAP was applied for 12 to 24 h at an airway pressure of 10 cm H2O to patients in the study group (n = 25). Subjects in the control group (n = 25) received standard treatment including intermittent nCPAP (10 cm H2O for 10 min) every 4 h. MEASUREMENTS AND RESULTS: In the study group, nCPAP was applied for a mean (+/- SD) duration of 23 +/- 3 h at an airway pressure of 10 +/- 1 cm H2O, which improved pulmonary oxygen transfer without altering hemodynamics (ie, heart rate, mean arterial BP, and central venous pressure). The application of nCPAP was associated with fewer pulmonary complications (Pa(O2)/fraction of inspired oxygen [F(IO2)] <100, atelectasis, pneumonia, reintubation rate) compared to the control group (7 of 25 patients vs 24 of 25 subjects, respectively; p = 0.019). The mean duration of intensive care treatment tended to be shorter in the study group compared to the control group (8 +/- 1 vs 12 +/- 2 days, respectively; difference not significant), while the mean length of hospital stay was shorter with nCPAP therapy (22 +/- 2 vs 34 +/- 5 days, respectively; p = 0.048). CONCLUSIONS: The prophylactic application of nCPAP at airway pressures of 10 cm H2O significantly reduced pulmonary morbidity and length of hospital stay following the surgical repair of thoracoabdominal aortic aneurysms. Thus, it can be recommended as a standard treatment procedure for this patient group.     

Impact of Antiretroviral Therapy on Health-Related Quality of Life among South African Women in the CAPRISA 002 Acute Infection Study

Concerns are often raised regarding potentially adverse effects of antiretroviral therapy (ART) on health-related quality of life (HRQoL), but there is limited longitudinal data to prove this. Building on our prior investigation, we examined the impact of ART on HRQoL among HIV-infected South African women with extensive follow-up in the CAPRISA 002 Acute Infection Cohort Study. Overall HRQoL and five sub-domains [physical well-being (PWB), emotional well-being (EWB), functional and global well-being (FGWB), social well-being (SWB) and cognitive functioning (CF)] were assessed using the Functional Assessment of HIV Infection (FAHI) instrument. Our analyses comparing FAHI scores between pre-ART (established infection) and ART phases using paired Wilcoxon signed-rank tests and adjusted mixed-effects regression models revealed improvements on ART in overall HRQoL, and in PWB, EWB, and SWB, but not in FGWB and CF. No long-term adverse impact of ART on HRQoL was detected, providing additional non-biomedical support to early treatment strategies.     

Prevalence and risk factors of cataract after chemotherapy with or without central nervous system irradiation for childhood acute lymphoblastic leukaemia: an LEA study

Corticosteroid and central nervous system (CNS) irradiation can induce cataract in childhood lymphoblastic leukaemia survivors. Few prospective studies with systematic ophthalmological evaluation have been published. Cataract was prospectively assessed by serial slip lamp tests in 517 patients. All had acute lymphoblastic leukaemia, all had been treated by chemotherapy with or without CNS irradiation, and none had received haematopoietic stem cell transplantation. Median ages at last evaluation and follow‐up duration from leukaemia diagnosis were 16·8 and 10·9 years, respectively. Cataract was observed in 21/517 patients (4·1%). Cumulative incidence was 4·5 ± 1·2% at 15 years and reached 26 ± 8·1% at 25 years. CNS irradiation was the only risk factor: prevalence was 11·1% in patients who had received irradiation and 2·8% in those who did not. We did not detect any steroid dose effect: cumulative dose was 5133 and 5190 mg/m² in patients with and without cataract, respectively. Cataract occurrence did not significantly impact quality of life. We conclude that, in the range of steroid dose reported here, the cataract risk proves very low 15 years after treatment without CNS irradiation but an even more prolonged follow‐up is required because of potential very late occurrence.     

Worksite Health and Wellness Programs: Canadian Achievements & Prospects

Canada has experienced a substantial reduction in mortality related to cardiovascular disease (CVD). There is a general consensus that more effective and widespread health promotion interventions may lead to further reductions in CVD risk factors and actual disease states. In this paper, we briefly outline the prevalence of selected risk factors for CVD in Canada, describe characteristics of the Canadian labor market and workforce, and depict what is known about health and wellness program delivery systems in Canadian workplaces. Our review indicates that there have been numerous and diverse relevant legislative and policy initiatives to create a context conducive to improve the healthfulness of Canadian workplaces. However, there is still a dearth of evidence on the effectiveness of the delivery system and the actual impact of workplace health and wellness programs in reducing CVD risk in Canada. Thus, while a promising model, more research is needed in this area.