Impact of COVID-19 Pandemic on Organ Donation in Hong Kong: A Single-Center Observational Study

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic was expected to have a negative impact on organ donation. With the differences in health care systems and lockdown policies in various regions, the pandemic's effect on organ donation and transplant service may vary. Most of the deceased donor organ referrals in our hospital came from non–intensive care units (ICUs). The objective of this study is to report our experience and quantify the effects of the COVID-19 pandemic on deceased donor organ donation in our center.MethodsThis was a retrospective observational study comparing the deceased donor organ donation activity during the period January 23 to November 30, 2020 with the same period in 2018 in Queen Elizabeth Hospital, Hong Kong.ResultsThere was a 26.9% reduction in deceased donor organ donor referral in 2020 compared with 2018. No significant difference in the proportion of referrals from ICU or non-ICU areas between the 2 time periods was observed. The brain death confirmation rate was significantly higher in 2020 (40.8% vs 20.2%, P = .003). Nine patients had family consent for organ donation in 2020 (vs 7 patients in the same period in 2018). There were no significant differences in consent rate and number of recovered organs between the 2 periods.ConclusionsWith effective measures to limit the spread of COVID-19 in a community, it is possible to support the needs of both patients with COVID-19 and deceased donor organ donation services.     

Osteopontin inhibits macrophage nitric oxide synthesis to enhance tumor proliferation

BACKGROUND: Interactions between tumor cells and their host environment can play a major role in regulating survival programs required for tumor progression. Osteopontin (OPN) is a glycophosphoprotein overexpressed by tumors, and is a key molecule for tumor progression and metastasis. OPN also inhibits expression of autocrine and paracrine inducible nitric oxide synthase (iNOS). Given the cytotoxic effects of macrophage NO expression, we hypothesized that tumor-derived OPN inhibits expression of local macrophage iNOS to potentiate tumor survival. METHODS: We used a coculture system of murine CT26 colorectal cancer cells with RAW264.7 murine macrophage cells. CT26 expresses OPN at high levels. RNA interference was utilized to produce long-term specific silencing of OPN in CT26. RESULTS: Inhibition of constitutive OPN synthesis in CT26 upregulates local NO production with inhibition of CT26 proliferation and promotion of CT26 apoptosis. Macrophage iNOS expression is accompanied by increased binding activity of nuclear factor-kappaB DNA. When the CT26 culture media were examined for a panel of proinflammatory cytokines, elevated concentrations of granulocyte colony-stimulating factor (G-CSF) were found. Subsequently, in CT26 cells treated with antisense-G-CSF, NO levels in CT26-RAW cocultures were significantly decreased. CONCLUSION: In our system of CT26-RAW264.7 coculture, we conclude that inhibition of OPN synthesis in CT26 results in G-CSF-mediated induction of macrophage iNOS expression with resultant inhibition of CT26 proliferation via increased apoptosis. Our results suggest that tumor-derived OPN may enhance tumor survival by down regulating expression of NO in the local microenvironment. This is one mechanism by which OPN may potentiate cancer survival and progression.     

Rapamycin, but not cyclosporine or FK506, alters natural killer cell function

Infiltration of natural killer (NK) cells into solid organ allografts is observed in clinical and experimental transplantation. Studies suggest a role for NK cells in acute and chronic rejection of solid organ allografts; however, the effects of immunosuppressive agents on NK cells are not clearly established. Rat NK cell lines were analyzed for proliferation and cytotoxicity in the presence of cyclosporine, FK506, or rapamycin. Lewis recipients of DA liver allografts received immunosuppressive agents after transplantation. NK cells demonstrated robust function both in the absence and presence of cyclosporine and FK506. In contrast, rapamycin significantly inhibited proliferation and cytotoxicity of NK cells. NK cell numbers remained stable in graft recipients treated with cyclosporine and FK506, whereas there was a significant decrease in NK cells in rapamycin-treated recipients. These data indicate that immunosuppressive drugs have differential effects on NK cell function that may impact the immune response of transplant recipients.     

Charlson Co‐morbidity Index and albumin significantly associated with fracture risk in peritoneal dialysis patients

Published literature on fracture in dialysis patients seldom addressed the effect of co‐morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co‐morbidity Index (CCI) and biochemical parameters were also collected. Non‐fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient‐years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty‐four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self‐ambulatory patients (47.1%) became non‐ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non‐ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.     

Energy homeostasis and cachexia in chronic kidney disease

Loss of protein stores, presenting as clinical wasting, is reported to have a prevalence of 30–60% and is an important risk factor for mortality in chronic kidney disease (CKD) patients. There is debate as to whether the clinical wasting in CKD patients represents malnutrition or cachexia. Malnutrition results from inadequate intake of nutrients, despite a good appetite, and manifests as weight loss associated with adaptive metabolic responses such as decreased basic metabolic rate and preservation of lean body mass at the expense of fat mass. Furthermore, the abnormalities in malnutrition can usually be overcome simply by supplying more food or altering the composition of the diet. In contrast, cachexia is characterized by maladaptive responses such as anorexia, elevated basic metabolic rate, wasting of lean body tissue, and underutilization of fat tissue for energy. Diet supplementation and intradialytic parenteral nutrition have not been successful in reversing cachexia in CKD. The etiology of cachexia in CKD is complex and multifactorial. Two major factors causing muscle wasting in uremia are acidosis and decreased insulin responses. Inflammation secondary to cytokines may also play a significant role. The hypoalbuminemia of CKD patients is principally associated with inflammation and not changes in food intake. There is also recent evidence that hypothalamic neuropeptides may be important in the downstream signaling of cytokines in the pathogenesis of cachexia in CKD. Elevated circulating levels of cytokines, such as leptin, may be an important cause of uremia-associated cachexia via signaling through the central melanocortin system. Further research into the molecular pathways leading to cachexia may lead to novel therapeutic therapy for this devastating and potentially fatal complication of CKD.Supported by grants from the National Institute of Health R01 DK 50780 and K24 DK59574 to RHM.     

Prevalence of metabolic syndrome in patients with psoriasis: a cross-sectional study in Singapore

INTRODUCTIONPsoriasis is a chronic inflammatory condition that affects the skin and joints, and is associated with cardiovascular risk factors, including metabolic syndrome (MetS). We aimed to assess the prevalence of MetS in patients with psoriasis and determine whether there was a correlation between psoriasis severity and MetS in a Singapore population.METHODSThis was a cross-sectional study of patients with psoriasis, aged 18–69 years, who attended a tertiary dermatology referral centre in Singapore from October 2007 to February 2009. Fasting glucose, lipids, blood pressure, Psoriasis Area and Severity Index, and body mass index were measured. MetS was diagnosed in the presence of three or more criteria of the modified National Cholesterol Education Program Adult Treatment Panel III.RESULTSAmong 338 patients with psoriasis, there were 238 (70.4%) men and 100 (29.6%) women, who were Chinese (n = 228; 67.5%), Malay (n = 52; 15.4%) and Indian (n = 58; 17.2%). The prevalence of MetS was 45.1%. MetS was 44% more prevalent in patients older than 50 years (p = 0.02). Malay patients with psoriasis were significantly more likely to have hypertriglyceridaemia, elevated fasting plasma glucose and abdominal obesity. There was no significant correlation between psoriasis severity and risk of MetS.CONCLUSIONThe prevalence of MetS in patients with psoriasis in Singapore was 45.1%, or nearly threefold higher than the Singapore general population. Patients with psoriasis should be screened yearly for MetS and any modifiable cardiovascular risk factors should be actively controlled.