Many studies have demonstrated that the endocannabinoid system (ECS) is altered in different tumor types, including colon cancer. However, little is known about the role of the ECS in tumor progression. Here we report the correlation between CB2 expression and pathological data in a series of 175 colorectal cancer patients, as well as the response of the HT29 colon cancer-derived cell line upon CB2 activation. CB2 mRNA was detected in 28.6% of samples tested. It was more frequent in N+ patients and predicts disease free survival and overall survival in colon cancer. In positive samples, CB2 was expressed with great intensity in tumor epithelial cells and correlated with tumor growth. Treatment of HT29 with CB2 agonist revealed membrane loss of E-cadherin and SNAIL1 overexpression. A direct correlation between CB2 and SNAIL1 expression was also found in human tumors. CB2 receptor expression is a poor prognostic marker for colon cancer and the activation of this receptor, with non-apoptotic doses of agonists, could be collaborating with disease progression. These results raise the question whether the activation of CB2 should be considered as anti-tumoral therapy.
We present a retrospective study of 30 children of mean age 3.02 +/- 1.81 years with steroid-resistant nephrotic syndrome (SRNS) treated with intravenous injection of methylprednisolone plus orally administered prednisone; 24 children also received cyclophosphamide (CP). Sixteen were resistant to steroids from the beginning, and 14 after a mean of 11.26 +/- 16.61 months. The initial histological diagnosis was: 18 minimal change disease (MCD), 11 focal segmental glomerulosclerosis (FSGS) and one diffuse mesangial proliferative glomerulonephritis (DMPG). Total remission was achieved in 22 patients (73.3%), partial response in three (10%) and no response in five (16.6%), two of whom were brothers carrying an NPHS2 gene double mutation. There was no difference in response between the MCD and FSGS patients; the only patient with DMPG did not respond. Only initial resistance was a sign of bad prognosis. At follow-up (6.4 +/- 3.6 years from last pulse), 21/22 were still in remission, 14/21 were without treatment. Six patients required cyclosporine or mycophenolate mofetil because of steroid dependence. Two non-responders developed end-stage renal failure (ESRF); the remaining patients maintained normal glomerular filtration. The treatment was well tolerated. In conclusion, most of the patients treated with sequential therapy consisting of methylprednisolone (MP) (100%) and CP (80%) showed remission and preserved renal function, but 20% developed steroid dependence.
Background
Kidney replacement therapy (KRT) confers the highest risk of death from COVID-19. However, most data refer to the early pandemic waves. Whole year analysis in comparison with prior secular trends are scarce.
Methods
We present the 2020 REMER Madrid KRT registry, corresponding to the Spanish Region hardest hit by COVID-19.
Results
In 2020, KRT incidence decreased 12% versus 2019 while KRT prevalence decreased (−1.75%) for the first time since records began and the number of kidney transplants (KT) decreased by 16%. Mortality on KRT was 10.2% (34% higher than the mean for 2008–2019). The 2019 to 2020 increase in mortality was larger for KT (+68%) than for HD (+24%) or PD (+38%). The most common cause of death was infection (n = 419, 48% of deaths), followed by cardiovascular (200, 23%). Deaths from infection increased by 167% year over year and accounted for 95% of excess deaths in 2020 over 2019. COVID-19 was the most common cause of death (68% of infection deaths, 33% of total deaths). The bulk of COVID-19 deaths (209/285, 73%) occurred during the first COVID-19 wave, which roughly accounted for the increased mortality in 2020. Being a KT recipient was an independent risk factor for COVID-19 death.
Conclusions
COVID-19 negatively impacted the incidence and prevalence of KRT, but the increase in KRT deaths was localized to the first wave of the pandemic. The increased annual mortality argues against COVID-19 accelerating death of patients with short life expectancy and the temporal pattern of COVID-19 mortality suggests that appropriate healthcare may improve outcomes.
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