The Effect of Antiretroviral Combination Treatment on Epstein-Barr Virus (EBV) Genome Load in HIV-Infected Patients

We evaluated the effect of combination anti-retroviral treatment (cART) on the host control of EBV infection in moderately immunosuppressed HIV-1 patients. Twenty HIV-1 infected individuals were followed for five years with repeated measurements of EBV DNA load in peripheral blood lymphocytes in relation to HIV-RNA titers and CD4+ cell counts. Individuals with optimal response, i.e. durable non-detectable HIV-RNA, showed a decline of EBV load to the level of healthy controls. Individuals with non-optimal HIV-1 control did not restore their EBV control. Long-lasting suppression of HIV-replication after early initiation of cART is a prerequisite for re-establishing the immune control of EBV

Impact of sepsis and HIV-1 infection on neutrophil radical production, lipids and lipoproteins

In clinical sepsis a decrease in total serum cholesterol caused by reduced HDL and LDL cholesterol occured early in the course of the infection with a normalisation after 2 months. This "sepsis HDL" was shown to contain the acute phase reactant SAA and it affected several functions of the neutrophil. However, the clearance of the exogenously delivered lipid emulsion, Intralipid, was found not to be impaired in infected patients with a hyperdynamic circulation. In HIV-1 infected patients, we observed an increased radical production by the neutrophils. High levels of malondialdehyde (MDA) in plasma, together with increased oxygen radical production by neutrophils and low plasma cysteine and glutathione levels, suggested the occurence of oxidative stress in such patients. Although treatment with the scavenger N acetylcysteine (NAC) reduced radical production in HIV-1-negative subjects, it did not change the radical production by neutrophils in HIV-1 infected patients. However, some other beneficial effects were found in the treatment study of HIV-1 patients. Thus plasma cysteine was normalised, the decrease in the number of CD4+ cells was counteracted and there was a decrease in TNFa. In contrast, NAC did not significantly reduce the high frequency of trimethopri-sulphamethoxazole (TMP-SMX)-induced drug reactions i n HIV-1-infected patients. However, low levels of plasma glutathione and plasma cysteine support the theory of antioxidant depletion when TMP SMX therapy creates a free sulpha metabolite radical and increases the oxidant burden

Increased risk for renal cell carcinoma in end stage renal disease : a population-based case-control study

Purpose: End-stage renal disease (ESRD) is a known risk factor for the development of renal cell carcinoma (RCC). This case-control study was performed to assess the risk in a nationwide cohort and evaluate tumor characteristics and survival in the ESRD-RCC population. Methods: In this study, 9,299 patients with RCC identified in the National Swedish Kidney Cancer Register from 2005 until 2014 and 93,895 matched controls were linked to the Swedish Renal Registry and the National Patient Register. ESRD was defined as chronic kidney disease stage 5, kidney transplantation or kidney dialysis 0–40 years before the diagnosis of RCC. Results: A total of 117 patients with ESRD and subsequent RCC were identified and compared with 9,087 patients with RCC. There was a 4.5-times increased risk for RCC among ESRD patients (95% CI = 3.6–5.6; p < 0.001) compared to matched controls. Longer time with ESRD increased the risk of RCC (ESRD > 9 years, OR = 10.2, 95% CI = 7.0–14.8). The ESRD-RCC patients were younger (p = 0.002), had smaller tumors (p < 0.001) and had lower tumor stage (p = 0.045). The incidence of papillary and chromophobe RCC was higher and clear cell RCC lower among the ESRD patients (p < 0.001). The 5-year overall survival was 50% in ESRD-RCC patients and 63% in RCC-only patients (p < 0.05). Conclusion: More than 9 years with ESRD increased the risk of developing RCC 10-times compared to individuals without ESRD and the tumors showed a different histopathological pattern. Despite a less advanced tumor stage at diagnosis, the overall survival in ESRD-RCC patients was lower compared to patients with RCC-only

Predictors for complication in renal cancer surgery : a national register study

OBJECTIVE: Nationwide register data provide unique opportunities for real-world assessment of complications from different surgical methods. This study aimed to assess incidence of, and predictors for, post-operative complications and to evaluate 90-day mortality  following different surgical procedures and thermal ablation for renal cell carcinoma (RCC). MATERIAL AND METHODS: All patients undergoing surgical treatment and thermal ablation for RCC in Sweden during 2015-2019 were identified from the National Swedish Kidney Cancer Register. Frequencies and types of post-operative complications were analysed. Logistic regression models were used to identify predictors for 90-day major (Clavien-Dindo grades III-V) complications, including death. RESULTS: The overall complication rate was 24% (1295/5505), of which 495 (8.7%) were major complications. Most complications occurred following open surgery, of which bleeding and infection were the most common. Twice as many complications were observed in patients undergoing open surgery compared to minimally invasive surgery (20% vs. 10%, P < 0.001). Statistically significant predictors for major complications irrespective of surgical category and technique were American society of anesthiologists (ASA) score, tumour diameter and serum creatinine. Separating radical and partial nephrectomy, surgical technique remained a significant risk factor for major complications. Most complications occurred within the first 20 days. The overall 90-day readmission rate was 6.2%, and 30- and 90-day mortality rates were 0.47% and 1.5%, respectively. CONCLUSIONS: In conclusion, bleeding and infection were the most common major complications after RCC surgery. Twice as many patients undergoing open surgery suffer a major post-operative complication as compared to patients subjected to minimally invasive surgery. General predictors for major complications were ASA score, tumour size, kidney function and surgical technique

End-stage renal disease after renal cancer surgery : risk factors and overall survival

OBJECTIVE: Several risk factors for end-stage renal disease (ESRD), in patients undergoing surgical treatment for renal cell carcinoma (RCC), have been suggested by others. This study aimed to investigate such risk factors and disclose the effect of developing ESRD, postoperatively, on overall survival. The risk of developing ESRD after RCC diagnosis was also evaluated. MATERIAL AND METHODS: The data of 16,220 patients with RCC and 162,199 controls were extracted from the Renal Cell Cancer Database Sweden, with linkages across multiple national registers between 2005 and 2020. Cox proportional hazards regression, Kaplan-Meier curves and cumulative incidence were used for statistical analysis. RESULTS: The 5-year cumulative incidence of ESRD following RCC diagnosis was 2.4% (95% confidence interval [CI] 2.1-2.6) and 0.4% (95% CI 0.3-0.4) for the patients with RCC and controls, respectively. Age, chronic kidney disease, higher T-stage and radical nephrectomy (RN) were significant risk factors for ESRD within 1-year of surgery. A total of 104 and 12,152 patients with and without ESRD, respectively, survived 1-year postoperatively. The 5-year overall survival rates of patients with ESRD and those with RCC only were 50% (95% CI 0.40-0.60) and 80% (95% CI 0.80-0.81), respectively. CONCLUSIONS: Patients who developed ESRD following renal cancer surgery had significantly poorer survival outcomes. Advanced age, comorbidities, higher-stage tumours and RN were identified as risk factors for developing ESRD. Surgical decisions are crucial. Efforts to spare renal function, including nephron-sparing surgery and active surveillance in appropriate cases, are highly relevant to reduce the development of severe kidney dysfunction