BACKGROUNDHypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain.METHODSWe conducted a prospective ...cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed.RESULTSWe included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 43-170 vs. 38 24-64 mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 24-54 vs. 27 19-40 pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80).CONCLUSIONSLong-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.
Resistant minority variants present before ART can be a source of virological failure. This has been shown for NRTIs, NNRTIs and CCR5 inhibitors. However, very few data are available for the ...detection of such minority resistant variants that could be selected at virological failure and not detected using classical Sanger sequencing.
We studied 26 patients treated with tenofovir, emtricitabine and efavirenz with their first virological failure (defined as two consecutive viral loads >50 copies/mL). We performed standard Sanger sequencing and ultradeep sequencing (UDS; Roche 454(®) Life Sciences) in plasma at failure. For UDS, mutations >1% were considered. We compared the presence of reverse transcriptase mutations between the two techniques, using the latest ANRS algorithm.
UDS detected more resistance mutations in 38.5% of cases (10/26 patients) and the genotypic sensitivity score (GSS) was reduced for 6 of them (23.1%). The GSS was impacted more often for NRTIs than for NNRTIs, for which most mutations were already detected by Sanger sequencing. Resistant minority variants were detected even in patients with low viral load at failure.
These results strongly argue for the use of next-generation sequencing in patients failing on an NRTI+NNRTI regimen, as UDS has the potential to modify the choice of the subsequent regimen.
Quantitative measurement of hepatitis B surface antigen (HBsAg) has been proposed as a surrogate marker of treatment efficacy when HBV DNA load becomes undetectable. Our main objective was to study ...the kinetics of HBsAg level in HIV-HBV-coinfected patients with undetectable HBV DNA load under treatment containing tenofovir disoproxil fumarate (TDF).
A retrospective analysis was performed on frozen serum samples of 33 HIV-HBV-coinfected patients who were treated with TDF and had undetectable HBV DNA for ≥1 year. Baseline and serial follow-up samples were assayed for HBsAg levels.
The characteristics of the patients at TDF initiation were median age 43.6 years, median HBV DNA load 2 log(10) IU/ml and median HBsAg concentration 3.4 log(10) IU/ml. Ten patients were positive for hepatitis B e antigen. Baseline median HBsAg concentration, defined 1 year after HBV DNA became undetectable, was 3.1 log(10) IU/ml. Overall, from years 1 to 6 and a median duration of TDF treatment of 2.6 years, the median HBsAg concentration decreased slowly. Notably, only 13 (39%) patients presented a constant decrease of HBsAg concentration, whereas the remaining had fluctuating or increasing HBsAg concentrations. The slope was not influenced by HBeAg status, HIV infection duration and CD4(+) T-cell count at baseline or at nadir.
Despite control of HBV DNA replication under efficient TDF treatment, HBsAg levels persistently decreased in only 39% of HIV-HBV-coinfected patients. Larger follow-up studies are needed to determine whether HBsAg concentration monitoring under analogue treatment can be used as a reliable marker for HBV clearance.
A quantitative study of the T cell receptor repertoire was performed ex vivo on CD4 and CD8 T cell subsets of human T cell leukemia virus type I (HTLV-I)–infected asymptomatic carriers and patients ...with HTLV-I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). Indexes of oligoclonality that compiled all repertoire modifications were calculated for peripheral blood mononuclear cells and for CD4 and CD8 T cell subsets. Both patients with HAM/TSP and asymptomatic carriers had greater T lymphocyte expansions than did uninfected donors, which was independent of age and at least twice higher in the CD8 than in the CD4 cell compartment. Some expanded CD8 T cells corresponded to cytotoxic T lymphocytes directed against various epitopes of the immunodominant Tax protein. Patients with HAM/TSP had significantly higher CD8 cell expansions than did asymptomatic carriers. These results highlight the prognostic value of measuring CD8 T cell expansions during follow-up of HTLV-I infection
Due to strict environmental regulations, the construction sector has observed extensive use of supplementary cementitious materials (SCMs) in recent years. As a result, new alternative SCMs have ...emerged and research in this particular area has considerably developed. Although a large number of research devoted to cement-based materials blended with SCMs has been conducted, there continue to be debates about their characteristics, effects on the hydration, and the durability of cement pastes, mortars and concrete. Therefore, this review summarized the most widespread methods for SCMs characterization, major characteristics, and the role of each of the five widely used SCMs including coal fly ash, silica fume, ground granulated blast furnace slag, limestone powder, and metakaolin in the hydration and durability of cement-based materials. Ultimately, their environmental and economic advantages were also reviewed. A huge variation in the SCMs physical and chemical characteristics has been highlighted as the major concern when it comes to the establishment of standards and characterization methods. The literature has also shown that the hydration, compressive strength and durability of cement-based materials blended with SCMs typically depend on the replacement ratios, fineness and synergic effect of the SCMs’ reactivity mechanisms. Owing to their high specific surface area and pozzolanic activity, partial cement replacement with a suitable amount of silica fume and metakaolin considerably accelerates the hydration and increases the heat of hydration of cement-based materials. Besides, limestone powder and ground granulated blast slag reportedly present better environmental and economic benefits compared to metakaolin and silica fume.
A flexible synthetic access to six-membered l- and d-iminosugar C-glycosides is reported starting from the easily available 6-azido-6-deoxy-2,3,4-tri-O-benzyl-d-glucopyranose precursor. This ...methodology involves a highly diastereoselective tandem ring enlargement/alkylation and a stereocontrolled ring contraction. It allows an efficient synthesis of iminosugar C-glycosides displaying structural diversity at both C-1 and C-6.
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