Κυριακή 31 Ιουλίου 2022

Incidence, risk factors, outcomes, and clinical management of BK viremia in the modern era of kidney transplantation

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ABSTRACT

Background

: BK viremia is endemic among kidney transplant recipients (KTR). Incidence, risk factors, outcomes, and clinical management of detectable versus high BK viremia have not been considered previously in KTR in the modern era.

Methods

: This observational study examined KTR transplanted between January 1, 2009 and December 31, 2016. Any BK viral load in the serum constituted detectable BK viremia and ≥103 copies/mL constituted high viremia.

Results

: Among 1,193 KTR, the cumulative probability of developing detectable and high BK viremia within two years post-transplant were 27.8% and 19.6%, respectively. Significant risk factors for detectable BK viremia included recipient age (HR 1.02 [95% CI: 1.01, 1.03]) and donor age (HR 1.01 [95% CI: 1.00, 1.02]). Recipient age also predicted high BK viremia (HR 1.02 [95% CI: 1.01, 1.03]), whereas White race (HR 0.70 [95% CI: 0.52, 0.95]), non-depleting induction therapy (HR 0.61 [95% CI: 0.42, 0.89]), and delayed graft function (HR 0.61 [95% CI: 0.42, 0.88]) were protective. Mean estimated glomerular filtration rates were 4.28 mL/min/1.72 m2 (95% CI: 2.71, 5.84) lower with detectable BK viremia. Although low viral load was usually not acted upon at first presentation, anti-proliferative dose reductions were the most common initial management.

Conclusion

: BK viremia remains a common early complication in a modern cohort of KTR. These findings highlight the benefit of early BKV monitoring in addition to intensive clinical management. Clinical responses beyond first positive BK viremia tests, and their implications for graft outcomes, merit further investigation.

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A modified dentin infection model with Fluorescent Lipopolysaccharide and LPS sampling technique to compare XP‐Endo finisher and passive ultrasonic irrigation

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Abstract

Aim

The LPS-dentine-infection models and sampling techniques frequently used to evaluate LPS disinfection have limitations. In this study, a lipopolysaccharides-dentine-infection (LPS-dentine-infection) model was devised using fluorescent conjugate LPS. Secondly, a sampling technique using cryogenic grinding for intraradicular LPS analysis was evaluated. Thirdly, the effectiveness of the XP-endo Finisher (XP-EF) was compared with passive ultrasonic irrigation (PUI) in removing LPS from root canal system.

Methodology

Sixty-nine mandibular premolars was submitted to dentine pretreatment and inoculated with fluorescent LPS conjugate (Alexa Fluor® 594). Twenty-three teeth were analysed under confocal laser scanning microscopy (CLSM) to validate this modified LPS-dentine-infection model. Forty-six teeth were randomly divided into two experimental groups: XP-EF (n = 23) and PUI (n = 23). All teeth were instrumented with XP-endo shaper (XPS; FKG Dentaire, La Chaux-de-Fonds, Switzerland) and 2.5% NaOCl. The root canals were sampled with paper points before (s1) and after (s2) instrumentation and after supplemental treatment (s3) with XP-EF and PUI. After s3, all roots were cryogenically ground for intraradicular LPS analysis (s4). Limulus amebocyte lysate (LAL) assay was used for LPS quantification. The Friedman test was used for differences in LPS among four timepoints (s1, s2, s3, and s4). Dunn's test was used for pairwise testing of timepoints. The significance level wa s set at 5% (P < .05).

Results

Fluorescent LPS conjugate was detected in 100% of the samples under CLSM with a penetration depth of approximately 400 μm into dentine. Chemo-mechanical preparation using XPS files significantly reduced LPS levels (p < .05). Both the XPS and PUI improved the LPS disinfection (p < .05), with no difference between them (p > .05). LPS was recovered from all samples after cryogenic grinding. The residual amount of LPS detected using the cryogenically sampling technique at s4 was approximately 3 times greater than with the paper point sampling technique at s3.

Conclusion

This study established a modified LPS-dentine-infection model using fluorescent conjugate LPS, and validated a LPS sampling technique for using cryopulverization intraradicular LPS analysis. Moreover, both the XP-EF and PUI further improved LPS disinfection from the root canals, and the innovative XP-EF was as effective as PUI.
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Case volume regionalization and volume‐based outcome differences in cutaneous head and neck melanoma

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Abstract

Background

Hospital volume has emerged as a prognostic factor in oncology but is not currently known whether volume is associated with improved outcomes for cutaneous head and neck (HN) melanoma.

Methods

A total of 556 079 cutaneous melanoma cases reported by the 2004–2016 National Cancer Database were separated into two cohorts (HN and non-HN) and facilities within each cohort were classified by case volume. Analysis employed chi-square, analysis of variance, Kaplan–Meier, and Cox proportional hazards models.

Results

Only 41 facilities (3.1% of 1326) treating HN melanoma and 50 facilities (3.7% of 1344) treating non-HN melanoma were classified as high-volume facilities (HVFs). The estimated 5-year overall survival (OS) was 62.7% (standard error [SE]: 0.4%) for patients with HN at low-volume facilities (LVFs), 69.3% (SE: 0.4%) at IVFs, and 71.8% (SE 0.4%) at HVFs (p < 0.001). Differences in OS remained significant between HVFs versus LVFs after adjusting for confounders.

Conclusion

Volume is independently associated with OS and improved surgical outcomes for HN melanoma.
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Menopausal hormone therapy and subclinical cardiovascular disease in women with and without HIV

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Abstract
Background
Estrogen-based hormone therapy (HT) may have beneficial cardiovascular effects when initiated in early menopause. This has not been examined in women with HIV who have heightened immune activation and cardiovascular risks.
Methods
Among 609 post-menopausal women (1,234 person-visits) in the Women's Interagency HIV Study, we examined the relationship of ever HT use (oral, patch, or vaginal) with subclinical atherosclerosis – carotid artery intima-media thickness (CIMT), distensibility, and plaque assessed via repeated B-mode ultrasound imaging (2004-2013). We also examined associations of HT with cross-sectional biomarkers of immune activation and D-dimer. Statistical models were adjusted for sociodemographic, behavioral, and cardiometabolic factors.
Results
Women (mean age = 51, 80% HIV+) who ever used HT at baseline were older, and more likely to be non-Hispanic White and report higher income, than never users. Women who ever used HT had 43% lower prevalence of plaque (prevalence ratio = 0.57; 95% CI = [0.40, 0.80]; p < 0.01), 2.51 µm less progression of CIMT per year (95% CI = [-4.60, -0.41]; p = 0.02), and marginally lower incidence of plaque over ∼7 years (risk ratio = 0.38; 95% CI = [0.14, 1.03]; p = 0.06), compared with never users, adjusting for covariates; ever HT use was not associated with distensibility. These findings were similar for women with and without HIV. Ever HT use was associated with lower serum D-dimer, but not with biomarkers of immune activation after covariate adjustment.
Conclusions
HT may confer a subclinical cardiovascular benefit in women with HIV. These results begin to fill a knowledge gap in menopausal care for women with HIV, in whom uptake of HT is very low.
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Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe COVID-19: The PANCOVID Randomized Clinical Trial

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Abstract
Background
This study was designed to evaluate if patients with high risk for severe COVID-19 would benefit from treatment with TDF/FTC followed by baricitinib in case of hypoxemia and systemic inflammation.
Methods
PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥ 2 comorbidities or older than 60 years conducted between 10 October 2020 and 23 September 2021. In the first randomization patients received TDF/FTC or not TDF/FTC. In the second randomization patients with room-air O2 saturation <95% and at least one increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in th e number of cases and a mortality rate substantially lower than expected EudraCT registration number: 2020-001156-18.
Results
Of the 355 included participants 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% CI 0.52-5.91; p= 0.379); it was 0.42 (95% CI 0.11-1.59; p= 0.201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI 0.66-1.40; p = 0.774); it was 0.90 (95%CI 0.61-1.33; p = 0.687) for those treated with baricitinib.
Conclusions
Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials.
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Cytocompatibility and bioactive potential of AH Plus Bioceramic Sealer: an in vitro study

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Abstract

Abstract

Aim

To assess the cytocompatibility and bioactive potential of the new calcium silicate cement-based sealer AH Plus Bioceramic Sealer (AHPbcs) on human periodontal ligament stem cells (hPDLSCs) compared to the epoxy resin-based sealer AH Plus (AHP) and the calcium silicate cement-based sealer Endosequence BC Sealer (ESbcs).

Methodology

Standardized sample discs and 1:1, 1:2, and 1:4 eluates of the tested materials were prepared. The following assays were performed: surface element distribution via SEM-EDX, cell attachment and morphology via SEM, cell viability via a MTT assay, cell migration/proliferation via a wound-healing assay, osteo/cemento/odontogenic marker expression via RT-qPCR, and cell mineralized nodule formation via Alizarin Red S staining. HPDLSCs were isolated from extracted third molars. Comparisons were made with hPDLSCs cultured in unconditioned (negative control) or osteogenic (positive control) culture media. Statistical significance was established at p<0.05.

Results

A higher peak of Ca2+ was detected from ESbcs compared with AHPbcs and AHP in SEM-EDX. Both AHPbcs and ESbcs showed significantly positive results in the cytocompatibility assays (cell viability, migration/proliferation, attachment, and morphology) compared with a negative control group, while AHP showed significant negative results. Both AHPbcs and ESbcs exhibited an upregulation of at least one osteo/odonto/cementogenic marker compared to the negative and positive control groups. Both ESbcs and AHPbcs showed a significantly higher calcified nodule formation than the negative and positive control groups, indicative of their biomineralization potential, and were also significantly higher than AHP group.

Conclusion

AH Plus Bioceramic Sealer exhibited a significantly higher cytocompatibility and bioactive potential than AH Plus, and a similar cytocompatibility to that of Endosequence BC Sealer. Endosequence BC Sealer exhibited a significantly higher mineralization potential than the other tested sealers. The results from this in vitro study act as supporting evidence for the use of AH Plus bioceramic sealer in root canal treatment.
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Πέμπτη 28 Ιουλίου 2022

Facial nerve palsy: Narrative review on the importance of the eye and its assessment

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Abstract

New solutions are emerging that address specific facial regions in facial nerve palsy (FNP). However the most dreaded consequence of FNP is paralytic lagophthalmos threatening the eye. A way to prioritize these regions is thus required. A review of the literature is conduced to capture the current concepts in evaluating FNP. Overall, patients are assessed from three perspectives: from the clinician's perspective using validated clinician-based grading instruments, from patient's perspective based on FNP-specific patient-reported outcome measures, and from the perspective of the layperson. The existing tools however provide limited information regarding the relative importance of different regions of the face. The eye appears to be an area of great concern for the patient where most surgical therapies are directed at. Addressing ocular problems in FNP carry a high priority but this is not clearly reflected by the standard systems.
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STATIN USE MAY BE ASSOCIATED WITH A LOWER RISK OF INVASIVE ASPERGILLOSIS IN LUNG TRANSPLANT RECIPIENTS

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Abstract
Background
Statins are competitive inhibitors of HMG-CoA reductase that catalyses HMG-CoA conversion to mevalonate, a process involved in synthesizing cholesterol in humans and ergosterol in fungi. The effect of statin use on the risk of development of invasive aspergillosis (IA) in lung transplant recipients (LTRs) is not well documented.
Methods
This retrospective study included LTRs from 2010 to 2017 who were followed for one-year post-transplant. Proven or probable IA was diagnosed as per ISHLT criteria. We performed a multivariable Cox proportional hazards model of the association between IA and statin use (minimum of two weeks duration prior to IA), adjusting for other known IA risk factors.
Results
We identified 785 LTRs, 44% female, mean age 53 years old, the most common underlying disease being pulmonary fibrosis (23.8%). 451 LTRs (57%) received statins post-transplant, atorvastatin was the most commonly used statin (68%). The mean duration of statins post-transplant was 347 days (IQR: 305 to 346). 55 (7%) LTRs developed IA in the first-year post-transplant. Out of these 55 LTRs, 9 (16.3%) had received statin before developing IA. In multivariable analysis, statin use was independently associated with a lower risk of IA (p = 0.002, SHR 0.30, CI 95% 0.14-0.64). Statin use was also associated with a lower incidence of post-transplant Aspergillus colonization, 114 (34%) in the no statin group vs. 123 (27%) in the statin group (p = 0.038).
Conclusions
The use of statin for a minimum of two weeks during the first-year post-transplant was associated with a 70% risk reduction of IA in LTRs.
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Τετάρτη 27 Ιουλίου 2022

Neuropsychological, behavioral, and quality‐of‐life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series

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Abstract

Background/objectives

Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT.

Design/methods

Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol.

Results

Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ = 92.1, SD 9.0; n = 8) and 2 years post-HCT (mean FSIQ = 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = −.54) and fine motor speed and dexterity (Cohen's d = −.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44).

Conclusion

Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.
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Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid‐associated thrombocytopenia

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Pharmacokinetic and pharmacodynamic simulation for the quantitative risk assessment of linezolid-associated thrombocytopenia

Utility of safety target achievement rate based on PK/PD simulation for predicting linezolid-induced thrombocytopenia-stratified on the duration of linezolid therapy.


Abstract

What Is Known and Objective

Linezolid (LZD) may cause thrombocytopenia, which can result in discontinuation of treatment. In this study, the blood LZD trough concentration was estimated based on population pharmacokinetic (PK) parameters derived from two previously published models in the Japanese population to determine the rate of achieving the target trough value when the risk of thrombocytopenia is low and to clarify its relationship with the onset of thrombocytopenia.

Methods

This study included adult patients hospitalized at Shimane University Hospital, who received LZD treatment for at least 4 days from January 2010 to December 2017. Patients whose platelet count fell below 70% before LZD administration were categorized as the thrombocytopenic group. Patient PK parameters were calculated based on the population PK models described by Matsumoto et al. and Sasaki et al., and these parameters were designated A and B, respectively. Based on these parameters, the rate of achieving an LZD trough concentration of less than 8 μg/ml, which is the safety target achievement rate, was calculated using a random simulation for each patient. We further analysed the association between the incidence of thrombocytopenia and patient factors, including safety target achievement rate, through univariate, multivariate, and receiver operating characteristic (ROC) analyses.

Results and Discussion

Patients (n = 77) aged 72 ± 11 years and weighing 56.7 ± 10.9 kg, with a creatinine clearance (CLcr) of 60.5 ± 47.2 ml/min and a cirrhosis prevalence of 9.1%, were analysed. All patients received LZD at a dose of 600 mg twice daily for a total of 10.9 ± 8.9 days. Univariate analyses revealed significant differences (p < 0.05) in the duration of LZD therapy, serum creatinine, creatinine clearance, LZD clearance, and the safety target achievement rate for parameters A and B between the thrombocytopenic and non-thrombocytopenic groups. A multivariate analysis of these factors stratified with the cutoff values obtained by ROC analysis revealed that the duration of LZD therapy and the safety target achievement rates for parameters A and B were significant factors (odds ratios for duration of LZD therapy: 7.436 [95% confidence interval (CI): 1.918–28.831] and 4.712 [95% CI: 1.567–14.163]; odds ratio for safe ty target achievement rate: 0.060 [95% CI: 0.016–0.232] and 0.167 [95% CI: 0.056–0.498] for parameters A and B, respectively). When the safety target achievement rates for patients treated with LZD were compared between the thrombocytopenic and non-thrombocytopenic groups, the safety target achievement rate was higher in the non-thrombocytopenic group in both the patients treated with LZD for less than 10 days and those for 10 days or more.

Therefore, the safety target achievement rate estimated by the PK/PD simulation may represent to be an important index for risk assessment of LZD-induced thrombocytopenia.

What Is New and Conclusion

The risk of LZD-induced thrombocytopenia, which increased with the duration of LZD therapy, may be predicted using the safety target achievement rate obtained by the blood concentration simulation.
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