Δευτέρα 8 Αυγούστου 2022

Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial

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Abstract
BackgroundCervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells.
Methods
Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry.
Results
Unlike the LNG implant or copper-IUD, DMPA-IM was as sociated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4β7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non–Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post–DMPA-IM (P = .03), although this did not influence barrier function.
Conclusions
Our data suggest that D MPA-IM–driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity.
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Κυριακή 7 Αυγούστου 2022

Leucovorin (folinic acid) rescue for high‐dose methotrexate: A review

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Leucovorin (folinic acid) rescue for high-dose methotrexate: A review

Leucovorin rescue is a cornerstone for toxicity prevention in high dose methotrexate treatment. Leucovorin rescue protocols differ greatly across tumor types and medical institutions. Leucovorin rescue protocols were reviewed for patients with ALL, lymphomas, and osteosarcoma.


Abstract

High-dose methotrexate (HDMTX) is active against various malignancies; it possesses serious toxicities and is associated with patient characteristics, dosage regimens, comedications, and physiological status. There are many strategies to overcome HDMTX-induced toxicities, such as hydration, alkalization, leucovorin rescue, and haemodialysis. Leucovorin rescue is a cornerstone for toxicity prevention in HDMTX treatment. However, the leucovorin dose adjustment and the existence of leucovorin overrescue are still controversial. At present, various methods for calculating leucovorin doses in different tumour types have been proposed, including empirical calculations based on MTX plasma concentration, the Bleyer nomogram, and other methods. Nonetheless, leucovorin rescue protocols differ greatly across tumour types and medical institutions. Further studies are needed to investigate the optimal dosage regimen for leucovorin rescue in various tumours using HDMTX.

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Angiotensin II-induced miR-31-5p upregulation promotes vascular smooth muscle cell proliferation and migration

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Publication date: Available online 5 August 2022

Source: Experimental Cell Research

Author(s): Bing Zhou, Nan Wu, Yuan Yan, Lu-Lu Wu, Guo-Qing Zhu, Xiao-Qing Xiong

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Πέμπτη 4 Αυγούστου 2022

Prognostic capacity of the transcriptional expression of lactate dehydrogenase A in patients with head and neck squamous cell carcinoma

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Abstract

Background

To analyze the relationship between the transcriptional expression of lactate dehydrogenase A (LDHA) and the disease control in patients with a head and squamous cell carcinoma (HNSCC).

Methods

We determined the transcriptional expression of LDHA in 110 HNSCC patients treated with surgery.

Results

Five-year disease-free survival for patients with a high transcriptional expression of LDHA (n = 51) was 39.2% (95% confidence interval [CI]: 25.3%–53.1%), and for patients with a low expression (n = 59), it was 63.6% (95% CI: 51.1%–76.1%) (p = 0.004). According to the results of a multivariate analysis, patients with a high transcriptional expression of LDHA had a 3.4-fold increased risk of tumor recurrence. Patients with a high transcriptional expression of LDHA tended to show a higher intensity of immunohistochemical expression of LDHA at the tumor cells (p = 0.086).

Conclusion

In HNSCC patients treated with surgery, a high transcriptional expression of LDHA was associated with a significant decrease in disease-free survival.

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Epstein-Barr Virus–Positive Plasma Cell Neoplasm of Nasal Cavity in an Immunocompetent Adult

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This case report describes patient in their 40s with a medical history of sleep apnea and diabetes and no history of immunosuppression who presented with left-sided nasal obstruction for 1 year and was found to have an Epstein-Barr virus–positive plasmacytoma.
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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta‐analysis

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Transoral Laser Microsurgery in Recurrent Laryngeal Cancer: A Systematic Review and Meta-analysis

The aim of this systematic review and meta-analysis was to determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer. We demonstrated that TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines.


Objective

To determine the oncological outcomes of salvage transoral laser microsurgery (TLM) in the treatment of patients suffering from recurrent laryngeal cancer.

Methods

PubMed/MEDLINE, Cochrane Library, and Scopus databases were searched. English language, original studies investigating oncological outcomes of TLM in adult patients with recurrent laryngeal cancer were included. Data were pooled using a distribution-free approach for estimating summary local control (LC), disease-specific survival (DSS), and overall survival (OS) curves with random effects.

Results

Two hundred and thirty-five patients underwent salvage TLM after primary (chemo)radiotherapy. The mean follow-up time was 60.8 months (95% CI: 32.7–88.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 74.2% (61.7–89.4), 53.9% (38.5–75.3), and 39.1% (25.2–60.8). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 88.4% (82.0–95.3), 67.8% (50.9–90.3), and 58.9% (42.7–81.1). Two hundred and seventy-one patients underwent TLM after primary laser treatment. The mean follow-up time was 70.9 months (95% CI: 36.9–104.9). Estimated pooled LC rates (95% CI) at 1, 3 and 5 years were 72.2% (64.7–80.6), 53.2% (42.2–66.9), and 40.4% (29.6–55.2). Estimated pooled DSS rates (95% CI) at 1, 3 and 5 years were 92.1% (85.5–99.1), 77.0% (64.4–92.0), and 67.1% (51.6–87.3).

Conclusions

TLM is a valuable treatment option for the management of locally recurrent laryngeal carcinoma if performed by experienced surgeons and following rigorous patients' selection criteria. Further studies should be conducted to define stage-based clinical guidelines.

Level of Evidence

NA Laryngoscope, 2022

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Survival and complications of implant‐supported cantilever fixed dental prostheses with zirconia and metal frameworks: A retrospective cohort study

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Abstract

Background

Current evidence about long-term survival of all-ceramic implant-supported cantilever fixed dental prostheses (cFDP) is limited.

Purpose

To evaluate the survival and complication rates of all-ceramic and metal–ceramic implant-supported cFDPs located in anterior and posterior sites, under consideration of risk factors.

Methods of study

The retrospective analysis compared an experimental group (75 implant-supported cFDPs among 48 patients [mean age 60.47 ± 9.25 years; 21 men]; mean observation period 3.56 years) with a control group (300 implant-supported non-cantilever FDPs [ncFDP] among 241 patients [mean age 62.85 ± 10.72 years; 109 men]; mean observation period 7.25 years). Kaplan–Meier estimates were used to describe the long-term survival and success of both groups. Log-rank tests were used for group comparisons. Mixed-effects Cox proportional hazards regression models were used to examine the effects of restoration- and site-specific risk factors. A random intercept was included in the models to take multiple FDPs per patient into account.

Results

Five-year cumulative survival until loss of restoration was 97.1% (95% confidence interval [CI] 0.93–1.00) for cFDPs and 97.0% (95% CI 0.95–0.99) for ncFDPs. Ten-year survival was 93.7% (95% CI 0.86–1.00) for cFDPs and 92.8% (95% CI 0.87–0.98) for ncFDPs, no difference between the survival curves of these groups was observed. Success differed between cFDPs and ncFDPs (p Log  = 0.002), zirconia and metal frameworks (p Log  < 0.001), and provisional and definitive cements (p Log  = 0.025). The effects of the variables "framework material" and "attachment method" were confirmed in a mixed-effects Cox regression model. Loss of retention was the predominant complication for both cFDPs and ncFDPs and usually affected provisionally cemented FDPs.

Conclusions

cFDPs do not differ from ncFDPs with regard to long-term failure, whereas additional complications were higher for cFDPs. Fewer complications were observed for zirconia frameworks without occlusal veneers and definitive cemented FDPs.

Clinical trial registration: the trial has no registration number because it commenced before January 31, 2017.

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