Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Tuesday, August 2, 2022

Urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs) and timing of pubertal development: The California PAH Study

alexandrossfakianakis shared this article with you from Inoreader

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Background: Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals. Few studies have evaluated the association between pubertal development in girls and PAH exposures quantified by urinary biomarkers. Methods: We examined associations of urinary PAH metabolites with pubertal development in 358 girls aged 6-16 years from the San Francisco Bay Area enrolled in a prospective cohort from 2011-2013 and followed until 2020. Using baseline data, we assessed associations of urinary PAH metabolites with pubertal development stage. In prospective analyses limited to girls who at baseline had not yet started breast (N=176) or pubic hair (N=179) development or menstruation (N=267), we used multivariable Cox proportional hazards regression to assess associations of urinary PAH metabolites with onset of breast and pubic hair development, menstruation, and pubertal tempo (interval between onset of breast development and menstruation). Results: We detected PAH metabolites in >98% of girls. In cross-sectional analyses using baseline data, PAH metabolites were not associated with pubertal development stage. In prospective analyses, higher concentrations (≥ median) of some PAH metabolites were associated with two-fold higher odds of earlier breast development (2-hydroxynaphthalene, 1-hydroxyphenanthrene, summed hydroxyphenanthrenes, total summed metabolites) or pubic hair development (1-hydroxynaphthalene) among girls overweight at baseline (body mass index (BMI)-for-age percentile ≥85) compared to non-overweight girls with lower metabolites concentrations. PAH metabolites were not associated with age at menarche or pubertal tempo. Conclusions: PAH exposures were widespread in our sample. Our results support the hypothesis that, in overweight girls, PAHs impact the timing of pubertal development, an important risk factor for breast cancer. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable HIV Viremia in an Urban HIV Clinic

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
Background
Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naïve or experienced people living with HIV (PLWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PLWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART.
Methods
Ward 86 is a large HIV clinic in San Francisco that serves publicly insured or underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. Descriptive statistics evaluated program outcomes.
Results
Between June 2021-April 2022, 51 patients initiated LAI-ART, with 39 receiving at least two follow-up injections by database closure (median age 46; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients initiating injections with viral suppression (median CD4 706), 100% (95% CI 86-100%) maintained viral suppression. Of 15 patients initiating injections with detectable viremia (median CD4 99, mean log10 viral load 4.67 SD 1.16), 12 (80%; 95% CI 55-93%) achieved viral suppression and the other 3 had a 2-log viral load decline by a median of 22 days.
Conclusions
This small demo nstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.
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Spatiotemporal trends in norovirus outbreaks in the United States, 2009–2019

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
Background
Globally, noroviruses cause infections year-round but have recognized winter seasonality in the northern hemisphere and yearly variations in incidence. With candidate norovirus vaccines in development, understanding temporal and geographic trends in norovirus disease is important to inform potential vaccination strategies and evaluate vaccine impact.
Methods
We analyzed data from the National Outbreak Reporting System (NORS) and CaliciNet on single-state norovirus outbreaks that occurred from August 2009–July 2019 in the contiguous United States. We defined norovirus season onset and offset as the weeks by which 10% and 90% of norovirus outbreaks in a surveillance year occurred, respectively, and duration as the difference in weeks between onset and offset. We compared norovirus seasons across surveillance years and geographic regions.
Results
During August 2009–July 2019, 24,995 single-state norovirus outbreaks were reported to NORS and/or CaliciNet. Nationally, median norovirus season duration was 24 weeks, with onset occurring between October–December and offset occurring between April–May. Across all years combined, we observed a west-to-east trend in seasonality, with the earliest onset (October) and latest offset (May) occurring in western regions and the latest onset (December) and earliest offset (April) occurring in northeastern regions.
Conclusions
Timing and duration of the US norovi rus season varied annually, but generally occurred during October–May. Norovirus wintertime seasonality was less distinct in western regions and was progressively more pronounced moving east. Further understanding the drivers of spatiotemporal dynamics of norovirus could provide insights into factors promoting virus transmission and help guide future interventions.
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Induction chemotherapy of modified docetaxel, cisplatin, 5‐fluorouracil for laryngeal preservation in locally advanced hypopharyngeal squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Previous studies have investigated the value of induction chemotherapy (IC) in organ preservation strategies for head and neck cancers. This study evaluated the effectiveness of sequential IC with radiotherapy as a laryngeal preservation strategy for locally advanced hypopharyngeal carcinoma (LAHSCC).

Methods

One hundred and forty-two consecutive patients with LAHSCC were retrospectively analyzed who received three IC regimens from 2015 to 2019.

Results

In the TP (docetaxel plus cisplatin), TPF (TP plus 5-fluorouracil), and TPX (TP plus capecitabine) IC groups, there were 51, 29, and 62 patients, respectively. The primary tumor objective response rates were 51%, 55.2%, and 71%, and the 3-year survival rates with preserved larynx were 36.6%, 31.8%, and 51.2%, respectively (p = 0.03). There was no difference in overall survival and the adverse events were tolerable.

Conclusions

The TPX regimen displayed good efficacy and safety, indicating its potential as a therapeutic IC regimen for LAHSCC.

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Lymphoepithelial carcinoma of the parotid gland: Clinicopathological analysis of 146 cases from a single institute

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Parotid lymphoepithelial carcinoma (LEC) is a rare malignant tumor. The purpose of this study was to investigate the clinicopathological features of parotid LEC.

Methods

All patients clinicopathological information diagnosed parotid LEC from 2005 to 2017 were analyzed.

Results

A total of 146 cases of parotid LECs were identified. Of these, 126 (86.3%) were primary and 20 (13.7%) were secondary LECs. Patients with secondary LEC tended to have tumors with earlier TNM staging than those with primary (p = 0.031). The tumor cells in 87 (94.6%, 87/92) cases tested positive for Epstein–Barr virus (EBV). Cervical node metastases were present at diagnosis in 46 (31.5%) cases. Overall survival at 5 and 10 years was 97.0% and 90.8%, respectively. Older age was an adverse prognostic indicator for overall survival (p < 0.001).

Conclusions

Parotid LEC is associated with EBV and an increased rate of cervical node metastases. However, most patients, especially younger ones, have a good prognosis.

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The management of metastatic neck nodes following induction chemotherapy in N2/3 classification hypopharyngeal carcinoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

For patients with less chemosensitive neck nodes, poor prognosis after chemoradiotherapy (CRT) could be predicted and neck dissection is needed.

Methods

Ninety-two N2/3 hypopharyngeal carcinoma patients were retrospectively studied. According to response after induction chemotherapy (ICT), patients were treated with neck dissection followed by concurrent CRT (CCRT) (group 1), surgery plus postoperative CRT (group 2), or CCRT for primary and regional sites (group 3).

Results

Overall survival and disease-free survival rates of group 1 were significantly higher than group 2 (p = 0.038, p = 0.031) and group 3 (both p = 0.018). Regional control rate of group 1 was significantly higher than group 3 (p = 0.041). There were no significant differences between groups 1 and 2 regarding local and regional control (p = 0.746, p = 0.302).

Conclusions

Neck dissection followed by CCRT is the best choice for patients with responsive primary but nonresponsive nodes.

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Association between body composition and survival in head and neck cancer patients undergoing radiotherapy

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Body composition may influence the prognosis of head and neck cancer (HNC) patients. To find out the most crucial factors in this relationship, we explored the association between body composition and survival.

Methods

In this prospective longitudinal study, HNC patients who underwent radiotherapy (RT) from March 2017 to December 2018 were recruited. The association between body composition and survival was analyzed using Cox proportional hazard regression.

Results

Final analysis included 316 patients, with a median follow-up of 34.4 months. Multivariable analysis revealed that weight loss 6 months before RT and body composition changes during RT did not affect the survival outcome. However, patients with low appendicular skeletal muscle mass index (ASMI) before RT exhibited poor overall survival (OS). ASMI before RT was an independent prognostic factor for OS.

Conclusions

Body composition loss was common during RT, and ASMI before RT independently influenced the survival outcomes of HNC patients.

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Combined taxane, platinum, and cetuximab as a first‐line treatment for recurrent/metastatic head and neck squamous cell carcinoma: Retrospective study

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

There is limited evidence supporting the use of taxane-based chemotherapy combined with cetuximab to treat recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). This retrospective study aimed to explore treatment efficacy and safety in a first-line setting.

Methods

Fifty-nine patients received ≤6 cycles of combined cetuximab, platinum compounds, and taxane (median follow-up, 352 days). Kaplan–Meier survival curves were constructed.

Results

The median patient age was 54 years (23–75 years; 50 males and 9 females). The most common distant metastatic site was the lung. Patients received ≥2 cycles chemotherapy (33 [55.9%] received cetuximab, paclitaxel, and carboplatin; 21 [35.5%] received cetuximab maintenance; median progression-free survival, 7 months; overall survival, 12 months). The most common hematological toxicity was Grade 3 or 4 neutropenia, which was successfully managed through growth-stimulating factors and dose modifications. No treatment-associated deaths occurred.

Conclusions

Combined cetuximab, platinum, and taxane is effective and tolerable in R/M HNSCC.

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Recurrence risk stratification and treatment strategies of patients with stage IVa‐b hypopharyngeal squamous cell carcinoma

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Optimal treatment strategies for patients with stage IVa-b hypopharyngeal squamous cell carcinoma (HSCC) remain controversial. This study aimed to examine the high-risk factors of postoperative tumor recurrence after surgical resection of HSCC and devise individualized postoperative adjuvant treatment (POAT).

Methods

Overall, 218 patients with stage IVa-b HSCC who received surgery as initial treatment and with negative surgical margins were evaluated. Independent risk factors of recurrence were identified, and survival outcomes were compared according to recurrence risk and POAT use.

Results

POAT significantly improved recurrence-free survival (RFS) and overall survival (OS) only in the high-risk patients (p = 0.003 and 0.018, respectively). Compared with postoperative radiotherapy alone, postoperative chemoradiotherapy (pCRT) achieved significantly better RFS (p = 0.035) and OS (p = 0.048).

Conclusions

POATs are recommended for high-risk patients with stage Iva-b HSCC, with pCRT achieving superior outcomes. Regular re-examination after tumor resection is sufficient for low-risk patients.

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Noradrenergic Add-on Therapy with Extended-Release Guanfacine in Alzheimer’s Disease (NorAD): study protocol for a randomised clinical trial and COVID-19 amendments

alexandrossfakianakis shared this article with you from Inoreader

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Guanfacine is a α2A adrenergic receptor agonist approved for treating attention deficit hyperactivity disorder (ADHD). It is thought to act via postsynaptic receptors in the prefrontal cortex, modulating execu...
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