Κυριακή 13 Νοεμβρίου 2022

Comparison of passive versus active transcutaneous bone anchored hearing devices in the pediatric population

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Transcutaneous bone anchored hearing devices (BAHDs) were introduced in an effort to avoid potential complications associated with the abutment of percutaneous BAHDs. Transcutaneous BAHDs can be active or pass...
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Exhaled Mycobacterium tuberculosis Predicts Incident Infection in Household Contacts

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Abstract
BackgroundHalting transmission of Mycobacterium tuberculosis (Mtb) by identifying infectious individuals early is key to eradicating tuberculosis (TB). Here we evaluate face mask sampling as a tool for stratifying the infection risk of individuals with pulmonary TB (PTB) to their household contacts.
Methods
Forty-six sputum-positive PTB patients in The Gambia (August 2016–November 2017) consented to mask sampling prior to commencing treatment. Incident Mtb infection was defined in 181 of their 217 household contacts as QuantiFERON conversion or an increase in interferon-γ of ≥1 IU/mL, 6 months after index diagnosis. Multilevel mixed-effects logistical regression analysis with cluster adjustment by household was used to identify predictors of incident infection.
Results
Mtb was detected in 91% of PTB mask samp les with high variation in IS6110 copies (5.3 × 102 to 1.2 × 107). A high mask Mtb level (≥20 000 IS6110 copies) was observed in 45% of cases and was independently associated with increased likelihood of incident Mtb infection in contacts (adjusted odds ratio, 3.20 [95% confidence interval, 1.26–8.12]; P = .01), compared with cases having low-positive/negative mask Mtb levels. Mask Mtb level was a better predictor of incident Mtb infection than sputum bacillary load, chest radiographic characteristics, or sleeping proximity.
Conclusions
Mask sampling offers a sensitive and noninvasive tool to support the stratification of individuals who are most infectious in high-TB-burden settings. Our approach can provide b etter insight into community transmission in complex environments.
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VPM1002 as Prophylaxis Against Severe Respiratory Tract Infections Including COVID-19 in the Elderly: a phase III randomised, double-blind, placebo-controlled, multicenter clinical study

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Abstract
Background
Bacille Calmette–Guérin (BCG) vaccination can potentially reduce the rate of respiratory infections in vulnerable populations. This study evaluates the safety and efficacy of VPM1002 (a genetically modified BCG) as prophylaxis against severe respiratory tract infections including COVID-19 in an elderly population.
Methods
In this phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial, healthy elderly volunteers (n = 2064) were enrolled, randomized (1:1) to receive either VPM1002 or placebo, and followed up remotely for 240 days. The primary outcome was the mean number of days with severe respiratory infections at hospital and/or at home. Secondary endpoints included the incidence of self-reported fever, number of hospital and ICU admissions, and number of adverse events.
Results
A total of 31 participants in the VPM1002 group reported at least 1 day with severe respiratory disease and a mean number of days with severe respiratory disease of 9.39 ± 9.28 days while in the placebo group, 38 participants reported a mean of 14.29 ± 16.25 days with severe respiratory disease. The incidence of self-reported fever was lower in the VPM1002 group (odds ratio: 0.46; 95% CI: 0.28 to 0.74; p-value: 0.001) and consistent trends to less hospitalization and ICU admissions due to COVID-19 were observed after VPM1002-vaccination. Local reactions typical for BCG were observed in the V PM1002-vaccinated group, which were mostly of mild intensity.
Conclusions
Vaccination with VPM1002 is well tolerated and seems to have a prophylactic effect against severe respiratory diseases in the elderly. (ClinicalTrials.gov: NCT04435379)
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Posisep Versus PureRegen Gel for Post ESS Nasal Packing – A Randomized Blinded Prospective Study

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Objective

Endoscopic sinus surgery (ESS) is the procedure of choice for chronic rhinosinusitis (CRS). Adhesions are the most common postoperative complications, causing recurrent disease and revision surgery. Postoperative care is thus essential for the healing of the operated cavity. A wide variety of packing materials are used to prevent bleeding and adhesions postoperatively. Two main absorbable packing materials are used: Foam-based packs (e.g., Posisep and Nasopore) and gel-based packs (PureRegen Gel – PRG). The current study is a randomized, blinded, prospective analysis of cavity healing using Posisep and PRG in ESS, aiming to compare the pros and cons of the two.

Methods

Patients with bilateral symmetric CRS were recruited for the study. At the end of surgery, one side was randomly packed with Posisep, whereas the other was packed with PRG. The postoperative cavity cleaning was video recorded and a blinded physician evaluated the mucosal healing.

Results

The side packed with Posisep had significantly less middle turbinate (MT) lateralization and adhesions yet dissolved significantly slower than the PRG, causing more mucosal edema. Severe MT scarring requiring recurrent medialization and adhesiolysis was exclusively observed in the PRG group. All differences were observed in the early postoperative period (up to 12 weeks after surgery). By that time, only the MT position was significantly different between groups, despite recurrent adhesiolysis and medialization.

Conclusion

The authors recommend using Posisep for MT support only when it is unstable or lateralized. Packing the surgical cavity in other cases with PRG is more beneficial.

Level of Evidence

2 Laryngoscope, 2022

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MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer

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Abstract

Anlotinib is approved for refractory cases in advanced non-small-cell lung cancer (NSCLC). This is a novel oral multitarget tyrosine kinase inhibitor, but patients inevitably face prospects of drug resistance during the treatment process. Using anlotinib-resistant NSCLC models, this work investigated the underlying molecular mechanism and systematically addressed the issue of anlotinib resistance. We demonstrated that expression and activity of eukaryotic translation initiation factor 4E (eIF4E) were upregulated in NSCLC cells due to prolonged exposure to anlotinib. eIF4E depletion resulted in significant effects to anlotinib-resistant cells, showing proliferation inhibition and apoptosis inducement. We further showed that MAP kinase interacting serine/threonine kinase (MNK)-dependent eIF4E inhibition by cercosporamide was active against anlotinib-resistant cells and significantly augmented anlotinib's efficacy in parental NSCLC cells. Importantly, observations from in-vitro exp eriments are consistent in in vivo anlotinib-resistant and anlotinib-sensitive NSCLC cancer xenograft mouse models. Our work is the first to reveal that eIF4E is involved intimately in anlotinib resistance development in NSCLC, and this eIF4E activation can be reversed by cercosporamide or other MNK inhibitors.

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Evaluating the role of non-alcoholic fatty liver disease in cardiovascular diseases and type 2 diabetes: a Mendelian randomization study in Europeans and East Asians

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Abstract
BackgroundWhether non-alcoholic fatty liver disease (NAFLD) causes cardiovascular disease (CVD) and type 2 diabetes (T2D) is unclear and possible differences between ethnicities have not been thoroughly explored. We used Mendelian randomization (MR) to assess the role of NAFLD in CVD and T2D risk in Europeans and East Asians.
Methods
We conducted a MR study using genetic predictors of alanine aminotransferase (ALT), liability to NAFLD, aspartate transaminase (AST), liver magnetic resonance imaging corrected T1 and proton density fat fraction and combined them with genome-wide association studies (GWAS) summary statistics of CVD, T2D and glycaemic traits (sample size ranging from 14 400 to 977 320). Inverse-variance weighted analysis was used to assess the effect of NAFLD in these outcomes, with sensitivity analyses and replication in FinnGen. We conducted analyses in East Asians using ethnicity-specific genetic predictors of ALT and AST, and the respective outcome GWAS summary statistics.
Results
In Europeans, higher ALT was associated with higher T2D risk (odds ratio: 1.77 per standard deviation, 95% CI 1.5 to 2.08), with similar results for other exposures, across sensitivity analyses and in FinnGen. Although NAFLD proxies were related to higher coronary artery disease (CAD) and stroke risk, sensitivity analyses suggested possible bias by horizontal pleiotropy. In East Asians, higher ALT was possibly associated with higher T2D risk, and ALT and AST were inversely associated with CAD.
Conclusions
NAFLD likely increases the risk of T2D in Europeans and East Asians. Potential differential effects on CAD between Europeans and East Asians require further investigation.
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Neutrophil‐to‐lymphocyte and hypopharyngeal cancer prognosis: System review and meta‐analysis

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Abstract

Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14–2.82; PFS, HR = 1.88, 95CI%, 1.26–2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer.

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The association between serum 25‐hydroxyvitamin D and the prevalence of herpes simplex virus

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Abstract

Objective

Previous studies have reported a potential anti-infection effect for vitamin D. However, the relationship between vitamin D status and herpes simplex virus (HSV) infection has not yet been evaluated. Therefore, this study aimed to determine the association between serum 25-hydroxyvitamin D [25(OH)D] and infection with HSV types 1 and 2 (HSV-1 and HSV-2).

Methods

Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007-2016. The association between 25(OH)D and HSV prevalence was evaluated using propensity score matching (PSM) and univariate and multivariate logistic regression analyses.

Results

Overall, 14174 participants were included in the final analysis. Before PSM, 8639 (60.9%) had positive HSV-1 and 2636 (18.6%) had HSV-2. The HSV-1 and HSV-2 positive groups had more females and older individuals (P<0.05). The HSV-2 patients had lower 25(OH)D levels than those with HSV-1. Age and g ender did not differ in the groups after PSM (P>0.05). The 25(OH)D level was significantly lower in the HSV-1 and HSV-2 groups than in the non-HSV infection groups. Multivariate logistic regression showed that serum 25(OH)D level was negatively associated with HSV-1 and HSV-2 infection (OR=0.730 and 0.691, P<0.001, respectively). Vitamin D deficiency was an independent risk factor for both HSV-1 and HSV-2 (adjusted OR=2.205 and 2.704, P<0.001, respectively).

Conclusion

Lower serum 25(OH)D levels correlated significantly with increased HSV-1 and HSV-2 infection risk

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Transplacental transmission of SARS‐CoV‐2 immunoglobulin G antibody to infants from maternal COVID‐19 vaccine immunization before pregnancy

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Abstract

Background & aim

Coronavirus disease 2019 (COVID-19) vaccine generates functional antibodies in maternal circulation that are detectable in infants, while the information is restricted to the usage of COVID-19 vaccine during pregnancy. In this study, we aimed to evaluate the effect of maternal COVID-19 vaccines before pregnancy.

Method

Infants were included from mothers with no inactivated COVID-19 vaccine, 1-dose, 2-dose and 3-dose before pregnancy, and SARS-CoV-2 IgG antibodies were tested. Comparative analysis was done between the groups.

Results

A total of 130 infants were enrolled in the study. Significantly higher levels of SARS-CoV-2 IgG antibodies in infants born to mothers with 3-dose COVID-19 vaccine before pregnancy compared with 1-dose and 2-dose groups (p<0.0001). The levels of antibodies decreased significantly with age in infants born to mothers with the 3-dose COVID-19 vaccine before pregnancy (r=-0.338, p=0.035), and it w as still higher than that 2-dose COVID-19 vaccine group.

Conclusion

The maternal SARS-CoV-2 antibodies produced from the inactivated COVID-19 vaccine before pregnancy can be transferred to newborns via the placenta. Maternal immunization with 3-dose of the COVID-19 vaccine before pregnancy could be more beneficial for both mothers and infants.

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The use of electrodermal activity in pulpal diagnosis and dental pain assessment

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Abstract

Abstract

Aims

To explore whether electrodermal activity (EDA) can serve as a complementary tool for pulpal diagnosis (Aim 1) and an objective metric to assess dental pain before and after local anaesthesia (Aim 2).

Methodology

A total of 53 subjects (189 teeth) and 14 subjects (14 teeth) were recruited for Aim 1 and Aim 2, respectively. We recorded EDA using commercially available devices, PowerLab and Galvanic Skin Response (GSR) Amplifier, in conjunction with cold and electric pulp testing (EPT). Participants rated their level of sensation on a 0-10 visual analogue scale (VAS) after each test. We recorded EPT-stimulated EDA activity before and after the administration of local anaesthesia for participants who required root canal treatment (RCT) due to painful pulpitis. The raw data were converted to the time-varying index of sympathetic activity (TVSymp), a sensitive and specific parameter of EDA. Statistical analysis was performed using Python 3.6 and its Scikit-post hoc library.

Results

EDA activity was upregulated by the stimuli of cold and EPT testing in normal pulp. TVSymp signals were significantly increased in vital pulp compared to necrotic pulp by both, cold test and EPT. Teeth that exhibited intensive sensitivity to cold with or without lingering pain had increased peak numbers of TVSymp than teeth with mild sensation to cold. Pre- and post-anaesthesia EDA activity and VAS scores were recorded in patients with painful pulpitis. Post-anaesthesia EDA signals were significantly lower compared to pre-anaesthesia levels. Approximately 71 % of patients (10 out of 14 patients) experienced no pain during treatment and reported VAS score zero or 1. Majority of patients (10 out of 14) showed the reduction of TVSymp after the administration of anaesthesia. Two out of three patients who experienced increased pain during root canal treatment (post-treatment VAS > pre-treatment VAS) exhibited increased post-anaesthesia TVSymp.

Conclusions

Our data show promising results for using EDA in pulpal diagnosis and for assessing dental pain. While our testing was limited to subjects who had adequate communication skills, our future goal is to be able to use this technology to aid in the endodontic diagnosis of patients who have limited communication ability.

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