Αρχειοθήκη ιστολογίου

Κυριακή 13 Νοεμβρίου 2022

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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Association between emphysema and other pulmonary computed tomography patterns in COVID‐19 pneumonia

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Abstract:

Objectives

To evaluate the chest computed tomography (CT) findings of patients with Corona Virus Disease 2019 (COVID-19) on admission to hospital. And then correlate CT pulmonary infiltrates involvement with the findings of emphysema. We analyzed the different infiltrates of COVID-19 pneumonia using emphysema as the grade of pneumonia.

Methods

We applied open-source assisted software (3D Slicer) to model the lungs and lesions of 66 patients with COVID-19, which were retrospectively included. we divided the 66 COVID-19 patients into the following two groups: (A) 12 patients with less than 10% emphysema in the low-attenuation area less than −950 Hounsfield units (%LAA-950), (B) 54 patients with greater than or equal to 10% emphysema in %LAA-950. Imaging findings were assessed retrospectively by two authors and then pulmonary infiltrates and emphysema volumes were measured on CT using 3D Slicer software. Differences between pulmonary infiltrates, emphysema, Co llapsed, affected of patients with CT findings were assessed by Kruskal-Wallis and Wilcoxon test, respectively. Statistical significance was set at P<0.05.

Results

The left lung (A: affected left lung 20.00/affected right lung 18.50, B: affected left lung13.00/affected right lung 11.50) was most frequently involved region in COVID-19. In addition, collapsed left lung (A, collapsed left lung 4.95/collapsed right lung 4.65. B, collapsed left lung 3.65/collapsed right lung 3.15) was also more severe than the right one. There were significant differences between the group A and group B in terms of the percentage of CT involvement in each lung region (P<0.05), except for the inflated affected total lung (P=0.152). The median percentage of collapsed left lung in the group A was 20.00 (14.00-30.00), right lung was 18.50 (13.00-30.25) and the total was 19.00 (13.00-30.00), while the median percentage of collapsed left lung in the group B was 13.00 (1 0.00-14.75), right lung was 11.50 (10.00-15.00) and the total was 12.50 (10.00-15.00).

Conclusions

The percentage of affected left lung is an independent predictor of emphysema in COVID-19 patients. We need to focus on the left lung of the patient as it is more affected. The people with lower levels of emphysema may have more collapsed segments. The more collapsed segments may lead to more serious clinical feature.

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Electroacupuncture regulates macrophage, neutrophil, and oral microbiota to alleviate alveolar bone loss and inflammation in experimental ligature‐induced periodontitis

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Abstract

Aim

Electroacupuncture (EA) regulates distant body physiology through somatic sensory autonomic reflexes, balances the microbiome and can promote the release of immune cells into bloodstream, thereby inhibits severe systemic inflammation. This makes it possible to use EA as an integrated treatment for periodontitis.

Materials and methods

In this study, EA was applied to the ST36 acupoints in a ligature-induced periodontitis (LIP) mouse model. Then the effects of EA on periodontal myeloid cells, cytokines and microbiome were comprehensively analyzed using flow cytometry, qPCR and 16S sequencing.

Results

Results demonstrated that EA could significantly relieve periodontal bone resorption. EA also suppressed infiltration of macrophages and neutrophils, reduced gene expression of the pro-inflammatory cytokines IL-1β, IL-6, IL-17 and TNF-α, while increased expression of anti-inflammatory factors IL-4 and IL-10 in periodontal tissues. Moreover, composition of the periodontal microbiome was regulated by EA, finding that complex of microbiota, including supragingival Veillonella, subgingival Streptococcus, and subgingival Erysipelatoclostridium, were significantly reduced. Meanwhile, nitrate and nitrate-related activities of subgingival microbiota were reversed. Network analysis revealed close relationships among Veillonella, Streptococcus, and Bacteroides.

Conclusion

Our study indicated that EA effectively alleviated inflammation and bone resorption in LIP mice, potentially via regulation of myeloid cells, cytokines, and periodontal microbiome.

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Ultrasonographic Features of Salivary Glands after Radioiodine Therapy in Patients with Thyroid Cancer

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Ultrasonographic Features of Salivary Glands after Radioiodine Therapy in Patients with Thyroid Cancer

Chronic sialadenitis is the most common radioactive iodine (RAI) treatment complication. We explored the sonographic features of the major salivary glands in patients with papillary thyroid cancer (PTC) treated with RAI. RAI treatment following thyroidectomy is associated with a dose-response effect and adverse changes in the major salivary glands and should be prescribed carefully.


Objective

Chronic sialadenitis is the most common complication of radioactive iodine (RAI) treatment. The aim of the study was to ascertain sonographic features of the major salivary glands in patients with papillary thyroid cancer (PTC) treated with RAI.

Methods

The database of a tertiary medical center was retrospectively searched for consecutive patients who underwent total thyroidectomy for PTC in 2011–2020 with ultrasound follow-up after 1 year. Changes in ultrasound features of the major salivary glands were compared between patients treated or not treated with RAI postoperatively.

Results

The cohort included 158 patients, of whom 109 (69%) were treated postoperatively with RAI (mean dose, 131 mCi) and 49 were not (control group). Sonographic changes were observed in the major salivary glands in 43% of the study group and 18% of the control group (p = 0.002), including coarse echotexture, decreased echogenicity, fibrosis, and atrophy. Higher RAI doses were significantly correlated with the prevalence and severity of glandular changes (p < 0.0001).

Conclusion

RAI treatment following thyroidectomy is associated with a dose–response effect and adverse changes in the major salivary glands and should be prescribed carefully.

Level of Evidence

4 Laryngoscope, 2022

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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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Sensory neuromuscular electrical stimulation for dysphagia rehabilitation: A literature review

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Abstract

Background

Dysphagia is a common disorder following a cerebrovascular accident. It can cause detrimental effects on patient's quality of life and nutrition intake, especially in older adults. Neuromuscular electrical stimulation has been one of the management strategies for acceleration of the recovery. This review summarizes the current evidence on sensory threshold stimulation of the procedure.

Method

This review compiled data from the Internet database PubMed, Cochrane Library and Scopus using combination of MeSH thesaurus: "Sensory threshold", "electrical stimulation", "neuromuscular stimulation", "Deglutition", "Dysphagia". 11 studies were intergraded into the review.

Results

Most of the studies show significant improvement to the outcomes of sensory neuromuscular electrical stimulation treatment. In many cases, the results of the treatment are comparable or superior to motor threshold stimulation and conventional therapy. However, the study design and parameters of the procedure varied greatly without conclusive standardized guidelines.

Conclusion

The sensory neuromuscular electrical stimulation (SNMES) is a viable treatment option for treating oropharyngeal dysphagia. The most suggested application parameters are an intensity at sensory threshold, a frequency of 80 Hz, an impulse time of 700 μs, a combined total duration of 20 hours of stimulation in a 2-week period, placing the electrodes in the submental area of the neck. However, further research is necessary to construct a definitive guideline for clinicians.

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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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Nonpharmaceutical interventions for COVID‐19 disrupt the dynamic balance between influenza A virus and human immunity

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Abstract

Background

During the COVID-19 epidemic, nonpharmaceutical interventions (NPIs) blocked the transmission route of respiratory diseases. This study aimed to investigate the impact of NPIs on the influenza A virus (IAV) outbreak.

Methods

The present study enrolled all children with respiratory tract infections who came to the Children's Hospital of Zhejiang University between January 2019 and July 2022. A direct immunofluorescence assay kit detected IAV. Virus isolation and Sanger sequencing were performed.

Results

From June to July 2022, in Hangzhou, China, the positive rate of IAV infection in children has increased rapidly, reaching 30.41%, and children over three years old are the main infected population, accounting for 75% of the total number of infected children. Influenza A (H3N2) viruses are representative strains during this period. In this outbreak, H3N2 was isolated from a cluster of its own and is highly homologous with A/South_Dakota /22/2022 (2021-2022 northern hemisphere). Between isolated influenza A(H3N2) viruses and A/South_Dakota/22/2022, the nucleotide homology of the HA gene ranged from 97.3% to 97.5%; the amino acid homology was 97% - 97.2%, and the genetic distance of nucleotides ranged from 0.05 to 0.052. Compared with A/South_Dakota/22/2022, the isolated H3N2 showed S156H, N159Y, I160T, D186S, S198P, I48T, S53D, and K171N mutations. There was no variation in 13 key amino acid sites associated with neuraminidase inhibitor resistance in NA protein.

Conclusion

Long-term NPIs have significantly affected the evolution and transmission of the influenza virus and human immunity, breaking the dynamic balance between the influenza A virus and human immunity.

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