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Τετάρτη 18 Ιανουαρίου 2023

vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection

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Abstract

Background

The treatment of Helicobacter pylori (H. pylori) infection is a challenge for those who cannot use amoxicillin.

Objective

To evaluate the eradication rate and adverse effects of vonoprazan and tetracycline dual therapy as first-line and rescue treatment regimens used in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies.

Design

Patients enrolled were those who were H. pylori-positive with selected conditions: (1) allergic to penicillin, either naïve to treatment or had failed before; or (2) failed in previous amoxicillin-containing therapies. All enrolled patients accepted 14-day vonoprazan and tetracycline dual therapy (VT dual therapy) as follows: vonoprazan (20 mg b.i.d.) and tetracycline (500 mg t.i.d. [body weight < 70 kg] or 500 mg q.i.d. [body weight ≥ 70 kg]). H. pylori status was evaluated by 13C-urease breath test 6 weeks after treatment. All adverse effects were recorded. Some patients underwent bacterial culture and antibiotic susceptibility testing.

Results

A total of 62 patients were enrolled; 18 of them received VT dual therapy as first-line treatment, 44 patients received VT dual therapy as rescue treatment. Overall, 58 of 62 patients achieved successful eradication (93.5%), while all involved (100%,18/18) succeeded in the first-line treatment group and 40 cases (90.9%, 40/44) succeeded in the rescue treatment group. Sixty-one (61/62, 98.4%) patients completed the whole course of treatment. Adverse events occurred in 6 patients (6/62, 9.7%), while one patient quit because of skin rash. All adverse effects were mild and relieved spontaneously after H. pylori treatment. Five patients achieved successful H. pylori culture, and all strains isolated were sensitive to tetracycline.

Conclusions

For the treatment of H. pylori infection in special populations with penicillin allergy or failed in previous amoxicillin-containing therapies, a 14-day vonoprazan and tetracycline dual therapy was effective and safe as first-line and rescue treatment in our study. Further study is warranted to verify its efficacy, especially for those who cannot use amoxicillin.
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Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double strand break repair and augments efficacy of temozolomide in glioblastoma

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Abstract
Background
Efficient DNA repair in response to standard chemo and radiation therapies often contribute to GBM therapy resistance. Understanding the mechanisms of therapy resistance and identifying the drugs that enhance the therapeutic efficacy of standard therapies may extend the survival of GBM patients. In this study, we investigated the role of KDM1A/LSD1 in DNA double strand break (DSB) repair and combination of KDM1A inhibitor and TMZ in vitro and in vivo using patient derived GSCs.
Methods
Brain-bioavailability of the KDM1A inhibitor (NCD38) was established using LS-MS/MS. Effect of combination of KDM1A knockdown or inhibition with TMZ was studied using cell viability and self-renewal assays. Mechanistic studies were conducted using CUT&Tag-seq, RNA-seq, RT-qPCR, Western blot, HR and NHEJ reporter, immunofluorescence, and comet assays. Or thotopic murine models were used to study efficacy in vivo.
Results
TCGA analysis showed KDM1A is highly expressed in TMZ treated GBM patients. Knockdown or knockout or inhibition of KDM1A enhanced TMZ efficacy in reducing the viability and selfrenewal of GSCs. Pharmacokinetic studies established that NCD38 readily crosses the BBB. CUT&Tag-seq studies showed that KDM1A is enriched at the promoters of DNA repair genes and RNA-seq studies confirmed that KDM1A inhibition reduced their expression. Knockdown or inhibition of KDM1A attenuated HR and NHEJ-mediated DNA repair capacity and enhanced TMZ mediated DNA damage. Combination of KDM1A knockdown or inhibition and TMZ treatment significantly enhanced survival of tumor bearing mice.
Conclusions
Our results provide evidence that KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA DSB repair pathways.
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Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus

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AbstractCholinergic signaling shapes sound processing and plasticity in the inferior colliculus (IC), the midbrain hub of the central auditory system, but how cholinergic terminals contact and influence individual neuron types in the IC remains largely unknown. Using pharmacology and electrophysiology, we recently found that acetylcholine strongly excites VIP neurons, a class of glutamatergic principal neurons in the IC, by activating α3β4* nicotinic acetylcholine receptors (nAChRs). Here, we confirm and extend these results using tissue from mice of both sexes. First, we show that mRNA encoding α3 and β4 nAChR subunits is expressed in many neurons throughout the IC, including most VIP neurons, suggesting that these subunits, which are rare in the brain, are important mediators of chol...
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Τρίτη 17 Ιανουαρίου 2023

Vertical ridge augmentation with Ti‐reinforced dense polytetrafluoroethylene (d‐PTFE) membranes or Ti‐meshes and collagen membranes: 3‐year results of a randomized clinical trial

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Abstract

Background

The present study aimed to evaluate hard and soft tissue parameters around implants placed in augmented posterior mandible, comparing Ti-reinforced d-PTFE membranes with Ti-meshes covered with collagen membranes, after 3 years of follow-up.

Materials and Methods

Forty eligible patients were randomly assigned to group A (Ti-reinforced d-PTFE membrane) or group B (mesh covered with collagen membrane) for vertical ridge augmentation (VRA) and simultaneous implants. Implants were evaluated using specific peri-implant parameters for bone and soft tissues: probing pocket depth (PPD), modified plaque index (mPI), bleeding on probing (BoP), modified gingival index (mGI), thickness of keratinized tissue (tKT), width of keratinized tissue (wKT), fornix depth (FD), peri-implant bone level (PBL), interproximal bone peaks (IBP), marginal bone loss (MBL), interproximal bone loss (IBL).

Results

A total of 28 patients with 79 implants were evaluated after 3 years of follow-up. The mean value of MBL was 0.70 mm (group A = 0.73 mm; group B = 0.71 mm), while mean IBL was 0.54 mm (group A = 0.64 mm; group B = 0.40 mm). The treatment with meshes resulted not inferior to PTFE and their clinical results appeared similar. A strong correlation between PBL and IBP was confirmed. Both study groups showed an increase of tKT and wKT values.

Conclusion

In the posterior mandible, VRA using both techniques provides stable PBLs up to 3 years. A correct soft tissue management and a strict professional oral hygiene protocol play a crucial role on peri-implant health over time.
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Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center

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Abstract

Background and aims

Data on the outcome and prognostic indicators in extracranial relapsed/refractory germ cell tumors (rel/ref-GCTs) in children are limited to a few studies. This study looks at remission rates and outcomes of rel/ref-GCTs treated with conventional salvage chemotherapy (SC) regimens without stem cell rescue at a single center in the developing world.

Methods

Patients treated at our center from January 2009 to December 2018 were included. Risk at primary presentation was stratified as all completely excised teratomas and stage I gonadal tumors being low risk (LR); stage IV ovarian, stage III–IV extragonadal GCTs as high risk (HR), and the remaining as intermediate risk (IR). SC regimens were: vinblastine–ifosfamide–cisplatin/carboplatin or paclitaxel–ifosfamide–cisplatin/carboplatin, or cisplatin/carboplatin–etoposide–bleomycin. Local therapy was either surgery and/or radiotherapy.

Results

The analyzable cohort comprised 50 patients (44 = rel-GCTs; 6 = ref-GCTs) with a median age of 3.8 years and male:female ratio of 1.27:1. Primary location was ovary in 16 (32%), testicular in 10 (20%), and extragonadal in the rest (48%). Local, metastatic, and combined progression was noted in 28 (56%), 14 (28%), and eight (16%) patients, respectively, at a median time of 8.5 months. At a median follow-up of 60 months, the 5-year event-free survival (EFS) and overall survival (OS) of the entire cohort (n = 50) were 42.4% and 50.0%, respectively. In patients previously exposed to platinum analogs (n = 38), 5-year-EFS and OS were 27.7% and 31.7%, respectively. Local relapses did better when compared to metastatic and combined relapses (5-year EFS: 64% vs. 23% vs. 0%; p = .009). LR and IR tumors did better compared to HR (5-year EFS: 81.5% vs. 49.3% vs. 6.5%; p = .002). Patients with normalization of t umor markers after two cycles had a superior EFS (57.6% vs. 0%; p < .001). Relapsed tumors fared better than primary refractory GCTs (5-year EFS: 48.6% vs. 0%; p < .001).

Conclusions

Primary refractory GCTs, extragonadal rel-GCTs, and rel/ref-GCTs with a poor biochemical response did poorly with conventional SC and need alternative treatment strategies. The rel/ref-testicular GCTs had the best chance of salvage despite a second recurrence (5-year EFS and OS: 28.60% and 42.90%, respectively).
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Efficacy of carbon dioxide laser and caustic agent cauterisation for the focal granular myringitis: a randomised trial

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Abstract

Objectives

Granular myringitis (GM) is a troublesome disease with a high incidence of recurrence and relapse. CO2 laser vaporisation and trichloroacetic acid (TAA) have been applied in treating several otological diseases, both with favorable therapeutic efficacy. However, long-term therapeutic efficacy of both CO2 laser vaporisation and TAA cauterisation against GM have not yet been evaluated. We aimed to investigate the therapeutic potential of CO2 laser vaporisation and TAA cauterisation in GM management.

Study Design

Prospective, randomised study

Participants

A total of 88 GM patients who failed therapy with boric acid, alcohol, and glycerin ear drop (BAAG) otic solution between July 2009 and January 2018 were included. Participants were randomly assigned to receive CO2 laser vaporisation (n = 39) or TAA cauterisation (n = 49).

Main outcome measures

Main outcomes were treatment success, complications after four months of treatment, and recurrence within 4-12 months after treatment.

Results

The success rate was significantly higher in the CO2 group than in the TAA group (94.9% vs. 77.6%, p=0.023). After four months of treatment, the GM recurrence rate was comparable between the two groups (13.5% vs. 18.4%, p=0.562). The CO2 laser group had one case of perforation and one case of severe vertigo, while one participant in the TAA cauterisation group experienced hearing loss.

Conclusion

Both TAA cauterisation and CO2 laser vaporisation are safe and effective treatments for GM. The success rate of CO2 laser vaporisation for treating GM is higher than that of TAA cauterisation. Recurrence rates are comparable within one year.

This article is protected by copyright. All rights reserved.
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Functional and Symmetry Outcomes After Forehead Flap Reconstruction of Medial Peri‐Ocular Defects

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Functional and Symmetry Outcomes After Forehead Flap Reconstruction of Medial Peri-Ocular Defects

Orbital defects have a profound impact on orbital function and symmetry of the face and are difficult to reconstruct given the complexity of this area. The paramedian forehead flap is feasible for medial periorbital reconstruction with acceptable functional and symmetrical outcomes and low morbidity.


Background

Orbital defects have a profound impact on orbital function and symmetry of the face and are difficult to reconstruct given the complexity of this area. The paramedian forehead flap (PMFF) has not been well studied in reconstruction of orbital defects.

Methods

Retrospective review of patients who underwent reconstruction of periorbital defects with PMFF between 2016 and 2021. Variables were ocular adnexal asymmetry, functional outcomes, and orbital complications.

Results

Eighteen patients met inclusion criteria. Mean defect size was 11.1 ± 7.5 cm. The most common subsite involved was medial canthus in 88.9% of patients. There was no statistically significant difference between mean medial canthus to midline ratio and mean medial brow to midline ratio when compared to the assumed normal of 1. The medial canthus to pupil ratio and medial canthus to lateral canthus ratio had a statistically significant mean difference from 1.0 (p = 0.003 for both). In 22.2% of patients, the orbit was functional with impairment; the remaining had no impairment. Surgical sequelae occurred in 12/18 (66.7%) of patients, most commonly epiphora in 9/18 (50%) of patients, and ectropion in 5/18 (27.7%).

Conclusion

The PMFF is feasible for medial periorbital reconstruction with acceptable functional and symmetrical outcomes and low morbidity.

Level of Evidence

4 Laryngoscope, 2023
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Exogenous fetuin‐A protects against sepsis‐induced myocardial injury by inhibiting oxidative stress and inflammation in mice

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Abstract

Sepsis-induced myocardial injury is a consequence of septicemia and is one of the major causes of death in intensive care units. A serum glycoprotein called fetuin-A is secreted largely by the liver, tongue, placenta, and adipose tissue. Fetuin-A has a variety of biological and pharmacological properties. The anti-inflammatory and antioxidant glycoprotein fetuin-A has shown its efficacy in a number of inflammatory disorders including sepsis. However, its protective role against sepsis-induced myocardial injury remains elusive. The purpose of this work is to explore the role of fetuin-A in mouse models of myocardial injury brought on by cecal ligation and puncture (CLP). CLP significantly induced the myocardial injury assessed in terms of elevated myocardial markers (serum CK-MB, cTnI levels), inflammatory markers (IL-6, TNF-α) in the serum, and oxidative stress markers (increased MDA levels and decreased reduced glutathione) in heart tissue homogenate following 24 hours of ligati on and puncture. Further, hematoxylin and eosin (H&E) staining showed considerable histological alterations in the myocardial tissue of sepsis-developed mice. Interestingly, fetuin-A pretreatment (50 and 100 mg/kg) for four days before the CLP procedure significantly improved the myocardial injury and was evaluated in perspective of a reduction in the CK-MB, cTnI levels, IL-6, and TNF-α in sepsis-developed animals. Fetuin-A pretreatment significantly attenuated the oxidative stress and improved the myocardial morphology in a dose-dependent manner. The present study provides preliminary evidence that fetuin-A exerts protection against sepsis-induced cardiac dysfunction in vivo via suppression of inflammation and oxidative damage.
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Transmission routes and patterns of helicobacter pylori

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Abstract

Background and objective

Helicobacter pylori (H. pylori), a gram-negative bacterium that colonizes the stomach, can cause chronic gastritis and peptic ulcers, as well as gastric cancer as a Class I carcinogen. However, the modes of H. pylori transmission are not clear. This review aims to clarify the transmission routes and patterns of H. pylori and identify efficacious prevention measures.

Methods

Studies of H. pylori transmission were identified using PubMed, the Web of Science, and Cochrane Central; the retrieval deadline was October 2022.

Results

The transmission routes of H. pylori are discussed, focusing on the five primary transmission routes, namely fecal–oral, oral–oral, gastric–oral, anal–oral, and genital–oral. We propose that H. pylori is contracted through multiple transmission routes. Additionally, we summarize the key transmission patterns of H. pylori, including person-to-person and animal-to-human transmission, as well as foodborne and occupational exposure.

Conclusion

Fecal–oral appears to be the most common H. pylori transmission routes. Although the oral–oral pathway is also important, the evidence does not support that this route of transmission is universal. The gastric–oral route occurs primarily in children and patients who are prone to vomiting. Meanwhile, the anal–oral and genital–oral routes remain hypothetical. Person-to-person and foodborne infections represent the predominant transmission patterns of H. pylori, whereas strong environmental and occupational limitations are associated with animal-to-human and occupational exposure.
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Cardia and non‐cardia gastric cancer risk associated with Helicobacter pylori in East Asia and the West: A systematic review, meta‐analysis, and estimation of population attributable fraction

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objectives

To assess the region-specific relative risk of cardia/non-cardia gastric cancer (CGC/NCGC) associated with Helicobacter pylori (H. pylori) and quantify its contribution to gastric cancer burden using population attributable fraction (PAF).

Methods

PubMed, EMBASE, Web of Science, and Cochrane Central databases were searched by two reviewers until April 20, 2022. The association between H. pylori infection and NCGC/CGC was assessed using pooled odds ratios (ORs) with 95% confidence intervals (CIs). PAF was calculated using the formula of H. pylori prevalence and the pooled OR.

Results

One hundred and eight studies were included. A significant association was observed between H. pylori infection and NCGC in East Asia (OR, 4.36; 95% CI: 3.54–5.37) and the West (OR, 4.03; 95% CI: 2.59–6.27). Regarding CGC, a significant association was found only in East Asia (OR, 2.86; 95% CI: 2.26–3.63), not in the West (OR, 0.80; 95% CI: 0.61–1.05). For studies with a follow-up time of ≥10 years, pooled ORs for NCGC and CGC in East Asia were 5.58 (95% CI: 4.08–7.64) and 3.86 (95% CI: 2.69–5.55), respectively. Pooled OR for NCGC was 6.80 (95% CI: 3.78–12.25) in the West. PAFs showed that H. pylori infection accounted for 71.2% of NCGC, 60.7% of CGC in East Asia, and 73.2% of NCGC in the West.

Conclusions

Gastric cancer burden associated with H. pylori infection exhibits important geographical differences. Prolonged follow-up period could overcome the underestimation of the magnitude of the association between H. pylori infection and CGC/NCGC. Customized strategies for H. pylori screening and eradication should be implemented to prevent gastric cancer.
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