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

alexandrossfakianakis shared this article with you from Inoreader A real‐world exploratory study on the feasibility of vonoprazan and tetracycline dual therapy for the treatment of Helicobacter pylori infection in special populations with penicillin allergy or failed in previous amoxicillin‐containing therapies via Helicobacter 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. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double strand break repair and augments efficacy of temozolomide in glioblastoma

alexandrossfakianakis shared this article with you from Inoreader Lysine-specific histone demethylase 1A (KDM1A/LSD1) inhibition attenuates DNA double strand break repair and augments efficacy of temozolomide in glioblastoma via Neuro-Oncology Advance Access 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. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus

alexandrossfakianakis shared this article with you from Inoreader Cholinergic Boutons are Distributed Along the Dendrites and Somata of VIP Neurons in the Inferior Colliculus via JARO - Journal of the Association for Research in Otolaryngology via MedWorm.com 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... View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

alexandrossfakianakis shared this article with you from Inoreader 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 via Clinical Implant Dentistry and Related Research 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. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Genomic profiling and precision medicine in complex ameloblastoma

alexandrossfakianakis shared this article with you from Inoreader Genomic profiling and precision medicine in complex ameloblastoma via Head & Neck Abstract Background Ameloblastoma may present a significant treatment challenge in the locally advanced, recurrent and metastatic setting. Comprehensive genomic profiling (CGP) can identify targetable genomic alterations to aid in treatment. Methods Ameloblastoma samples were sequenced using hybrid-capture based sequencing. A systematic literature review was performed to examine outcomes in studies employing targeted treatment in ameloblastoma. Results We reviewed 14 cases of Ameloblastoma using CGP. There were six patients with activating BRAF mutations, five with PIK3CA, five with SMO, four with FGFR2, one with EGFR, and one with ROS1. All cases were MSI stable and the median TMB was 2.5 mutations/Mb. A separate literature review of clinical outcomes in ameloblastoma showed a predominance of at least partial response to targeted treatment (7/12 cases). Conclusion CGP is helpful in identifying specific driver mutations in patients with complex ameloblastoma. Targeted treatment has been employed with success in achieving treatment response. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of carbon dioxide laser and caustic agent cauterisation for the focal granular myringitis: a randomised trial

alexandrossfakianakis shared this article with you from Inoreader Efficacy of carbon dioxide laser and caustic agent cauterisation for the focal granular myringitis: a randomised trial via Clinical Otolaryngology 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. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

alexandrossfakianakis shared this article with you from Inoreader Functional and Symmetry Outcomes After Forehead Flap Reconstruction of Medial Peri‐Ocular Defects via The Laryngoscope 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 View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Transmission routes and patterns of helicobacter pylori

alexandrossfakianakis shared this article with you from Inoreader Transmission routes and patterns of helicobacter pylori via Helicobacter 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. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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 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 via Helicobacter 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. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Addressing adherence to guidelines on prevention of acute chemotherapy‐induced nausea and vomiting in pediatric patients

alexandrossfakianakis shared this article with you from Inoreader Addressing adherence to guidelines on prevention of acute chemotherapy‐induced nausea and vomiting in pediatric patients via Pediatric Blood & Cancer Abstract Background Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect in children receiving cancer treatment. There are evidence-based pediatric clinical practice guidelines (CPG) on chemotherapy emetogenicity and acute CINV prevention, but adherence to these guidelines is low. Procedure A quality improvement-based study was conducted at McMaster Children's Hospital. The SMART aim was to increase adherence to guidelines on prevention of acute CINV in hospitalized patients receiving high (HEC) and moderately emetogenic chemotherapy (MEC) from baseline 25% to more than 70% by June 2021. Barriers were identified by process mapping, and a series of interventions were implemented. Results Guideline adherence was assessed in 270 inpatient chemotherapy administrations (HEC, MEC). Data were collected on 131 charts pre interventions and 139 charts post interventions. Interventions included education, addition of guideline-recommended anti-emetics to the inpatient formulary, and implementation of a standardized CPG tool. Initial rates of total CINV guideline adherence were 25%, which improved to 72% post intervention (p < .001). In subgroup analysis, guideline adherence in the MEC group improved from 13% to 34% (p = .015), and in the HEC group from 32% to 93% (p < .001). The most common reason for nonadherence in the HEC group was failure to use aprepitant as anti-emetic, and in MEC was option for ondansetron monotherapy prophylaxis. Conclusion Using quality improvement methodology, barriers to guideline adherence were identified and interventions implemented. Guideline adherence for prevention of CINV improved, particularly in the HEC group but less for the MEC group. Future steps will include sustainability of interventions and addressing adherence in the MEC group. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.