Κυριακή 14 Νοεμβρίου 2021

A randomised trial of single or extended dosing ciprofloxacin versus no intervention for Prevention of Ventilation Tube Otorrhoea and Obstruction (PreVenTO2)

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Abstract

Objectives

To determine the effectiveness of ciprofloxacin 0.3% antibiotic eardrops in preventing clinically significant postoperative otorrhoea and tube obstruction following grommet insertion in children.

Design

3-arm parallel assessor-blinded randomised controlled trial. Randomisation in 1:1:1 ratio to single intraoperative application of ciprofloxacin drops, extended 5-day postoperative application and no drops. Patients were assessed by blinded assessors at 6 weeks postoperatively.

Setting

The study was conducted in a large tertiary health network in Melbourne, Australia.

Participants

All children, 17 years and under, undergoing bilateral MEVT surgery with or without concurrent upper airway surgery for recurrent acute otitis media and chronic otitis media with effusion were approached.

Main Outcome Measures

Presence of postoperative otorrhoea and ventilation tube obstruction at 6 weeks postoperatively.

Results

256 paediatric patients completed the study with a median age of 4.02 years. 153 participants were male. By ear-analysis (n=512) showed intraoperative antibiotics were more effective than no drops in preventing otorrhoea (RR=0.341, 95%CI 0.158–0.738, NNT= 11.25, p=.006). Postoperative antibiotics were more effective than no drops in preventing ventilation tube obstruction (RR=0.424, 95%CI 0.193 to 0.930, NNT=14.7 p=.032).

Conclusion

Intraoperative topical ciprofloxacin was effective at preventing early postoperative otorrhoea and a prolonged course was effective at preventing ventilation tube obstruction. Future studies on this topic should seek to clarify whether particular subgroups of patients benefit more from prophylactic topical antibiotics and model for cost-effectiveness.

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Pneumatosis intestinalis associated with lenvatinib during thyroid cancer treatment: a case report

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J Med Case Rep. 2021 Nov 12;15(1):556. doi: 10.1186/s13256-021-03158-w.

ABSTRACT

BACKGROUND: Pneumatosis intestinalis is a rare disease characterized by gas-filled cysts within the submucosa or serosa of the intestinal tract. In recent years, pneumatosis intestinalis was reported in patients undergoing cancer treatment, and some case reports exist that report that pneumatosis intestinalis occurs during administration of vascular endothelial growth factor inhibitors, such as bevaciz umab and sunitinib. Here, we report the first case of pneumatosis intestinalis during lenvatinib treatment.

CASE PRESENTATION: A 77-year-old Japanese man presented to our hospital with a chief complaint of numbness in the right leg and weakness of the lower limbs 9 years after right thyroid lobectomy. Computed tomography showed a tumor 90 mm in size from the lumbar spine to the sacrum, causing spinal cord compression. Blood tests showed that the patient's thyroglobulin level was increased to 11,600 ng/ml. We diagnosed him with thyroid cancer with bone metastases. External beam radiotherapy (39 Gy/13 Fr) was performed on the bone metastases, followed by total thyroidectomy and radioactive iodine therapy. Four months after radioactive iodine therapy, lenvatinib was introduced because the symptoms of numbness and weakness recurred. Lenvatinib was introduced at dose of 24 mg, and then it was reduced to 14 mg owing to Common Terminology Criteria for Adverse Event grade 3 paronychia of the right foot. Although no further significant adverse events occurred, a scheduled computed tomography image showed pneumatosis intestinalis of the ascending colon 14 weeks after the introduction of lenvatinib. No abdominal or digestive symptoms were observed; therefore, we selected conservative treatment. We discontinued lenvatinib for a week, but we were required to restart lenvatinib as the numbness in the right leg worsened after withdrawal. Since the introduction of lenvatinib, 3 years and 5 months passed; we continued lenvatinib treatment, and the therapeutic effect remains partial response. There has been no recurrence of pneumatosis intestinalis.

CONCLUSIONS: Although rare, it is important to recognize that pneumatosis intestinalis can occur in association with lenvatinib and should be differentiated from intestinal perforation. Pneumatosis intestinalis association with lenvatinib can be improved by withdrawal.

PMID:34763724 | DOI:10.1186/s13256-021-03158-w

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Demographic, anthropometric, and metabolic characteristics of obstructive sleep apnea patients from Romania before the COVID-19 pandemic

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Exp Ther Med. 2021 Dec;22(6):1487. doi: 10.3892/etm.2021.10922. Epub 2021 Oct 26.

ABSTRACT

Obstructive sleep apnea (OSA) syndrome is one of the major pathologies of modern life, with multiple etiologies intertwining: the increase in life expectancy, facial and dental changes, metabolic syndrome, and others. The current diagnosis is based on sleep studies, flexible endoscopy, imaging studies and a complete differential diagnosis from other possible pathologies. We present a retrospective study of 80 cases with OSA managed in 2019 prior to the beginning of the COVID-19 pandemic. We analyzed various demographic, anthropometric and metabolic data recorded in our study group. Some of the results, such as high levels of cholesterol and triglycerides, were consistent with worldwide literature. However, regarding the anthropometric data, we underline a general decrease in height in the Romanian population. In addition, demographic data have ch anged in the last decade due to the work immigration in the European Union. This data will be used in a future analysis for comparison with variables recorded from cases with OSA during the COVID-19 pandemic. Current cases with OSA are not a priority for healthcare systems, and patients avoid referral to a specialist as much as possible.

PMID:34765028 | PMC:PMC8576615 | DOI:10.3892/etm.2021.10922

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Environmental allergens house dust mite-induced asthma is associated with ferroptosis in the lungs

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Exp Ther Med. 2021 Dec;22(6):1483. doi: 10.3892/etm.2021.10918. Epub 2021 Oct 26.

ABSTRACT

Previous studies have indicated that allergens such as house dust mites (HDM) in the environment can induce allergic asthma. Ferroptosis is a newly discovered form of regulatory cell death characterized by aberrant lipid peroxidation and the accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological process of asthma remains to be elucidated. The present study used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and its underlying mechanisms. Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation, mucus secretion, IgE levels, cytokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mi tochondria, ROS levels, glutathione (GSH) levels and changes in ferroptosis pathway proteins were also determined in murine lungs. As a result, HDM exposure significantly increased AHR, inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE levels in the BALF, lung eosinophilia and a concomitant increase in IL-13 and IL-5 levels in BALF were observed. HDM inhalation increased ROS and decreased GSH levels in the lungs. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blotting demonstrated that the activities of glutathione peroxidase 4 and catalytic subunit solute carrier family 7 member 11 were significantly decreased, and that protein expression levels of acyl-CoA synthetase long-chain family member 4 and 15 lipoxygenase 1 were upregulated compared with mice in the normal control group. Overall, these results indicated that the AHR, airway inflammation, lipid peroxidation and ROS levels increased in HDM-induced asthma, and that HDM inhalation induced ferroptosis in the lungs, which helped to form an improved understanding of the pathogenesis of allergic asthma.

PMID:34765024 | PMC:PMC8576623 | DOI:10.3892/etm.2021.10918

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Epigenetic approaches for cervical neoplasia screening (Review)

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Exp Ther Med. 2021 Dec;22(6):1481. doi: 10.3892/etm.2021.10916. Epub 2021 Oct 25.

ABSTRACT

Human papillomavirus (HPV) infection is the leading cause of cervical cancer. The Papanicolaou cytology test is the usually employed type of screening for this infection; however, its sensibility is limited. Only a small percentage of women infected with high-risk HPV develop cervical cancer with an array of genetic and epigenetic modifications. Thus, it is necessary to develop rapid, reproducible and minimally invasive technologies for screening. DNA methylation has gained attention as an alternative method for molecular diagnosis and prognosis in HPV infection. The aim of the present review was to highlight the potential of DNA methylation in cervical neoplasia screening for clinical applications. It was observed that the methylation human and viral genes was correlated with high-grade lesions and cancer. Methylation biomarkers have shown a goo d capacity to discriminate between high-grade lesions with a transformative potential and cervical cancer, being able to detect these modifications at an early stage. With further research, the epigenetic profiles and subtypes of the tumors could be elaborated, which would aid in therapy selection by opening avenues in personalized precision medicine. Response to therapy could also be evaluated through such methods and the accessibility of liquid biopsies would allow a constant monitoring of the patient's status without invasive sampling techniques.

PMID:34765022 | PMC:PMC8576616 | DOI:10.3892/etm.2021.10916

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Effects of hydroxyapatite extract on rats with transient ischemia: Long-term potentiation and axon regeneration

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Exp Ther Med. 2021 Dec;22(6):1486. doi: 10.3892/etm.2021.10921. Epub 2021 Oct 26.

ABSTRACT

Hydroxyapatite (HA) has been extensively used as a reconstructive and prosthetic material for osseous tissue. The present study aimed to determine whether HA extract exerted effects on central nervous system injury following transient cerebral ischemia/reperfusion in rats. Male Wistar rats were treated with HA following bilateral common carotid artery clamping (two-vessel occlusion). The results demonstrated that treatment with HA extract attenuated the inhibition of long-term potential in a rat model of transient cerebral ischemia/reperfusion. Furthermore, HA extract improved axon regeneration, which was confirmed via the immunohistochemical analysis of growth associated protein 43 and glial fibrillary acidic protein. Taken together, the results of the present study provided preliminary evidence of the protective effect of HA on neuronal damage.

PMID:34765027 | PMC:PMC8576626 | DOI:10.3892/etm.2021.10921

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Heat-induced antigen retrieval in fluorescence in situ hybridization: An effective approach enhancing signal intensity in poor-quality FFPE sections

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Exp Ther Med. 2021 Dec;22(6):1480. doi: 10.3892/etm.2021.10915. Epub 2021 Oct 25.

ABSTRACT

Fluorescence in situ hybridization (FISH) serves as an ancillary tool for assessing chromosomal abnormalities and is important in differential diagnoses and treatment decisions. In clinical practice, pathologists encounter unsatisfactory formalin-fixed paraffin-embedded (FFPE) sections exhibiting weak fluorescence signals, mostly due to inappropriate tissue processing or preservation, leading to interpretation difficulties. For the present study, FFPE samples for which conventional FISH failed were collected. Instead of a pretreatment step using a commercial kit, heat-induced antigen retrieval (HIAR) was introduced using either citrate buffer or Tris-EDTA buffer, while the subsequent experimental workflow remained unchanged. After HIAR-assisted FISH, the hybridization efficiency and signal intensity were markedly enhanced and no difference in signal adequacy was observed when comparing the effect of the two AR solutions. The present study demonstrated that HIAR is a reliable tool for FISH, particularly for poor-quality FFPE sections yielding weak or no fluorescence signals in the conventional analysis.

PMID:34765021 | PMC:PMC8576618 | DOI:10.3892/etm.2021.10915

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FOXO1: a pivotal pioneer factor in oral squamous cell carcinoma

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Am J Cancer Res. 2021 Oct 15;11(10):4700-4710. eCollection 2021.

ABSTRACT

The transcription factor FOXO1 regulates cell cycle progression, apoptosis and oxidative stress. Interestingly, numerous studies have implicated their positive role in tumor suppression, angiogenesis and metastasis in oral squamous cell carcinoma (OSCC). Distinct post-transcriptional and post-translational modifications actuate the physiological role of FOXO1 in OSCC. Here, we evaluate the role of FOXO1 proteins in OSCC, their fundamental structure and the major players involved in FOXO1 regulation and how they are Pharmacologically modulated in OSCC. Finally, their role in regulating epithelial-mesenchymal transition (EMT), autophagy, stress tolerance and stemness, which would significantly aid in novel potential oversight for future research and thus developing strategies to prevent or reverse OSCC.

PMID:34765288 | PMC:PMC8569351

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Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study

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Am J Cancer Res. 2021 Oct 15;11(10):4966-4980. eCollection 2021.

ABSTRACT

To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA- GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.

PMID:34765304 | PMC:PMC8569355

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PD-1 antibody camrelizumab for Epstein-Barr virus-positive metastatic gastric cancer: a single-arm, open-label, phase 2 trial

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Am J Cancer Res. 2021 Oct 15;11(10):5006-5015. eCollection 2021.

ABSTRACT

Gastric cancer (GC) patients with Epstein-Barr virus (EBV) positivity have demonstrated promising response with immunotherapy. We assessed the efficacy and safety of camrelizumab as salvage treatment in EBV-positive mGC. In this single-arm, phase 2 prospective clinical trial (NCT03755440), stage IV EBV-positive GC patients who failed/could not tolerate previous lines of chemotherapy were given intravenous camrelizumab 200 mg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response, and toxicity. Exploratory analysis included the associations between treatment response and tumor mutation burden (TMB), programmed cell death ligand-1 (PD-L1) expression. Six eligible patients were enrolled in the first stage of the study. No patient achieved an objective response; thus, the study did not proceed to the second stage. The DCR was 67% (4/6). The median PFS rate was 2.2 months (95% CI: 1.5-not reached [NR]) and median OS was 6.8 months (95% CI: 1.7-NR). All treatment-related adverse events were grade 1-2, with reactive cutaneous capillary endothelial proliferation (n=4 [67%]) being the most commonly observed event. The only patient with PD-L1 combined positive score >1 had disease progression. Two stable disease and one disease progression were observed in three patients with TMB >10 Mut/Mb. EBV positivity may not be a good predictor for response to camrelizumab in mGC. Newer biomarkers are needed to identify EBV-positive mGC respondents who might benefit from immunotherapy.

PMID:34765307 | PMC:PMC8569350

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Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy

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Am J Cancer Res. 2021 Oct 15;11(10):5190-5213. eCollection 2021.

ABSTRACT

DDX5 (p68) is a well-known multifunctional DEAD-box RNA helicase and a transcription cofactor. Since its initial discovery more than three decades ago, DDX5 is gradually recognized as a potential biomarker and target for the treatment of various cancer types. Studies over the years significantly expanded our understanding of the functional diversity of DDX5 in various cancer types and extended our knowledge of its Mechanism of Action (MOA). This provides a rationale for the development of novel cancer therapeutics by using DDX5 as a biomarker and a therapeutic target. However, while most of the published studies have found DDX5 to be an oncogenic target and a cancer treatment-resistant biomarker, a few studies have reported that in certain scenarios, DDX5 may act as a tumor suppressor. After careful review of all the available relevant studies in the literature, we found that the multiple functions of DDX5 make it both a superior independent oncogenic biomarker and target for targeted cancer therapy. In this article, we will summarize the relevant studies on DDX5 in literature with a careful analysis and discussion of any inconsistencies encountered, and then provide our conclusions with respect to understanding the MOA of FL118, a novel small molecule. We hope that such a review will stimulate further discussion on this topic and assist in developing better strategies to treat cancer by using DDX5 as both an oncogenic biomarker and therapeutic target.

PMID:34765320 | PMC:PMC8569338

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