Monday, August 15, 2022

Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: a POLA network study

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Abstract
Background
Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described.
Methods
We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (with or without chemotherapy), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n=200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n=543) based on progression free survival before and after first progression.
Results
In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after radiotherapy. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted in the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after radiotherapy. The only factor associated with pseudoprogression occurrence was adjuvant PCV chemotherapy. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions.
Conclusion
In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after radiotherapy, the possibility of a pseudoprogression should be carefully considered.
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Occupational Exposure to β-d-Glucans, Mould Allergens, Endotoxins and Cultivable Fungi in Pig Farms

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Abstract
Airborne concentrations of organic dust on animal farms are known to be very high. This dust is partly composed of microorganisms such as bacteria, fungi and their components [endotoxins, (1→3)-β-d-glucans, mould allergens, mycotoxins], recognised as being responsible for numerous health effects. Several cross-sectional studies have measured levels of airborne bacteria, fungi and endotoxins on pig farms. However, the temporal dynamics of organic dust's components throughout the year have rarely been assessed, and airborne concentrations of (1→3)-β-d-glucans and mould allergens remain poorly understood in these work environments. This longitudinal, four-season study measured cultivable fungi, endotoxins, (1→3)-β-d-glucans, Aspergillus versicolor (AveX), Aspergillus fumigatus (Asp f1) and Alternaria sp (Alt a1) allergens on 31 pig farms in Switzerland. Results showed that exposure to AveX occurred in all four seasons. Total mean airborne concentration of endotoxins were between 3 and 4 times higher than the Swiss recommended limit value of 1000 EU m-3 and mean airborne concentrations of fungi were between 30 and 50 times higher than the Swiss recommended limit value of 1000 cfu m-3. Finally, accumulations of faecal matter on floors, humidity and dusty pathways were associated with increased c oncentrations of (1→3)-β-d-glucans. In conclusion, pig farmers require better information about biological occupational risks, and measures to improve air quality should be implemented, especially in winter.
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Optimized dual therapy for treatment‐naive patients of Helicobacter pylori infection: A large‐scale prospective, multicenter, open‐label, randomized controlled study

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Abstract

Background

The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection.

Materials and Methods

The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared.

Results

Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%–91.9%), 84.4% (95% CI 80.0%–88.3%), and 86.7% (95% CI 82.4%–90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%–93.3%), 85.5% (95% CI 81.1%–89.2%), and 87.8% (95% CI 83.6%–91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%–93.5%), 85.8% (95% CI 81.4%–89.5%), and 88.3% (95% CI 84.1%–91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% i n groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar.

Conclusions

Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

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A state-of-the-science review and guide for measuring environmental exposure biomarkers in dried blood spots

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Helicobacter pylori results in lysis and death after exposure to water

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Abstract

Background

Helicobacter pylori has a high infection rate, and it is possible that more than half of the world's population is infected. The route of transmission of H. pylori has not been completely elucidated yet. The coccoid form of H. pylori is generally considered to be in a VBNC (viable but nonculturable) state, and this form in the environment is thought to play an important role in infection and transmission, but its stability and survivability are still unknown.

Materials and methods

In order to promote its changing to coccoid form, the spiral form of H. pylori grown in a culture medium was exposed to sterile distilled water, and we investigated the bacterial cell number and the morphological changes by using fluorescence staining methods and electron microscopic observation. We also examined the dynamics of its growth ability by measuring the colony forming unit on an agar-plate medium.

Results

After exposure to sterile distilled water, the H. pylori spiral form rapidly lost its growth ability at 37°C. One day after exposure, approximately 95% of the spiral form disappeared and the proportion of the coccoid form increased. The total number of bacteria also decreased to less than half and continued to decrease over time. Epi-microscopic and electron microscopic observations revealed that deformation of bacterial cells, collapse, and leaking out of cell contents were promoted in exposure to sterile distilled water.

Conclusion

Helicobacter pylori quickly begins to transform into the coccoid form after exposure to sterile distilled water, rapidly loses its growth ability, and then lyses and dies. Water-exposure is lethal for H. pylori and it is unlikely to survive in the VBNC state in water.

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A Mediterranean and Low‐Fat dietary intervention in Non‐Alcoholic Fatty Liver Disease patients ‐Exploring participant experience and perceptions about dietary change.

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Abstract

Background

A Mediterranean Diet (MD) appears to be beneficial in NAFLD patients in Mediterranean countries, however the acceptability of a MD in non-Mediterranean populations has not been thoroughly explored. This study aimed to explore the acceptability, through understanding the barriers and enablers of MD and low-fat diet (LFD) interventions as perceived by Australian adults from multicultural backgrounds, with NAFLD, who participated.

Methodology

Semi-structured telephone interviews were performed with 23 NAFLD trial participants at the end of a 12-week dietary intervention in a multicentre, parallel, randomised clinical trial. Data was analysed using thematic analysis.

Results

Participants reported that they enjoyed taking part in the MD and LFD interventions and perceived that they had positive health benefits from their participation. Compared to the LFD, the MD group placed greater emphasis on enjoyment and intention to maintain dietary changes. Novelty, convenience and the ability to swap food/meals were key enablers for the successful implementation for both of the dietary interventions. Flavour and enjoyment of food, expressed more prominently by MD intervention participants, were fundamental components of the diets with regard to reported adherence and intention to maintain dietary change.

Conclusions

Participants randomised to the MD reported greater acceptability of the diet than those randomised to the LFD, predominantly related to perceived novelty and palatability of the diet.

This article is protected by copyright. All rights reserved.

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ImmunoModulatory Effect of IL‐35 Gene Transfected Mesenchymal Stem Cells on Allergic Asthma

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Abstract

Asthma is a common respiratory disease which has no definitive treatment at now. Immune response shifting from T helper (Th)1 to the Th2 is a main problem in asthma, and immunomodulation can help to control asthma. IL-35 and Mesenchymal Stem Cells (MSCs) have regulatory effect on the immune system, and may have the ability to control asthma pathology.

After culturing MSCs, expression vector of IL-35 (pUNO1-mIL35elasti) was transduced to the MSCs and then, asthmatic mice were treated with MSCs, MSCs-vector, MSCs-vector-IL-35 and no treatment. AHR, levels of the cytokines, total and OVA specific immunoglobulin (Ig)E, LTB4, and LTC4 were measured. Lung tissue histopathology was also done.

MSCs were successfully transduced by pUNO1-mIL35elasti vector, and IL-35 was produced in transduced cells. AHR, levels of the Cytokines, IgEs, LTs, goblet cell hyperplasia, mucus secretion, peribronchial and perivascular inflammation were controlled by MSCs therapy. In MSCs-IL-35 group, these controls were stronger than MSCs without IL-35 group.

MSCs had strong effect on control of asthma. Transfected MSCs by expressing IL-35 gene could significantly better control allergic asthma symptoms than MSCs without IL-35. In the future, identification of the IL-35 mechanism of action would be useful to improve cytokine-cell based therapies.

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Risk Factors for Post‐Tonsillectomy Respiratory Events in Children With Severe Obstructive Sleep Apnea

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Risk Factors for Post-Tonsillectomy Respiratory Events in Children With Severe Obstructive Sleep Apnea

This is a retrospective single-institution cohort study of pediatric patients with severe obstructive sleep apnea who were admitted postoperative after tonsillectomy. We identified multiple potential risk factors for postoperative respiratory events including Black ethnicity, Down syndrome, age, %sleep time with SpO2 <90% on sleep study.


Objectives/Hypothesis

To identify risk factors for postoperative respiratory events in pediatric patients with severe obstructive sleep apnea (OSA).

Methods

Retrospective single-institution retrospective cohort study of pediatric patients with severe OSA who were admitted postoperatively after tonsillectomy. Patients who experienced respiratory events after surgery were identified and differences between the respiratory event and no event groups were compared.

Results

There were 887 patients included in this study. 14.8% (n = 131) experienced a documented respiratory event. The following risk factors were found to be most significant: %sleep time with O2 < 90% (tb90) (95% CI = 1.07–1.14, OR = 1.10, p < 0.001), Black race (95% CI = 1.53–3.58, OR = 2.34, p < 0.001), primary neurologic co-morbidity (1.67–6.32, OR = 3.27, p < 0.001), Down syndrome (1.25–5.94, OR = 2.72, p = 0.01), and age (0.84–0.94, OR = 0.88, p < 0.001). Regression modeling demonstrated that the rate of respiratory events increased with tb90.

Conclusions

Our results demonstrate that there are other potential risk factors outside of AHI and O2 nadir that are associated with respiratory events after tonsillectomy. Black race and prolonged desaturations during polysomnography (PSG) are independent risk factors. Measures of abnormal gas exchange on PSG may be better at identifying at risk patients.

Level of Evidence

4 Laryngoscope, 2022

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Perioperative Blood Transfusion in Head and Neck Cancer Revisited

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Perioperative Blood Transfusion in Head and Neck Cancer Revisited

In the past, blood transfusions in head and neck cancer patients were associated with high rates of complications and mortality. This retrospective study of 590 patients with surgical treatment of incident HNC was performed to identify transfusion triggers and analyze survival rates of transfused patients in times of restrictive transfusion regimens. During a time span of 10 years, 37 patients received blood transfusions, triggers were a high ASA score, low preoperative hemoglobin levels, long duration of surgery and p16 negativity, survival of transfused and matched non transfused patients was similar.


Objective

To reevaluate the frequency of perioperative blood transfusion, transfusion triggers, and survival impact in patients with incident, surgically treated head and neck cancer (HNC) in restrictive transfusion regimens.

Methods

Retrospective analysis of surgically treated patients with incident HNC with and without perioperative blood transfusion between 2008 and 2019 at the Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, according to the department's clinical Head and Neck Tumor Registry.

Results

Of the 590 patients included, perioperative transfusions were administered in 6.3% (n = 37, transfusion group). Following multivariable logistic regression, likelihood of blood transfusions was increased in patients with poorer general health conditions (ASA score III/IV; OR 3.7; 95% CI 1.9–8.6; p = 0.002), hemoglobin <12.5 g/dL (OR 2.7; 95% CI 1.1–6.4; p = 0.03), longer duration of surgery (OR 1.006 per minute of surgery time; 95% CI 1.003–1.008; p < 0.001), and negative p16 status (OR 5.3; 95% CI = 1.1–25; p = 0.03). Based on 14 matching variables related to survival and perioperative blood transfusion, a control group of 37 matching patients without perioperative transfusion was identified. Using univariate analysis, overall survival in transfusion and control groups did not differ significantly (p = 0.25). After adjusting for four parameters with limited ma tching accuracy (Chi square p < 0.2) in Cox regression analysis, a transfusion related hazard ratio close to 1 (HR 0.92; 95% CI 0.34–2.51; p = 0.87) was observed.

Conclusion

Considering current restrictive transfusion regimens and general transfusion risks, the administration of blood products in HNC patients during the perioperative period is not associated with additional oncologic hazard.

Level of Evidence

III Laryngoscope, 2022

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GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization, mitochondria-targeting and -activating properties of human salivary histatin 1

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International Journal of Oral Science, Published online: 15 August 2022; doi:10.1038/s41368-022-00181-5

GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization, mitochondria-targeting and -activating properties of human salivary histatin 1
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