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Κυριακή 22 Μαΐου 2022

Diagnostic potential of extracellular vesicles in meningioma patients

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Abstract
Background
Extracellular vesicles (EVs) play an important role in cell-cell communication, and tumor-derived EVs circulating in patient blood can serve as biomarkers. Here, we investigated the potential role of plasma EVs in meningioma patients for tumor detection and determined whether EVs secreted by meningioma cells reflect epigenetic, genomic and proteomic alterations of original tumors.
Methods
EV concentrations were quantified in patient plasma (n = 46). Short-term meningioma cultures were established (n = 26) and secreted EVs were isolated. Methylation and copy number profiling was performed using 850k arrays, and mutations were identified by targeted gene panel sequencing. Differential quantitative mass spectrometry was employed for proteomic analysis.
Results
Levels of circulating EVs were elevated in meningioma patients compared to healthy individuals, and the plasma EV concentration correlated with malignanc y grade and extent of peritumoral edema. Postoperatively, EV counts dropped to normal levels, and the magnitude of the postoperative decrease was associated with extent of tumor resection. Methylation profiling of EV-DNA allowed correct tumor classification as meningioma in all investigated cases, and accurate methylation subclass assignment in almost all cases. Copy number variations present in tumors, as well as tumor-specific mutations were faithfully reflected in meningioma EV-DNA. Proteomic EV profiling did not permit original tumor identification but revealed tumor-associated proteins that could potentially be utilized to enrich meningioma EVs from biofluids.
Conclusions
Elevated EV levels in meningioma patient plasma could aid in tumor diagnosis and assessment of treatment response. Meningioma EV-DNA mirrors genetic and epigenetic tumor alterations and facilitates molecular tumor classification.
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Characteristics of Children ≤36 Months of Age with Diffuse Intrinsic Pontine Glioma (DIPG): A Report from the International DIPG Registry

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ABSTRACT:
Background
Children ≤36 months with Diffuse Intrinsic Pontine Glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes.
Methods
Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed.
Results
Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥ 5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3 -, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (p=0.018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation.
Conclusions
Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.
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The 2015 American Thyroid Association guidelines and trends in hemithyroidectomy utilization for pediatric thyroid cancer

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Abstract

Background

In 2015, the American Thyroid Association (ATA) released its inaugural recommendations for the management of thyroid cancer in children. We aim to evaluate whether there has been a change in hemithyroidectomy utilization for pediatric differentiated thyroid cancer, and the association between those changes and the release of the ATA guidelines.

Methods

The National Cancer Database was queried and identified 4776 patients ≤18 years old with differentiated thyroid cancer. Causal impact time-series analysis and logistic analysis were utilized to assess factors associated with use of hemithyroidectomy.

Results

Post-2015 hemithyroidectomy rate was greater than predicted based on preguideline trends (predicted: 8.4%, actual: 12.6%, p = 0.001). In logistic analysis of factors associated with hemithyroidectomy use, we find that Papillary histology, tumor size >1 cm, nodal examination, and positive nodes were associated with lower rate of hemithyroidectomy (OR: 0.23, 0.51, 0.62, and 0.18, respectively).

Conclusion

There has been a significant increase in hemithyroidectomy utilization for pediatric differentiated thyroid cancer.

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Markedly asymmetric facial nerve hypertrophy simulating a schwannoma in a patient with Charcot-Marie-Tooth disease

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Publication date: Available online 22 May 2022

Source: American Journal of Otolaryngology

Author(s): B. Jake Johnson, Felix E. Diehn, Alex A. Nagelschneider, Kendall K. Tasche, Matthew L. Carlson

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Effects of different doses of methylprednisolone on clinical outcomes in patients with severe community-acquired pneumonia: a study protocol for a randomized controlled trial

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The specific use of methylprednisolone in severe community-acquired pneumonia (SCAP) has not yet formed a consensus. It is not clear whether the clinical efficacy of methylprednisolone in SCAP is dose-dependen...
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Susceptibility to HIV-1 Acquisition linked to Malaria Exposure: A Case-control Study

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Abstract
HIV and malaria infection rates overlap across sub-Saharan Africa, but factors influencing their co-occurrence are unclear. In a case-control study, we investigated whether malaria exposure increases risk of HIV-1 acquisition. Prior to seroconverting, HIV-positive cases had significantly higher malaria-associated antibodies compared to HIV-negative controls, linking malaria exposure to HIV-1 acquisition.
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Ralstonia pickettii and Pseudomonas aeruginosa Bloodstream Infections Associated with Contaminated Extracorporeal Membrane Oxygenation Water Heater Devices

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Abstract
We report on probable factory-based contamination of portable water heaters with waterborne pathogens and two bloodstream infections potentially attributable to off-label use of these water heaters to warm extracorporeal membrane oxygenation circuits. Great caution is warranted when using water-based devices to care for critically ill patients.
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Effect of antiviral treatment on hepatitis B virus integration and hepatocyte clonal expansion

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
This study investigated the effect of nucleos(t)ide analogues (NUC) treatment on HBV DNA integration and hepatocyte clonal expansion, both of which are implicated in hepatocellular carcinoma (HCC) in chronic hepatitis B.
Methods
Twenty-eight patients receiving NUCs (11 lamivudine, 7 telbivudine, 10 entecavir) were included. All had liver biopsies at baseline and year 1, and seven had a third biopsy at year 10. HBV DNA integration and hepatocyte clone size were assessed by inverse PCR.
Results
All patients had detectable HBV integration at baseline, with a median integration frequency of 1.01×109 per liver and hepatocyte clone size of 2.41×105. Neither integration frequency nor hepatocyte clone size correlated with age and HBV virologic parameters. After one year of treatment, HBV integration was still detectable in all patients, with a median of 5.74×108 integration per li ver (0.22 log reduction; P = .008) and hepatocyte clone size of 1.22×105 (0.40 log reduction; P = .002). HBV integration remained detectable at year 10 of treatment, with a median integration frequency of 4.84×107 integration per liver (0.93 log reduction from baseline) and hepatocyte clone size of 2.55×104 (1.02 log reduction from baseline). From baseline through year 1 to year 10, there was a decreasing trend in both integration frequency and hepatocyte clone size (P = .066 and.018, respectively).
Conclusions
NUCs reduced both HBV DNA integration and hepatocyte clonal expansion, suggesting another alternative pathway besides direct viral suppression to reduce HCC risk. Our findings supported the notion for a long-term NUC treatment to prevent HCC.
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Treatment with reduced dose trimethoprim-sulfamethoxazole is effective in mild to moderate Pneumocystis jirovecii pneumonia in patients with hematologic malignancies

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Recent studies have reported that reduced dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP) but data is lacking for patients with hematologic malignancies.
Methods
This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at six Swedish University Hospitals. Treatment with 7.5-15 mg TMP/kg/day (reduced dose) was compared with >15-20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (ΔPaO2/FiO2) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30.
Results
Out of a total of 113 included patients, 80 patients received reduced dose, and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, neither before nor after controlling for potential confounders in an adjusted regression model (-13,6 mmHg [95% CI -56,7-29,5] and -9,4 mmHg, [95% CI -50.5-31.7], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups, 18% vs. 21% and 14% vs. 15%, respectively. Among patients with mild to moderate pneumonia, defined as PaO2/FiO2>200 mmHg, all 44 patients receiving reduced dose were alive at day 30.
Conclusion
In this cohort of 113 patients with hematologic malignancies, reduced dose TMP-SMX was effective and safe for treating mild to moderate PJP.
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Enhanced liver fibrosis score stratifies hepatocellular carcinoma risk in patients with hepatitis B surface antigen seroclearance

alexandrossfakianakis shared this article with you from Inoreader
Abstract
In this prospective study involving 337 chronic hepatitis B patients who achieved spontaneous HBsAg seroclearance (SC), serum Enhanced Liver Fibrosis (ELF) before SC was associated with hepatocellular carcinoma (HCC) (hazard ratio 2.588), and ELF <10.8 was associated with >97% reduction in risk of HCC development in patients with ageSC≥50 (n = 190).
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