Κυριακή 22 Μαΐου 2022

The clinical application of head-shaking test combined with head-shaking tilt suppression test in distinguishing between peripheral and central vertigo at bedside vs. examination room

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Publication date: Available online 20 May 2022

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Huiying Sun, Yinping Wang, Hong Jiang, Zhiqiang Gao, Haiyan Wu
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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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Infectious complications in acute graft‐versus‐host disease after Liver transplantation

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Abstract

Background

: Graft-versus-host disease (GVHD) following liver transplantation (LT) is rare but can lead to significant mortality. The leading cause of death following GVHD diagnosis is infectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims to provide the focused details of all infectious complications of acute GVHD following LT.

Methods

: We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described.

Results

: Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acute GVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5-99.0]. Ten (83.3%) patients developed severe infections leading to mortality. The most common cause of infection was nosocomial bacteremia from enteric bacteria such as vancomycin-resistant enterococci and gram-negative bacilli. Other infections included breakthrough invasive fungal infections, cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia – these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMV status. All GVHD patients with severe infections succumbed to these complications.

Conclusions

: Our study reiterates that despite prophylaxis, infectious complications in GVHD following LT are common and lead to exceptionally high mortality. Individualized antimicrobial treatment, prophylaxis and monitoring strategies remain a critical component of GVHD management. Further study to optimize these practices is required.

This article is protected by copyright. All rights reserved
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Association of neutrophil-to-lymphocyte ratio, radiotherapy fractionation/technique, and risk of development of distant metastasis among patients with locally advanced rectal cancer

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We investigated the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced rectal cancer (LARC) and whether modifiable factors in radiotherapy (RT) influenced the NLR.
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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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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

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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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Reduced Odds of SARS-CoV-2 Reinfection after Vaccination among New York City Adults, July–November 2021

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Abstract
Background
Belief that vaccination is not needed for individuals with prior infection contributes to COVID-19 vaccine hesitancy. Among individuals infected with SARS-CoV-2 before vaccines became available, we assessed whether vaccinated individuals had reduced odds of reinfection.
Methods
We conducted a case-control study among adult New York City residents who tested positive for SARS-CoV-2 infection in 2020, did not test positive again >90 days after initial positive test through July 1, 2021, and did not die before July 1, 2021. Case-patients with reinfection during July–November 2021 and control subjects with no reinfection were matched (1:3) on age, sex, timing of initial positive test in 2020, and neighborhood poverty level. Matched odds ratios (mOR) and 95% confidence intervals (CI) were calculated using conditional logistic regression.
Results
Of 349,827 eligible adults, 2,583 were reinfected during July� �November 2021. Of 2,401 with complete matching criteria data, 1,102 (45.9%) were known to be symptomatic for COVID-19-like-illness, and 96 (4.0%) were hospitalized. Unvaccinated individuals, compared with individuals fully vaccinated within the prior 90 days, had elevated odds of reinfection (mOR, 3.21; 95% CI, 2.70, 3.82), of symptomatic reinfection (mOR, 2.97; 95% CI, 2.31, 3.83), and of reinfection with hospitalization (mOR, 2.09; 95% CI, 0.91, 4.79). All three vaccines authorized or approved for use in the U.S. were similarly effective.
Conclusion
Vaccination reduced odds of reinfections when the Delta variant predominated. Further studies should assess risk of severe outcomes among reinfected persons as new variants emerge, infection- and vaccine-induced immunity wanes, and booster doses are administered.
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Supporting the Art: Medication Adherence Patterns in Persons Prescribed Ingestible Sensor-enabled Oral Pre-Exposure Prophylaxis to Prevent HIV Infection

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Abstract
Background
Timely, accurate adherence data may support oral PrEP success and inform prophylaxis choice. We evaluated an FDA-approved digital health feedback system (DHFS) with ingestible-sensor-enabled (IS) tenofovir-disoproxil-fumarate plus emtricitabine (Truvada®) in persons starting oral PrEP.
Methods
HIV-negative adults were prescribed IS-Truvada® with DHFS for 12 weeks to observe medication taking behavior. Baseline demographics, urine toxicology and self-report questionnaires were obtained. Positive detection accuracy and adverse events were computed as percentages, with Kaplan Meier Estimate for persistence-of-use. In participants persisting ≥ 28 days, adherence patterns (taking and timing) were analyzed and mixed-effects logistic regression modelled characteristics associated with treatment adherence.
Results
Seventy-one participants enrolled, mean age 37.6 years (range 18-69), 90.1% male, 77.5% white, 33.8% Hispanic, 95.8% housed and 74.6% employed. Sixty-three participants (88.7%) persisted ≥28 days, generating 4987 observation days, average 79.2 (29-105). Total confirmed doses were 86.2% (CI95 82.5, 89.4), decreasing over time, OR 0.899 (CI95 0.876, 0.923) per week, p < 0.001; 79.4% (CI95 66.7%, 87.3%) of participants had ≥80% adherence. Pattern analysis showed days without confirmed doses clustered (p = 0.003); regular dose timing was higher among participants with ≥80% confirmed doses (0.828, CI95 0.796 to 0.859) than among those with <80% (0.542, CI95 0.405 to 0.679) p < 0.001. In multi-predictor models, better adherence was associated with older age, OR 1.060 (CI95 1.033, 1.091) per year, p < 0.001; negative vs positive methamphetamine screen, OR 5.051 (CI95 2.252, 11.494), p < 0.001.
Conclusions
DHFS with IS-Truvada® distinguished adherent persons from those potentially at risk of prophylactic failure. Ongoing methamphetamine substance use may impact oral PrEP success.
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