Ετικέτες

Δευτέρα 15 Αυγούστου 2022

Accuracy of reverse‐transcription polymerase chain reaction and loop‐mediated isothermal amplification in diagnosing severe fever with thrombocytopenia syndrome: A systematic review and meta‐analysis

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Abstract

Background

Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports have been published on the accuracy of reverse-transcription polymerase chain reaction (RT-PCR) and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in the diagnosis of SFTS. Thus, we conducted a meta-analysis and systematic review to evaluate the accuracy of the two methods.

Methods

On June 19, 2022, we comprehensively searched the PubMed, Embase, Cochrane Library, Web of Science, Scoups, Ovid, Proquest, China National Knowledge Infrastructure Database, Wan Fang Data, Traditional Chinese Medicine Database (Sinomed), VIP Database and Reading Showing Database for articles on nucleic acid diagnostic techniques, such as RT-PCR and RT-LAMP, used to diagnose SFTS. Statistical analysis was performed using STATA 14.0 and Meta-Disc 1.4.

Results

Sixteen a rticles involving 2942 clinical blood samples were included in the analysis. RT-PCR and RT-LAMP were used as index tests, whereas RT-PCR or other detection methods were used as reference standards. The pooled values for the sensitivity, specificity, positive and negative likelihood ratios of the RT-PCR test were 0.97 (95% CI: 0.92, 0.99), 1.00 (95% CI: 0.98, 1.00), 483.87 (95% CI: 58.04, 4033.76), and 0.03 (95% CI:0.01, 0.08) respectively. Those for the RT-LAMP test were 0.95 (95% CI: 0.91, 0.97), 0.99 (95% CI: 0.93, 1.00), 111.18 (95% CI: 13.96, 885.27), and 0.05 (95% CI: 0.03, 0.09), respectively.

Conclusion

Both RT-PCR and RT-LAMP have high diagnostic value in SFTS and can be applied in different scenarios for laboratory confirmation or on-site screening.

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ELANE neutropenia and solid tumors: Four cases from the French severe chronic neutropenia registry

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Abstract

Neutropenia related to ELANE gene mutations predisposes patients to infection and leukemia/myelodysplasia, but little is known about the predisposition to cancer. Among a cohort of 147 patients, we identified four with malignant solid tumors (papillary thyroid cancer, anal squamous cell cancer, papillary renal cell carcinoma, and adrenocortical carcinoma), all aged 25–50 years. Three occurred with cyclic neutropenia, and one occurred with severe chronic neutropenia. Previous radiotherapy was identified as a risk factor in one patient. No genetic predisposition was identified in the three other patients.

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Middle Fossa Decompression for Recurrent Facial Palsy: Prevalence and Surgical Outcomes

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Middle Fossa Decompression for Recurrent Facial Palsy: Prevalence and Surgical Outcomes

Our study examined the facial nerve and audiometric outcomes of patients undergoing middle fossa decompression for recurrent facial nerve paresis. We found that facial nerve decompression for patients with incomplete functional recovery may be an effective treatment for decreasing the frequency and severity of facial palsy episodes.


Objective

To investigate the surgical outcomes in patients treated for recurrent facial nerve palsy (RFP) at a quaternary facial nerve referral center.

Methods

A retrospective chart review was performed on 132 patients with RFP who presented to our institution's facial nerve clinic from 2001 to 2021. Records were analyzed for etiology of palsy, facial nerve function, and recurrence rates. Pre- and post-operative audiometric outcomes were also assessed in surgically managed patients.

Results

6.8% of RFP patients underwent surgical decompression. For patients who did not undergo surgery, the House-Brackmann (HB) score was 2.9 ± 1.3 (SD) at the initial clinic visit, and 2.4 ± 1.3 (SD) at the last clinic visit. This difference was significantly different (p = 0.01, t-test). For surgical patients, the pre-operative HB score was 2.9 ± 0.9 (SD) and post-operative HB score was 1.8 ± 0.6 (SD), which were significantly different (p = 0.01, t-test). The number of facial palsy episodes also decreased pre- and post-operatively from 3.5 ± 0.8 (SD) to 0.2 ± 0.4 (SD) episodes, which were significantly different (p < 0,001, t-test). Audiometric outcomes were not significantly different pre- and post-surgery (p = 0.31, t-test for PTA; p = 0.34, t-test for WRS).

Conclusion

Facial nerve decompression for RFP patients with incomplete functional recovery may be an effective treatment for decreasing the frequency and severity of facial palsy episodes.

Level of Evidence

4 Laryngoscope, 2022

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Πέμπτη 11 Αυγούστου 2022

Discovery of novel 1,2,4‐triazole phenylalanine derivatives targeting an unexplored region within the interprotomer pocket of the HIV capsid protein

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Abstract

HIV capsid (CA) protein is a promising target for developing novel anti-HIV drugs. Starting from highly anticipated CA inhibitors PF-74, we used scaffold hopping strategy to design a series of novel 1,2,4-triazole phenylalanine derivatives by targeting an unexplored region composed of residues 106-109 in HIV-1 CA hexamer. Compound d19 displayed excellent antiretroviral potency against HIV-1 and HIV-2 strains with EC50 values of 0.59 µM and 2.69 µM, respectively. Additionally, we show via surface plasmon resonance spectrometry (SPR) that d19 preferentially interacts with the hexameric form of CA, with a significantly improved hexamer/monomer specificity ratio (Ratio = 59) than PF-74 (Ratio = 21). Moreover, we show via SPR that d19 competes with CPSF-6 for binding to CA hexamers with IC50 value of 33.4 nM. Like PF-74, d19 inhibits the replication of HIV-1 NL4.3 pseudo typed virus in both early and late stages. In addition, molecular docking and molecular dynamics simulations provide binding mode information of d19 to HIV-1 CA and rationale for improved affinity and potency over PF-74. Overall, the lead compound d19 displays a distinct chemotype form PF-74, improved CA affinity, and anti-HIV potency.

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Necrotizing Sialometaplasia in a Medically Compromised Patient

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This case report describes a woman in her 50s with type 2 diabetes mellitus, hypertension, and hypertensive kidney disease who presented with oral lesions with a duration of 1 month and was subsequently diagnosed with necrotizing sialometaplasia.
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Stimulation Rate and Voice Pitch Perception in Cochlear Implants

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We describe two experiments with 16 Nu cleus® CI users, where we controlled modulation characteristics and carrier rate using Spectral and Temporal Enhanced Processing (STEP), a novel experimental multichannel sound coder. We used a fixed set of threshold and comfortable stimulation levels for each subject, obtained from clinical MAPs. In the first experiment, we determined equivalence for voice pitch ranking and voice gender categorization between the Advanced Combination Encoder (ACE), a widely used clinical strategy in Nucleus® recipients, and STEP for fundamental frequencies (F0) 120–250 Hz. In the second experiment, loudn ess was determined as a function of the input amplitude of speech samples for carrier rates of 1000, 500, and 250 pps per channel. Then, using equally loud soun...
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Temporal Envelope Coding of the Human Auditory Nerve Inferred from Electrocochleography: Comparison with Envelope Following Responses

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AbstractNeural coding of the slow amplitude fluctuations of sound (i.e., temporal envelope) is thought to be essential for speech understanding; however, such coding by the human auditory nerve is poorly understood. Here, neural coding of the temporal envelope by the human auditory nerve is inferred from measurements of the compound action potential in response to an amplitude modulated carrier (CAPENV) for modulation frequencies ranging from 20 to 1000  Hz. The envelope following response (EFR) was measured simultaneously with CAPENV from active electrodes placed on the high forehead and tympanic membrane, respectively. Results support the hypothesis that phase locking to higher modulation frequencies (>  80 Hz) will be stronger for CAPENV, compared to EFR, consistent with the uppe...
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Regenerative endodontic therapy for external lateral inflammatory resorption following traumatic dental injuries. Evidence assessment of best practices

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Abstract

Introduction

External inflammatory resorption (EIR) following dental trauma is often caused by an injury to the lining of the cementoblasts and to the non-mineralized tissues (i.e., precementum) covering the root surface. Although EIR frequently occurs apically, it can also develop on the lateral root surfaces, which is termed external inflammatory lateral resorption (EILR). ELIR is a severe complication that can lead to significant root loss and tooth extraction.

Aim

The aim of this project was to review the current evidence in the literature on regenerative endodontic therapy (RET) for ELIR following traumatic injuries and assess the best treatment practices.

Methodology

Publications appearing in PubMed electronic database, from January 1, 2001 to January 9, 2022 were studied. Inclusion criteria were: (a) Publications in the English language; (b) Publications on regenerative endodontic therapy and ELIR; (c) Teeth subjected to dental trauma; and (d) Presence of intracanal bleeding and blood clots. Exclusion criteria were: (a) Conference proceedings; (b) Lectures; (c) Abstracts and (d) Letters to the editor; (e) Publications not in the English language. Additionally, a manual search was conducted. The data collected was analysed, and a descriptive statistical analysis was performed.

Results

A total of 355 publications were analysed, of which 9 met all inclusion criteria, which comprised of case reports and case series studies. In 10 (58.8%) teeth, Triple Antibiotic Paste (TAP) was used for an average of 26 days. Double Antibiotic Paste (DAP) was used in 3 (17.6 %) teeth for an average of 14 days. In 3 (17.6 %) cases, calcium hydroxide (Ca(OH)2) was used as intracanal medication for 14 days and negative pressure irrigation was applied once on 1 (6 %) tooth.

Conclusions

RET demonstrated a good treatment modality producing biologic repair and improving prognosis in cases of ELIR in post-traumatic tooth/pulp injuries. Hence, a meticulous follow up should be conducted when RET is performed in order to identify treatment failure and substitute it with long-term Ca(OH)2 root canal dressing. The key limitation in our review is that all publications included were either case reports or case series that usually tend to report successful outcome.

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Sodium‐glucose cotransporter‐2 inhibitor‐induced euglycemic diabetic ketoacidosis: A case report

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Sodium-glucose cotransporter-2 inhibitor-induced euglycemic diabetic ketoacidosis: A case report

SGLT-2i-induced euDKA.


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Τετάρτη 10 Αυγούστου 2022

The Interplay of Long Non‐Coding RNAs and Hepatitis B Virus

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ABSTRACT

Hepatitis B Virus (HBV) infections remain a major global health burden with an estimated 296 million people living with a chronic infection and 884,00 HBV-related deaths annually. Notably, patients with a chronic hepatitis B (CHB) infection are at a 30-fold greater risk of developing hepatocellular carcinoma (HCC), the 3rd deadliest cancer worldwide. Several groups have assessed HBV-related aberrant expression of host-cell long non-coding RNAs (lncRNAs) and how altered expression of specific lncRNAs affects HBV replication and progression to associated disease states. Given the challenges in establishing effective HBV models and analyzing transcriptomic data, this review focuses on lncRNA expression data primarily collected from clinical patient samples and primary human hepatocytes (PHHs), with subsequent mechanism of action analysis in cell lines or other model systems. Ultimately, understanding HBV-induced lncRNA-expression dysregulation could lead to new treatments and biomarkers for HBV infection and its associated diseases.

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A Phase I/II Study of Intrathecal Trastuzumab in HER-2 Positive Cancer with Leptomeningeal Metastases: Safety, Efficacy, and Cerebrospinal Fluid Pharmacokinetics

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Abstract
Background
Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive LMD.
Methods
This multicenter study enrolled 34 LMD patients in a combined Phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the Phase I; the Phase II was limited to HER2-positive breast cancer.
Results
Intrathecal trastuzumab was well tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended Phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80mg w ere included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for Phase 2 dose treated patients was 8.3 months (95% CI 5.2 to 19.6). The Phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2 to 20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable CSF concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations.
Conclusion
This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
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