Τρίτη 13 Δεκεμβρίου 2022

Wide mismatches in the sequences of primers and probes for Monkeypox virus diagnostic assays

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Abstract

Rapid and accurate diagnosis of infections is fundamental to containment of disease. Several monkeypox virus (MPV) real-time diagnostic assays have been recommended by the CDC; however, the specificity of the primers and probes in these assays for the ongoing MPV outbreak has not been investigated. We analyzed the primer and probe sequences present in the CDC recommended monkeypox virus (MPV) generic real-time PCR assay by aligning those sequences against 1,730 MPV complete genomes reported in 2022 worldwide. Sequence mismatches were found in 99.08% and 97.46% of genomes for the MPV generic forward and reverse primers, respectively. Mismatch-corrected primers were synthetized and compared to the generic assay for MPV detection. Results showed that the two primer-template mismatches resulted in a ~11-fold underestimation of initial template DNA in the reaction and 4-fold increase in the 95% LOD. We further evaluated the specificity of seven other real-time PCR assays used for MPV a nd orthopoxvirus (OPV) detection and identified two assays with the highest matching score (>99.6%) to the global MPV genome database in 2022. Genetic variations in the primer-probe regions across MPV genomes could indicate the temporal and spatial emergence pattern of monkeypox disease. Our results show that the current MPV real-time generic assay may not be optimal to accurately detect MPV, and the mismatch-corrected assay with full complementarity between primers and current MPV genomes could provide a more sensitive and accurate detection of MPV.

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Burden of Neutropenia and Leukopenia Among Adult Kidney Transplant Recipients

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Abstract

Background

: Leukopenia and neutropenia (L/N) may affect treatment decisions, potentially resulting in poor clinical and economic outcomes among kidney transplant recipients (KTRs). The burden of L/N is poorly quantified systematically. This systematic literature review aimed to summarize the incidence of, risk factors for, and clinical and economic outcomes associated with L/N post-KT.

Methods

: We systematically searched MEDLINE, Embase, and the Cochrane Library (from database inception-June 14, 2021) and conferences (past 3 years) to identify observational studies examining epidemiology, risk factors, or outcomes associated with L/N among adult KTRs.

Results

: Of 2,081 records, 82 studies met inclusion criteria. Seventy-three studies reported the epidemiology of L/N post-KT. Pooled incidence of neutropenia, defined as absolute neutrophil counts (ANC) <1000/μL, ranged from 13%-48% within 1 year post-transplant; ANC <500/μL ranged from 15%-20%. Leukopenia, defined as white blood cell counts <3500/μL, was 19%-83%. Eleven studies reported independent risk factors associated with L/N post-KT. D+/R- cytomegalovirus (CMV) status, mycophenolic acid (MPA), and tacrolimus use were the most consistent risk factors across studies. Fourteen studies reported L/N-associated clinical outcomes. We noted a trend toward a positive association between neutropenia and acute rejection/opportunistic infections. Mixed findings were noted on the association between L/N and graft failure or mortality. Dosage modifications of valganciclovir, MPA, cotrimoxazole, and anti-thymoglobulin and the need for G-CSF use were common with L/N.

Conclusion

: Findings suggest post-transplant L/N were common and associated with frequent modifications of immunosuppressive agents, requiring G-CSF use, and rejection or opportunistic infections. Findings highlight the need for interventions to reduce risk of L/N post-KT.

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Trigeminal Sensitivity in Patients With Allergic Rhinitis and Chronic Rhinosinusitis

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Trigeminal Sensitivity in Patients With Allergic Rhinitis and Chronic Rhinosinusitis

Allergic patients react more sensitively to trigeminal stimuli in the nose than a comparable control group. This is important because it supports the suggestion that local factors in the nasal mucosa are significantly involved in influencing the trigeminal system of the nose.


Objective

Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of high importance in otorhinolaryngology. Some of their symptoms are related to changes in the nasal trigeminal sensitivity. The aim of this study was to compare nasal trigeminal sensitivity in patients with AR, CRSwNP, and healthy controls (HC).

Methods

A total of 75 individuals participated (age 19–78 years; 34 AR, 10 CRSwNP and 31 HC). Olfactory function was determined using the extended Sniffin' Sticks test battery. Trigeminal sensitivity was assessed with CO2 detection thresholds. Trigeminal negative mucosal potentials (NMP) and EEG-derived event-related potentials (ERP) were recorded in response to selective olfactory (phenylethyl alcohol) and trigeminal (CO2) stimuli using high-precision air-dilution olfactometry.

Results

In comparison to HC, AR patients had lower CO2 thresholds, also reflected in shorter peak latencies in NMP and trigeminal ERP measurements. CRSwNP patients had a decreased sensitivity for trigeminal stimuli, also reflected in prolonged trigeminal ERP latencies, and reduced olfactory function compared to HC.

Conclusion

AR patients seemed to be more sensitive to trigeminal stimuli than CRSwNP patients. Importantly, the differences could be shown on psychophysical and electrophysiological levels. The changes in trigeminal sensitivity appear to be present already at the level of the respiratory epithelium. The differences between the two groups may depend on the specific inflammatory changes accompanying each disorder, the degree of inflammatory activity, or duration of the inflammatory disorder. However, because the sample sizes are relatively small, these results need to be confirmed in the future studies with larger groups.

Level of Evidence

4 Laryngoscope, 2022

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Malnutrition and clinical outcomes post allogeneic stem cell transplantation

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Abstract

Background

Malnutrition has been linked with higher risk of poor outcomes post-allogeneic stem cell transplantation (alloSCT), however few studies have used a validated nutrition assessment tool such as the Patient Generated Subjective Global Assessment (PG-SGA) to measure nutritional status and investigate associations with long-term clinical outcomes. This study aimed to assess the incidence of malnutrition prior to alloSCT and determine if there was an association between nutritional status pre-transplant and post-transplant clinical outcomes including acute kidney injury, graft-versus-host disease, intensive care admission (ICU), need for haemodialysis and survival.

Methodology

A retrospective analysis of 362 patients (213 m:149 f, mean age±SD 47.8±14.1y) who underwent alloSCT from 2008 to 2013 was conducted. Data on clinical outcomes was obtained for five years post-transplant.

Results

Fifteen percent (n=56) of patients were identified as malnourished pre-admission. Malnutrition was associated with longer hospital stay (p=0.007), increased requirement for haemodialysis (p=0.016), and increased admissions to ICU (p=0.003). There was no association between malnutrition and acute kidney injury, graft-versus-host disease or survival. Following multivariate analyses, malnutrition remained significantly associated with increased admission rates to ICU (OR 3.8, 95%CI 1.3 – 10.5, p=0.011) and increased LOS>30 days (OR 3.6. 95%CI 1.8-7.4, p=<0.001).

Conclusion

These findings add importance to the need for nutrition screening and assessment to be routinely undertaken for patients prior to alloSCT and throughout hospitalisation in order to provide early nutrition intervention for the prevention of malnutrition, poor clinical outcomes, and increased healthcare costs.

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Zygomatic implant placement using a robot-assisted flapless protocol: proof of concept

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Robotic assistance can help in physically guiding the drilling trajectory during zygomatic implant positioning. A new robot-assisted strategy for a flapless zygomatic implant placement protocol is reported here. In this protocol, a preoperative computed tomography scan is used to plan the surgical path. After surface registration, the ROSA robot (Zimmer Biomet Robotics) guides several steps, which are performed with shared control. The surgeon performs the drilling and tapping, guided by the robotic arm, which is positioned according to the planned trajectory. (Source: International Journal of Oral and Maxillofacial Surgery)
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Δευτέρα 12 Δεκεμβρίου 2022

State-of-the-art: septal perforation repair

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imagePurpose of review To provide a comprehensive overview of the evolution of the different techniques described for the surgical repair of nasal septal perforation, and a surgical decision-making algorithm for its surgical treatment. Recent findings Septal perforation surgery has evolved and improved in recent years. It has gone from being an avoided or discouraged surgical procedure to a procedure with success rates of >90%. Nowadays, there is no standard approach or single technique. The different techniques described include unilateral random pattern flaps, interposition grafts, unilateral pedicle septal local flaps, free mucosal grafts and bilateral random patter flaps. The incidence of success is higher in pediculated septal flaps such as the anterior ethmoidal artery flap or the greater palatine artery pedicled flap combined with additional techniques. Summary Nowadays, surgical closure of septal perforation is possible and should be an option to consider in symptomatic patients without response to medical treatment. The surgical approach that we recommend when planning the surgical closure of nasal septum (or nasoseptal) perforation is based on the osseocartilaginous support and the location of the defect.
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The link between allergic rhinitis and chronic rhinosinusitis

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imagePurpose of review Allergic rhinitis and chronic rhinosinusitis (CRS) are common disorders affecting millions of people worldwide. Although allergic rhinitis and CRS are distinct clinical entities, certain CRS endotypes share similar pathological mechanisms as those seen in patients with allergic rhinitis. This review assesses the literature behind the similarities and differences seen in patients with CRS and allergic rhinitis, and the role atopy might play in the pathophysiology of CRS. Recent findings In examining the associations between allergic rhinitis and CRS, most studies have focused primarily on CRS with nasal polyps and type 2 inflammation in CRS. Recent studies have demonstrated the similarities and differences in pathologic mechanisms behind allergic rhinitis and CRS, with an emphasis on patient endotypes, genetics, and the nasoepithelial immunologic barrier. Related immunopathology shared by allergic rhinitis and type 2 inflammation in CRS has allowed for therapeutic overlap with biologic treatments. Summary Allergic rhinitis and CRS often present as comorbid conditions, and understanding the relationship between allergic rhinitis and CRS is important when considering treatment options. Advances in understanding the genetics and immunology, as well as biologic and immunotherapeutic treatments have improved outcomes in patients with CRS, especially in the setting of atopy.
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