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Κυριακή 30 Οκτωβρίου 2022

The Use of Dissemination and Implementation to Improve Multimodal Analgesia in Head and Neck Surgery

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The Use of Dissemination and Implementation to Improve Multimodal Analgesia in Head and Neck Surgery

The use of a multimodal analgesia approach in a Randomized Clinical Trial including acetaminophen, ketorolac, gabapentin, and a neurogenic extremity block in patients undergoing major head and neck ablative and reconstructive surgery significantly reduced the need for opioids in the immediate postoperative period of a seven-day hospital stay. Coordination of care and reducing variability in pain medication administration were highly dependent on dissemination and implementation processes put in place for perioperative phases of care.


Objectives

To optimize the delivery of multimodal analgesia to patients undergoing major head and neck oncologic surgeries.

Methods

Pilot study included patients enrolled to receive either scheduled acetaminophen and as-needed opioids (control group) or scheduled acetaminophen, gabapentin, ketorolac, and as-needed opioids (experimental group). RCT, a hybrid type 1 effectiveness-implementation pragmatic trial, was designed to test the effectiveness of the intervention. Arm A received scheduled acetaminophen and as-needed opioids. Arm B received scheduled gabapentin, ketorolac, a regional nerve block at the free tissue donor site, scheduled acetaminophen and as-needed opioids.

Results

Pilot: Thirty-one patients undergoing major head and neck surgery were enrolled. Mean MMEs administered in control group (n = 15) was 251.60 mg (SD = 224.57 mg); mean MMEs in Experimental group (n = 16) was 195.78 mg (SD = 131.08 mg), p = 0.401. LOS was 8.0 days in control versus 7.0 days in experimental group (p = 0.054).

RCT: Interim analysis for safety and futility was planned during trial's design after 30 patients (n = 14 Arm A, and n = 16 Arm B). Mean MMEs administered were 135.1 mg in Arm A, (SD = 86.0 mg) versus mean MME of 51.3 mg in Arm B (SD = 43.3 mg, (p < 0.05)). Given clear superiority results, the trial was prematurely terminated. Functional pain scores, LOS, and complications were similar between the arms (p > 0.05). Variability of mean MME was compared before and after implementation of the management protocols: SD in RCT#1 was 181.46 mg versus 124.6 mg in RCT#2.

Conclusion

Multimodal analgesia significantly reduced the need for opioids in patients undergoing major head and neck surgery.

Level of Evidence

1, Randomized Clinical Trial Laryngoscope, 2022

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The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center

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Abstract

Background

Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center.

Methods

Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database.

Results

The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model.

Conclusions

The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.

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Off‐label pharmacological treatment for neuropathic pain: A Delphi study by the Spanish Pain Society Neuropathic Pain Task Force

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Abstract

Objectives

The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use.

Methods

A two-round standard Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 40-item questionnaire prepared by the authors. Consensus on each statement was defined as at least either 80% endorsement or rejection after the second round.

Results

Forty-three and thirty-seven panelists participated in the first and second round, respectively. Consensus was reached in 34 out of 40 statements. Endorsed alternatives for unresponsive patients include non-gabapentinoid antiepileptics (oxcarbazepine and eslicarbazepine), venlafaxine, intravenous lidocaine (when doses can be optimized), and some vaporized cannabinoids (under appropriate surveillance). In addition, lacosamide, low-dose naltrexone, propofol or ketamine could prove beneficial if subjected to more research. Other options were rejected, and there was controversy about the usefulness of topical preparations.

Discussion

For patients who do not respond to standard NP treatments, some other viable pharmacological options can be attempted before advancing to other therapeutic stages. This may help patients who are reluctant to or have some contraindication for interventional therapies.

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Computational fluid dynamics and NOSE scale to assess nasal respiratory function, and correlation with linear maxillary measurements after surgically assisted rapid maxillary expansion

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Nasal obstruction is common in patients with a transverse maxillary deficiency. The aim of this study was to determine the variation in nasal airway resistance in adult patients with a transverse maxillary deficiency before and after surgically assisted rapid maxillary expansion (SARME) by computational fluid dynamics (CFD) using computed tomography scans, and to correlate this variation with maxillary linear measurements obtained by means of plaster models. The subjective symptoms of nasal obstruction were also analysed using a visual analogue scale (VAS) for nasal breathing and the Nasal Obstruction Symptom Evaluation (NOSE) scale. (Source: International Journal of Oral and Maxillofacial Surgery)
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Παρασκευή 28 Οκτωβρίου 2022

Broadly Neutralizing Antibodies for HIV Treatment: Broad in Theory, Narrow in Reality

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Abstract
In this viewpoint we briefly review the status of antiretroviral therapy, its unmet needs, and the role that broadly neutralizing antibodies (bNAbs) might have in the near future for the treatment of HIV. We summarize advances in the development of bNAbs as antiretroviral therapy, the results of main clinical trials of bNAbs for HIV treatment and prevention, and its role in cure trials. The limitations of broadly neutralizing antibodies are the current need for primary re sistance testing, the still unclear number of antibodies that must be combined, the lack of penetration in anatomical reservoirs and the role they might play in cure studies. We compare the advantages and disadvantages of "classical ART" and therapy based on broadly neutralizing antibodies. We conclude that broadly neutralizing antibodies still need considerable improvements before they can be considered an alternative to "classical ART".
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Τετάρτη 26 Οκτωβρίου 2022

LANA regulates miR‐155 /GATA3 signaling axis by enhancing c‐Jun/c‐Fos interaction to promote the proliferation and migration of KSHV‐infected cells

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Abstract

Kaposi's sarcoma (KS) is the second most common tumor in people infected with human immunodeficiency virus worldwide, but its pathogenesis is still unclear. In this study, we discovered that the expression of GATA-binding protein 3 (GATA3) was lowly expressed in KS tissues and KSHV-infected cells, while microRNA-155 (miR-155) was highly expressed in KS serum and KSHV-infected cells. miR-155 promoted the proliferation, migration and invasion of KSHV infection by targeting GATA3. Further, The KSHV-encoded protein, the Latency associated nuclear antigen (LANA), promotes the proliferation, migration and invasion of KSHV-infected cells by regulating the miR-155/GATA3 axis. Regarding the molecular mechanism, c-Jun and c-Fos interact to form a complex. LANA up-regulates the expression of c-Jun and c-Fos and enhances the formation of c-Jun/c-Fos complex. The complex binds to the -95 ~ -100 bp site of miR-155 promoter and transcriptionally activates miR-155. All in a ll, LANA enhances the c-Jun/c-Fos interaction, resulting in enhanced transcriptional regulation of miR-155 by the c-Jun/c-Fos complex, thereby downregulating GATA3 and promoting the proliferation, migration and invasion of KSHV-infected cells. The discovery of LANA/c-Jun/c-Fos/miR-155/GATA3 further refines the pathogenesis of KS, potentially opening a new avenue for developing effective drugs against KS.

This article is protected by copyright. All rights reserved.

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Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants

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Abstract
Background
Aerosol inhalation is recognized as the dominant mode of SARS-CoV-2 transmission. Three highly transmissible lineages evolved during the pandemic. One hypothesis to explain increased transmissibility is that natural selection favors variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. We aimed to measure the infectivity and rate of SARS-CoV-2 shedding into exhaled breath aerosol (EBA) by individuals during the Delta and Omicron waves and compared those rates with those of prior SARS-CoV-2 variants from our previously published work.
Methods
COVID-19 cases (n = 93, 32 vaccinated and 20 boosted) were recruited to give samples, including 30-minute breath samples into a Gesundheit-II exhaled breath aerosol sampler. Samples were quantified for viral RNA using RT-PCR and cultured for virus.
Results
Alpha (n = 4), Delta ( n = 3), and Omicron (n = 29) cases shed significantly more viral RNA copies into exhaled breath aerosols than cases infected with ancestral strains and variants not associated with increased transmissibility (n = 57). All Delta and Omicron cases were fully vaccinated and most Omicron cases were boosted. We cultured virus from the EBA of one boosted and three fully vaccinated cases.
Conclusions
Alpha, Delta, and Omicron independently evolved high viral aerosol shedding phenotypes, demonstrating convergent evolution. Vaccinated and boosted cases can shed infectious SARS-CoV-2 via EBA. These findings support a dominant role of infectious aerosols in transmission of SARS-CoV-2. Monitoring aerosol shedding from new variants and emerging pathogens can be an important component of future threat assessments and guide interventions to prevent transmission.
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Subgingival host‐microbiome metatranscriptomic changes following scaling and root planning in Grade II/III Periodontitis

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Abstract

Aims

To assess the effects of scaling and root planning (SRP) on the dynamics of gene expression by the host and the microbiome in subgingival plaque samples.

Methods

Fourteen periodontitis patients were closely monitored in the absence of periodontal treatment for 12 months. During this period, comprehensive periodontal examination and subgingival biofilm sample collection were performed bi-monthly. After 12 months, clinical attachment level (CAL) data was compiled and analyzed using linear mixed models (LMM) fitted to longitudinal CAL measurements for each tooth site. LMM classified sites as stable (S), progressing (P), or fluctuating (F). After 12 month visit, subjects received SRP and at 15 months they received comprehensive examination and supportive periodontal therapy (SPT). Those procedures were repeated at the 18 month visit, when patients were also sampled. Each patient contributed with one S, one P and one F site collected at 12 and 18 month visits. Samples were analyzed using Dual RNA-Sequencing to capture host and bacterial transcriptomes simultaneously.

Results

Microbiome and host response behavior were specific to the site's progression classification (i.e., S, P or F). Microbial profiles of pre and post-treatment samples exhibited specific microbiome changes, with progressing sites showing the most significant changes. Among them, P. gingivalis was reduced after treatment, while F. nucleatum showed an increase in proportion. Transcriptome analysis of the host response showed that IL-17, TNF signaling pathways, and neutrophil extracellular trap (NETs) formation were the primary immune response activities impacted by periodontal treatment.

Conclusion

Scaling and root planing resulted in a significant "rewiring" of host and microbial activities in the progressing sites, while in stable and fluctuating sites, the restructuring of the microbiome was minor.

This article is protected by copyright. All rights reserved.

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Τρίτη 25 Οκτωβρίου 2022

Second‐degree burn induced by high‐concentration topical capsaicin with mobility sequelae: a case report

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Abstract

High-concentration topical capsaicin is used as a second line treatment for neuropathic pain. Transient, mild burning sensation and erythema are expected adverse drug reactions. Here, we report the first case of second degree burn after the application of a high-concentration topical capsaicin patch with secondary mobility sequelae. Nine months after the application, neuropathic pain still remained and the patient described mobility difficulties in daily activities, preventing her from returning to work. This report aims to raise the question of the benefit/risk ratio of high concentration topical capsaicin.

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Tone in Noise Detection in Children with a History of Temporary Conductive Hearing Loss

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AbstractChildren with a history of temporary conductive hearing loss (CHL) during early development may show long-term impairments in auditory processes that persist after restoration of normal audiometric hearing thresholds. Tones in noise provide a simplified paradigm for studying hearing in noise. Prior research has shown that adults with sensorineural hearing loss may alter their listening strategy to use single-channel energy cues for tone-in-noise (TIN) detection rather than rove-resistant envelope or spectral profile cues. Our objective was to determine the effect of early CHL on TIN detection in healthy children compared to controls. Children ages 4 –7 years, with and without a history of CHL due to otitis media with effusion (OME) before age 3 years, participated in a two-alte...
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