Αρχειοθήκη ιστολογίου

Τετάρτη 22 Δεκεμβρίου 2021

In vitro and in vivo effects of AVA4746, a novel competitive antagonist of the ligand binding of VLA-4, in B-cell acute lymphoblastic leukemia

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Exp Ther Med. 2022 Jan;23(1):47. doi: 10.3892/etm.2021.10969. Epub 2021 Nov 15.

ABSTRACT

Treatment of resistant or recurrent acute lymphoblastic leukemia (ALL) remains a challenge. It was previously demonstrated that the adhesion molecule integrin α4, referred to hereafter as α4, mediates the cell adhesion-mediated drug resistance (CAM-DR) of B-cell ALL by binding to vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stroma. In addition, it was previously observed that the blockade of α4 with natalizumab or inhibition using the small molecule antagonist TBC3486 sensitized relapsed ALL cells to chemotherapy. However, α4-targeted therapy is not clinically available for the treatment of leukemia to date. In the present study, the use of a novel non-peptidic small molecule integrin α4 antagonist, AVA4746, as a potential new approach to combat drug-resistant B-ALL was explored. An in vitro co-culture = model of primary B- ALL cells and an in vivo xenograft model of patient-derived B-ALL cells were utilized for evaluation of AVA4746. VLA-4 conformation activation, cell adhesion/de-adhesion, endothelial tube formation, in vivo leukemia cell mobilization and survival assays were performed. AVA4746 exhibited high affinity for binding to B-ALL cells, where it also efficiently blocked ligand-binding to VCAM-1. In addition, AVA4746 caused the functional de-adhesion of primary B-ALL cells from VCAM-1. Inhibition of α4 using AVA4746 also prevented angiogenesis in vitro and when applied in combination with chemotherapy consisting of Vincristine, Dexamethasone and L-asparaginase, it prolonged the survival of ~33% of the mice in an in vivo xenograft model of B-ALL. These data implicate the potential of targeting the α4-VCAM-1 interaction using AVA4746 for the treatment of drug-resistant B-lineage ALL.

PMID:34934426 | PMC:PMC8652384 | DOI:10.3892/etm.2021.10969

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Lumbar Pneumorrhachis Associated With Basilar Skull Fractures

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Cureus. 2021 Nov 18;13(11):e19703. doi: 10.7759/cureus.19703. eCollection 2021 Nov.

ABSTRACT

Lumbar pneumorrhachis following head injury is rare and commonly asymptomatic but can be indicative of skull fracture and cerebrospinal fluid (CSF) leak, which may warrant intervention. A PubMed review of the literature was performed using a keyword search to identify cases examining lumbar pneumorrhachis following head injury. Our case series included two patients who had lumbar pneumorrhachis between September 2019 and May 2020 at our center. The literature review summarizes 16 patients from 14 prior reports of pneumorrhachis. In our two-patient case series, neither patient required direct intervention for either pneumorrhachis or CSF leak. Pneumorrhachis is rare following an isolated head injury and is associated with basilar skull fractures and CSF leak. Pneumorrhachis should alert clinicians to the possibility of a CSF leak, which may require int ervention.

PMID:34934572 | PMC:PMC8684351 | DOI:10.7759/cureus.19703

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Voluntary Cough Effectiveness and Airway Clearance in Neurodegenerative Disease

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J Speech Lang Hear Res. 2021 Dec 22:1-19. doi: 10.1044/2021_JSLHR-21-00308. Online ahead of print.

ABSTRACT

PURPOSE: Voluntary cough dysfunction is highly prevalent across multiple patient populations. Voluntary cough has been utilized as a screening tool for swallowing safety deficits and as a target for compensatory and exercise-based dysphagia management. However, it remains unclear whether voluntary cough dysfunction is associated with the ability to effectively clear the airwa y.

METHOD: Individuals with neurodegenerative disorders performed same-day voluntary cough testing and flexible endoscopic evaluations of swallowing (FEES). Participants who were cued to cough after exhibiting penetration to the vocal folds and/or aspiration with thin liquids during FEES met inclusion criteria. One-hundred and twenty-three trials were blinded, and the amount of residue before and after a cued cough on FEES was measured with a visual analog scale. Linear and binomial mixed-effects models examined the relationship between cough airflow during voluntary cough testing and the proportion of residue expelled.

RESULTS: Peak expiratory flow rate (p = .004) and cough expired volume from the entire epoch (p = .029) were significantly associated with the proportion of aspiration expelled from the subglottis. Peak expiratory flow rate values of 3.00 L/s, 3.50 L/s, and 5.30 L/s provided high predicted probabilities that ≥ 25%, ≥ 50%, and ≥ 80% asp irate was expelled. Accounting for depth of aspiration significantly improved model fit (p < .001).

CONCLUSIONS: These findings suggest that voluntary cough airflow is associated with cough effectiveness to clear aspiration from the subglottis, although aspiration amount and depth may play an important role in this relationship. These findings provide further support for the clinical utility of voluntary cough in the management of dysphagia.

PMID:34936376 | DOI:10.1044/2021_JSLHR-21-00308

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The Nonrecurrent Laryngeal Nerve Without Abnormal Subclavian Artery: Report of Two Cases and Review of the Literature

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Ear Nose Throat J. 2021 Dec 22:1455613211056547. doi: 10.1177/01455613211056547. Online ahead of print.

ABSTRACT

As a variant of recurrent inferior laryngeal nerve (RILN), the nonrecurrent inferior laryngeal nerve (NRILN) is closely related to the occurrence of abnormal subclavian artery (ASA). The nonrecurrent inferior laryngeal nerve has been found in patients without arterial abnormalities, which is seen in the coexistence of NRILN and RILN, but it is easily confused with sympathetic-inferior laryngeal anastomosis branch (SILAB). We encountered 2 right NRILN patients without ASA during thyroid surgery. This article summarizes the characteristics of these cases and proposes methods to distinguish the coexistence of NRILN and RILN from SILAB. So far, 11 articles have reported 16 cases of NRILN without arterial abnormalities. In patients without artery abnormality, the vagus nerve could send out a descending branch NRILN at the bifurcation of the carotid artery and enter the larynx after anastomosis with RILN. Adequate dissection of the carotid sheath may avoid confusion with SILAB, and neural monitoring is also expected to provide a reference for the identification.

PMID:34935547 | DOI:10.1177/01455613211056547

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Τρίτη 21 Δεκεμβρίου 2021

Paracrine mechanisms of endothelial progenitor cells in vascular repair

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Via histochem

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Acta Histochem. 2021 Dec 17;124(1):151833. doi: 10.1016/j.acthis.2021.151833. Online ahead of print.

ABSTRACT

Endothelial progenitor cells (EPCs) play an important role in repairing damaged blood vessels and promoting neovascularization. However, the specific mechanism of EPCs promoting vascular repair is still unclear. Currently, there are two different views on the repair of damaged vessels by EPCs, one is that EPCs can directly differentiate into endothelial cells (ECs) a nd integrate into injured vessels, the other is that EPCs act on cells and blood vessels by releasing paracrine substances. But more evidence now supports the latter. Therefore, the paracrine mechanisms of EPCs are worth further study. This review describes the substances secreted by EPCs, some applications based on paracrine effects of EPCs, and the studies of paracrine mechanisms in cardiovascular diseases--all of these are to support the view that EPCs repair blood vessels through paracrine effects rather than integrating directly into damaged vessels.

PMID:34929523 | DOI:10.1016/j.acthis.2021.151833

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Reconstruction of midline abdominal defects with a deep inferior epigastric artery keystone-type perforator flap

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J Plast Reconstr Aesthet Surg. 2021 Dec 7:S1748-6815(21)00650-1. doi: 10.1016/j.bjps.2021.11.103. Online ahead of print.

NO ABSTRACT

PMID:34930700 | DOI:10.1016/j.bjps.2021.11.103

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Filler-induced complications of the lips: 10 years experience with intralesional laser treatment and refinements

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J Plast Reconstr Aesthet Surg. 2021 Nov 15:S1748-6815(21)00586-6. doi: 10.1016/j.bjps.2021.11.042. Online ahead of print.

ABSTRACT

BACKGROUND: The number of minimally invasive cosmetic procedures has steadily increased every year. In the last decade, the rates of filler injection reactions have also increased. This study presents our experience in the management and treatment of permanent filler complications to the lips. Undoubtedly, in these adverse reactions, the lips are the hallmark that most stigmatizes an unnatural look of the face.

METHODS: One hundred and eighty-one patients (168 female and 13 male) with permanent filler complications to the lips were treated from September of 2009 to September of 2019 at the University Hospital of Modena. One hundred and thirty-five patients underwent intralesional laser treatment (ILT). Forty-six patients underwent a stab incision and drainage and 10 of these patients had solid and cal cified nodules and therefore underwent a combined technique. Thirty-three patients underwent further cosmetic procedures.

RESULTS: In 95% of patients there was a clinical improvement of which complete resolution in 38.7% and partial improvement in 34.2% of cases. Nine patients stopped the treatment because they were not satisfied. No patient was considered to have worsened after the treatment. Thirty-three patients underwent further treatments.

CONCLUSIONS: A systematic combined approach between antibiotic therapy and treatments (ILT and a stab incision) represents the best therapeutic approach in dealing with permanent fillers complications to the lips. This treatment modality allows both the removal of the foreign material and the inflammatory reaction with low morbidity and little cosmetic disfigurement. Further cosmetic procedures may be applied to improve aesthetic appearance once most of the non-resorbable substance has been removed.

PMID:34930702 | DOI:10.1016/j.bjps.2021.11.042

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Cerebrospinal Fluid Leak Detection with a Carbon Nanotube-Based Field-Effect Transistor Biosensing Platform

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ACS Appl Mater Interfaces. 2021 Dec 21. doi: 10.1021/acsami.1c19120. Online ahead of print.

ABSTRACT

Cerebrospinal fluid (CSF) leakage may lead to life-threatening complications if not detected promptly. However, gel electrophoresis, the gold-standard test for confirming CSF leakage by detecting beta2-transferrin (β2-Tf), requires 3-6 h and is labor-intensive. We developed a new β2-Tf detection platform for rapid identification of CSF leakage. The three-step design, which includes two steps of affinity chromatography and a rapid sensing step using a semiconductor-enriched single-walled carbon nanotube field-effect transistor (FET) sensor, circumvented the lack of selectivity that antitransferrin antibody exhibits for transferrin isoforms and markedly shortened the detection time. Furthermore, three different sensing configurations for the FET sensor were investigated for obtaining the optimal β2-Tf sensing results. Finally, body fluid (CSF and serum) tests employing our three-step strategy demonstrated high sensitivity, suggesting its potential to be used as a rapid diagnostic tool for CSF leakage.

PMID:34932323 | DOI:10.1021/acsami.1c19120

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Δευτέρα 20 Δεκεμβρίου 2021

Oligometastatic adenoid cystic carcinoma: Correlating tumor burden and time to treatment with outcomes

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Abstract

Background

There is limited information on the management and outcomes of oligometastases (OM) in adenoid cystic carcinoma (ACC).

Methods

Retrospective study of 42 patients with metastatic ACC of the head and neck. Imaging studies were analyzed to identify patients with OM (1–5 lesions) at any point during follow-up.

Results

There was radiographic evidence of OM in 33/42 (79%) patients. Eighteen patients had OM when treated for metastases, with median overall survival (OS) of 36.0 versus 9.2 years for patients with polymetastases (6+ lesions, HR 0.38, 95%CI 0.14–0.89). Earlier locally ablative treatment, but not systemic treatment, of patients with OM predicted improved survival 3 years after metastasis (HR 0.15, 95%CI 0.02–0.63) and postponed systemic treatment by 80 more months (HR 0.22, 95%CI 0.07–0.71).

Conclusions

There is a considerable population of ACC patients with detectable oligometastases, and early locally ablative treatment of oligometastases may be associated with improved outcomes.

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Assessment of deep inferior epigastric perforator flap perfusion with near-infrared fluorescence: A pilot study and description of a standardized working protocol

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J Plast Reconstr Aesthet Surg. 2021 Nov 16:S1748-6815(21)00590-8. doi: 10.1016/j.bjps.2021.11.043. Online ahead of print.

ABSTRACT

Fat necrosis (FN) is a common complication after autologous breast reconstruction (ABR) using a free flap, which can influence reconstruction outcome and patient satisfaction. Intraoperative near-infrared fluorescence imaging using indocyanine green (ICG) permits the visualization of flap perfusion. The aim of this study was to assess the effect of near-infrared fluorescence on FN incidence in patients undergoing an ABR with a deep inferior epigastric perforator flap (DIEP) and to propose a standard working protocol for this technique. In this prospective study, patients undergoing one-sided ABR with a DIEP were included. The standard DIEP procedure was complemented with near-infrared fluorescence imaging using the fluorescent tracer ICG to evaluate flap perfusion. This cohort was compared to a retrospectiv e cohort of DIEP procedures without near-infrared fluorescence imaging. Patients and surgery characteristics, as well as postoperative complications, were registered and compared. In both cohorts, 24 patients were included. No significant differences were present between patients and surgery characteristics, including no difference in duration of surgery. In the prospective and retrospective group, the incidence of FN was 4.2% and 33%, respectively (p-value = 0.023). Moreover, microsurgeons were positive about using near-infrared fluorescence as it either provided additional information about perfusion or confirmed the clinical assessment. Our pilot study showed a significant decrease of FN in patients undergoing an ABR with a DIEP when near-infrared fluorescence imaging was used to assess flap perfusion. This study provides a standardized working protocol for near-infrared fluorescence imaging. In the future, large multicenter studies should focus on the quantification of near-infr ared fluorescence imaging.

PMID:34924327 | DOI:10.1016/j.bjps.2021.11.043

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Pharyngo‐Esophageal Modulatory Swallow Responses to Bolus Volume and Viscosity Across Time

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Objectives/Hypothesis

Modulation of the pharyngeal swallow to bolus volume and viscosity is important for safe swallowing and is commonly studied using high-resolution pharyngeal manometry (HRPM). Use of unidirectional pressure sensor technology may, however, introduce variability in swallow measures and a fixed bolus administration protocol may induce time and order effects. We aimed to overcome these limitations and to investigate the effect of time by repeating randomized measurements using circumferential pressure sensor technology.

Study Design

Sub-set analysis of data from the placebo arm of a randomized, repeated measures trial.

Methods

HRPM with impedance was recorded using a solid-state catheter with 36 circumferential pressure sensors and 18 impedance segments straddling from hypopharynx to stomach. Testing included triplicates of 5, 10, and 20 ml thin liquid and 10 ml thick liquid boluses, the order of the thin liquid boluses was randomized. The swallow challenges were repeated approximately 10 minutes after finishing the baseline measurement.

Results

We included 19 healthy adults (10/9 male/female; age 24.5 ± 4.1 year). Intrabolus pressure, all upper esophageal sphincter (UES) opening and relaxation metrics, and flow timing metrics increased with larger volumes. A thicker viscosity decreased UES relaxation time, UES basal pressure, and flow timing metrics, whereas UES opening extent increased. Pre-swallow UES basal pressure and post-swallow UES contractile integral decreased over time.

Conclusion

Using circumferential pressure sensor technology, the effects of volume and viscosity were largely consistent with previous reports. UES contractile pressures reduced over time. The growing body of literature offers a benchmark for recognizing aberrant pharyngo-esophageal motor responses.

Level of Evidence

3 Laryngoscope, 2021

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