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Κυριακή 3 Απριλίου 2022

In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation

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Abstract

Modern therapeutic approaches have led to an improvement in the chances of surviving a diagnosis of cancer. However, this may come with side effects, with patients experiencing adverse cardiovascular events or exacerbation of underlying cardiovascular disease related to their cancer treatment. Rodent models of chemotherapy-induced cardiotoxicity are useful to define pathophysiological mechanisms of cardiac damage and to identify potential therapeutic targets. The key mechanisms involved in cardiotoxicity induced by specific different antineoplastic agents are summarized in this state-of-the-art review, as well as the rodent models of cardiotoxicity by different classes of anticancer drugs, along with the strategies tested for primary and secondary cardioprotection. Current approaches for early detection of cardiotoxicity in preclinical studies with a focus on the application of advanced imaging modalities and biomarker strategies are also discussed.

Graphical abstract

Potential applications of cardiotoxicity modelling in rodents are illustrated in relation to the advancements of promising research topics of cardiotoxicity. Created with BioRender.com.

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Functional Impact and Regulation of Alternative Splicing in Mouse Heart Development and Disease

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Abstract

Alternative splicing (AS) plays a major role in the generation of transcript diversity. In the heart, roles have been described for some AS variants, but the global impact and regulation of AS patterns are poorly understood. Here, we studied the AS profiles in heart disease, their relationship with heart development, and the regulatory mechanisms controlling AS dynamics in the mouse heart. We found that AS profiles characterized the different groups and that AS and gene expression changes affected independent genes and biological functions. Moreover, AS changes, specifically in heart disease, were associated with potential protein–protein interaction changes. While developmental transitions were mainly driven by the upregulation of MBNL1, AS changes in disease were driven by a complex regulatory network, where PTBP1 played a central role. Indeed, PTBP1 over-expression was sufficient to induce cardiac hypertrophy and diastolic dysfunction, potentially by perturb ing AS patterns.

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The Role of Angiogenesis and Arteriogenesisin Myocardial Infarction and Coronary Revascularization

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Abstract

Surgical myocardial revascularization is associated with long-term survival benefit in patients with multivessel coronary artery disease. However, the exact biological mechanisms underlying the clinical benefits of myocardial revascularization have not been elucidated yet. Angiogenesis and arteriogenesis biologically leading to vascular collateralization are considered one of the endogenous mechanisms to preserve myocardial viability during ischemia, and the presence of coronary collateralization has been regarded as one of the predictors of long-term survival in patients with coronary artery disease (CAD). Some experimental studies and indirect clinical evidence on chronic CAD confirmed an angiogenetic response induced by myocardial revascularization and suggested that revascularization procedures could constitute an angiogenetic trigger per se. In this review, the clinical and basic science evidence regarding arteriogenesis and angiogenesis in both CAD and coro nary revascularization is analyzed with the aim to better elucidate their significance in the clinical arena and potential therapeutic use.

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Analysis of Different Techniques of Tonsillectomy: An Insight

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Abstract

Tonsillectomy is one of the most commonly performed surgical procedure in otolaryngology especially in children. This is an age old procedure which has seen continuous changes in the surgical technique from guillotine method to snare technique to coblation tonsillectomy, and is still evolving day by day. But there are no consensus as to which technique is the best or most appropriate for tonsillectomy. The objective of this study is to compare three different surgical techniques of tonsillectomy namely the Cold dissection snare technique (CDST), Bipolar electro-dissection technique (BEDT) and Harmonic scalpel technique (HST) and to identify the method which is safe, with less operative time, which offers decreased intra-operative blood loss and with lowest post-operative morbidity and complications. This prospective and comparative study was conducted over a time duration of 1 year 6 months from January 2018 to July 2019 after the approval from ethical committee. Total 150 cases of tonsillectomy were done by dividing into three groups of 50 cases each. The study showed maximum cases of tonsillitis in the age group less than 10 years and the most common indication for tonsillectomy being chronic recurrent tonsillitis. Harmonic scalpel technique (HST) had least operative time, least intra-operative blood loss, took minimum time for resumption of normal diet and normal activity and also had least pain score on post-operative day 1st, 5th, 10th and 15th. STATISTICS: Kruskall-Wallis and the non-parametric Analysis of variance (ANOVA) tests were applied to determine statistically significant variances. All the differences are found to be significant P < 0.05. Harmonic Scalpel Technique (HST) is the latest technique as it is associated with quicker procedure, less intraoperative blood loss and less post-operative pain.

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Endoscopic Adenoidectomy Replacing the Outdated Curette Adenoidectomy: Comparison of the Two Methods at a Tertiary Care Centre

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Abstract

To compare intraoperative and postoperative parameters of the two techniques of adenoidectomy, endoscope and microdebrider powered adenoidectomy and conventional adenoidectomy. Study Design Prospective study. Setting: Academic tertiary referral centre. In our study, cases of adenoid hypertrophy were randomly selected from the outpatient department of department of ORL & HNS. Out of these patients, 30 underwent Endoscopic adenoidectomy (EA) (Group A) and 30 underwent Conventional adenoidectomy (CA) (Group B). All of the patients were assessed pre-operatively, intra-operatively and post-operatively to compare the various parameters. The most common complaint in both the groups was mouth breathing with snoring. Intra-operative bleeding was 29.15 ml in group EA and 15.2 ml in group CA. Operative time for CA was shorter at 21.8 min as compared to 32.1 min for group EA. Residual adenoids and injury to adjacent structures were more common in group CA. Hospital stay was 3.2 days for EA patients and 3.43 days for CA patients. Resolution of symptoms was near comparable in both groups. Operative time and intra-operative bleeding are both significantly reduced with the CA as opposed to EA. However, injury to adjacent structures and residual adenoids occur significantly less in group EA. After weighing the risks and benefits, we can conclude that EA is comparatively better than CA.

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A Study to Assess the Effect of Size & Site of Tympanic Membrane Perforation on Hearing Loss

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Abstract

The objective of the study was to assess the effect of size & site of tympanic membrane perforation on hearing loss. The study was carried out in ENT department of a tertiary health care hospital, between October 2018 and March 2020 (a total of 18 months). Patients aged 15–50 years having chronic otitis media with dry central perforation were included in the study after taking informed written consent and were evaluated with detailed history, clinical examination including otomicroscopy, tuning fork tests and pure tone audiometry. The patients were then posted for Tympanoplasty and just prior to the procedure, the tympanic membrane perforation size was measured using the Castroviejo caliper and site was noted using otomicroscopy. The status of the middle ear mucosa and ossicles were also analyzed to ensure normal middle ear mucosa and normal ossicular mobility and continuity and only then were these patients included in the study. All the patients in the study were evaluated for hearing loss using air conduction measurements in pure tone audiometry done at 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 3000 Hz and 4000 Hz. Hearing loss was found to be directly proportional to the size of perforation in our study. The site of the perforation has a significant association with the degree of hearing loss. Those perforations with posterior quadrant involvement and multiple quadrant involvement had a higher hearing loss. From our study, we concluded that there is a significant relationship between size and site of the perforation and the amount of hearing loss.

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Development and Validation of Instrument for Operative Competency Assessment in Selective Neck Dissection

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Annals of Otology, Rhinology &Laryngology, Ahead of Print.
Background:Instruments to assess surgical skills have been validated for several key indicator procedures in otolaryngology. Selective neck dissection is a core procedure for which trainees must integrate knowledge of complex head and neck anatomy with technical surgical skills. An instrument for assessment of surgical performance in selective neck dissection has not been previously developed. The objective of the current study is to develop and validate an instrument for assessing surgical competency for level II-IV selective neck dissection.Design:A Delphi working group comprised of 23 fellowship trained head and neck surgeons from 17 institutions was assembled. The modified Delphi method encompassed a 3-step process, including 2 anonymous voting rounds to successively refine individual items and establish levels of consensus. Thresholds for achieving strong consensus, at >80% agreement, were determined a p riori. The resulting instrument was subsequently validated in a prospective cohort of 17 resident surgeons, spanning postgraduate year 1 to 5 training experience. Participants were asked to perform a level II-IV selective neck dissection on fresh-frozen cadaveric specimens. Performance was scored by 2 independent, blinded observers using the devised instrument and construct validity was assessed.Results:Through the modified Delphi process a final list of 30 items, considered to be the most essential items for achieving the goals of a level II-IV selective neck dissection, was developed. Construct validity was supported by a positive association between instrument scores compared to both resident postgraduate year level and number of head and neck rotations completed.Conclusion:The development and validation of a novel instrument for assessment of surgical competency in level II-IV selective neck dissection, a key indicator case in otolaryngology, is described. This new instrument ma y be used to provide objective feedback on overall and task-specific competency to identify surgical deficiencies and offer granular feedback to enhance surgical training.
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Readmission Rates Following Major Head and Neck Surgery With Concurrent Tracheostomy

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Annals of Otology, Rhinology &Laryngology, Ahead of Print.
Objectives:To determine the influence of major head and neck procedures on readmission and complication rates following tracheostomy.Methods:A retrospective cohort study using the 2005 to 2017 National Surgical Quality Improvement Program (NSQIP) database. Current Procedural Terminology codes were used to identify tracheostomy patients and to define the underlying head and neck procedure. Patients under the age of 18 and with unknown pre-operative variables were excluded. Univariate and multivariable analyses were performed.Results:A total of 3240 tracheostomy patients undergoing major head and neck surgery were identified in NSQIP. The 30-day mortality rate was 104 (3.2%) and 258 (9.0%) patients were readmitted. 637 (19.7%) patients had an unplanned return to the operating room. There were 1606 (49.6%) non-tracheostomy specific complications, which included 850 (26.2%) medical and 1142 (35.2%) surgical complica tions. On multivariable analysis, we found that the underlying procedures did not impact the risk of readmission (P > .05 for all). The underlying procedure was also not associated with unplanned return to the operating room except for thyroidectomies, which had a lower risk than free tissue graft reconstruction (OR = 0.53 (95%CI 0.31, 0.88), P = .018).Conclusion:While almost 1 in every 2 patients had a complication following major head and neck surgery that included creation of a tracheostomy, the rate of readmission is comparatively low and is not associated with the underlying procedure. These findings should reassure head and neck surgeons that properly managed tracheostomies do not constitute a disproportionate risk of readmission.
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The Effect of Topical Tranexamic Acid in Endoscopic Sinus Surgery: A Triple Blind Randomized Clinical Trial

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Annals of Otology, Rhinology &Laryngology, Ahead of Print.
Objective:Our aim is to evaluate the effect of topical tranexamic acid (TA) on bleeding and surgical quality field in the functional endoscopic sinus surgery (FESS).Methods:A total of 74 patients who underwent FESS due to chronic rhinosinusitis were included. The patients were randomized into 2 groups. TA group (n = 37) received a topical cotton pledget soaked with TA and placebo (PL) group (n = 37) received a pledget soaked with saline solution.Results:A significant effect was noted for the TA group versus the PL group in the grade 1 of the Boezaart scale at 35 minutes (4 for TA group and no case for PL group). This effect was absent for higher grades. We did not notice a significant effect between the 2 groups at 5 minutes. Blood loss was 359 ml in the TA group versus 441 ml in the PL group. No significant change was observed between the 2 groups concerning the blood parameters. No side effects were reported.Conclusion:Despite its safety when administrated locally and its low cost, TA provides limited effect on quality of surgical field after 35 minutes of the start of FESS in the patients with chronic rhinosinusitis. This effect was absent at the start of the intervention and when analyzing the blood loss and hematologic parameters.
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Cervical Necrotizing Fasciitis and Free Tissue Transfer

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Annals of Otology, Rhinology &Laryngology, Ahead of Print.
Objectives:Aggressive surgical debridement is required in cervical necrotizing fasciitis, and in severe defects, subsequent free tissue transfer might be necessary. However, there is concern that the inflammatory environment of the infection site may threaten free flap viability, particularly with concerns for thrombosis of feeding vessels and compromised tissue integration. Cases in the head and neck area are rare, so there are limited data regarding outcomes of free tissue transfer in these patients.Methods:A retrospective chart review assessed patients with cervical necrotizing fasciitis treated at an academic tertiary hospital between 2015 and 2021. Twenty-five patients were identified, and eight required free tissue transfer after adequate surgical debridement. Treatment, hospital course, and demographic data were collected on these eight patients.Results:All flaps had full survival at follow up (median fol low up 3 months, range 1-39 months) without concerns for vascular compromise.Conclusion:These data suggest that in patients with large soft tissue defects due to cervical necrotizing fasciitis, free tissue transfer may be a safe treatment modality.
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Benign paroxysmal positional vertigo

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Benign paroxysmal positional vertigo (BPPV) is characterized by positional vertigo (brief attacks of rotatory vertigo triggered by head position changes in the direction of gravity) and is the most common peripheral cause of vertigo. There are two types of BPPV pathophysiology: canalolithiasis and cupulolithiasis. In canalolithiasis, otoconial debris is detached from the otolithic membrane and floats freely within the endolymph of the canal. In cupulolithiasis, the otoconial debris released from the otolithic membrane settles on the cupula of the semicircular canal and the specific gravity of the cupula is increased.
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Πέμπτη 31 Μαρτίου 2022

A Mass in the Infratemporal Fossa

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A 51-year-old woman presented with headache, jaw pain, paresthesia, trismus, and a history of anxiety, depression, emphysema, hyperlipidemia, migraines, pseudoseizures, and no pertinent surgery nor head trauma. What is your diagnosis?
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