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Traditionally viewed as poorly plastic, neutrophils are now recognized as functionally diverse; however, the extent and determinants of neutrophil heterogeneity in humans remain unclear. We performed a comprehensive immunophenotypic and transcriptome analysis, at a bulk and single-cell level, of neutrophils from healthy donors and patients undergoing stress myelopoiesis upon exposure to growth factors, transplantation of hematopoietic stem cells (HSC-T), development of pancreatic cancer and viral infection. We uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation and exposure to environmental signals. Integrated control of developmental and inducible transcriptional programs linked flexible granulopoietic outputs with elicitation of stimulus-specific functional responses. In this context, we detected an acute interferon (IFN) response in the blood of patients receiving HSC-T that was mirrored by marked upregulation of IFN-stimulated genes in neutrophils but not in monocytes. Systematic characterization of human neutrophil plasticity may uncover clinically relevant biomarkers and support the development of diagnostic and therapeutic tools.
Subject(s)
Myelopoiesis , Neutrophils , Biomarkers/metabolism , Humans , Interferons/genetics , Interferons/metabolism , Neutrophils/metabolism , Plastics/metabolismABSTRACT
Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.
Subject(s)
Adenocarcinoma , Carcinoma, Squamous Cell , Nose Neoplasms , Paranasal Sinus Neoplasms , Paranasal Sinuses , Humans , Adenocarcinoma/pathology , Nose Neoplasms/diagnosis , Nose Neoplasms/genetics , Nose Neoplasms/therapy , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/genetics , Paranasal Sinus Neoplasms/therapyABSTRACT
OBJECTIVE: Open partial horizontal laryngectomies (OPHLs) represent a comparable alternative to total laryngectomy and nonsurgical protocols in selected cases. While short-term functional outcomes of OPHLs have been widely investigated, few have focused on the effect of aging on residual laryngeal structures. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic center. METHODS: Patients who underwent OPHLs after at least 1 year follow-up and optimal functional rehabilitation were included in the study. Swallowing function was assessed according to PAS (Penetration aspiration scale) and Pooling scores. Spectrogram analysis of voice was conducted according to Yanagihara classification and acoustic parameters were also recorded. Subjective questionnaire data about phonation and swallowing were also recorded. Data obtained were compared among patients according to age at time of surgery, evaluation and duration of follow-up. RESULTS: Ninety-seven patients were enrolled with a mean age at surgery and evaluation of 63 and 70 years old, respectively. Median follow-up length was 5 years. OPHL type II was mostly performed. No significant correlation was observed between most of the analyzed variables and patient's age at the time of surgery and at the time of evaluation. Some acoustic parameters were negatively correlated with follow-up length, while Jitter, NHR (Noise-Harmonic Ratio), and Global grade and Roughness were significantly higher in patients >65 years old. CONCLUSION: Patients who complete rehabilitation reach equally good results as their younger peers with stability over time. Finally, the effects of aging on residual larynx are of minor entity compared to the nonoperated patients. LEVEL OF EVIDENCE: Level IV-retrospective cohort study.
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OBJECTIVE: To evaluate if fusion computed tomography-diffusion-weighted magnetic resonance imaging may have a role in the pre-operative assessment of congenital middle-ear cholesteatoma. METHODS: A retrospective chart review of surgically treated congenital middle-ear cholesteatoma patients over a 2-year timespan was conducted. Pre-operative staging was performed on computed tomography and fusion computed tomography-diffusion-weighted magnetic resonance imaging based on extension of the disease according to the ChOLE classification system and the Potsic classification system. Intra-operative staging was compared to imaging findings to evaluate accuracy of the two imaging modalities in predicting congenital middle-ear cholesteatoma extent. RESULTS: Computed tomography was able to correctly predict congenital middle-ear cholesteatoma extent in three out of six cases according to the ChOLE classification system, all of which were staged as Ch1a and Ch1b on pre-operative computed tomography. Cases in which computed tomography was not able correctly to determine congenital middle-ear cholesteatoma extent were staged as Ch3 on pre-operative computed tomography. Fusion scans correctly determined congenital middle-ear cholesteatoma extent in all cases according to the ChOLE classification. CONCLUSIONS: Fusion computed tomography-diffusion-weighted magnetic resonance imaging may be helpful in cases of congenital middle-ear cholesteatoma where pre-operative computed tomography shows mastoid and antrum opacification, in which computed tomography alone may overestimate cholesteatoma extension beyond the level of the lateral semi-circular canal.
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OBJECTIVE: Diffusion of endoscopic techniques for the resection of ethmoid bone malignancies through a transcribriform approach (TA) has raised new challenges regarding reconstruction options to reduce post-operative complications. Although there is consensus on the advantages of vascularized flaps over free grafts for large defects, no standard protocol exists on reconstruction procedures. In addition, although the pedicled nasoseptal flap has been extensively discussed, few studies have been published on extranasal pedicled flaps. The aim of this manuscript is to provide a detailed description of a reconstruction technique for large anterior skull base defects with the pericranial flap as part of a multilayered reconstruction. Moreover, patients treated with this approach were retrospectively assessed for post-operative complications. METHODS: A detailed description of the reconstruction procedure as performed in our departments is provided. Pictures depicting the main surgical steps are also included. In addition, preliminary functional results from a retrospective series of patients who underwent a TA and subsequent pericranial flap-based multilayer reconstruction for ethmoid roof malignancies between 2016 and 2022 at two institutional centers are reported. RESULTS: 16 patients were included in the study. Nine patients (56.3%) underwent adjuvant radiotherapy. Two patients had a biochemically-confirmed postoperative CSF leak. Only one of the two patients required surgical revision. During follow-up (mean 13 months), no other early nor delayed complications were observed. CONCLUSION: A standardized surgical technique with pericranial flap as part of a multilayered reconstruction for large anterior skull base defects following resection of sinonasal malignancies is proposed, which appears to be a safe choice when endonasal flaps are not available. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 133:2942-2947, 2023.
Subject(s)
Plastic Surgery Procedures , Skull Base Neoplasms , Humans , Retrospective Studies , Skull Base/surgery , Surgical Flaps/surgery , Endoscopy/methods , Skull Base Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgeryABSTRACT
Management of vestibular schwannoma (VS) is a complex process aimed at identifying a clinical indication for fractionated stereotactic radiotherapy (sRT) or microsurgical resection or wait and scan (WS). The aim of the review was to clarify which patient and tumor parameters may lead to different therapeutic choices, with a view to a personalized VS approach. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between February and March 2022. The authors defined six parameters that seemed to influence decision-making in VS management: 1-incidental VS; 2-tumor size; 3-tumor regrowth after sRT; 4-subtotal resection; 5-patients' age; 6-symptoms. The initial search yielded 3532 articles, and finally, 812 articles were included. Through a qualitative synthesis of the included studies, management strategies were evaluated and discussed. An individualized proposal of procedures is preferable as compared to a single gold-standard approach in VS decision-making. The most significant factors that need to be considered when dealing with a VS diagnosis are age, tumor size and hearing preservation issues.
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The aim of the present study is to investigate a possible delay in diagnosis and therapy administration for Head and Neck oncological patients, during the Sars-Cov2 pandemic and to compare the median tumor stage (MTS) at presentation. This is a retrospective review on patients who presented at the University Hospital of Modena with a newly diagnosis of Head and Neck cancer (HNC), comparing the first pandemic period (from March 1st, to October 15th 2020) to the same period of 2019. The time in days from the diagnostic suspicion to the beginning of the treatment, hereafter referred to as delay in treatment initiation (DTI), and the tumor stage were calculated for all the enrolled patients. Mean percentage of reduction of the clinical and surgical activities was - 25.8% (range: - 66-1.5%), with higher percentages in phase 1 for all the analyzed activities. 125 HNC patients were enrolled in the analysis as the study group, compared with a cohort of 140 patients from the previous year. The MTS was III for both groups, however a significant statistical difference was determined in the stage comparison, p = 0.023. When DTI was analyzed no statistically significant differences were appreciated. A more advanced stage at presentation was demonstrated at our institution for HNC patients during the first phase of the Covid-19 pandemic in 2020. However, a statistically significant delay in time between diagnosis and therapy administration was not assessed, thus confirming the maintenance of a high level of care even in the COVID-19 era.
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INTRODUCTION: Ossiculoplasty is aimed at improving or maintaining the conductive portion of hearing in patients subjected to otologic surgery. However, satisfying hearing is frequently observed after tympanoplasty even in the absence of ossicular chain reconstruction. Aims of this article would be to evaluate hearing outcomes, in terms of pure tone average air-bone gap (PTA-ABG), in patients subjected to tympanoplasty for middle ear disease whose ossicular chain has not been reconstructed, and then to investigate factors influencing those outcomes. MATERIALS AND METHODS: Retrospective chart review of patients who underwent ear surgery from year 2003 to 2021 at the Otolaryngology-Head and Neck surgery department of the University Hospital of Modena was performed. Audiometric test results from patients who did not receive any ossicular chain reconstruction were collected and analyzed. SETTING: Tertiary University referral center. RESULTS: The mean patients' follow-up was 34.1 months. Overall, mean PTA-ABG in the study population was 23.5 dB. Integrity of stapes superstructure, malleus handle and malleus head, together with the use of tragal cartilage graft over autologous temporalis fascia to reconstruct the tympanic membrane were found to be significantly associated with better hearing outcomes, as demonstrated by lower PTA-ABG values. Stapes superstructure was found to be associated with more favorable outcomes in multivariate analysis, net of confounding factors. CONCLUSION: Good hearing performance can be obtained in patients subjected to middle ear surgery, even if the ossicular chain is not reconstructed. Presence of ossicular chain remnants and the use of a rigid material for tympanic membrane reconstruction are the factors that seem to most favorably influence hearing outcomes after surgery for middle ear disease.
Subject(s)
Ossicular Prosthesis , Ossicular Replacement , Hearing , Humans , Ossicular Replacement/methods , Retrospective Studies , Treatment Outcome , Tympanoplasty/methodsABSTRACT
This systematic review aims to (a) define what instruments are available to measure quality of life (QoL) in patients undergoing tympanoplasty for chronic otitis media (COM) and what is the most commonly selected timing to do so; (b) compare outcomes from different surgical techniques; and (c) describe any reported correlation between subjective and functional results. This review was conducted following the PRISMA statement recommendations. Of the 151 articles screened, 24 were included. Most studies had a prospective design. The mean age at surgery was 44.5 years. A microscopic retroauricular approach was the most common surgical technique. Most articles included both primary and revision surgeries. The most commonly used questionnaire was the Glasgow Benefit Inventory (GBI), followed by the Chronic Ear Survey (CES), the Chronic Otitis Media Outcome Test 15 (COMOT-15) and the Zurich Chronic Middle Ear Inventory (ZCMEI-21). Questionnaires were administered about 12 months after surgery in most studies. Ten studies reported possible associations between hearing results and QoL. QoL assessment after COM surgery variably relies on disease-specific and non-specific questionnaires. Patients are usually evaluated 12 months after surgery, and this appears to be a suitable timing to contrast the possible bias effect of different tympanoplasty techniques associated with different healing times. A comparison between QoL outcomes in different surgical approaches cannot be made, as several influencing factors have not been detailed in the included studies. Few studies have investigated the correlation between subjective and objective outcomes of tympanoplasty for COM so far.