Acoustic outcomes and voice-related quality of life in male-to-female transsexuals undergoing Wendler glottoplasty: a single-centre experience.

INTRODUCTION: Many transsexual women seek to feminise their voice through pitch elevation surgeries so that it becomes congruent with their gender identity. This study aims to determine the safety and effectiveness of Wendler glottoplasty (WG) in vocal feminisation through the assessment of acoustic and aerodynamic parameters of the voice, as well as voice-related quality of life (QoL) in male-to-female transsexuals. MATERIAL AND METHODS: We retrospectively reviewed the medical records of transsexual women who underwent WG for voice feminisation at our institution between 2016 and 2023. All acoustic and aerodynamic analyses, a voice self-assessment, and a videolaryngostroboscopic evaluation were performed in the immediate preoperative period and at the follow-up visit 6 weeks after the procedure. RESULTS: A total of 11 patients with a mean age of 32.73 years were included. After WG, there was a significant fundamental frequency and speaking fundamental frequency increase of 109.64 Hz and 83.48 Hz, respectively (p < 0.001), representing an average rise by 9.71 semitones and 8.36 semitones (STs), respectively. No significant differences were found between the mean pre- and postoperative values of fundamental frequencies, frequency range, upper limit of the frequency range of spoken voice, and maximum phonation time. Contrarily, the mean lower limit of frequency range rose by 75.56 Hz (p < 0.001), representing an average increase of 10.56 STs. None of the assessed spirometric parameters changed significantly after WG (p > 0.05). The mean overall Voice Handicap Index (VHI) and Voice-Related Quality of Life (V-RQOL) scores significantly improved after the surgery, decreasing by 24.54 points (p = 0.008) and 11.5 points (p = 0.001), respectively. A significant improvement was observed in the functional and emotional domains of VHI. Additionally, significantly fewer patients considered the overall quality of their voice to be "poor" after WG. CONCLUSIONS: WG constitutes an effective method of surgical voice feminisation in male-to-female transsexuals with concurrent improvement in their voice-related QoL. Furthermore, it remains a safe procedure without persistent complications and negative influence on the acoustic-aerodynamic measures of the voice.

Impact of Wendler glottoplasty on acoustic measures and quality of voice in transgender women: a systematic review and meta-analysis.

PURPOSE: Since new evidence regarding the impact of Wendler glottoplasty (WG) on the voice in transgender women became available in the literature in recent years, we aimed to perform an updated systematic review and meta-analysis to determine the actual safety and efficacy of WG in the process of vocal feminization. METHODS: PubMed, Embase, and Cochrane were searched for English-language articles published until July 4, 2023. Studies were found eligible if they evaluated the impact of WG on the acoustic-aerodynamic measures and quality of voice in transgender women. RESULTS: Twenty-three studies were identified. After exclusion of three studies due to incomplete data, 20 studies including 656 patients were included in the meta-analysis. After WG, there was a significant increase of fundamental frequency, speaking fundamental frequency, and lower limit of the frequency range (p < 0.001). Concurrently, a significant reduction of frequency range and maximum phonation time was observed (p < 0.001). No significant differences were found between the pre- and postoperative values regarding the Grade, Roughness, Breathiness, Asthenia, and Strain scale score (p = 0.339). The overall score in the Trans Woman Voice Questionnaire (TWVQ) significantly improved after WG (p < 0.001). CONCLUSIONS: WG is an effective voice feminization method in transgender women, associated with a high procedural success and low risk of postoperative complications. Significantly improved TWVQ score after surgery suggests its positive impact on the voice-related quality of life. Postoperative decrease of maximum phonation time and frequency range does not seem to significantly impact the effectiveness of voice production.

Mast Cells as a Target-A Comprehensive Review of Recent Therapeutic Approaches.

Mast cells (MCs) are the immune cells distributed throughout nearly all tissues, mainly in the skin, near blood vessels and lymph vessels, nerves, lungs, and the intestines. Although MCs are essential to the healthy immune response, their overactivity and pathological states can lead to numerous health hazards. The side effect of mast cell activity is usually caused by degranulation. It can be triggered by immunological factors, such as immunoglobulins, lymphocytes, or antigen-antibody complexes, and non-immune factors, such as radiation and pathogens. An intensive reaction of mast cells can even lead to anaphylaxis, one of the most life-threatening allergic reactions. What is more, mast cells play a role in the tumor microenvironment by modulating various events of tumor biology, such as cell proliferation and survival, angiogenesis, invasiveness, and metastasis. The mechanisms of the mast cell actions are still poorly understood, making it difficult to develop therapies for their pathological condition. This review focuses on the possible therapies targeting mast cell degranulation, anaphylaxis, and MC-derived tumors.

Oncolytic Adenoviruses Armed with Co-Stimulatory Molecules for Cancer Treatment.

In clinical trials, adenovirus vectors (AdVs) are commonly used platforms for human gene delivery therapy. High genome capacity and flexibility in gene organization make HAdVs suitable for cloning. Recent advancements in molecular techniques have influenced the development of genetically engineered adenovirus vectors showing therapeutic potential. Increased molecular understanding of the benefits and limitations of HAdVs in preclinical research and clinical studies is a crucial point in the engineering of refined oncolytic vectors. This review presents HAdV species (A-G) used in oncotherapy. We describe the adenovirus genome organizations and modifications, the possibilities oncolytic viruses offer, and their current limitations. Ongoing and ended clinical trials based on oncolytic adenoviruses are presented. This review provides a broad overview of the current knowledge of oncolytic therapy. HAdV-based strategies targeting tumors by employing variable immune modifiers or delivering immune stimulatory factors are of great promise in the field of immune oncologyy This approach can change the face of the fight against cancer, supplying the medical tools to defeat tumors more selectively and safely.

Transoral Robotic Surgery in the Management of Submandibular Gland Sialoliths: A Systematic Review.

This study aimed to systematically review the literature to determine the efficacy and safety of transoral robotic surgery (TORS) in the management of submandibular gland (SMG) sialolithiasis. PubMed, Embase, and Cochrane were searched for English-language articles evaluating TORS in the management of SMG stones published up to 12 September 2022. Nine studies with a total of 99 patients were included. Eight patients underwent TORS followed by sialendoscopy (TS); 11 patients underwent sialendoscopy followed by TORS and sialendoscopy (STS); 4 patients underwent sialendoscopy followed by TORS only (ST); and 4 patients underwent TORS without sialendoscopy (T). The mean operative time amounted to 90.97 min. The mean procedure success rate reached 94.97%, with the highest for ST (100%) and T (100%), followed by the TS (95.04%) and STS (90.91%) variants. The mean follow-up time was 6.81 months. Transient lingual nerve injury occurred in 28 patients (28.3%) and was resolved in all of them within the mean of 1.25 months. No permanent lingual nerve injury was reported. TORS is a safe and effective management modality for hilar and intraparenchymal SMG sialoliths, with high procedural success in terms of successful sialolith removal, SMG preservation, and reduced risk of permanent postoperative lingual nerve damage.

External validation of the Chicago Chiari Outcome Scale in adults with Chiari malformation type I.

OBJECTIVE: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients. METHODS: The authors retrospectively analyzed the medical records of symptomatic patients with CM-I who underwent posterior fossa decompression between 2010 and 2018 in six neurosurgical departments. Each patient was clinically assessed at the latest available follow-up. Gestalt outcome was determined as improved, unchanged, or worsened compared with the preoperative clinical state. Additionally, the CCOS score was calculated for each patient based on the detailed clinical data. To verify the ability of the CCOS to determine clinical improvement, the area under the receiver operating characteristic (AUROC) curve was evaluated. A logistic regression analysis using all four components of the CCOS (pain symptoms, nonpain symptoms, functionality, and complications) was performed to establish predictors of the improved outcome. RESULTS: Seventy-five individuals with a mean age of 42 ± 15.32 years were included in the study. The mean follow-up duration was 52 ± 33.83 months. Considering gestalt outcome evaluation, 41 patients (54.7%) were classified as improved, 24 (32%) as unchanged, and 10 (13.3%) as worsened. All patients with a CCOS score of 14 or higher improved, while all those with a CCOS score of 8 or lower worsened. The AUROC was 0.986, suggesting almost perfect accuracy of the CCOS in delineating clinical improvement. A CCOS score of 13 showed high sensitivity (0.93) and specificity (0.97) for identifying patients with clinical improvement. Additionally, a meaningful correlation was found between higher CCOS scores in each component and better outcomes. Patient stratification by total CCOS score showed that those categorized as improved, unchanged, and worsened scored prevalently between 13 and 16 points, 10 and 12 points, and 4 and 9 points, respectively. CONCLUSIONS: In this adult cohort, the CCOS was found to be almost perfectly accurate in reflecting postoperative clinical improvement. Moreover, all four CCOS components (pain symptoms, nonpain symptoms, functionality, and complications) significantly correlated with patient clinical outcomes.

External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort.

PURPOSE: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales. METHODS: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year. RESULTS: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively. CONCLUSION: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.

Contrast-Enhanced Ultrasound in the Differentiation between the Most Common Benign Parotid Gland Tumors: A Systematic Review and Meta-Analysis.

Recently, contrast-enhanced ultrasound (CEUS) has become a promising tool in distinguishing benign from malignant parotid gland tumors. However, its usefulness in differentiating various benign parotid tumors has not been determined so far. This study aimed to systematically review the literature to determine the utility of CEUS in the preoperative differentiation between pleomorphic adenomas (PAs) and Warthin's tumors (WTs) of the parotid gland. PubMed, Embase, and Cochrane were searched for English-language articles published until 21 July 2022. Fifteen studies were included. On CEUS examination, a significantly greater percentage of PAs displayed heterogeneous enhancement texture compared to WTs. Contrarily, the enhanced lesion size, the enhancement margin, and the presence of the enhancement rim did not differ significantly between the entities. Significantly longer normalized mean transit time (nMTT) and time to peak (TTP) were observed in PAs. Contrarily, the mean values of area under the curve (AUC) and time from peak to one half (TPH) were significantly higher for WTs. Due to the considerable overlap among the qualitative CEUS characteristics of PAs and WTs, the reproducible, investigator-independent quantitative CEUS measurements have a greater potential to distinguish PAs from WTs, which might influence the selection of an appropriate management strategy.

Content Quality and Audience Engagement Analysis of Online Videos for Anterior Lumbar Interbody Fusion.

OBJECTIVE: For the majority of patients, the Internet constitutes the first source of health information influencing their medical decision-making. We aimed to assess the quality of the online videos regarding anterior lumbar interbody fusion (ALIF). METHODS: YouTube database was searched using 3 different phrases: "anterior lumbar interbody fusion", "ALIF", and "ALIF surgery". The first 50 videos for each phrase were selected. Video content was evaluated by 3 independent researchers using the DISCERN instrument. Qualitative data, quantitative data, and the source of upload were analyzed. RESULTS: A total of 24 videos were included. The mean DISCERN score was 38.21, indicating the poor quality of ALIF videos on YouTube. Video duration was positively correlated with DISCERN score (r = 0.71, P < 0.001) but not with the video power index (VPI). A negative correlation between time since upload and DISCERN score (r = -0.8 P < 0.001) was found. Furthermore, videos containing surgical complications, risk factors, and postoperative prognosis had a significantly higher DISCERN score. Neither DISCERN score nor a VPI correlated with the presence of intraoperative recordings. Videos including the explanation of the spine anatomy had a significantly higher number of likes (P = 0.018). CONCLUSIONS: Despite the increasing educational value of ALIF videos over time, the overall quality of YouTube videos on ALIF remains poor. However, the majority of videos can be recommended to the patient as an informative source of basic knowledge on the surgical details of the ALIF procedure. Longer video duration increases its quality without simultaneous negative influence on its popularity.

Clinical application of diffusion tensor imaging and fiber tractography in the management of brainstem cavernous malformations: a systematic review.

This study aimed to systematically review the literature to determine the clinical utility and perspectives of diffusion tensor imaging (DTI) in the management of patients with brainstem cavernous malformations (BSCMs). PubMed, Embase, and Cochrane were searched for English-language articles published until May 10, 2021. Clinical studies and case series describing DTI-based evaluation of patients with BSCMs were included. Fourteen articles were included. Preoperative DTI enabled to adjust the surgical approach and choose a brainstem safe entry zone in deep-seated BSCMs. Preoperatively lower fractional anisotropy (FA) of the corticospinal tract (CST) correlated with the severity of CST injury and motor deficits. Postoperatively increased FA and decreased apparent diffusion coefficient (ADC) corresponded with the normalization of the perilesional CST, indicating motor improvement. The positive (PPV) and negative predictive value (NPV) of qualitative DTI ranged from 20 to 75% and from 66.6 to 100%, respectively. The presence of preoperative and postoperative motor deficits was associated with a higher preoperative resting motor threshold (RMT) and lower FA. A higher preoperative CST score was indicative of a lower preoperative and follow-up Medical Research Council (MRC) grade. DTI facilitated the determination of a surgical trajectory with minimized risk of WMTs' damage. Preoperative FA and RMT might indicate the severity of preoperative and postoperative motor deficits. Preoperative CST score can reliably reflect patients' preoperative and follow-up motor status. Due to high NPV, normal CST morphology might predict intact neurological outcomes. Contrarily, sparse and relatively low PPV limits the reliable prediction of neurological deficits.

The Antifungal Action Mode of N-Phenacyldibromobenzimidazoles.

Our study aimed to characterise the action mode of N-phenacyldibromobenzimidazoles against C. albicans and C. neoformans. Firstly, we selected the non-cytotoxic most active benzimidazoles based on the structure-activity relationships showing that the group of 5,6-dibromobenzimidazole derivatives are less active against C. albicans vs. 4,6-dibromobenzimidazole analogues (5e-f and 5h). The substitution of chlorine atoms to the benzene ring of the N-phenacyl substituent extended the anti-C. albicans action (5e with 2,4-Cl2 or 5f with 3,4-Cl2). The excellent results for N-phenacyldibromobenzimidazole 5h against the C. albicans reference and clinical isolate showed IC50 = 8 µg/mL and %I = 100 ± 3, respectively. Compound 5h was fungicidal against the C. neoformans isolate. Compound 5h at 160-4 µg/mL caused irreversible damage of the fungal cell membrane and accidental cell death (ACD). We reported on chitinolytic activity of 5h, in accordance with the patterns observed for the following substrates: 4-nitrophenyl-N-acetyl-ß-d-glucosaminide and 4-nitrophenyl-ß-d-N,N',N″-triacetylchitothiose. Derivative 5h at 16 µg/mL: (1) it affected cell wall by inducing ß-d-glucanase, (2) it caused morphological distortions and (3) osmotic instability in the C. albicans biofilm-treated. Compound 5h exerted Candida-dependent inhibition of virulence factors.

In Vitro Anti-Candida Activity and Action Mode of Benzoxazole Derivatives.

A newly synthetized series of N-phenacyl derivatives of 2-mercaptobenzoxazole, including analogues of 5-bromo- and 5,7-dibromobenzoxazole, were screened against Candida strains and the action mechanism was evaluated. 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanone (5d), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichloro-phenyl)ethanone (5i), 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,4,6-trichlorophenyl)ethanone (5k) and 2-[(5-bromo-1,3-benzoxazol-2-yl)sulfanyl]-1-phenylethanone (6a) showed anti-C. albicans SC5314 activity, where 5d displayed MICT = 16 µg/mL (%R = 100) and a weak anti-proliferative activity against the clinical strains: C. albicans resistant to azoles (Itr and Flu) and C. glabrata. Derivatives 5k and 6a displayed MICP = 16 µg/mL and %R = 64.2 ± 10.6, %R = 88.0 ± 9.7, respectively, against the C. albicans isolate. Derivative 5i was the most active against C. glabrata (%R = 53.0 ± 3.5 at 16 µg/mL). Benzoxazoles displayed no MIC against C. glabrata. Benzoxazoles showed a pleiotropic action mode: (1) the total sterols content was perturbed; (2) 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(3,4-dichlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(2,3,4-trichlorophenyl)ethanol (8h-i) at the lowest fungistatic conc. inhibited the efflux of the Rho123 tracker during the membrane transport process; (3) mitochondrial respiration was affected/inhibited by the benzoxazoles: 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-chlorophenyl)ethanol and 2-(1,3-benzoxazol-2-ylsulfanyl)-1-(4-bromophenyl)ethanol 8c-d and 8i. Benzoxazoles showed comparable activity to commercially available azoles due to (1) the interaction with exogenous ergosterol, (2) endogenous ergosterol synthesis blocking as well as (3) membrane permeabilizing properties typical of AmB. Benzoxazoles display a broad spectrum of anti-Candida activity and action mode towards the membrane without cross-resistance with AmB; furthermore, they are safe to mammals.

Clinical Application of Diffusion Tensor Imaging in Chiari Malformation Type I- Advances and Perspectives. A Systematic Review.

BACKGROUND: Diffusion tensor imaging (DTI) application in Chiari malformation type I (CMI) is still poorly defined. This study aimed to systematically review the literature and propose perspectives toward the clinical application of DTI in CMI. METHODS: PubMed and Embase were searched for English-language articles published until October 20, 2020. Clinical studies and case series, evaluating fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), or radial diffusivity values in patients with CMI, were included. RESULTS: Eight articles were included. Lower FA values were found at the syrinx level, which decreased with syrinx extent and intensity of symptoms, reflecting myelopathy severity. Decreased AD and MD in the middle cerebellar peduncles in symptomatic patients with CMI might explain the presence of cerebellar signs. Increased FA in various supratentorial structures positively correlated with pain severity. Worse performance in neuropsychological tests correlated with decreased FA, increased MD, and radial diffusivity, reflecting axonal degeneration. Postoperative FA decrease in the brainstem compression area reflects successful decompression. A positive correlation was found between the extent of tonsillar ectopia and increased FA, MD, and AD values, which could act as an early indicator of acute brainstem compression. CONCLUSIONS: DTI might provide a valuable insight into the neurobiological foundation of symptomatic CMI presentation. The severity of white matter injury evident on DTI could serve as a reliable predictor of postoperative outcomes, therefore facilitating selection of appropriate surgical candidates. Postinterventional DTI reassessment might enable differentiation between unsuccessful surgical technique and irreversible myelopathy. The extent of tonsillar ectopia reflects the severity of microstructural brainstem injury.

Multimodal Treatment of Pediatric Ruptured Brain Arteriovenous Malformations: A Single-Center Study.

Bleeding from ruptured brain arteriovenous malformations (bAVMs) represents the most prevalent cause of pediatric intracranial hemorrhage, being also the most common initial bAVM manifestation. A therapeutic approach in these patients should aim at preventing rebleeding and associated significant morbidity and mortality. The purpose of this study was to determine the clinical outcomes of pediatric patients who initially presented at our institution with ruptured bAVMs and to review our experience with a multimodality approach in the management of pediatric ruptured bAVMs. We retrospectively reviewed pediatric patients' medical records with ruptured bAVMs who underwent interventional treatment (microsurgery, embolization, or radiosurgery; solely or in combination) at our institution between 2011 and 2020. We identified 22 patients. There was no intraoperative and postoperative intervention-related mortality. Neither procedure-related complications nor rebleeding were observed after interventional treatment. Modified Rankin Scale (mRS) assessment at discharge revealed 19 patients (86.4%) with favorable outcomes (mRS 0-2) and 3 patients (13.6%) classified as disabled (mRS 3). Microsurgery ensured the complete obliteration in all patients whose postoperative digital subtraction angiography (DSA) was available. Management of high-grade bAVMs with radiosurgery or embolization can provide satisfactory outcomes without a high disability risk.