Background: Laryngeal cancer affects quality of life (QoL), speech, and swallowing. Total laryngectomy (TL) causes severe impairments, while partial laryngectomy (PL) and chemoradiotherapy (CRT) preserve the organ but yield variable outcomes. This study assesses QoL, speech rehabilitation, swallowing, and social reintegration across these treatments. Methods: This prospective observational cohort study was conducted at the ENT Clinic, Victor Babeș University of Medicine and Pharmacy, Timișoara; recruitment was conducted between October 2019 and January 2024. Seventy-five patients diagnosed with laryngeal squamous cell carcinoma (LSCC) were initially enrolled but only 15 patients (20%) completed the 12-month follow-up, with an attrition rate of 80%. Tumor stages ranged from T1 to T4a, with TL patients having a higher proportion of advanced-stage disease (Stage III–IV: 76%) compared to PL (45%) and CRT (50%). Validated instruments, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (EORTC QLQ-H&N35), the Voice Handicap Index-30 (VHI-30), the Hospital Anxiety and Depression Scale (HADS), and the Dysphagia Outcome and Severity Scale (DOSS), were used to assess QoL, voice function, swallowing function, and psychological impact. Results: At 12 months, the global QoL score from the EORTC QLQ-H&N35 was lowest in TL patients (49.8 ± 10.9), significantly lower than both PL (61.2 ± 9.6, p = 0.002) and CRT (64.1 ± 7.8, p < 0.001). Post hoc Bonferroni analysis confirmed significant pairwise differences between TL vs. PL (p = 0.002) and TL vs. CRT (p < 0.001), while the difference between PL and CRT was non-significant (p = 0.14). TL patients had higher speech-related disability (VHI: 88.3 ± 12.6) and dysphagia prevalence (DOSS: 4.0 ± 1.2), with 16% remaining enteral feeding-dependent. Anxiety (HADS-A: 7.5 ± 2.9) and depression (HADS-D: 9.0 ± 3.2) were highest in TL patients, with 36% meeting clinical depression criteria at 12 months. Multivariable regression identified TL (OR = 3.92, 95% CI: 2.14–5.79, p < 0.001) and advanced tumor stage (OR = 2.85, 95% CI: 1.79–4.21, p = 0.002) as strong predictors of poor QoL. Kaplan–Meier analysis showed no significant OS differences (p = 0.12), but CRT patients had lower DFS (78%) compared to TL (82%) and PL (85%) (p = 0.048). Conclusions: TL patients experience the most significant impairments in QoL, speech, and social reintegration despite rehabilitation. CRT patients show higher recurrence rates but better QoL, while PL offers the best balance of function and survival. These findings highlight the need for long-term survivorship support tailored to treatment type.

Laryngeal cancer significantly affects not only survival but also core functions such as speech, swallowing, and breathing. These impairments often result in substantial psychological distress and reduced health-related quality of life (HRQoL). This review aims to synthesize current evidence regarding the psychological impact, quality of life outcomes, and system-level challenges faced by laryngeal cancer patients while identifying strategies for integrated survivorship care. Anxiety and depressive symptoms are highly prevalent among laryngeal cancer patients, particularly those undergoing total laryngectomy or chemoradiotherapy. HRQoL outcomes vary significantly depending on treatment modality, with long-term deficits noted in domains such as voice, swallowing, and emotional well-being. Access to psychological support and rehabilitation remains inconsistent, hindered by institutional, socioeconomic, and cultural barriers. Structured survivorship models, psychological screening, and patient-centered rehabilitation have demonstrated benefits but are not universally implemented. Comprehensive care for laryngeal cancer must extend beyond tumor control to address persistent functional and psychological sequelae. A multidisciplinary, anticipatory, and personalized approach—centered on integrated rehabilitation and mental health support—is essential to optimize survivorship outcomes and improve long-term quality of life.

Exosome-derived microRNAs (miRNAs) have been proposed as minimally invasive biomarkers for laryngeal squamous- cell carcinoma (LSCC). Because oral and maxillofacial surgeons are integral to head-and-neck oncologic and reconstructive pathways, such liquid-biopsy signals could support perioperative decision-making (selection for organ-preserving surgery), margin surveillance, and reconstructive planning. We conducted a preregistered, protocol-driven search of PubMed/MEDLINE, Web of Science, and Scopus from inception to 1 June 2025. Given the very small number of clinically comparable diagnostic studies, discordant index tests/thresholds, and high heterogeneity, we did not perform quantitative pooling or publication-bias testing. Instead, we undertook a narrative synthesis and constructed an evidence map; risk of bias tools (QUADAS-2; ROBINS-I) were applied descriptively to inform qualitative confidence. Nine studies were formally analysed based on eligibility to the study topic. Two serum-based case–control investigations (111 LSCC, 80 controls) reported areas under the ROC curve of 0.876 (miR-21 + HOTAIR) and 0.797 (miR-941), with corresponding sensitivities of 94% and 82%. Seven mechanistic papers showed that vesicular cargos—including miR-1246, circPVT1, and LINC02191—drive STAT3-dependent M2 polarisation, NOTCH1-mediated stemness, Rap1b-VEGFR2 angiogenesis, and glycolytic re-programming, producing 1.6–2.6-fold increases in invasion, tube formation, or xenograft growth. Only three studies fulfilled MISEV-2018 characterisation criteria, and none incorporated external validation. This narrative review and evidence map identifies promising but preliminary diagnostic signals and biologically plausible mechanisms for exosomal miRNAs in LSCC; however, the evidence is sparse, single-region, methodologically inconsistent, and at high risk of bias. Findings do not support clinical implementation at this stage. Priorities include harmonised EV workflows, prespecified thresholds, and prospective, multi-centre validation.

Background: Long COVID, or post-COVID-19 condition (PCC), affects around 36% of individuals following SARS-CoV-2 infection, manifesting as persistent fatigue, cognitive dysfunction, and dysautonomia among its hallmark features. Affecting an estimated 400 million individuals globally, it imposes an annual economic burden exceeding $1 trillion, yet no pharmacological therapy has demonstrated consistent efficacy in adequately powered randomized controlled trials. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a candidate intervention targeting the autonomic dysfunction and neuroinflammation responsible for PCC pathophysiology. Methods: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420261287286) searching PubMed, Scopus, Cochrane, and Web of Science databases from inception to January 2026 for studies evaluating any form of VNS in adults with Long COVID. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, the JADAD scale, and the PEDro scale. Certainty of evidence was evaluated using the GRADE framework. Narrative synthesis followed SWiM guidelines. Results: Five studies (n = 154 participants) (three randomized controlled trials (RCTs) and two single-arm studies) met inclusion criteria. Three of five studies (60%) were rated high overall risk of bias; only two RCTs achieved “some concerns.” The only adequately double-blinded RCT found no significant between-group differences across all outcomes. Paradoxically, in the best-powered RCT (Percin et al.), sham stimulation produced significantly greater fatigue improvement than active taVNS, despite active taVNS producing significant HRV increases consistent with cardiac autonomic modulation. All efficacy outcomes were rated “very low” certainty (GRADE); safety was rated “low” certainty. Conclusions: Currently available evidence supporting the use of taVNS for Long COVID remains limited, and the absence of reliable target engagement markers in the included studies constrains confidence in this approach. Nonetheless, the physiological rationale remains sound, and the favorable safety profile across all included studies supports the feasibility of future investigation. However, given that positive findings were confined to inadequately controlled studies, enthusiasm for further research should be directed first toward mechanistic clarification and rigorous dose-finding work. Large-scale, double-blind, sham-controlled trials incorporating validated markers of vagal engagement are required before taVNS can be firmly recommended for COVID-19 sequelae management.

Background and Objectives: Coronavirus disease 2019 (COVID-19) is characterized by excessive inflammatory responses, including the so-called cytokine storm, which contributes substantially to morbidity and mortality in hospitalized patients. The vagus nerve, through the cholinergic anti-inflammatory pathway, represents a theoretically attractive therapeutic target for modulating systemic inflammation. Vagus nerve stimulation (VNS) has emerged as a potential adjunctive treatment for COVID-19, with several randomized controlled trials (RCTs) investigating its efficacy on inflammatory biomarkers and clinical outcomes. The quality of this evidence base has not been rigorously evaluated. This systematic review critically appraises all available RCT evidence for VNS in hospitalized COVID-19 patients. Materials and Methods: We systematically searched PubMed, Scopus, Cochrane (CENTRAL), and Web of Science from database inception to January 2026, for RCTs evaluating any form of VNS (invasive, non-invasive, cervical, or auricular) in hospitalized patients with confirmed acute COVID-19. Two reviewers independently screened titles, abstracts, and full texts according to pre-specified eligibility criteria. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, with assessments initially performed using multiple artificial intelligence tools and subsequently validated by the authors in accordance with PRISMA 2020 guidelines. Given substantial heterogeneity and high risk of bias, narrative synthesis was performed rather than meta-analysis. Also, GRADE assessment was performed. Results: From 437 records identified, six RCTs comprising 221 patients met the inclusion criteria. Five trials (83%) were rated as high risk of bias, primarily due to inadequate blinding, substantial baseline imbalances, significant missing data and extensive multiple testing without statistical correction. The single double-blind trial with a credible sham control (Rangon et al.) found null results across all outcomes, including clinical progression, ICU transfer, and mortality, while the five “high” risk-of-bias trials generally reported positive findings on various inflammatory markers and clinical outcomes. One trial (Corrêa et al.) measured heart rate variability as a direct indicator of vagal activation and found no change despite claiming anti-inflammatory effects, contradicting the proposed mechanism of action. Significant cognitive findings from an interim analysis (Uehara et al., n = 21) disappeared in the larger completed trial (Corrêa et al., n = 52), providing empirical demonstration of false positive findings in small, underpowered studies. Conclusions: Currently available evidence supporting the use of VNS for acute COVID-19 remains scarce; however, the physiological rationale remains sound, although the absence of reliable target engagement markers in the included studies limits confidence in this treatment method. Large-scale, double-blind, sham-controlled trials are required before VNS can be firmly recommended for COVID-19 management.

Background/Objectives: Treatment for laryngeal cancer often impacts voice, swallowing, communication, and quality of life. Patient-reported outcome measures (PROMs) are increasingly used to evaluate survivorship, but their application and connection with objective functional measures vary widely. The objective was to explore how PROMs are used in laryngeal cancer research, identify the functional areas they assess, analyze their link with objective clinical outcomes, and identify methodological gaps in current studies. Methods: This scoping review followed PRISMA-ScR guidelines. Searches were conducted in PubMed/MEDLINE, Scopus, and Web of Science from their start until April 2026. Included studies involved adults with laryngeal cancer reporting PROMs and/or objective functional outcomes. Data on study features, PROM tools, evaluated domains, and how PROMs relate to objective outcomes were extracted and summarized descriptively. Results: Ninety-five studies with 10,807 participants were included. Most were observational (84.2%) and conducted at a single center (72.6%). Voice-related outcomes were the most common (86.3%), followed by psychological (72.6%) and swallowing outcomes (65.3%). Less frequently assessed were nutritional (22.1%) and supportive care domains (41.1%). The Voice Handicap Index family was the most used PROM group (30.5%). Over half the studies reported PROMs and objective measures separately without statistical integration (51.6%), while only 13.7% performed analytical integration, and none used predictive multivariable models. Significant variation existed in PROM choices, assessed domains, and integration approaches. Conclusions: PROM use in laryngeal cancer survivorship research is heterogeneous and predominantly focused on voice-related outcomes. Limited analytical integration with objective measures hampers a comprehensive understanding of recovery. There is a need for standardized, multidimensional assessment frameworks that include functional, nutritional, psychosocial, and objective outcomes to effectively support patient-centered survivorship care and rehabilitation planning.