In vitro effects of gamma-secretase inhibition in HPV-positive and HPV-negative head and neck squamous cell carcinoma.

BACKGROUND: New chemotherapy agents are warranted for head and neck squamous cell carcinoma (HNSCC), particularly for incidence-rising HPV-positive tumors. Based on the evidence of Notch pathway involvement in cancer promotion and progression, we aimed to gain insights into the in vitro antineoplastic effects of gamma-secretase inhibition in HPV-positive and -negative HNSCC models. METHODS: All in vitro experiments were conducted in two HPV-negative (Cal27 and FaDu) and one HPV-associated HNSCC cell line (SCC154). The influence of the gamma-secretase inhibitor PF03084014 (PF) on proliferation, migration, colony forming, and apoptosis was assessed. RESULTS: We observed significant anti-proliferative, anti-migratory, anti-clonogenic, and pro-apoptotic effects in all three HNSCC cell lines. Furthermore, synergistic effects with concomitant radiation were observable in the proliferation assay. Interestingly, effects were slightly more potent in the HPV-positive cells. CONCLUSION: We provided novel insights into the potential therapeutic relevance of gamma-secretase inhibition in HNSCC cell lines in vitro. Therefore, PF may become a viable treatment option for patients with HNSCC, particularly for patients with HPV-induced malignancy. Indeed, further in vitro and in vivo experiments should be conducted to validate our results and decipher the mechanism behind the observed anti-neoplastic effects.

Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab.

PURPOSE: First-line immune checkpoint blockade has improved the prognosis of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but response rates remain low. In this study, we aimed to investigate the prognostic value of CRP and its early kinetics to predict response and survival in R/M HNSCC. METHODS: A total of 87 patients who received first-line pembrolizumab for R/M HNSCC were analyzed. Three-fold cross-validation was used to estimate cut-off points of CRP at baseline and on-treatment (day 40 ± 10). Treatment response and survival were analyzed according to early CRP kinetics. The neutrophil-to-lymphocyte ratio (NLR) was used as a benchmark for the prognostic performance of CRP. RESULTS: On-treatment CRP below 2 mg/dl, 4x the upper limit of normal (ULN), was associated with increased overall survival (OS), while on-treatment CRP below 3 mg/dl (6x ULN) was correlated with a higher disease control rate (DCR) and increased progression-free survival (PFS). CRP flare-responders and CRP responders showed a higher DCR and longer PFS than CRP non-responders. An NLR above 6 was a negative prognosticator for progression. In multivariable analysis, on-treatment CRP prevailed as the only significant prognosticator for OS (HR: 4.97, CI95%: 2.18-11.32, p < 0.001) and PFS (HR: 2.07, CI95%: 1.07-3.99, p = 0.030). CONCLUSION: On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely available and cost-effective biomarker.

The ATR inhibitor berzosertib acts as a radio- and chemosensitizer in head and neck squamous cell carcinoma cell lines.

Alterations in the DNA damage response play a crucial role in radio- and chemoresistance of neoplastic cells. Activation of the Ataxia telangiectasia and Rad3-related (ATR) pathway is an important DNA damage response mechanism in head and neck squamous cell carcinoma (HNSCC). Berzosertib, a selective ATR inhibitor, shows promising radio- and chemosensitizing effects in preclinical studies and is well tolerated in clinical studies. The aim of this study was to elucidate the effect of berzosertib treatment in combination with radiation and cisplatin in HNSCC. The HNSCC cell lines Cal-27 and FaDu were treated with berzosertib alone and in combination with radiation or cisplatin. Cell viability and clonogenic survival were evaluated. The effect of combination treatment was evaluated with the SynergyFinder or combination index. Apoptosis was assessed via measurement of caspase 3/7 activation and migration was evaluated using a wound healing assay. Berzosertib treatment decreased cell viability in a dose-dependent manner and increased apoptosis. The IC50 of berzosertib treatment after 72 h was 0.25-0.29 µM. Combination with irradiation treatment led to a synergistic increase in radiosensitivity and a synergistic or additive decrease in colony formation. The combination of berzosertib and cisplatin decreased cell viability in a synergistic manner. Additionally, berzosertib inhibited migration at high doses. Berzosertib displays a cytotoxic effect in HNSCC at clinically relevant doses. Further evaluation of combination treatment with irradiation and cisplatin is strongly recommended in HNSCC patients as it may hold the potential to overcome treatment resistance, reduce treatment doses and thus mitigate adverse events.

Peripheral eosinophil count and eosinophil-to-lymphocyte ratio are associated with revision sinus surgery.

PURPOSE: The aim of this study was to assess whether hematological indices of the peripheral blood are associated with revision surgery in patients with chronic rhinosinusitis (CRS) undergoing endoscopic sinus surgery (ESS). METHODS: This retrospective, cross-sectional, single-center study included 541 CRS patients that underwent ESS. Demographics and laboratory parameters were retrieved, and group comparisons were performed. We computed binary logistic regression models to associate clinical characteristics (i.e., aeroallergen allergies, asthma, presence of nasal polyps), absolute blood counts of different leukocyte types (i.e., lymphocytes, neutrophils, basophils, and eosinophils), and hematological indices of the peripheral blood [i.e., neutrophil-to-lymphocyte ratio (NLR), basophil-to-lymphocyte ratio (BLR), eosinophil-to-lymphocyte ratio (ELR), and eosinophil-to-neutrophil ratio (ENR)] with revision surgery as outcome. RESULTS: The study population included 435 primary surgeries and 106 revision cases. Patients undergoing revision ESS showed significantly higher absolute preoperative eosinophil counts (381.6 ± 265.6 per µl), ELR (0.205 ± 0.195), and ENR (0.105 ± 0.074) compared to primary cases (all p < 0.001). Binary logistic regression analysis revealed higher odds for revision surgery in patients higher in age (ß = 1.026, p < 0.001), with presence of aeroallergen allergies (ß = 1.865, p = 0.011), presence of asthma (ß = 3.731, p = 0.001), higher preoperative eosinophil counts (ß = 1.002, p < 0.001), and higher ELR (ß = 155.663, p = 0.015). CONCLUSIONS: We found that higher peripheral eosinophil count and higher ELR were associated with revision ESS in CRS patients. Preoperative assessment of hematological indices of the peripheral blood might be a valuable indicator of disease severity, thus facilitating better treatment selection.

Meteorological extremes and their impact on tinnitus-related emergency room visits: a time-series analysis.

PURPOSE: Extreme weather events are rising due to the accelerating pace of climate change. These events impact human health and increase emergency room visits (EV) for many morbidities. Tinnitus is a common cause of EVs within otolaryngology in Germany and Austria. The effect of extreme weather conditions on tinnitus-related EVs is unknown. METHODS: A total of 526 tinnitus-related EVs at a tertiary care hospital in Vienna were identified. A distributed lag non-linear model with a maximum lag period of 14 days was fitted to investigate the immediate and delayed effect of single-day and prolonged (three-day) extreme atmospheric pressure, relative humidity, mean temperature, precipitation and mean wind speed on EV rates. Extreme conditions were defined as the 1st, 5th, 95th, and 99th percentile of the meteorological variables. Relative risk (RR) is defined as risk for tinnitus-related EVs at an extreme condition compared to the risk at the median weather condition. Cumulative RR (cRR) is the total cumulated EV risk for a given time period. RESULTS: High relative humidity increased same-day RR for tinnitus-related EVs to 1.75. Both low and high atmospheric pressure raised cRR as early as three days after an event to a maximum of 3.24. Low temperatures mitigated cRR within 4 days, while high temperatures tended to increase risk. Prolonged precipitation reduced cRR within one day. CONCLUSION: Extreme meteorological conditions are associated with tinnitus-related EV rates. Further investigation into potential causative links and underlying pathophysiological mechanisms is warranted.

Inhibition of beta-catenin shows therapeutic potential in head and neck squamous cell carcinoma in vitro.

Beta-catenin is known to be a vital component of the canonical Wnt signaling cascade, involved in the carcinogenesis of different solid tumors. We aimed to evaluate the effects of Beta-catenin inhibition in head and neck squamous cell carcinoma (HNSCC) in vitro. The small molecular compound MSAB was used to inhibit Wnt/Beta-catenin signaling in a human papillomavirus (HPV)-positive and HPV-negative cell line and its effects on cell proliferation, migration, colony formation, apoptosis, as well as radiosensitizing properties were assessed. Significant antineoplastic effects were observed in both cell lines. Interestingly, stronger anti-neoplastic and radiosensitizing effects were observed in the HPV-negative cell line, whereas stronger anti-migratory potential was detected in HPV-positive HNSCC cells. In conclusion, our findings suggest MSAB as a potential therapeutic agent for HNSCC. Further studies are warranted to unravel the mechanistic background of our findings.

Interobserver variability of cochlear duct measurements in pediatric cochlear implant candidates.

PURPOSE: The objective of the study was to evaluate the proposed cochlear duct length estimation based on the cochlear 'A value'. Furthermore, we assessed the interobserver variability between radiology and otolaryngology attending physicians and otolaryngology trainees. METHODS: Thirteen pediatric cochlear implant candidates were retrospectively analyzed by three otolaryngology physicians (attending physician, second year, and fourth year trainees) and a radiology attending. The cochlear duct length was calculated based on the formula of Grover et al. The differences in acquired measurements between observers were compared using the Wilcoxon matched signed-rank test. RESULTS: The differences in measurements between the attending otolaryngologist and radiologist were not statistically different, while several significant differences were observed with regard to measurements of attending doctors compared to both residents. In particular, a significant difference between the second year otolaryngology resident and otolaryngology and radiology attending was observed for one side (right ear p = 0.034 and p = 0.012, respectively). Moreover, the fourth year resident calculated significantly different cochlear duct measurements when compared to the attending otolaryngologist (left ear p = 0.014) and radiologist (right ear p = 0.047). Interestingly, differently experienced otolaryngology residents provided significantly different measurements for both ears. CONCLUSIONS: Based on these results, cochlear duct length measurement according to the proposed method may be a reliable and cost-effective method. Indeed, otolaryngology training may be sufficient to provide measurements comparable to radiologists. On the other hand, additional efforts should be invested during otolaryngology training in terms of the evaluation of radiological imaging which may increase the capabilities of otolaryngology residents in this regard.

A novel electrosurgical divider: performance in a self-controlled tonsillectomy study.

PURPOSE: Tonsillectomies are among the most common surgeries in otorhinolaryngology. A novel electrosurgical temperature-controlled instrument (device) promises rapid tonsillectomies and might reduce postoperative pain, but comparative studies to assess performance are warranted. METHODS: This randomized self-controlled clinical trial was conducted from October 2019 to October 2020 at the Department of Otorhinolaryngology, Head and Neck Surgery of the Medical University of Vienna. Forty-eight patients underwent a tonsillectomy with the device on one side and using cold-steel with localized bipolar cauterization on the other side (control). Main outcomes were the time for tonsil removal (per side) and the time to stop bleeding (per side). Secondary measurements were postoperative pain, assessed once on day 0 and five times on days 1, 3, 5, 7, and 10. Postoperative bleeding episodes and consequences were recorded. RESULTS: Device tonsillectomies were performed significantly faster than controls; the mean surgical time difference was 209 s (p < 0.001, 95% CI 129; 288). Intraoperative blood loss was significantly lower on the device side (all p < 0.05). Postoperative measurements of pain and bleeding were similar for both sides. Two return-to-theatre secondary bleeding events were recorded for the control side. CONCLUSION: The novel electrosurgical temperature-controlled divider reduced the tonsillectomy surgical time and intraoperative blood loss, with no apparent negative effects on postoperative pain or bleeding, compared to a cold-steel tonsillectomy with localized bipolar cauterization. In time-restricted settings, the device could be beneficial, particularly after familiarization with device handling. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03793816.

Biannual Differences in Interest Peaks for Web Inquiries Into Ear Pain and Ear Drops: Infodemiology Study.

BACKGROUND: The data retrieved with the online search engine, Google Trends, can summarize internet inquiries into specified search terms. This engine may be used for analyzing inquiry peaks for different medical conditions and symptoms. OBJECTIVE: The aim of this study was to analyze World Wide Web interest peaks for "ear pain," "ear infection," and "ear drops." METHODS: We used Google Trends to assess the public online interest for search terms "ear pain," "ear infection," and "ear drops" in 5 English and non-English-speaking countries from both hemispheres based on time series data. We performed our analysis for the time frame between January 1, 2004, and December 31, 2019. First, we assessed whether our search terms were most relevant to the topics of ear pain, ear infection, and ear drops. We then tested the reliability of Google Trends time series data using the intraclass correlation coefficient. In a second step, we computed univariate time series plots to depict peaks in web-based interest. In the last step, we used the cosinor analysis to test the statistical significance of seasonal interest peaks. RESULTS: In the first part of the study, it was revealed that "ear infection," "ear pain," and "ear drops" were the most relevant search terms in the noted time frame. Next, the intraclass correlation analysis showed a moderate to excellent reliability for all 5 countries' 3 primary search terms. The subsequent analysis revealed winter interest peaks for "ear infection" and "ear pain". On the other hand, the World Wide Web search for "ear drops" peaked annually during the summer months. All peaks were statistically significant as revealed by the cosinor model (all P values <.001). CONCLUSIONS: It can be concluded that individuals affected by otitis media or externa, possibly the majority, look for medical information online. Therefore, there is a need for accurate and easily accessible information on these conditions in the World Wide Web, particularly on differentiating signs and therapy options. Meeting this need may facilitate timely diagnosis, proper therapy, and eventual circumvention of potentially life-threatening complications.

Peaks in online inquiries into pharyngitis-related symptoms correspond with annual incidence rates.

OBJECTIVE: To assess whether web-based public inquiries into pharyngitis-related search terms follow annual incidence peaks of acute pharyngitis in various countries from both hemispheres. METHODS: Google Trends (GT) was utilized for systematic acquisition of pharyngitis-related search terms (sore throat, cough, fever, cold). Six countries from both hemispheres including four English (United Kingdom, United States, Canada, and Australia) and two non-English speaking countries (Austria and Germany) were selected for further analysis. Time series data on relative search interest for pharyngitis-related search terms, covering a timeframe between 2004 and 2019 were extracted. Following reliability analysis using the intra-class correlation coefficient, the cosinor time series analysis was utilized to determine annual peaks in public-inquiries. RESULTS: The extracted datasets of GT proved to be highly reliable with correlation coefficients ranging from 0.83 to 1.0. Graphical visualization showed annual seasonal peaks for pharyngitis-related search terms in all included countries. The cosinor time series analysis revealed these peaks to be statistically significant during winter months (all p < 0.001). CONCLUSION: Our study revealed seasonal variations for pharyngitis-related terms which corresponded to winter incidence peaks of acute pharyngitis. These results highlight the need for easily accessible information on diagnosis, therapy, and red-flag symptoms for this common disease. Accurately informed patients might contribute to a reduction of unnecessary clinic visits and potentially cutback the futile antibiotic overuse.

Expression of inhibitors of apoptosis proteins in salivary gland adenoid cystic carcinoma: XIAP is an independent marker of impaired cause-specific survival.

OBJECTIVES: Inhibitors of apoptosis proteins are crucial to carcinogenesis since their expression results in evasion of apoptosis. Overexpression of inhibitors of apoptosis has repeatedly been associated with resistance to treatment and poor prognosis in various cancers. The role of inhibitors of apoptosis in adenoid cystic carcinoma of the salivary gland is still unclear. The aim of this study was to investigate the expression of inhibitors of apoptosis and their potential prognostic value in adenoid cystic carcinoma. DESIGN, SETTING AND PARTICIPANTS: Forty-nine patients, diagnosed with adenoid cystic carcinoma of the salivary gland between 1996 and 2016, were retrospectively included in this study. The expression of cIAP1, cIAP2, XIAP, Birc6, Livin and Survivin was assessed using immunohistochemistry, and their association of survival and prognosis was evaluated during a median follow-up of 6.4 years. MAIN OUTCOME MEASURE: Cause-specific survival and recurrence-free survival rates. RESULTS: XIAP, cIAP2, Livin and nuclear Survivin showed high expression levels in adenoid cystic carcinoma in most patients. There was no significant association of cIAP1, cIAP2, Livin, Birc6 and Survivin with outcome. However, high XIAP expression was associated with worse cause-specific survival and worse response to radiotherapy and proved to be an independent marker in multivariable analysis. CONCLUSION: Our data indicate that high expression of XIAP may be used as a prognosticator for poor survival and poor response to radiotherapy in adenoid cystic carcinoma patients.

Presentation Rates for Acute Pharyngitis in the Emergency Room Are Influenced by Extreme Weather Events.

OBJECTIVE: Extreme weather events are becoming more prevalent with the increasing pace of climate change. These events negatively impact human health and put considerable strain on health care resources, including emergency departments. Within otolaryngology, acute pharyngitis is a common reason for emergency room visits (ERV). Therefore, we aimed to investigate the impact of extreme meteorological conditions on ERV rates related to acute pharyngitis. STUDY DESIGN: Retrospective time-series study. SETTING: ERVs related to acute pharyngitis (n = 1511) were identified at a tertiary care hospital in Vienna, Austria, between 2015 and 2018. METHODS: The effects of single-day and prolonged (3-day) extreme weather events on ERVs were analyzed using a distributed lag nonlinear model. Relative risk (RR) and cumulative relative risk (cRR) were calculated over a lag period of 14 days. RR refers to the risk for pharyngitis-related ERV at extreme conditions (1st, 5th, 95th, or 99th percentile) compared to the risk at median conditions. RESULTS: Same-day RR (lag0) was elevated more than 3-fold after prolonged extremely low mean temperatures (P = .028). Furthermore, same-day RR after single-day and prolonged extremely high relative humidity was elevated by 51% (P = .024) and 46% (P = .036), respectively. Significant delayed effects on cRR were observed for extreme mean temperatures, relative humidity, and mean wind speeds within 8 days and for extreme atmospheric pressure within 14 days. CONCLUSION: Extreme weather events impact ERV rates for acute pharyngitis. Extremely low temperatures, high relative humidity, high atmospheric pressure, and low and high wind speeds were risk-promoting factors.

The dual role of autophagy in HPV-positive head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV+ HNSCC. METHODS: Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV- and HPV+ HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized. RESULTS: The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients. CONCLUSION: HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.

Impact of the COVID-19 pandemic on management of surgically treated laryngeal squamous cell carcinoma.

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the treatment of cancer patients, particularly in terms of treatment choices. This study aimed to assess the effects of the COVID-19 pandemic on the management of surgically treated laryngeal squamous cell carcinoma (LSCC) patients, focusing specifically on changes in treatment modalities. We retrospectively analyzed the data from 102 patients who underwent surgical treatment for LSCC between January 1, 2019, and December 31, 2021, at our tertiary medical center. Patient demographics, histological characteristics, and treatment modalities were extracted from electronic medical records and compared between two time periods: pre-COVID-19 and during COVID-19, marked by the introduction of the hospital entry triage. Of the total patients, 53 (52%) were in the pre-COVID-19 group, and 49 (48%) were in the COVID-19 group. No significant differences in patient characteristics at the initial work-up were observed between the two groups. However, a significant shift in treatment modalities was noted. Fewer patients received postoperative adjuvant therapy in the COVID-19 group (70.5%) compared to the pre-COVID-19 group (95.5%). Importantly, this change did not significantly impact the one-year overall survival (OS) rates. The reduction in the use of postoperative adjuvant therapy during the COVID-19 pandemic may be attributed to efforts to minimize hospital visits due to the risk of COVID-19 infection. Further research is warranted to validate these findings and to investigate the potential effects of such changes in treatment modalities on the long-term survival.

Changes in management of head and neck malignancies during the COVID-19 pandemic.

Objective: Despite multiple studies from high-income countries, reports from low- and middle-income countries on the impact of COVID-19 on head and neck cancer care remain sparse. This study aimed to assess the effects of the COVID-19 pandemic on head and neck cancer patients at a tertiary reference centre in Bosnia and Herzegovina. Methods: We included 228 patients with malignant head and neck tumours evaluated and treated between January 1, 2019, and December 31, 2021. Patient demographics, histological characteristics, and treatment modalities were retrospectively obtained and compared between the pre-pandemic period (pre-COVID-19 group) and the period after the implementation of COVID-19 restrictive measures (COVID-19 group). Results: Patients were significantly older during the COVID-19 pandemic. In particular, 63 patients (44.7%) were under 65 and 78 (55.3%) were 65 or older, while in the pre-COVID-19 period, 53 patients (60.9%) were under 65 and 34 (39.1%) were 65 or older (p = 0.017). The pre-COVID-19 and COVID-19 groups did not significantly differ regarding other patient- and tumour characteristics, or primary treatment modalities. Conclusions: During the COVID-19 pandemic, significantly fewer patients were under 65 at the time of initial work-up, potentially reflecting the more enhanced disease-related anxiety of the younger population. Future studies are warranted to address this population's specific educational and psychological needs to ensure appropriate cancer care.

Lymphocyte-to-Monocyte Ratio Might Serve as a Prognostic Marker in Young Patients with Tongue Squamous Cell Carcinoma.

BACKGROUND: Young patients with tongue squamous cell carcinoma (TSCC) mostly lack typical prognostic markers and face a dire prognosis. The aim of this study was to analyze the prognostic relevance of lymphocyte-to-monocyte ratio (LMR) in TSCC patients, with a special emphasis on patients under 45 years. METHODS: This retrospective study included all patients primarily treated for TSCC. The prognostic relevance of LMR was investigated in terms of predicting the overallsurvival (OS) and disease-free survival (DFS). RESULTS: A total of 74 patients were included and the young cohort (<45 years) comprised 27 individuals. The mortality and recurrence rates were 39.2% (n = 29) and 37.8% (n = 28), respectively. OS and DFS were significantly shorter in the low LMR group within the whole cohort. Furthermore, low LMR was associated with worse prognosis, particularly inferior OS (median OS 1.7 vs. 14.6 years, p = 0.0156) and worse DFS (median DFS 0.8 years vs. not reached, p = 0.0405) in the young patient cohort. CONCLUSIONS: Our results reveal that pretreatment LMR might become a prognostic tool for young TSCC patients, especially due to its availability. However, further studies on larger cohorts are necessary to validate our results.

Early Results With the New Active Bone-Conduction Hearing Implant: A Systematic Review and Meta-Analysis.

OBJECTIVE: The bone conduction implant (BCI) 602 is a new transcutaneous BCI with smaller dimensions. However, limited patient numbers restrict the statistical power and generalizability of the current studies. The present systematic review and meta-analysis summarize early audiological and medical outcomes of adult and pediatric patients implanted with the BCI 602 due to mixed or conductive hearing loss. DATA SOURCE: Following the Preferred Reporting items for Systematic Reviews and Meta-analyses guidelines, 108 studies were reviewed, and 6 (5.6%) were included in the meta-analysis. REVIEW METHOD: The data on study and patient characteristics, surgical outcomes, and audiological test results were extracted from each article. Meta-analysis employed the fixed-effect and random-effects models to analyze the mean differences (MDs) between pre- and postoperative performances. RESULTS: In total, 116 patients were evaluated, including 64 (55%) adult and 52 (45%) pediatric patients. No intraoperative adverse events were reported, while postoperative complications were reported in 2 (3.1%) adult and 2 (3.8%) pediatric patients. Studies consistently showed significant improvements in audiological outcomes, quality of life, and sound localization in the aided condition. In the meta-analysis, we observed a significant difference in the unaided compared to the aided condition in sound field thresholds (n = 112; MD, -27.05 dB; P < 0.01), signal-to-noise ratio (n = 96; MD, -6.35 dB; P < 0.01), and word recognition scores (n = 96; MD, 68.89%; P < 0.01). CONCLUSION: The implantation of the BCI 602 was associated with minimal surgical complications and excellent audiological outcomes for both the pediatric and the adult cohort. Therefore, our analysis indicates a high level of safety and reliability. Further research should focus on direct comparisons with other BCIs and long-term functional outcomes.