Understanding Patient Utilization Patterns of Cochlear Implant Processors.

OBJECTIVE: To evaluate the extent of benefit the second processor provides and to better understand utilization patterns regarding cochlear implant (CI) sound processors. BACKGROUND: Institutional contracts determine the external CI sound processor hardware that a patient is eligible for. Despite the high prevalence of CI worldwide, there is a paucity in the literature regarding patient preferences and how patients utilize provided external hardware. METHODS: A close-ended, multiple-choice survey was mailed to all patients over the age of 18 years who underwent CI between 2016 to 2020 at a tertiary academic medical center. Patients who received their CI hardware prior to 2018 were provided 2 processors, whereas those who received their hardware in 2018 or later were provided 1 processor. RESULTS: A total of 100/263 surveys were returned for a response rate of 38.0%. Of the cohort with 1 processor, 31.3% experienced a period without a functioning processor and access to sound compared to 5.6% of the cohort with 2 processors (P = -.003). Of the cohort with 2 processors, 24.3% noted that they often or always utilize their second processor. When asked how important having a second processor was, 62.9% of the 2-processor group responded that it was very important (P = .001). The most common reason for utilizing the second processor was a damaged primary processor. Patients who received 2 processors had a significantly lower number of postoperative audiology clinic visits for device troubleshooting (P < .001). CONCLUSION: Patients who have 2 CI external processors identify this as being very important to them and experience significantly less time without access to sound due to lack of a functioning processor. As institutional contracts often dictate whether a patient will receive 1 or 2 sound processors with their CI hardware, it is important to understand patient preferences and utilization patterns in order to guide patient-centric policies.

Tympanomastoidectomy versus parenteral antibiotic therapy for pediatric otorrhea.

OBJECTIVE: To evaluate the efficacy of tympanomastoidectomy versus parenteral antibiotic therapy for otorrhea as a result of chronic suppurative otitis media (CSOM) without cholesteatoma in the pediatric population. METHODS: A retrospective review of 221 patients treated for otorrhea at a tertiary academic pediatric hospital was performed to evaluate the impact of tympanomastoidectomy versus parenteral antibiotic therapy on resolution of otorrhea. Inclusion criteria were age 0-18 years, prior treatment with otic and/or oral antibiotic, prior history of tympanostomy tube placement for recurrent otitis media, history of otorrhea, treatment with tympanomastoidectomy or parenteral antibiotic therapy, and follow-up of at least 1 month after intervention. Time to resolution was compared between the two modalities adjusting for age, bilateral ear disease status, and comorbidities using a Cox proportional hazard model. RESULTS: Eighty-three ears from 58 children met the inclusion criteria. Ears that initially underwent tympanomastoidectomy had a significantly shorter time to resolution of symptoms (median time to resolution) 9 months (95 % confidence interval CI: 6.2-14.8) vs. 48.5 months (95 % lower CI 9.4, p = 0.006). On multivariate analysis, however, only bilateral ear disease status was independently associated with time to resolution of symptoms (hazard ratio 0.4, 95 % CI 0.2-0.9, p = 0.03). There was no statistically significant difference in the rate of treatment-related complications when comparing tympanomastoidectomy to parenteral antibiotic therapy (p = 0.37). CONCLUSION: When adjusting for age, bilateral ear disease status, and comorbidities, there does not appear to be a significant difference in time to resolution of symptoms when comparing parenteral antibiotic therapy to tympanomastoidectomy. An informed discussion regarding risks and benefits of each approach should be employed when deciding on the next step in management for patients with CSOM who have failed more conservative therapies.

Vascular permeability in HPV+ oropharyngeal cancers aids in fluorescent image-guided transoral robotic surgery using indocyanine green.

BACKGROUND: Indocyanine green (ICG) fluorescent image (FI)-guided surgery has demonstrated success in improving intraoperative visualization and tumor resections. The objectives were to evaluate the use of IGC in FI-guided transoral robotic surgery (TORS) and the underlying molecular mechanism. METHODS: HPV+ oropharyngeal squamous cell carcinoma (OPSCCa) patient (n = 10) undergoing TORS were enrolled in this prospective study. Participants received intravenous ICG. Excised tissues were evaluated for ICG accumulation, tumor demarcation, and pathological characteristics using In-vivo imaging system (IVIS), histology, and RNA sequencing. RESULTS: ICG accumulation was significantly increased in primary tumor and pathological lymph nodes compared with normal tissues (p < 0.001). IVIS was 91.3% accurate in identifying OPSCCa in excised tissues; the correlation between IVIS- and histologically determined tumor tissues was significant (R2 = 0.8301; p = 0.001). Genes associated with vascular and angiogenic signaling pathways were significantly upregulated in OPSCCa tissues. CONCLUSION: ICG effectively demarcates tumor margins in OPSCCa, due to the increased upregulation of genes associated with vascular permeability.

Expanding Understanding of Electrocochleography in Cochlear Implantation: Auditory Neuropathy Spectrum Disorder With Normal Pure Tone Average.

Objective: Describe the preoperative decision-making, intraoperative electrocochleographic (ECoG) findings, and outcome of cochlear implantation (CI) in a patient with auditory neuropathy spectrum disorder (ANSD) and normal pure-tone thresholds. Patients: A 19-year-old with a history of hypoxic ischemic encephalopathy and seizures was referred for hearing rehabilitation in the setting of typical hearing by pure tone audiometry but poor speech understanding. A diagnosis of ANSD was made based on acoustic brainstem response (ABR), distortion product otoacoustic emission, and acoustic reflex testing. Imaging revealed no central cause of hearing impairment. Interventions: Right-sided CI. Main Outcome Measures: Preoperative and postoperative audiometric data. Intraoperative ECoG. Results: Preoperatively the patient underwent comprehensive audiologic testing with behavioral audiometry, ABR testing, and CI candidacy evaluation. In the right ear, the pure tone average (PTA) was 15 dB and word recognition score was 36%. ABR confirmed ANSD. Preoperative CNC and AzBio in quiet were 8% and 0%, respectively. Intraoperative ECoG amplitudes and audiometry showed responses in the 100 uV range and estimated PTA of 42 dB HL. Postoperative testing at 1-month post-initial activation revealed PTA of 45 dB HL and unchanged word and sentence scores. However, the patient cites an improved ability to communicate and increased confidence and averages over 14 hours of device use daily. Conclusions: To our knowledge, this is the first reported case of CI in an ear with normal PTA. Given that nearly all presently available ECoG data comes from patients with greater degrees of hearing loss, this unique case adds to our understanding of hearing preservation in CI.

Association of Baseline Frailty Status and Age With Postoperative Complications After Cochlear Implantation: A National Inpatient Sample Study.

OBJECTIVE: To conduct a national registry-based evaluation of the independent associations of chronological age and frailty, as measured by 5- and 11-factor modified frailty index (mFI-5, mFI-11) score, on postoperative outcomes of participants undergoing cochlear implantation (CI). STUDY DESIGN: Cross-sectional analysis. SETTING: Multicenter national database. PARTICIPANTS: Adults 18 years or older who underwent CI during 2001 to 2018. MAIN OUTCOME MEASURES: Any postoperative complications (determined as the presence of major, minor, or implant-specific), extended hospital length of stay (eLOS) (≥75th percentile of study population), and nonhome discharge destination. RESULTS: There were 5,130 participants included with a median age of 60 years (interquartile range, 44-73 y) and slight female predominance (53.5%). Under mFI-5 scoring, there were 2,979 (58.1%) robust (mFI-5 = 0), 1710 (33.3%) prefrail (mFI-5 = 1), 362 (7.1%) frail (mFI-5 = 2), and 78 (1.5%) severely frail (mFI-5 ≥ 3) participants. Three hundred twenty-eight (6.49%) participants experienced a postoperative complication, with 320 (6.2%) discharged to a nonhome destination. Multivariate analysis showed no statistically significant correlation between increasing participant age or frailty status and postoperative complications; however, increasing baseline frailty tier showed an independent association with risk of eLOS (severely frail: odds ratio, 4..83; 95% confidence interval, 3.00-7.75; p < 0.001) and nonhome discharge (severely frail: odds ratio, 6.51; 95% confidence interval, 3.81-11.11; p < 0.001). The mFI-11 showed very similar trends. CONCLUSION: Among those evaluated, this study demonstrates that CI is a low-risk procedure in participants of all ages. Increasing frailty does not predispose to postoperative complications. However, frail patients are at additional risk for an eLOS and nonhome discharge. Short follow-up time, hospital-coding errors, and selection bias of more robust patients may limit the true results of this study.

Cochlear Implantation in Patients With Known Cognitive Impairment: What Are the Benefits?

OBJECTIVE: To evaluate the outcomes of cochlear implantation (CI) in adults with preoperatively diagnosed cognitive impairment. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic center. PATIENTS: Adults undergoing CI with preexisting cognitive impairment. INTERVENTIONS: Cochlear implantation. MAIN OUTCOME MEASURES: 1) Hearing improvement after CI; 2) morbidity and mortality associated with surgery. RESULTS: Eight patients met inclusion criteria with mean age 77.8 years (SD, 9.6 y) at time of implantation; 7 were included in subsequent analysis as one did not have speech recognition scores. Average preoperative MoCA cognitive score of 22.6 (SD, 3.9, ≤25 demonstrates cognitive impairment). Average follow-up was 29.0 months (SD, 33.3 mo). Two patients passed away at an average 58.0 months (SD, 31.1 mo) after surgery. Median preoperative pure tone average was 86.3 dB HL ( interquartile range 31.3 dB HL) compared with 33.8 dB HL (IQR 5.0 dB HL) postoperatively ( p = <0.001). Median preoperative speech testing score (AzBio/HINT) was 21% (IQR, 24%) compared with 44% (IQR, 21%) postoperatively ( p = <0.001). There were no observed surgical complications during the follow-up period. CONCLUSIONS: This study demonstrates that patients with cognitive impairment before CI can experience improved hearing, no increased risk of complications, and good longevity after CI. Further prospective studies are needed to further define the utility of CI in patients with impaired cognition.

Perigeniculate Giant Cell Tumor of Temporal Bone.

Giant cell tumors of bone (GCTBs) are benign osteolytic neoplasms that can be treated with either gross-total resection or subtotal resection with adjuvant radiotherapy. For the rare GCTB of the temporal bone, close proximity to critical structures can produce functional deficits and make gross-total resection difficult to achieve without significant morbidity. We present the case of a 28-year-old woman with progressive facial paresis, otalgia, neck pain, imbalance, and subjective hearing loss. She was found to have a facial nerve mass centered at the geniculate ganglion extending into the labyrinthine segment and vestibule. We achieved gross-total resection with preserved facial nerve function as the tumor did not originate from the facial nerve and could be dissected free from the nerve. Final pathology was consistent with GCTB.

Cognitive and behavioral effects of hearing loss.

PURPOSE OF REVIEW: Hearing loss is one of the largest modifiable risk factors for developing dementia, accounting for up to 9% of the overall modifiable risk. The neuropsychologic and psychosocial impacts of hearing loss are becoming increasingly appreciated. The objective of this review is to explore the recent literature regarding the cognitive and behavioral effects of hearing loss and the role of hearing rehabilitation, particularly in older adults. RECENT FINDINGS: Cognitive decline may begin while patients have subclinical hearing loss, earlier than previously thought. Hearing rehabilitation, either via hearing amplification, middle ear surgery, or cochlear implantation, likely plays a role in preventing or slowing the rate of cognitive decline in patients with hearing loss. Hearing loss can increase the likelihood of social isolation, loneliness and depression in older adults, but it is unclear at this time what effect hearing rehabilitation has on these domains. SUMMARY: Hearing loss is one of the largest modifiable risk factors for cognitive decline, and hearing rehabilitation can play a significant role in preserving cognitive function. Understanding the cognitive and psychosocial impact of hearing loss can help facilitate the development of approaches for prevention and treatment.

The Impact of Cochlear Implantation: Cognitive Function, Quality of Life, and Frailty in Older Adults.

This review examines the relationship between cochlear implantation and cognition and quality of life in older adults, as well as how frailty affects outcomes for older patients with cochlear implants. A growing body of evidence suggests that there is a strong association between hearing loss and cognitive impairment. Preliminary studies suggest that cochlear implantation in older adults may be protective against cognitive decline. While studies have observed a positive impact of cochlear implantation on quality of life, currently it is unclear what factors contribute the most to improved quality of life. Frailty, as a measurement of general health, likely plays a role in complication rates and quality-of-life outcomes after cochlear implantation, though larger prospective studies are required to further elucidate this relationship.

Superior Semicircular Canal Dehiscence Syndrome Following Head Trauma: A Multi-institutional Review.

OBJECTIVE: To evaluate patients who become symptomatic from superior semicircular canal dehiscence (SSCD) following head trauma. STUDY DESIGN: Case series assessing patients presenting with SSCD after a trauma. METHODS: A case series was completed assessing patients presenting with SSCD after trauma. Data from three academic medical centers were evaluated, including the following: imaging, videonystagmography (VNG)/vestibular evoked myogenic potential (VEMP) testing, audiometric assessment, and surgical repair. Outcome measures included the following: 1) Description of audio-vestibular symptoms, 2) mean pre- and post-operative pure tone average (PTA), word recognition score (WRS), and air bone gap (ABG). RESULTS: A total of 14 patients were included; 86% were male. Approximately 43% were found to have bilateral SSCD on imaging, with 57% of patients pursuing surgical management. The most common presenting symptoms included pulsatile tinnitus (93%), autophony (79%), and hearing loss (64%). Approximately 36% of patients underwent VNG/VEMP testing, with 83.3% of those demonstrating abnormal results. The mean audiometric findings on the symptomatic side included an air-conduction PTA of 38.0 dB, bone-conduction PTA of 24.3 dB, WRS of 81%, and ABG of 17.9 dB. Among patients who underwent surgery (57%), there was no significant change in the air-conduction PTA, bone-conduction PTA, or WRS (P > .05). However, there was an improvement in the ABG (preoperative = 22.8 dB versus postoperative = 9.7 dB; P = .005). CONCLUSION: Head trauma may be a potentiating event for SSCD syndrome. This study advances the hypothesis that these patients likely have underlying radiographic SSCD prior to their trauma, and a traumatic event increases in intra-vestibular or intracranial pressures, unmasking SSCD syndrome. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E2810-E2818, 2021.

The Rhox gene cluster suppresses germline LINE1 transposition.

Transposable elements (TEs) are mobile sequences that engender widespread mutations and thus are a major hazard that must be silenced. The most abundant active class of TEs in mammalian genomes is long interspersed element class 1 (LINE1). Here, we report that LINE1 transposition is suppressed in the male germline by transcription factors encoded by a rapidly evolving X-linked homeobox gene cluster. LINE1 transposition is repressed by many members of this RHOX transcription factor family, including those with different patterns of expression during spermatogenesis. One family member-RHOX10-suppresses LINE1 transposition during fetal development in vivo when the germline would otherwise be susceptible to LINE1 activation because of epigenetic reprogramming. We provide evidence that RHOX10 suppresses LINE transposition by inducing Piwil2, which encodes a key component in the Piwi-interacting RNA pathway that protects against TEs. The ability of RHOX transcription factors to suppress LINE1 is conserved in humans but is lost in RHOXF2 mutants from several infertile human patients, raising the possibility that loss of RHOXF2 causes human infertility by allowing uncontrolled LINE1 expression in the germline. Together, our results support a model in which the Rhox gene cluster is in an evolutionary arms race with TEs, resulting in expansion of the Rhox gene cluster to suppress TEs in different biological contexts.

Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet.

BACKGROUND: Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. OBJECTIVE: To develop and evaluate a novel, biologic antimicrobial coating for medical implants. METHODS: Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per a protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release over time from gentamicin-infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). RESULTS: Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not produce any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was gradual and remained above the minimal inhibitory concentration for gentamicin-sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic load within 24 hours. Overall, heparin-associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. CONCLUSION: We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

Radiofrequency Ablation vs Electrocautery Blinded Randomized Trial: Impact on Clinically Meaningful Outcomes.

OBJECTIVE: To analyze patients' return to normal activity, pain scores, narcotic use, and adverse events after undergoing tonsillectomy or adenotonsillectomy with monopolar electrocautery or radiofrequency ablation. STUDY DESIGN: Randomized double-blinded clinical trial based on prospective parallel design. SETTING: Academic medical center and tertiary children's hospital between March 2018 and July 2019. METHODS: Inclusion criteria included patients aged ≥3 years with surgical indication of recurrent tonsillitis or airway obstruction/sleep-disordered breathing. Patients were randomly assigned to monopolar electrocautery or radiofrequency ablation. Patients were blinded to treatment assignment. Survey questions answered via text or email were collected daily until postoperative day 15. The primary outcome was the patient's return to normal activity. Secondary outcomes included daily pain score, total amount of postoperative narcotic use, and adverse events. RESULTS: Of the 236 patients who met inclusion criteria and were randomly assigned to radiofrequency ablation or monopolar electrocautery, 230 completed the study (radiofrequency ablation, n = 112; monopolar electrocautery, n = 118). There was no statistically significant difference between the groups in the number of days for return to normal activity (P = .89), daily pain scores over 15 postoperative days (P = .46), postoperative narcotic use (P = .61), or return to hospital for any reason (P = .60), including bleeding as an adverse event (P = .13). CONCLUSIONS: As one of the largest randomized controlled trials examining instrumentation in tonsillectomy, our data do not show a difference between monopolar electrocautery and radiofrequency ablation with regard to return to normal activity, daily pain scores, total postoperative narcotic use, or adverse events.

Characterization of Malignant Head and Neck Paragangliomas at a Single Institution Across Multiple Decades.

Importance: Malignant head and neck paragangliomas (HNPGLs) are rare entities, and there are limited data regarding optimal treatment recommendations to improve clinical outcomes. Objective: To classify succinate dehydrogenase (SDH) germline mutations associated with malignant HNPGLs, evaluate time from diagnosis to identification of malignant tumor, describe locations of metastases and the functional status of malignant HNPGLs, and determine the role of selective neck dissection at the time of initial surgical resection. Design, Setting, and Participants: A retrospective cohort study was completed of patients diagnosed with paragangliomas on various sites on the body at an academic tertiary cancer hospital between the years 1963 and 2018. A subanalysis of HNPGLs was also completed. Data regarding diagnosis, gene and mutation, tumor characteristics and location, and treatments used were reviewed between February 2017 and March 2018. Main Outcomes and Measures: Mutations of SDH genes associated with benign and malignant HNPGLs, treatments used, time to the discovery of malignancy, and location of metastasis. Results: Of the 70 patients included in the study, 40 (57%) were male, and the mean (SD) age was 47 (21.1) years. Of patients with tumors isolated to the head and neck, 38 (54%) had benign HNPGLs, which were associated with mutations in the genes SDH subunit B (SDHB) (n = 18; 47%), SDH subunit C (n = 2; 5%), and SDH subunit D (n = 18; 47%). Among those with malignant HNPGLs, all but 1 patient had mutations in SDHB (n = 5; 83%); 1 patient had no mutation associated with their disease. The average age at diagnosis for malignant HNPGLs was 35 years, while benign tumors were diagnosed at an average age at 36 years. All patients with malignant disease underwent surgery. Four patients were found to have metastasis at the time of selective neck dissection. Among patients with malignant HNPGLs, 5 (83%) were treated with adjuvant radiation, and 1 (17%) was treated with adjuvant chemotherapy. Conclusions and Relevance: Malignant HNPGLs are rare entities that are difficult to diagnose and are typically identified by the presence of regional or distant metastasis. The results of this study found the prevalence of malignant HNPGLs to be 9%. These data suggest that it is beneficial to perform a selective neck dissection at the time of tumor excision. All patients with malignant HNPGLs but 1 had SDHB mutations.

Clinical Significance of Sarcopenia among Patients with Advanced Oropharyngeal Cancer.

OBJECTIVES: We investigated the prevalence and impact of sarcopenia on disease-free survival (DFS) and overall survival (OS) in advanced oropharyngeal cancer. STUDY DESIGN: Retrospective study. SETTING: Single-institution tertiary cancer care center. SUBJECTS AND METHODS: We identified patients with advanced oropharyngeal cancer with pretreatment positron emission tomography-computed tomography scans for image analysis. Data were collected on the following variables: age, sex, smoking and alcohol status, stage (TNM and American Joint Committee on Cancer), human papillomavirus (HPV) status, body mass index (BMI), and treatment modality. RESULTS: Of 113 patients identified with oropharyngeal cancer, 32 had sarcopenia: these patients were older (63.5 vs 57.6 years, P = .01), were less likely to be male (53.1% vs 76.5%, P = .03), and had a lower mean BMI (24.5 vs 28.4 kg/m2, P = .009). Eighty-five subjects had HPV-positive disease, and they had a higher BMI (28.2 vs 24.2 kg/m2, P = .01) than that of patients without HPV. Twenty-one subjects who were HPV positive had less cancer recurrence (24.7% vs 48.1%, P = .04) than that of their HPV-negative counterparts. Log-rank testing showed no difference in DFS ( P = .06) associated with sarcopenia but a significant difference in OS ( P = .049). There were differences in DFS ( P = .009) and OS ( P = .023) based on HPV status. According to univariable and multivariable models, HPV positivity exhibited improved DFS and OS. Sarcopenia was not statistically significant in survival models; however, it was associated with increased mortality and recurrence. CONCLUSION: Sarcopenia is a prognostic factor affecting OS independent of HPV status in advanced oropharyngeal cancer.

Clinical significance of tumor mitotic rate and lack of epidermal attachment in melanoma of the head and neck.

BACKGROUND: The primary purpose of this study was to identify the prognostic role of primary dermal melanoma and tumor mitotic rate in melanomas of the head and neck. METHODS: A retrospective review of the histopathologic, clinical, and demographic data of 256 patients was performed to investigate the impact of primary dermal melanoma and tumor mitotic rate on sentinel lymph node positivity, recurrence, and 5-year overall and disease-free survival. RESULTS: Increased tumor mitotic rate, but not primary dermal melanoma, is a significant predictor of sentinel lymph node positivity and higher likelihood of recurrence. Survival analysis demonstrated that both increased tumor mitotic rate and primary dermal melanoma decreased the 5-year overall and disease-free survival rates of patients with head and neck melanoma lesions. CONCLUSION: Tumor mitotic rate and primary dermal melanoma may have prognostic significance for both overall and disease-free survival in patients with head and neck melanoma. A larger prospective study is warranted to further elucidate prognostic factors for melanoma in the head and neck region.

Lobular capillary hemangiomas: Case report and review of literature of vascular lesions of the nasal cavity.

Vascular tumors of the nasal cavity can represent a variety of pathologies. In this case report, we discuss two patients presenting with a large vascular lesion occupying the nasal cavity. Significant bleeding was encountered during the initial attempts for endoscopic surgical resection. One lesion was successfully excised following preoperative embolization while a second following sphenopalatine artery vascular ligation. In both cases, final pathology showed lobular capillary hemangioma (LCH). We present a literature review and discussion of LCH and other vascular tumors that present in the nasal cavity. In addition, we discuss the utility of pre-resection vascular control of these tumors.

The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment.

The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor-RHOX10-critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.