Prediction of Cochlear Implant Fitting by Machine Learning Techniques.

OBJECTIVE: This study aimed to evaluate the differences in electrically evoked compound action potential (ECAP) thresholds and postoperative mapping current (T) levels between electrode types after cochlear implantation, the correlation between ECAP thresholds and T levels, and the performance of machine learning techniques in predicting postoperative T levels. STUDY DESIGN: Retrospective case review. SETTING: Tertiary hospital. PATIENTS: We reviewed the charts of 124 ears of children with severe-to-profound hearing loss who had undergone cochlear implantation. INTERVENTIONS: We compared ECAP thresholds and T levels from different electrodes, calculated correlations between ECAP thresholds and T levels, and created five prediction models of T levels at switch-on and 6 months after surgery. MAIN OUTCOME MEASURES: The accuracy of prediction in postoperative mapping current (T) levels. RESULTS: The ECAP thresholds of the slim modiolar electrodes were significantly lower than those of the straight electrodes on the apical side. However, there was no significant difference in the neural response telemetry thresholds between the two electrodes on the basal side. Lasso regression achieved the most accurate prediction of T levels at switch-on, and the random forest algorithm achieved the most accurate prediction of T levels 6 months after surgery in this dataset. CONCLUSION: Machine learning techniques could be useful for accurately predicting postoperative T levels after cochlear implantation in children.

A Randomized Crossover Study in Single-Sided Deafness Comparing a Cartilage Conduction CROS System and an Air-Conduction CROS System.

OBJECTIVE: To investigate if cartilage conduction (CC) rerouting devices are noninferior to air-conduction (AC) rerouting devices for single-sided deafness (SSD) patients by measuring objective and subjective performance using speech-in-noise tests that resemble a realistic hearing environment, sound localization tests, and standardized questionnaires. STUDY DESIGN: Prospective, single-subject randomized, crossover study. SETTING: Anechoic room inside a university. PATIENTS: Nine adults between 21 and 58 years of age with severe or profound unilateral sensorineural hearing loss. INTERVENTIONS: Patients' baseline hearing was assessed; they then used both the cartilage conduction contralateral routing of signals device (CC-CROS) and an air-conduction CROS hearing aid (AC-CROS). Patients wore each device for 2 weeks in a randomly assigned order. MAIN OUTCOME MEASURES: Three main outcome measures were 1) speech-in-noise tests, measuring speech reception thresholds; 2) proportion of correct sound localization responses; and 3) scores on the questionnaires, "Abbreviated Profile of Hearing Aid Benefit" (APHAB) and "Speech, Spatial, and Qualities of Hearing Scale" with 12 questions (SSQ-12). RESULTS: Speech reception threshold improved significantly when noise was ambient, and speech was presented from the front or the poor-ear side with both CC-CROS and AC-CROS. When speech was delivered from the better-ear side, AC-CROS significantly improved performance, whereas CC-CROS had no significant effect. Both devices mainly worsened sound localization, whereas the APHAB and SSQ-12 scores showed benefits. CONCLUSION: CC-CROS has noninferior hearing-in-noise performance except when the speech was presented to the better ear under ambient noise. Subjective measures showed that the patients realized the effectiveness of both devices.

Impact of COVID-19 pandemic on the number of otolaryngologic surgeries in Japan.

OBJECTIVE: Previous studies show that the COVID-19 pandemic affected the number of surgeries performed. However, data on the association between the COVID-19 pandemic and otolaryngologic surgeries according to subspecialties are lacking. This study was performed to evaluate the impact of the COVID-19 pandemic on various types of otolaryngologic surgeries. METHODS: We retrospectively identified patients who underwent otolaryngologic surgeries from April 2018 to February 2021 using a Japanese national inpatient database. We performed interrupted time-series analyses before and after April 2020 to evaluate the number of otolaryngologic surgeries performed. The Japanese government declared its first state of emergency during the COVID-19 pandemic in April 2020. RESULTS: We obtained data on 348,351 otolaryngologic surgeries. Interrupted time-series analysis showed a significant decrease in the number of overall otolaryngologic surgeries in April 2020 (-3619 surgeries per month; 95% confidence interval, -5555 to -1683; p < 0.001). Removal of foreign bodies and head and neck cancer surgery were not affected by the COVID-19 pandemic. In the post-COVID-19 period, the number of otolaryngologic surgeries, except for ear and upper airway surgeries, increased significantly. The number of tracheostomies and peritonsillar abscess incisions did not significantly decrease during the COVID-19 pandemic. CONCLUSION: The COVID-19 pandemic was associated with a decrease in the overall number of otolaryngologic surgeries, but the trend differed among subspecialties.

Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies.

Heavy metals are often found in soil and can contaminate drinking water, posing a serious threat to human health. Molecular pathways and curation therapies for mitigating heavy metal toxicity have been studied for a long time. Recent studies on oxidative stress and aging have shown that the molecular foundation of cellular damage caused by heavy metals, namely, apoptosis, endoplasmic reticulum stress, and mitochondrial stress, share the same pathways as those involved in cellular senescence and aging. In recent aging studies, many types of heavy metal exposures have been used in both cellular and animal aging models. Chelation therapy is a traditional treatment for heavy metal toxicity. However, recently, various antioxidants have been found to be effective in treating heavy metal-induced damage, shifting the research focus to investigating the interplay between antioxidants and heavy metals. In this review, we introduce the molecular basis of heavy metal-induced cellular damage and its relationship with aging, summarize its clinical implications, and discuss antioxidants and other agents with protective effects against heavy metal damage.

Efficacy of Chemotherapy After Immune Checkpoint Inhibitor Discontinuation in Head and Neck Cancer.

OBJECTIVE: Immune checkpoint inhibitors (ICI) have become widely used becuse of their effectiveness and relatively low rate of severe adverse events. However, active treatment should be continued after discontinuation of ICI as response rates are lower than that of conventional cytotoxic chemotherapy. The purpose of the present study was to determine the efficacy of treatment after ICI discontinuation. METHODS: This was a retrospective study from hospital charts of 99 consecutive cases treated with ICI at our facility since 2017. Of these, 79 cases of squamous cell carcinoma which had already discontinued ICI were enrolled in the present study. RESULTS: After discontinuation of ICI, 40 cases received active treatment with salvage chemotherapy (SCTx; 33 cases) or surgery or radiotherapy (seven patients) and 39 cases received nonactive treatment. SCTx comprising paclitaxel and cetuximab (PTX-Cmab) was administered to 15 cases and other SCTx regimens to 18 cases. A significant increase in overall survival (OS) was observed with active treatment compared with nonactive treatment. No significant differences in OS or progression-free survival (PFS) were observed between SCTx regimens; however, there was a trend toward increased survival with PTX-Cmab. Univariate analysis of overall response rate (ORR) demonstrated significant differences in the site of disease at ICI and SCTx regimens. A significant difference in disease control rate was observed between SCTx regimens. Multivariate analysis of ORR demonstrated a significant correlation with PTX-Cmab treatment. CONCLUSION: Active treatment after ICI discontinuation and the use of PTX-Cmab as SCTx may increase OS in head and neck squamous cell carcinoma. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:228-235, 2024.

Cochlear implantation for progressive hearing loss caused by an A8296G mutation in mitochondrial DNA.

Mitochondrial DNA mutations such as A3243G or A1555G are widely reported to cause hearing loss, but few reports exist on the A8296G mutation, which can also cause hearing loss. This report presents the case of a patient with the A8296G mutation and severe bilateral sensorineural hearing loss (SNHL) that progressed over two decades. The patient had no history of diabetes, but did have a family history of SNHL in her father and maternal grandmother. She was first diagnosed with SNHL at 45 years of age, and an A8296G mutation was found. The hearing threshold in the low-frequency range of the right ear was preserved at diagnosis, but eventually declined resulting in severe bilateral hearing loss by the age of 66 years, and cochlear implantation (CI) was performed in the left ear. The hearing threshold three months after CI was 25-45 dB HL, and the phoneme speech discrimination score in the left ear improved from 20% without CI to 74% with CI. SNHL patients with the A8295G mutation are good candidates for treatment with CI.

Hearing and Hearing Loss Progression in Patients with GJB2 Gene Mutations: A Long-Term Follow-Up.

We aimed to investigate whether the degree of hearing loss with GJB2 mutations could be predicted by distinguishing between truncating and non-truncating mutations and whether the genotype could predict the hearing loss level. Additionally, we examined the progression of hearing loss in individuals monitored for over 2 years for an average of 6.9 years. The proportion of truncating mutations was higher in patients with profound and severe hearing loss, but it was not accurate enough to predict the degree of hearing loss. Via genotype analysis, mutations of the p.Arg143Trp variants were associated with profound hearing loss, while mutations of the p.Leu79Cysfs*3 allele exhibited a wide range of hearing loss, suggesting that specific genotypes can predict the hearing loss level. Notably, there were only three cases of progression in four ears, all of which involved the p.Leu79Cysfs*3 mutation. Over the long-term follow-up, 4000 Hz was significant, and there was a trend of progression at 250 Hz, suggesting that close monitoring at these frequencies during follow-up may be crucial to confirm progression. The progression of hearing loss was observed in moderate or severe hearing loss cases at the time of the initial diagnosis, emphasizing that children with this level of hearing loss need regular follow-ups.

Analysis of postural stability using foam posturography in patients with persistent postural-perceptual dizziness.

BACKGROUND/OBJECTIVE: Persistent postural-perceptual dizziness (PPPD) is worsened in a standing posture, or by body movement, or visual stimulation. We aimed to evaluate postural stability in PPPD patients using foam posturography and to investigate the dependence on visual and somatosensory input in the standing posture. METHODS: Foam posturography was performed on 53 PPPD patients, and data from the PPPD patients were compared with the data from an age- and sex-matched healthy controls. The PPPD patients were divided into four groups based on the findings of vestibular function tests and the effect of vestibular function on posturographic data was examined. RESULTS: Romberg's ratios were significantly higher in PPPD patients than in controls. The median Romberg's ratios in PPPD patients with normal vestibular function were also higher than those in controls. However, foam ratio was significantly lower in PPPD patients than in controls. The median foam ratios in PPPD patients with vestibular dysfunction were also lower than those in controls. CONCLUSIONS: In a standing posture, PPPD patients may be more dependent on visual input and less dependent on somatosensory input than healthy subjects. Higher dependence on visual and lower dependence on somatosensory input in PPPD may be a feature unaffected by vestibular function.

Inter-day and intra-day variations in effective intensity of noisy galvanic vestibular stimulation to improve postural stability in bilateral vestibulopathy.

BACKGROUND: The reproducibility of the effective intensity of noisy galvanic vestibular stimulation (nGVS) to improve postural stability is not well known. OBJECTIVE: We aimed to investigate inter-day and intra-day variations in effective intensity in patients with bilateral vestibulopathy (BVP). METHODS: Thirteen BVP patients were measured for center-of-pressure movements in the standing posture at five time points: morning of the first test day, morning and evening of the second test day, and morning and evening of the third test day. The mean velocity, the envelopment area, and the root mean square were measured in the eyes-closed condition for 30 s during nGVS application ranging from 0 to 1000µA. The effective intensity was defined as the intensity at which all the three parameters measured during the stimulation were simultaneously smaller than the values at baseline (0µA). RESULTS: Seven of the 13 patients had a common effective intensity throughout the three test days. Six patients on the second test day and five patients on the third test day had no common effective intensity between morning and evening. CONCLUSIONS: The effective intensity of nGVS changes depending on the time during the day as well as between the days.

Endoplasmic reticulum stress associated with lead (Pb)-induced olfactory epithelium toxicity in an olfactory dark basal cell line.

Lead (Pb) can damage organs and also have undesirable effects on neural development. To explore the effects of Pb on olfactory cells, we investigated Pb-induced cell toxicity in the DBC1.2 olfactory cell line, with a focus on endoplasmic reticulum (ER) stress, apoptosis, and necroptosis. Representative markers of ER stress, apoptosis, and necroptosis were analyzed by quantitative PCR. The mRNA expression levels of GRP94, GRP78, spliced XBP1, PERK, and ATF6 increased significantly after Pb exposure in a dose-dependent manner. The expression of Caspase 3 and Caspase 12 did not increase after Pb exposure, which suggested that apoptosis-induced cell death was not activated after Pb exposure. However, the mRNA of RIPK3 and MLKL showed increases in expression, which indicated that necroptosis-induced cell death was activated after Pb exposure. These results indicate that Pb exposure induced dose-dependent cytotoxicity through ER stress and necroptosis pathways in DBC1.2 cells, whereas the apoptosis pathway was not significantly stimulated. HEPES buffer showed a partial protective effect in terms of ER stress, apoptosis, and necroptosis. In summary, the necroptosis pathway plays a crucial rule in Pb exposure-induced cytotoxicity in olfactory cells.

TERT promoter mutation positive oral cavity carcinomas, a clinically and genetically distinct subgroup of head and neck squamous cell carcinomas.

BACKGROUNDS: The importance of TERT promoter (pTERT) mutation of oral cavity squamous cell carcinoma (OCSCC) with clinical features and genetic alterations are not well recognized. METHODS: We retrospectively analyzed genetic data from multiple databases, including 260 cases from the C-CAT database, 407 cases from the MSK-MetTropism database, and 40 OCSCC datasets from in-house clinical samples. RESULTS: From C-CAT database, TP53 (66%), CDKN2A (51%), and pTERT (29%) were the most frequent mutations observed. pTERT mutations were more prevalent in OCSCC (63%), younger individuals, and women (46%), with lower rates of alcohol abuse and smoking and co-mutated with TP53, HRAS, and CASP8. MSK-MetTroposim data validated with the enrichment of pTERT mutations in OCSCC, among women and Asian individuals. In-house datasets OCSCC with pTERT mutation (50%) characterized by fewer recurrent neck metastases. CONCLUSION: The study suggests that OCSCC with pTERT mutation represents a distinct subgroup with unique clinical and genetic characteristics.

Predicting synkinesis caused by Bell's palsy or Ramsay Hunt syndrome using machine learning-based logistic regression.

Objective: To investigate whether machine learning (ML)-based algorithms, namely logistic regression (LR), random forest (RF), k-nearest neighbor (k-NN), and gradient-boosting decision tree (GBDT), utilizing early post-onset parameters can predict facial synkinesis resulting from Bell's palsy or Ramsay Hunt syndrome more accurately than the conventional statistics-based LR. Methods: This retrospective study included 362 patients who presented to a facial palsy outpatient clinic. Median follow-up of synkinesis-positive and -negative patients was 388 (range, 177-1922) and 198 (range, 190-3021) days, respectively. Electrophysiological examinations were performed, and the rate of synkinesis in Bell's palsy and Ramsay Hunt syndrome was evaluated. Sensitivity and specificity were assessed using statistics-based LR; and electroneurography (ENoG) value, the difference in the nerve excitability test (NET), and scores of the subjective Yanagihara scaling system were evaluated using early post-onset parameters with ML-based LR, RF, k-NN, and GBDT. Results: Synkinesis rate in Bell's palsy and Ramsay Hunt syndrome was 20.2% (53/262) and 40.0% (40/100), respectively. Sensitivity and specificity obtained with statistics-based LR were 0.796 and 0.806, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.87. AUCs measured using ML-based LR of "ENoG," "difference in NET," "Yanagihara," and all three components ("all") were 0.910, 0.834, 0.711, and 0.901, respectively. Conclusion: ML-based LR model shows potential in predicting facial synkinesis probability resulting from Bell's palsy or Ramsay Hunt syndrome and has comparable reliability to the conventional statistics-based LR. Level of Evidence: 3.

Visual fixation suppression of caloric nystagmus in progressive supranuclear palsy - A comparison with Parkinson's disease.

BACKGROUND: Impairment of visual fixation suppression (VS) in progressive supranuclear palsy (PSP) is not well documented. OBJECTIVE: To evaluate the usefulness of impaired VS of caloric nystagmus as an index for differential diagnosis between PSP and Parkinson's disease (PD), which is often difficult, especially in the early stage. METHODS: Subjects comprised 26 PSP patients and 26 PD patients clinically diagnosed at Tokyo Metropolitan Neurological Hospital. We retrospectively investigated VS of caloric nystagmus, horizontal pursuit, saccades, and horizontal optokinetic nystagmus recorded on direct-current-electronystagmography, and neuroradiological findings. RESULTS: The median of the average VS% was 0% and 50.0% in PSP and PD patients, respectively. In PSP, VS was impaired even in the early stage of disease. We found a significant correlation between VS and velocity of saccades or maximum slow phase velocity of optokinetic nystagmus only in PSP patients. PSP patients with atrophy of the subthalamic nucleus or with decreased blood flow in the frontal lobe showed significantly more severe impairment of VS. CONCLUSIONS: VS may be a useful biomarker to differentiate patients with PSP from those with PD. Cerebellar networks that connect with the cerebral cortex and basal ganglia may contribute to impaired VS of caloric nystagmus in PSP.

The effect of self-management vestibular rehabilitation on persistent postural-perceptual dizziness.

Objective: To investigate the effects of self-management vestibular rehabilitation (VR) on the subjective symptoms of dizziness and postural stability in persistent postural-perceptual dizziness (PPPD). Study design: Retrospective case review. Methods: The medical records of 30 patients newly diagnosed with PPPD based on the Bárány Society's diagnostic criteria were reviewed. Nineteen patients (4 males and 15 females; age range 27-84 years, mean age ± standard deviation 57.4 ± 14.2 years) who was newly instructed to self-management VR were included and instructed to perform self-management VR for 2 months. Results: One patient did not visit the outpatient clinic again, and in the remaining 18 patients, 4 (22%) discontinued VR at their own discretion. In the 12 patients who completed 2 months of VR (67%), there was a significant improvement in Niigata PPPD Questionnaire (NPQ) and Dizziness Handicap Inventory (DHI) scores after VR compared to those before VR (p < .05). However, the mean velocity of center of pressure (COP) movement (velocity) and the envelopment area traced by COP movement (area), as well as the Romberg ratio and foam ratio of velocity and area, did not differ significantly after VR when compared to those before VR (p > .05). Conclusions: For PPPD, self-management VR improved subjective symptoms of dizziness, but not stability of standing posture. It is necessary to improve patients' adherence to the treatment. Level of evidence: 4.

Heterogeneous Damage to the Olfactory Epithelium in Patients with Post-Viral Olfactory Dysfunction.

OBJECTIVES: Post-viral olfactory dysfunction (PVOD) is a neurogenic disorder caused by a common cold virus. Based on the homology of deduced amino acid sequences, olfactory sensory neurons (OSNs) in both mice and humans express either class I or class II odorant receptor genes encoding class I and class II OSNs. The purpose of this study was to determine whether OSN damage in PVOD occurs uniformly in both neuron types. MATERIALS AND METHODS: The characteristics of PVOD patients were compared with those of patients with chronic rhinosinusitis (CRS) or post-traumatic olfactory dysfunction (PTOD). Briefly, subjects underwent orthonasal olfaction tests using five different odors (T&T odors) and a retronasal olfaction test using a single odor (IVO odor). The regions in the mouse olfactory bulb (OB) activated by the T&T and the IVO odors were also examined. RESULTS: Multivariate analysis of 307 cases of olfactory dysfunction (PVOD, 118 cases; CRS, 161 cases; and PTOD, 28 cases) revealed that a combination of responses to the IVO odor, but not to the T&T odors, is characteristic of PVOD, with high specificity (p < 0.001). Imaging analysis of GCaMP3 mice showed that the IVO odor selectively activated the OB region in which the axons of class I OSNs converged, whereas the T&T odors broadly activated the OB region in which axons of class I and class II OSNs converged. CONCLUSIONS: A response to T&T odors, but not IVO odor, in PVOD suggests that class I OSNs are injured preferentially, and that OSN damage in PVOD may occur heterogeneously in a neuron-type-dependent manner.

Etiology, Severity, Audiogram Type, and Device Usage in Patients with Unilateral Moderate to Profound Sensorineural Hearing Loss in Japan.

BACKGROUND: Few studies have reported on the etiology, severity, or device usage of unilateral sensorineural hearing loss (UHL) compared to bilateral hearing loss. Therefore, this study investigated the characteristics of UHL in adults and children. METHODS: We performed a survey using questionnaires for secondary and tertiary otolaryngology institutions. RESULTS: We included 15,981 patients (1549 children and 14,432 adults) from 196 institutions with otolaryngology residency programs and 2844 patients (336 children and 2508 adults) from 27 institutions with board members of the Japan Audiology Society. The latter submitted audiological data. Among children, most diagnoses were made at age 0. Approximately half of them had profound hearing loss, and 37 children (2.2%) used hearing devices. Among adults, the number of cases increased with age, but decreased when people reached their 80s and 90s. More than half of them had moderate hearing loss. Sudden sensorineural hearing loss was the most common cause of UHL of all ages; 4.4% of UHL patients used hearing devices, and most of the device users (98.6%) selected a conventional hearing aid. CONCLUSIONS: Hearing aid use is limited in children and adults with UHL in Japan. There could be many candidates with UHL for intervention such as a cochlear implant.

Effects of early local administration of high-dose bFGF on a recurrent laryngeal nerve injury model.

BACKGROUND: Research on regenerative medicine using basic fibroblast growth factor (bFGF) has recently advanced in the field of laryngology. We previously reported that local administration of bFGF 1 month after recurrent laryngeal nerve (RLN) paralysis compensated for atrophy of the thyroarytenoid muscle. The objective of this study was to elucidate the effects of early bFGF administration on the thyroarytenoid muscle after RLN transection and to investigate the underlying mechanisms. METHODS: A rat model of RLN paralysis was established in this study. One day after RLN transection, low- (200 ng) or high-dose (2000 ng) bFGF or saline (control) was administered to the thyroarytenoid muscle. The larynges were excised for histological and immunohistochemical examinations at 1, 7, 14, 28, and 56 days after administration. RESULTS: The cross-sectional thyroarytenoid muscle area was significantly larger in the high-dose group than in the saline and low-dose groups on days 28 and 56. Immunohistochemistry indicated that bFGF significantly increased the number of satellite cells in the thyroarytenoid muscle up to day 14 and that of neuromuscular junctions on days 28 and 56. CONCLUSIONS: A single, early local administration of high-dose bFGF prevented atrophic changes in the thyroarytenoid muscles by activating satellite cell proliferation and reforming neuromuscular junctions. As increased neuromuscular junctions are expected to maintain myofiber volume, bFGF administration may prevent thyroarytenoid muscle atrophy in the mid to long term.

Live Imaging of the Dehydration Effect of Isosorbide on the Normal and Hydropic Guinea Pig Cochleae Using Optical Coherence Tomography.

OBJECTIVE: To investigate the isosorbide-induced dehydration effect on the endolymphatic space by intratympanic administration of isosorbide. BACKGROUND: Isosorbide, an osmotic diuretic, is used orally as a typical conservative therapy for Menière's disease (MD) in Japan. The dehydration effect occurs 6 hours after isosorbide ingestion. Intratympanic administration of isosorbide resolves endolymphatic hydrops faster than oral ingestion. In addition, the dehydration effect has never been shown directly. Therefore, we investigated the dehydration effect of intratympanic administration of isosorbide on endolymphatic hydrops using optical coherence tomography. METHODS: We used eight Hartley guinea pigs, divided into normal and hydrops groups. In the hydrops group, the animals underwent endolymphatic sac obliteration to create endolymphatic hydrops. We obtained midmodiolar section images of the cochleae using optical coherence tomography. Then, 50 to 70% isosorbide was sequentially administered intratympanically for 5 minutes, and the apical turn of the cochlea was observed. The relative midmodiolar cross-sectional area of the scala media was calculated for quantitative assessment of the endolymphatic space. RESULTS: In the normal group, 50% isosorbide had a slight but significant dehydration effect on the scala media; at 55 to 70%, Reissner's membrane became flat. In the hydrops group, 50% isosorbide slightly reduced endolymphatic hydrops; 65% flattened Reissner's membrane, and 70% slightly concaved it toward the basilar membrane. CONCLUSION: The results suggest that we could select the concentration of isosorbide according to the stage or severity of MD and relief from acute attack. Intratympanic administration of isosorbide may be a promising treatment for patients with MD.

Multi-Armed Star-Shaped Block Copolymers of Poly(ethylene glycol)-Poly(furfuryl glycidol) as Long Circulating Nanocarriers.

Multi-arm star-shaped block copolymers with precisely tuned nano-architectures are promising candidates for drug delivery. Herein, we developed 4- and 6-arm star-shaped block copolymers consisting of poly(furfuryl glycidol) (PFG) as the core-forming segments and biocompatible poly(ethylene glycol) (PEG) as the shell-forming blocks. The polymerization degree of each block was controlled by adjusting the feeding ratio of a furfuryl glycidyl ether and ethylene oxide. The size of the series of block copolymers was found to be less than 10 nm in DMF. In water, the polymers showed sizes larger than 20 nm, which can be related to the association of the polymers. The star-shaped block copolymers effectively loaded maleimide-bearing model drugs in their core-forming segment with the Diels-Alder reaction. These drugs were rapidly released upon heating via a retro Diels-Alder step. When the star-shaped block copolymers were injected intravenously in mice, they showed prolonged blood circulation, with more than 80% of the injected dose remaining in the bloodstream at 6 h after intravenous injection. These results indicate the potential of the star-shaped PFG-PEG block copolymers as long-circulating nanocarriers.