Nagoya Journal of Medical Science

Stability during walking is essential because falling accidents may lead to severe injuries. In this study, we calculated the margin of stability (MoS) and the maximum Lyapunov exponent (λ_s), which are two major stability indices for walking, using a gait database representing 300 healthy people. Previously, the relationships between these indices and other gait parameters, including joint angles, have not been investigated in such a large subject pool. Therefore, we determined the relationships between these stability indices and the gait parameters by calculating correlation coefficients and performing multiple regression analysis. The results indicated that MoS is dominated by walking speed in the forward direction and associated with various joint angles in the lateral direction. Conversely, no relationships were identified between λ_s and the gait parameters. Although both MoS and λ_s are considered as measures of gait stability, they are independent. The results of this study suggest that MoS and λ_s represent different aspects of gait motion.

Hook plate fixation and locking plate fixation are two standard internal fixation implants for treating distal clavicle fractures. We aimed to clarify the following: 1) Does the locking plate offer better clinical outcomes than the hook plate? 2) Is bone union better with a locking plate than hook plate? and 3) Are complications different between the locking plate and hook plate? We conducted a retrospective multicenter study of 338 patients who underwent surgery from 2014 to 2018 in our 10 hospitals, which comprise the TRON group. Of them, 208 patients treated using any plates were eligible. After 30 patients were excluded for various reasons, 178 patients were included. We classified them into two groups, locking plate group (Group L) and hook plate group (Group H), using propensity score matching. We confirmed bone union with an X-ray, evaluated the UCLA shoulder score, and compared the frequency of complications. After matching, Group L and Group H included 49 patients each. The UCLA score was higher in Group L than in Group H at each follow-up point. We confirmed bone union in all patients in Group L, but it was not confirmed in three patients (6.1%) in Group H. No statistically significant differences were observed except for plate migration, which was observed in nine patients (18.4%) in Group H but in no patients in Group L. The postoperative UCLA score was significantly better in Group L. We recommend the locking plate as a surgical treatment for distal clavicle fractures.

In genetic causes of male infertility, Y chromosome microdeletions are the second most common after Klinefelter’s syndrome. Although sperm recovery rate is relatively high for subjects with azoospermic factor (AZF) c chromosome microdeletion, intracytoplasmic sperm injection (ICSI) results using retrieved sperm has been reported to be poor. We retrospectively examined the infertility treatment for subjects with AZF microdeletion. From October 2017 to September 2020, chromosomal examination of 67 azoospermic subjects and 12 cryptozoospermia were performed. Of these, twenty-three subjects (29.1%) had AZF microdeletion. Twelve subjects with AZFc microdeletion and one subtype with unknown classification (Ym-9; P3 deletion) received sperm retrieval surgery due to azoospermia. Two subjects obtained motile sperm by microscopic epididymal sperm aspiration (MESA) and four subjects by microscopic testicular sperm extraction (micro-TESE). Pregnancy and healthy delivery were achieved in 6 of 14 subject (42.9%; including one twin) using ICSI. This was comparable with previous reports. Since there were two cases of obstructive azoospermia, we employed MESA to avoid testicular damage. Following observation of the testis and epididymis under operative microscope, a decision was made to perform sperm retrieval surgery to avoid unnecessary testicular damage. Furthermore, since AZFc microdeletion is passed to the next generation, long term follow-up is necessary.

The local control rates of T1 bulky and T2 glottic carcinoma treated via radiation therapy alone are unsatisfactory; thus, we aimed to evaluate the efficacy and safety of our treatment protocol for early glottic carcinoma. Patients with early glottic squamous cell carcinoma treated via radiation therapy from January 2007 to November 2019 were reviewed. Patients were treated with: 63–67.5 Gy/28–30 fractions of radiation therapy alone for T1 non-bulky; concurrent chemoradiotherapy with S-1 and 60 Gy/30 fractions for T1 bulky and T2 favorable; and concurrent chemoradiotherapy with high-dose cisplatin and 66–70 Gy/33–35 fractions for T2 unfavorable glottic carcinoma. Local failure rates were estimated using the cumulative incidence function, overall and disease specific survival rates were estimated using Kaplan-Meier analysis, and adverse events were evaluated. Eighty patients were analyzed; the median age was 69.5 (range, 26–90) years, the median follow-up time for survivors was 40.1 (range, 1.9–128.4) months, and the 3-year local failure, disease specific survival, and overall survival rates were 5.8%, 98.3%, and 94.4%, respectively. In T1 bulky and T2 cases, the local failure rate was significantly lower in the concurrent chemoradiotherapy than in the radiation therapy alone group. Grade 3 acute dermatitis and mucositis were noted in nine and four patients, respectively. There were no acute adverse events of Grade 4 or higher, or late adverse events of Grade 2 or higher. The treatment protocol was effective and well-tolerated; thus, the efficacy of concurrent chemoradiotherapy was suggested in T1 bulky and T2 cases.

In lateral skull base reconstruction, it is necessary to seal the defect in the lateral skull base, fill the dead space, and, sometimes, reconstruct the facial nerve. However, this procedure is difficult to perform with a standard musculocutaneous flap. Therefore, for such cases, an omental flap is used in our hospital because of its flexibility. In this study, we report our experience with the procedure (lateral skull base reconstruction with a free omental flap) and its long-term outcome and facial nerve reconstruction, with special focus on facial nerve recovery. This study is a technical note and a retrospective review. It was conducted in Nagoya University Hospital. Overall, 16 patients (12 women and 4 men; mean age: 55.1 years) underwent lateral skull base reconstruction with a free omental flap after subtotal temporal bone resection or lateral temporal bone resection during 2005–2017. The main outcome measures were postoperative complications and facial nerve recovery: Yanagihara score and House-Brackmann grading system. Complications included partial necrosis and minor cerebrospinal fluid leakage in 2 patients. Facial nerve recovery could be observed more than 12 months after surgery, with a mean Yanagihara score of 19.6 and House-Brackmann grade of 3.60. The free omental flap is a reliable method for lateral skull base reconstruction, especially in cases where facial nerve reconstruction is needed. To the best of our knowledge, this is the first report on facial nerve recovery after lateral skull base reconstruction.

Bioequivalence test should be carried out for copy medicine, including dihydroartemisinin-piperaquine (DHP), which is used to treat critical diseases requiring medication. To predict the bioequivalence of film coated DHP generic tablets compared to the reference, a randomized controlled trial, single blind, single dose cross over design, two sequences, 2 periods, and wash-out period 7 days was conducted on 8 healthy adults. Blood samples were taken at certain times; plasma levels of dihydroartemisinin (DHA) were determined and analyzed for pharmacokinetics profile using UPLC MS MS system. The mean ±SD of AUC_0-24, C_max, T_max, and T½ of the test drug (T) in the following order were 220.07 ± 64.48 ng.mL-1.hour; 119.00 ± 37.66 ng.mL-1.hour; 1.16 ± 0.30 hour; and 1.06 ± 0.31 hour. The mean ±SD of AUC_0-24, C_max, T_max, and T½ of the reference drug (R) were 301.91 ± 161.30 ng.mL-1.hour; 203.60 ± 91.04 ng.mL-1.hour; 0.94 ± 0.35 hour; and 0.80 ± 0.21 hour. Based on statistical analysis, the geometrics mean ratio (T/R) for the C_max and AUC_0-t were 0.6083 with 90% CI (0.4853–0.7624) and 0.7769 with 90% CI (0.6493–0.9295) respectively. Kinetic profiles between the two products were the same, however the test drug is relatively inferior compared to the reference drug.

Locomotive syndrome is a musculoskeletal disease of individuals who are highly likely to require nursing care. There is no systematic review that systematically evaluates and consolidates the findings of randomized controlled trials, although the number of randomized controlled trials considering the intervention effect on locomotive syndrome has been increasing with the spread of the concept. Therefore, this systematic review of randomized controlled trials is aimed at consolidating evidence regarding effective interventions to improve locomotive syndrome. We searched seven databases electronically. Studies were included in this systematic review if the following were met: (1) the articles were randomized controlled trials written in English or Japanese in a peer-reviewed journal, and (2) the clinical evaluation of the locomotive syndrome should include at least one of the following: the stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale. This systematic review included 10 studies. Several individual papers showed that the intervention group significantly improved the outcome measure for the diagnosis of locomotive syndrome compared with the control group. Only oral glucosamine intake provided sufficient information to conduct a meta-analysis, but the results were not statistically significant. This systematic review and meta-analysis did not provide strong evidence for specific interventions in improving locomotive syndrome, although individual randomized controlled trials have shown that oral intake of glucosamine, electrical stimulation, and exercise could improve locomotive syndrome. We hope that more high-quality randomized controlled exercise intervention trials aimed at improving locomotive syndrome, which is a musculoskeletal dysfunction, will be carried out in the future.

This study aims to determine the relationship between systemic inflammatory biomarkers and primary acquired nasolacrimal duct obstruction and to evaluate whether they can be used as indicators in determining the risk of recurrence after dacryocystorhinostomy. This retrospective, comparative case series was conducted with 57 primary acquired nasolacrimal duct obstruction patients and 58 age- and gender-matched controls. All subjects underwent a complete ophthalmologic examination and complete blood count measurements. The mean neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index were significantly higher in patients with primary acquired nasolacrimal duct obstruction (p = 0.005, p = 0.01, and p = 0.003, respectively). In recurrent patients, the neutrophil-to-lymphocyte ratio was significantly higher than in those who did not develop a recurrence (p = 0.029). The area under the curve was determined as 0.775 (p = 0.029) for the neutrophil-to-lymphocyte ratio in predicting recurrence. The neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index levels were significantly higher in patients with primary acquired nasolacrimal duct obstruction compared to healthy controls. The neutrophil-to-lymphocyte ratio might be used as a simple and inexpensive indicator for predicting recurrence in patients with primary acquired nasolacrimal duct obstruction.

In the evaluation of endolymphatic hydrops (EH) using magnetic resonance (MR) imaging, hybrid of reversed image of positive endolymph signal and native image of perilymph signal multiplied with heavily T2-weighted MR cisternography (HYDROPS-Mi2) imaging with the intravenous administration of a gadolinium-based contrast agent (IV-GBCA) has been utilized. Recently, MR cisternography (MRC) without GBCA has been proposed as a potential alternative method. However, the feasibility of EH evaluation by MRC without GBCA has not been established. The present study aimed to compare HYDROPS-Mi2 imaging with IV-GBCA to MRC without IV-GBCA for the evaluation of EH. In 40 ears of 20 patients with clinically suspected EH, MRC at pre-IV-GBCA and HYDROPS-Mi2 images from 4 h post-IV-GBCA were analyzed. The saccular height on the MRC (SH-MRC) was measured. The percentage of the volume of the endolymphatic space within the whole lymphatic space of the vestibule on the HYDROPS-Mi2 image (%EL_volume-HYD) was measured. The correlation between the SH-MRC and %EL_volume-HYD was calculated. The receiver operating characteristic (ROC) of the SH-MRC and %EL_volume-HYD for the clinical diagnosis of EH was evaluated. The Spearman’s rank correlation coefficient between the SH-MRC and %EL_volume-HYD was 0.102. The areas under the ROC curve were 0.570 for the SH-MRC, and 0.926 for the %EL_volume-HYD. In conclusion, there was no significant correlation between the MRC without IV-GBCA and the HYDOROPS-Mi2 with IV-GBCA in the evaluation of EH.

Central laboratory measurements are time consuming, while rapid fibrinogen level measurements within the operating room improve transfusion strategies. We aimed to clarify the correlation between fibrinogen concentrations (measured using Fibcare® and the Clauss fibrinogen assay in a central laboratory) during cardiovascular surgery with cardiopulmonary bypass. Data of patients whose Fibcare, traditional laboratory-based testing, and thromboelastographic results were measured using the same blood sample during cardiopulmonary bypass from February 2021 to January 2022 were retrospectively examined. We analyzed correlation in categories of body temperature during cardiopulmonary bypass: total cases, mild hypothermia (28–34°C), and moderate or severe hypothermia (<28°C). The Clauss fibrinogen assay was performed in 123 cases, Fibcare in 107, and thromboelastography in 91. For mild hypothermia, moderate or severe hypothermia, and overall, the root mean squared error and R-square in Fibcare were 16.1 and 0.86, 13.1 and 0.87, and 14.9 and 0.87, respectively, and for thromboelastography, they were 3.26 and 0.74, 2.70 and 0.79, and 3.08 and 0.75, respectively. A significant relationship was noted between Fibcare and Claus fibrinogen analysis regardless of body temperature during cardiopulmonary bypass. The measurement of fibrinogen levels using Fibcare allows for faster transfusion preparation than that of the traditional Clauss fibrinogen assay.

The purpose of this study was to examine the usefulness of an online learning program, Learning Program for New Faculty Members, in conveying knowledge of educational practice to newly appointed nursing faculty members. The study participants were assistant professors and research associates from nursing programs in Japan, with less than 5 years of educational experience. In total, 99 people participated in this study, and data from 97 were analyzed. Participants in the control group (43) were frequency matched to those in the intervention group (54) for sex, age, final degree, clinical experience, and academic experience. A pre-test was conducted using an original questionnaire, and there were no significant differences between the two groups in knowledge about educational practice. The intervention group then participated in the Learning Program for New Faculty Members online, at their convenience. After the intervention, a post-test was conducted. In the intervention group, post-test scores were significantly higher for all items except Item 3 (Conducting Class). The intervention and control groups’ post-test scores were 23.55 vs 16.90 for Item 1 (Student Understanding and Support), 28.20 vs 22.17 for Item 2 (Syllabus and Class Design) and 5.40 vs 2.97 for Item 4 (Understanding of Educational Theories). The Learning Program for New Faculty Members was therefore considered to be effective in helping newly appointed nursing faculty members to acquire knowledge. The program was able to overcome the time and environmental constraints of newly appointed nursing faculty members.

Use of instrumentation has become widespread in spinal surgery due to intraoperative spinal cord monitoring, navigation, and improvement and development of implant materials. However, recent advances in spine surgery may have also led to an increase in medical costs. The purpose of this study is to investigate the trends of operative resource utilization and the costs of surgery for adolescent idiopathic scoliosis (AIS) over 15 years. Surgery for AIS was performed for 118 patients from January 2004 to December 2019 at national University Hospital. Trends were examined through retrospective calculation of the costs for outpatient, inpatient, and surgical services, and changes over time and the characteristics of fees were examined. Differences between groups were analyzed by Mann-Whitney U test and Student t-test. During the 15-year period, the length of hospital stay decreased, but costs for scoliosis surgery increased by 1.6 times and the total cost increased by 1.3 times. The fee for intensive care per day per person increased by 1.5 times. There were slight increases in MRI and CT fees, but no changes in fees for radiography, rehabilitation, subsequent visits, and prescriptions. New charges for medical supervision, medical clerk support, medical safety measures, and prevention of infection were added at different times during the 15-year period. Itemized costs related to surgery have increased with technological advances. Although these results only show changes in costs for AIS surgery, the findings indicate the challenges faced by the healthcare economy and the need for spine surgeons to understand medical costs.

Although intraventricular hemorrhage (IVH) frequently develops secondary to intraparenchymal or subarachnoid hemorrhage, pure IVH―non-traumatic spontaneous intracranial hemorrhage confined to the cerebral ventricular system―is rare. Moreover, pure IVH caused by ruptured proximal aneurysm is an extremely rare but life-threatening condition. Herein, we present a case of pure IVH due to a ruptured internal carotid artery -anterior choroidal artery (ICA-AChA) aneurysm and review related literature. A 77-year-old man presenting with altered mental status was hospitalized due to a massive pure IVH with ventriculomegaly. The patient was conservatively managed because his consciousness level improved. On the following day, computed tomography angiography revealed a right ICA-AChA aneurysm embedded in the temporal lobe adjacent to the anterior part of the inferior horn of the lateral ventricle, which was consistent with the hemorrhagic origin. Coil embolization of the aneurysm was successfully performed, and the postprocedural course was uneventful. To date, only a few cases have described pure IVH caused by a ruptured proximal aneurysm. If the ruptured proximal aneurysm remains unnoticed, catastrophic rehemorrhage may occur. Aneurysm obliteration should precede the treatment of acute hydrocephalus. Neurosurgeons/neurointerventionalists must be aware about pure IVH caused by a ruptured proximal aneurysm even if it rarely occurs.

Posterior cerebral artery (PCA) aneurysms are rare and often fusiform. We describe two cases of complex proximal PCA aneurysm in two women in their 60’s, which probably resulted from segmental arterial degeneration. Both presented with subarachnoid hemorrhage and had common angiographic and intraoperative findings: tortuous configuration of the affected P1 segment, whitish or yellowish appearance of a portion of the lesion, lesion calcification, and multiple aneurysms in the segment. Interestingly, no significant atherosclerotic changes were noted in other cerebral arteries. The ruptured aneurysm could be successfully trapped, with superficial temporal artery (STA)-PCA bypass in one and without bypass in the other, and both patients recovered well. As complex aneurysm formation in the cases described here are probably related to proximal PCA segmental degeneration, we recommend trapping the lesion, with or without STA-PCA bypass, depending on the size and patency of the posterior communicating artery.

Cyclic vomiting syndrome (CVS) is characterized by recurrent episodes of severe vomiting with a completely asymptomatic interictal interval. Relatively few patients develop CVS in the neonatal period, and an early diagnosis is difficult. We experienced an infant who was diagnosed with neonatal-onset CVS in early infancy. An 8-day-old girl was admitted to our neonatal intensive care unit because of frequent vomiting beginning 12 h after birth and weight loss reaching 84.2% of her birth weight. Despite extensive examinations, no abnormalities to explain the vomiting were found. She continued to vomit, and a cyclical pattern with a vomiting phase lasting for three days followed by a non-vomiting phase lasting for about one to two weeks became obvious. Based on her clinical course, the family history of migraine and the effectiveness of Phenobarbital, she was diagnosed with CVS at three months old. Although CVS is a diagnosis of exclusion, a family history of migraine can aid its early diagnosis. If the illness is suspected in the neonatal period, diagnostic treatment with Phenobarbital may be considered. The case suggests the need to include CVS in the differential diagnosis of neonates with unexplained repetitive vomiting.

We report a Vietnamese family with complete androgen insensitivity syndrome that included several phenotypic females who have a 46,XY karyotype with an extremely rare mutation of the androgen receptor gene. The proband was a 27-year-old phenotypic adult female referred to our department for karyotyping due to primary amenorrhea. Ultrasound examination revealed a small uterus. Chromosomal analysis showed a 46,XY karyotype. A polymerase chain reaction assay revealed the presence of the sex-determining region Y gene. Next-generation sequencing detected the NM_000044.6(AR):c.2170C>T(p.Pro274Ser) mutation, which was confirmed by Sanger sequencing. There is only one previous report of this mutation in a child with complete androgen insensitivity syndrome. In the family presented in this study, there were four more phenotypic adult females with primary amenorrhea and a phenotypic female infant with testes in the inguinal canals. The infant (first cousin once removed of the proband) presented with inguinal hernia/swelling in a phenotypic female and one of the four abovementioned adults had similar genetic analysis results. This is the second report of a missense mutation NM 000044.6(AR):c.2170C>T in the world and the first study to document a pedigree consisting of several individuals with CAIS as a result of this mutation. The presence of a tiny uterus in the proband, which is a rare occurrence in complete androgen insensitivity syndrome, is a unique clinical indicator of the disorder’s variable expressivity.

Congenital hypothyroidism (CH) is a common heterogeneous endocrine disorder. The thyroid-stimulating hormone receptor gene (TSHR) is one of the major candidate genes associated with CH. Studies have investigated the possible correlations between the specific clinical features and the presence of TSHR variants. However, only a few reports have focused on the long-term follow-up of patients with CH. Here we present a case of CH-associated TSHR p.Arg109Gln and p.Arg450His rare compound heterozygous variants, with a follow-up performed until adolescence. The patient had high serum TSH levels during newborn screening. Oral administration of levothyroxine (l-T4) was initiated at 1 month of age. The ultrasonogram revealed normal thyroid morphology and blood flow. Reduced uptake of I-123 and negative perchlorate test was observed. A small amount of l-T4 remained needed although l-T4 could be steadily reduced by puberty. The patient was diagnosed with orthotopic, nongoitrous, and permanent CH. He had no nonclassical TSH resistance. Patients with the TSHR p.Arg109Gln compound heterozygous variant exhibit permanent CH with high TSH levels and normal or slightly lower fT4 levels. In the future, genotype identification could help predict the long-term prognosis and reduce the requirement for detailed examinations. More case studies are needed to determine the relationship between genetic variants and clinical features in CH.

The potential mechanism of augmented response on cervical vestibular evoked myogenic potential (cVEMP) testing and its decrease following treatment in a patient with Meniere’s disease (MD) are discussed. Changes of static posturography and cVEMP testing before and after a glycerol drip in a 69-year-old man with unilateral MD, in which significant endolymphatic hydrops (EH) was confirmed on magnetic resonance imaging (MRI) on the diseased side, were evaluated. Values of total locus lengths, areas of postural sway, and their Romberg ratios were decreased after the glycerol drip. On cVEMP testing, the diseased ear demonstrated a 375% larger amplitude than the contralateral ear before treatment, but both ears showed almost the same responses after treatment. An augmented response on cVEMP testing and a decrease following treatment for MD reflect the diversity of clinical findings in MD. Responses on cVEMP testing may relate not only to the degree of EH, but also be due to abnormal acoustic energy absorbance transmitted into the saccule.

M1 large circumferential aneurysms are clinically challenging because they cannot be treated by simple neck clipping and they may involve the lenticulostriate arteries (LSAs). Although some reports have described endovascular and direct surgical treatment of these aneurysms, the optimal treatment approach remains uncertain. We report a case involving a ruptured large M1 circumferential aneurysm that was treated with bypass-assisted trapping surgery and showed favorable outcomes. The patient was a 47-year-old man presenting with subarachnoid hemorrhage. Digital subtraction angiography revealed a large circumferential aneurysm in the right middle cerebral artery M1 segment with involvement of the lateral and medial LSAs. We successfully performed trapping surgery with the assistance of a superficial temporal artery (STA)-M2 bypass while preserving the medial and lateral LSAs. Although left hemiparesis caused by medial LSA thrombosis appeared in the early postoperative period, the patient showed good recovery from symptoms with rehabilitation and could independently perform daily activities at the five-month follow-up. The treatment of M1 large circumferential aneurysms should involve considerations for prevention of rebleeding, blood supply to the distal area, and preservation of perforating arteries. The treatment strategy for this challenging aneurysm should be planned based on the patient’s condition and individual anatomy.

Bilateral variation of the parotid gland is an anatomically rare entity. In this study, we present a 91-year-old female cadaver with aplasia of the parotid gland on the left side of the face and hypoplasia of the parotid gland on the right side of the face. The accessory parotid glands on both sides were of normal size, while bilateral submandibular glands were found to be larger than normal. The surgical anatomy of the parotid gland is very important because this region of the face is a complex structure intertwined with important vessels and nerves. Patients with aplasia, atresia, agenesis, or hypoplasia of the parotid gland should be diagnosed early and proper treatment must be planned. Consequently, this case was found to be remarkable in terms of the coexistence of parotid gland aplasia and hypoplasia.

A 19-year-old woman presented with swelling of the left forehead without pain. She did not have any relevant past or family history. Computed tomography showed destruction of the outer cortex of the frontal bone. A solitary mass lesion with a fluid collection was detected with magnetic resonance imaging. Because the swelling of the left forehead had enlarged rapidly with osteolytic changes, surgical removal of the lesion was performed. The lesion appeared to be enveloped in a fibrous capsule. The soft lesion was removed from the frontal bone. The outer frontal bone was absent, although the inner frontal bone was preserved. Then, the frontal bone was resected with margins from the edge of the erosion. The dura mater under the lesion was intact. A cranioplasty was performed using titanium mesh. On histological examination, the trabecular bones revealed irregular shapes and arrangements, indicating fibrous dysplasia. There was a continuous high-cell-concentration pathological lesion outside the fibrous dysplasia. There were numerous cells, such as mononuclear cells, osteoclast-like multinucleated giant cells, foam cells, and red blood cells. The osteoclast-like multinucleated giant cells and other cells did not show significant nuclear atypia. Immunostaining with H3.3G34W was negative, and the ubiquitin-specific peptidase 6/Tre-2 gene showed no rearrangements. The histopathological diagnosis was secondary aneurysmal bone cyst with fibrous dysplasia. Additional postsurgical therapy was not performed. There has been no evidence of recurrence of the lesion for two years.