Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS). Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI ≥70％(RDI 70 group,N=70)or RDI＜70％(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were ＜0.10 in univariate analysis. Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3％ vs. 28.3％,P＜0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7％ vs. 11.3％,P＜0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P＜0.01).Multivariate analysis showed that RDI ≥70％(hazard ratio(HR)=0.55,P=0.025),hypertension grade ≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P＜0.01)were independently associated with improved OS.RDI ≥70％ was not statistically significant in multivariate analysis. Conclusions:Our study revealed the importance of achieving RDI ≥70％ in the first 30 days of treatment to maximize the effects of LEN.

Introduction: To evaluate the utility of vagus nerve stimulation (VNS) therapy for patients with intractable postencephalitic epilepsy in the reduction of seizure frequency and quality of life (QOL). Methods: We studied five patients with intractable postencephalitic epilepsy, the age ranged from 21 to 46 years. QOL of the patients was evaluated with the questionnaire, QOLIE-31-P. Results: VNS therapy improved seizure frequency in four patients (80%). One patient (20%) had no reduction of seizure frequency. Three patients had improvements in QOLIE-31-P (p < 0.024) and became socially independent. Two other patients continued to be dependent, and have lesser degree of improvements in their QOLIE-31-P scores.Conclusion: VNS is effective for patients with intractable postencephalitic epilepsy and is able to improve the QOL.

Background & Objective: It is well established that the effectiveness of vagus nerve stimulation (VNS) therapy increases over 2-3 years. When increasing the dose of VNS, some patients were noted to respond even at low-dose stimulation in the first few months. The purpose of this study was to evaluate the relationship between an initial response to VNS and long-term response in a retrospective study of patients with intractable epilepsy. Method: We retrospectively analysed 56 patients who had VNS implantation in our centre. All patients had undergone complete presurgical evaluation. After implantation, the patients were examined at regular intervals of one month for 6-9 months and then followed up regularly for more than 2 years. Their seizure frequency and intensity were documented in their seizure logs. Results: Six patients achieved Engel class I (11%) seizure outcome, 16 achieved Engel class II (28%), and 19 achieved Engel class III (34%). Of the 22 patients with Engel I and II, the 19 in Engel class I (100%) and II (81%) showed an initial response within 6 months, an earlyonset response of VNS implantation. Conclusions: Early-onset response could be an independent predictor for achievement of Engel class I and II in long-term follow-up. Keyword: Background & Objective: It is well established that the effectiveness of vagus nerve stimulation (VNS) therapy increases over 2-3 years. When increasing the dose of VNS, some patients were noted to respond even at low-dose stimulation in the first few months. The purpose of this study was to evaluate the relationship between an initial response to VNS and long-term response in a retrospective study of patients with intractable epilepsy. Method: We retrospectively analysed 56 patients who had VNS implantation in our centre. All patients had undergone complete presurgical evaluation. After implantation, the patients were examined at regular intervals of one month for 6-9 months and then followed up regularly for more than 2 years. Their seizure frequency and intensity were documented in their seizure logs. Results: Six patients achieved Engel class I (11%) seizure outcome, 16 achieved Engel class II (28%), and 19 achieved Engel class III (34%). Of the 22 patients with Engel I and II, the 19 in Engel class I (100%) and II (81%) showed an initial response within 6 months, an earlyonset response of VNS implantation. Conclusions: Early-onset response could be an independent predictor for achievement of Engel class I and II in long-term follow-up. Keyword: Vagus nerve stimulation, long term outcome, early onset response, predictor, epilepsy

Morphine is the only opioid that has been found effective for the relief of dyspnea in cancer patients. However, efficacy has not been fully demonstrated for other opioids such as fentanyl. Here, we report a case of lung cancer in which the use of fentanyl was effective for the relief of dyspnea. The patient was an 88-year-old man who had cT4N2M0, cStage IIIB lung cancer with right bronchial involvement and mediastinal lymph node metastases. Although the patient complained of dyspnea, he was not given morphine due to underlying renal dysfunction. He instead received oxygen therapy, and treatment with oral steroids and oxycodone. As oral administration became more difficult with subsequent lung cancer progression, the patient underwent opioid switching from oxycodone to subcutaneous injections of fentanyl. Dyspnea was not exacerbated following the switching, and was thereafter effectively managed by increasing the fentanyl dose and using rescue medication. Fentanyl is suggested to be a possible therapeutic option for dyspnea in cases where the use of morphine is difficult.

Objectives : Muscle imbalance poses a problem for adequate motor function in patients with cerebral palsy. The adductor and flexor muscles around the hip become dominant, leading to a high risk of hip dislocation. When left untreated, flexion and adduction contracture progresses, leading to various impairments ; hence, it is important to undertake preventive measures at an early stage. Selective muscle release is one form of surgical treatment that has been proven effective, but there is no consensus on the timing of the surgery. Here, we investigated the difference in outcome after muscle release surgery with respect to age. Subjects and methods : The subjects were 26 patients (52 hips) from our medical center who underwent muscle release (partial modification of Matsuo's method) around the hip and were followed up for at least 6 months. Abduction was retained postoperatively by using a cast or prosthetic device. Migration percentage (MP) was measured by simple hip radiography image, and the rates of improvement (preoperative MP . final MP during observation/preoperative MP ×100%) were compared. Results : Higher rates of improvement were observed among patients aged 5 years or less at the time of surgery than those among patients aged 6 years or more. Conclusion : We consider that surgery performed at the age of 5 years or less could lead to favorable results.

OBJECTIVES: We conducted multi-directional language development tests as a part of the Research on Sensory and Communicative Disorders (RSVD) in Japan. This report discusses findings as well as factors that led to better results in children with severe-profound hearing loss. METHODS: We evaluated multiple language development tests in 33 Japanese children with cochlear implants (32 patients) and hearing aid (1 patient), including 1) Test for question and answer interaction development, 2) Word fluency test, 3) Japanese version of the Peabody picture vocabulary test-revised, 4) The standardized comprehension test of abstract words, 5) The screening test of reading and writing for Japanese primary school children, 6) The syntactic processing test of aphasia, 7) Criterion-referenced testing (CRT) for Japanese language and mathematics, 8) Pervasive development disorders ASJ rating scales, and 9) Raven's colored progressive matrices. Furthermore, we investigated the factors believed to account for the better performances in these tests. The first group, group A, consisted of 14 children with higher scores in all tests than the national average for children with hearing difficulty. The second group, group B, included 19 children that scored below the national average in any of the tests. RESULTS: Overall, the results show that 76.2% of the scores obtained by the children in these tests exceeded the national average scores of children with hearing difficulty. The children who finished above average on all tests had undergone a longer period of regular habilitation in our rehabilitation center, had their implants earlier in life, were exposed to more auditory verbal/oral communication in their education at affiliated institutions, and were more likely to have been integrated in a regular kindergarten before moving on to elementary school. CONCLUSION: In this study, we suggest that taking the above four factors into consideration will have an affect on the language development of children with severe-profound hearing loss.
Aphasia ; Asian Continental Ancestry Group ; Child ; Child Development Disorders, Pervasive ; Cochlear Implants ; Communication Disorders ; Comprehension ; Hearing ; Hearing Aids ; Hearing Loss ; Humans ; Japan ; Language Development ; Mass Screening ; Mathematics ; Rehabilitation Centers ; Vocabulary ; Weights and Measures ; Writing

OBJECTIVES: The number of patients with bilateral cochlear implant (CI) has gradually increased as patients and/or parents recognize its effectiveness. The purpose of this report is to evaluate the efficacy of 29 bilateral CI out of 169 pediatric CI users, who received auditory-verbal/oral habilitation at our hearing center. METHODS: We evaluated the audiological abilities 29 Japanese children with bilateral CIs including wearing threshold, word recognition score, speech discrimination score at 1 m from front speaker (SP), 1 m from second CI side SP, speech discrimination score under the noise (S/N ratio=80 dB sound pressure level [SPL]/70 dB SPL, 10 dB) at 1 m from front SP, word recognition score under the noise (S/N ratio=80 dB SPL/70 dB SPL, 10 dB) at 1 m from front SP. RESULTS: Binaural hearing using bilateral CI is better than first CI in all speech understanding tests. Especially, there were significant differences between the results of first CI and bilateral CI on SDS at 70 dB SPL (P=0.02), SDS at 1 m from second CI side SP at 60 dB SPL (P=0.02), word recognition score (WRS) at 1 m from second CI side SP at 60 dB SPL (P=0.02), speech discrimination score (SDS) at 1 m from front SP under the noise (S/N=80/70; P=0.01) and WRS at 1 m from front SP under the noise (S/N=80/70; P=0.002). At every age, a second CI is very effective. However, the results of under 9 years old were better than of over 9 years old on the mean SDS under the noise (S/N=80/70) on second CI (P=0.04). About use of a hearing aid (HA) in their opposite side of first CI, on the WRS and SDS under the noise, there were significant differences between the group of over 3 years and the group of under 10 months of HA non user before second CI. CONCLUSION: These results may show important binaural effectiveness such as binaural summation and head shadow effect. Bilateral CI is very useful medical intervention for many children with severe-to-profound hearing loss in Japan as well as elsewhere.
Asian Continental Ancestry Group ; Child ; Cochlear Implantation ; Cochlear Implants ; Head ; Hearing ; Hearing Aids ; Hearing Loss ; Humans ; Japan ; Noise ; Parents ; Speech Perception

When adipose-derived stem cells (ASCs) are retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells are introduced and the current profiles of their cellular nature are summarized. Under proper induction culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenic and myogenic potentials. In angiogenic conditions, DFAT cells could exhibit perivascular characteristics and elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.
Adipocytes ; physiology ; Adult Stem Cells ; Animals ; Cell Culture Techniques ; Cell Dedifferentiation ; Cell Lineage ; Gene Expression Profiling ; Humans ; Mesenchymal Stromal Cells ; Multipotent Stem Cells ; Neovascularization, Physiologic ; Pericytes ; cytology ; Tissue Engineering ; methods

The purpose of the present study was to discuss the effects of risedronate on osteoarthritis (OA) of the knee by reviewing the existing literature. The literature was searched with PubMed, with respect to prospective, double-blind, randomized placebo-controlled trials (RCTs), using the following search terms: risedronate, knee, and osteoarthritis. Two RCTs met the criteria. A RCT (n = 231) showed that risedronate treatment (15 mg/day) for 1 year improved symptoms. A larger RCT (n = 1,896) showed that risedronate treatment (5 mg/day, 15 mg/day, 35 mg/week, and 50 mg/week) for 2 years did not improve signs or symptoms, nor did it alter radiological progression. However, a subanalysis study (n = 477) revealed that patients with marked cartilage loss preserved the structural integrity of subchondral bone by risedronate treatment (15 mg/day and 50 mg/week). Another subanalysis study (n = 1,885) revealed that C-terminal crosslinking telopeptide of type II collagen (CTX-II) decreased with risedronate treatment in a dose-dependent manner, and levels reached after 6 months were associated with radiological progression at 2 years. The results of these RCTs show that risedronate reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone. The review of the literature suggests that higher doses of risedronate (15 mg/day) strongly reduces the marker of cartilage degradation (CTX-II), which could contribute to attenuation of radiological progression of OA by preserving the structural integrity of subchondral bone.
Animals ; Calcium Channel Blockers/pharmacology/*therapeutic use ; Cartilage/drug effects ; Diphosphonates/therapeutic use ; Etidronic Acid/*analogs & derivatives/pharmacology/therapeutic use ; Humans ; Osteoarthritis, Knee/*drug therapy