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1.
Pain Ther ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896199

RESUMO

INTRODUCTION: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group. CONCLUSIONS: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04094662.

2.
Front Neurol ; 15: 1356300, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751878

RESUMO

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG.

3.
Diabetol Int ; 15(1): 19-27, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264223

RESUMO

Aim/introduction: This study aims to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective (JDCP) study. Materials and methods: In the study, 6338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using t test, chi-square test, and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Results: Of the total participants, 5451 patients (mean age 61.4 years old and duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased risk for DSPN: age [odds ratio (OR) 1.57, 95% confidence intervals (CI) 1.42-1.73], duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39), and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). Conclusions: The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also revealed the risk factors of DSPN.

4.
J Diabetes Investig ; 15(2): 247-253, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213265

RESUMO

This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t-test, χ2 -test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42-1.73), duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39) and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Polineuropatias , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Prospectivos , Japão/epidemiologia , Prevalência , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/diagnóstico , Polineuropatias/epidemiologia , Polineuropatias/etiologia
5.
Intractable Rare Dis Res ; 12(4): 246-250, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38024578

RESUMO

Varicella zoster virus (VZV) causes chickenpox at the primary infection and then becomes latent in the spinal dorsal root ganglia; VZV can reactivate with aging, immunosuppression, stress, and other factors, occurring as herpes zoster (HZ) at 1-2 skin segments. HZ peripheral nerve complications caused by VZV reactivation include Hunt syndrome, segmental HZ paresis, post-herpetic neuralgia, and Guillain-Barré syndrome (GBS). We have encountered the rare HZ complications of upper-limb paresis, myeloradiculitis, and polyradiculoneuritis: an adult woman with upper-limb paresis consistent with the nerve root on segments above the thoracic HZ dermatome; another woman exhibiting ascending myeloradiculitis originating at the Th11-12 roots; an elderly woman with ascending VZV polyradiculoneuritis resembling GBS; an adult with VZV quadriplegia with disseminated HZ; and an elderly patient with VZV-associated polyradiculoneuritis. The three polyradiculoneuritis cases may be a new subtype of HZ peripheral neuropathy, but the pathophysiology for these HZ peripheral nerve complications unrelated to HZ dermatomes is unclear. We analyzed host factors, skin lesions, neurological and virological findings, and MRI results including 3D NerveVIEW in 15 Japanese patients treated at our facility for HZ peripheral neuropathy, including six differing from the HZ dermatome. Based on the clinical findings including MRI results of spinal ganglia and roots, we identified four possible routes for the patterns of VZV spread: (i) ascending spinal roots, (ii) ascending spinal cord, (iii) polyradiculopathy, and (iv) intrathecal spread. The incidence of HZ is increasing with the aging of many populations, and clinicians should be aware of these HZ neuropathies.

7.
Surg Today ; 53(4): 443-450, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36181567

RESUMO

PURPOSES: Fine-needle aspiration cytology (FNAC) is a specific and important test used for the diagnosis of thyroid gland cancer. We developed a thyroid gland phantom using original manufacturing techniques and direct three-dimensional (3D) printing. The aim of this study was to confirm the effectiveness of this phantom by collecting data to evaluate puncture training. METHODS: Data from 45 ultrasonography-guided thyroid nodule FNAC procedures performed on our thyroid phantom were evaluated in our department. The first group comprised qualified physicians who specialized in thyroid gland treatment (group A; n = 10). The second and third groups comprised senior and junior residents (group B; n = 8 and group C; n = 12; respectively). The fourth group comprised students (group D; n = 15). We measured the times taken by these groups to complete each task. RESULTS: The skills of all participants in groups B, C, and D improved after using this phantom involving the major (parallel)- (0.47 ± 0.07) and short (orthogonal)-axes (0.52 ± 0.07) methods (P < 0.001). The number of erroneous punctures decreased from 53 to 3. CONCLUSIONS: Our original phantom improved the puncture skills of students and junior doctors and was suitable as a tailored training model for practicing thyroid gland transfixion.


Assuntos
Internato e Residência , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Biópsia por Agulha Fina/métodos , Ultrassonografia/métodos , Estudantes
8.
Sci Rep ; 12(1): 14059, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982150

RESUMO

In Japan, asymptomatic metastatic breast cancer (MBC) is often detected using tumor markers or imaging tests. We aimed to investigate differences in clinicopathological features, prognosis, and treatment between asymptomatic and symptomatic MBCs. Patients with MBC were retrospectively divided into asymptomatic and symptomatic groups to compare their prognosis by breast cancer subtype: luminal, human epidermal growth factor receptor 2 positive, and triple negative. Of 204 patients with MBC (114 asymptomatic, 90 symptomatic), the symptomatic group had a higher frequency of multiple metastatic sites and TN subtype. All cohorts in the asymptomatic group tended to or had longer post-recurrence survival (PRS) than those in the symptomatic group. In contrast, all cohorts and TN patients in the asymptomatic group tended to have or had longer overall survival (OS) than those in the symptomatic group, although no significant difference was observed in the luminal and HER2 subtypes. In the multivariate analysis, TN, recurrence-free survival, multiple metastatic sites, and symptomatic MBC were independently predictive of PRS. Regarding the luminal subtype, the asymptomatic group had longer chemotherapy duration than the symptomatic group, with no significant difference in OS between the groups. Asymptomatic and symptomatic MBCs differ in terms of subtypes and prognosis, and whether they require different treatment strategies for each subtype warrants further investigation.


Assuntos
Neoplasias da Mama , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
10.
Mol Brain ; 15(1): 26, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35346312

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by specific social symptoms, restricted interests, stereotyped repetitive behaviors, and delayed language development. The 3q29 microdeletion (3q29del), a recurrent copy number variant, confers a high risk for ASD and schizophrenia, and serves as an important pathological model for investigating the molecular pathogenesis of a large number of neurodevelopmental and psychiatric conditions. Recently, mouse models carrying a deletion of the chromosomal region corresponding to the human 3q29 region (Df/+ mice) were generated and demonstrated neurodevelopmental and psychiatric conditions associated behavioral abnormalities, pointing to the relevance of Df/+ mice as a model for these conditions with high construct and face validity. Currently, the molecular pathogenesis of these behavioral phenotypes in Df/+ mice remains unclear. The oxytocin (OXT) system plays a central role in social behavior across species and has a potential role in ASD. In this study, to elucidate the molecular mechanisms behind impaired social behavior in Df/+ mice, we investigated the possible involvement of OXT signaling in impaired social behavior in Df/+ mice. We demonstrated that OXT administration restored the impaired social behavior in Df/+ mice. We also demonstrated that the number of OXT-positive cells in the paraventricular nucleus (PVN) was significantly lower in Df/+ mice than in wild-type (WT) littermates. Consistent with this, the level of OXT peptide in the cerebral cortex of Df/+ mice was lower than in WT littermates. Our study may provide important insights into the molecular pathophysiological basis of neurodevelopmental and psychiatric conditions, including ASD.


Assuntos
Transtorno do Espectro Autista , Deleção Cromossômica , Deficiência Intelectual , Ocitocina , Comportamento Social , Animais , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Encéfalo , Cromossomos Humanos Par 3 , Deficiências do Desenvolvimento , Modelos Animais de Doenças , Camundongos , Ocitocina/farmacologia
11.
Biochem Biophys Res Commun ; 605: 45-50, 2022 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313230

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by altered social communication, restricted interests, and stereotypic behaviors. Although the molecular and cellular pathogeneses of ASD remain elusive, impaired neural stem cell differentiation and neuronal migration during cortical development are suggested to be critically involved in ASD. ANK2, which encodes for a cytoskeletal scaffolding protein involved in recruiting membrane proteins into specialized membrane domains, has been identified as a high-confidence ASD risk gene. However, the role of ANK2 in early neural development remains unclear. In this study, we analyzed the role of ANK2 in the cerebral cortex of developing mouse using in utero electroporation. We provide evidence suggesting that ANK2 regulates neural stem cell differentiation and neuronal migration in the embryonic cerebral cortex, where Ank2 is highly expressed. We also demonstrated that Ank2 knockdown alters the expression of genes involved in neural development. Taken together, these results support the view that ANK2 haploinsufficiency in patients may impair neural development, resulting in an increased risk of ASD. Our study findings provide new insights into the molecular and cellular pathogenesis of ASD, given that among high-confidence ASD genes, ANK2 is rare in that it encodes for a scaffolding protein for the membrane protein complex required for neuronal functions.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Células-Tronco Neurais , Animais , Anquirinas/genética , Anquirinas/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno Autístico/genética , Humanos , Camundongos , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Neurônios/metabolismo
12.
Asian J Surg ; 45(1): 208-212, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34049788

RESUMO

BACKGROUND/OBJECTIVE: With increased life expectancy, the incidence of colorectal cancer in oldest-old patients has been rising. Advanced age is a risk factor for adverse outcomes after surgery. This study aimed to evaluate the short- and long-term outcomes of curative resection for colorectal cancer in nonagenarians. METHODS: Patients who had undergone curative resection for colorectal cancer (CRC) at Stage I to III from January 2010 to December 2019 were included. Cases of emergent surgery were excluded. The clinical characteristics were documented retrospectively, and factors affecting the long-term outcome were analyzed using multivariate analysis. RESULTS: Fifty patients met the selection criteria. Most of them were women (58.0%), and the median age was 92 years. Among these patients, 29 (58.0%) had a poor performance status (ASA-PS≥3). Laparoscopic surgery was performed in 42.0% of the patients, and 50% of the patients had postoperative complications classified as Clavien-Dindo grade 2 or severer, including 3 patients (6.0%) with grade 3 disease. No postoperative mortality occurred. The 30-day, 180-day, 1-year, 3-year and 5-year survival rates were 100%, 80.4%, 71.0%, 46.3%, and 33.8%, respectively. Multivariate analysis showed that a preoperative poor performance status (ASA-PS≥3) (HR: 3.067; 95% CI: 1.220-7.709; p = 0.017) was an independent prognostic factor for OS. CONCLUSION: Curative elective resections for CRC in nonagenarians were performed safely without postoperative mortality. The preoperative performance status was significantly associated with OS after curative elective resection of colorectal cancer in nonagenarians. Our results suggest that excellent long-term outcomes can be achieved in a selected group with a good performance status.


Assuntos
Neoplasias Colorretais , Nonagenários , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco
13.
Transl Psychiatry ; 11(1): 548, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697299

RESUMO

An increasing body of evidence suggests that impaired synapse development and function are associated with schizophrenia; however, the underlying molecular pathophysiological mechanism of the disease remains largely unclear. We conducted a family-based study combined with molecular and cellular analysis using induced pluripotent stem cell (iPSC) technology. We generated iPSCs from patients with familial schizophrenia, differentiated these cells into neurons, and investigated the molecular and cellular phenotypes of the patient's neurons. We identified multiple altered synaptic functions, including increased glutamatergic synaptic transmission, higher synaptic density, and altered splicing of dopamine D2 receptor mRNA in iPSC-derived neurons from patients. We also identified patients' specific genetic mutations using whole-exome sequencing. Our findings support the notion that altered synaptic function may underlie the molecular and cellular pathophysiology of schizophrenia, and that multiple genetic factors cooperatively contribute to the development of schizophrenia.


Assuntos
Células-Tronco Pluripotentes Induzidas , Esquizofrenia , Diferenciação Celular , Humanos , Neurônios , Receptores de Dopamina D2/genética , Esquizofrenia/genética
14.
J Surg Case Rep ; 2021(8): rjab350, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34476075

RESUMO

Schwannomas that occur in the retroperitoneal cavity are rare. We herein report a patient who underwent safe laparoscopic resection by using a preoperative 3D computed tomography (CT) image and a fluorescent ureteral stent during the surgery. A 47-year-old man presented with left lower abdominal pain. CT showed a 10-cm continuous retroperitoneal tumor originating at the third lumbar nerve in the lower left abdomen. Schwannoma was suspected. We underwent laparoscopic resection of the tumor guided by 3D images obtained preoperatively. A fluorescent ureteral stent was implanted during the surgery to improve visibility and protect the left ureter. The resection was completed without injury of other organs and vessels. The patient was discharged on postoperative Day 5. By performing a preoperative simulation using 3D CT images, we could anticipate the anatomical findings and easily identify them intraoperatively. In addition, the fluorescent ureteral stent provided visual support, thereby contributing to safe surgery.

15.
Clin Ther ; 43(5): 822-835.e16, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34059327

RESUMO

PURPOSE: Mirogabalin besylate has been approved in several countries to treat peripheral neuropathic pain. This pooled analysis, using data from the two pivotal Phase III studies in Asian patients with diabetic peripheral neuropathic pain and post-herpetic neuralgia, aimed to provide clinicians with more detailed and precise information relating to mirogabalin's safety and efficacy. METHODS: Data were pooled from 2 multicenter, double-blind, placebo-controlled, parallel-group, 14-week treatment studies of mirogabalin conducted at ∼350 study sites (Japan, South Korea, Taiwan, Singapore, Malaysia, and Thailand). Eligible patients in both studies were randomized in a 2:1:1:1 ratio, stratified according to a baseline average daily pain score (ADPS) of <6 or ≥6, to placebo, mirogabalin 15-mg once daily (QD), mirogabalin 10-mg twice daily (BID), or mirogabalin 15-mg BID treatment groups. Safety was assessed based on treatment-emergent adverse events identified from the adverse events collected throughout both studies. The primary efficacy end point of both studies was the change from baseline in ADPS at week 14. FINDINGS: In total, 1587 patients (824 with diabetic peripheral neuropathic pain; 763 with post-herpetic neuralgia) who received at least 1 dose of study drug were analyzed (633 received placebo, 954 treated with mirogabalin). Treatment-emergent adverse events included somnolence (3.8%, 10.8%, 14.5%, and 19.1%) and dizziness (2.7%, 5.7%, 9.1%, and 13.1%) in patients receiving placebo, mirogabalin 15 mg QD, mirogabalin 10 mg BID, and mirogabalin 15 mg BID, respectively. In patients treated with mirogabalin 15 mg QD, 2 (0.6%) of 316 patients discontinued due to somnolence. In the mirogabalin 10-mg BID group, somnolence, edema, and peripheral edema each resulted in 3 (0.9%) of 318 patient discontinuations. In the mirogabalin 15-mg BID group, 6 (1.9%) of 320 patients discontinued due to dizziness and 3 (0.9%) due to somnolence. At week 14, mirogabalin 10 mg BID and 15 mg BID statistically significantly improved ADPS versus placebo, with least squares mean changes (95% CI) of -0.31 (-0.55, -0.08) and -0.63 (-0.86, -0.40). Post hoc analysis showed a statistically significant difference 2 days after administration in the mirogabalin 10-mg and 15-mg BID groups compared with placebo. Female sex, age ≥65 years, and baseline weight <60 kg may influence the safety of mirogabalin, particularly regarding the incidence of somnolence and dizziness, but had no notable impact on efficacy. ClinicalTrials.gov identifiers: NCT02318706 and NCT02318719. IMPLICATIONS: This pooled analysis showed that mirogabalin was efficacious and well-tolerated by Asian patients with peripheral neuropathic pain.


Assuntos
Neuropatias Diabéticas , Neuralgia , Preparações Farmacêuticas , Idoso , Analgésicos , Compostos Bicíclicos com Pontes , Neuropatias Diabéticas/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Neuralgia/tratamento farmacológico , Resultado do Tratamento
16.
Asian Pac J Cancer Prev ; 22(5): 1531-1535, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34048182

RESUMO

OBJECTIVE: Resection is usually recommended for locally recurrent rectal cancer (LRRC) for which R0 resection is possible, but its suitability varies by individual patient risk. Here, we report outcomes of resected LRRC in our hospital. METHODS: We retrospectively evaluated short- and long-term results of 33 patients who underwent resections for LRRC from January 2003 to December 2019. RESULTS: At the initial surgeries for these 33 patients, their disease stages at that time were Stage I: n=2, Stage II: n=12, Stage III: n=11, Stage IV: n=6, and unknown: n=2. Patients with Stage IV disease at their initial surgeries underwent radical one-step or two-step procedures. Metastasis to other organs was observed in 5 patients at the their initial LRRC diagnoses. At the LRRC surgeries, 7 patients received palliative surgeries; 26 received intent-to-treat resections, of which 17 were R0 resections. All-grade postoperative complications were observed in 11 patients, including 1 surgery-related death. Five-year overall survival rates were all cases: 38.4%; R0 group: 52.3%, R1 or R2 group: 19.4%, and palliative surgery group: 0%. The R0 group thus had significantly better prognosis than other patients (P = 0.0012). Eleven patients in the R0 group (64.7%) suffered re-recurrences but some patients achieved long-term survival through chemotherapy, radiation therapy, and surgery for metastasis to other organs, even after re-recurrence. CONCLUSION: Long-term prognosis after surgery for LRRC was significantly better for patients with R0 margins. Multimodal treatments may greatly improve survival for patients who suffer re-recurrences after local recurrence resections.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida
17.
Mol Brain ; 14(1): 56, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726803

RESUMO

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Ocitocina/uso terapêutico , Comportamento Social , Transposases/genética , Administração Intranasal , Animais , Transtorno do Espectro Autista/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Humanos , Camundongos , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ocitocina/administração & dosagem , Ocitocina/farmacologia , Mutação Puntual , Regiões Promotoras Genéticas , Ligação Proteica , Receptores de Ocitocina/biossíntese , Receptores de Ocitocina/genética , Receptores de Vasopressinas/biossíntese , Receptores de Vasopressinas/genética , Transcrição Gênica , Transposases/fisiologia
18.
In Vivo ; 35(1): 555-561, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402509

RESUMO

BACKGROUND/AIM: Perforation and postoperative complications have a negative effect on long-term outcomes in patients with colorectal cancer (CRC). The aim of this study was to evaluate the clinical factors with special reference to postoperative complications predicting the long-term outcome in those for whom curative resection for perforated CRC was performed. PATIENTS AND METHODS: Patients who underwent curative resection for perforated CRC at stage II or III from April 2003 to March 2020 were included. Clinical factors were retrospectively analyzed. RESULTS: Forty-four patients met the selection criteria. The 30-day mortality rate was 4.5% and the complication rate was 47.7%. Excluding 30-day mortality, five-year recurrence-free survival (RFS) and overall survival (OS) were 62.3% and 73.6%, respectively. Multivariate analysis showed that postoperative complications (p=0.005) and pT4 pathological factor (p=0.009) were independent prognostic factors for RFS. Only postoperative complications (p=0.023) were an independent prognostic factor for OS. CONCLUSION: Postoperative complications were significantly associated with RFS and OS, and pT4 was associated with RFS. The prevention and management of postoperative adverse events may be important for perforated CRC.


Assuntos
Neoplasias Colorretais , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Humanos , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos
19.
Rinsho Shinkeigaku ; 61(1): 39-42, 2021 Jan 29.
Artigo em Japonês | MEDLINE | ID: mdl-33328423

RESUMO

A 63-year-old Japanese female in an immunocompetent state developed right Ramsay Hunt syndrome and left shoulder pain, and left upper limb motor paresis with herpes zoster (HZ) duplex in the right auricle and left shoulder regions. With her Ramsay Hunt syndrome, neural deafness, tinnitus and vestibular symptoms were observed, and she lacked facial nerve palsy. Cerebrospinal fluid (CSF) findings revealed an increase in lymphocytes (21 cells/µl) and protein content (29 mg/dl), and polymerase chain reaction for varicella-zoster virus DNA in CSF was negative. Cervical root MRI using 3D Nerve VIEW (Philips) imaging showed high-intensity lesions on the C5-C8 spinal roots with contrast enhancements. No abnormalities were observed in the median or ulnar motor sensory nerve conduction velocity conduction studies including the F wave. PubMed search revealed no report of a patient with this profile, and to the best of our knowledge HZ duplex with concomitant neurological impairments has not been reported. We compare our present case with several similar cases from the literature.


Assuntos
Herpes Zoster da Orelha Externa/complicações , Herpes Zoster/complicações , Imunoglobulinas Intravenosas/administração & dosagem , Ombro , Feminino , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster da Orelha Externa/diagnóstico , Herpes Zoster da Orelha Externa/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Paresia/etiologia , Polirradiculoneuropatia/diagnóstico , Polirradiculoneuropatia/tratamento farmacológico , Polirradiculoneuropatia/etiologia , Raízes Nervosas Espinhais/diagnóstico por imagem
20.
Intern Med ; 60(3): 469-472, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32863367

RESUMO

Mild palmar digital neuropathy may be underestimated because selective nerve conduction studies (NCS) of the palmar digital nerve are challenging. We herein report two cases of palmar digital neuropathy. We performed sensory NCS in each finger using the standard approach. Both cases showed a decrease in the amplitude of sensory nerve action potential (SNAP) in the localized finger. Furthermore, the sensory nerve inching test identified the lesion site. When performing NCS in patients with finger sensory impairment, we recommend recording the SNAP in each finger using standard NCS at the wrist, as well as sensory nerve inching testing.


Assuntos
Condução Nervosa , Doenças do Sistema Nervoso Periférico , Potenciais de Ação , Dedos , Humanos , Nervos Periféricos , Punho
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