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BACKGROUND: Nursing shortages are an ongoing concern for neonatal units, with many struggling to meet recommended nurse to patient ratios. Workforce data underlines the high proportion of neonatal nurses nearing retirement and a reduced number of nurses joining the profession. In order to recommend strategies to increase recruitment and retention to neonatal nursing, we need to understand the current challenges nurses are facing within the profession. The aim of this study is to investigate current job satisfaction, burnout, and intent to stay in neonatal nursing in England and Wales. METHODS: This study has two parts: (1) a systematic review exploring job satisfaction, burnout and intent to stay in neonatal nursing, and any previous interventions undertaken to enhance nurse retention, (2) an online survey of neonatal nurses in England and Wales exploring job satisfaction, burnout and intent to stay in neonatal nursing. We will measure job satisfaction using the McCloskey Mueller Satisfaction Scale (MMSS), burnout using the Copenhagen Burnout Inventory (CBI) and the Nurse Retention Index (NRI) will be used to measure intent to stay. All nurses working in neonatal units in England and Wales will be eligible to participate in the nursing survey. DISCUSSION: Retention of neonatal nurses is a significant issue affecting neonatal units across England and Wales, which can impact the delivery of safe patient care. Exploring job satisfaction and intent to stay will enable the understanding of challenges being faced and how best to support neonatal nurses. Identifying localised initiatives for the geographical areas most at risk of nurses leaving would help to improve nurse retention.
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Esgotamento Profissional , Satisfação no Emprego , Reorganização de Recursos Humanos , Humanos , País de Gales , Inglaterra , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Reorganização de Recursos Humanos/estatística & dados numéricos , Enfermagem Neonatal , Intenção , Inquéritos e QuestionáriosAssuntos
Maturidade Cervical , Colo do Útero , Gravidez , Feminino , Humanos , Colo do Útero/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the predictive value of obstetric findings when using dinoprostone (prostaglandin E2 [PGE2]) vaginal inserts for cervical ripening, and to assess the optimal cervical-ripening method between PGE2 vaginal insert and/or cervical dilators. METHODS: This prospective observational study enrolled pregnant women who underwent cervical ripening for labor induction in 37-41 week' gestation in 2020. In evaluation 1, optimal obstetric findings predictive of rapid cervical ripening using PGE2 were assessed. In evaluation 2, the duration from PGE2 administration to labor onset and perinatal outcomes were compared between cases in which only PGE2 was used and cases that were treated with PGE2 after mechanical cervical dilators (Dilapan®) for extremely immature cervical ripening (uterine cervical os <2 cm). RESULTS: In evaluation 1, uterine dilatation before the use of a PGE2 vaginal insert was mostly correlated with the time from PGE2 administration to labor onset (r = -0.428, p < 0.001). When the uterine cervical os dilatation was ≥2 cm, a shorter time-to-labor onset was found. In addition, os dilatation, effacement, and station at the time of PGE2 vaginal insert removal also significantly progressed. In evaluation 2, the median duration from PGE2 administration to labor onset was 1740 min in cases where only PGE2 was used, and 610 min in those where PGE2 was used after mechanical cervical dilators (p = 0.011). CONCLUSION: PGE2 vaginal inserts are relatively effective when the uterine cervical os is ≥2 cm in diameter. However, in cases of extremely immature cervical-ripening, it was feasible to use PGE2 vaginal inserts before mechanical cervical dilatation.
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Dinoprostona , Ocitócicos , Feminino , Gravidez , Humanos , Dinoprostona/farmacologia , Ocitócicos/farmacologia , Maturidade Cervical , Preparações de Ação Retardada , Japão , Trabalho de Parto Induzido/métodos , Administração IntravaginalRESUMO
OBJECTIVE: To examine the prevalence trends of minimally invasive hysterectomy for benign indications in Japan and investigate regional disparities. STUDY DESIGN: A retrospective cohort and ecological study using "The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data". SETTING: Nationwide Japan. PATIENTS: Individuals who underwent hysterectomy for benign indications from 2014 to 2020. INTERVENTIONS: Trend analysis of minimally invasive surgery (MIS) rates through laparoscopic hysterectomies (LH) and robotic-assisted laparoscopic hysterectomies (RA-LH) at the national and prefecture levels. Examination of regional factors contributing to the disparity in MIS implementation rates by second medical service area (SMSA). RESULTS: The number of LH has increased from 16,016 in 2014 to 27,755 in 2020. The nationwide MIS hysterectomy rate increased from 29% in 2014 to 55% in 2020 (p less than 0.001). More than 50% of hysterectomies have been performed as MIS since 2019. There was an increasing trend in MIS rates in all age groups. All prefectures except one showed a significant upward trend (p less than 0.05) in the MIS rates, but MIS rates varied widely (23-84%). In a multivariable model, the MIS was more likely to be performed in the SMSAs in western Japan (p = 0.011), in the SMSAs where the number of laparoscopy-qualified gynecologists is 5-10 (p = 0.013), and 11 or higher (p less than 0.001). CONCLUSIONS: This study reveals a shift towards minimally invasive surgery (MIS) in total hysterectomy procedures in Japan. However, significant disparities in the prevalence of MIS hysterectomy exist, potentially influenced by the number of laparoscopy-qualified gynecologists.
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Laparoscopia , Feminino , Humanos , Japão/epidemiologia , Estudos Retrospectivos , Bases de Dados Factuais , HisterectomiaRESUMO
OBJECTIVE: To describe our individualized management protocol for women with an antenatal diagnosis of vasa previa (VP) and to report maternal and neonatal outcomes in patients managed according to our protocol. METHODS: A retrospective study of prospectively collected data of antenatally diagnosed VP managed at our hospital between 2014 and 2021. Obstetric and neonatal outcomes were reviewed and analyzed. RESULTS: Fourteen cases of antenatally diagnosed VP in 5150 total deliveries were analyzed (0.3%) Five cases (36%) of VP were diagnosed during the routine fetal morphological ultrasound screening, and nine cases (64%) were referred to our hospital due to perinatal complications. There were nine cases that required hospitalization (due to fetal growth restriction [FGR] [1], preterm labor [3], patients' request [5]). The other five were asymptomatic. Eight patients were delivered by scheduled cesarean section at around 36 weeks and only three neonates were admitted to NICU with transient tachypnea of newborn. However, six patients required CS before the scheduled dates because of other complications (preterm labor [3], abnormal cardiotocogram patterns [1], FGR [1] and twin pregnancy [1]). Four neonates born by CS before their scheduled dates were admitted to NICU. No cases required prolonged hospitalization and there were no serious neonatal complications. CONCLUSION: Individualized management may lead to favorable outcomes with VP. Outpatient management may be considered in patients without risk factors. However, maternal hospitalization and earlier scheduled CS should be considered in symptomatic patients or those at risk for preterm delivery.
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Nascimento Prematuro , Vasa Previa , Recém-Nascido , Gravidez , Feminino , Humanos , Vasa Previa/diagnóstico por imagem , Vasa Previa/terapia , Estudos Retrospectivos , Cesárea , Diagnóstico Pré-Natal , Ultrassonografia Pré-NatalRESUMO
INTRODUCTION: To clarify whether the declaration of an emergency state due to the spread of COVID-19 in Japan affected the number of maternal transports and premature births. METHODS: A questionnaire-based descriptive study was conducted in perinatal centers throughout Japan in 2020. The incidence of maternal transport and preterm delivery rates every month after the COVID-19 spread in 2020 were compared with those in 2019. RESULTS: Participants were recruited from 52 perinatal centres. The maternal transport rate (maternal transports per number of deliveries) was 10.6% in April and 11.0% in June 2020, compared with 12.5% in 2019 (P < 0.05). The maternal transport rate due to preterm labor was 4.8% in April 2020 and 5.8% in 2019 (P < 0.05). The maternal transport rate during the declaration of emergency state decreased by 21% in April 2020 in non-emergency-declared prefectures, and decreased by 17% in May 2020 in emergency-declared prefectures. However, there was no significant difference in the preterm delivery rate between 2020 and 2019, regardless of the prefecture and gestational period. CONCLUSION: Declaration of the emergency status due to COVID-19 spread in Japan reduced maternal transport due to preterm labor, but did not reduce preterm delivery itself.
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COVID-19 , Trabalho de Parto Prematuro , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Nascimento Prematuro/epidemiologia , Japão/epidemiologia , Trabalho de Parto Prematuro/epidemiologia , IncidênciaRESUMO
BACKGROUND: One cause of the increase in cervical cancer rates in Japan is the long-term stagnation in the cervical cancer screening consultation rate. Therefore, improving the screening consultation rate is of urgent concern to reduce cervical cancer incidence. Self-collected human papilloma virus (HPV) tests have been successfully adopted in several countries, such as the Netherlands and Australia, as a measure of individuals who have not undergone cervical cancer screening in national programs. This study aimed to verify whether self-collected HPV tests presented an effective countermeasure for individuals who had not undergone the recommended cervical cancer screenings. METHODS: This study was conducted from December 2020 to September 2022 in Muroran City, Japan. The primary evaluated endpoint was the percentage of citizens who underwent cervical cancer screening at a hospital with positive self-collected HPV test results. The secondary endpoint was the percentage of included participants who were diagnosed with cervical intraepithelial neoplasia (CIN) or higher among those who visited a hospital and underwent cervical cancer screening. RESULTS: The included study participants were 7,653 individuals aged 20-50 years with no record of previous cervical cancer examination in the past 5 years. We mailed these participants information on self-administered HPV tests as an alternative screening procedure and sent the kit to 1,674 women who requested the test. Among them, 953 returned the kit. Among the 89 HPV-positive individuals (positive rate, 9.3%), 71 (79.8%) visited the designated hospital for an examination. A closer examination revealed that 13 women (18.3% of hospital visits) had a CIN finding of CIN2 or higher, among whom one each had cervical cancer and vulvar cancer, eight presented with CIN3, and three presented with CIN2; two cases of invasive gynecologic cancer were also identified. CONCLUSIONS: We conclude that the self-collected HPV tests showed a certain efficacy as a measure of individuals who had not undergone the recommended cervical cancer screening. We devised ways to have the unexamined patients undergo HPV testing and ensure that HPV-positive individuals visited the hospital. Despite a few limitations, our findings suggest the effectiveness of this public health intervention.
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Programas de Rastreamento , Infecções por Papillomavirus , Autoteste , Feminino , Humanos , Detecção Precoce de Câncer/métodos , Papillomavirus Humano , Japão/epidemiologia , Programas de Rastreamento/métodos , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço VaginalRESUMO
INTRODUCTION: Autoimmune encephalitis (AIE) is a relatively newly described category of immune-mediated diseases involving the central nervous system with a wide spectrum of clinical presentations, ranging from relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with medically refractory seizures. Single or multifocal seizures accompanied by neuropsychiatric symptoms and cognitive or memory impairments are suggestive of clinical features at AIE onset. CASE REPORT: A six-year-old boy presented with repetitive focal seizures, slowly progressive emotional liability, and attention-deficit/hyperactivity disorder-like symptoms. Seizure types varied during the clinical course, sometimes emerging as clusters or statuses. MRI performed during seizure clustering/status revealed moving signal abnormalities. We successfully treated the patient with high-dose intravenous methylprednisolone. Cerebrospinal fluid analysis revealed pleocytosis and marked elevation of antibodies against N-terminals of N-methyl-d-aspartate type glutamate receptor subunits and granzyme B. CONCLUSION: We report a case of moving seizure foci with abnormal MRI findings. Although the onset of psychiatric symptoms slowly progressed to those atypical for AIE, responsiveness to immunotherapy, cerebrospinal fluid pleocytosis, and autoantibodies all indicated AIE. We thus suggest that moving seizure foci and abnormal MRI signals may be findings of AIE.
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Doenças Autoimunes do Sistema Nervoso , Leucocitose , Masculino , Humanos , Criança , Leucocitose/complicações , Convulsões/etiologia , Autoanticorpos , Receptores de N-Metil-D-AspartatoRESUMO
BACKGROUND: Human papillomavirus (HPV) testing using self-collected vaginal samples and urine samples is convenient and effective for improving the screening rate. But, to serve as an alternative cervical cancer screening technique, such tests must offer sensitivity equivalent to the HPV testing of physician-collected cervical samples. To examine the effectiveness of HPV testing using self-collected samples and urine samples, we compared the results of HPV testing using these samples with those of HPV testing using physician-collected samples and cytological examinations. METHODS: The study population included 300 women (age: 20-50 years) with abnormal cervical cytology. The results of HPV testing using self-collected samples and urine samples and physician-collected samples and cervical cytology were compared. RESULTS: For all HPV types, the κ-value was 0.773 for physician- and self-collected samples and 0.575 for physician-collected and urine samples. The κ-value for HPV type 16-positive samples was 0.988 for physician- and self-collected samples and 0.896 for physician-collected and urine samples. The κ-value for HPV type 18-positive samples was 0.856 for physician- and self-collected samples and 0.831 for physician-collected and urine samples. For other HPV types, the value was 0.809 for physician- and self-collected samples and 0.617 for physician-collected and urine samples. CONCLUSIONS: The obtained results were consistent between physician- and self-collected samples as well as between physician-collected and urine samples. Considering that the agreement rate was particularly high for the high-risk HPV types 16 and 18, HPV testing using physician-collected samples, self-collected samples, and urine samples was equally effective for the types with high carcinogenicity.
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Alphapapillomavirus , Infecções por Papillomavirus , Médicos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Detecção Precoce de Câncer/métodos , Sensibilidade e Especificidade , Esfregaço Vaginal/métodos , Manejo de Espécimes/métodos , DNA Viral , Displasia do Colo do Útero/diagnósticoRESUMO
As placenta accreta spectrum (PAS) pathologies affect only the extremely thin tissues between the placenta and the uterine myometrium, superficial endometrial damage such as that caused by placenta creta and increta can be diagnosed only through histopathology. We performed direct uterine ultrasound of PAS using an ultrahigh frequency (33 MHz; i33LX9 Aplio i800) linear transducer. Here, we describe two cases with ultrasound images of placentas with PAS and a case without PAS to compare histological findings. In cases of PAS at the previous Cesarean scar, ultrasonography clearly revealed a thin uterine myometrium with some island-shaped sites where placental tissue was focally anchored to the uterine myometrium near the scar. Speckle blood flow pattern was absent at these sites during scanning with B-mode, but was detectable elsewhere. Histopathology samples from the same site revealed that villous tissue was directly attached to the uterine myometrium with a large area of infarction. In another case of diffuse PAS, speckle blood flow pattern was generally absent, and histopathology revealed deep fibrinoid deposits. We believe that histological evaluation following ultrasound use will improve the accuracy of ultrasound diagnosis and perinatal management of PAS in clinical practice.
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Placenta Acreta , Placenta Prévia , Cesárea , Cicatriz/patologia , Feminino , Humanos , Placenta/irrigação sanguínea , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/patologia , GravidezRESUMO
Per- and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.
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Razão Digital , Receptor alfa de Estrogênio , Fluorocarbonos , Criança , Receptor alfa de Estrogênio/genética , Feminino , Fluorocarbonos/toxicidade , Humanos , Japão , Masculino , Gravidez , Estudos Prospectivos , Estudos RetrospectivosRESUMO
INTRODUCTION: Recent guidelines do not recommend routine screening of vesicoureteral reflux after a first febrile urinary tract infection in children without abnormal findings on ultrasound or atypical/recurrent urinary tract infection. Currently, there are no clear ultrasonographic parameters for detecting abnormalities in renal size, especially in young children. The aim of the present study was to determine an optimal cutoff value for detecting small kidney in children without apparent congenital anomalies except vesicoureteral reflux by retrospective chart review. PATIENTS AND METHODS: Children aged ≤3 years who had undergone nuclear renal scans and ultrasound were enrolled. Small kidney was defined as split renal function of <40%. Optimal cutoff values of various ultrasonographic parameters for detecting small kidney were calculated. RESULTS: Of the 69 children included in the present study, small kidney was identified in 20. There was a significant difference in renal size between each kidney in patients with small kidney, whereas there was no significant difference in those without small kidney. With a ratio of estimated renal area of 74.26%, maximum area under the curve with the highest sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate were obtained. In addition, simple measurement of renal length with a cutoff of 4.97 cm showed high specificity comparable with estimated renal area. CONCLUSION: Small kidney may be screened by two-dimensional measurement on ultrasonographic examination, even in young children. With the cutoff described, risk stratification or an individualized approach may be possible.
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Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.
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Neoplasias dos Ductos Biliares/mortalidade , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/mortalidade , Proteínas de Neoplasias/metabolismo , gama-Sinucleína/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Extra-Hepáticos/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Intervalo Livre de Doença , Feminino , Seguimentos , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Prognóstico , gama-Sinucleína/análise , gama-Sinucleína/genéticaRESUMO
OBJECTIVE: We aimed to assess the efficacy and safety of high-dose pyridoxine treatment for seizures and its effects on development in patients with inherited glycosylphosphatidylinositol deficiencies (IGDs). METHODS: In this prospective open-label multicenter pilot study, we enrolled patients diagnosed with IGDs using flow cytometry and/or genetic tests. The patients received oral pyridoxine (20-30 mg/kg/day) for 1 year, in addition to previous treatment. RESULTS: All nine enrolled patients (mean age: 66.3 ± 44.3 months) exhibited marked decreases in levels of CD16, a glycosylphosphatidylinositol-anchored protein, on blood granulocytes. The underlying genetic causes of IGDs were PIGO, PIGL, and unknown gene mutations in two, two, and five patients, respectively. Six patients experienced seizures, while all patients presented with developmental delay (mean developmental age: 11.1 ± 8.1 months). Seizure frequencies were markedly (>50%) and drastically (>90%) reduced in three and one patients who experienced seizures, respectively. None of the patients presented with seizure exacerbation. Eight of nine patients exhibited modest improvements in development (P = 0.14). No adverse events were observed except for mild transient diarrhea in one patient. CONCLUSION: One year of daily high-dose pyridoxine treatment was effective in the treatment of seizures in more than half of our patients with IGDs and modestly improved development in the majority of them. Moreover, such treatment was reasonably safe. These findings indicate that high-dose pyridoxine treatment may be effective against seizures in patients with IGDs, although further studies are required to confirm our findings. (University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number: UMIN000024185.).
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Glicosilfosfatidilinositóis/deficiência , Piridoxina/farmacologia , Convulsões/tratamento farmacológico , Complexo Vitamínico B/farmacologia , Adolescente , Criança , Pré-Escolar , Feminino , Glicosilfosfatidilinositóis/genética , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , Estudos Prospectivos , Piridoxina/administração & dosagem , Convulsões/complicações , Convulsões/etiologia , Convulsões/genética , Complexo Vitamínico B/administração & dosagemRESUMO
Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo ATP1A3 variants in eight patients. Mutated ATP1A3 causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS). However, our patients showed no clinical features of AHC, RDP, or CAPOS and had a completely different phenotype: a severe form of polymicrogyria with epilepsy and developmental delay. Detected variants had different locations in ATP1A3 and different functional properties compared with AHC-, RDP-, or CAPOS-associated variants. In the developing cerebral cortex of mice, radial neuronal migration was impaired in neurons overexpressing the ATP1A3 variant of the most severe patients, suggesting that this variant is involved in cortical malformation pathogenesis. We propose a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.
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BACKGROUND: Incontinentia pigmenti (IP) is an X-linked neurocutaneous disorder that can present with cerebral arteriopathy during early infancy. However, no previous reports have demonstrated arteriopathic manifestations during postinfantile childhood in patients with IP. PATIENT DESCRIPTION: We describe a case of IP in a 2-year-old girl who developed encephalopathic manifestations associated with influenza A infection. She presented diffuse magnetic resonance imaging abnormalities involving the cortices, subcortical white matter, corpus callosum, basal ganglia, and thalami, resembling the findings in early infantile cases reported in the previous literatures. Magnetic resonance angiography demonstrated attenuation of the cerebral arteries. Proinflammatory cytokines and chemokines were upregulated in the cerebrospinal fluid. Left hemiplegia remained following the remission of the arteriopathic manifestations. Genetic analyses revealed a novel type of mutation in the IKBKG gene. CONCLUSION: Our findings indicate that patients with IP can develop destructive cerebral arteriopathy even after early infancy. The similarities in magnetic resonance imaging abnormalities between our patient and the previously reported infantile patients may be explained by the underlying immunologic pathophysiology of IP.
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Encéfalo/diagnóstico por imagem , Doenças Arteriais Cerebrais/complicações , Incontinência Pigmentar/complicações , Doenças Arteriais Cerebrais/diagnóstico por imagem , Doenças Arteriais Cerebrais/genética , Pré-Escolar , Análise Mutacional de DNA , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Quinase I-kappa B/genética , Incontinência Pigmentar/diagnóstico por imagem , Incontinência Pigmentar/genética , Angiografia por Ressonância Magnética , Mutação , Substância Branca/diagnóstico por imagemRESUMO
PURPOSE: To clarify the incidence of and risk factors for febrile urinary tract infection in children with persistent vesicoureteral reflux (VUR) after the discontinuation of continuous antibiotic prophylaxis (CAP), retrospective chart review was performed. PATIENTS AND METHODS: Among children with primary VUR at 10 years of age or younger at presentation, those who had persistent VUR despite conservative management with CAP and who were subsequently followed after discontinuation of CAP were included. Kaplan-Meier curve and Cox's proportional hazard regression model were used for evaluation of the incidence of and risk factors for febrile urinary tract infection (fUTI) after stopping CAP. RESULTS: Among 144 children (99 boys and 45 girls), fUTI developed in 34. The 5-year fUTI-free rate after discontinuation of CAP was 69.4%. On multivariate analyses, girls (p = 0.008) and abnormalities on nuclear renal scans (p = 0.0019), especially focal defect (p = 0.0471), were significant factors for fUTI. Although the fUTI-free rate was not different between children who had no or 1 risk factor, it was significantly lower in children with 2 risk factors than in those with no or 1 risk factor. CONCLUSIONS: The present study revealed that girls and abnormal renal scan, especially focal defect, are risk factors for fUTI. Active surveillance without CAP for persistent VUR seems to be a safe option for children with no or 1 risk factor. Prophylactic surgery or careful conservative follow-up may be an option for girls with abnormal renal scan results if VUR persists under CAP.
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Antibioticoprofilaxia , Cicatriz/complicações , Febre/epidemiologia , Febre/etiologia , Nefropatias/complicações , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Refluxo Vesicoureteral/complicações , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Suspensão de TratamentoRESUMO
PURPOSE: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaceted roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression, and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. EXPERIMENTAL DESIGN: A novel multiplex IHC-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naïve PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein α (FAP)-dominant fibroblast-rich stroma, and α smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses and with clinicopathologic factors, including CD8+ cell density. RESULTS: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status, and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival [HR, 0.57; 95% confidence interval (CI), 0.33-0.99], while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06-2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8+ cell infiltrates and intense neutrophil infiltration. CONCLUSIONS: This study identified three distinct stroma types differentially associated with survival, immunity, and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of antistromal therapies.
Assuntos
Fibroblastos Associados a Câncer/imunologia , Carcinoma Ductal Pancreático/imunologia , Pâncreas/patologia , Neoplasias Pancreáticas/imunologia , Microambiente Tumoral/imunologia , Actinas/análise , Actinas/metabolismo , Idoso , Linfócitos T CD8-Positivos/imunologia , Fibroblastos Associados a Câncer/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Colágeno/análise , Colágeno/metabolismo , Endopeptidases/análise , Endopeptidases/metabolismo , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Pâncreas/imunologia , Pâncreas/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , PrognósticoRESUMO
INTRODUCTION: Dravet syndrome (DS) is severe myoclonic epilepsy in infancy and associated with a heterozygous mutation of the gene for the sodium channel alpha 1 subunit (SCN1A). Recently, adult patients with DS have been reported to show parkinsonism, but no corresponding neuroimaging data are available. Here, we present neuroimaging data in 2 adult patients with DS showing parkinsonian symptoms. CASE REPORT: Case 1: A man who had intractable seizures from the age of 1 year and 2 months was diagnosed with DS at 7 with a mutation in the SCN1A gene. At 18, he had parkinsonian symptoms such as masked face and bradykinesia. At 20, he was admitted to our department. Dopamine transporter single-photon emission computed tomography (DAT SPECT) showed no decrease in striatal binding of 123I-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane (123I-FP-CIT), and myocardial scintigraphy showed no decrease in cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG). Levodopa showed no significant improvement in his symptoms. Case 2: A woman who had febrile seizures at 4 months of age and myoclonic seizures at 1 year and 5 months was diagnosed with DS at 31. She had myoclonus, resting tremor, hypertonia, antecollis, crouch gait, and bradykinesia. DAT SPECT imaging showed no decrease in striatal FP-CIT binding, and levodopa did not improve her symptoms. DISCUSSION: The normal DAT SPECT and 123I-MIBG results suggest that dopaminergic neurons projecting onto striatal neurons were not impaired in our patients, explaining the lack of response to levodopa. Thus, dopamine imaging can help to guide treatment decisions in patients with DS and parkinsonism.
Assuntos
Neurônios Dopaminérgicos , Epilepsias Mioclônicas/complicações , Transtornos Parkinsonianos/complicações , Adulto , Epilepsias Mioclônicas/diagnóstico por imagem , Feminino , Humanos , Masculino , Imagem de Perfusão do Miocárdio , Transtornos Parkinsonianos/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
Phthalates and bisphenol A (BPA) are estrogenic endocrine disruptors. Polymorphisms in the gene encoding estrogen receptor 1 (ESR1) may contribute to the ratio of the lengths of the second and fourth digits (2D:4D), which is considered an index of prenatal exposure to sex hormones. Thus, we investigated whether ESR1 polymorphisms modify the effects of prenatal exposure to phthalates and BPA on 2D:4D in a birth cohort. Maternal serum in the first trimester was used to determine prenatal exposure to these compounds. Six hundred twenty-three children (7 years of age) provided mean 2D:4D from photocopies and were genotyped for single nucleotide polymorphisms in ESR1, particularly PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The associations among compound exposure, mean 2D:4D, and ESR1 polymorphisms were assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the AG/GG genotype at rs2077647 in the group exposed to high levels of mono(2-ethylhexyl) phthalate (MEHP) or Σ Di(2-ethylhexyl) phthalate (DEHP) showed feminized 2D:4D compared with boys with the AA genotype at rs2077647 who had low exposure to MEHP or ΣDEHP (MEHP: increase in mean 2D:4D of 1.51%, 95% confidence interval [CI]: 0.40-2.63; ΣDEHP: increase in mean 2D:4D of 1.37%, 95% CI: 0.25-2.49). No significant differences were found among girls. There were no associations between mean 2D:4D and metabolites other than MEHP or BPA. These data suggest that ESR1 polymorphisms modify the effects of prenatal exposure to DEHP on mean 2D:4D among boys.