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INTRODUCTION AND HYPOTHESIS: This study evaluated the association between pelvic organ prolapse (POP), frailty, and sarcopenia to explore how POP treatment can extend healthy life expectancy in elderly women. METHODS: We conducted a retrospective study of prospectively collected data, comparing women with mild POP (stages 0-II) with those with advanced POP (stages III and IV). The inclusion criteria for this study were women who visited the clinic with at least one symptom of pelvic floor dysfunction and underwent imaging studies between April 2020 and November 2022. Initially, 119 patients met these inclusion criteria. Patients were excluded if they had a history of previous POP treatment, did not respond to the study survey, or were lost to follow-up. After applying these exclusion criteria, 82 patients were included in the final analysis, of whom 65 underwent surgery (laparoscopic sacrocolpopexy, colpocleisis, tension-free vaginal tape, and native tissue repair). Assessments included POP Quantification, Kihon Checklist, Pelvic Organ Prolapse Quality of Life (P-QOL) questionnaire, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Incontinence Symptom Questionnaire (ICIQ-SF). Pelvic muscles were measured using MRI or CT. Immunohistochemical analysis of estrogen receptor alpha (ERα), estrogen receptor beta , and androgen receptor was performed on surgical specimens from 43 patients. RESULTS: The median age of participants was 75 years. Of the 82 patients, 48 (58.5%) were classified as frail or pre-frail, and 22 (26.8%) exhibited motor impairment. Advanced POP (stages 3 and 4) was seen in 41 patients. These patients had more motor function impairments (advanced, 16; mild, 6; p = 0.01). Patients with advanced POP had poorer P-QOL, ICIQ-SF (median: 9.5 vs 4, p = 0.006) and OABSS (7 vs 4, p = 0.008) scores, and smaller pubococcygeus muscle diameter (2.5 vs 3 cm, p = 0.017). Postoperatively, significant improvements were seen in P-QOL (all domains except personal relationships: p < 0.001), total IPSS (11 vs 4, p < 0.001), OABSS (6 vs 5, p = 0.033), and ICIQ-SF scores (6 vs 2, p < 0.001). ERα expression was associated with preoperative frailty (r = -0.37, p = 0.014). CONCLUSIONS: Advanced POP correlates with poorer QOL, worse urinary symptoms, and reduced pubococcygeus muscle diameter, consistent with sarcopenia, compared with mild POP.
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In the present study, we examined the inter-relationships between body water balance, nutritional risk, sarcopenia, and outcome after acute ischemic stroke (AIS) in patients who were living independently. We defined abnormal body water balance as overhydration, with an extracellular fluid/total body water ratio > 0.390. A geriatric nutritional risk index (GNRI) < 98 was considered low GNRI. Sarcopenia was defined according to the 2019 Asian Working Group for sarcopenia criteria. Poor outcome was defined as a modified Rankin scale (mRS) score ≥ 3 at discharge. Among 111 eligible patients (40 females, median age: 77 years), 43 had a poor prognosis, 31 exhibited overhydration, 25 had low GNRI, and 44 experienced sarcopenia. Patients with poor outcomes had significantly higher National Institutes of Health Stroke Scale (NIHSS) scores, which were significantly more common with overhydration, low GNRI, and sarcopenia (p < 0.001 for all). Concomitant overhydration, low GNRI, and sarcopenia were associated with poorer outcomes. In multivariate analysis, overhydration [odds ratio (OR) 5.504, 95% confidence interval (CI) 1.717-17.648; p = 0.004], age (OR 1.062, 95%CI 1.010-1.117; p = 0.020), and NIHSS score (OR 1.790, 95%CI 1.307-2.451; p < 0.001) were independent prognostic factors for poor outcome. The results indicated that the combination of overhydration, low GNRI, and sarcopenia predict poor outcomes following AIS. Overhydration was particularly associated with poor outcomes.
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Accidente Cerebrovascular Isquémico , Estado Nutricional , Sarcopenia , Equilibrio Hidroelectrolítico , Humanos , Femenino , Masculino , Anciano , Estudios Prospectivos , Accidente Cerebrovascular Isquémico/complicaciones , Anciano de 80 o más Años , Factores de Riesgo , Pronóstico , Evaluación Geriátrica/métodos , Persona de Mediana Edad , Agua Corporal/metabolismo , Evaluación NutricionalRESUMEN
BACKGROUND: Prostate cancer is dependent on androgen receptor (AR) signaling, and androgen deprivation therapy (ADT) has proven effective in targeting prostate cancer. However, castration-resistant prostate cancer (CRPC) eventually emerges. AR signaling inhibitors (ARSI) have been also used, but resistance to these agents develops due to genetic AR alterations and epigenetic dysregulation. METHODS: In this study, we investigated the role of OCT1, a member of the OCT family, in an AR-positive CRPC patient-derived xenograft established from a patient with resistance to ARSI and chemotherapy. We conducted a genome-wide analysis chromatin immunoprecipitation followed by sequencing and bioinformatic analyses using public database. RESULTS: Genome-wide analysis of OCT1 target genes in PDX 201.1 A revealed distinct OCT1 binding sites compared to treatment-naïve cells. Bioinformatic analyses revealed that OCT1-regulated genes were associated with cell migration and immune system regulation. In particular, C-terminal Binding Protein 2 (CTBP2), an OCT1/AR target gene, was correlated with poor prognosis and immunosuppressive effects in the tumor microenvironment. Metascape revealed that CTBP2 knockdown affects genes related to the immune response to bacteria. Furthermore, TISIDB analysis suggested the relationship between CTBP2 expression and immune cell infiltration in prostate cancer, suggesting that it may contribute to immune evasion in CRPC. CONCLUSIONS: Our findings shed light on the genome-wide network of OCT1 and AR in AR-positive CRPC and highlight the potential role of CTBP2 in immune response and tumor progression. Targeting CTBP2 may represent a promising therapeutic approach for aggressive AR-positive CRPC. Further validation will be required to explore novel therapeutic strategies for CRPC management.
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Oxidorreductasas de Alcohol , Proteínas Co-Represoras , Regulación Neoplásica de la Expresión Génica , Factor 1 de Transcripción de Unión a Octámeros , Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Ratones , Animales , Factor 1 de Transcripción de Unión a Octámeros/metabolismo , Factor 1 de Transcripción de Unión a Octámeros/genética , Oxidorreductasas de Alcohol/genética , Oxidorreductasas de Alcohol/metabolismo , Regulación hacia Arriba , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Microambiente Tumoral , Transducción de SeñalRESUMEN
A 38-year-old rice farmer visited a hospital for abdominal pain. Computed tomography (CT) showed a liver tumor and magnetic resonance imaging (MRI) revealed a hypovascular tumor, both in segment 4. Thus, he was diagnosed with liver abscess. Ten days later, CT showed a new liver tumor in segment 8, but the size of the liver tumor in segment 4 had decreased. He was suspected with parasitic disease because of eosinophilia. Enzyme-linked immunosorbent assay showed a high level of serum Fasciola antibody. The patient was diagnosed with fascioliasis and was treated with triclabendazole. Post-treatment, CT revealed that the liver tumors had shrunk. Eosinophilia and multiple lesions were characteristic findings of parasitic disease.
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Eosinofilia , Fascioliasis , Absceso Hepático , Neoplasias Hepáticas , Masculino , Humanos , Adulto , Fascioliasis/diagnóstico por imagen , Fascioliasis/tratamiento farmacológico , Neoplasias Hepáticas/diagnósticoRESUMEN
Autoimmune encephalitis (AE) subacutely causes severe and multiple symptoms; however, most patients achieve neurologically favorable outcomes. Despite the substantial recovery in motor function, persistent impairments in mental/social aspects lasting for several years have been recognized, and its potential effect on health-related quality of life (HRQOL) has been argued. To urgently evaluate the long-term effects of AE on patients' HRQOL, we investigated patient-oriented long-term outcomes and assessed the HRQOL of patients with AE. Data of patients who were diagnosed with probable/definite AE, defined by Graus AE criteria 2016, and treated at our hospital between January 2011 and October 2020 were retrospectively retrieved. Their long-term (≥2 years) outcomes, which included various sequelae and handicaps in social activities such as returning to previous work/school life through structured interview forms, were evaluated, and the HRQOL was assessed using Neuro-QOL battery. We identified 32 patients who met the Graus AE criteria 2016 and eventually enrolled 21 patients in the study. The median interval between disease onset and survey period was 63 (25-156) months, and 43% of the patients had persistent neuropsychiatric symptoms, including memory disorders, personality changes, and seizures. No more than 71% returned to their previous work/school life. Although most of the patients had global QOL within normal limits, 48% had social QOL under normal limits. Patients with sequelae were significantly less likely to return to previous work/school and had worse global/social quality of life than patients without sequelae. In conclusion, nearly half of patients with AE had social QOL under normal limits 5 years after onset. The difficulty in returning to work/school and a worse HRQOL were notable in patients with sequelae.
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Enfermedades Autoinmunes del Sistema Nervioso , Encefalitis , Humanos , Calidad de Vida , Estudios Retrospectivos , Progresión de la EnfermedadRESUMEN
New-onset refractory status epilepticus (NORSE) is a rare and devastating condition and the prognosis is often poor, with half to two-thirds of survivors experiencing drug-resistant epilepsy, residual cognitive impairment, or functional disability, and the mortality rate is 16% to 27% for adults. We describe a patient with cryptogenic NORSE and favorable recovery from drug-resistant super-refractory SE after the use of intravenous lidocaine. The patient experienced fever and presented with refractory generalized tonic-clonic seizures. The cause was not found by performing extensive examinations, including cell surface autoantibodies and rat brain immunohistochemistry evaluations. The refractory SE with unresponsiveness to multiple anti-epileptic and prolonged sedative medications, which are necessary for prolonged mechanical ventilation, were ameliorated by additive treatment with intravenous lidocaine initiating at 1 mg/kg/h and maintaining at 2 mg/kg/h for 40 days, which led to freedom from intravenous sedative medication and mechanical ventilation. The patient was able to return to school. Lidocaine may be an optional treatment for cryptogenic NORSE.
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A 58-year-old woman with a history of systemic lupus erythematosus (SLE) who was taking prednisolone and mycophenolate mofetil presented with gait disturbances that progressively worsened over a period of 3 months. Her blood test and cerebrospinal fluid (CSF) examination results did not indicate active SLE. Initial brain magnetic resonance imaging (MRI) revealed a small spotty lesion in the left cerebellar peduncle. The clinical course was consistent with rapidly progressive cerebellar syndrome (RPCS), which sometimes involves neuronal antibodies. The line blot assay detected anti-Yo antibodies, but no malignancy was found. Immunohistological techniques using rat brain sections yielded a negative result for anti-Yo antibodies. The second MRI revealed a focal lesion and surrounding spotty lesion in the left cerebellar peduncle, which was consistent with the punctate pattern observed in progressive multifocal leukoencephalopathy (PML). The CSF JCV-DNA test indicated the presence of cerebellar PML. Immunosuppressants were reduced, and mefloquine and mirtazapine were initiated. After approximately 2 years and 1 month, the CSF JCV-DNA results became negative. Cerebellar PML may exhibit a clinical course that is consistent with RPCS. The punctate pattern should be recognized as an early manifestation of PML. The CSF JCV-DNA copy number may serve as a useful indicator of PML stabilization.
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Amphiphysin (AMPH) autoimmunity is associated with a variety of neurological complications, including encephalitis, peripheral neuropathy, myelopathy, and cerebellar syndrome. Its diagnosis is based on clinical neurological deficits and the presence of serum anti-AMPH antibodies. Active immunotherapy, such as intravenous immunoglobulins, steroids, and other immunosuppressive therapies, has been reported to be effective in most patients. However, the extent of recovery varies depending on the case. Herein, we report the case of a 75-year-old woman with semi-rapidly progressive systemic tremors, visual hallucinations, and irritability. Upon hospitalization, she developed a mild fever and cognitive impairment. Brain magnetic resonance imaging (MRI) showed semi-rapidly progressive diffuse cerebral atrophy (DCA) over 3 months, while no clear abnormal intensities were observed. The nerve conduction study revealed sensory and motor neuropathy in the limbs. The fixed tissue-based assay (TBA) failed to detect antineuronal antibodies; however, based on commercial immunoblots, the presence of anti-AMPH antibodies was suspected. Therefore, serum immunoprecipitation was performed, which confirmed the presence of anti-AMPH antibodies. The patient also had gastric adenocarcinoma. High-dose methylprednisolone, and intravenous immunoglobulin were administered and tumor resection was performed, resulting in resolution of the cognitive impairment and improvement in the DCA on the post-treatment MRI. After immunotherapy and tumor resection, the patient's serum was analyzed using immunoprecipitation, which showed a decrease in the level of anti-AMPH antibodies. This case is noteworthy because the DCA showed improvement after immunotherapy and tumor resection. Additionally, this case demonstrates that negative TBA with positive commercial immunoblots do not necessarily indicate false positive results.
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Background: Patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) usually achieve neurologically favorable outcomes in the post-acute-phase. Even when motor function recovers, many patients experience numerous non-motor sequelae and cannot resume their pre-NMDARE lives even years later. Additionally, the needs of patients with NMDARE may impose a severe caregiver burden. Unfortunately, few studies have comprehensively examined patients recovering from NMDARE. We investigated the long-term effects of NMDARE on patients' quality of life (QOL). Methods: Data collected via structured self-reported questionnaires included clinical features, long-term outcomes, and QOL. These questionnaires were administered to adult members of the Japanese Anti-NMDARE Patients' Association. We used the NeuroQOL battery to assess QOL in physical, mental, and social domains. Raw NeuroQOL scores were converted to T-scores for comparison with controls. Results: Twenty-two patients completed the questionnaire. The median interval between disease onset and questionnaire response was 78 months. Forty-six percent of patients reported persistent sequelae, with only 73% able to resume prior work/school activities. Although patients' Global QOL was similar to controls, patients with NMDARE had significantly worse social QOL. Patients with worse social QOL had more frequent sequelae than those with better social QOL. Furthermore, patients with persistent sequelae had significantly worse Global QOL than those without sequelae and controls. Conclusion: Patients with NMDARE had worse social QOL than controls. Given the adverse effects of disease sequelae on QOL, treatment strategies that minimize sequelae during the acute-phase may improve patients' QOL, even years post-disease onset.
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Since the discovery of a series of antineuronal surface antibodies (NSAs), the diagnostic approach and management of patients with autoimmune encephalitis (AE) and related disorders have undergone a "paradigm shift." However, recent topics described below are also announcing the dawn of the next era in the practice of patients with AE. As the clinical spectrum of NSA-associated AE expands, some types of AE (e.g., anti-DPPX antibody-associated and anti-IgLON5 antibody-associated disorders) can be misclassified into reconsider diagnosis when using the previously published diagnostic criteria. Nobel active immunization animal models of NSA-associated disorders (e.g., anti-NMDAR encephalitis model) can remarkably emphasize the understanding of the pathophysiological effects and main syndrome induced by NSAs. Additionally, several international clinical trials (e.g., rituximab, inebilizumab, ocrelizumab, bortezomib, and rozanolixizumab) for AE treatments, including anti-NMDAR encephalitis, have been implemented. Data from these clinical trials can be used to establish the best treatment of AE.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Enfermedad de Hashimoto , Animales , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , AutoanticuerposRESUMEN
A 46-year-old male patient with a drinking history presented at our hospital with jaundice. He was diagnosed with moderate alcoholic hepatitis based on laboratory data. The white blood cell (WBC) counts were gradually increased and the prothrombin time was prolonged after hospitalization. Methylprednisolone (1000mg/day for 3 days) followed by oral prednisolone (40mg/day) was administered. However, the liver function was not improved and the patient progressed to severe alcoholic hepatitis. Therefore, we performed granulocytapheresis (GCAP). The WBC counts and interleukin-6 decreased and the liver function improved after 3 GCAP sessions.
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Hepatitis Alcohólica , Masculino , Humanos , Persona de Mediana Edad , Hepatitis Alcohólica/terapiaRESUMEN
(1) Introduction: Spontaneous spinal epidural hematoma (SSEH) points to hematoma within the epidural space of the spinal cord without traumatic or iatrogenic causes. (2) Case Reports: One patient showed paraplegia, numbness of both legs with acute onset, acute myelopathic signs, subsequent to back pain. Magnetic resonance imaging (MRI) showed hematoma in the posterior part of the thoracic spinal cord. Another patient showed acute numbness in the shoulder, upper part of the back, and the upper extremity on the right side after pain in the back, shoulder, and neck on the right side. Sagittal computed tomography (CT) images of the cervical bone showed a high-density area behind the spinal cord between C4 and C7. MRI analysis showed hematoma in the right diagonally posterior part of the cervical spinal cord. These 2 patients lacked traumatic or iatrogenic events, and their symptoms abated without surgical operation. (3) Conclusions: The location of hematoma correlated with symptoms in each patient. SSEH is rare but should be taken into account in patients with myelopathy or radiculopathy with acute onset subsequent to back pain. The usefulness of emergent CT scans of the spinal cord prior to MRI analysis was shown in the diagnosis of SSEH.
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This study aimed to evaluate the clinical characteristics of acute ischemic stroke (AIS) patients who experienced hypoesthesia as the initial symptom. We retrospectively analyzed the medical records of 176 hospitalized AIS patients who met our inclusion and exclusion criteria and evaluated their clinical features and MRI findings. Among this cohort, 20 (11%) patients presented with hypoesthesia as the initial symptom. MRI scans of these 20 patients identified lesions in the thalamus or pontine tegmentum in 14 and brain lesions at other sites in 6. The 20 hypoesthesia patients had higher systolic (p = 0.031) and diastolic blood pressure (p = 0.037) on admission, and a higher rate of small-vessel occlusion (p < 0.001) than patients without hypoesthesia. The patients with hypoesthesia had a significantly shorter average hospital stay (p = 0.007) but did not differ significantly from those without hypoesthesia in National Institutes of Health Stroke Scale scores on admission (p = 0.182) or the modified Rankin Scale scores for neurologic disability on discharge (p = 0.319). In the patients with acute onset hypoesthesia, high blood pressure, and neurological deficits were more likely to be due to AIS than other causes. Since most of the lesions in AIS patients with hypoesthesia as the initial symptom were found to be small, we recommend performing MRI scans with such patients to confirm AIS.
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Post-stroke pneumonia (PSP) has an impact on acute ischemic stroke (AIS). Although predictive scores for PSP have been developed, it is occasionally difficult to predict. Clarifying how PSP was treated after its onset in clinical practice is important. Admitted patients with AIS over a 2-year period were retrospectively reviewed. Of 281 patients with AIS, 24 (8.5%) developed PSP. The integer-based pneumonia risk score was higher in patients with PSP. The onset of PSP was frequently seen up to the 4th day of hospitalization. Of patients with PSP, sputum examination yielded Geckler 4 or 5 in only 8.3%. Angiotensin-converting enzyme inhibitor (ACE-I) was more frequently administered to patients with PSP; however, all these cases were started with ACE-I following PSP onset. Nasogastric tubes (NGTs) were inserted in 16 of the patients with PSP, of whom 11 were inserted following PSP onset. Multivariate analysis showed that PSP onset was a poor prognostic factor independent of the female sex, urinary tract infection, and National Institutes of Health Stroke Scale. PSP treatment would benefit from the administration of antimicrobials and ACE-I, as well as NGT insertion. To select effective agents for PSP and evaluate the indications for NGT insertion, further case studies are needed.
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The coexistence of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) autoantibodies in the same individual is surprisingly often observed. We herein report the first case of LGI1 encephalitis followed by Isaacs syndrome in which LGI1 and CASPR2 antibodies in the serum and cerebrospinal fluid (CSF) were measured during the entire disease course. After the resolution of limbic encephalitis, LGI1 antibodies disappeared from the CSF simultaneously with the appearance of CASPR2 antibodies in the serum. The alternating presence of these pathogenic autoantibodies along with the clinical and phenotypic alternations suggested that LGI1 encephalitis was associated with CASPR2 autoantibody production in the peripheral tissue, leading to CASPR2-associated Isaacs syndrome.
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Encefalitis , Síndrome de Isaacs , Encefalitis Límbica , Humanos , Autoanticuerpos , Leucina , Síndrome de Isaacs/complicaciones , Péptidos y Proteínas de Señalización Intracelular , Encefalitis/diagnóstico , Encefalitis/complicaciones , Encefalitis Límbica/complicaciones , ContactinasRESUMEN
RATIONALE: Acute encephalopathy is a severe neurological complication of coronavirus disease 2019 (COVID-19). Most cases of acute encephalopathy associated with COVID-19 occur within several weeks of COVID-19 onset. We describe a case series of 6 patients who developed delayed encephalopathy (DE) after COVID-19. PATIENT CONCERNS AND DIAGNOSES: We evaluated patients who recovered from COVID-19 and showed acute disturbance of consciousness or focal neurological deficits without recurrence of pneumonitis. Six patients, 2 females and 4 males, with ages ranging from 65 to 83 years were included. Durations of hospitalization due to COVID-19 were between 25 and 44 days. The severity of COVID-19 was moderate in 5 and severe in 1 patient. Patients were rehospitalized for acute disturbance of consciousness concomitant with postural tremor and, abnormal behavior, hemiplegia, aphasia, or apraxia between 34 and 67 days after the onset of COVID-19. Chest computed tomography showed no exacerbation of pneumonitis. Brain magnetic resonance imaging showed no specific findings except in 1 patient with an acute lacunar infarction. Electroencephalogram demonstrated diffuse slowing in all patients. Repeat electroencephalogram after recovery from encephalopathy demonstrated normal in all patients. One of the 6 patients had cerebrospinal fluid (CSF) pleocytosis. CSF protein levels were elevated in all patients, ranging from 51 to 115 mg/dL. CSF interleukin-6 levels ranged from 2.9 to 10.9 pg/mL. The immunoglobulin index was 0.39 to 0.44. Qlim(alb) < QAlb indicating dysfunction of the blood-brain barrier was observed in all patients. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction of CSF was negative in all patients. Neuronal autoantibodies were absent in serum and CSF. INTERVENTIONS AND OUTCOMES: Immunotherapy including steroid pulses was administered to 3 patients; however, symptoms of encephalopathy resolved within several days in all patients, regardless of treatment with immunotherapy, and their consciousness levels were recovered fully. Notably, postural tremor remained for 2 weeks to 7 months. LESSONS: In our patients, DE after COVID-19 was characterized by symptoms of acute encephalopathy accompanied with tremor in the absence of worsening pneumonitis after the fourth week of COVID-19 onset. Our findings indicate blood-brain barrier dysfunction may contribute to the pathogenesis of DE after COVID-19.
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Encefalopatías , COVID-19 , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Autoanticuerpos , Encefalopatías/diagnóstico , Encefalopatías/virología , COVID-19/complicaciones , TemblorRESUMEN
OBJECTIVE: Meningitis and encephalitis are neurological emergencies requiring rapid diagnosis and treatment. The performance of the FilmArray® Meningitis/Encephalitis (ME) panel, a multiplex polymerase chain reaction test, and conventional methods for diagnosing meningitis and encephalitis was compared. METHODS: This retrospective study assessed 20 patients diagnosed with meningitis or encephalitis according to clinical symptoms and laboratory examination findings between January 2018 and December 2019. The results of the FilmArray® ME panel were compared with those of conventional methods. RESULTS: Pathogens were identified in 11 (55%) patients using the FilmArray® ME panel and in nine (45%) patients using conventional methods. The test identified herpes simplex virus type 1 in two patients, herpes simplex virus type 2 in one, varicella-zoster virus in four, Streptococcus pneumoniae in three, and Cryptococcus neoformans in one. Furthermore, additional pathogens were detected (n = 1, S. pneumoniae and n = 1, varicella-zoster virus). The median times to pathogen identification were 2 hours using the FilmArray® ME panel and 96 hours with conventional methods. CONCLUSIONS: The sensitivity of the FilmArray® ME panel for rapidly detecting the most common pathogens was similar to that of conventional methods. Hence, this method could decrease the time to definitive diagnosis and treatment initiation.
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Encefalitis , Meningitis , Humanos , Laboratorios , Meningitis/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex/métodos , Estudios RetrospectivosRESUMEN
Autoimmune disorders, such as choreoathetosis and abnormal behavior secondary to herpes simplex encephalitis (HSE), are discussed in this review. These disorders are known to develop without any evidence of HSE relapse, while they respond to immunotherapies such as intravenous corticosteroids. Recent evidence, including a prospective Spanish cohort study of HSE, revealed that autoimmune encephalitis (AE) can be triggered by HSE, which is closely related to several neuronal surface antibodies (NSAs). Anti-N-methyl-D-aspartate encephalitis (NMDARE) is the most common phenotype of AE post-HSE. Moreover, approximately 30% of cases of AE post-HSE are caused by NSAs against undetermined antigens. Thus, patients suspected of having AE post-HSE should be tested for NSAs using comprehensive techniques combining tissue-based and cultured live neuron assays. The primary syndrome of AE post-HSE is age dependent, as demonstrated in non-post-HSE onset NMDARE. Choreoathetosis is the most common symptom in infants and toddlers, while abnormal behavior and psychiatric symptoms are the most common symptoms in adolescents and adults. Regarding the treatment, current knowledge reveals that intensive immunotherapies can be used to treat AE post-HSE and lead to better outcomes although a minority of cases show recovery without immunotherapy administration.
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Encefalitis por Herpes Simple , Estudios de Cohortes , Ácido D-Aspártico , Encefalitis , Encefalitis por Herpes Simple/complicaciones , Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/terapia , Enfermedad de Hashimoto , Humanos , Estudios ProspectivosRESUMEN
RATIONALE: Neurosyphilis presenting as limbic encephalitis (LE) is an important differential diagnosis of autoimmune LE (ALE) defined by Graus in 2016. However, data on the clinical differences and similarities between neurosyphilis presenting as LE and ALE are limited. Herein, we report neurosyphilis presenting as ALE that fulfilled the main items of the Graus ALE criteria. Moreover, a literature review of neurosyphilis presenting as LE was performed. PATIENT CONCERNS: A 66-year-old Japanese man developed nonconvulsive status epilepticus. He presented with progressive personality change and working memory deficits within 3 months prior to admission. A hyperintense lesion localized in the bilateral medial temporal area was observed on T2-weighted fluid-attenuated inversion recovery brain magnetic resonance imaging. Cerebrospinal fluid analysis showed mild pleocytosis and the presence of oligoclonal band. However, in-house assays did not detect antineuronal antibodies. Electroencephalogram showed lateralized rhythmic delta activity in the right temporal area. The serum and cerebrospinal fluid serological and antigen tests for syphilis had positive results. DIAGNOSIS: ALE was initially suspected based on the patient's symptoms and ancillary test findings that fulfilled the Graus ALE criteria. However, based on the positive confirmatory test results for syphilis, a diagnosis of neurosyphilis was eventually made. INTERVENTION: The patient received intravenous midazolam, oral levetiracetam, and lacosamide to control nonconvulsive status epilepticus. In addition, he was treated with intravenous benzylpenicillin at a dose of 24 million units/day for 14 days. OUTCOMES: The patient's cognitive function relatively improved after antibiotic treatment. However, he presented with persistent mild working memory deficit, which was evaluated with the Wechsler Adult Intelligence Scale, 3rd edition. Therefore, on day 103 of hospitalization, he was transferred to another hospital for rehabilitation and long-term care due to limitations in performing activities of daily living. LESSONS: The present case was diagnosed with neurosyphilis presenting as ALE, but meanwhile, in most case, neurosyphilis presenting as LE developed at a slower progressive rate, and it had a broader or restricted involvement on brain MRI than ALE based on the literature review. Therefore, an appropriate differential diagnosis of LE can be obtained by identifying clinical differences between the 2 conditions.
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Encefalitis Límbica , Neurosífilis , Estado Epiléptico , Sífilis , Actividades Cotidianas , Adulto , Anciano , Enfermedades Autoinmunes , Humanos , Encefalitis Límbica/diagnóstico , Encefalitis Límbica/tratamiento farmacológico , Encefalitis Límbica/etiología , Imagen por Resonancia Magnética , Masculino , Neurosífilis/complicaciones , Neurosífilis/diagnóstico , Neurosífilis/tratamiento farmacológicoRESUMEN
Androgens and androgen receptor (AR) have a central role in prostate cancer progression by regulating its downstream signaling. Although androgen depletion therapy (ADT) is the primary treatment for most prostate cancers, they acquires resistance to ADT and become castration resistant prostate cancers (CRPC). AR complex formation with multiple transcription factors is important for enhancer activity and transcriptional regulation, which can contribute to cancer progression and resistance to ADT. We previously demonstrated that OCT1 collaborates with AR in prostate cancer, and that a pyrrole-imidazole (PI) polyamide (PIP) targeting OCT1 inhibits cell and castration-resistant tumor growth (Obinata D et al. Oncogene 2016). PIP can bind to DNA non-covalently without a drug delivery system unlike most DNA targeted therapeutics. In the present study, we developed a PIP modified with a DNA alkylating agent, chlorambucil (ChB) (OCT1-PIP-ChB). Then its effect on the growth of prostate cancer LNCaP, 22Rv1, and PC3 cells, pancreatic cancer BxPC3 cells, and colon cancer HCT116 cells, as well as non-cancerous MCF-10A epithelial cells, were analyzed. It was shown that the IC50s of OCT1-PIP-ChB for 22Rv1 and LNCaP were markedly lower compared to other cells, including non-cancerous MCF-10A cells. Comprehensive gene expression analysis of CRPC model 22Rv1 cells treated with IC50 concentrations of OCT1-PIP-ChB revealed that the gene group involved in DNA double-strand break repair was the most enriched among gene sets repressed by OCT1-PIP-ChB treatment. Importantly, in vivo study using 22Rv1 xenografts, we showed that OCT1-PIP-ChB significantly reduced tumor growth compared to the control group without showing obvious adverse effects. Thus, the PIP combined with ChB can exert a significant inhibitory effect on prostate cancer cell proliferation and castration-resistant tumor growth, suggesting a potential role as a therapeutic agent.