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Is the category paraphilia a natural kind? That is, do different paraphilias share anything scientifically interesting or are they classified together because they are unusual and sometimes problematic? We investigated this question systematically in 11 samples of paraphilic males (N = 4,617) and 11 samples of control males (N = 1,494). Primary data consisted of responses to the 11-item Paraphilic Interests Scale. Contrary to our initial hypothesis, the scale mean was similar for paraphilic and control samples. Using logistic regression and the same items, we derived three highly correlated measures that robustly discriminated paraphilic and control samples (ds ranging from 0.86 to 0.92). These successful measures capitalized on the unanticipated fact that some items (especially those assessing transvestism and masochistic humiliation) were positively associated with membership in paraphilic samples, while others (especially those assessing voyeurism) were negatively associated with such membership. Subsequent analyses focused on one of the measures, the Paraphilic Interests Scale Contrast (PISC). Consistent with prior findings distinguishing paraphilias and homosexual orientation, PISC was not elevated among homosexual males compared with heterosexual males among the control groups. Within four paraphilic samples, PISC was positively associated with additional paraphilic phenomena. Results provide tentative support for both the proposition that paraphilia is a natural kind and the usefulness of PISC as a measure of paraphilia.
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Introduction: Current vaccines against COVID-19 administered via parenteral route have limited ability to induce mucosal immunity. There is a need for an effective mucosal vaccine to combat SARS-CoV-2 virus replication in the respiratory mucosa. Moreover, sex differences are known to affect systemic antibody responses against vaccines. However, their role in mucosal cellular responses against a vaccine remains unclear and is underappreciated. Methods: We evaluated the mucosal immunogenicity of a booster vaccine regimen that is recombinant protein-based and administered intranasally in mice to explore sex differences in mucosal humoral and cellular responses. Results: Our results showed that vaccinated mice elicited strong systemic antibody (Ab), nasal, and bronchiole alveolar lavage (BAL) IgA responses, and local T cell immune responses in the lung in a sex-biased manner irrespective of mouse genetic background. Monocytes, alveolar macrophages, and CD103+ resident dendritic cells (DCs) in the lungs are correlated with robust mucosal Ab and T cell responses induced by the mucosal vaccine. Discussion: Our findings provide novel insights into optimizing next-generation booster vaccines against SARS-CoV-2 by inducing spike-specific lung T cell responses, as well as optimizing mucosal immunity for other respiratory infections, and a rationale for considering sex differences in future vaccine research and vaccination practice.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunidade nas Mucosas , Imunogenicidade da Vacina , SARS-CoV-2 , Vacinas de Subunidades Antigênicas , Animais , Feminino , Camundongos , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/virologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Masculino , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Pulmão/imunologia , Pulmão/virologia , Linfócitos T/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Camundongos Endogâmicos C57BL , Administração Intranasal , Fatores Sexuais , Imunoglobulina A/imunologia , Células Dendríticas/imunologia , Imunização Secundária , Imunidade HumoralRESUMO
Alnuctamab, a B-cell maturation antigen (BCMA)-targeting T-cell engager, has demonstrated encouraging antitumor activity in the phase I study CC-93269-MM-001 treating patients with relapsed or refractory multiple myeloma. Identification of a recommended Phase III dose (RP3D) was a key objective, as such population pharmacokinetic (PopPK) and exposure-response analysis was critical. Intravenous (IV) alnuctamab was administered in fixed doses (0.15-10 mg) or in step-up doses to a maximum 10-mg target dose. Subcutaneous (SC) step-up doses of 3 and 6 mg were followed by a target dose range of 10-60 mg. Concentration data from IV and SC alnuctamab administration was pooled and was well described by a two-compartment PopPK model with first-order absorption and elimination. Covariate analysis determined that the inclusion of baseline soluble BCMA (sBCMA) on clearance significantly improved model fitting. Individual exposure parameters were estimated from the final model to characterize exposure-response relationships. Switching from IV to SC administration improved the safety profile of alnuctamab by limiting the frequency of grade ≥2 CRS events. A significant exposure-CRS relationship was observed after the first SC dose, but not subsequent dose administrations. Exposure-safety analysis did not find a statistically significant relationship between increasing exposure and the probability of key safety events of interest. Logistic regression analysis for patients administered SC alnuctamab identified that increased exposure significantly increased the probability of response, although the additional benefit was minimal at exposures above 30 mg target dose. Considering the totality of exposure-response data, the clinical pharmacology assessment supported a SC RP3D of 3/6/30 mg.
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Antígeno de Maturação de Linfócitos B , Relação Dose-Resposta a Droga , Mieloma Múltiplo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Mieloma Múltiplo/tratamento farmacológico , Complexo CD3/imunologia , Injeções Subcutâneas , Adulto , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Modelos Biológicos , Idoso de 80 Anos ou mais , Antineoplásicos/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversosRESUMO
BACKGROUND: Chest pain is among the most common reasons for presentation to the emergency department (ED) worldwide. Additional studies on most cost-effective ways of differentiating serious vs. benign causes of chest pain are needed. OBJECTIVES: Our study aimed to evaluate the effectiveness of a novel risk stratification pathway utilizing 5th generation high-sensitivity cardiac troponin T assay (Hs-cTnT) and HEART score (History, Electrocardiogram, Age, Risk factors, Troponin) in assessing nontraumatic chest pain patients in reducing ED resource utilization. METHODS: A retrospective chart review was performed 6 months prior to and after the implementation of a novel risk stratification pathway that combined hs-cTnT with HEART score to guide evaluation of adult patients presenting with nontraumatic chest pain at a large academic quaternary care ED. Primary outcome was ED length of stay (LOS); secondary outcomes included cardiology consult rates, admission rates, number of ED boarders, and number of eloped patients. RESULTS: A total of 1707 patients and 1529 patients were included pre- and postimplementation, respectively. Median overall ED LOS decreased from 317 to 286 min, an absolute reduction of 31 min (95% confidence interval 22-41 min), after pathway implementation (p < 0.001). Furthermore, cardiology consult rate decreased from 26.9% to 16.0% (p < 0.0001), rate of admission decreased from 30.1% to 22.7% (p < 0.0001), and number of ED boarders as a proportion of all nontraumatic chest pain patients decreased from 25.13% preimplementation to 18.63% postimplementation (p < 0.0001). CONCLUSIONS: Implementation of our novel chest pain pathway improved numerous ED throughput metrics in the evaluation of nontraumatic chest pain patients.
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Dor no Peito , Serviço Hospitalar de Emergência , Troponina T , Humanos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Troponina T/sangue , Troponina T/análise , Medição de Risco/métodos , Idoso , Adulto , Eletrocardiografia/métodos , Tempo de Internação/estatística & dados numéricos , Biomarcadores/sangue , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Artificial intelligence models in radiology are frequently developed and validated using data sets from a single institution and are rarely tested on independent, external data sets, raising questions about their generalizability and applicability in clinical practice. The American Society of Functional Neuroradiology (ASFNR) organized a multicenter artificial intelligence competition to evaluate the proficiency of developed models in identifying various pathologies on NCCT, assessing age-based normality and estimating medical urgency. MATERIALS AND METHODS: In total, 1201 anonymized, full-head NCCT clinical scans from 5 institutions were pooled to form the data set. The data set encompassed studies with normal findings as well as those with pathologies, including acute ischemic stroke, intracranial hemorrhage, traumatic brain injury, and mass effect (detection of these, task 1). NCCTs were also assessed to determine if findings were consistent with expected brain changes for the patient's age (task 2: age-based normality assessment) and to identify any abnormalities requiring immediate medical attention (task 3: evaluation of findings for urgent intervention). Five neuroradiologists labeled each NCCT, with consensus interpretations serving as the ground truth. The competition was announced online, inviting academic institutions and companies. Independent central analysis assessed the performance of each model. Accuracy, sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were generated for each artificial intelligence model, along with the area under the ROC curve. RESULTS: Four teams processed 1177 studies. The median age of patients was 62 years, with an interquartile range of 33 years. Nineteen teams from various academic institutions registered for the competition. Of these, 4 teams submitted their final results. No commercial entities participated in the competition. For task 1, areas under the ROC curve ranged from 0.49 to 0.59. For task 2, two teams completed the task with area under the ROC curve values of 0.57 and 0.52. For task 3, teams had little-to-no agreement with the ground truth. CONCLUSIONS: To assess the performance of artificial intelligence models in real-world clinical scenarios, we analyzed their performance in the ASFNR Artificial Intelligence Competition. The first ASFNR Competition underscored the gap between expectation and reality; and the models largely fell short in their assessments. As the integration of artificial intelligence tools into clinical workflows increases, neuroradiologists must carefully recognize the capabilities, constraints, and consistency of these technologies. Before institutions adopt these algorithms, thorough validation is essential to ensure acceptable levels of performance in clinical settings.
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Inteligência Artificial , Humanos , Masculino , Estados Unidos , Pessoa de Meia-Idade , Adulto , Feminino , Idoso , Tomografia Computadorizada por Raios X/métodos , Sociedades Médicas , Encefalopatias/diagnóstico por imagem , Sensibilidade e Especificidade , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: Acute neurological manifestation is a common complication of acute Coronavirus Disease 2019 (COVID-19) disease. This retrospective cohort study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. METHODS AND FINDINGS: Patients hospitalized for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection between 03/01/2020 and 4/16/2020 in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to 01/23/2023 (3 years post-COVID-19). This cohort consisted of 414 patients with COVID-19 with significant neurological manifestations and 1,199 propensity-matched patients (for age and COVID-19 severity score) with COVID-19 without neurological manifestations. Neurological involvement during the acute phase included acute stroke, new or recrudescent seizures, anatomic brain lesions, presence of altered mentation with evidence for impaired cognition or arousal, and neuro-COVID-19 complex (headache, anosmia, ageusia, chemesthesis, vertigo, presyncope, paresthesias, cranial nerve abnormalities, ataxia, dysautonomia, and skeletal muscle injury with normal orientation and arousal signs). There were no significant group differences in female sex composition (44.93% versus 48.21%, p = 0.249), ICU and IMV status, white, not Hispanic (6.52% versus 7.84%, p = 0.380), and Hispanic (33.57% versus 38.20%, p = 0.093), except black non-Hispanic (42.51% versus 36.03%, p = 0.019). Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were neuroimaging findings (hemorrhage, active and prior stroke, mass effect, microhemorrhages, white matter changes, microvascular disease (MVD), and volume loss). More patients in the neurological cohort were discharged to acute rehabilitation (10.39% versus 3.34%, p < 0.001) or skilled nursing facilities (35.75% versus 25.35%, p < 0.001) and fewer to home (50.24% versus 66.64%, p < 0.001) than matched controls. Incidence of readmission for any reason (65.70% versus 60.72%, p = 0.036), stroke (6.28% versus 2.34%, p < 0.001), and MACE (20.53% versus 16.51%, p = 0.032) was higher in the neurological cohort post-discharge. Per Kaplan-Meier univariate survival curve analysis, such patients in the neurological cohort were more likely to die post-discharge compared to controls (hazard ratio: 2.346, (95% confidence interval (CI) [1.586, 3.470]; p < 0.001)). Across both cohorts, the major causes of death post-discharge were heart disease (13.79% neurological, 15.38% control), sepsis (8.63%, 17.58%), influenza and pneumonia (13.79%, 9.89%), COVID-19 (10.34%, 7.69%), and acute respiratory distress syndrome (ARDS) (10.34%, 6.59%). Factors associated with mortality after leaving the hospital involved the neurological cohort (odds ratio (OR): 1.802 (95% CI [1.237, 2.608]; p = 0.002)), discharge disposition (OR: 1.508 (95% CI [1.276, 1.775]; p < 0.001)), congestive heart failure (OR: 2.281 (95% CI [1.429, 3.593]; p < 0.001)), higher COVID-19 severity score (OR: 1.177 (95% CI [1.062, 1.304]; p = 0.002)), and older age (OR: 1.027 (95% CI [1.010, 1.044]; p = 0.002)). There were no group differences in radiological findings, except that the neurological cohort showed significantly more age-adjusted brain volume loss (p = 0.045) than controls. The study's patient cohort was limited to patients infected with COVID-19 during the first wave of the pandemic, when hospitals were overburdened, vaccines were not yet available, and treatments were limited. Patient profiles might differ when interrogating subsequent waves. CONCLUSIONS: Patients with COVID-19 with neurological manifestations had worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for patients with COVID-19 with neurological manifestations, as their disease course involving initial neurological manifestations is associated with enhanced morbidity and mortality.
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COVID-19 , Acidente Vascular Cerebral , Humanos , Feminino , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Estudos Retrospectivos , Seguimentos , Assistência ao Convalescente , Alta do Paciente , Convulsões , Acidente Vascular Cerebral/epidemiologiaRESUMO
Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30. Cognitive flexibility (n = 460) and inhibition (n = 466) were measured using neuropsychological assessment (D-KEFS), and conflict monitoring and error monitoring were measured by event-related potentials (conflict N2: n = 394; error-related negativity: n = 389). After separately testing relations between the different measures of cognitive function and sexual functioning, we assessed whether results (1) remained after covarying for externalizing and internalizing dimensions (PID-5; n = 489) or (2) varied by gender. Finally, we tested whether any aspects of cognitive function were unique predictors of sexual functioning. Cognitive flexibility and error monitoring (i.e., error-related negativity) were both significantly related to sexual functioning among males and females, such that poorer cognitive flexibility and heightened error monitoring were related to lower sexual functioning. No significant effects emerged for inhibition or conflict monitoring. In a multiple regression model, cognitive flexibility and error monitoring each accounted for a unique portion of variance in sexual functioning beyond other aspects of cognitive function and psychopathology-related traits. Results suggest that cognitive function is a meaningful correlate of sexual functioning in young adulthood, which should be considered further in future research.
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Cognição , Potenciais Evocados , Masculino , Humanos , Feminino , Idoso , Adulto Jovem , Adulto , Potenciais Evocados/fisiologia , Cognição/fisiologia , Comportamento Sexual , Testes Neuropsicológicos , EletroencefalografiaRESUMO
In a structure-function study of sulfatides that typically stimulate type II NKT cells, we made an unexpected discovery. We compared analogs with sphingosine or phytosphingosine chains and 24-carbon acyl chains with 0-1-2 double bonds (C or pC24:0, 24:1, or 24:2). C24:1 and C24:2 sulfatide presented by the CD1d monomer on plastic stimulated type II, not type I, NKT cell hybridomas, as expected. Unexpectedly, when presented by bone marrow-derived DCs (BMDCs), C24:2 reversed specificity to stimulate type I, not type II, NKT cell hybridomas, mimicking the corresponding ß-galactosylceramide (ßGalCer) without sulfate. C24:2 induced IFN-γ-dependent immunoprotection against CT26 colon cancer lung metastases, skewed the cytokine profile, and activated conventional DC subset 1 cells (cDC1s). This was abrogated by blocking lysosomal processing with bafilomycin A1, or by sulfite blocking of arylsulfatase or deletion of this enyzme that cleaves off sulfate. Thus, C24:2 was unexpectedly processed in BMDCs from a type II to a type I NKT cell-stimulating ligand, promoting tumor immunity. We believe this is the first discovery showing that antigen processing of glycosylceramides alters the specificity for the target cell, reversing the glycolipid's function from stimulating type II NKT cells to stimulating type I NKT cells, thereby introducing protective functional activity in cancer. We also believe our study uncovers a new role for antigen processing that does not involve MHC loading but rather alteration of which type of cell is responding.
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Células T Matadoras Naturais , Neoplasias , Humanos , Sulfoglicoesfingolipídeos/metabolismo , Antígenos CD1d/genética , Apresentação de Antígeno , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Sulfatos/metabolismoRESUMO
Some men sexually attracted to types of persons (e.g., women) or things (e.g., animals) also have internalized sexual attractions: sexual arousal by the idea of being the type of person or thing to whom they are attracted. Consequently, some of these men develop erotic target identity inversions, in which they imitate, yearn to be, or identify as an instance of their erotic target. Erotic Target Identity Inversion Theory predicts that for every external erotic target to which men are attracted, a subset of men will develop an internalized sexual attraction, which may cause an erotic target identity inversion. We examined these predictions in Internet surveys of three samples of men with paraphilic sexual interests: 322 men attracted to amputees, 1501 men attracted to animals, and 402 men attracted to severely obese persons. All samples included substantial minorities of men reporting internalized sexual attractions and erotic target identity inversions specific to their external sexual attractions (e.g., men attracted to amputees who are also aroused by the fantasy of being amputees and wish to become amputees). The correlation between degree of each internalized sexual attraction and degree of its corresponding erotic target identity inversion was approximately 1.0 after correction for attenuation. In each sample, participants' specific internalized sexual attraction was positively correlated with autogynephilia, likely the most common internalized sexual attraction in men. Erotic Target Identity Inversion Theory can potentially explain a variety of otherwise puzzling phenomena, including transgender identity among female-attracted natal males and men seeking amputations of healthy limbs.
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Ectopic pituitary tumors are neoplasms with no connection to the pituitary gland and are commonly deposited in other areas of the anterior skull base. A 32-year-old woman presented with a 3-month history of right-sided facial weakness, sensorineural hearing loss, diplopia, and severe headaches. Physical examination revealed a mid-dilated sluggishly reactive right pupil with slight limitation in all gazes, as well as right-sided orbicularis weakness, lagophthalmos, and decreased facial sensation. A magnetic resonance imaging (MRI) of the head without contrast revealed a 3.7 × 1.8 × 2.6 cm mildly enhancing mass in the right internal acoustic meatus and along the petrous ridge. The case was brought before the institution's tumor board, where concern for higher grade pathology, such as hemangiopericytoma, was discussed. Per patient preference, surgical biopsy of the tumor was performed. Immunohistochemical staining revealed a World Health Organization (WHO) grade II neuroendocrine tumor, with cells staining positive for synaptophysin, chromogranin, and CD56, with a K i -67 index of 8%. In addition to the ectopic location, this pituitary tumor was noted to be aggressive in nature based on its high K i -67 index. Surgical excision and radiologic therapy of tumors involving the CPA are appropriate treatments in most cases.
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Adult baby/diaper lovers (AB/DLs) enjoy role-playing as babies and/or wearing diapers. They also engage in other related activities, such as urinating or defecating themselves and having an adult care for them. Previous surveys have revealed that AB/DLs commonly report sexual motivation, a finding that is corroborated by case reports in the psychiatric literature and some media interviews. The fact that AB/DLs change their appearance and behavior to become more like babies raises the possibility that they have an erotic target identity inversion (ETII). In ETIIs, a person's external erotic target is inverted into the self, resulting in sexual arousal by the fantasy of being a member of the target class or by imitating one. If AB/DLs are sexually motivated by an ETII, they should experience both sexual attraction to babies and sexual arousal by the fantasy of being a baby. We surveyed 207 male AB/DLs recruited from the Internet about their sexual orientation, sexual motivation, and sexual interests for a primarily quantitative analysis. Consistent with past research, a substantial minority of participants reported non-heterosexual identities (42%), and a large majority reported some degree of sexual motivation for being AB/DLs (93%). Wearing diapers and urinating or defecating oneself were rated as especially sexual. Even though 40% of participants reported sexual arousal by the fantasy of being a baby, only 4% reported sexual attraction to babies. This pattern of results is contrary to predictions from the concept of ETIIs. Instead, participants indicated that physical or mental pain, humiliation, and an adult woman were important to their sexual fantasies of being a baby. Masochism appears to be a promising alternative to an ETII for explaining the sexual motivation of AB/DLs.
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Motivação , Comportamento Sexual , Adulto , Masculino , Humanos , Feminino , Comportamento Sexual/psicologia , Masoquismo , Inquéritos e Questionários , Literatura Erótica/psicologia , FantasiaRESUMO
PURPOSE: We sought to establish a comprehensive imaging score indicating the likelihood of higher WHO grade meningiomas pre-operatively. METHODS: All surgical intracranial meningioma patients at our institution between 2014 and 2018 underwent retrospective chart review. Preoperative MRI sequences were reviewed, and imaging features were included in the score based on statistical and clinical significance. Point values for each significant feature were assigned based on the beta coefficients obtained from multivariate analysis. The imaging score was calculated by adding up the points, for a total score of 0 to 5. The predictive ability of the score to identify higher-grade meningiomas was evaluated. RESULTS: Ninety patients, 50% of whom had a postoperative diagnosis of WHO grade II meningioma, were included. The mean age for the population was 59.9 years and 70% were female. Tumor volume ≥ 36.0 cc was assigned 2 points, presence of irregular tumor borders was assigned 2 points, and presence of peritumoral edema was assigned 1 point. The probability of having a WHO grade II meningioma was 0% with a score of 0, 25.0% with a score of 1, 38.5% with a score of 2, 65.4% with a score of 3, and 83.3% with a score of 4 or greater. A threshold of ≥ 3 points achieved a recall of 0.80, precision of 0.73, F1-score of 0.77, accuracy of 0.76, and AUC of 0.82. CONCLUSION: The proposed imaging scoring system had good predictive capability for WHO grade II meningiomas with good discrimination and calibration. External validation is needed.
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Neoplasias Meníngeas , Meningioma , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Meningioma/patologia , Neoplasias Meníngeas/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Carga TumoralRESUMO
BACKGROUND: Degree of cerebrovascular stenosis in pediatric patients with sickle cell anemia (SCA) informs need for chronic transfusion therapy, which has significant risks. Flow artifact, intrinsic to magnetic resonance angiography (MRA), is dependent on technical parameters and can lead to overinterpretation of stenosis. The primary objective of this study was to document any change in stroke prevention therapy that could be attributed to the implementation of a standardized MRA scanning protocol for patients with SCA. METHODS: A standardized MRA scanning protocol with an echo time of less than 5 ms was implemented at Montefiore Medical Center (MMC), NY in May 2016. Retrospective chart review identified 21 pediatric patients with SCA, with an MRA head both pre- and post-May 2016. Arterial stenosis on MRA, machine parameters, and treatment plans were compared pre- and post-implementation. RESULTS: Ten of the 21 patients met inclusion criteria. Previously seen stenosis was re-classified to a lower degree in six of the 10 patients, leading to discontinuation of transfusions in five patients. No patients required escalation of therapy to chronic transfusions. CONCLUSION: Optimizing flow artifact by decreasing echo time to less than 5 ms can improve accurate interpretation of cerebrovascular disease, and ensure appropriate treatment plans are in place for stroke prevention. This is especially important for implementing "TCD With Transfusions Changing to Hydroxyurea (TWiTCH)" clinical trial results in the real-world setting.
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Anemia Falciforme , Acidente Vascular Cerebral , Criança , Humanos , Angiografia por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Estudos Retrospectivos , Constrição Patológica , Anemia Falciforme/terapia , Anemia Falciforme/tratamento farmacológico , Ultrassonografia Doppler TranscranianaRESUMO
INTRODUCTION: Pilocytic astrocytoma, a World Health Organization grade 1 tumor, is the most common brain tumor in children between 5 and 14 years of age and the second most common in children younger than 5 and older than 14. Although classical to the cerebellum and hypothalamic regions, it can also arise in the spinal cord. Larotrectinib, a selective inhibitor of tropomyosin receptor kinase, has been effective in pediatric tumors with NTRK fusion mutations in children as young as 1-month-old. CASE: We share the case of a 9-month-old boy who presented with a 4-month history of regression of his milestones and severe constipation who was found to have a large spinal pilocytic astrocytoma with multiple intracranial periventricular lesions.
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Astrocitoma , Neoplasias Encefálicas , Neoplasias da Medula Espinal , Humanos , Lactente , Masculino , Astrocitoma/complicações , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Neoplasias Encefálicas/cirurgia , Constipação Intestinal , Neoplasias da Medula Espinal/cirurgiaRESUMO
The development of multiple sclerosis (MS) is multifactorial. Elevated levels of vitamin D may lower the risk and reduce relapses by immunomodulatory mechanisms. Conversely, vitamin D-dependent rickets (VDDR), an inheritable form of rickets secondary to impairment in vitamin D synthesis or action, may increase MS risk. This has been described in three patients with VDDR type 1A. Here, we present a patient with VDDR type 2 - unclear if type 2A or 2B based on historical genetic testing - who subsequently developed MS. She presented with 8 weeks of binocular horizontal diplopia and was found to have 8 prism dioptres of esotropia in primary gaze and a mild limitation of abduction in both eyes. Radiological workup was consistent with MS demyelination. She was started on solumedrol infusions, with full resolution of the esotropia and abduction deficits. She has since been transitioned to ocrelizumab with vitamin D supplementation and has not had a relapse to date. It is important to consider MS in patients genetically predisposed to low vitamin D levels or functional impairment, as with VDDR. Vitamin D supplementation can achieve remission in some forms of VDDR, and its role in MS prevention in these patients should be considered. In patients with type 2A or 2B VDDR, who have impairment in receptor function, additional treatment modalities require investigation. Lastly, demyelination is a rare cause of bilateral cranial nerve 6 palsy. This case illustrates the importance of considering MS in cranial nerve palsies, particularly in patients with vitamin D deficiencies or functional impairment.
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Blanchard proposed that autogynephilia is a natal male's paraphilic sexual arousal in response to the thought or fantasy of being a woman. Furthermore, based on evidence collected from natal males with gender dysphoria, Blanchard argued that autogynephilia is the fundamental motivation among nonhomosexual males (i.e., those not exclusively attracted to men) who pursue sex reassignment surgery or live as transgender women. These ideas have been challenged by several writers who have asserted, or offered evidence, that autogynephilia is common among women. However, their evidence was weakened by problematic measures and limited comparison groups. We compared four samples of autogynephilic natal males (N = 1549), four samples of non-autogynephilic natal males (N = 1339), and two samples of natal females (N = 500), using Blanchard's original measure: the Core Autogynephilia Scale. The autogynephilic samples had much higher mean scores compared with non-autogynephilic natal males and natal females, who were similar. Our findings refute the contention that autogynephilia is common among natal females.
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Disforia de Gênero , Cirurgia de Readequação Sexual , Pessoas Transgênero , Transexualidade , Fantasia , Feminino , Identidade de Gênero , Humanos , MasculinoRESUMO
Neuroborreliosis can manifest with cranial nerve (CN) palsies, commonly CN VII. Rarely have isolated or multiple palsies been reported. We describe a case of a young female from a Lyme endemic region who presented with bilateral CN VI palsies and a dilated right pupil, possibly a partial CN III palsy. She later developed CN VII palsy and bilateral enhancement of multiple cranial nerves on neuroimaging. She was diagnosed with Lyme disease by serological testing, with gradual improvement on antibiotics. Our case illustrates that neuroborreliosis can present as any or multiple CN palsies, and should be considered particularly in endemic areas.