RESUMEN

The link between specific human leukocyte antigen (HLA)-B genes and congenital adrenal hyperplasia (CAH) has been a subject of interest. This study investigates the association between specific HLA-B haplotypes and CAH through a meta-analysis. Google Scholar was used as a database. Articles were included if the research was conducted between 1970 and 2022, was not a meta-analysis, and had odds ratios or enough data points to calculate an odds ratio. The National Institutes of Health (NIH) quality assessment tool of case-control studies was used to evaluate the risk of bias in individual studies, and MetaXL was used to generate data and create a forest plot for analysis. Twelve studies met the selection criteria and were included in the study (641 patients and 3,614 controls). Two HLA-B haplotypes showed increased odds of CAH compared to controls: B14 (OR=3.81; 95%CI=2.88, 5.05; I2=3%) and B35 (OR=1.88; 95%CI=1.22, 2.90; I2=25%). All other HLAs either showed no significant effect or had high heterogeneity. The results suggest that specific HLA-B haplotypes have increased odds of developing CAH, specifically B14 and B35. These findings may prove helpful in the pre- and post-natal diagnosis of CAH as well as the identification of carriers and prediction of patient prognosis.

RESUMEN

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such measurements of cellular metabolism can yield critical missing information about a patient's physiologic state and help limit secondary damage. Glucose management in traumatic brain injury is still an unresolved question. As cerebral glucose metabolism may be uncoupled from systemic glucose levels due to the metabolic dysfunction, measurement of cerebral extracellular glucose concentrations could provide more predictive information and prove to be a better biomarker to avoid secondary injury of at-risk brain tissue. Based on data obtained from cerebral microdialysis, specific interventions such as ICP-directed therapy, blood glucose increment, seizure control, and/or brain oxygen optimization can be instituted to minimize or prevent secondary insults. Thus, microdialysis measurements of parenchymal metabolic function provides clinically valuable information that cannot be obtained by other monitoring adjuncts in the standard ICU setting.

RESUMEN

As of October 21, 2022, a total of 27,884 monkeypox cases (confirmed and probable) have been reported in the United States.§ Gay, bisexual, and other men who have sex with men have constituted a majority of cases, and persons with HIV infection and those from racial and ethnic minority groups have been disproportionately affected (1,2). During previous monkeypox outbreaks, severe manifestations of disease and poor outcomes have been reported among persons with HIV infection, particularly those with AIDS (3-5). This report summarizes findings from CDC clinical consultations provided for 57 patients aged ≥18 years who were hospitalized with severe manifestations of monkeypox¶ during August 10-October 10, 2022, and highlights three clinically representative cases. Overall, 47 (82%) patients had HIV infection, four (9%) of whom were receiving antiretroviral therapy (ART) before monkeypox diagnosis. Most patients were male (95%) and 68% were non-Hispanic Black (Black). Overall, 17 (30%) patients received intensive care unit (ICU)-level care, and 12 (21%) have died. As of this report, monkeypox was a cause of death or contributing factor in five of these deaths; six deaths remain under investigation to determine whether monkeypox was a causal or contributing factor; and in one death, monkeypox was not a cause or contributing factor.** Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States (6,7), particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy†† in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox.§§ Engaging all persons with HIV in sustained care remains a critical public health priority.

Asunto(s)

Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Estados Unidos/epidemiología , Humanos , Masculino , Adolescente , Adulto , Femenino , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Etnicidad , Vigilancia de la Población , Grupos Minoritarios , Mpox/epidemiología

RESUMEN

Aim: 106 donor conceived people (DCP) responded to an anonymous survey study that examined the impact of the method of genetic identity disclosure and age at the time of the disclosure on their emotional wellbeing, familial relations, and perceptions of donor conception practices.Methods: Participants were asked to select the way in which they were informed they are DCP and the age group at which this occurred, and then were asked to select strongly agree, agree, neither agree or disagree, disagree, or strongly disagree in response to 26 statements that examined their perceptions of the topics listed above. Responses were grouped based on the age of genetic identity disclosure and the method of genetic identity disclosure, then numerically compared by assigning each type of response a number. Statistical analysis using repeatedmeasures ANOVA was performed to identify differences among these factors.Results: This analysis revealed that most participants 18 ≥ years and most participants who discovered their genetic identity through means other than through their parent(s) had worse emotional wellbeing and familial relations. However, most participants among all categories had a negative perception of donor conception practices.Conclusion: Continued work is needed to understand and support the growing DCP population.

Asunto(s)

Revelación , Concepción de Donantes , Adulto , Humanos , Padres , Linaje , Donantes de Tejidos/psicología

RESUMEN

BACKGROUND: Patients with severe traumatic brain injury (TBI) are at risk of the development of acute respiratory distress syndrome (ARDS). TBI and ARDS pathophysiologic mechanisms are known to independently involve significant inflammatory responses. The literature on the association between plasma inflammatory cytokines and ARDS in patients with TBI is sparse. METHODS: The study was a secondary analysis of the safety of a randomized trial of erythropoietin and transfusion threshold in patients with severe TBI. Inflammatory markers within the first 24 hours after injury were compared in patients who developed ARDS and patients without ARDS, using Cox proportional hazards models. RESULTS: There were 200 patients enrolled in the study. The majority of plasma and cerebrospinal fluid (CSF) cytokine levels were obtained within 6 hours. Plasma proinflammatory markers IL-6 and IL-8 and anti-inflammatory marker IL-10 were associated with the development of ARDS (adjusted hazard ratio (HR) = 1.55, confidence interval (CI) = 1.14, 2.11, P = 0.005 for IL-6; adjusted HR = 1.32, CI = 1.10, 1.59, P = 0.003 for IL-8). CONCLUSION: Plasma markers of IL-6, IL-8, and IL-10 are associated with ARDS in patients with severe TBI. TRIAL REGISTRATION: NCT00313716 registered 4/2006.

Asunto(s)

Biomarcadores/análisis , Lesiones Traumáticas del Encéfalo/fisiopatología , Síndrome de Dificultad Respiratoria/fisiopatología , Adolescente , Adulto , Biomarcadores/sangre , Femenino , Humanos , Interleucina-10/análisis , Interleucina-10/sangre , Interleucina-6/análisis , Interleucina-6/sangre , Interleucina-8/análisis , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales

RESUMEN

Obesity has attained pandemic proportions, and bariatric surgery is increasingly being employed resulting in turn to more neurological complications which must be recognized and managed. Neurological complications may result from mechanical or inflammatory mechanisms but primarily result from micro-nutritional deficiencies. Vitamin B12, thiamine, and copper constitute the most frequent deficiencies. Neurological complications may occur at reasonably predictable times after bariatric surgery and are associated with the type of surgery used. During the early post-operative period, compressive or stretch peripheral nerve injury, rhabdomyolysis, Wernicke's encephalopathy, and inflammatory polyradiculoneuropathy may occur. Late complications ensue after months to years and include combined system degeneration (vitamin B12 deficiency) and hypocupric myelopathy. Bariatric surgery patients require careful nutritional follow-up with routine monitoring of micronutrients at 6 weeks and 3, 6, and 12 months post-operatively and then annually after surgery and multivitamin supplementation for life. Sustained vigilance for common and rare neurological complications is essential.

Asunto(s)

Cirugía Bariátrica/efectos adversos , Enfermedades del Sistema Nervioso/etiología , Complicaciones Posoperatorias , Humanos , Estado Nutricional , Periodo Perioperatorio

RESUMEN

BACKGROUND: Erythropoietin (Epo) improves post-traumatic cerebral blood flow (CBF), pressure autoregulation, and vascular reactivity to l-arginine. This study examines the dependence of these cerebral hemodynamic effects of Epo on nitric oxide generated by endothelial nitric oxide synthase (eNOS). METHODS: Using laser Doppler flow imaging, CBF was monitored in wild-type (WT) and eNOS-deficient mice undergoing controlled cortical impact followed by administration of Epo (5000 U/kg) or normal saline. RESULTS: Cerebral blood flow decreased in all groups post-injury with the greatest reductions occurring at the impact site. Epo administration resulted in significantly higher CBF in the peri-contusional sites in the WT mice [70.2 ± 3.35% in Epo-treated compared to 53 ± 3.3% of baseline in saline-treated mice (p < 0.0001)], but no effect was seen in the eNOS-deficient mice. No CBF differences were found at the core impact site where CBF dropped to 20-25% of baseline in all groups. CONCLUSION: These differences between eNOS-deficient and WT mice indicate that the Epo mediated improvement in CBF in traumatic brain injury is eNOS dependent.

RESUMEN

As a result of global migration, a significant number of people with Trypanosoma cruzi infection now live in the United States, Canada, many countries in Europe, and other non-endemic countries. Trypanosoma cruzi meningoencephalitis is a rare cause of ring-enhancing lesions in patients with acquired immunodeficiency syndrome (AIDS) that can closely mimic central nervous system (CNS) toxoplasmosis. We report a case of CNS Chagas reactivation in an AIDS patient successfully treated with benznidazole and antiretroviral therapy in the United States.

Asunto(s)

Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Enfermedad de Chagas/diagnóstico , Meningoencefalitis/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/parasitología , Fármacos Anti-VIH/uso terapéutico , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Diagnóstico Diferencial , Femenino , Humanos , Meningoencefalitis/complicaciones , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/parasitología , Persona de Mediana Edad , Nitroimidazoles/uso terapéutico , Toxoplasmosis Cerebral/diagnóstico , Resultado del Tratamiento , Tripanocidas/uso terapéutico , Trypanosoma cruzi/patogenicidad , Trypanosoma cruzi/fisiología

RESUMEN

INTRODUCTION: We report a rare case of fulminant vasculitic mononeuropathy resulting in brachial diplegia, with suspected brainstem and autonomic nervous system involvement in a patient with diabetes mellitus. CASE PRESENTATION: A 58-year-old Hispanic Caucasian man with diabetes mellitus presented with a 1-year history of progressive bilateral upper extremity weakness, orthostatic intolerance and progressive memory decline. Diagnostic evaluation including laboratory tests for progressive encephalopathies, systemic inflammatory and non-inflammatory neuropathies, cerebrospinal fluid analyses, electrodiagnostic studies, and nerve biopsy were performed. Clinical examination revealed moderate cognitive deficits on the Montreal Cognitive Assessment scale, bilateral facial weakness and weakness of bilateral shoulder girdle and intrinsic hand muscles. Cerebrospinal fluid analyses revealed elevated protein and an elevated immunoglobulin G synthesis rate, suggesting an immune-mediated process. Further laboratory work up was non-diagnostic. Electrodiagnostic studies demonstrated chronic asymmetric axonal mononeuropathies with ongoing denervation. A superficial radial nerve biopsy showed a chronic vasculitic neuropathy. Glucocorticosteroid treatment, symptomatic pharmacologic and supportive non-pharmacologic therapies resulted in improved clinical outcomes despite challenges with glycemic control. CONCLUSIONS: This case report emphasizes the importance of a thorough evaluation of atypical or uncommon neuromuscular presentations in diabetic patients without etiological presumptions. This is necessary in order to promptly establish a diagnosis, initiate appropriate therapies and prevent irreversible nerve injury.

RESUMEN

Brain metastatic breast cancer (BMBC) is uniformly fatal and increasing in frequency. Despite its devastating outcome, mechanisms causing BMBC remain largely unknown. The mechanisms that implicate circulating tumor cells (CTCs) in metastatic disease, notably in BMBC, remain elusive. We characterize CTCs isolated from peripheral blood mononuclear cells of patients with breast cancer and also develop CTC lines from three of these patients. In epithelial cell adhesion molecule (EpCAM)-negative CTCs, we identified a potential signature of brain metastasis comprising "brain metastasis selected markers (BMSMs)" HER2+ / EGFR+ / HPSE+ / Notch1+. These CTCs, which are not captured by the CellSearch platform because of their EpCAM negativity, were analyzed for cell invasiveness and metastatic competency in vivo. CTC lines expressing the BMSM signature were highly invasive and capable of generating brain and lung metastases when xenografted in nude mice. Notably, increased brain metastatic capabilities, frequency, and quantitation were detected in EpCAM- CTCs overexpressing the BMSM signature. The presence of proteins of the BMSM CTC signature was also detected in the metastatic lesions of animals. Collectively, we provide evidence of isolation, characterization, and long-term culture of human breast cancer CTCs, leading to the description of a BMSM protein signature that is suggestive of CTC metastatic competency to the brain.

Asunto(s)

Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , Células Neoplásicas Circulantes/patología , Animales , Neoplasias Encefálicas/metabolismo , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Desnudos , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor ErbB-2/metabolismo

RESUMEN

Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current studies examined the hypothesis that SP mediates seizures in NCC. We demonstrated by immunostaining that 5 of 5 brain biopsies from NCC patients contained substance P (SP)-positive (+) cells adjacent to but not distant from degenerating worms; no SP+ cells were detected in uninfected brains. In a rodent model of NCC, seizures were induced after intrahippocampal injection of SP alone or after injection of extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice. Seizure activity correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal pre-injection of SP receptor antagonist. Furthermore, extracts of granulomas from WT mice caused seizures when injected into the hippocampus of WT mice, but not when injected into SP receptor (NK1R) deficient mice. These findings indicate that SP causes seizures in NCC, and, suggests that seizures in NCC in humans may be prevented and/or treated with SP-receptor antagonists.

Asunto(s)

Encefalopatías/complicaciones , Granuloma/parasitología , Neurocisticercosis/complicaciones , Convulsiones/etiología , Sustancia P/metabolismo , Animales , Encéfalo/patología , Encefalopatías/parasitología , Encefalopatías/patología , Modelos Animales de Enfermedad , Femenino , Eliminación de Gen , Granuloma/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Neurocisticercosis/parasitología , Neurocisticercosis/patología , Antagonistas del Receptor de Neuroquinina-1/uso terapéutico , Ratas , Ratas Sprague-Dawley , Receptores de Neuroquinina-1/genética , Receptores de Neuroquinina-1/fisiología , Convulsiones/tratamiento farmacológico , Convulsiones/parasitología , Convulsiones/prevención & control , Sustancia P/análisis , Sustancia P/antagonistas & inhibidores , Sustancia P/aislamiento & purificación , Taenia/fisiología

RESUMEN

Heparanase (HPSE) is a potent protumorigenic, proangiogenic, and prometastatic enzyme that is overexpressed in brain metastatic breast cancer (BMBC). However, little is known about the regulation of this potential therapeutic target in BMBC, which remains very poorly managed in the clinic. We hypothesized that HPSE gene expression might be regulated by micro RNA that might be exploited therapeutically. Using miRanda and RNAhybrid, we identified miR-1258 as a candidate micro RNA that may directly target HPSE and suppress BMBC. In support of our hypothesis, we found that miR-1258 levels inversely correlated with heparanase expression, enzymatic activity, and cancer cell metastatic propensities, being lowest in highly aggressive BMBC cell variants compared with either nontumorigenic or nonmetastatic human mammary epithelial cells. These findings were validated by analyses of miR-1258 and heparanase content in paired clinical specimens of normal mammary gland versus invasive ductal carcinoma, and primary breast cancer versus BMBC. In regulatory experiments, miR-1258 inhibited the expression and activity of heparanase in BMBC cells, whereas modulating heparanase blocked the phenotypic effects of miR-1258. In functional experiments, stable expression of miR-1258 in BMBC cells inhibited heparanase in vitro cell invasion and experimental brain metastasis. Together, our findings illustrate how micro RNA mechanisms are linked to brain metastatic breast cancer through heparanase control, and they offer a strong rationale to develop heparanase-based therapeutics for treatment of cancer patients with brain metastases, BMBC in particular.

Asunto(s)

Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/terapia , Neoplasias de la Mama/terapia , Glucuronidasa/genética , MicroARNs/administración & dosificación , Animales , Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/genética , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Terapia Genética , Glucuronidasa/biosíntesis , Humanos , Ratones , Ratones Desnudos , MicroARNs/genética , Terapia Molecular Dirigida , Invasividad Neoplásica , Transfección , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

INTRODUCTION: concurrent toxoplasmosis infection of the brain, spinal cord, and muscle has never been reported together in a patient antemortem. Toxoplasma gondii is the most common focal central nervous system opportunistic infection in the acquired immune deficiency syndrome (AIDS) population. Despite this fact, isolated toxoplasmosis infection in the spinal cord is rarely reported. In addition, toxoplasmic myositis is also rarely diagnosed and Toxoplasma cysts are seldom found on biopsy. We present a patient with AIDS and toxoplasmosis resistant to standard anti-Toxoplasma therapy. CASE REPORT: a 34-year-old man with a history of untreated AIDS presented with symptoms of myelopathy. Pathologically proven toxoplasmosis of the spinal cord was diagnosed and no brain lesions were found. However, despite appropriate treatment and initiation of highly active antiretroviral therapy, the patient developed worsening symptoms, including myopathy and autonomic instability. Muscle biopsy revealed Toxoplasma cysts, and there was laboratory evidence of a restored immune system. CONCLUSION: we report the first case of toxoplasmosis presenting initially with myelitis in the absence of encephalitis that subsequently progressed to myositis despite antiparasitic treatment. We also discuss the possibility of immune reconstitution inflammatory syndrome as a cause of his deterioration.

Asunto(s)

Infecciones Oportunistas Relacionadas con el SIDA/fisiopatología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Síndrome Inflamatorio de Reconstitución Inmune/fisiopatología , Toxoplasmosis/complicaciones , Toxoplasmosis/fisiopatología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/patología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Terapia Antirretroviral Altamente Activa , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/patología , Masculino , Toxoplasmosis/tratamiento farmacológico , Toxoplasmosis/patología , Resultado del Tratamiento

RESUMEN

The purpose of this study was to determine whether the potassium channel, TREK-1, was neuroprotective after traumatic brain injury (TBI). Since there are no selective blockers, we used TREK-1 knockout (KO) mice for our study. Wild-type (WT) and TREK-1 KO mice were anesthetized and subjected to controlled-cortical impact injury (deformation of the brain by 1.5 mm by a 3-mm diameter rod traveling at a 3 m/s). Laser Doppler perfusion (LDP) decreased by ∼80% in the injured cortex and remained at that level in both WT and TREK-1 KO mice (n=10 and 11, respectively). Laser Doppler perfusion decreased by 50% to 60% in cortical areas directly adjacent to the site of injury. There were no statistical differences in LDP between genotype. The contusion volume, determined 15 days after the TBI using hematoxylin and eosin-stained coronal brain sections, was 4.1±0.8 (n=10) and 5.1±0.5 (n=11) mm(3) for WT and TREK-1 KO, respectively (not significant, P=0.34). Cell counts of viable neurons in the CA1 and CA3 regions of the hippocampus were similar between WT and TREK-1 KO mice (P=0.51 and 0.84 for CA1 and CA3, respectively). We conclude that TREK-1 expression does not provide brain protection after TBI.

Asunto(s)

Lesiones Encefálicas/metabolismo , Fármacos Neuroprotectores/metabolismo , Canales de Potasio de Dominio Poro en Tándem/deficiencia , Animales , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Recuento de Células , Supervivencia Celular , Corteza Cerebral/irrigación sanguínea , Hipocampo/patología , Hipocampo/fisiopatología , Flujometría por Láser-Doppler , Masculino , Ratones , Ratones Noqueados , Neuronas/patología , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Flujo Sanguíneo Regional

RESUMEN

The prevalence of HIV is increasing in countries where neurocysticercosis is endemic. Co-infection rates are expected to rise; however, no systematic reviews of the subject are available. We performed a literature review of neurocysticercosis (NCC) occurring in HIV-infected patients and described the clinical and immunophenotypic characteristics of a NCC case presenting with probable immune reconstitution inflammatory syndrome. We identified 27 cases of NCC-HIV co-infection. The most frequent presentation (61%) was with multiple parenchymal lesions. Seven patients (30%) had other concomitant neurologic infections (e.g., tuberculosis, toxoplasmosis). Thirteen patients received cysticidal therapy, and 85% responded to therapy. Only three patients died (12%). Immunohistochemistry of brain tissue in our case revealed abundant CD3+, CD8+, and CD68+ cells. NCC should be included in the differential diagnosis of neurologic infections in HIV patients in endemic populations. Consideration of the patient's immune status should alert the clinician to potential atypical presentations.

Asunto(s)

Infecciones por VIH/diagnóstico , Neurocisticercosis/diagnóstico , Adulto , Recuento de Linfocito CD4 , Infecciones por VIH/complicaciones , Humanos , Inmunohistoquímica , Masculino , Neurocisticercosis/complicaciones , Neurocisticercosis/diagnóstico por imagen , Neurocisticercosis/patología , Neurocisticercosis/cirugía , Tomografía Computarizada por Rayos X , Carga Viral