Cell-based treatments have been considered a promising therapy for neurological diseases. However, currently there are no clinically available methods to monitor whether the transplanted cells reach ...and remain in the brain. In this study we investigated the feasibility of detecting the distribution and homing of autologous bone-marrow mononuclear cells (BMMCs) labeled with Technetium-99 m (
99mTc) in a cell-based therapy clinical study for chronic ischemic stroke. Six male patients (ages 24–65 years) with ischemic cerebral infarcts within the middle cerebral artery (MCA) between 59 and 82 days were included. Cell dose ranged from 1.25
×
10
8 to 5
×
10
8. Approximately 2
×
10
7 cells were labeled with
99mTc and intra-arterially delivered together with the unlabeled cells via a catheter navigated to the MCA. None of the patients showed any complications on the 120-day follow-up. Whole body scintigraphies indicated cell homing in the brain of all patients at 2 h, while the remaining uptake was mainly distributed to liver, lungs, spleen, kidneys and bladder. Moreover, quantification of uptake in Single-Photon Emission Computed Tomography (SPECT) at 2 h showed preferential accumulation of radioactivity in the hemisphere affected by the ischemic infarct in all patients. However, at 24 h homing could only distinguished in the brains of 2 patients, while in all patients uptake was still seen in the other organs. Taken together, these results indicate that labeling of BMMCs with
99mTc is a safe and feasible technique that allows monitoring the migration and engraftment of intra-arterially transplanted cells for at least 24 h.
Chronic pain is an important public health issue. Moreover, its adequate management is still considered a major clinical problem, mainly due to its incredible complexity and still poorly understood ...pathophysiology. Recent scientific evidence coming from neuroimaging research, particularly functional magnetic resonance (fMRI) and positron emission tomography (PET) studies, indicates that chronic pain is associated with structural and functional changes in several brain structures that integrate antinociceptive pathways and endogenous modulatory systems. Furthermore, the last two decades have witnessed a huge increase in the number of studies evaluating the clinical effects of noninvasive neuromodulatory methods, especially transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), which have been proved to effectively modulate the cortical excitability, resulting in satisfactory analgesic effects with minimal adverse events. Nevertheless, the precise neuromechanisms whereby such methods provide pain control are still largely unexplored. Recent studies have brought valuable information regarding the recruitment of different modulatory systems and related neurotransmitters, including glutamate, dopamine, and endogenous opioids. However, the specific neurocircuits involved in the analgesia produced by those therapies have not been fully elucidated. This review focuses on the current literature correlating the clinical effects of noninvasive methods of brain stimulation to the changes in the activity of endogenous modulatory systems.
•Intravascular devices are widely used in neonatal units.•Neonatal sepsis is the most frequent infection in neonatal units.•Central venous catheters are the main risk factor for neonatal sepsis.•The ...diagnosis of catheter-related bloodstream infection remains challenging.
We found that low birth weight and type of central venous catheter were associated with catheter-related bloodstream infection in neonates. In the multivariate analysis, only central venous catheter type (dissected veins, tunneled catheters, and short-term nontunneled catheters) remained significantly associated with catheter-related bloodstream infection.
Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent ...studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (
Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat
Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.
The use of broad-spectrum antimicrobials, such as third and fourth-generation, are responsible for emergence of multidrug-resistant microorganisms in neonatal units. Furthermore, antimicrobial daily ...doses are not standardized in neonatology. This study aimed to investigate the association between the use of antimicrobial broad spectrum to bacterial sensitivity profile in a referral unit of neonatal progressive care.
This is a cohort study conducted in a referral neonatal progressive care unit from January 2008 to December 2016. The data of all hospitalized neonates was collected daily. The infection criteria used were the standardized national criteria, based on definitions of Center for Diseases Control and Prevention. In this study, the use of antimicrobials was evaluated as antimicrobial-day (ATM-day) and the ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was also calculated. The study was approved by the Institutional Review Board of the Universidade Federal de Minas Gerais (ETIC 312/08 e CAAE 58973616.2.0000.5149).
From 2008 to 2016, 2751 neonates were hospitalized, corresponding to 60,656 patient-days. The ratio of multidrug-resistant microorganisms per 1000 ATM-day of broad spectrum was 1,3 in the first period and 4,3 in the second period (p=0,005).
It was observed that use of broad-spectrum antimicrobials, especially those with coverage for Gram-negative bacteria, was associated with an increase of multidrug-resistant bacteria.
Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, ...intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS <8, modified Rankin Scale scores of 0–1 in patients with NIHSS 8–14, or modified Rankin Scale scores 0–2 in patients with NIHSS >14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.
Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in ...the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.
Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. ...Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.
Abstract Objective: To evaluate the accuracy of preoperative positron emission tomography/computed tomography with 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA PET/CT) for staging ...prostate cancer and compare it with magnetic resonance imaging (MRI) using histopathology of surgical specimens as the gold standard. Materials and Methods: In this retrospective study, 65 patients with prostate cancer were analyzed. Results: The accuracy of 68Ga-PSMA PET/CT for tumor detection was 95%, and that of MRI was 91%. There was no difference between 68Ga-PSMA PET/CT and MRI regarding localization of the lesion. The sensitivity of 68Ga-PSMA PET/CT for detecting extraprostatic extension was quite low (14%). For detection of seminal vesicle invasion, 68Ga-PSMA PET/CT showed a sensitivity of 57% and accuracy of 91%. There was a moderate correlation between the maximum standardized uptake value (SUVmax) and the serum level of prostate-specific antigen (p < 0.01; ρ = 0.368) and between the SUVmax and the International Society of Urological Pathology (ISUP) grade (p < 0.01; ρ = 0.513). Conclusion: 68Ga-PSMA PET/CT is a promising tool for detecting and evaluating the primary tumor, which can alter the staging and management of the disease.
Resumo Objetivo: Avaliar a acurácia da tomografia por emissão de pósitrons/tomografia computadorizada com PSMA (PET-PMSA) pré-operatória para estadiamento do câncer de próstata e compará-la com a ressonância magnética (RM) utilizando o histopatológico cirúrgico como padrão ouro. Materiais e Métodos: Neste estudo retrospectivo foram analisados 65 pacientes com câncer de próstata. Resultados: A acurácia da PET-PSMA para a detecção tumoral foi de 95% e a da RM foi de 91%. Não houve diferença entre a PET-PSMA e a RM quanto à localização da lesão. A PET-PSMA apresentou baixa sensibilidade (14%) para detecção de extensão extraprostática em comparação ao histopatológico. Para detecção de invasão de vesícula seminal, a PET-PSMA apresentou sensibilidade de 57% e acurácia de 91% em comparação ao histopatológico. Houve correlação moderada entre o SUVmax e o PSA (p < 0,01; ρ = 0,368) e entre o SUVmax e o ISUP (p < 0,01; ρ = 0,513). Conclusão: A PET-PSMA é uma ferramenta promissora para detecção e avaliação do tumor primário, alterando o estadiamento e a conduta do paciente.
Myasthenia gravis (MG) is an uncommon autoimmune disease mediated by antibodies that attack the postsynaptic acetylcholine receptors (AchRs) at the neuromuscular junction, causing fluctuating muscle ...weakness, aggravated with use, and relieved with rest.
A 32-year-old woman with a diagnosis of MG based on clinical findings, eletroneuromyography, and brain magnetic resonance imaging (MRI) was admitted to our hospital with dysphagia, dysphonia, diplopia, and intense weakness, associated with a 2-day viral gastroenteritis.
Physical examination revealed globally reduced deep tendon reflexes, and tetraparesis, with muscle strength grade 4 in the left limbs and grade 2 in the right limbs. Autoantibody dosing against AchR was elevated and computed tomography scan of the thorax revealed a thymic remnant.
Pyridostigmine and human immunoglobulin were infused.
After 7 days of the reintroduction of pyridostigmine and human immunoglobulin infusion, the patient developed complete resolution of symptoms, being discharged from the hospital. Her symptoms are still well controlled 6 months later. The patient was evaluated by a thoracic surgeon and is awaiting elective thymectomy.
Although our patient presented all the diagnostic criteria of MG, the markedly asymmetric limb weakness presented in previous history and clinical examination of admission was an unusual and unexpected presentation, especially considering the pathophysiology of the disease. MRI of brain without abnormalities was fundamental to rule out another associated etiology. Our review of the literature revealed just 1 case report of MG with similar presentation. This clinical manifestation becomes valuable because it contributes to the list of unexpected presentation that should motivate its suspicion.
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