Atypical Hemolytic Uremic Syndrome in a Patient With Bothrops asper Envenomation.

Bothrops asper envenomation is common in Colombia and is characterized by local tissue injury and venom-induced consumption coagulopathy (VICC). Rarely, thrombotic microangiopathy is associated with envenomation by this species. The case of a 57-y-old man with B asper bite and envenomation on the left foot is presented. The patient was admitted 8 h after the event and progressively developed edema, hemorrhage at the site of the bite, and hemorrhagic blisters. His coagulation test results (prothrombin and partial thromboplastin times) were prolonged, and his fibrinogen levels were severely reduced. The diagnosis of VICC was made. Administration of Colombian polyvalent viper antivenom controlled the VICC within a few hours. Subsequently, the patient developed severe microangiopathic anemia, thrombocytopenia, and acute kidney injury. A diagnosis of thrombotic microangiopathy was made, and the patient met the criteria for hemolytic uremic syndrome. Management with hemodialysis in addition to therapeutic plasma exchange and replacement with fresh frozen plasma was indicated. The patient's condition resolved 14 d later. To the best of our knowledge, this is the first case of B asper envenomation in which the patient presented with hemolytic uremic syndrome after VICC. A proposal is made regarding the pathogenesis of this chain of events.

Nose-to-Brain Delivery of Dexamethasone: Biodistribution Studies in Mice.

Neuroinflammation (NI) is an important physiologic process which promotes the tissue repair and homeostatic maintenance in the central nervous system after different types of insults. However, when it is exacerbated and sustained in time, NI plays a critical role in the pathogenesis of different neurologic diseases. The high systemic doses required for brain-specific targeting lead to severe undesirable effects. The intranasal (IN) route has been proposed as an alternative drug administration route for a better NI control. Herein, the brain biodistribution of intranasally administered dexamethasone versus intravenously administered one is reported. A higher amount of dexamethasone was found in every analyzed region of those brains of intranasally administered mice. HPLC analysis also revealed that IN administration allows Dex to arrive faster and in a greater concentration to the brain in comparison with intravenous administration, data confirmed by immunofluorescence and HPLC analysis. These data support the proposal of the IN administration of Dex as an alternative for a more efficient control of NI. SIGNIFICANCE STATEMENT: This work highlights the biodistribution of dexamethasone after its intranasal administration. Intranasal administration allows for a faster arrival, better distribution, and a higher concentration of the drug within the brain compared to its intravenous administration. These results explain some of the evidence shown in a previous work in which dexamethasone controls neuroinflammation in a murine stroke model and can be used to propose alternative treatments for neuroinflammatory diseases.

Rituximab for Inflammatory Myopathies in a Colombian Cohort.

INTRODUCTION/OBJECTIVES: Rituximab (RTX) is a treatment for refractory inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). This study describes the characteristics of patients receiving RTX for myositis in our institution to evaluate its efficacy. METHOD: We collected demographic data from all patients diagnosed with DM or PM who received RTX between 2011 and 2018. Clinical and serological variables (including creatine phosphokinase [CPK] levels) were analyzed. Remission of disease was defined as no evidence of disease activity (active myositis) for longer than a 6-month continuous period while undergoing myositis therapy or no medication. RESULTS: Eighteen patients who had received first-line immunosuppressants were included. Fifteen (83%) had DM, 2 (11%) had PM, 1 had juvenile dermatomyositis, and 14 (77%) were women. All patients received glucocorticoids. Three patients (16.6%) were treated with RTX as monotherapy, and 15 (83.3%) were treated with RTX combined with other immunosuppressants. On average, there were 2 RTX treatment cycles. Improved muscular weakness was found in 13 cases (72%), and improved serum CPK levels were found in 15 cases (83%). Twelve patients (66%) achieved remission. CONCLUSIONS: Most patients experienced an objective improvement, as reflected in their serum CPK values and degree of muscular weakness. This suggests that RTX could be helpful in treating refractory myositis.

Systemic Sclerosis at an Intensive Care Unit: A Case Series and Literature Review.

INTRODUCTION: Systemic sclerosis (SSc) is a multisystemic autoimmune disease. Few studies have focused on the outcomes of SSC patients who require intensive care unit (ICU) admission, largely due to the absence of protocols for the optimal management of this disease during an ICU stay. OBJECTIVES: This study aimed to describe the outcomes of a series of SSc patients admitted to the ICU at a single center in Cali, Colombia. METHODS: Case series of SSc patients admitted to the ICU were reviewed. The main outcome was ICU mortality. Statistical analysis was performed with measures of central tendency and proportions. RESULTS: All the patients (n = 14) were female and either middle-aged or elderly; 9 (64%) were diagnosed with diffuse cutaneous sclerosis, and the remaining 5 patients with limited cutaneous sclerosis. Some were readmitted; therefore, the total number of ICU admissions was 21. The principal causes of ICU admissions were non-SSc-related causes (n = 15 [71.4%]). The respiratory system was the most involved on ICU admissions. The ICU mortality rate was 43% (n = 6). CONCLUSIONS: The severity of the disease at ICU admission and comorbidity are independently associated with ICU-related mortality. Furthermore, the optimal management of SSc patients includes accurate detection of SSc-associated organ involvement. More studies involving this category of patients are needed to establish the best effective protocols.

Geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples, and its possible relationship with the prevalence of enamel fluorosis in children in four municipalities of the department of Huila (Colombia).

Fluoride is an element that affects teeth and bone formation in animals and humans. Though the use of systemic fluoride is an evidence-based caries preventive measure, excessive ingestion can impair tooth development, mainly the mineralization of tooth enamel, leading to a condition known as enamel fluorosis. In this study, we investigated the geochemical characterization of fluoride in water, table salt, active sediment, rock and soil samples in four endemic enamel fluorosis sentinel municipalities of the department of Huila, Colombia (Pitalito, Altamira, El Agrado and Rivera), and its possible relationship with the prevalence of enamel fluorosis in children. The concentration of fluoride in drinking water, table salt, active sediment, rock, and soil was evaluated by means of an ion selective electrode and the geochemical analyses were performed using X-ray fluorescence. Geochemical analysis revealed fluoride concentrations under 15 mg/kg in active sediment, rock and soil samples, not indicative of a significant delivery to the watersheds studied. The concentration of fluoride in table salt was found to be under the inferior limit (less than 180 µg/g) established by the Colombian regulations. Likewise, exposure doses for fluoride water intake did not exceed the recommended total dose for all ages from 6 months. Although the evidence does not point out at rocks, soils, fluoride-bearing minerals, fluoridated salt and water, the hypothesis of these elements as responsible of the current prevalence of enamel fluorosis cannot be discarded since, aqueducts might have undergone significant changes overtime.

Subcortical (thalamic) automated seizure detection: A new option for contingent therapy delivery.

The feasibility of automated detection of cortical-onset epileptic seizures from subcortical structures such as the thalamus was investigated via simultaneous recording of electroencephalography (EEG) and anterior and centromedian thalamic nuclei electrical signals (electrothalamography) in nine subjects with pharmacoresistant seizures admitted to an epilepsy monitoring unit after deep brain stimulating electrode implantation. Thalamic electrical signals were analyzed using a validated seizure detection algorithm, and times of seizure onset and termination were compared to those determined through visual analysis of video-EEG. Ictal activity was recorded from the scalp and thalamic nuclei in three subjects who had seizures during the 3-4-day recording period. In the majority of seizures, ictal activity in the thalamic nuclei preceded electrographic onset as determined from the EEG or clinical onset as determined from behavioral observations. Interictal epileptiform discharges were also recorded from the thalamus and in certain instances had no scalp representation. Subcortical/thalamic detection of cortical-onset seizures is feasible. This approach would enable contingent therapy delivery and may be particularly valuable for subjects with multiple or difficult-to-localize epileptogenic regions.

Competition for neuronal processing time: a physiological seizure control mechanism?

Cognitive means for seizure control remain underinvestigated in clinical epileptology. Since administration of a complex reaction time (CRT) test triggered by a seizure detection algorithm is a unique research paradigm, its effects on seizure frequency and severity were examined in 14 subjects undergoing invasive epilepsy surgery evaluation. These variables were compared with those of 37 subjects evaluated using the same surgical protocol, but to whom the CRT test was not administered. The results were analyzed for statistical significance using the t-test and the chi-squared test. Eight of fourteen subjects who took the CRT test had fewer than 5 clinical seizures, and 7 of 14 subjects had fewer than 5 clinical and subclinical seizures over 8.9 days compared with 37 subjects who did not take this test, each of whom had a minimum of 5 clinical seizures over 6.7 days (chi-square=25.08; p<0.001). The monitoring duration difference (2.2 days longer for CRT test takers) was statistically significant (p~0.04). In one subject, seizure severity was lower (p<0.001) during testing compared with nontesting periods. It is posited that seizure frequency reduction is a beneficial, unconditioned, and, probably, contingent effect of the CRT test. These and other experimental observations form the basis for a hypothetical physiological antiseizure mechanism, the "competition for neuronal processing time".

Severe cerebral edema related to oral methadone: A case report and literature review.

Introduction: Opioids are widely used for pain management, and increased intracranial pressure (ICP) has been evidenced in some cases. We reported a patient with severe cerebral edema after initiating methadone and its complete resolution upon discontinuing the medication. Additionally, a review of the literature is made. Case report: A 53-year-old woman patient with a history of systemic lupus erythematosus developed mechanic chronic lower back pain, refractory to conventional treatments. She presented improvement with oxycodone. She withdrew this medication due to a lack of supplies in her country (Colombia) and showed withdrawal symptoms. She consulted the emergency department, where oral methadone was started and symptom control was achieved. Three days after admission, she presented intense headaches and emesis. A brain CT scan was performed in which severe cerebral edema was appreciated. Methadone was discontinued, and neurological symptoms quickly disappeared. A follow-up brain CT scan was performed later, finding full resolution of the edema. Conclusion: A case of severe cerebral edema associated with the initiation of oral methadone and its rapid resolution without neurological sequelae after its withdrawal is presented, clinicians must be attentive to this adverse event.

Viperidae snake envenomation from a highly complex hospital in southwestern Colombia.

Background: Snake envenomation is a medical condition with high morbidity and mortality in southwestern Colombia. Objectives: To describe the characteristics of the envenomation caused by Viperidae snakes view in a highly complex hospital in Southwestern Colombia. Methods: A cross-sectional study was carried out. Patients treated for Viperidae snake envenomation from 2001 to 2020 in a Hospital Fundación Valle del Lili, Cali, Colombia, were studied. Results: Twenty-eight patients were included. Envenomation was caused by the genera Bothrops, Bothriechis, Porthidium, and Bothrocophias. The median age was 37.7 (±20.6), and they were predominantly male (19, 68%). Bites occurred on the upper extremities in 16 (57%) patients. Pain (23, 81%) and edema (22, 78%) were the most common clinical symptoms. Thirteen (46%) patients presented coagulopathy. Prolonged prothrombin and activated partial thromboplastin times were common: (22, 78% and 15, 53%, respectively). Twenty (71%) patients were treated with polyvalent antivenom (median dose of 6 (2-15) vials). The median time between the accident and antivenom administration was 9 h (5.5-17). Door-to-needle time was 37.5 (0-62) min. Eighteen (64%) patients were admitted to the intensive care unit. Three (11%) patients had serum sickness. Seven (25%) developed infectious complications, four (14%) had surgery, one (3%) had compartment syndrome, one (3%) underwent amputation of the affected limb, and one (3%) patient died. Conclusions: Local manifestations and coagulopathy were common clinical features. Polyvalent antivenom was an effective treatment for disease control. Significant complications were associated with delays in seeking medical care.

Microperfusion of 3-MPA into the brain augments GABA.

In vivo effects of microperfusion of a GABA synthesis inhibitor (3-MPA) into the striatum and hippocampus on amino acid concentrations and electrical neuronal activity were investigated. Paradoxical elevations in GABA in the striatum (5-fold in anesthetized and 50-fold in awake rats) and hippocampus (2-fold in anesthetized and 15-fold in awake rats) were documented under steady-state concentrations of 3-MPA along with expected increases in glutamate (a 15-fold increase and a 250-fold increase in the striatum of anesthetized and awake rats, respectively; a 7-fold increase and a 25-fold increase in the hippocampus of anesthetized and awake rats, respectively). There was no clear epileptiform or seizure activity. Explanations for the paradoxical increase in GABA are offered, and emphasis is placed on the dependency of disinhibition on the model in which its effects are studied as well as on the prevailing level of activation of the probed network.

Eosinophil-related diseases during treatment with glucagon-like peptide one receptor (GLP-1 RA): a case report and review of the literature.

Glucagon-like peptide one-receptor agonists (GLP-1 RA) are drugs that differ in their pharmacological composition and homology to human GLP-1 and are used most frequently for the treatment of type 2 diabetes and weight loss. There are isolated reports of eosinophilic adverse reactions associated with GLP-1 RA. We present the case of a 42-year-old female patient who, after starting weekly subcutaneous semaglutide, developed eosinophilic fasciitis with favorable clinical evolution after the discontinuation of semaglutide and the initiation of immunosuppression. A review of the eosinophilic adverse events that have been previously reported with GLP-1 RA is provided.

Standardizing an Experimental Murine Model of Extraparenchymal Neurocysticercosis That Immunologically Resembles Human Infection.

BACKGROUND: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. METHODS: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. RESULTS: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. CONCLUSIONS: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.

Improvement of the autoimmune phenomenon after treatment of primary hyperparathyroidism: Possible role of dynamics of parathyroid hormone-1-receptor in B-lymphocytes.

We report a case of 65-year-old male patient with primary hyperparathyroidism (PHPT) who was admitted to the hospital for autoimmune manifestations (including autoimmune hepatitis and autoantibody development) and exhibited subsequent clinical and paraclinical improvement after parathyroidectomy. By flow cytometry, the expression of PTH receptor 1 (PTHR1) on B lymphocytes of peripheral blood was documented to be higher than that in healthy controls. After parathyroidectomy, autoimmune manifestations improved, while PTH1R expression on B-lymphocytes increased. The possible role of the dynamics of B-lymphocyte PTHR1 in the development of this autoimmune phenomenon is discussed.