Corrigendum: Clinical and genetic analysis of Costa Rican patients with Parkinson's disease.

[This corrects the article DOI: 10.3389/fneur.2021.656342.].

Thrombolysis Experience in Costa Rica Compared Against Individual Patient Data from two Randomized Controlled Trials.

OBJECTIVES: We sought to compare thrombolysis outcomes from the Costa Rican Stroke Registry Program (CRSRP) with published individual patient data from NINDS and CLOTBUST-ER trials using matching and outcome modeling from randomized clinical trials (RCTs). MATERIALS AND METHODS: A retrospective observational study matching subjects on baseline characteristics, from the CRSRP, the control arm of CLOTBUST-ER, and the interventional arm of NINDS trials. Day 7-10/discharge modified Rankin Score (mRS), and early mortality was compared between matched subjects. A mortality model derived from RCTs was developed, and outcomes were compared at similar baseline NIHSS scores. CRSRP symptomatic hemorrhage (SICH) rate was compared with an Ibero-American cohort (IAC). RESULTS: Of 540 CRSRP patients, 351 received rt-PA under 3 hours and were matched with NINDS subjects yielding 292 pairs; 161 CRSRP subjects treated within 4.5 hours were matched with CLOTBUST-ER subjects resulting in 151 pairs. The proportion of patients achieving excellent outcomes (mRS 0-1) did not differ between CRSRP and either NINDS or CLOTBUST-ER (CRSRP vs NINDS: 36.6% vs 32.9%, p=0.3; CRSRP vs CLOTBUST-ER: 26.5% vs 24.5%, p=0.8). Mortality was higher for CRSRP vs CLOTBUST-ER (7.3% vs 0.7%, p=0.006), but not vs NINDS (6.5% vs 4.5%, p=0.4). A pooled mortality model derived from 15 RCTs representing 4410 patients (R2=0.39) showed CRSRP and NINDS within expected mortality, while CLOTBUST-ER showed lower than expected mortality. CRSRP SICH rate equaled IAC (5.7% vs 5.7%; p=0.9). CONCLUSIONS: Functional outcomes and SICH of thrombolysed Costa Rican patients compared favorably with published datasets, with a potential increase in early mortality.

Implementation of systematic safety checklists in a neurocritical care unit: a quality improvement study.

BACKGROUND AND OBJECTIVES: Structured and systematised checklists have been shown to prevent complications and improve patient care. We evaluated the implementation of systematic safety checklists in our neurocritical care unit (NCCU) and assessed its effect on patient outcomes. DESIGN/METHODS: This quality improvement project followed a Plan-Do-Study-Act (PDSA) methodology. A checklist for medication reconciliation, thromboembolic prophylaxis, glycaemic control, daily spontaneous awakening, breathing trial, diet, catheter/lines duration monitoring and antibiotics de-escalation was implemented during daily patient rounds. Main outcomes included the rate of new infections, mortality and NCCU-length of stay (LOS). Intervened patients were compared with historical controls after propensity score and Euclidean distance matching to balance baseline covariates. RESULTS: After several PDSA iterations, we applied checklists to 411 patients; the overall average age was 61.34 (17.39). The main reason for admission included tumour resection (31.39%), ischaemic stroke (26.76%) and intracerebral haemorrhage (10.95%); the mean Sequential Organ Failure Assessment (SOFA) score was 2.58 (2.68). At the end of the study, the checklist compliance rate throughout the full NCCU stays reached 97.11%. After controlling for SOFA score, age, sex and primary admitting diagnosis, the implementation of systematic checklists significantly correlated with a reduced LOS (ß=-0.15, 95% CI -0.24 to -0.06), reduced rate of any new infections (OR 0.59, 95% CI 0.40 to 0.87) and reduced urinary tract infections (UTIs) (OR 0.23, 95% CI 0.09 to 0.55). Propensity score and Euclidean distance matching yielded 382 and 338 pairs with excellent covariate balance. After matching, outcomes remained significant. DISCUSSION: The implementation of safety checklists in the NCCU proved feasible, easy to incorporate into the NCCU workflow, and a helpful tool to improve adherence to practice guidelines and quality of care measurements. Furthermore, our intervention resulted in a reduced NCCU-LOS, rate of new infections and rate of UTIs compared with propensity score and Euclidean distance matched historical controls.

Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease.

Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls. Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2. Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R. Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.

Acute encephalitis, myoclonus and Sweet syndrome after mRNA-1273 vaccine.

A patient presented with fever, generalised rash, confusion, orofacial movements and myoclonus after receiving the first dose of mRNA-1273 vaccine from Moderna. MRI was unremarkable while cerebrospinal fluid showed leucocytosis with lymphocyte predominance and hyperproteinorrachia. The skin evidenced red, non-scaly, oedematous papules coalescing into plaques with scattered non-follicular pustules. Skin biopsy was consistent with a neutrophilic dermatosis. The patient fulfilled the criteria for Sweet syndrome. A thorough evaluation ruled out alternative infectious, autoimmune or malignant aetiologies, and all manifestations resolved with glucocorticoids. While we cannot prove causality, there was a temporal correlation between the vaccination and the clinical findings.

High-Density Lipoprotein, Mean Platelet Volume, and Uric Acid as Biomarkers for Outcomes in Patients With Sepsis: An Observational Study.

BACKGROUND: We conducted an observational study evaluating the association between uric acid, mean platelet volume (MPV), and high-density lipoprotein (HDL) with complications and outcomes of patients with sepsis in a critical care setting. METHODS: We followed patients with a diagnosis of severe sepsis and septic shock for a maximum of 28 days. Main outcomes assessed included length of stay (LOS), the need for renal replacement therapy (RRT), assisted mechanical ventilation (AMV), and vasopressor support as well as in-unit mortality. RESULTS: The overall average age of the 37 patients enrolled was 48.1 (19.8) years; among them, 37.8% were male. Abdominal related (43.2%) and pulmonary (29.7%) were the main sites of infection. The overall Acute Physiology and Chronic Health Evaluation 2 (APACHE-2) median score was 19 (9-24). Acute kidney injury (AKI) was observed in 46.9% of the sample. In all, 54.1% required vasopressor support, 54.1% AMV, and 35.1% RRT. Patients with bacteremia were significantly more likely to require vasopressor support and those with urinary tract infections were significantly younger. We found increasing ΔMPV levels, higher APACHE-2 scores, lower HDL values, and a reduced age to be associated with a longer LOS. Higher scores on the APACHE-2 scale and lower levels of HDL significantly associated with higher odds for developing AKI. The need for vasopressor support was significantly associated with higher values of 72-hour MPV and with higher levels of baseline uric acid and lower values of initial HCO3. Initial and 72-hour levels of MPV and higher scores in the APACHE-2 were all significantly correlated with the need for AMV. An increased probability of dying during follow-up was significantly correlated with increasing age. CONCLUSION: We were able to establish significant associations between our candidate biomarkers and relevant outcomes for patients with sepsis. Our results support the use of these low-cost biomarkers in the assessment of prognosis of patients with sepsis.

Epidemiology of Stroke in Costa Rica: A 7-Year Hospital-Based Acute Stroke Registry of 1319 Consecutive Patients.

BACKGROUND: Limited data on stroke exist for Costa Rica. Therefore, we created a stroke registry out of patients with stroke seen in the Acute Stroke Unit of the Hospital Calderon Guardia. METHODS: We analyzed 1319 patients enrolled over a 7-year period, which incorporated demographic, clinical, laboratory, and neuroimaging data. RESULTS: The mean age of patients with stroke was 68.0 ± 15.5 years. Seven hundred twenty-five were men and the age range was 13-104 years. The most prevalent risk factors were hypertension (78.8%), dyslipidemia (36.3%), and diabetes (31.9%). Fifteen percent had atrial fibrillation and 24.7% had a previous stroke or transient ischemic attack. Prevalence of hypertension and atrial fibrillation increased with age; however, younger patients were more associated with thrombophilia. We documented 962 (72.9%) ischemic and 270 (20.5%) hemorrhagic strokes. Of the ischemic strokes, 174 (18.1%) were considered secondary to large-artery atherothrombosis, 175 (18.2%) were due to cardiac embolism, 19 (2.0%) were due to lacunar infarcts, and 25 (2.6%) were due to other determined causes. Five hundred sixty-nine (59.1%) remained undetermined. Atherothrombotic strokes were mostly associated with dyslipidemia, diabetes, metabolic syndrome, and obesity, whereas lacunar infarcts were associated with hypertension, smoking, sedentary lifestyle, and previous stroke or transient ischemic attack. Of our patients, 69.9% scored between 0 and 9 in the initial National Institutes of Health Stroke Scale (NIHSS). CONCLUSIONS: We found differences in sociodemographic features, risk factors, and stroke severity among stroke subtypes. Risk factor prevalence was similar to other registries involving Hispanic populations.

A rare neurological complication of Waldenstrom's Macroglobulinemia.

Bilateral and simultaneous facial nerve palsy (FNP) is a rare clinical condition occurring in 0.3-2.0% of facial palsy cases and is typically a manifestation of an underlying systemic disease. We here describe a case of a 67-year-old Hispanic man with a known history of Waldenstrom's Macroglobulinemia (WM) who presented to the clinic with a sub-acute onset of bilateral facial weakness. No alternate etiology for the facial weakness was identified after a thorough diagnostic approach. WM is a rare hematological condition due to low-grade B cell lymphoma, where lymphoplasmacytoid cells infiltrate different tissues and secrete monoclonal IgM. Peripheral neuropathy develops in 15-30% of the cases, being usually a chronic, progressive, symmetric, predominantly distal polyneuropathy. Facial nerve impairment is unusual; however, it could be caused by anoxic damage as a result of an increased blood viscosity from IgM monoclonal gammopathy, direct nerve infiltration of tumorous cells and an antibody (anti-MAG) mediated demyelinating process. Treatment is directed to the established mechanism for neural injury. This report highlights a rare condition (WM) with a rare complication (bilateral facial nerve palsy) and illustrates the broad differential comprised by this presenting complaint.

Spinal epidural empyema extending from a pleural empyema: case description and anatomical overview.

We present a case of a patient with diabetes with a pleural empyema originated from a pyomyositis process established after a central line procedure. This empyema later on extended into the spinal canal deriving into an epidural empyema, leading towards a spinal neurogenic shock and death. We discuss the anatomical substrate for this extension as well as the anatomopathological findings observed in the autopsy.

First clinical and genetic description of a family diagnosed with late-onset Pompe disease from Costa Rica.

Glycogen storage disease type II, also known as Pompe disease, is an autosomal recessive disorder caused by deficiency of enzymatic activity of acid alpha-glucosidase. The wide phenotypical variation of this disease relates to the amount of residual enzymatic activity depending on the combination of mutations on each allele. We confirmed Pompe disease in a patient that presented with progressive weakness, recurrent episodes of respiratory failure associated with pneumonia, a predominantly demyelinating mixed sensorimotor polyneuropathy and paraspinal complex repetitive discharges. Genetic analysis of the GAA gene from this patient revealed two pathogenic compound heterozygous mutations: c.-32-13T>G (rs386834236, intronic), c.2560C>T (rs121907943, p.Arg854Ter); and one variant of unknown significance: c.1551+42G>A (rs115427918, intronic). We found expected mutations in two siblings and two nieces. Genetic variants reported in this family reflect on the European and African ancestry that we carry in our Costa Rican population.

Effect of insulin therapy and dietary adjustments on safety and performance during simulated soccer tests in people with type 1 diabetes: study protocol for a randomized controlled trial.

BACKGROUND: Despite the reduction in glycemic derangement in patients with type 1 diabetes mellitus (T1D) through dietary and therapeutic adjustments implemented before, during and after continuous exercise, evidence for its effectiveness with intermittent forms of exercise, such as soccer, is still lacking. METHODS/DESIGN: We designed a study protocol for a randomized, crossover, double-blinded, controlled trial, for the evaluation of the effect that a strategy of dietary and therapeutic modifications may have on safety and performance of persons with T1D in soccer training sessions and cognitive testing. Inclusion criteria comprise: age older than 18 years, more than 2 years since T1D diagnosis, low C-peptide level, a stable insulin regimen, HbA1c less than 9.0% and regular participation in soccer activities. Our primary outcome evaluates safety regarding hypoglycemia events in patients using dietary and therapeutic adjustments, compared with the performance under the implementation of current American Diabetes Association (ADA) usual recommendations for nutritional and pharmacological adjustments for exercise. Additionally, we will evaluate as secondary outcomes: soccer performance, indexed by performance in well-established soccer skill tests, cognitive functions (indexed by Stroop, digital vigilance test (DVT), Corsi block-tapping task (CBP), and rapid visual information processing (RVIP) tests), and glycemic control measured with a continuous glucose monitor (CGM). DISCUSSION: Dietary and insulin adjustments standardized under a 4-step method strategy have never been tested in a clinical trial setting with intermittent forms of exercise, such as soccer. We hypothesize that through this strategy we will observe better performance by persons with T1D in soccer and cognitive evaluations, and more stable control of glycemic parameters before, during and after exercise execution, indexed by CGM measurements. TRIAL REGISTRATION: ISRCTN, ISRCTN17447843. Registered on 5 January 2017.

Does non-invasive brain stimulation modify hand dexterity? Protocol for a systematic review and meta-analysis.

INTRODUCTION: Dexterity is described as coordinated hand and finger movement for precision tasks. It is essential for day-to-day activities like computer use, writing or buttoning a shirt. Integrity of brain motor networks is crucial to properly execute these fine hand tasks. When these networks are damaged, interventions to enhance recovery are frequently accompanied by unwanted side effects or limited in their effect. Non-invasive brain stimulation (NIBS) are postulated to target affected motor areas and improve hand motor function with few side effects. However, the results across studies vary, and the current literature does not allow us to draw clear conclusions on the use of NIBS to promote hand function recovery. Therefore, we developed a protocol for a systematic review and meta-analysis on the effects of different NIBS technologies on dexterity in diverse populations. This study will potentially help future evidence-based research and guidelines that use these NIBS technologies for recovering hand dexterity. METHODS AND ANALYSIS: This protocol will compare the effects of active versus sham NIBS on precise hand activity. Records will be obtained by searching relevant databases. Included articles will be randomised clinical trials in adults, testing the therapeutic effects of NIBS on continuous dexterity data. Records will be studied for risk of bias. Narrative and quantitative synthesis will be done. ETHICS AND DISSEMINATION: No private health information is included; the study is not interventional. Ethical approval is not required. The results will be reported in a peer-review journal. REGISTRATION DETAILS: PROSPERO International prospective register of systematic reviews registration number: CRD42016043809.

Detección del receptor tipo 2 del factor de crecimiento epidérmico humano (her2/neu): inmunohistoquímica en carcinomas de mama / Human epidermal growth factor receptor type 2 (her2/neu) immunohistochemical detection in breast carcinoma

Antecedentes: la incidencia y mortalidad por cáncer de mama han presentado un aumento neto. Uno de los tipos de esta heterogénea enfermedad se caracteriza por la amplificación y alta expresión del gen ERBB2, que codifica el receptor tipo 2 del factor de crecimiento epidérmico humano (HER2). Este receptor estimula procesos oncogénicos y dichos tumores se asocian a un peor pronóstico. El objetivo del estudio fue analizar las características de tumores HER-2+ en un grupo de pacientes con carcinoma de mama. Métodos: se estudió los casos de mujeres con biopsia diagnóstica de cáncer de mama registrados durante 2006 en los archivos del Servicio de Anatomía Patológica del Hospital San Juan de Dios; entre los que contaban con estudios inmunohistoquímicos, se estudió la expresión de HER-2 y se realizó análisis estadísticos. Resultados: se halló 34 tumores HER-2+ (15,7%), 24 con expresión fuerte (11,1%) y 10 con débil (4,6%). La edad media al diagnóstico de las pacientes con expresión fuerte fue de 46,9 años (42,5-51,1 IC 95%), y con expresión débil fue de 54,4 años (46,7-62,1 IC 95%); la edad promedio para los tumores HER-2- fue de 58,1 años (56,2-60,0 IC 95%). Las pacientes <50 años tuvieron un OR=3,477 de tener HER-2+. De 21 tumores, el 90,5% presentó un grado histológico alto, y de 16 casos, únicamente 3 tenían un tamaño <2 cm. Conclusión: se encontró una asociación del tipo HER-2+ con pacientes jóvenes, tumores de mayor tamaño y alto grado histológico. Los datos encontrados en este primer reporte son similares a las últimas estimaciones mundiales.

Background: The incidence and mortality due to breast cancer has suffered a net increase. One type of this heterogeneous disease is characterized by an amplification and higher expression of the ERBB2 gene that codifies for human epidermal growth factor receptor type 2 (HER-2). This receptor mediates oncogenic processes and such tumors have been associated with a worse prognosis. The aim of this study was to analyze the characteristics of HER-2+ tumors in a group of patients with breast cancer. Methods: This study included cases of breast cancer diagnosed through biopsy, registered during 2006 in the archives of the Pathology Department of the San Juan de Dios Hospital. The HER-2 expression was studied and statistical analyses were performed in cases that had immunohistochemical studies. Results: Thirty-four HER-2+ tumors were found (15.7 %), 24 with a strong expression (11.1%) and 10 with a weak expression (4.6%). The average age at diagnosis of patients with a strong expression was 46.9 years (42.5-51.1 IC 95%) and in those with a weak expression, 54.4 years (46.7-62.1 IC 95%). In the case ofHER-2- tumors, de mean age at diagnosis was 58.1 years (56.2-60.0 IC 95%). Patients <50 years had an OR=3.477 of having HER-2+. Out of 21 tumors, 90.5% showed a high histologic grade and out of 16 cases, only 3 measured <2 cm. Conclusion: The data found is similar to the latest global statistics. An association was found between HER-2+ type tumor and young patients, larger size tumors and higher histologic grade.