Value contribution of blood-based neurofilament light chain as a biomarker in multiple sclerosis using multi-criteria decision analysis.

Introduction: Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease that represents a leading cause of non-traumatic disability among young and middle-aged adults. MS is characterized by neurodegeneration caused by axonal injury. Current clinical and radiological markers often lack the sensitivity and specificity required to detect inflammatory activity and neurodegeneration, highlighting the need for better approaches. After neuronal injury, neurofilament light chains (NfL) are released into the cerebrospinal fluid, and eventually into blood. Thus, blood-based NfL could be used as a potential biomarker for inflammatory activity, neurodegeneration, and treatment response in MS. The objective of this study was to determine the value contribution of blood-based NfL as a biomarker in MS in Spain using the Multi-Criteria Decision Analysis (MCDA) methodology. Materials and methods: A literature review was performed, and the results were synthesized in the evidence matrix following the criteria included in the MCDA framework. The study was conducted by a multidisciplinary group of six experts. Participants were trained in MCDA and scored the evidence matrix. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. Results: MS was considered a severe condition as it is associated with significant disability. There are unmet needs in MS as a disease, but also in terms of biomarkers since no blood biomarker is available in clinical practice to determine disease activity, prognostic assessment, and response to treatment. The results of the present study suggest that quantification of blood-based NfL may represent a safe option to determine inflammation, neurodegeneration, and response to treatments in clinical practice, as well as to complement data to improve the sensitivity of the diagnosis. Participants considered that blood-based NfL could result in a lower use of expensive tests such as magnetic resonance imaging scans and could provide cost-savings by avoiding ineffective treatments. Lower indirect costs could also be expected due to a lower impact of disability consequences. Overall, blood-based NfL measurement is supported by high-quality evidence. Conclusion: Based on MCDA methodology and the experience of a multidisciplinary group of six stakeholders, blood-based NfL measurement might represent a high-value-option for the management of MS in Spain.

[Translated Article] Disease-modifying treatments for patients with multiple sclerosis in Spain.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system and long-term disabling. Different disease-modifying treatments are available. These patients, despite being generally young, have high comorbidity and risk of polymedication due to their complex symptomatology and disability. OBJECTIVE PRIMARY: To determine the type of disease-modifying treatment in patients seen in Spanish hospital pharmacy departments. SECONDARY OBJECTIVES: to determine concomitant treatments, determine the prevalence of polypharmacy, identify the prevalence of interactions and analyze pharmacotherapeutic complexity. METHOD: Observational, cross-sectional, multicentre study. All patients with a diagnosis of multiple sclerosis and active disease-modifying treatment who were seen in outpatient clinics or day hospitals during the second week of February 2021 were included. Modifying treatment, comorbidities and concomitant treatments were collected to determine multimorbidity pattern, polypharmacy, pharmacotherapeutic complexity (Medication Regimen Complexity Index) and drug-drug interactions. RESULTS: 1407 patients from 57 centres in 15 autonomous communities were included. The most frequent form of disease presentation was the relapsing remitting form (89.3%). The most prescribed disease-modifying treatment was dimethyl fumarate (19.1%), followed by teriflunomide (14.0%). Of the parenteral disease-modifying treatments, the two most prescribed were glatiramer acetate and natalizumab with 11.1% and 10.8%. 24.7% of the patients had 1 comorbidity and 39.8% had at least 2 comorbidities. 13.3% belonged to at least one of the defined patterns of multimorbidity and 16.5% belonged to 2 or more patterns. The concomitant treatments prescribed were psychotropic drugs (35.5%); antiepileptic drugs (13.9%) and antihypertensive drugs and drugs for cardiovascular pathologies (12.4%). The presence of polypharmacy was 32.7% and extreme polypharmacy 8.1%. The prevalence of interactions was 14.8%. Median pharmacotherapeutic complexity was 8.0 (IQR: 3.3-15.0). CONCLUSIONS: We have described the disease-modifying treatment of patients with multiple sclerosis seen in Spanish pharmacy services and characterized concomitant treatments, the prevalence of polypharmacy, interactions, and their complexity.

Disease-modifying treatments for patients with multiple sclerosis in Spain. / Tratamientos modificadores de la enfermedad en pacientes con esclerosis múltiple en España.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system and long-term disabling. Different disease-modifying treatments are available. These patients, despite being generally young, have high comorbidity and risk of polymedication due to their complex symptomatology and disability. OBJECTIVE PRIMARY: To determine the type of disease-modifying treatment in patients seen in Spanish hospital pharmacy departments. SECONDARY OBJECTIVES: To determine concomitant treatments, determine the prevalence of polypharmacy, identify the prevalence of interactions and analyse pharmacotherapeutic complexity. METHOD: Observational, cross-sectional, multicentre study. All patients with a diagnosis of multiple sclerosis and active disease-modifying treatment who were seen in outpatient clinics or day hospitals during the second week of February 2021 were included. Modifying treatment, comorbidities and concomitant treatments were collected to determine multimorbidity pattern, polypharmacy, pharmacotherapeutic complexity (Medication Regimen Complexity Index) and drug-drug interactions. RESULTS: 1,407 patients from 57 centres in 15 autonomous communities were included. The most frequent form of disease presentation was the relapsing remitting form (89.3%). The most prescribed disease-modifying treatment was dimethyl fumarate (19.1%), followed by teriflunomide (14.0%). Of the parenteral disease-modifying treatments, the two most prescribed were glatiramer acetate and natalizumab with 11.1% and 10.8%. 24.7% of the patients had one comorbidity and 39.8% had at least 2 comorbidities. 13.3% belonged to at least one of the defined patterns of multimorbidity and 16.5% belonged to 2 or more patterns. The concomitant treatments prescribed were psychotropic drugs (35.5%); antiepileptic drugs (13.9%) and antihypertensive drugs and drugs for cardiovascular pathologies (12.4%). The presence of polypharmacy was 32.7% and extreme polypharmacy 8.1%. The prevalence of interactions was 14.8%. Median pharmacotherapeutic complexity was 8.0 (IQR: 3.3 -- 15.0). CONCLUSIONS: We have described the disease-modifying treatment of patients with multiple sclerosis seen in Spanish pharmacy services and characterised concomitant treatments, the prevalence of polypharmacy, interactions, and their complexity.

Comparative study of in vitro activity of tedizolid and linezolid against Mycobacterium avium complex.

OBJECTIVES: The aim of this study is to compare the in vitro activity and minimal inhibitory concentration (MIC) distributions of tedizolid and linezolid against Mycobacterium avium complex (MAC) strains using a reference broth microdilution assay and a macrodilution assay with the Bactec-MGIT-960. METHODS: A total of 37 clinical isolates of MAC were included in the study. Reference broth microdilution was performed according to CLSI guidelines in a range of concentrations from 64 to 0.064 mg/L. Macrodilution was performed with the Bactec-MGIT-960 system. The cut-off points defined by CLSI for linezolid (resistant: > 16 mg/L, intermediate: 16 mg/L, susceptible: <16 mg/L) were used to define clinical categories of this drug. Essential agreement for both linezolid and tedizolid and categorical agreement for linezolid were defined following FDA criteria. RESULTS: The MIC50 (16mg/L) and MIC90 (32mg/L) values for linezolid were identical with both methods. However, the MIC50 and MIC90 of tedizolid by microdilution (4 mg/L and 8 mg/L, respectively) were one twofold dilution higher than by macrodilution (2 mg/L and 4 mg/L, respectively). Ninety-four percent and 2.7% of the strains had MICs of tedizolid ≤4 mg/L and ≤ 0.5 mg/L, respectively, by the reference method. The linezolid macrodilution assay showed a categorical agreement of 40.5%, a minor error rate of 56.7% and a major error rate of 2.7% with respect to the reference method. CONCLUSIONS: Tedizolid showed higher in vitro activity than linezolid against the tested MAC isolates. Macrodilution using the BD Bactec-MGIT-960 system is a practical approach to determine the susceptibility of MAC strains to tedizolid.

Patient Experience Evaluation of the CMO-Based Pharmaceutical Care Model vs Usual Care in People Living with HIV.

Objective: To compare patient experience in a real-life population of people living with HIV (PLWH) who received pharmaceutical care (PC) based on the Capacity-Motivation-Opportunity (CMO) model versus the traditional model. Methods: Prospective cohort study in PLWH receiving either CMO-based PC or traditional PC in Spain between October 2019 and June 2021 (24 weeks), performed by the pharmacy department of 14 Spanish hospitals. Participants were adult patients with a clinical diagnosis of HIV treated with antiretrovirals who had been monitored in the participating hospital pharmacies for >1 year. Patient experience (IEXPAC questionnaire), clinical outcomes (cholesterol, triglycerides, HDL, glycated haemoglobin, and blood pressure), adherence to treatment, virologic control and patient satisfaction were determined. Results: Patient experience in the CMO group at week 24 was significantly better (7.6 vs 6.9) than in the traditional group, with a higher mean improvement. Adherence was better in the CMO group, particularly with regard to concomitant medications (53.2% to 91.7%, p<0.001); no changes were observed in the traditional group. Patient satisfaction improved in the CMO group vs the traditional group (48 vs 44, p<0.001). Conclusion: To our knowledge, this is the first study to compare CMO vs traditional methodology. The CMO model showed an overall improvement in real-life patient experience, satisfaction, and adherence to treatment compared to the traditional methodology.

Catatonia and Mutism: Neurotic, Psychotic, or Organic Disorder?

Background. Catatonia is caused by a variety of psychiatric and organic conditions. The onset, clinical profile, and response to treatment may vary depending on the underlying cause. Catatonia is more likely to be associated with neurotic and psychotic disorders, but some psychiatric symptoms are key components in the clinical presentation of other medical conditions. Case Report. We report the case of a woman who started showing paroxysmal recurrent episodes since the age of 57 years, characterized by surrounding disconnection, disorientation, and muscle spasm (myoclonus), followed by a postictal state. In the following months, the symptoms evolved to akinetic mutism, catatonia, and rapidly progressive vision and audition loss. She underwent a battery of tests, most of them inconclusive, until a neoplastic meningoencephalitis was diagnosed after more than two years of symptoms. Numerous medical conditions can mimic psychiatric disorders. This uncommon presentation may lead to a late diagnosis and treatment initiation, increasing significantly morbidity and mortality. A differential diagnosis with infectious, autoimmune, and neoplastic etiologies should always be carried out.

Intraoperative brain mapping during awake surgery in symptomatic supratentorial cavernomas.

BACKGROUND: Complete resection of symptomatic supratentorial cavernoma (SCA) and removal of the surrounding gliotic area is recommended to minimize the risk of persistent seizures or (re)bleeding. Surgery of SCA located in an eloquent area, can carry out severe postoperative neurological morbidity. We report a study aimed to assess feasibility, extent of resection and outcome after surgical removal of CA by cortico-subcortical intraoperative brain stimulation (ioBS) in the awake patient. METHODS: Six patients diagnosed of symptomatic SCA located on an eloquent area and operated on while awake under local anaesthesia ioBS, were included. Preoperative planning included neuropsychologic assessment of language-related functions, sociocognitive functions and executive functions. Intraoperatively, we recorded the results achieved in the planned neuropsychological tasks when stimulation was applied (cortical and subcortical). Postoperative control 3D MRI was scheduled at 1 month after surgery to calculate extent of resection. Neuropsychological assessment at 6 months after surgery was performed in all cases. RESULTS: Six patients (5 females, 1 male) aged 24-48 years were included in our study. Locations of the lesions were right insular (n=1), left insular (n=1), left temporo-insular (n=1), left temporal (n=2) and left frontal (n=1). In all patients, positive findings were obtained during ioBS. In 5 patients, complete surgical resection was achieved. Two patients had postoperative transient neurological deficits, one case of hemiparesis, one case of dysnomia, both cleared over a 6-month period. Clinical follow-up revealed that all patients experienced complete recovery from preoperative symptoms within a year and five patients with seizures showed marked improvement and eventually quit antiepileptic drugs. Neuropsychological assessment at 6 months provided normal results compared to preoperative baseline in all domains. CONCLUSIONS: Our study suggests that ioBS in the awake surgery of symptomatic SCA located in eloquent areas, allows to increase the rate of complete resection, minimizing postoperative neurological and neuropsychological deficit, and improving postoperative seizures control.

Intraoperative brain mapping of language, cognitive functions, and social cognition in awake surgery of low-grade gliomas located in the right non-dominant hemisphere.

OBJECTIVE: The aim of our study was to evaluate the usefulness of cortical-subcortical intraoperative brain mapping (ioBM) in resective awake surgery of low-grade gliomas (LGG) of the right non-dominant hemisphere (RndH). It was estimated how ioBM may affect both the extent of resection and postoperative outcome of language, spatial cognition, social cognition, and executive functions including attention and working memory. PATIENTS AND METHODS: Fifteen patients that underwent ioBM in resective awake surgery of LGG located on the RndH, were included. A cohort of 15 patients with the same tumour location operated under general anaesthesia without brain mapping was used as control. Specific intraoperative tasks for each location were carried out and results registered. Neuropsychological assessment was performed preoperatively and at 6 months after surgery. RESULTS: In the group of patients operated by using ioBM in awake surgery, an 86.66 % mean of resection was obtained compared to 60.33 % in the control group. Speech arrest and incorrect naming responses were elicited in higher proportion in frontal and insular locations. Parietal stimulation associated higher number of incorrect responses in social cognition task. Parietal and temporal stimulation were more frequently associated with incorrect performance of spatial cognition task. Parietal stimulation associated with higher frequency incorrect execution of attention and working memory tasks. After comparing clinical and neuropsychological results in both cohorts, worst outcome at 6 months was observed in the group of patients operated under general anaesthesia without brain mapping, especially in parietal and insular locations. CONCLUSIONS: Intraoperative identification of language, cognitive functions, and social cognition of RndH by means of ioBM, can be of paramount importance in improving the extent of resection of low-grade gliomas and positively affects clinical and neuropsychological outcome at six months.

The impact of COVID-19 in hemodialysis patients: Experience in a hospital dialysis unit.

INTRODUCTION: COVID-19 is a very high transmission disease with a variable prognosis in the general population. Patients in hemodialysis therapy are particularly vulnerable to developing an infectious disease, but the incidence and prognosis of hemodialysis patients with COVID-19 is still unclear. The main objective is to describe the experience of our dialysis unit in preventing and controlling the spread of SARS-CoV-2 infection. METHODS: Preventive structural and organizational changes were applied to all patients and health care personnel in order to limit the risk of local transmission of SARS-CoV-2 infection. FINDINGS: The Nephrology department at Sant Joan Despí Moises Broggi Hospital-Consorci Sanitari Integral is a reference for two satellite hemodialysis centers caring for 156 patients. We combine our own hemodialysis maintenance program for 87 patients with hospitalized patients from peripheral hemodialysis centers. In this area, the reported incident rate of COVID-19 in these peripherical hemodialysis centers was 9.5% to 19.9% and the death rate 25% to 30.5%. In our hemodialysis program, the incidence rate was 5.7%. Three out of five required hospitalization (60%) and nobody died. DISCUSSION: Although the risk of local transmission of the disease was very high due to the increase in hemodialysis patients from peripheral centers admitted to hospital, the incidence rate of COVID-19 was very low in our own hemodialysis patients. We believe that the structural and organizational changes adopted early on and the diagnosis algorithm played an important role in minimizing the spread of the disease.

Intraoperative brain mapping during awake surgery in symptomatic supratentorial cavernomas.

BACKGROUND: Complete resection of symptomatic supratentorial cavernoma (SCA) and removal of the surrounding gliotic area is recommended to minimize the risk of persistent seizures or (re)bleeding. Surgery of SCA located in an eloquent area, can carry out severe postoperative neurological morbidity. We report a study aimed to assess feasibility, extent of resection and outcome after surgical removal of CA by cortico-subcortical intraoperative brain stimulation (ioBS) in the awake patient. METHODS: Six patients diagnosed of symptomatic SCA located on an eloquent area and operated on while awake under local anaesthesia ioBS, were included. Preoperative planning included neuropsychologic assessment of language-related functions, sociocognitive functions and executive functions. Intraoperatively, we recorded the results achieved in the planned neuropsychological tasks when stimulation was applied (cortical and subcortical). Postoperative control 3D MRI was scheduled at 1 month after surgery to calculate extent of resection. Neuropsychological assessment at 6 months after surgery was performed in all cases. RESULTS: Six patients (5 females, 1 male) aged 24-48 years were included in our study. Locations of the lesions were right insular (n=1), left insular (n=1), left temporo-insular (n=1), left temporal (n=2) and left frontal (n=1). In all patients, positive findings were obtained during ioBS. In 5 patients, complete surgical resection was achieved. Two patients had postoperative transient neurological deficits, one case of hemiparesis, one case of dysnomia, both cleared over a 6-month period. Clinical follow-up revealed that all patients experienced complete recovery from preoperative symptoms within a year and five patients with seizures showed marked improvement and eventually quit antiepileptic drugs. Neuropsychological assessment at 6 months provided normal results compared to preoperative baseline in all domains. CONCLUSIONS: Our study suggests that ioBS in the awake surgery of symptomatic SCA located in eloquent areas, allows to increase the rate of complete resection, minimizing postoperative neurological and neuropsychological deficit, and improving postoperative seizures control.

Antituberculosis drug resistance in isolates of Mycobacterium tuberculosis complex in southeast Spain.

OBJECTIVES: The aim of this study was to determine resistance to antituberculosis (anti-TB) drugs in Mycobacterium tuberculosis complex isolates from patients diagnosed with Tuberculosis (TB) in southeast Spain and to study related epidemiological factors. METHODS: This retrospective study analysed 5-year data (2012-2016) obtained in southeast Spain for a total equivalent population of 1 735 608 inhabitants. Clinical samples were examined from 557 patients with suspected pulmonary TB (n=470; 84.4%) or extrapulmonary TB (n=87; 15.6%), taking into account patient age, sex, human immunodeficiency virus (HIV) infection, country of birth and prior anti-TB treatment. RESULTS: TB was found more frequently in men than in women (66.6% vs. 33.4%), and the age group with the most cases (43.7%) was 36-55 years. Among the first-line anti-TB drugs, 7.0% of patients harboured isolates resistant to isoniazid (INH) and 1.6% to rifampicin (RIF); moreover, 1.4% of isolates were multidrug-resistant TB (MDR-TB) and 0.7% were extensively drug-resistant TB. There was a statistically significant relationship (P=0.028) between MDR-TB isolates and non-Spanish-born patients, but not between the latter and INH resistance. CONCLUSION: Resistance to INH and RIF was observed at levels similar to those published nationwide, with rates of MDR-TB being somewhat lower. Rates of HIV/TB co-infection have decreased considerably between 2012 and 2016.

Impact of telemedicine on the clinical outcomes and healthcare costs of patients with chronic heart failure and mid-range or preserved ejection fraction managed in a multidisciplinary chronic heart failure programme: A sub-analysis of the iCOR randomized trial.

Background: The efficacy of telemedicine in the management of patients with chronic heart failure and left ventricular ejection fraction ≥40% is poorly understood. The aim of our analysis was to evaluate the efficacy of a telemedicine-based intervention specifically in these patients, as compared to standard of care alone. Methods: The Insuficiència Cardiaca Optimització Remota (iCOR) study was a single centre, randomised, controlled trial, designed to evaluate a telemedicine intervention added to an existing hospital/primary care multidisciplinary, integrated programme for chronic heart failure patients. 178 participants were randomised to telemedicine or usual care, and were followed for six months. For the present sub-analysis, only iCOR participants (n = 116) with left ventricular ejection fraction ≥40% were included. The primary study endpoint was the incidence of an acute non-fatal heart failure event, defined as a new episode of worsening of symptoms and signs consistent with acute heart failure requiring intravenous diuretic therapy. The healthcare-related costs in each study group were also evaluated. Results: The incidence of the first occurrence of the primary endpoint was significantly lower in the telemedicine arm (22% vs 56%, p<0.001), with a hazard ratio of 0.33 comparing to the usual care arm (95% confidence interval 0.17­0.64). Telemedicine was also associated with lower mean overall chronic heart failure care-related costs compared to usual care (8163€ vs 4993€, p=0.001). The results were consistent in both left ventricular ejection fraction of 40­49% and left ventricular ejection fraction ≥50% patients. Conclusions: Our results suggest that telemedicine is a promising strategy for the management of chronic heart failure patients with left ventricular ejection fraction ≥40%. These findings should be replicated in larger cohorts.

Las funciones ecológicas de los bambúes en la recuperación de servicios ambientales y en la restauración productiva de ecosistemas

Este artículo es una revisión bibliográfica sobre las funciones ecológicas que caracterizan a los bambúes, por las cuales merecen un mayor reconocimiento e inclusión en los programas de restauración ecológica. Los bambúes son un grupo de plantas muy diverso, de amplia distribución geográfica y económicamente importante. Aunque son más reconocidos por los usos comerciales, su potencial de uso en programas de restauración ecológica es prometedor, ya que pueden ser eficientes en la prestación de varios servicios ambientales relacionados con el suelo, el agua y el secuestro de carbono. Su rápido crecimiento, junto con su capacidad para controlar la erosión y mantener el agua a nivel del suelo, así como para proporcionar nutrientes mediante la descomposición de la hojarasca, convierte a los bambúes en un grupo valioso para la recuperación de áreas degradadas y para la restauración productiva de ecosistemas, en particular a través de sistemas agroforestales. Los enfoques agroforestales pueden combinar diferentes especies de bambú con otros cultivos, para satisfacer las necesidades humanas y generar a la vez beneficios para los ecosistemas. De manera similar, los bosques o plantaciones de bambúes, junto con sistemas agroforestales mixtos, pueden actuar como áreas de conexión y corredores biológicos, en paisajes muy fragmentados, proporcionando refugio y alimento para una amplia diversidad de organismos. A pesar de las percepciones de que los bambúes pueden ser invasivos, las pruebas para apoyar esto son limitadas. Recomendamos una evaluación cuidadosa de las características biológicas de las especies de bambúes seleccionadas, antes de su implementación en proyectos de restauración productiva y de recuperación de los servicios ambientales.

This article is a bibliographic review on the ecological functions that distinguish bamboos, for which they deserve greater recognition and inclusion in ecological restoration programs. Bamboos are a highly diverse, geographically widespread and economically important plant group. Although they are more recognized by commercial uses, their potential for use in ecological restoration programs is promising, as they can be effective in delivery of several environmental services related to soil, water and carbon sequestration. Their rapid growth, along with their abilities to control erosion and maintain water at soil level, as well as provide nutrients by litterfall decomposition, make them a valuable group for recovery of degraded areas and in productive restoration of ecosystems, in particular via agroforestry systems. Agroforestry approaches can combine different bamboo species with other crops, to meet human needs while generating benefits for ecosystems. Similarly, bamboo forests or plantations together with mixed agroforestry systems can act as stepping-stones and biological corridors, in very fragmented landscapes by providing shelter and food for a wide diversity of organisms. Despite perceptions that bamboos can be invasive, evidence to support this is limited. We recommend careful evaluation of the biological characteristics of bamboo species selected, prior to deployment in productive restoration projects and for the recovery of environmental services.

Kainate Receptor-Mediated Depression of Glutamate Release Involves Protein Kinase A in the Cerebellum.

Kainate (KA) receptors (KAR) have important modulatory roles of synaptic transmission. In the cerebellum, the action mechanisms of KAR-mediated glutamatergic depression are unknown. We studied these mechanisms by recording evoked excitatory postsynaptic currents (eEPSCs) from cerebellar slices using the whole-cell configuration of the patch-clamp technique. We observed that 3 µM KA decreased the amplitude of eEPSCs and increased the number of failures at the synapses established between parallel fibers (PF) and Purkinje neurons, and the effect was antagonized by NBQX under the condition where AMPA receptors were previously blocked. The inhibition of protein kinase A (PKA) suppressed the effect of KAR activation on eEPSC, and effect was not prevented by protein kinase C inhibitors. Furthermore, in the presence of Pertussis toxin, the depression of glutamate release mediated by KAR activation was prevented, invoking the participation of a Gi/o protein in this modulation. Finally, the KAR-mediated depression of glutamate release was not prevented by blocking calcium-permeable KARs or by treatments that affect calcium release from intracellular stores. We conclude that KARs present at these synapses mediate an inhibition of glutamate release through a mechanism that involves the activation of G-protein and protein kinase A.

In Vitro Activity of Tedizolid against Mycobacterium tuberculosis.

Tedizolid is a novel oxazolidinone with activities against Gram-positive microorganisms, including mycobacteria. We studied the in vitro activity of tedizolid against 120 Mycobacterium tuberculosis strains, including susceptible, first-line-resistant, and multidrug-resistant isolates. MIC was tested using the Bactec 960 MGIT system. MIC90 and MIC50 were 0.5 and 0.25 µg/ml, respectively, in susceptible and resistant strains. Tedizolid may be an alternative in the treatment of resistant M. tuberculosis.

Oral Isotretinoin for the treatment of Aripiprazol-induced acneiform rash.

Acneiform rash is a commonly reported side effect to certain types of medications, including antipsychotic agents. Its clinical presentation consists mainly of papulopustular lesions. Other types of lesions, such as nodular or cystic, can also be observed. Body distribution of the lesions follows a similar pattern to acne vulgaris. Depending on the severity of the case, drug-induced acne may be treated in different ways. In mild cases, the use of topical antibiotics and retinoids in combination is usually effective. With more severe forms, it may be necessary to add oral antibiotics, such as tetracyclines, but a good response is not always achieved. Identification of the drug responsible for the side-effect is mandatory in refractory eruptions. Herein, we present the case of an Aripiprazole-induced acneiform rash successfully treated with oral Isotretinoin. The treatment was effective and well tolerated and there was no need to discontinue the psychopharmacological medication. This is the first study to report this modality of treatment.

Cerebellar Kainate Receptor-Mediated Facilitation of Glutamate Release Requires Ca2+-Calmodulin and PKA.

We elucidated the mechanisms underlying the kainate receptor (KAR)-mediated facilitatory modulation of synaptic transmission in the cerebellum. In cerebellar slices, KA (3 µM) increased the amplitude of evoked excitatory postsynaptic currents (eEPSCs) at synapses between axon terminals of parallel fibers (PF) and Purkinje neurons. KA-mediated facilitation was antagonized by NBQX under condition where AMPA receptors were previously antagonized. Inhibition of protein kinase A (PKA) suppressed the effect of KA on glutamate release, which was also obviated by the prior stimulation of adenylyl cyclase (AC). KAR-mediated facilitation of synaptic transmission was prevented by blocking Ca2+ permeant KARs using philanthotoxin. Furthermore, depletion of intracellular Ca2+ stores by thapsigargin, or inhibition of Ca2+-induced Ca2+-release by ryanodine, abrogated the synaptic facilitation by KA. Thus, the KA-mediated modulation was conditional on extracellular Ca2+ entry through Ca2+-permeable KARs, as well as and mobilization of Ca2+ from intracellular stores. Finally, KAR-mediated facilitation was sensitive to calmodulin inhibitors, W-7 and calmidazolium, indicating that the increased cytosolic [Ca2+] sustaining KAR-mediated facilitation of synaptic transmission operates through a downstream Ca2+/calmodulin coupling. We conclude that, at cerebellar parallel fiber-Purkinje cell synapses, presynaptic KARs mediate glutamate release facilitation, and thereby enhance synaptic transmission through Ca2+-calmodulin dependent activation of adenylyl cyclase/cAMP/protein kinase A signaling.

Surveillance of Drug-Resistant Tuberculosis in Spain (2001-2015).

Multidrug-resistant tuberculosis (MDR-TB) is a cause of increasing concern. This study investigated first-line anti-TB drug resistance in Mycobacterium tuberculosis strains submitted to the Tuberculosis Reference Center in Córdoba (Spain) between 2001 and 2015. A total of 1,207 cultures were tested against first-line drugs using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 207 strains (17.2%), the greatest resistance being found in INH (5.3%) followed by streptomycin (3%), pyrazinamide (2.2%), rifampicin (1%), and ethambutol (0.2%). A total of 1.9% of strains were MDR-TB. Six strains displayed resistance to four drugs, and three strains to five drugs. In view of resistance observed, careful surveillance of drug resistance is recommended.

Evaluation of a new automated Abbott RealTime MTB RIF/INH assay for qualitative detection of rifampicin/isoniazid resistance in pulmonary and extra-pulmonary clinical samples of Mycobacterium tuberculosis.

A new automated real-time PCR assay for the detection of rifampicin (RIF) and isoniazid (INH) resistance in Mycobacterium tuberculosis (MTB) was evaluated. A total of 163 clinical samples (128 pulmonary and 35 extra-pulmonary) were processed using four PCR assay kits: Abbott RealTime MTB RIF/INH, Genotype MTBDRplus, Xpert/MTB RIF, and Anyplex MTB/MDR. The results of phenotypic drug-susceptibility testing using BACTECMGIT 960 were used as reference. The sensitivity and specificity of the new Abbott RealTime MTB RIF/INH assay in comparison with phenotypic testing was 96.3% (95%CI 87.32%-100%) for RIF and 100% (95%CI 99.3%-100%) for INH; the sensitivity was 78.8% (95%CI 66.8%-90.9%) and the specificity was 100% (95%CI 98.9%-100%). The Abbott RealTime MTB RIF/INH test could be a valid method for detecting the most common mutations in strains resistant to RIF and INH.

Two-Dimensional Ultrasound Evaluation of the Fetal Cerebral Aqueduct: Improving the Antenatal Diagnosis and Counseling of Aqueductal Stenosis.

OBJECTIVE: To describe a technique for the visualization and measurement of cerebral aqueduct diameter through a 2D sagittal median plane, and to report its aspect and measurement in fetuses with aqueductal stenosis (AS). METHODS: This was a cross-sectional study of 207 morphologically normal fetuses in low-risk pregnancies between 20 and 36 weeks of gestation. The cerebral aqueduct was visualized transvaginally in a midsagittal plane, and measurements of its greatest diameter (ampulla) were taken independently by an expert and a nonexpert sonographer. In addition, the aqueduct morphology from 7 fetuses with AS and complete follow-up were compared to the reference range. RESULTS: Aqueductal measurements were obtained in 206 of 207 normal fetuses. Aqueductal growth occurred linearly with gestational age. Our method demonstrated excellent interobserver reproducibility. Among the 7 fetuses with AS, the aqueductal lumen could not be identified in 6 and had a funneling aspect in 1. DISCUSSION: Our study demonstrated that it is possible to visualize and measure the cerebral aqueduct directly through a 2D ultrasound median plane. In fetuses with severe ventriculomegaly, the morphology and width of this structure could represent a relevant tool in improving AS diagnosis, differentiating it from other causes of significant ventricular dilation that carry a different outcome.