Normal Pressure Hydrocephalus Following Cranial Radiation: Identification of Shunting Responders.

BACKGROUND: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). METHODS: Patients who completed cranial RT at least 2 years before with clinically suspected NPH and an Evans' index (EI) ≥ 0.30 underwent a cognitive and a cerebrospinal fluid (CSF) volumetric (MRI) analysis (n = 36). For those in whom VPS was placed (n = 14), we explored whether adding a CSF volumetric analysis to classical MRI and LIT (Tap Test) features would better identify VPS responders. RESULTS: Nearly 80% exhibited cognitive impairment. The CSF volume at NPH diagnoses was significantly larger in the group of VPS responders (p = 0.04). The addition of CSF volume to NPH diagnoses increased accuracy to 93%, with a positive and negative predictive value of 91% and 100%, respectively. CONCLUSION: The addition of a quantitative MRI analysis of CSF volume to classical MRI and LIT NPH criteria, along with a high clinical suspicion of NPH, may help to identify VPS responders, thus improving the clinical management and prognosis of long-term survivors.

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity.

Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or treat OXAIPN. Thus, it is necessary to early predict the occurrence of OXAIPN during treatment and possibly modify the OXA-based regimen in patients at high risk as an early diagnosis and intervention may slow down neuropathy progression. However, identifying which patients are more likely to develop OXAIPN is clinically challenging. Several objective and measurable early biomarkers for OXAIPN prediction have been described in recent years, becoming useful for informing clinical decisions about treatment. The purpose of this review is to critically review data on currently available or promising predictors of OXAIPN. Neurological monitoring, according to predictive factors for increased risk of OXAIPN, would allow clinicians to personalize treatment, by monitoring at-risk patients more closely and guide clinicians towards better counseling of patients about neurotoxicity effects of OXA.

Encephalitis Induced by Immune Checkpoint Inhibitors: A Systematic Review.

Importance: Encephalitis is a severe immune-related adverse event secondary to treatment with immune checkpoint inhibitors (ICIs). The spectrum of ICI-induced encephalitis (ICI-iE) ranges from disease that resolves fully to lethal forms. Moreover, ICIs may unmask a paraneoplastic encephalitis. To our knowledge, the factors associated with ICI-iE prognosis are unknown. Objectives: To evaluate the presentation of ICI-iE and to identify features helpful in assessing outcomes. Evidence Review: This systematic review pooled case series from the published literature (n = 77) and medical records from 1 center (n = 5) to assess the association between the form of ICI-iE presentation and its prognosis. Eligibility criteria included references identified by searches of PubMed and Web of Knowledge databases in the English literature from June 2000 (first patient dose of ipilimumab) to April 17, 2020, that examined patients with encephalitis with presumed autoimmune etiologic features induced by ICIs. Information regarding clinical, cerebrospinal fluid, and neuroimaging (magnetic resonance imaging) features, as well as treatment given, were extracted. Findings: A total of 82 patients (52 men [63%]; median age, 61.0 years [interquartile range, 52.5-70.0 years]) were included. Most patients presented with focal syndromes (39 [48%]) or meningoencephalitis (36 [44%]). Seven patients (9%) had nonclassifiable ICI-iE. Neuronal autoantibodies were detected in 23 patients with focal syndromes and 1 patient with nonclassifiable ICI-iE. Most autoantibodies were onconeuronal (17 of 24 [71%]), targeting intracellular antigens. Patients without a focal syndrome or with a negative-antibody focal syndrome had a good prognosis (49 of 55 [89%]). Among patients with autoantibodies, those with anti-glutamic acid decarboxylase or anticell surface responded to treatment and had a favorable prognosis (100%). However, patients with other autoantibodies had poor outcomes (17 of 24 [71%]). Antineuronal autoantibodies (13 of 24 [54%] vs 5 of 41 [12%]; P < .001), focal syndrome (16 of 39 [41%] vs 4 of 43 [9%]; P = .001), and abnormal magnetic resonance imaging findings (14 of 39 [36%] vs 4 of 32 [13%]; P = .02) were associated with poor outcomes. Conversely, fever (21 of 23 [91%] vs 41 of 59 [70%]; P = .04) and more inflammatory changes in cerebrospinal fluid (30 of 31 [97%] vs 21 of 33 [64%]; P = .001) were associated with a better prognosis. Conclusions and Relevance: Immune checkpoint inhibitors may induce mainly 2 different encephalitic syndromes: a focal limbic or extralimbic encephalitis and a meningoencephalitis. Immune checkpoint inhibitor-induced encephalitis is associated with an overall favorable outcome, with a low rate of fatal events. An undetected preexisting paraneoplastic encephalitic syndrome may be triggered by ICIs, and this type of syndrome has the worst outcome among all the different types of ICI-induced encephalitis syndromes. Clinical presentation and systematic measurement of autoantibodies will be a helpful guide for the therapeutic strategy and for counseling regarding prognosis.

Comprehensive tackling to the safe handling of hazardous drugs: a multidisciplinary approach to clinical practice.

OBJECTIVES: The aim of this study is to present the adaptation and implementation of the recommendations of the National Institute for Safety and Health at Work (Instituto Nacional de Seguridad y Salud en el Trabajo - INSHT) in the authors' hospital to achieve a safer handling of hazardous drugs. MATERIAL AND METHODS: In 2016, INSHT published the first document on hazardous drugs in Spain. In the authors' center, a project was developed to implement the recommendations presented in that document in 2 phases: 1) analysis: to identify drugs and processes susceptible to not being handled as hazardous, and to search for safer alternatives and preventive measures; and 2) development: to ensure information, training, the adaptation of standardized work procedures, the minimization of risks associated with handling, safety devices, personal protective equipment (PPE), as well as health monitoring. RESULTS: The authors detected 80 commercial presentations manipulated without adhering to safety conditions, mainly oral (74%) from lists 1 (7.5%), 2 (37.5%) and 3 (55%) of the National Institute for Occupational Safety and Health. The following measures were envisaged to reduce the risk: introducing new presentations (4 lower doses, 1 liquid dose) and centralizing new preparations in the pharmacy service (11 oral formulas, 6 parenteral drugs). Management, spillage and exposure procedures were adapted. Safety measures were included in the prescription and administration applications, and there were some indications of risks in the storage. Overall, 48 referents and 690 nurses were trained. Each unit was provided with PPE and safety devices (e.g., closed systems, RX CRUSH®). The steps prior to the administration were moved to the patient's bedside to align patient and professional safety. During the first 6 months after the implementation, 22 cases of pregnancy (64% among the nursing staff), 4 cases of lactation, and 1 case of conceiving problems were reported. In the cases of oxytocin and the repackaging of list 3, risk management was applied. CONCLUSIONS: The multidisciplinary approach has allowed to achieve a global and safer control of hazardous drugs with a minimal impact on the center. It is important to continuously evaluate the effects of these measures, and to take into account the data of this analysis and any possible new evidence. Int J Occup Med Environ Health. 2020;33(5):621-34.

External quality assessment schemes for inorganic elements in the clinical laboratory: Lessons from the OELM scheme.

Measurements of inorganic elements in clinical laboratories produce results used for the diagnosis, the treatment and the monitoring of deficiencies or overloads. The main objective of External Quality Assessment Schemes is to verify, on a regular frequency, that clinical laboratory results correspond to the quality requirement for patient care. Therefore, External Quality Assessment Schemes represent an essential component of a laboratory's quality management system. However, External Quality Assessment Schemes within the same analytical field remain heterogeneous for different reasons such as samples, determination of assigned value, acceptable limits, content of the reports. The aim of this review was to describe and illustrate some major critical aspects of External Quality Assessment Schemes based on Occupational and Environmental Laboratory Medicine external quality assessment scheme experience.

Recomendaciones para el diseño e implementación de un programa de aseguramiento de la calidad de la fase preanalítica / Recommendations for the design and implementation of a Pre-analytical Phase Quality Assurance Program

El aseguramiento de la calidad de la fase preanalítica se orienta hacia 2 aspectos clave: la gestión de los errores preanalíticos desde la perspectiva de la seguridad del paciente, y la mejora y armonización de los procedimientos, basada en la aplicación de normativa además de recomendaciones profesionales. Al igual que el resto de las fases, debe incluir un programa interno de aseguramiento y la participación en programas de intercomparación entre laboratorios. El control de calidad interno debe basarse fundamentalmente en la identificación de riesgos, detección sistemática de errores y establecimiento de indicadores. La selección de los indicadores priorizando el impacto en el paciente, la forma de detectar y registrar los errores de forma sistemática y fácilmente explotable, así como las variables utilizadas en su cálculo, son aspectos importantes para medir la eficacia de las acciones de mejora y permitir la comparabilidad entre laboratorios. En este sentido, los programas externos de la calidad de la fase preanalítica basados en la comparación de indicadores, son una herramienta útil para el diseño e implantación de un programa de aseguramiento de la calidad. Este documento pretende servir de apoyo para que cada laboratorio seleccione, implante y evalúe sus propios indicadores, de acuerdo a las características individuales de sus procedimientos preanalíticos, pero sin perder de vista la armonización entre laboratorios

The quality assurance of the pre-analytical phase is oriented towards two key aspects; the management of pre-analytical errors from the perspective of patient safety, and the improvement and harmonisation of procedures, based on the application of regulations and professional recommendations. Like the rest of the phases, it should include an internal quality assurance program, as well as the participation in external quality assurance programs. The internal quality control should mainly be based on the identification of risks, systematic detection of errors, and establishment of indicators. The selection of indicators prioritising the impact on the patient, the way to detect and record errors in a systematic and easily exploitable manner, and also the variables used in the calculations, are important aspects to measure the effectiveness of improvement actions and to allow comparability between laboratories. In this sense, the external quality assurance programs of the pre-analytical phase based on the comparison of indicators are a useful tool for the design and implementation of a quality assurance program. This document is intended as a support for each laboratory to select, implement, and evaluate its own indicators, according to the individual characteristics of its pre-analytical procedures, but without losing sight of the harmonisation between laboratories

Coexistence of microhemorrhages and acute spontaneous brain hemorrhage: correlation with signs of microangiopathy and clinical data.

PURPOSE: To evaluate prospectively with magnetic resonance (MR) imaging the coexistence of microhemorrhages (MHs) in white patients with acute spontaneous intraparenchymal hemorrhage (IPH) and acute ischemic stroke and to study the association with imaging findings of microangiopathy and various clinical data. MATERIALS AND METHODS: Before examinations, informed consents were signed by either the patient or a relative. The study was carried out with the approval of the local ethics committee. MR imaging was performed in 90 patients with acute stroke: 45 with acute spontaneous IPHs (24 men and 21 women; median age, 65 and 68 years, respectively) and 45 age-matched control subjects without intracranial hemorrhages (26 men and 19 women; median age for both, 67 years), as determined at computed tomography. MR imaging included transverse T1- and T2-weighted spin-echo, transverse fluid-attenuated inversion recovery, transverse and coronal T2*-weighted gradient-echo, and, in 50 patients, diffusion-weighted sequences. Presence of MHs and signs of microangiopathy, such as T2 hyperintensities or lacunae, were recorded in the white and deep gray matter. The relationships between MH and IPH and between MH and T2 hyperintensities were analyzed by means of regression analysis. Different clinical features, such as arterial hypertension or diabetes, were registered and correlated with the image findings by means of regression analysis. RESULTS: MHs were found in 64% of patients with IPH (29 of 45) and 18% of control subjects (eight of 45). A statistically significant relationship between MH and IPH was determined (P < .001). Among the 29 patients with IPH and MH, 24 (83%) had T2 hyperintensities and 13 (45%) had lacunae; among the 16 patients without MH, seven (44%) had T2 hyperintensities and three (19%) had lacunae. A relationship between MH and occurrence and extent of T2 hyperintensities was also identified (P < .001). There was no clear relationship with the clinical data studied. CONCLUSION: The results support a correlation between the presence of imaging signs of cerebral microangiopathy, clinically silent MHs, and acute IPHs.

Novel bis-betaines and betaines within [1(4)]meta-heterophane frameworks.

After prior selection of betaine building blocks for the construction of quadrupolar heterophane frameworks, a convergent "3+1" synthetic strategy is reported for the synthesis of the title macrocycles composed of heterocyclic betaine subunit(s). These typify the first example of simple cyclophanes constructed out of both highly pi-excessive and highly pi-deficient heteroaromatic moieties linked in a 1,3-alternating fashion. The chemical reactivity of the quadrupolar heterophanes 1a and 1c toward electrophiles under neutral conditions corroborated their bis-betaine structure. The structural features of the bis-betaines 1, betaines 2 x PF6 and 5 x X, and the corresponding dicationic [1(4)]heterophanes 3 x 2X and 4 x 2Cl were studied by 1H and 13C NMR spectroscopy and electrospray ionization mass spectrometry, and confirmed by single-crystal X-ray diffraction analysis of macrocycles 1a and 2a x PF6.