[Cognitive impairment in children with organic asthenic disorder]. / Kognitivnye narusheniya u detei s organicheskim astenicheskim rasstroistvom.

OBJECTIVE: To study cognitive impairment and neurophysiological characteristics in children with organic asthenia, as well as the effectiveness of the drug Cogitum in the treatment of this pathology. MATERIAL AND METHODS: The main study group included 40 children aged 8 to 10 years with a diagnosis of «Organic asthenic disorder¼ (F06.6). The control group consisted of 30 children aged 8 to 10 years without manifestations of asthenia. The following research methods were used in the work: the asthenic state scale (ASS) by L.D. Malkova to assess the severity of asthenic syndrome, the S. Lee «SCT¼ (sluggish cognitive tempo) scale to assess manifestations of low cognitive tempo, the «Random Access Memory¼ method to quantify working memory, the TOVA (The Test of Variables of Attention) computer test to quantify assessment of attention disorders and impulsivity level, electroencephalogram (routine and spectral analysis) (p<0.05). For the treatment of patients from the study group, the drug Cogitum was used at a dose of 10 ml of a drinking solution per day for 30 days. RESULTS: In was shown that children from the study group were characterized by a decrease in working memory (7.8±2.9 vs 14.9±5.4), a statistically significant increase in SCT scores (p<0.05), a significantly greater degree of inattention and impulsivity with a tendency to an increase in the number of errors in the second half of the TOVA test (p<0.05). Comparative analysis of EEG relative power data showed a statistically significant increase in the power of waves in the alpha and theta ranges in the fronto-central leads of both hemispheres in the group of children with organic asthenic disorder (p<0.05). When re-evaluating the condition of children after treatment, a statistically significant decrease in the manifestations of asthenia on the ASS scale was recorded in 77.5% of cases. At the same time, there was a significant improvement in attention, memory, and indicators characterizing a low cognitive pace. The results of an electroencephalographic study after a course of treatment showed a decrease in the relative power of the EEG in the theta and alpha ranges in the anterior sections of the cerebral cortex (p<0.05), which indicates an increase in the level of activation of neocortical structures. CONCLUSION: Thus, the use of the drug Cogitum for the treatment of organic asthenic disorder leads not only to a decrease in asthenia and cognitive impairment, but also to an improvement in the functional state of the brain.

[Cognitive impairment in patients of cardiac surgery with senile asthenia syndrome and preastenia]. / Narusheniya kognitivnykh funktsii u patsientov kardiokhirurgicheskogo profilya s sindromom starcheskoi astenii i preastenii.

OBJECTIVE: To identify the features of the cognitive status in patients with cardiac surgery profile with senile asthenia syndrome (SAS) and preasthenia. MATERIAL AND METHODS: A study included 272 patients admitted for coronary artery bypass grafting (CABG). Screening for preasthenia and SAS in patients before surgery was performed using the Brief Battery of Physical Functioning Tests. SAS and preasthenia were detected in 15% of patients (n=41). Seventy-five patients were selected in the comparison group without asthenia. Assessment of the state of cognitive functions was carried out using screening neuropsychological scales - the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). RESULTS: The median of the MMSE score (27 [26; 28] and 28 [27; 29], p=0.04), and the MoCA score (23 [19; 25] and 25 [23; 27], p=0.0085) was significantly lower in patients with asthenia and pre-asthenia compared to patients without asthenia. According to the MoCA, about 60% of patients in the pre-asthenia-asthenia group had severe cognitive impairment, while in the group without asthenia, more than 30% of cases had normal cognitive functions (p=0.003). Significant intergroup differences were found in MoCA subtests, reflecting visuospatial skills, abstraction, verbal fluency and working memory (p=0.01-0.04). Regression analysis showed that age and physical functioning index (severity of asthenia) most significantly contributed to the basic cognitive status assessed by MoCA. CONCLUSION: Features of the cognitive status in patients of cardiac surgery with the SAS and preasthenia are impairments of visuospatial thinking, verbal fluency, abstract thinking and working memory. The MoCA was shown to be informative in determining the basic cognitive status of cardiac surgical patients. At the same time, the greatest contribution to the basic cognitive status is made by age and the indicator of physical functioning, which characterizes the degree of asthenia.

Psychometric validation of the French Multidimensional Chronic Asthenia Scale (MCAS) in a sample of 621 patients with chronic fatigue.

BACKGROUND: Psychometric validation of the Multidimensional Chronic Asthenia Scale (MCAS) was conducted in order to provide an effective tool for assessing the health-related quality of life of French-speaking patients with chronic asthenia (CA). METHODS: Items resulting from the initial formulation of the self-reported MCAS (along with other materials) were completed by French-speaking volunteers with inactive or active inflammatory bowel disease (IBD-I vs. IBD-A) or chronic fatigue syndrome (CFS). Responses from 621 participants (180 patients with IBD-A, 172 with IBD-I, 269 with CFS) collected in a single online survey were divided into three subsamples to test the construct validity of the MCAS (Step 1, N = 240), to confirm its factorial structure (Step 2, N = 204) and to explore its convergent-discriminant validity with the Fatigue Symptoms Inventory (FSI) and revised Piper Fatigue Scale (r-PFS, Step 3, N = 177). RESULTS: Steps 1 and 2 showed that, as expected, MCAS has four dimensions: feeling of constraint (FoC), physical (PC), life (LC) and interpersonal consequences (IC), which are also related to the duration of CA (i.e., the longer it lasts, the more the dimensions are impacted). The results further showed that the MCAS is sensitive enough to capture between-group differences, with the CFS group being the most impaired, followed by IBD-A and IBD-I. While convergent-discriminant validity between the 4 factors of MCAS and FSI and r-PFS, respectively, was satisfactory overall, Step 3 also pointed to some limitations that call for future research (e.g., shared variances between the PC and IC dimensions of MCAS and behavioral dimension of r-PFS). CONCLUSION: Despite these limitations, the MCAS clearly constitutes a promising tool for measuring quantitative differences (i.e., severity/intensity) in CA associated with various diseases, but also, and importantly, the clinically important differences in domains of its expression (i.e., qualitative differences).

[Chronic fatigue: What investigations? And what for?] / Fatigue chronique : quelles investigations ? Dans quels objectifs ?

Chronic fatigue is a frequent complaint, expressed at all levels of the healthcare system. It is perceived as disabling in a high proportion of cases, and internists are frequently called upon to find "the" cause. The etiological diagnostic approach of an unexplained state of fatigue relies on the careful search for more specific clues by questioning and clinical examination. It is necessary to recognize the limited place of complementary examinations apart from the basic biological parameters. Simple rating scales can be useful in the etiological and differential diagnosis of fatigue. Chronic fatigue syndrome (CFS), in the current state of knowledge, cannot be considered as a specific pathological entity distinct from idiopathic chronic fatigue states, and does not have validated biomarkers. It is important to know that a state of chronic asthenia often results from several intricated etiological factors (biological, psychological and social), to be classified as predisposing, precipitating and perpetuating. The metabolic and cardiorespiratory exercise test has a major place in the assessment and management of fatigue, as a prerequisite for personalized retraining or adapted physical activity (APA), which are the treatments of choice for chronic fatigue.

[Clinical and psychological manifestations of emotional burnout in mothers of children with neuropsychiatric diseases (on a model of ADHD)]. / Kliniko-psikhologicheskie proyavleniya emotsional'nogo vygoraniya u materei detei s psikhonevrologicheskimi zabolevaniyami (na modeli SDVG).

OBJECTIVE: To evaluate the therapeutic efficacy of Pantogam aktiv in the treatment of clinical manifestations of burnout in mothers of children with ADHD. MATERIAL AND METHODS: Under observation were 108 mothers of children with attention deficit hyperactivity disorder (ADHD) aged 25 to 50 years, who had symptoms of burnout in the clinical picture during the initial visit. The following research methods were used in the work: clinical history taking, neurological examination, S. Maslach questionnaire for assessing the burnout manifestations, subjective asthenia rating scale (MFI-20) with five subscales, digital fatigue rating scale (10-point variant), quantitative assessment of autonomic changes (questionnaire A.M. Wein), Spielberger-Khanin Scale for assessing emotional disorders, psychophysiological study of cognitive functions: test of attention variables TOVA (the Test of Variables of Attention). For the treatment of patients, the drug Pantogam Active was used in capsules of 300 mg, at a daily dose of 900 mg (2 capsules in the morning and 1 capsule in the afternoon) for 8 weeks. RESULTS: A re-examination after a course of treatment showed improvement in 68.5% of patients. After treatment, there was a significant decrease in the severity of such indicators of burnout as emotional exhaustion and depersonalization, a significant decrease in the average values according to the A.M. Wayne, a decrease in reactive anxiety, a statistically significant improvement in attention and a decrease in impulsivity (p<0.05). CONCLUSION: Thus, the results of the study indicate that the use of Pantogam active in the treatment of clinical manifestations of parental burnout is characterized by high efficiency. After treatment, there is a significant decrease in fatigue, asthenia, anxiety, and total indicators characterizing burnout. The data obtained make it possible to recommend the use of Pantogam aktiv in the treatment of clinical manifestations of parents burnout in children with neurological diseases.

[Clinical features of asthenic disorders in chronic heart failure]. / Klinicheskie osobennosti astenicheskikh rasstroistv pri khronicheskoi serdechnoi nedostatochnosti.

OBJECTIVE: The aim of the study is to study the clinical features of asthenic disorders in chronic heart failure (CHF) considering the reaction to the disease. MATERIAL AND METHODS: 62 inpatients with CHF II-IV functional class (FC) according to NYHA were examined. Research methods included somatic, psychopathological and pathopsychological examination using psychometric scales. RESULTS: According to a pathopsychological study using the Multidimensional Fatigue Inventory (MFI-20), asthenic disorders were discovered in all examined patients, realized mainly by «general fatigue¼ (75.8%) and «physical fatigue¼ (72.6%), more rarely «mental fatigue¼ was observed (32.2%). Correlations of «general fatigue¼ with the age of patients were revealed (p=0.018). There was a relationship between the severity of asthenic disorders and the severity of CHF, as evidenced by the correlation between «general fatigue¼ and reduced ejection fraction (EF) of the left ventricle (p=0.005), as well as «physical fatigue¼ and FC according to NYHA (p=0.022). The negative impact of all components of the dimensions of asthenic disorders on the quality of life was determined (p<0.05). According to the concept of the formation of different perceptions of the manifestations of a somatic disease, two types of reactions to asthenic disorders were identified: 1. Dissociative reactions, manifested by a discrepancy between the severity of CHF and a subjective assessment of the condition with an underestimation of the asthenic symptoms denial of its influence on the usual lifestyle and associated with an unfavorable course of CHF and 2. Adaptive reactions, realized by a harmonious perception of asthenia, awareness of the need to change lifestyle considering the presence of CHF symptoms. CONCLUSION: In accordance with the results, the described clinical features of asthenic disorders allow to distinguish asthenia in CHF and other pathology, and the identified types of reactions can contribute to the timely verification of asthenia, prevention of further progression of CHF, and the development of appropriate treatment approaches.

[The role of routine clinical examination in the selection of patients for screening of geriatric syndromes.]

The great complexity of complex geriatric assessment makes it relevant to search for methods that facilitate the selection of patients who really need it. The article presents the results of studying the possibility of using a routine clinical examination to select elderly cardiological patients with an increased risk of senile asthenia. The study involved 52 elderly patients with heart and vascular pathology. All of them underwent a generally accepted clinical and laboratory-instrumental examination, the results of which were compared with the data of the questionnaire «Age is not a hindrance¼. To identify the relationships between the parameters of clinical and geriatric status, analysis of variance and correlation analysis were used; summary frequency tables were built and analyzed. The significance threshold (p-value) was less than 5% (p<0,05). As a result of the study, it was found that the general condition of patients differing from satisfactory, complaints of shortness of breath, headaches, the presence of peripheral edema, lack of pulse on the dorsalis pedis arteries and posterior tibial arteries indicate an increased likelihood of senile asthenia in the subjects (p<0.05).

[Stress, asthenia and cognitive disorders]. / Stress, asteniya i kognitivnye rasstroistva.

Asthenia is a clinical syndrome that nearly any somatic and neurological pathologies can manifest with. Being is essence a defense mechanism that signals the depletion of energy resources, asthenia can become a pathological, extremely disabling condition, and even transform into a nosology of its own - the chronic fatigue syndrome, an immune-mediated disease. Besides, asthenia is often combined with affective and cognitive disorders, which facilitates difficulties in the establishing of the primary diagnosis. In this article we examine the complicated weave of asthenia, chronic fatigue syndrome, cognitive, and affective disorders.

Hereditary Equine Regional Dermal Asthenia homozygote adult working horse with mild signs - A Case Report.

Hereditary Equine Regional Dermal Asthenia (HERDA) is an autosomal recessive condition present in the American Quarter Horse and other related breeds. Resulting from a mutation in the peptidyl-prolyl cis-trans isomerase B (PPIB) gene, HERDA is homologous to Ehlers-Danlos syndrome in humans. Characterized by fragile, hyperelastic, skin, HERDA affected horses often present first with slow-healing wounds usually on the dorsum, and resulting in atrophic scars, seromas, and ulcers. As there is no treatment for the condition affected horses are typically reported to be unrideable, and if persistent wounds are sufficiently severe, may require euthanasia. This case report describes clinical presentation and genetic diagnostics of HERDA in an 8-year-old horse with notably mild clinical signs, previously undiagnosed. On recommendation from the referring veterinarian, the horse owners pursued genetic diagnostics for HERDA following development of painful dorsal skin lesions under the saddle area during a riding clinic. The individual was confirmed homozygous for HERDA c.115G>A missense mutation in the PPIB gene by commercial testing service (Etalon Diagnostics Inc.). Further objective studies on the severity and clinical presentation of HERDA are necessary to evaluate complex elements of this disease. Furthermore, mildly affected individuals may be underdiagnosed as a result of not demonstrating the clinical signs that commonly encourage genetic testing.

[Asthenic disorders as a manifestation of chronic fatigue syndrome]. / Astenicheskie rasstroistva kak proyavlenie sindroma khronicheskoi ustalosti.

The article explains the changes in terminology and diagnostic criteria for asthenic disorders as manifestations of chronic fatigue syndrome CFS (myalgic encephalomyelitis). Chronic fatigue syndrome is defined as neuroimmune endocrine dysfunction with a purely clinical diagnosis. Probably, viral infections can play a leading role in the pathogenesis. Published diagnostic criteria reveal possible correlations between chronic fatigue syndrome and COVID-19 disease. A promising strategy for the therapy and rehabilitation of patients is the use of smart peptides, a representative of which is the drug cortexin.

[Clinical features of asthenia in the context of adjustment disorders]. / Klinicheskie osobennosti astenii v ramkakh rasstroistv adaptatsii.

OBJECTIVE: To study asthenic symptoms in patients with adjustment disorders and to assess the efficacy of cytoflavin in their treatment. MATERIAL AND METHODS: The study included 100 patients, aged 20 to 43 years, with a diagnosis of adjustment disorder. Clinical, neurophysiological and parametric methods were used. An asthenic state scale, the Multidimensional Fatigue Inventory (MFI-20), a digital rating scale (a 10-point variant) and the Headache Impact Test (HIT-6), the Psychological Stress Measure (PSM-25), the Cognitive Emotion Regulation Questionnaire, the Test of Variables of Attention (TOVA) were administered. Cytoflavin was used in a dose of 2 tab. 2 times a day for 25 days for the treatment of patients from the study group. RESULTS: In the study group, 48.0% of patients had a pronounced degree of asthenia, and 52% had a moderate one. The clinical improvement was achieved in 73.0%. In the subgroup with moderate asthenia, the improvement was recorded in 88.5% of cases, in the subgroup of patients with severe asthenia in 56.3% of patients. There was a significant decrease in the severity of indicators on the scales of general asthenia, decreased activity and mental asthenia; a significant decrease in the integral indicator of mental tension, a significant improvement in the indicator of attention, a decrease in the frequency and intensity of headache. The improvement in the functional state of the brain in the form of a decrease in the power of the alpha rhythm in the anterior cerebral cortex was shown. CONCLUSION: The results of the study allow us to conclude that the use of cytoflavin is effective in the treatment of adjustment disorders.

[Asthenic disorders in schizophrenia (schizoasthenia) on the model of hypochondriac schizophrenia]. / Astenicheskie rasstroistva pri shizofrenii (shizoasteniya) na modeli ipokhondricheskoi shizofrenii.

OBJECTIVE: To determine the structure and mechanisms of interaction of asthenic disorders with negative and positive psychopathological symptoms in hypochondriac schizophrenia. MATERIAL AND METHODS: The study included male and female patients, aged 17-69 years, with a diagnosis of hypochondriac schizophrenia (F20.80 according to ICD-10) and asthenia symptoms. The main research method was clinical, which was supplemented by pathopsychological examination and the use of psychometric scales (PANSS, SANS, MFI-20,VAS asthenia). RESULTS AND CONCLUSION: Asthenia in case of hypochondriac schizophrenia (schizoasthenia) integrates two unrelated phenomena: «weakness¼ and «exhaustion¼ (intolerance to stress), and also acts within the framework of three psychopathological syndromes: neurotic, senestopathic/hypochondriac and overvalued hypochondria. Asthenia with hypochondriac schizophrenia is a predictor of an unfavorable social and clinical prognosis. Integrating into the structure of the clinical manifestations of hypochondriac schizophrenia, asthenia forms close relationships with positive and negative disorders of the type of «general syndromes¼, but remains outside the categories of both positive and negative symptoms of the disease, thus forming a separate «dimension¼ in the psychopathological space of schizophrenia.

[Diagnostics and treatment of non-alcoholic fatty liver disease with concomitant asthenic syndrome].

AIM: Analysis of the effectiveness of therapy for non-alcoholic fatty liver disease (NAFLD) with severe asthenic syndrome. MATERIALS AND METHODS: In the period from 2017 to 2019, on the basis of the gastroenterology center of the Vishnevsky 3-rd Central Military Clinical Hospital, 247 patients with NAFLD, including those at the stage of steatohepatitis, and severe asthenic syndrome were examined and treated. The main group included 124 patients, the control group 123 patients. All patients underwent complex laboratory and instrumental diagnostics and neuropsychological research using the subjective asthenia assessment scale (MFI-20). In both groups, domestic drugs were included in the therapy regimen: from the 1st to the 10th day, Heptrong solution 3 ml intramuscularly in the morning; from the 1st to the 60th day UDCA 250 mg orally, 3 capsules at bedtime, Omega-3 forte 1000 mg, 2 capsules in the morning with meals. In group I patients received additionally from the 1st to the 10th day intravenous drip Cytoflavin 10 ml + 0.9% NaCl solution 200 ml; pentoxifylline solution 5 ml + 0.9% NaCl solution 200 ml. Then, from the 11th to the 60th day, Cytoflavin inside, 2 tablets 2 times a day. Pentoxifylline inside 400 mg 1 tablet 3 times a day. All patients underwent neuropsychological examination using the subjective asthenia rating scale (MFI-20). RESULTS: The effectiveness of treatment in patients of both groups was assessed by clinical, laboratory data and neuropsychological studies. In the main group, a significant reduction in asthenic syndrome was achieved against the background of diagnosed NAFLD compared with the control group. CONCLUSION: The early inclusion of patients with NAFLD and severe asthenic syndrome in the treatment regimen, in addition to the basic therapy of Cytoflavin, achieved a significantly high therapeutic effect in the form of normalization of the main clinical, laboratory and instrumental parameters, as well as a significant reduction in the manifestations of asthenia.

[Cognitive bias in the context of epidemic]. / Effet tunnel en contexte d'épidémie.

In connection with the scope and duration of the COVID-19 pandemic, the clinical judgement of clinicians and medical practitioners could be influenced such that diagnostic errors (delays and inaccuracies) may ensue. We hereby recall through two clinical scenarios the constant need for practitioners to take a step back in reflecting of the diagnostic process to avoid the « tunnel effect ¼ which may result in delaying common and frequent infectious diseases. The flu-like symptoms presented by these patients (fever, myalgia and asthenia…) quickly prompted our emergency room colleagues to suspect SARS-CoV-2 infection. However, further investigations including imagery and blood cultures revealed completely different but common infectious disease conditions, which are potentially fatal.

Dans le contexte de la pandémie de Covid-19, exceptionnelle tant par son ampleur que par sa durée, nous rappelons, à travers deux situations cliniques, la constante nécessité du corps médical de distanciation, de recul durant la démarche diagnostique, afin d'éviter l'« effet tunnel ¼ qui peut conduire à manquer ou retarder le diagnostic d'autres pathologies infectieuses. Les tableaux cliniques pseudo-grippaux (toux, état fébrile, asthénie, myalgies…) des patients présentés dans cet article orientent rapidement le personnel soignant des urgences hospitalières vers des suspicions d'infection à SARS-CoV-2. Il apparaît à la suite des investigations et du résultat de cultures que les diagnostics sont finalement différents des classiques, potentiellement mortels.

Titinopathy, an atypical respiratory failure.

Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation.

[A rare cause of impaired general condition: Muscular and cardiac toxicity of antimalarials]. / Une cause rare d'altération de l'état général : cardiopathie et myopathie aux antipaludéens de synthèse.

INTRODUCTION: This case report signifies the need to systemically assess antimalarial toxicity in those undergoing long-term treatment. CASE REPORT: A 59-year-old man with a history of ischemic-labeled heart disease revealed by conduction disorders and cutaneous lupus treated initially with hydroxychloroquine followed by chloroquine consulted for asthenia and weight loss. Clinically, he had a muscular atrophy, a motor deficit, and an abolition of the osteo-tendinous reflexes in the lower limbs. Adverse drug effects of the antimalarial therapy were suspected-specifically, muscular and cardiac toxicity. The diagnosis was confirmed with a muscle biopsy, which showed typical and florid vacuolar myopathy. Cessation of the drug resulted in a slow regression of symptoms. CONCLUSION: Cardiac and muscular toxicity related to antimalarials are rare and sometimes fatal; thus, they must be systematically assessed in a patient with several years of exposure. A muscle biopsy could be sufficient to allow for the diagnosis.

[Gitelman syndrome]. / Síndrome de Gitelman.

Gitelman syndrome is one of the salt losing tubulopathies. Hypokalemia and hypomagnesemia appear in the setting of the partial blockade of salt absorption in the distal tubule. We conducted a descriptive study of a case series of five patients with Gitelman syndrome (4 women, from 28 to 85 years) in our institution, between the years 2004 and 2015. The most frequent form of diagnosis in our series was by laboratory finding. The only acknowledged clinical symptom was malaise. Regarding laboratory findings, the mean potassemia was of 2.5 ± 0.5 mmol/l, with a minimum value of 2.1 mmol/l. Additionally, the serum magnesium value was of 1.3 ± 0.3 mg/dl. In conclusion, we observed that the forms of presentation consist of biochemical alterations with or without nonspecific manifestations, which currently represents the greatest diagnostic difficulty and reinforces the importance to achieve a timely diagnosis, especially in young patients with critical serum potassium values.

El síndrome de Gitelman forma parte de las denominadas tubulopatías perdedoras de sal. El bloqueo parcial de la reabsorción de sodio en el túbulo contorneado distal determina la aparición de hipokalemia e hipomagnesemia. Se realizó un estudio descriptivo de una serie de cinco casos de síndrome de Gitelman (4 mujeres, de 28 a 85 años de edad) atendidos en nuestra institución entre los años 2004 y 2015. La forma de diagnóstico más frecuente en nuestra serie fue por hallazgo de laboratorio. El único síntoma clínico manifestado en forma espontánea fue astenia. En cuanto a los valores de laboratorio, la potasemia fue 2.5 ± 0.5 mmol/l, con un valor mínimo de 2.1. Adicionalmente, el valor de magnesio en sangre fue 1.3 ± 0.3 mg/dl. Como conclusión, observamos que las formas de presentación consisten en alteraciones bioquímicas con o sin manifestaciones inespecíficas, lo que representa actualmente la mayor dificultad diagnóstica y refuerza la importancia de lograr un diagnóstico oportuno, en especial en pacientes jóvenes y con valores críticos de potasio sérico.

Síndrome de Gitelman / Gitelman syndrome

El síndrome de Gitelman forma parte de las denominadas tubulopatías perdedoras de sal. El bloqueo parcial de la reabsorción de sodio en el túbulo contorneado distal determina la aparición de hipokalemia e hipomagnesemia. Se realizó un estudio descriptivo de una serie de cinco casos de síndrome de Gitelman (4 mujeres, de 28 a 85 años de edad) atendidos en nuestra institución entre los años 2004 y 2015. La forma de diagnóstico más frecuente en nuestra serie fue por hallazgo de laboratorio. El único síntoma clínico manifestado en forma espontánea fue astenia. En cuanto a los valores de laboratorio, la potasemia fue 2.5 ± 0.5 mmol/l, con un valor mínimo de 2.1. Adicionalmente, el valor de magnesio en sangre fue 1.3 ± 0.3 mg/dl. Como conclusión, observamos que las formas de presentación consisten en alteraciones bioquímicas con o sin manifestaciones inespecíficas, lo que representa actualmente la mayor dificultad diagnóstica y refuerza la importancia de lograr un diagnóstico oportuno, en especial en pacientes jóvenes y con valores críticos de potasio sérico.

Gitelman syndrome is one of the salt losing tubulopathies. Hypokalemia and hypomagnesemia appear in the setting of the partial blockade of salt absorption in the distal tubule. We conducted a descriptive study of a case series of five patients with Gitelman syndrome (4 women, from 28 to 85 years) in our institution, between the years 2004 and 2015. The most frequent form of diagnosis in our series was by laboratory finding. The only acknowledged clinical symptom was malaise. Regarding laboratory findings, the mean potassemia was of 2.5 ± 0.5 mmol/l, with a minimum value of 2.1 mmol/l. Additionally, the serum magnesium value was of 1.3 ± 0.3 mg/dl. In conclusion, we observed that the forms of presentation consist of biochemical alterations with or without nonspecific manifestations, which currently represents the greatest diagnostic difficulty and reinforces the importance to achieve a timely diagnosis, especially in young patients with critical serum potassium values.

Pharmacokinetic/Pharmacodynamic Relationship of Enzalutamide and Its Active Metabolite N-Desmethyl Enzalutamide in Metastatic Castration-Resistant Prostate Cancer Patients.

INTRODUCTION: Enzalutamide (ENZA) is an oral androgen receptor inhibitor approved by the Food and Drug Administration and the European Medicines Agency for the treatment of metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). ENZA is extensively metabolized by cytochrome P450 3A4 into N-desmethyl ENZA (NDE), an active metabolite. We aimed to explore the pharmacokinetic/pharmacodynamic relationship for ENZA and NDE in metastatic CRPC patients from a real-world setting. PATIENTS AND METHODS: Trough plasma concentration (Ctrough) of ENZA and NDE were assayed using liquid chromatography coupled with UV detection. The relationship between ENZA, NDE, and composite (ENZA with NDE) plasma concentration and requirement of ENZA dose reduction was investigated using the Mann-Whitney test. A survival univariate analysis was conducted to explore association between progression-free survival (PFS), overall survival (OS), and plasma Ctrough (ENZA, NDE, and composite). RESULTS: Twenty-two metastatic CRPC patients treated with ENZA (median age, 75.5 years; 13 patients (59%) with Eastern Cooperative Oncology Group status 0-1) were prospectively included. Mean plasma Ctrough of ENZA and NDE were 12.4 ± 3.0 µg/mL and 8.8 ± 2.1 µg/mL, respectively. Neither PFS nor OS were statistically associated with ENZA, NDE, or composite plasma Ctrough. In 4 patients (18%) who required ENZA dose reduction because of severe clinical toxicity, an increased ENZA plasma Ctrough was observed compared with 18 remaining patients (16.1 ± 2.4 µg/mL vs. 11.6 ± 2.6 µg/mL, respectively; P = .027). CONCLUSION: The low interindividual variability in ENZA and NDE Ctrough and the lack of relationship with survival do not support the need for plasma drug monitoring. Severe asthenia might be related to higher exposure and could be improved by decreasing ENZA dosing.