[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.

[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.

[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.

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.

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.

Relevance of CYP3A4*20, UGT1A1*37 and UGT1A1*28 variants in irinotecan-induced severe toxicity.

Severe irinotecan-induced toxicity is associated with UGT1A1 polymorphisms. However, some patients develop side-effects despite harbouring a normal UGT1A1 genotype. As CYP3A4 is also an irinotecan-metabolizing enzyme, our study aimed to elucidate the influence of the CYP3A4*20 loss-of-function allele in the toxicity profile of these patients. Three-hundred and eight metastatic colorectal cancer patients treated with an irinotecan-containing chemotherapy were studied. The presence of CYP3A4*20, UGT1A1*37 and UGT1A1*28 alleles was tested. Associations between these genetic variants and toxicity were evaluated. UGT1A1*28 was significantly associated with severe diarrhoea, neutropenia and asthenia (P = 0.002, P = 0.037 and P = 0.041, respectively). One patient with the UGT1A1*28/*37 genotype presented with grade IV neutropenia and lethal septic shock. One heterozygous UGT1A1 (*1/*28) patient also carried the CYP3A4*20 allele but did not develop toxicity. We confirm that UGT1A1*37 and UGT1A1*28 are associated with severe toxicity and suggest that the CYP3A4*20 allele does not play a role in irinotecan-induced toxicity.

[CLINICAL AND PSYCHOLOGICAL CORRELATIONS IN FIBROMYALGIA PATIENTS].

The features of clinical symptoms, neurotic disorders and the level of subjective control were studied in patients with fibromyalgia. The analysis of relationship between the level of subjective control and neurotic symptoms (asthenia, depression, anxiety, hypochondria) depending the severity of main clinical manifestations of the disease was carried out. It was found that high intensity of fatigue, muscle pain, stiffness, insomnia, and an increase in the number of diagnostic tender points contribute to the formation of inverse correlation between the level of subjective control and neurotic disturbances. Thus, the increase of the externality of the level of subjective control allows indicating to the formation of patients' passivity in relation to their disease, the lack of adherence to prescribed course of treatment (low compliance). Although drug therapy is the main component of complex treatment of fibromyalgia patients, patients require significantly more - successful treatment requires active involvement of patients in the therapy process, as well as changes in their attitudes and lifestyle, which can be achieved by training in so-called "schools" for patients, use of psychotherapeutic methods.

[Not Available]. / Complications non-chirurgicales de la chirurgie bariatrique: à propos de quatre cas et revue de la littérature.

In Belgium and around the world, the weight-control surgery has grown significantly since the beginning of the 21st century. The principal argument in favour of this type of surgery is the expected reduction of the obesity-associated morbidities. However, the expectatif reduction of mortality associated with this kind of surgery is based on a low level of evidence. Besides the mechanical complications, there are a number of health-related problems associated with the post-operative metabolic changes. Authors of the present article have observed four cases presenting with serious affections consecutive to bariatric interventions and reviewed the literature. The most frequent consequence of bariatric surgery is anaemia (15%), which is either due to iron or cyanocobalamine deficiency, followed by neuropathies, bone mineral loss, substance abuse or postprandial hypoglycaemia syndrome. Rare but severe complications are Wernicke's encephalopathy, fulminant hepatitis or hyperoxaluric tubular disease. The prevention, diagnosis and management of these new diseases are becoming a major public health concern.

Cutaneous asthenia (Ehlers-Danlos-like syndrome) of Burmese cats.

OF CASES: A 6-month-old Burmese kitten developed focal skin lesions following a routine ovariohysterectomy. These were eventually attributed to the patient struggling during catheter placement and induction of anaesthesia. The lesions were caused by fluid extravasation in the subcutis and ischaemic necrosis of the overlying dermis, giving rise to an eschar-like appearance. Such lesions have been seen previously in Burmese cats with cutaneous asthenia and it is thought that they arise due to poor collagenous support for dermal blood vessels. An increased skin extensibility index (>23%) supported a diagnosis of cutaneous asthenia (Ehlers-Danlos-like syndrome), which has been reported as an inherited condition of Burmese cats in Australia, New Zealand and Europe. An additional Burmese cat with cutaneous asthenia is presented in detail, with lifetime follow-up and further salient observations by the owner, a veterinarian. Photographs of three other affected Burmese cats are provided to illustrate the range of presentations encountered with this condition. All five affected cats were presented with eschars, atrophic alopecia and increased skin extensibility, while one cat also had skin ulcers. Routine histopathological examination, including use of special stains such as trichrome, was unhelpful in establishing the diagnosis. CLINICAL REVIEW: The clinical features of this genetic disease of Burmese cats are reviewed, especially in relation to the postulated 'vasculopathy' that gives rise to characteristic skin lesions. Long term management of this condition is discussed briefly.

Post-thyroidectomy chronic asthenia: self-deception or disease?

There is clinical evidence that post-total thyroidectomy (TT) patients can present persistent asthenia. The aim of this study was to evaluate the prevalence of asthenia symptoms in such patients, assess whether a chronic asthenia syndrome could be caused by TT or become evident after it. An observational study was carried out comparing two groups of 100 patients each, all with homogeneous characteristics. Group A was treated with total lobectomy (TL), Group B with TT. All patients presented normal thyroid hormone levels. The patients were interviewed in order to identify the ones affected by post-operative asthenia persisting for at least six months, with reduced ability to perform physical and mental work, not showing improvement with rest. The severity of the symptoms has been measured by means of the brief fatigue inventory (BFI). Statistical analysis was performed to evaluate statistically significative differences between groups and prognostic factors in TT group. The incidence of post-operative asthenia was 0 % after TL and 25 % after TT, with the operation being the only significant variable. Asthenia is well known as symptom of post-thyroidectomy, but it has not been adequately investigated as consequence of surgery. We demonstrated that the complete removal of the thyroid gland could determine chronic post-thyroidectomy asthenia, although with intensity limited to low/moderate. Post-thyroidectomy asthenia is a relevant sequela interfering with quality of life of at least 25 % of patients operated, suggesting the need to identify its real causes and limit the indication to TT only when strictly required.

[Constitutional syndrome: clinical entity or a mixed bag]. / Síndrome constitucional: entidad clínica o cajón de sastre.

Fatigue, anorexia and involuntary weight loss have been included under the term constitutional syndrome. These manifestations accompany many diseases in which the diagnosis is made by specific symptoms and signs. However, these events are generally the main reason for consultation and the patient does not report other specific data. This forces us to rigorously investigate the possible causes of the disorder. Usually, three manifestations coexist: asthenia, anorexia and weight loss, but sometimes the patient has only one or two of them. The causes of constitutional symptoms are varied and can be divided into three groups: psychiatric diseases, neoplasms and non-neoplastic diseases. The etiological identification is usually done with a simple protocol, which rules out malignancy; the rest of the cases of uncertain etiology are subject to evolution. The constitutional syndrome correlates well with good prognosis or medical functional processes. Although no clinical guidelines have been developed, score scales may help for the etiological assessment. Given the myriad of different causes of the constitutional syndrome, the treatment of this illness depends primarily on the etiology.

Bajo el término de síndrome constitucional se engloba la manifestación de astenia, anorexia y pérdida involuntaria de peso. Por separado o juntas, estas manifestaciones acompañan a muchas enfermedades cuyo diagnóstico se formula por otros síntomas y signos específicos. Sin embargo, en ocasiones, son el motivo principal de consulta, sin que el paciente refiera otros datos orientadores. Ello obliga a indagar de forma rigurosa las posibles causas del trastorno. Por lo general coexisten las tres manifestaciones (astenia, anorexia y pérdida de peso), pero a veces solo existe una o dos. Las causas del síndrome constitucional son variadas, pero en una primera aproximación pueden dividirse en tres grandes grupos: psiquiátricas, neoplásicas y orgánicas no neoplásicas. Generalmente la identificación etiológica se realiza con un protocolo sencillo que descarta neoplasia; algunos casos de etiología incierta se correlacionan con enfermedades médicas de buen pronóstico o con procesos funcionales. Aunque no existen guías de estudio, se han creado tablas de puntuación que ayudan a la valoración etiológica. Dada la miríada de causas de naturaleza diversa, el tratamiento del síndrome constitucional depende básicamente de su etiología.

Delayed diagnosis of Sheehan's syndrome in a developed country: a retrospective cohort study.

BACKGROUND: Little is known about Sheehan's syndrome (SS), even though it is believed that its incidence is low. The aims of this study were to determine the clinical features and diagnostic delay of SS and to ascertain whether early signs could have allowed earlier diagnosis. SUBJECTS AND METHODS: All patients with SS diagnosed in reference units in the southeast of France between 1980 and 2011 were recruited for this study. Data on obstetrical history, clinical symptoms suggestive of hypopituitarism, early signs, hormone analysis, and magnetic resonance imaging were collected. RESULTS: Of the 40 women found to have SS, 39 were studied. Mean delay in the diagnosis of SS was 9 ± 9.7 years. We found that four of the 35 assessable patients were diagnosed with agalactia, 16 of the 29 assessable ones with amenorrhea, 19 of the 39 with hypothyroidism, eight with acute adrenal insufficiency, and 15 with asthenia. Among the patients for whom there was a diagnostic delay of more than 1 year (n=28), seven had headaches during the postpartum period, all assessable patients had agalactia, six of the 22 assessable ones had amenorrhea, seven of 28 had hypothyroidism, and 12 of 28 had asthenia. CONCLUSION: Most signs of SS are aspecific and classical signs such as agalactia and amenorrhea are often difficult to detect, which can explain the long diagnostic delay. We suggest that all women failing to lactate after postpartum hemorrhage (PPH) should be evaluated by measuring prolactin levels and women with signs such as amenorrhea and asthenia, even several years after PPH, should undergo a blood test including assessment of thyroxine, TSH, 0800  h ACTH-cortisol, and IGF1 levels.