Is Satoyoshi syndrome an autoimmune disease? A systematic review.

OBJECTIVES: Satoyoshi syndrome is a rare multisystem disease of presumed autoimmune aetiology. We carried out a systematic review to evaluate the available evidence to support that autoimmune hypothesis. METHODS: We searched for Satoyoshi syndrome cases in PubMed, the Web of Science and Scopus up to January 2022, using keywords 'Satoyoshi syndrome' or 'Komuragaeri disease'. Data on symptoms, associated autoimmune diseases, presence of autoantibodies and response to treatment were collected. RESULTS: A total of 77 patients from 57 articles published between 1967 and 2021 were included; 59 patients were women. The mean age at diagnosis was 21.2 years. All cases had painful muscular spasms and alopecia. Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. Satoyoshi syndrome was associated with other autoimmune diseases: myasthenia gravis, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, atopic dermatitis, bronchial and lupus erythematosus. Autoantibody determinations were performed in 39 patients, of which 27 had positive results. The most frequently detected autoantibodies were ANAs. Other less frequently found autoantibodies were: anti-acetylcholine receptor antibodies, anti-DNA antibodies, antithyroid antibodies, anti-glutamic acid decarboxylase (anti-GAD) and anti-gliadin antibodies. Pharmacological treatment was reported in 50 patients. Most of them improved with CS, immunosuppressants and immunoglobulins, or a combination of these medications. CONCLUSION: Satoyoshi syndrome is associated with other autoimmune diseases and a variety of autoantibodies. Improvement after CS or other immunosuppressant treatment was observed in 90% of cases. These data support an autoimmune aetiology for Satoyoshi syndrome. More studies including systematic determination of autoantibodies in all patients with Satoyoshi syndrome will help us advance in our understanding of this disease.

Global trends of dalbavancin: A bibliometric analysis.

WHAT IS KNOWN AND OBJECTIVE?: Dalbavancin is used against gram-positive pathogens such as Staphylococcus aureus in acute bacterial skin and skin-structure infections. METHODS: Our main goal was to identify the key articles sustaining the current knowledge of this drug's therapeutic possibilities through a bibliometric analysis of the available literature. RESULTS AND DISCUSSION: On 15 March 2021, we searched the Web of Science electronically for documents that contain within its title the term "dalbavancin." We found a total of 675 documents that average 20.23 citations/publication with a density of 682.60 citations per/year, yielding an h-index of 58. After ranking them by the number of times cited, we extracted the top 100 most-cited records (T100). Number of citations/publication ranged from 13 to 231, publication years were 2002-2019, with the top-cited article published in 2014. All T100 publications were written in English. JMI Laboratories was the institution with the most articles in the T100 (22 documents), and the United States was the top country (75 documents). Five authors participated in at least five of the T100, led by Jones RN with 20 articles. Positions #1, #2, #5, and #9 were clinical trials for acute bacterial skin and skin structure infections (ABSSSI), the on-label indication for dalbavancin. Only one article in the top 10 (T10) was an off-label indication that was published in 2005 with 186 citations, and occupied the third position among the T100. Using the VOSviewer© programme, we observed that the most used keywords were: dalbavancin, lipoglycopeptide, gram-positive, osteomyelitis, vancomycin, and MRSA. WHAT IS NEW AND CONCLUSIONS?: Our study identifies the most significant research on dalbavancin, including the highest impact publications, and highlights the recent trend of dalbavancin in new therapies. The T10 articles include the most important dalbavancin clinical trials, along with other studies and reviews that support the growing role of this antibiotic in clinical use. Emphasis has been on the favourable pharmacokinetic profile that allows administration once-weekly, with minimal risk of severe adverse events.

Common Laboratory Parameters Are Useful for Screening for Alcohol Use Disorder: Designing a Predictive Model Using Machine Learning.

The diagnosis of alcohol use disorder (AUD) remains a difficult challenge, and some patients may not be adequately diagnosed. This study aims to identify an optimum combination of laboratory markers to detect alcohol consumption, using data science. An analytical observational study was conducted with 337 subjects (253 men and 83 women, with a mean age of 44 years (10.61 Standard Deviation (SD)). The first group included 204 participants being treated in the Addictive Behaviors Unit (ABU) from Albacete (Spain). They met the diagnostic criteria for AUD specified in the Diagnostic and Statistical Manual of mental disorders fifth edition (DSM-5). The second group included 133 blood donors (people with no risk of AUD), recruited by cross-section. All participants were also divided in two groups according to the WHO classification for risk of alcohol consumption in Spain, that is, males drinking more than 28 standard drink units (SDUs) or women drinking more than 17 SDUs. Medical history and laboratory markers were selected from our hospital's database. A correlation between alterations in laboratory markers and the amount of alcohol consumed was established. We then created three predicted models (with logistic regression, classification tree, and Bayesian network) to detect risk of alcohol consumption by using laboratory markers as predictive features. For the execution of the selection of variables and the creation and validation of predictive models, two tools were used: the scikit-learn library for Python, and the Weka application. The logistic regression model provided a maximum AUD prediction accuracy of 85.07%. Secondly, the classification tree provided a lower accuracy of 79.4%, but easier interpretation. Finally, the Naive Bayes network had an accuracy of 87.46%. The combination of several common biochemical markers and the use of data science can enhance detection of AUD, helping to prevent future medical complications derived from AUD.

Acute Bacterial Skin and Skin-Structure Infections, efficacy of Dalbavancin: a systematic review and meta-analysis.

OBJECTIVES: To know the efficacy of different doses of dalbavancin in acute bacterial skin and skin-structure infections (ABSSSIs) and versus other antibiotics. METHODS: We performed a systematic review of dalbavancin efficacy for ABSSSIs. We selected 10 clinical trials from MEDLINE and Cochrane databases for qualitative review. Of these, five trials compared one or two doses of dalbavancin versus other antibiotics such as vancomycin or linezolid. RESULTS: Treatment outcomes with other antibiotics were not significantly different versus two doses of dalbavancin (OR 1.13; 95% CI 0.75-1.71; p = 0.55) or single dose dalbavancin (OR 0.98; 95% CI 0.19-5.17; p = 0.98). One dose versus two doses of dalbavancin did not show significant differences in any of the treatment groups. In contrast, the global microbiological assessment results indicated a favorable outcome for two doses of dalbavancin compared to the single dose of dalbavancin (OR 2.96; 95% CI 1.19-7.39; p = 0.02) in both methicillin-resistant and methicillin-susceptible Staphylococcus aureus. CONCLUSION: Either single dose or two dose dalbavancin treatment is as clinically effective as other antibiotics such as vancomycin and linezolid for the treatment of ABSSSIs.Abbreviations ABSSI: acute bacterial skin and skin-structure infection; AUC: area under the concentration-time curve; CE: clinical evaluable; CI: confidence interval; EOT: end of treatment; ITT: intention-to-treat; LOS: length of stay; MIC: minimum inhibitory concentration; MIC90: minimum concentration to inhibit growth of 90% of isolates; MR: methicillin resistant; MRSA: methicillin-resistant Staphylococcus aureus; MS: methicillin susceptible; MSSA: methicillin-susceptible Staphylococcus aureus; OPAT: Outpatient Parenteral Antimicrobial Therapy; OR: odds ratio; PI: penicillin intermediate; PR: penicillin resistant; PS penicillin susceptible; SIRS: systemic inflammatory response syndrome; SSTI: skin and soft tissue infection; TOC: test of cure; VR: vancomycin resistant; VS: vancomycin susceptible.

What do beta-lactams add to vancomycin or daptomycin in the treatment of patients with methicillin-resistant Staphylococcus aureus bacteraemia? A review.

Several studies have documented the synergy between vancomycin/daptomycin and various beta-lactams, and clinical studies have studied this combination therapy in humans. We review the published literature on this topic to know the utility of the combined treatment with beta-lactams in treating bacteraemia methicillin-resistant Staphylococcus aureus (MRSA) infections. Fifteen observational studies, three randomised clinical trials and three systematics reviews are analysed in this article. Observational studies used ceftaroline, cefazolin, piperacillin/tazobactam or cefepime among the beta-lactams. Clinical trials used cloxacillin or flucloxacillin as the most used beta-lactam in two trials and ceftaroline in one. Three systematic reviews are published. One of them only includes studies with vancomycin and included six studies. The other two systematic reviews include patients with daptomycin or vancomycin and included 15 and 9 studies, respectively. Adding a beta-lactam to vancomycin or daptomycin may help shorten bacteraemia and avoid recurrences in patients with MRSA bacteraemia. There is no evidence that combined therapy improves mortality. Nephrotoxicity in clinical trials precludes the use of combination therapy mainly with cloxacillin or flucloxacillin, but systematic reviews have not found a significant difference in this point in observational studies with other beta-lactams. The role of other beta-lactams such as ceftaroline should be thoroughly studied in these patients.

Current Evidence on the Antimicrobial Treatment and Chemoprophylaxis of Human Leptospirosis: A Meta-Analysis.

BACKGROUND: Leptospirosis is a worldwide zoonotic infection, and its management needs to be refined. This study aims to discern which antibiotic would be the best option to treat leptospirosis disease and analyze the efficacy of chemoprophylaxis regimens to prevent this illness. METHODS: systematic review and meta-analysis on the efficacy of antibiotic treatment and chemoprophylaxis of leptospirosis in humans. RESULTS: Ten clinical trials compared an antibiotic treatment with placebo or other antibiotic treatments in leptospirosis (the most recent one was published in 2007). The meta-analysis shows no effect of penicillin treatment on mortality compared to placebo (OR 1.65; 95% CI 0.76-3.57; p = 0.21). There are no differences between penicillin and cephalosporins or doxycycline. Penicillin does not reduce the time of defervescence (MD-0.16; 95% CI (-1.4) -1.08; p = 0.80) nor hospital stay (MD 0.15; 95% CI (-0.75)-1.06; p = 0.74). Besides, the data did not demonstrate any effectiveness of the use of penicillin in terms of the incidence of oliguria/anuria, the need for dialysis treatment, time to creatinine normalization, incidence of jaundice, or the liver function normalization time. Eight trials have assessed prophylactic treatment against leptospirosis with different strategies. A weekly dose of 200 mg of doxycycline does not show benefit versus placebo regarding the number of new cases of symptomatic leptospirosis (OR 0.20; 95% CI 0.02-1.87; p = 0.16). A single dose of doxycycline at exposure to flood water could have a beneficial effect (OR 0.23; 95% CI 0.07-0.77; p = 0.02). None of the other chemoprophylaxis regimens tested have shown a statistically significant effect on the number of new symptomatic cases. CONCLUSION: There is no evidence that antibiotics are a better treatment than placebo regarding mortality, shortening of fever, liver and kidney function, or reduction in the hospital stay. On the other hand, neither doxycycline nor penicillin, nor azithromycin have shown statistically significant differences in preventing symptomatic infection. Well-designed clinical trials, including other antibiotics such as quinolones or aminoglycosides, are urgently needed to improve our understanding of the treatment for this infection, which continues to be a neglected disease.

Intestinal Spirochetosis in an HIV-positive Patient.

We present the case of an HIV-positive patient admitted because of costal pain secondary to neoplasia. During investigations, a colonoscopy showed non-specific ulcerations. Histological examination resulted in a diagnosis of intestinal spirochetosis. This infection can be asymptomatic or cause non-specific symptoms such as diarrhoea or abdominal pain. Intestinal spirochetosis should be included in the differential diagnosis of colon lesions in patients with HIV infection. LEARNING POINTS: Intestinal spirochetosis is associated with chronic diarrhoea and often with normal colonoscopy.This infection should be included in the differential diagnosis of HIV patients with digestive symptomatology in the absence of other more frequent causes.

A Bibliometric Evaluation of the Top 100 Cited Dimethyl Fumarate Articles.

Dimethyl fumarate is a cytoprotective and immunomodulatory drug used in the treatment of multiple sclerosis. We performed a bibliometric study examining the characteristics and trends of the top 100 cited articles that include dimethyl fumarate in the title. On 21 September 2020 we carried out an electronic search in the Web of Science (WOS), seeking articles that include the following terms within the title: dimethyl fumarate, BG-12, or Tecfidera. To focus our investigation on original research, we refined the search to include only articles, early access, others, case report, and clinical trials. We obtained a total of 1115 items, which were cited 7169 times, had a citation density of 6.43 citations/item, and an h-index of 40. Around 2010, there was a jump in the number of published articles per year, rising from 5 articles/year up to 12 articles/year. We sorted all the items by the number of citations and selected the top 100 most cited (T100). The T100 had 4164 citations, with a density of 37 citations/year and contained 16 classic research articles. They were published between 1961 and 2018; the years 2010-2018 amassed nearly 80% of the T100. We noted 17 research areas with articles in the T100. Of these, the number one ranking went to neurosciences/neurology with 39 articles, and chemistry ranked second on the T100 list with 14 items. We noticed that the percentage of articles belonging to different journals changed depending on the time period. Chemistry held the highest number of papers during 1961-2000, while pharmacology andneurosciences/neurology led the 2001-2018 interval. A total of 478 authors from 145 institutions and 25 countries were included in the T100 ranking. The paper by Gold R et al. was the most successful with 14 articles, 1.823 citations and a density of 140.23 citations/year. The biotechnological company Biogen led the T100 list with 20 articles. With 59 published articles, the USA was the leading country in publications. We concluded that this study analyzed the use of and research on dimethyl fumarate from a different perspective, which will allow the readership (expert or not) to understand the relevance of classic and recent literature on this topic.

Generation and validation of in-hospital mortality prediction score in COVID-19 patients: Alba-score.

BACKGROUND: COVID-19 has a wide range of symptoms reported, which may vary from very mild cases (even asymptomatic) to deadly infections. Identifying high mortality risk individuals infected with the SARS-CoV-2 virus through a prediction instrument that uses simple clinical and analytical parameters at admission can help clinicians to focus on treatment efforts in this group of patients. METHODS: Data was obtained retrospectively from the electronic medical record of all COVID-19 patients hospitalized in the Albacete University Hospital Complex until July 2020. Patients were split into two: a generating and a validating cohort. Clinical, demographical and laboratory variables were included. A multivariate logistic regression model was used to select variables associated with in-hospital mortality in the generating cohort. A numerical and subsequently a categorical score according to mortality were constructed (A: mortality from 0% to 5%; B: from 5% to 15%; C: from 15% to 30%; D: from 30% to 50%; E: greater than 50%). These scores were validated with the validation cohort. RESULTS: Variables independently related to mortality during hospitalization were age, diabetes mellitus, confusion, SaFiO2, heart rate and lactate dehydrogenase (LDH) at admission. The numerical score defined ranges from 0 to 13 points. Scores included are: age ≥71 years (3 points), diabetes mellitus (1 point), confusion (2 points), onco-hematologic disease (1 point), SaFiO2 ≤ 419 (3 points), heart rate ≥ 100 bpm (1 point) and LDH ≥ 390 IU/L (2 points). The area under the curve (AUC) for the numerical and categorical scores from the generating cohort were 0.8625 and 0.848, respectively. In the validating cohort, AUCs were 0.8505 for the numerical score and 0.8313 for the categorical score. CONCLUSIONS: Data analysis found a correlation between clinical admission parameters and in-hospital mortality for COVID-19 patients. This correlation is used to develop a model to assist physicians in the emergency department in the COVID-19 treatment decision-making process.

Gastrointestinal manifestations in Satoyoshi syndrome: a systematic review.

BACKGROUND: Satoyoshi syndrome (SS) [OMIM 600705; ORFHA 3130] is a multisystemic disease with a probable autoimmune basis, whose main symptoms are muscle spasms, alopecia, diarrhea and skeletal alterations. Chronic diarrhea may be severe and result in malnutrition, anemia, growth retardation, cachexia, disability and even death. However, to date, no review of the digestive symptoms has been carried out. METHODS: A search was performed in MEDLINE, Scopus and Web of Science databases. Cases of SS, without language or date restrictions, were recorded. Sixty-seven cases of SS were found up until December 2019. Thirty-nine cases described gastrointestinal manifestations. RESULTS: Chronic diarrhea was the main digestive symptom (92.3%). Other symptoms such as abdominal pain (15.4%), nausea (7.7%) and vomiting (7.7%), were less frequent. The D-xylose test was positive in 10 out of 12 patients, and 9 out of 13 cases showed a flattened oral glucose tolerance test suggesting carbohydrate malabsorption. Antinuclear antibodies were detected in 8 out of 16 cases. Antibodies to stomach or duodenum tissue lysates were also detected by Western blot. Histological data revealed predominantly lymphoplasmacytic inflammatory infiltrate that can affect any section of the digestive tract. In 6 out of 10 patients, diarrhea improved with a treatment regimen that included corticosteroids. Other treatments, such as methotrexate, carbohydrate restricted diets or otilonium bromide, improved digestive symptoms in isolated patients. Improvement of symptoms up to three years of follow-up has been described. None of the three patients who died had received corticosteroids or immunosuppressants. CONCLUSION: Chronic diarrhea with malabsorption is one of the most disabling symptoms in SS. The early recognition of this disease is essential for immunosuppressive treatment and a better outcome.

Treatment of Satoyoshi syndrome: a systematic review.

BACKGROUND: Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. Clinical course without treatment may result in serious disability or death. A review of treatment and its response is still pending. RESULTS: Sixty-four cases of Satoyoshi syndrome were published between 1967 and 2018. 47 cases described the treatment administered. Drugs used can be divided into two main groups of treatment: muscle relaxants/anticonvulsants, and corticosteroids/immunosuppressants. Dantrolene improved muscle symptoms in 13 out of 15 cases, but not any other symptoms of the disease. Other muscle relaxants or anticonvulsant drugs showed little or no effect. 28 out of 30 cases responded to a regimen that included costicosteroids. Other immunosuppressive drugs including cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus and cyclophosphamide were used to decrease corticosteroid dose or improve efficacy. Immunoglobulin therapy was used in nine patients and four of them obtained a favorable response. CONCLUSION: Corticosteroids was the most widely treatment employed with the best results in Satoyoshi syndrome. Further studies are needed to determine optimal dose and duration of corticosteroids as well as the role of other immunosuppressants and immunoglobulin therapy. Genetic or autoimmune markers will be useful to guide future therapies.

[Comprehensive Care Home Unit: reduction of hospital resources during influenza outbreaks]. / Unidad domiciliaria de atención integral: Reducción de recursos hospitalarios durante brotes de gripe.

OBJECTIVE: The Comprehensive Care Home Unit of the General Hospital of Villarrobledo is a unit formed by a geriatrician who sees people in nursing homes to improve their quality of care. The activity of the Unit has been analyzed, mainly with the objective of avoiding referral to the emergency room, avoiding hospital admissions, avoiding hospital readmissions and reducing the number of hospital admission days. METHODS: We retrospectively described the clinical activity of the Unit during the influenza outbreak of 2017 and 2018. We selected sociodemographical variables, functional assessment scales (Katz index, Barthel index and the Functional Ambulation Classification), and the Global Deterioration Scale. We registered mortality, type of treatment, oncological patients and patients with supplementary tests. The population was divided into four subgroups: hospital admission avoided, hospital re-admission avoided, referral to the emergency department avoided and reduction of admission days. The demographic characteristics were described, including the mode or mean of the variables. An economic report was made, and an analysis of cost per process according to the subgroups, means of Related Groups for the Diagnosis and degree of dependency measured by the Barthel index. RESULTS: We selected 112 patients, they had a mean age of 82.2 years, Katz G (34.8%), IB 28.8 (DE 34.9), FAC 0 (63.4%) and GDS 7 (22.3%). The most frequent disease seen was respiratory infection (63.2%), 71.4% received active treatment, 10.7% complementary tests were performed, 17.9% oncological and 17% mortality. Cost analysis: hospital readmission avoided (€ 4,128 per patient) and patients with total disability (BI 0-20, € 3,623 per patient) presented more economic saving. The economic savings were more than € 230,000. CONCLUSIONS: The contribution of the Unit during periods of influenza outbreak is cost saving because of reduced numbers of admissions, numbers of readmissions, days of admission and emergency room visits.

OBJETIVO: La Unidad Domiciliaria de Atención Integral (UDAI) del Hospital General de Villarrobledo está formada por un geriatra que atiende a las personas institucionalizadas para mejorar su calidad asistencial. Se analizó la actividad de la UDAI, principalmente en el objetivo de evitar ingresos y reingresos hospitalarios, evitar visitas a urgencias y facilitar el alta hospitalaria prematura. METODOS: Describimos de forma retrospectiva la actividad de la UDAI durante los brotes de gripe del 2017 y 2018. Aportamos variables sociodemográficas, escalas de valoración funcional (índice de Katz, índice de Barthel y la Escala de Valoración Funcional de la Marcha), y la Escala de Deterioro Global. Registramos mortalidad, tipo de tratamiento, pacientes oncológicos y pruebas complementarias. Se dividió la población en cuatro subgrupos: ingreso hospitalario evitado, reingreso hospitalario evitado, derivación a urgencias evitada y reducción días de ingreso. Se describieron las características demográficas, incluido la moda o media de las variables. Se realizó una memoria económica, y un análisis de coste por proceso según los subgrupos, medias de Grupos Relacionados por el Diagnóstico y grado de dependencia medido por el Índice de Barthel. RESULTADOS: Se seleccionaron 112 pacientes, presentaban una edad media de 82,2 años, Katz G (34,8%), IB 28,8 (DE 34,9), FAC 0 (63,4%) y GDS 7 (22,3%). La enfermedad más frecuente fue la infección respiratoria (63,4%), recibieron tratamiento activo un 71,4%, se realizaron pruebas complementarias en un 10,7%, oncológico 17,9% y exitus 17%. Análisis de costes: el reingreso hospitalario evitado (4.128 € por paciente) y los pacientes con discapacidad total (IB 0 ­ 20, 3.623 € por paciente) presentaron un mayor ahorro de costes. El ahorro económico fue de más de 230.000€. CONCLUSIONES: La contribución de la UDAI durante los periodos de brote de gripe supone un ahorro de costes basado en disminuciones de hospitalizaciones, disminución de reingresos, acortamiento de estancias hospitalarias y reducción de derivaciones a urgencias.

Treatment of pulmonary brucellosis: a systematic review.

INTRODUCTION: Pulmonary involvement is a rare, focal complication of human brucellosis. The aim of this review is to describe clinical and radiologic features, treatment administered and clinical course of these patients. Areas covered: We conducted a systematic search of scientific reports of brucellosis with pulmonary involvement published from January 1985 to July 2016. Four main patterns of disease were observed: pneumonia, pleural effusion, nodules and interstitial pattern. Cough and fever were the most common symptoms. Brucella spp. culture was obtained from blood (50%) or pleural fluid. Treatment is based on the same antibiotics and combinations of antibiotics as for patients with acute no complicated brucellosis. The most frequent antimicrobial combination was doxycycline and rifampin for six weeks. The clinical course was favorable in most reports, and mortality was remarkably low (<1%). Expert commentary: Non-specific clinical and radiological manifestations were the main reason for the delay in proper treatment. Difficulty in distinguishing Brucellosis from other pulmonary infections, such as tuberculosis, sometimes posed an added diagnostic challenge.

[Latrepirdine: a systematic review of the preclinical studies]. / Latrepirdina: revision sistematica de los estudios preclinicos.

We conduct a systematic review of the preclinical studies published to date involving the use of latrepirdine (Dimebon ®). Latrepirdine is capable of modulating different targets, such as those related with mitochondria, acetylcholinesterase activity or intraneuronal calcium levels, perhaps thanks to its action upon the N-methyl-D-aspartate-type receptor, which belongs to the glutamate family. The findings published on the possible effect of latrepirdine in protein aggregation processes in disorders such as Alzheimer's disease and Parkinson's disease are quite controversial. Likewise, the possible neuroprotective effect of latrepirdine has been evaluated in animal models of neurodegenerative diseases, again with heterogeneous results. Consequently, it can be concluded that no preclinical scientific evidence has been found to justify carrying out clinical trials.

TITLE: Latrepirdina: revision sistematica de los estudios preclinicos.Se realiza una revision sistematica sobre los estudios preclinicos publicados en los que se utiliza latrepirdina (Dimebon ®). La latrepirdina es capaz de modular diferentes dianas, como las relacionadas con la mitocondria, la actividad de la acetilcolinesterasa o los niveles de calcio intraneuronales, quizas gracias a su accion sobre el receptor tipo N-metil-D-aspartato, de la familia del glutamato. Los resultados publicados sobre el posible efecto de la latrepirdina en procesos de agregacion proteica en trastornos como la enfermedad de Alzheimer y la enfermedad de Parkinson muestran una gran controversia. Asimismo, el posible efecto neuroprotector de la latrepirdina se ha evaluado en modelos animales de enfermedades neurodegenerativas, y muestra de nuevo resultados heterogeneos. Por todo ello, se concluye que no se ha localizado la evidencia cientifica preclinica que avale la realizacion de los ensayos clinicos.

Detection of IgM antibrucella antibody in the absence of IgGs: a challenge for the clinical interpretation of brucella serology.

The use of enzyme-linked immunosorbent assay (ELISA) for the detection of IgG and IgM antibodies antibrucella has become widespread in the diagnosis of human brucellosis. IgM anti-Brucella antibodies are indicative of acute infection. Between 2009-2013, 5307 patients were evaluated for serologic diagnosis at the Microbiology Laboratory of the Albacete General Hospital. A ELISA IgM-positive, IgG-negative anti-Brucella antibody serology pattern was detected in 17 of those patients. Epidemiology data, symptoms, laboratory data, treatment and outcome from these patients were reviewed. Sixteen patients presented with musculoskeletal pain, fatigue and/or fever and 1 was asymptomatic. Five patients received treatment with doxycycline combined with rifampin, gentamycin or streptomycin during 6-12 weeks, with no improvement. None of the 17 patients were finally diagnosed with brucellosis. Our results indicate that anti-Brucella IgM positive serology, per se, is not enough to diagnose acute brucellosis and other methods should be used for confirmation. Brucella serology data should be interpreted taking into account the patient's clinical history and epidemiological context.

On the clinical evidence leading to tetrazepam withdrawal.

INTRODUCTION: In July 2013, the European Medicines Agency suspended the marketing authorizations of tetrazepam across the European Union. Herein, we examine the various kinds of adverse drug reactions (ADRs) reported to be associated with tetrazepam. AREAS COVERED: We undertook a two-sided systematic approach. First, we conducted a search in Medline for all studies that have published about tetrazepam ADRs in peer-reviewed journals. Second, we collected tetrazepam ADRs from pharmacovigilance system databases. Our study reveals discrepancies in the information provided by these two different sources, both in the number of cases reported as well as in the kind of reported ADRs. Whereas cutaneous alterations are the only ADRs reported in peer-reviewed journals, pharmacovigilance system databases include others (hepatobiliary, neurological and psychiatric). EXPERT OPINION: We noted the lack of randomized controlled clinical trials evaluating tetrazepam efficiency and safety. We failed to find a turning point in the amount of ADRs reported following tetrazepam withdrawal to underpin the validity of the withdrawal. We stress the importance of a better communication of knowledge in scientific literature, pharmacovigilance agencies, and from doctors to prevent marketed usage of drugs with well-established side effects during long periods.