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Calixto Machado

Dr. Calixto Machado graduated as MD in 1976. He continued his medical training to become Specialist in Neurology and Clinical Neurophysiology, First Degree in 1980, and Second Degree in 1984. In 1990 he became the youngest Dr. in Sciences in his country. Dr. Machado received clinical training in specialized neurology centers in Sweden, Italy, and Austria. Dr. Machado has trained many medical students, neurology residents, fellows, and doctorate students in neurosciences from Cuba and the rest of the world. During the last 30 years he has run many research protocols, such as: brain death, coma, persistent vegetative states and other disorders of consciousness, stroke, autism, etc. He has published more than 260 peer reviewed articles, book chapters, and 3 books. His Book “Brain Death: A Reappraisal” has been recognized with great enthusiasm among neurologist, neurosurgeons, intensivists, and physicians specialized in transplants.In 1992, he was the first Cuban neurologist who was a member of the American Academy of Neurology (AAN), nominated as a Corresponding Fellow. He has been the President of the Organizing Committee of the International Symposia on Brain Death, and the International Symposia on Disorders of Consciousness, since the 90’s. In December 2015, he will hold the “VII International Symposium on Brain Death and Disorders of Consciousness”. He has been awarded 17 times with the Best Annual Scientific Medical Research in Cuba. In 2005 he was bestowed with the American Academy of Neurology “Lawrence McHenry Award”, for the excellence in neurology, and in 2011, he was awarded as the “Researcher of Year” by the International Academy for Child Brain Development (Philadelphia, USA), and by the International Association of Functional Neurology and Rehabilitation (Orlando, USA). These were the first times that a Hispanic neurologist, and a neuroscientist from a developing country, received those acknowledgements. He is Senior Professor and Researcher in neurology and clinical neurophysiology at the Institute of Neurology and Neurosurgery, Havana, Cuba. He is the President of the Cuban Society of Clinical Neurophysiology. Leading the National Commission for the Determination of Death, he chaired the edition of the Cuban Law for the diagnosis of death. Dr. Machado is a Corresponding Fellow of the American Academy of Neurology, Chairman of the Network on Defining Death of the International Association of Bioethics, member of The World Federation of Neurology, and the International League against Epilepsy. He is a Senior Academics of the Cuban Academy of Sciences. In the academic field Dr. Machado is recognized as a world expert in neurological disorders such as brain death, coma, disorders of consciousness, neuroimaging, clinical neurophysiology, and stroke. His appointments as visiting professor includes: Miami University (Department of Philosophy and Bioethics), Memorial Sloan-Kettering Cancer and Cornell University in New York, the Institute of Neurology at Columbia University, the Neuroanesthesia and Neurocritical Care Service at Johns Hopkins Hospital, the George Washington University, and the Department of Neurology and Neurosurgery at Jackson's Memorial Center in Miami.During the last 10 years Dr. Machado has been invited at Johns Hopkins on several occasions, as a key-note speaker, and he has impressed the Neuroscience Critical Care team, stimulating scholars to begin a fruitful scientific exchange with Dr. Machado. He has been supported by an International Visiting Scholarship Program co-sponsored by the Johns Hopkins University and a private foundation.Dr. Machado has continuously demonstrated a strong desire to develop and maintain close relations between U.S.-based and Cuban Neuroscientists, and he is recognized by the American Academy of Neurology as the only bridge among American and Cuban scholars..

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Papers by Calixto Machado

Goal: Fast Fourier transform (FFT), has been the main tool for EEG spectral analysis (SPA). As EE... more Goal: Fast Fourier transform (FFT), has been the main tool for EEG spectral analysis (SPA). As EEG can show nonlinear and non-stationary behavior, FFT may at times be meaningless. A novel method was developed for analyzing nonlinear and non-stationary signals using the Hilbert-Huang transform. Methods: We compared spectral analyses of EEG using FFT with Hilbert marginal spectra (HMS) with a multivariate empirical mode decomposition algorithm. Segments of continuous 60-sec EEGs recorded from 19 leads of 47 healthy volunteers were studied. Results: HMS showed a reduction of the alpha activity (-5.64%), with increments in the beta-1 (+1.67%), and gamma (+1.38%) fast activity bands, an increment in theta (+2.14%), and in delta (+0.45%) bands, and vice versa for the FFT method. For weighted mean frequencies, insignificant mean differences (lower than 1Hz) were observed between both methods for delta, theta, alpha, beta-1 and beta-2 bands, and only for gamma band values. The HMS were 3 Hz higher than the FFT method. Conclusion: HMS may be considered a good alternative for SPA of the EEG when nonlinearity or non-stationarity may be present.

Considering the properties of the empirical mode decomposition to extract from a signal its natur... more Considering the properties of the empirical mode decomposition to extract from a signal its natural oscillatory components known as intrinsic mode functions (IMFs), the spectral analysis of these IMFs could provide a novel alternative for the quantitative EEG analysis without a priori establish more or less arbitrary band limits. This approach has begun to be used in the last years for studies of EEG records of patients included in database repositories or including a low number of individuals or of limited EEG leads, but a detailed study in healthy humans has not yet been reported. Therefore, in this study the aims were to explore and describe the main spectral indices of the IMFs of the EEG in healthy humans using a method based on the FFT and another on the Hilbert-Huang transform (HHT). The EEG of 34 healthy volunteers was recorded and decomposed using a recently developed multivariate empirical mode decomposition algorithm. Extracted IMFs were submitted to spectral analysis wit...

The fast Fourier transform (FFT), has been the main tool for the EEG spectral analysis (SPA). How... more The fast Fourier transform (FFT), has been the main tool for the EEG spectral analysis (SPA). However, as the EEG dynamics shows nonlinear and non-stationary behavior, results using the FFT approach may result meaningless. A novel method has been developed for the analysis of nonlinear and non-stationary signals known as the Hilbert-Huang transform method. In this study we describe and compare the spectral analyses of the EEG using the traditional FFT approach with those calculated with the Hilbert marginal spectra (HMS) after decomposition of the EEG with a multivariate empirical mode decomposition algorithm. Segments of continuous 60-seconds EEG recorded from 19 leads of 47 healthy volunteers were studied. Although the spectral indices calculated for the explored EEG bands showed significant statistical differences for different leads and bands, a detailed analysis showed that for practical purposes both methods performed substantially similar. The HMS showed a reduction of the al...

Journal of Cardiac Critical Care TSS, 2020

In effectively resuscitated out-of-hospital cardiac arrest (OHCA) patients who progress to brain ... more In effectively resuscitated out-of-hospital cardiac arrest (OHCA) patients who progress to brain death (BD), resuscitated OHCA with predominantly nonshockable initial rhythms was independently associated with the following five risk factors associated with progression toward BD: female gender, young age, neurologic cause of cardiac arrest, duration of low-flow period, and persistent hemodynamic shock, all of which were independently associated with BD. We require employment of neuroprotection methods to those cases suffering from OHCA, or even from intrahospital cardiac arrests, based on the examination of prognostic risk factors.

SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease ca... more SARS-CoV-2 (CoV-2) is a coronavirus which is causing the actual COVID-19 pandemic. The disease caused by 2019 new coronavirus (2019-nCoV) was named coronavirus disease-19 (COVID-19) by the World Health Organization in February 2020. Primary non-specific reported symptoms of 2019-nCoV infection at the prodromal phase are malaise, fever, and dry cough. The most commonly reported signs and symptoms are fever (98%), cough (76%), dyspnea (55%), and myalgia or fatigue (44%). Nonetheless, recent reports suggest an association between COVID-19 and altered olfactory and taste functions, although smell seems to be more affected than taste. These associations of smell and taste dysfunctions and CoV-2 are consistent with case reports describing a patient with SARS with long term anosmia after recovery from respiratory distress, with the observation that olfactory function is commonly altered after infection with endemic coronaviruses, and with data demonstrating that intentional experimental in...

Neurology, 2019

I applaud the Brain Death Working Group for working toward uniform standards for determination of... more I applaud the Brain Death Working Group for working toward uniform standards for determination of brain death.1

Brain Injury, 2019

Primary objective: To assess and compare the functional state of the autonomic nervous system in ... more Primary objective: To assess and compare the functional state of the autonomic nervous system in healthy individuals with patients in coma using measures of heart rate variability (HRV), and to evaluate its efficiency in predicting mortality. Research design: Retrospective group comparison study of patients in coma, classified into two subgroups, according to their Glasgow coma score, with a healthy control group. Methods and procedures: HRV indices were calculated from 7 minutes of free of artifacts electrocardiograms using the Hilbert-Huang method in the spectral range 0.02-0.6 Hz. A special procedure was applied to avoid the effect of confounding factors. Stepwise multiple regression logistic analysis (SMLRA), followed by ROC curve analysis were applied to evaluate predictions. Results: Progressive reduction of HRV associated with deepening of coma was confirmed and a mortality score model including three spectral HRV indices: absolute power values of the very low, low frequency, and the power in normalized units of the very high frequency bands (0.4-0.6 Hz). The SMLRA model showed sensitivity of 95.65%, specificity of 95.83%, positive predictive value of 95.65%, and overall efficiency of 95.74%. Conclusions: HRV is a reliable method to assess the integrity of the neural control of the caudal brainstem centres upon the heart, of patients in coma, and predict mortality.

Consciousness and Cognition, 2016

International Journal on Disability and Human Development, 2016

Objective: To develop a method to correct the nonlinear effect of the heart rate (HR) on differen... more Objective: To develop a method to correct the nonlinear effect of the heart rate (HR) on different heart rate variability (HRV) indices of heart rate variability. Methods: The study included 265 healthy participants (17-69 years old), a group of 36 type 1 diabetes mellitus patients, including 15 patients with positive diagnosis of cardiovascular autonomic neuropathy (CAN), and a group of 24 CAN positive type-2 spinocerebellar ataxia patients. HR and HRV indices were calculated for 5-min resting ECG recordings. The proposed correction method (CM) included the joint application of multiple regression analysis and Z-transformations of HR and HRV indices. To assess the effect of the CM, correlation analysis, multivariate factor analysis, and the ANOVA test were applied to both groups before and after corrections. Results: The CM was able to remove the effect of HR on HRV indices, and at the same time, were preserved the expected differences between HR and HRV indices between controls and patients. Sample size was not a factor. Conclusions: Our method may be considered a novel approach, and may represent an alternative to the use of currently developed procedures. Significance: Studies of HRV without an appropriately HR correction should not be considered in the future.

European Journal of Cancer Supplements, 2008

Medicina Intensiva, 2015

Muerte encefálica; Doppler transcraneal; Diagnóstico; Donante de órganos Resumen El Doppler trans... more Muerte encefálica; Doppler transcraneal; Diagnóstico; Donante de órganos Resumen El Doppler transcraneal permite demostrar la parada circulatoria cerebral que acompaña a la muerte encefálica, siendo especialmente útil en pacientes sedados, o en los que no puede realizarse la exploración neurológica completa. El Doppler transcraneal es una técnica portátil, no invasiva y de alta disponibilidad. Entre sus limitaciones está la ausencia de ventana sónica y los casos falsos negativos. En pacientes con diagnóstico clínico de muerte encefálica, que tienen cráneos abiertos o anoxia como causa de la muerte, puede sonorizarse flujo sanguíneo cerebral, ya que la parada circulatoria cerebral no siempre es sincrónica con el diagnóstico clínico. Su rentabilidad diagnóstica es, por tanto, dependiente del tiempo, hecho que debe ser reconocido para no retrasar la declaración de muerte. A pesar de sus limitaciones, el Doppler transcraneal ayuda a resolver frecuentes problemas diagnósticos, evita un consumo innecesario de recursos y puede optimizar la obtención de órganos para trasplante.

Atherosclerosis Supplements, 2006

Rheumatology, 2006

for the Juvenile Scleroderma Working Group of the Pediatric Rheumatology European Society (PRES) ... more for the Juvenile Scleroderma Working Group of the Pediatric Rheumatology European Society (PRES) Objective. Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. Methods. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Results. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. Conclusion. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.

Proceedings of the National Academy of Sciences, 2001

Simple phylogenetic tests were applied to a large data set of nucleotide sequences from two nucle... more Simple phylogenetic tests were applied to a large data set of nucleotide sequences from two nuclear genes and a region of the mitochondrial genome of Trypanosoma cruzi , the agent of Chagas' disease. Incongruent gene genealogies manifest genetic exchange among distantly related lineages of T. cruzi . Two widely distributed isoenzyme types of T. cruzi are hybrids, their genetic composition being the likely result of genetic exchange between two distantly related lineages. The data show that the reference strain for the T. cruzi genome project (CL Brener) is a hybrid. Well-supported gene genealogies show that mitochondrial and nuclear gene sequences from T. cruzi cluster, respectively, in three or four distinct clades that do not fully correspond to the two previously defined major lineages of T. cruzi . There is clear genetic differentiation among the major groups of sequences, but genetic diversity within each major group is low. We estimate that the major extant lineages of T. ...

Journal of Clinical Epidemiology, 1999

Objective: To compare the efficacy and safety of Xuezhikang, a relatively inexpensive locally pro... more Objective: To compare the efficacy and safety of Xuezhikang, a relatively inexpensive locally produced medication used for lowering blood lipids, and Lovastatin in hyperlipidemic patients with hypertension.

Circulation, 2001

Background Implantable cardioverter-defibrillators (ICDs) can terminate some ventricular tachycar... more Background Implantable cardioverter-defibrillators (ICDs) can terminate some ventricular tachycardias (VTs) painlessly with antitachycardia pacing (ATP). ATP has not routinely been applied for VT >188 bpm because of concerns about efficacy, risk of acceleration, and delay of definitive shock therapy. This prospective, multicenter study evaluated the efficacy of empirical ATP to terminate fast VT (FVT; >188 bpm). Methods and Results Two hundred twenty coronary artery disease patients received ICDs for standard indications. Empirical, standardized therapy was programmed so that all FVT episodes (average cycle length [CL] 240 to 320 ms, 250 to 188 bpm) were treated with 2 ATP sequences (8-pulse burst pacing train at 88% of the FVT CL) before shock delivery. A total of 1100 episodes of spontaneous ventricular tachyarrhythmias occurred during a mean of 6.9±3.6 months of follow-up. Fifty-seven percent were classified as slow VT (CL≥320 ms), 40% as FVT (240 ms≤CL<320 ms), and 3% a...

Neurology, 2010

Objective: To provide an update of the 1995 American Academy of Neurology guideline with regard t... more Objective: To provide an update of the 1995 American Academy of Neurology guideline with regard to the following questions: Are there patients who fulfill the clinical criteria of brain death who recover neurologic function? What is an adequate observation period to ensure that cessation of neurologic function is permanent? Are complex motor movements that falsely suggest retained brain function sometimes

Advances in Experimental Medicine and Biology

Key autonomic functions are in continuous development during adolescence which can be assessed us... more Key autonomic functions are in continuous development during adolescence which can be assessed using the heart rate variability (HRV). However, the influence of different demographic and physiological factors on HRV indices has not been fully explored in adolescents. In this study we aimed to assess the effect of age, gender, and heart rate on HRV indices in two age groups of healthy adolescents (age ranges, 13-16 and 17-20 years) and two groups of healthy young adults (21-24 and 25-30 years). We addressed the issue using 5-min ECG recordings performed in the sitting position in 255 male and female participants. Time, frequency, and informational domains of HRV were calculated. Changes in HRV indices were assessed using a multiple linear regression model to adjust for the effects of heart rate, age, and gender. We found that heart rate produced more significant effects on HRV indices than age or gender. There was a progressive reduction in HRV with increasing age. Sympathetic influence increased with age and parasympathetic influence progressively decreased with age. The influence of gender was manifest only in younger adolescents and young adults. In conclusion, age, gender, and particularly heart rate have a substantial influence on HRV indices, which ought to be considered to avoid biases in the study of the autonomic nervous system development. The lack of the gender-related effects on HRV indices in late adolescence could be related to non-completely achieved maturity of the autonomic mechanisms, which deserves further exploration.