Delirium in oncological palliative care and clinical cardiology units: A comparative analysis.

OBJECTIVE: The aim of this study was to compare the sociodemographic and clinical characteristics of delirium in patients treated in a clinical cardiology unit (CCU) and an oncological palliative care unit (OPCU) at a high-complexity institution. CONTEXT: Delirium is a neuropsychiatric syndrome with multicausal etiology, associated with increased morbidity and mortality. METHOD: This was a cross-sectional, analytical observational study. CCU and OPCU patients were evaluated for 480 days. The diagnosis was made according to DSM-V. Sociodemographic characteristics, the Karnofsky index, and the Charlson index were evaluated. Possible etiologies were verified. Severity was assessed with the Delirium Severity Scale (DRS-R98). RESULTS: A total of 1,986 patients were evaluated, 205 were eligible, and 110 were included in the study (CCU: 61, OPCU: 49). Delirium prevalence was 11.35% in the CCU and 9.87% in the OPCU. CCU patients were 12 years older (p < 0.03) and a history of dementia (41 vs. 8.2%; p < 0.001). Organ failure was the most frequent etiology of delirium in the CCU (41.0%), and in the OPCU, the etiologies were neoplasms (28.6%), side effect of medication (22.4%), and infections (2.5%). Differences were found in the clinical characteristics of delirium evaluated by DRS-R98, with the condition being more severe and with a higher frequency of psychotic symptoms in OPCU patients. CONCLUSION: Delirium was a common condition in hospitalized patients in the CCU and the OPCU. The clinical characteristics were similar in both groups; however, significant differences were found in OPCU patients in terms of age, personal history of dementia, and opioid use, as well as the severity of delirium and a greater association with psychotic symptoms. These findings have implications for the early implementation of diagnostic and therapeutic strategies.

Chest tomography for COVID-19 screening in head and neck cancer elective surgery. Is it enough?

INTRODUCTION: Head and neck cancer patients are at high risk of SARS-CoV-2 infection; surgery in them involves risk for patients, surgeons, health personnel, medical institutions and society, since it is associated with prolonged and inadvertent production of aerosols and emergency procedures that facilitate the breach of protective measures by health personnel. OBJECTIVE: To find out if pulmonary tomographic findings are sufficient to preoperatively identify patients with COVID-19. METHODS: Retrospective, cross-sectional, analytical study of patients with cervical-facial neoplasms who were candidates for surgery, preoperatively evaluated by simple chest computed tomography based on the CO-RADS classification. In CO-RADS ≥ 3 patients, surgery was suspended and PCR was performed using nasopharyngeal swab. RESULTS: 322 patients were included, all without COVID-19 symptoms. Tomography was positive in 35 (10.87%); in 30, nasopharyngeal swab was performed: 28 were negative and two were positive; none developed COVID-19 symptoms. CONCLUSIONS: Chest tomography is not useful as the only preoperative screening procedure for COVID-19, since its findings are nonspecific, with a high rate of false-positive results. Clinical evaluation, with PCR and tomography, is the best form of preoperative screening.

INTRODUCCIÓN: Los pacientes con cáncer de cabeza y cuello tienen alto riesgo de infección por SARS-CoV-2; la cirugía en ellos implica riesgo para pacientes, cirujanos, personal de salud, institución médica y sociedad, ya que se asocia a aerosolización prolongada e inadvertida y a procedimientos de urgencia que facilitan la ruptura de las medidas de protección del personal de salud. OBJETIVO: Conocer si los hallazgos tomográficos pulmonares son suficientes para identificar en forma preoperatoria a los pacientes con COVID-19. MÉTODOS: Estudio retrospectivo, transversal y analítico de pacientes con neoplasias cervicofaciales candidatos a cirugía, evaluados preoperatoriamente mediante tomografía axial computarizada simple de tórax con base en la clasificación CO-RADS. En los pacientes CO-RADS ≥ 3 se suspendió la cirugía y se realizó PCR por hisopado nasofaríngeo. RESULTADOS: Se incluyeron 322 pacientes, todos sin síntomas de COVID-19. La tomografía fue positiva en 35 (10.87 %); en 30 se efectuó hisopado nasofaríngeo: 28 fueron negativos y dos, positivos; ninguno desarrolló síntomas de COVID-19. CONCLUSIONES: La tomografía torácica no es útil como procedimiento único de tamizaje preoperatorio de COVID-19, ya que sus hallazgos son inespecíficos, con tasa alta de resultados falsos-positivos. La evaluación clínica, con PCR y tomografía es la mejor forma de pesquisa preoperatoria.

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials.

Objectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non- albicans Candida species. Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5-10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population. Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%-80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin. Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population.

Epoxy resin-based root canal sealers: An integrative literature review.

The correct obturation of the root canal system achieved by means of a core and a cement is essential for the success of endodontic treatment. There are several root canal cements (RCCs) on the market; however, because of their excellent characteristics, epoxy resin-based sealers (ERBSs) have been widely used. The main aim of this review was to analyze and integrate the available information on different ERBSs. An electronic search was performed in the PubMed and Scopus databases, using "epoxy resin" AND "root canal treatment", and "epoxy resin" AND "endodontics" as search terms. In general, ERBSs have good flow properties, film thickness, solubility, dimensional stability, sealing capacity, and radiopacity. They are also able to adhere to dentin while exhibiting low toxicity and some antibacterial effects. However, their main disadvantage is the lack of bioactivity and biomineralization capability. A large number of ERBSs are available on the market, and AH Plus keeps being the gold standard RCC. Yet, information on many of them is limited or non-existent, which could be due to the fact that some of them are relatively new. The latter emphasizes the need for relevant research on the physicochemical and biological properties of some ERBSs, with the aim of supporting their clinical use with sufficient evidence via prospective and long-term studies.

Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity.

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit, receiving strong input from the indirect pathway and regulating a variety of functions, including locomotor output and habit formation. We recently showed that it also acts as a gatekeeper of cocaine-induced behavioral plasticity, as inhibition of parvalbumin-positive cells in the GPe (GPe PV ) prevents the development of cocaine-induced reward and sensitization. However, the molecular and circuit mechanisms underlying this function are unknown. Here we show that GPe PV cells control cocaine reward and sensitization by inhibiting GABAergic neurons in the substantia nigra pars reticulata (SNr GABA ), and ultimately, selectively modulating the activity of ventral tegmental area dopamine (VTA DA ) cells projecting to the lateral shell of the nucleus accumbens (NAcLat). A major input to GPe PV cells is the indirect pathway of the dorsomedial striatum (DMS D 2 ), which receives DAergic innervation from collaterals of VTA DA →NAcLat cells, making this a closed-loop circuit. Cocaine likely facilitates reward and sensitization not directly through actions in the GPe, but rather in the upstream DMS, where the cocaine-induced elevation of DA triggers a depression in DMS D 2 cell activity. This cocaine-induced elevation in DA levels can be blocked by inhibition of GPe PV cells, closing the loop. Interestingly, the level of GPe PV cell activity prior to cocaine administration is correlated with the extent of reward and sensitization that animals experience in response to future administration of cocaine, indicating that GPe PV cell activity is a key predictor of future behavioral responses to cocaine. Single nucleus RNA-sequencing of GPe cells indicated that genes encoding voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability are downregulated in GPe PV cells following a single cocaine exposure, contributing to the elevation in GPe PV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPe PV cell excitability and also impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its potential as a therapeutic to counteract psychostimulant use disorder. Our findings illuminate the molecular and circuit mechanisms by which the GPe orchestrates brain-wide changes in response to cocaine that are required for reward, sensitization, and self-administration behaviors.

Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity.

The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.

Psychiatric disorders in pregnant women admitted to the high-risk obstetric service in a Colombian university clinic between 2013 and 2017.

OBJECTIVE: To determine the psychiatric diagnoses and treatments of patients admitted to the high-risk obstetric service who underwent a consultation with a liaison psychiatrist. METHODS: A descriptive observational study that included pregnant women from the high-risk obstetric service of a highly specialised clinic in Medellín, who had a liaison psychiatry consultation between 2013 and 2017. The main variables of interest were psychiatric and obstetric diagnoses and treatments, in addition to biopsychosocial risk factors. RESULTS: A total of 361 medical records were screened, with 248 patients meeting the inclusion criteria. The main prevailing psychiatric diagnosis was major depressive disorder (29%), followed by adaptive disorder (21.8%) and anxiety disorders (12.5%). The pharmacologic treatments most used by the psychiatry service were SSRI antidepressants (24.2%), trazodone (6.8%) and benzodiazepines (5.2%). The most common primary obstetric diagnosis was spontaneous delivery (46.4%), and the predominant secondary obstetric diagnoses were hypertensive disorder associated with pregnancy (10.4%), gestational diabetes (9.2%) and recurrent abortions (6.4%). Overall, 71.8% of the patients had a high biopsychosocial risk. CONCLUSIONS: The studied population's primary psychiatric disorders were major depressive disorder, adjustment disorder and anxiety disorders, which implies the importance of timely recognition of the symptoms of these perinatal mental pathologies, together with obstetric and social risks, in the prenatal consultation. Psychiatric intervention should be encouraged considering the negative implications of high biopsychosocial risk in both mothers and children.

Mimicking opioid analgesia in cortical pain circuits.

The anterior cingulate cortex plays a pivotal role in the cognitive and affective aspects of pain perception. Both endogenous and exogenous opioid signaling within the cingulate mitigate cortical nociception, reducing pain unpleasantness. However, the specific functional and molecular identities of cells mediating opioid analgesia in the cingulate remain elusive. Given the complexity of pain as a sensory and emotional experience, and the richness of ethological pain-related behaviors, we developed a standardized, deep-learning platform for deconstructing the behavior dynamics associated with the affective component of pain in mice-LUPE (Light aUtomated Pain Evaluator). LUPE removes human bias in behavior quantification and accelerated analysis from weeks to hours, which we leveraged to discover that morphine altered attentional and motivational pain behaviors akin to affective analgesia in humans. Through activity-dependent genetics and single-nuclei RNA sequencing, we identified specific ensembles of nociceptive cingulate neuron-types expressing mu-opioid receptors. Tuning receptor expression in these cells bidirectionally modulated morphine analgesia. Moreover, we employed a synthetic opioid receptor promoter-driven approach for cell-type specific optical and chemical genetic viral therapies to mimic morphine's pain-relieving effects in the cingulate, without reinforcement. This approach offers a novel strategy for precision pain management by targeting a key nociceptive cortical circuit with on-demand, non-addictive, and effective analgesia.

Cationic peptides erase memories by removing synaptic AMPA receptors through endophilin-mediated endocytosis.

Administration of the Zeta Inhibitory Peptide (ZIP) interferes with memory maintenance and long-term potentiation (LTP). However, mice lacking its putative target, the protein kinase PKMζ, exhibit normal learning and memory as well as LTP, making ZIP's mechanism unclear. Here, we show that ZIP disrupts LTP by removing surface AMPA receptors through its cationic charge alone. This effect was fully blocked by drugs that block macropinocytosis and is dependent on endophilin A2 (endoA2)-mediated endocytosis. ZIP and other cationic peptides selectively removed newly inserted AMPAR nanoclusters, providing a mechanism by which these peptides erase memories without effects on basal synaptic function. Lastly, cationic peptides can be administered locally and/or systemically and can be combined with local microinjection of macropinocytosis inhibitors to modulate memories on local and brain-wide scales. Our findings have critical implications for an entire field of memory mechanisms and highlight a previously unappreciated mechanism by which memories can be lost.

[Orange oily anal leakage: a new entity linked to dietary changes]. / Escurrimiento oleoso anaranjado o "keriorrea", ("orange oily anal leakage"): una nueva enfermedad ligada a cambios de hábito alimentario.

INTRODUCTION: Information is accumulating on exceptional cases of oily orange anal leakage, probably caused by certain foods and their form of consumption. The leakage is usually inadvertent and is worrisome for patients. METHOD: Clinical data was gathered on a case series presenting with massive and inadvertent orange oily anal leakage, without sphincter sensation, causing the patients to feel alarmed. This condition usually occurs after eating fish, especially Japanese cuisine. RESULTS: Eleven patients were included (four women and seven men). The mean age was 47.3 years. Colonoscopy had previously been performed in four patients, with normal results. The symptoms, described as keriorrhea, were probably produced by accumulation of indigestible "wax esters", es Mero present in some oily fish, recently incorporated in raw fish dishes (sashimi) or as Japanese Mero sea bass. These oils, which cannot be absorbed or digested, accumulate in the rectum and may also filter spontaneously and induce toxin-related sphincter dysfunction. The same symptoms are sometimes produced after consumption of cooked versions of these species. The diagnosis is given by clinical data, prior ingestion of these types of fish and the self-limiting nature of the symptoms, without the need for further investigations. CONCLUSION: We describe a case series of a recently described entity associated with dietary changes. This entity is benign and self-limiting. Clinicians should be familiar with the symptoms to inform patients correctly and avoid unnecessary laboratory studies.

Dental Pulp Fibroblast: A Star Cell.

INTRODUCTION: Dental pulp fibroblasts (DPFs) are the most abundant cell type in the dental pulp. They play pivotal roles; however, they are often mistaken to be involved only in the repair and maintenance of this connective tissue. METHODS: We used the search terms "pulp fibroblast," "complement system proteins," "pulp inflammation," "angiogenesis," and "dentin pulp regeneration" to identify articles from the PubMed and Scopus databases. RESULTS: These sentinel cells produce all complement system proteins participating in defense processes, control of inflammation, and dentin-pulp regeneration; produce several proinflammatory cytokines and chemokines and express pattern-recognition receptors, demonstrating their involvement in immunoregulatory mechanisms; express neuropeptides and their receptors, playing an important role in neurogenic inflammation and dental pulp wound healing; secrete angiogenic growth factors as well as neurotrophic proteins, essential for dentin-pulp regeneration; regulate neuronal plasticity processes; and can sense the external environment. CONCLUSIONS: This review highlights that DPFs are more than mere passive cells in pulp biology and presents an integrative analysis of their roles and functions.

Adipokines in dental pulp: Physiological, pathological, and potential therapeutic roles.

BACKGROUND: Hundreds of adipokines have been identified, and their extensive range of endocrine functions-regulating distant organs such as oral tissues-and local autocrine/paracrine roles have been studied. In dentistry, however, adipokines are poorly known proteins in the dental pulp; few of them have been studied despite their large number. This study reviews recent advances in the investigation of dental-pulp adipokines, with an emphasis on their roles in inflammatory processes and their potential therapeutic applications. HIGHLIGHTS: The most recently identified adipokines in dental pulp include leptin, adiponectin, resistin, ghrelin, oncostatin, chemerin, and visfatin. They have numerous physiological and pathological functions in the pulp tissue: they are closely related to pulp inflammatory mechanisms and actively participate in cell differentiation, mineralization, angiogenesis, and immune-system modulation. CONCLUSION: Adipokines have potential clinical applications in regenerative endodontics and as biomarkers or targets for the pharmacological management of inflammatory and degenerative processes in dental pulp. A promising direction for the development of new therapies may be the use of agonists/antagonists to modulate the expression of the most studied adipokines.

An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.

Although midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.

Not the same, but is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non- medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9 years, ranging from 16 to 84 years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12 months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12 months after the switch (P > .05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS 28 after 12 months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non- biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Beliefs of parents of children with mental disorders in a university hospital out-patient clinic in Colombia. / Creencias de los padres acerca de los trastornos mentales de sus hijos en una consulta universitaria en Colombia.

OBJECTIVE: Describe the beliefs of parents about the mental disorders of their children who attended a paediatric outpatient clinic at a university hospital. METHODS: This was a descriptive study with parents of children with mental disorders seen from January to May of 2018 at a high complexity hospital in Medellin, Colombia. Ninety-eight (98) parents of children and adolescents attending their first outpatient consultation with Paediatric Psychiatry were studied. An instrument designed by the investigators was applied to obtain demographic variables and beliefs about the origin of their child's mental disorder, treatment and adjuvants. RESULTS: 49.9% of the 98 parents believed that their child had a mental disorder. 43.9% believed the disorder was inherited and 41.8% believed its cause was organic. 95.9% of the parents believed the child needed treatment, including psychotherapy (90.4%) and medication (58.51%). Among the alternative treatments the parents believed the child needed, healing was the most commonly cited by 27.5% of the parents. Of the adjuvant methods, the most commonly cited were reinforcing positive behaviour (82.7%) and correcting with words and setting a good example (72.4%). CONCLUSIONS: Nearly half of the parents believed their child had a mental disorder, the treatment that was most commonly considered was psychotherapy above medication, and the best adjuvant methods cited by parents were reinforcing positive behaviour, correcting with words and setting a good example.

Beliefs of parents of children with mental disorders in a university hospital out-patient clinic in Colombia.

OBJECTIVE: Describe the beliefs of parents about the mental disorders of their children who attended a paediatric outpatient clinic at a university hospital. METHODS: This was a descriptive study with parents of children with mental disorders seen from January to May of 2018 at a high complexity hospital in Medellin, Colombia. Ninety-eight (98) parents of children and adolescents attending their first outpatient consultation with Paediatric Psychiatry were studied. An instrument designed by the investigators was applied to obtain demographic variables and beliefs about the origin of their child's mental disorder, treatment and adjuvants. RESULTS: 49.9% of the 98 parents believed that their child had a mental disorder. 43.9% believed the disorder was inherited and 41.8% believed its cause was organic. 95.9% of the parents believed the child needed treatment, including psychotherapy (90.4%) and medication (58.51%). Among the alternative treatments the parents believed the child needed, healing was the most commonly cited by 27.5% of the parents. Of the adjuvant methods, the most commonly cited were reinforcing positive behaviour (82.7%) and correcting with words and setting a good example (72.4%). CONCLUSIONS: Nearly half of the parents believed their child had a mental disorder, the treatment that was most commonly considered was psychotherapy above medication, and the best adjuvant methods cited by parents were reinforcing positive behaviour, correcting with words and setting a good example.

Detection of Persistent Viruses by High-Throughput Sequencing in Tomato and Pepper from Panama: Phylogenetic and Evolutionary Studies.

High-throughput sequencing from symptomatic tomato and pepper plants collected in Panama rendered the complete genome of the southern tomato virus (isolate STV_Panama) and bell pepper endornavirus (isolate BPEV_Panama), and almost-complete genomes of three other BPEV isolates. Tomato chlorosis virus, tomato mosaic virus, and impatiens necrotic spot virus were also detected. Analysis of the complete genome of STV and BPEV worldwide isolates revealed nucleotide diversities of 0.004246 and 0.070523, respectively. Bayesian phylogenetic analysis showed two main groups for each virus (I and II), and several subgroups for BPEV (IA, IB, IC, IIA and IIB). Isolate STV_Panama clustered with NC_12-03-08 from USA and Tom3-T from France (99.97% nucleotide identity) in Group I and BPEV_Panama was close to the Canadian isolate BPEV_Ontario (99.66% nucleotide identity) in Subgroup IB. No correlation was observed between geographic and genetic distances for both viruses. Panamanian BPEV isolates were divergent, belonging to Groups I and II (nucleotide identities > 87.33%). Evolutionary analysis showed purifying selection in all encoding regions of both viruses, being stronger in the overlapping region of both STV genes. Finally, recombination was detected in BPEV but not in STV. This is the first report of STV and BPEV in Panama.

Not the same, but ¿is it the same? Cycling of biologic agents in rheumatoid arthritis. Experience in the Instituto Mexicano del Seguro Social. / No es el mismo pero ¿es igual? Cycling de agentes biológicos en artritis reumatoide. Experiencia en el Instituto Mexicano del Seguro Social.

INTRODUCTION: Available data for biocomparable drugs are not enough to make clear decisions with respect to the potential consequences of a change for non-medical reasons in efficacy, security and inmunogenicity in patients. In the near future, options on biological treatments, biocomparable drugs, non biocomparable drugs and new chemical synthesis options will grow. Therefore, it is important to know how patients behave in persistence of treatment after a change for non-medical reasons, which already happens on a regular basis in social security institutions in Mexico. This information will help us to better understand the standard of treatment for patients with chronic immunomediated conditions. OBJECTIVE: The primary objective was to measure the impact of change for non-medical reasons in patients with rheumatoid arthritis (RA) treated with an innovative biological on persistence of treatment after changing to a biocomparable drug or a non-biocomparable drug, compared with those patients staying with the innovative biological. STUDY DESIGN: This is an observational study (non-interventionist) of paired cohorts, where an historic cohort obtained by review of clinical records of stable patients in which no modifications to treatment were made for at least six months is compared with two cohorts of patients whose treatments were switched to another treatment with the same therapeutic mechanism for-non-medical reasons (cycling). RESULTS: We included 264 RA patients (ACR/EULAR, 2010); 132 were switched for non-medical reasons, and 132 were not switched. Two-hundred and thirty (87.1%) were female. Average age was 53.9years, ranging from 16 to 84years. Two-hundred and sixty-three patients were Latino (99.6%); one was Caucasian. Persistence of treatment 12months after the change was 84.8% (85.8% in Enbrel/Infinitam, 78.9% for Remicade/Remsima). No statistical difference was found with respect to RA clinical activity measured by DAS28 12months after the switch (P>.05). In the 134 switched patients, 20 discontinued the new treatment due to lack of efficacy of the new drug and were changed to a different drug with a different biologic target. Although no differences were found in the cohorts of switched patients with respect to DAS28 after 12months of use, we did find differences in the frequency of adverse events. Forty-two patients had an adverse event in the drug switch cohorts: 33 in the Enbrel-Infinitam group and 9 in the Remicade-Remsima group. CONCLUSIONS: The persistence of treatment after switching from an innovative drug to a biocomparable or a non-biocomparable in RA patients did not show statistically significative differences in our cohorts, but we did find a higher number of adverse events when comparing those who were changed with those who continued on an innovative drug. Twenty patients in the switch groups had to receive a new drug with a different biological target due to lack of efficacy of the switched drug.

Failures of the Fontan System in Univentricular Hearts and Mortality Risk in Heart Transplantation: A Systematic Review and Meta-Analysis.

The Fontan procedure (FP) is the standard surgical treatment for Univentricular heart diseases. Over time, the Fontan system fails, leading to pathologies such as protein-losing enteropathy (PLE), plastic bronchitis (PB), and heart failure (HF). FP should be considered as a transitional step to the final treatment: heart transplantation (HT). This systematic review and meta-analysis aims to establish the risk of death following HT according to the presence of FP complications. There was a total of 691 transplanted patients in the 18 articles, immediate survival 88% (n = 448), survival from 1 to 5 years of 78% (n = 427) and survival from 5.1 to 10 years of 69% (n = 208), >10 years 61% (n = 109). The relative risk (RR) was 1.12 for PLE (95% confidence interval [CI] = 0.89-1.40, p = 0.34), 1.03 for HF (0.7-1.51, p = 0.88), 0.70 for Arrhythmias (0.39-1.24, p = 0.22), 0.46 for PB (0.08-2.72, p = 0.39), and 5.81 for CKD (1.70-19.88, p = 0.005). In patients with two or more failures, the RR was 1.94 (0.99-3.81, p = 0.05). After FP, the risk of death after HT is associated with CKD and with the presence of two or more failures.