RESUMEN
During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue1,2. Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPOLPS) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPOLPS neurons. Finally, we show that VMPOLPS neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPOLPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection.
Asunto(s)
Apetito , Fiebre , Infecciones , Neuronas , Área Preóptica , Animales , Apetito/efectos de los fármacos , Depresores del Apetito/farmacología , Fiebre/inducido químicamente , Fiebre/fisiopatología , Hibridación Fluorescente in Situ , Infecciones/inducido químicamente , Infecciones/fisiopatología , Lipopolisacáridos , Neuronas/efectos de los fármacos , Comunicación Paracrina , Poli I-C , Área Preóptica/citología , Área Preóptica/efectos de los fármacos , Área Preóptica/fisiologíaRESUMEN
Passive whole-body hyperthermia increases limb blood flow and cardiac output ( Q Ì $\dot Q$ ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q Ì $\dot Q$ . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single-leg heating; (3) 3 h of two-leg heating; and (4) 2.5 h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q Ì $\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q Ì $\dot Q$ through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q Ì $\dot Q$ ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and Q Ì $\dot Q$ . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented Q Ì $\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.
Asunto(s)
Gasto Cardíaco , Hipertermia , Humanos , Masculino , Adulto , Hipertermia/fisiopatología , Gasto Cardíaco/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Flujo Sanguíneo Regional/fisiología , Fiebre/fisiopatología , Adulto Joven , Calor , HemodinámicaRESUMEN
Febrile seizures (FSs) are the most common convulsion in infancy and childhood. Considering the limitations of current treatments, it is important to examine the mechanistic cause of FSs. Prompted by a genome-wide association study identifying TMEM16C (also known as ANO3) as a risk factor of FSs, we showed previously that loss of TMEM16C function causes hippocampal neuronal hyperexcitability [Feenstra et al., Nat. Genet. 46, 1274-1282 (2014)]. Our previous study further revealed a reduction in the number of warm-sensitive neurons that increase their action potential firing rate with rising temperature of the brain region harboring these hypothalamic neurons. Whereas central neuronal hyperexcitability has been implicated in FSs, it is unclear whether the maximal temperature reached during fever or the rate of body temperature rise affects FSs. Here we report that mutant rodent pups with TMEM16C eliminated from all or a subset of their central neurons serve as FS models with deficient thermoregulation. Tmem16c knockout (KO) rat pups at postnatal day 10 (P10) are more susceptible to hyperthermia-induced seizures. Moreover, they display a more rapid rise of body temperature upon heat exposure. In addition, conditional knockout (cKO) mouse pups (P11) with TMEM16C deletion from the brain display greater susceptibility of hyperthermia-induced seizures as well as deficiency in thermoregulation. We also found similar phenotypes in P11 cKO mouse pups with TMEM16C deletion from Ptgds-expressing cells, including temperature-sensitive neurons in the preoptic area (POA) of the anterior hypothalamus, the brain region that controls body temperature. These findings suggest that homeostatic thermoregulation plays an important role in FSs.
Asunto(s)
Regulación de la Temperatura Corporal/genética , Canales de Cloruro/genética , Fiebre/genética , Hipertermia/genética , Área Preóptica/metabolismo , Convulsiones Febriles/genética , Potenciales de Acción/fisiología , Animales , Animales Recién Nacidos , Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/fisiología , Canales de Cloruro/deficiencia , Femenino , Fiebre/inducido químicamente , Fiebre/metabolismo , Fiebre/fisiopatología , Expresión Génica , Hipocampo/metabolismo , Hipocampo/fisiopatología , Hipertermia/metabolismo , Hipertermia/fisiopatología , Ácido Kaínico/administración & dosificación , Masculino , Ratones , Ratones Noqueados , Neuronas/metabolismo , Neuronas/patología , Área Preóptica/fisiopatología , Isoformas de Proteínas/deficiencia , Isoformas de Proteínas/genética , Ratas , Convulsiones Febriles/inducido químicamente , Convulsiones Febriles/metabolismo , Convulsiones Febriles/fisiopatologíaRESUMEN
Body temperature must be monitored in patients receiving Hospital-at-Home (HaH) care for COVID-19 and other infectious diseases. Continuous temperature telemonitoring (CTT) detects fever and patient deterioration early, facilitating decision-making. We performed a validation clinical study assessing the safety, comfort, and impact on healthcare practice of Viture®, a CTT system, compared with a standard digital axillary thermometer in 208 patients with COVID-19 and other infectious diseases treated in HaH at the Navarra University Hospital (HUN). Overall, 3258 pairs of measurements showed a clinical bias of -0.02 °C with limits of agreement of -0.96/+0.92 °C, a 95% acceptance rate, and a mean absolute deviation of 0.36 (SD 0.30) °C. Viture® detected 3 times more febrile episodes and revealed fever in 50% more patients compared with spot measurements. Febrile episodes were detected 7.23 h (mean) earlier and modified the diagnostic and/or therapeutic approach in 43.2% of patients. Viture® was validated for use in a clinical setting and was more effective in detecting febrile episodes than conventional methods.
Asunto(s)
Temperatura Corporal , COVID-19 , Fiebre , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Masculino , Femenino , Fiebre/diagnóstico , Fiebre/fisiopatología , Persona de Mediana Edad , Anciano , SARS-CoV-2/aislamiento & purificación , Telemedicina , Adulto , Termómetros , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentación , Anciano de 80 o más AñosRESUMEN
Exercise is a common trigger of heat-related illness (HRI) events in dogs, accounting for 74% of canine HRI cases treated under primary veterinary care in the United Kingdom. However, few empirical studies have evaluated the effectiveness of differing cooling methods for dogs with exertional hyperthermia or HRI. This study aimed to prospectively evaluate effects of ambient conditions and post-exercise management practices (cooling methods and vehicular confinement) on the post-exercise temperature change of dogs participating in UK canicross events. Canine temperature was recorded at three intervals post-exercise: as close as possible to 0- (immediately post-exercise), 5-, and 15-min post-exercise. Ambient conditions and post-exercise management were recorded for 115 cooling profiles from 52 dogs. In 28/115 (24.4%) profiles, the dog's temperature increased during the first 5-min post-exercise. Overall, 68/115 (59.1%) profiles included passive cooling (stood or walked outside), 35 (30.4%) active cooling (cold-water immersion or application of a cooling coat), and 12 (10.4%) involved no cooling and were immediately housed in vehicles. No dogs developed hypothermia during the study and no adverse effects were observed from any cooling method. In hyperthermic dogs, overall post-exercise body temperature change was significantly negatively associated (i.e. the dogs cooled more) with 0-min post-exercise body temperature (ß = -0.93, p < 0.001), and not being housed in a vehicle (ß = -0.43, p = 0.013). This study provides evidence cold-water immersion (in water at 0.1-15.0 °C) can be used to effectively and safely cool dogs with exertional hyperthermia. Progressive temperature increases in many dogs - even after exercise has terminated - supports the message to "cool first, transport second" when managing dogs with HRI. When transporting dogs post-exercise or with HRI even after active cooling, care should be taken to cool the vehicle before entry and promote air movement around the dog during transport to facilitate ongoing cooling and prevent worsening of hyperthermia during travel.
Asunto(s)
Hipertermia , Condicionamiento Físico Animal , Perros , Animales , Masculino , Hipertermia/terapia , Hipertermia/veterinaria , Hipertermia/fisiopatología , Enfermedades de los Perros/terapia , Enfermedades de los Perros/fisiopatología , Femenino , Reino Unido , Temperatura Corporal , Fiebre/terapia , Fiebre/veterinaria , Fiebre/fisiopatología , Regulación de la Temperatura Corporal , DeportesRESUMEN
Fever is a conserved and prominent response to infection. Yet, the issue of how CD4 T cell responses are modulated if they occur at fever temperatures remains poorly addressed. We have examined the priming of naive CD4 T cells in vitro at fever temperatures, and we report notable fever-mediated modulation of their cytokine commitment. When naive CD4 T cells were primed by plate-bound anti-CD3 and anti-CD28 monoclonal antibodies at moderate fever temperature (39 °C), they enhanced commitment to IL4/5/13 (Th2) and away from IFNg (Th1). This was accompanied by up-regulation of the Th2-relevant transcription factor GATA3 and reduction in the Th1-relevant transcription factor Tbet. Fever sensing by CD4 T cells involved transient receptor potential vanilloid cation channels (TRPVs) since TRPV1/TRPV4 antagonism blocked the febrile Th2 switch, while TRPV1 agonists mediated a Th2 switch at 37 °C. The febrile Th2 switch was IL4 independent, but a γ-secretase inhibitor abrogated it, and it was not found in Notch1-null CD4 T cells, identifying the Notch pathway as a major mediator. However, when naive CD4 T cells were primed via antigen and dendritic cells (DCs) at fever temperatures, the Th2 switch was abrogated via increased production of IL12 from DCs at fever temperatures. Thus, immune cells directly sense fever temperatures with likely complex physiological consequences.
Asunto(s)
Linfocitos T CD4-Positivos/fisiología , Diferenciación Celular/fisiología , Fiebre/fisiopatología , Receptores Notch/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Temperatura Corporal/fisiología , Linfocitos T CD4-Positivos/citología , Células Cultivadas , Calor , Ratones , Modelos BiológicosRESUMEN
We compared clinical symptoms, laboratory findings, radiographic signs and outcomes of COVID-19 and influenza to identify unique features. Depending on the heterogeneity test, we used either random or fixed-effect models to analyse the appropriateness of the pooled results. Overall, 540 articles included in this study; 75,164 cases of COVID-19 (157 studies), 113,818 influenza type A (251 studies) and 9266 influenza type B patients (47 studies) were included. Runny nose, dyspnoea, sore throat and rhinorrhoea were less frequent symptoms in COVID-19 cases (14%, 15%, 11.5% and 9.5%, respectively) in comparison to influenza type A (70%, 45.5%, 49% and 44.5%, respectively) and type B (74%, 33%, 38% and 49%, respectively). Most of the patients with COVID-19 had abnormal chest radiology (84%, p < 0.001) in comparison to influenza type A (57%, p < 0.001) and B (33%, p < 0.001). The incubation period in COVID-19 (6.4 days estimated) was longer than influenza type A (3.4 days). Likewise, the duration of hospitalization in COVID-19 patients (14 days) was longer than influenza type A (6.5 days) and influenza type B (6.7 days). Case fatality rate of hospitalized patients in COVID-19 (6.5%, p < 0.001), influenza type A (6%, p < 0.001) and influenza type B was 3%(p < 0.001). The results showed that COVID-19 and influenza had many differences in clinical manifestations and radiographic findings. Due to the lack of effective medication or vaccine for COVID-19, timely detection of this viral infection and distinguishing from influenza are very important.
Asunto(s)
COVID-19/fisiopatología , Gripe Humana/fisiopatología , Infecciones del Sistema Respiratorio/fisiopatología , COVID-19/diagnóstico por imagen , COVID-19/epidemiología , COVID-19/mortalidad , Tos/diagnóstico , Tos/fisiopatología , Disnea/diagnóstico , Disnea/fisiopatología , Registros Electrónicos de Salud , Fiebre/diagnóstico , Fiebre/fisiopatología , Humanos , Periodo de Incubación de Enfermedades Infecciosas , Virus de la Influenza A/patogenicidad , Virus de la Influenza A/fisiología , Virus de la Influenza B/patogenicidad , Virus de la Influenza B/fisiología , Gripe Humana/diagnóstico por imagen , Gripe Humana/epidemiología , Gripe Humana/mortalidad , Faringitis/diagnóstico , Faringitis/fisiopatología , Infecciones del Sistema Respiratorio/diagnóstico por imagen , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/mortalidad , Rinorrea/diagnóstico , Rinorrea/fisiopatología , SARS-CoV-2/patogenicidad , SARS-CoV-2/fisiología , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n = 15) and influenza (n = 13) patients. We identified a large set of differentially expressed proteins (n = 132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.
Asunto(s)
Proteínas Sanguíneas/inmunología , Infecciones por Coronavirus/inmunología , Tos/inmunología , Síndrome de Liberación de Citoquinas/inmunología , Fiebre/inmunología , Cefalea/inmunología , Gripe Humana/inmunología , Mialgia/inmunología , Neumonía Viral/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/patogenicidad , Proteínas Sanguíneas/genética , COVID-19 , Niño , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Tos/genética , Tos/fisiopatología , Tos/virología , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/fisiopatología , Síndrome de Liberación de Citoquinas/virología , Citocinas/genética , Citocinas/inmunología , Femenino , Fiebre/genética , Fiebre/fisiopatología , Fiebre/virología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Cefalea/genética , Cefalea/fisiopatología , Cefalea/virología , Humanos , Gripe Humana/genética , Gripe Humana/fisiopatología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Mialgia/genética , Mialgia/fisiopatología , Mialgia/virología , Orthomyxoviridae/patogenicidad , Pandemias , Neumonía Viral/genética , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Análisis por Matrices de Proteínas , Proteoma/genética , Proteoma/inmunología , Receptores de Citocinas/genética , Receptores de Citocinas/inmunología , SARS-CoV-2 , Transducción de Señal/inmunologíaRESUMEN
BACKGROUND: Maternal intrapartum fever has a serious impact on mother and child. However, the corresponding study seems to be in short. METHODS: The role of inflammatory cells in patients who were diagnosed with intrapartum fever lived in part of Eastern China was evaluated. The obstetrics outcomes, complete blood cell count (CBC) and thereby converted neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, monocyte to lymphocyte ratio (MLR), and vaginal secretion were compared in different groups. RESULTS: Prepartum values of white blood cell (WBC), red blood cell (RBC), and hemoglobin (Hb) were all a little higher in the febrile group than in the afebrile group, and postpartum WBC in the afebrile group was still higher while postpartum RBC and Hb were inferior to non-fever maternity. Postpartum NLR and MLR were all higher in the fever group but not preferred overtly difference before delivery. Additionally, the comparison of WBC, RBC, Hb, platelets, neutrophils, and monocytes in prepartum and postpartum all showed significant differences. CONCLUSION: The parturition could bring about the value change of CBC and intrapartum fever might aggravate or alleviate this change. Besides, the intrapartum fever might not be caused mainly by infection and the difference between bacteria and fungus could reflect in the CBC.
Asunto(s)
Fiebre , Periodo Periparto/fisiología , Complicaciones del Embarazo , Adulto , Recuento de Células Sanguíneas , China/epidemiología , Estudios Transversales , Femenino , Fiebre/epidemiología , Fiebre/fisiopatología , Humanos , Recién Nacido , Parto , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/fisiopatología , Resultado del Embarazo/epidemiologíaRESUMEN
Fever is a common phenomenon during infection or inflammatory conditions. This stereotypic rise in body temperature (Tb) in response to inflammatory stimuli is a result of autonomic responses triggered by prostaglandin E2 action on EP3 receptors expressed by neurons in the median preoptic nucleus (MnPOEP3R neurons). To investigate the identity of MnPOEP3R neurons, we first used in situ hybridization to show coexpression of EP3R and the VGluT2 transporter in MnPO neurons. Retrograde tracing showed extensive direct projections from MnPOVGluT2 but few from MnPOVgat neurons to a key site for fever production, the raphe pallidus. Ablation of MnPOVGluT2 but not MnPOVgat neurons abolished fever responses but not changes in Tb induced by behavioral stress or thermal challenges. Finally, we crossed EP3R conditional knock-out mice with either VGluT2-IRES-cre or Vgat-IRES-cre mice and used both male and female mice to confirm that the neurons that express EP3R and mediate fever are glutamatergic, not GABAergic. This finding will require rethinking current concepts concerning the central thermoregulatory pathways based on the MnPOEP3R neurons being GABAergic.SIGNIFICANCE STATEMENT Body temperature is regulated by the CNS. The rise of the body temperature, or fever, is an important brain-orchestrated mechanism for fighting against infectious or inflammatory disease, and is tightly regulated by the neurons located in the median preoptic nucleus (MnPO). Here we demonstrate that excitatory MnPO neurons mediate fever and examine a potential central circuit underlying the development of fever responses.
Asunto(s)
Fiebre/fisiopatología , Ácido Glutámico , Inflamación/fisiopatología , Neuronas , Área Preóptica/fisiopatología , Subtipo EP3 de Receptores de Prostaglandina E , Animales , Temperatura Corporal , Regulación de la Temperatura Corporal , Femenino , Fiebre/inducido químicamente , Globo Pálido/fisiopatología , Inflamación/inducido químicamente , Lipopolisacáridos , Masculino , Ratones , Ratones Noqueados , Actividad Motora , Vías Nerviosas/fisiopatología , Área Preóptica/citología , Estrés Psicológico , Proteína 2 de Transporte Vesicular de Glutamato/genéticaRESUMEN
With the growing number of COVID-19 cases in recent times. significant set of patients with extra pulmonary symptoms has been reported worldwide. Here we venture out to summarize the clinical profile, investigations, and radiological findings among patients with SARS-CoV-2-associated meningoencephalitis in the form of a systemic review. This review was carried out based on the existing PRISMA (Preferred Report for Systematic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase, and Cochrane library and Preprint servers up till 30 June 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes "SARS-COV-2," "COVID-19," and "meningoencephalitis." All peer reviewed, case-control, case report, pre print articles satisfying our inclusion criteria were involved in the study. Quantitative data was expressed in mean ± SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p < 0.05 considered to be statistically significant. A total of 61 cases were included from 25 studies after screening from databases and preprint servers, out of which 54 of them had completed investigation profile and were included in the final analysis. Clinical, laboratory findings, neuroimaging abnormalities, and EEG findings were analyzed in detail. This present review summarizes the available evidences related to the occurrence of meningoencephalitis in COVID-19.
Asunto(s)
COVID-19/fisiopatología , Tos/fisiopatología , Fatiga/fisiopatología , Fiebre/fisiopatología , Meningoencefalitis/fisiopatología , SARS-CoV-2/patogenicidad , Adulto , Anciano , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , COVID-19/diagnóstico por imagen , COVID-19/virología , Confusión/diagnóstico por imagen , Confusión/tratamiento farmacológico , Confusión/fisiopatología , Confusión/virología , Tos/diagnóstico por imagen , Tos/tratamiento farmacológico , Tos/virología , Disnea/diagnóstico por imagen , Disnea/tratamiento farmacológico , Disnea/fisiopatología , Disnea/virología , Electroencefalografía , Fatiga/diagnóstico por imagen , Fatiga/tratamiento farmacológico , Fatiga/virología , Femenino , Fiebre/diagnóstico por imagen , Fiebre/tratamiento farmacológico , Fiebre/virología , Humanos , Hidroxicloroquina/uso terapéutico , Masculino , Meningoencefalitis/diagnóstico por imagen , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/virología , Persona de Mediana Edad , Neuroimagen , SARS-CoV-2/efectos de los fármacos , Tratamiento Farmacológico de COVID-19RESUMEN
Opsoclonus-myoclonus-ataxia syndrome is a heterogeneous constellation of symptoms ranging from full combination of these three neurological findings to varying degrees of isolated individual sign. Since the emergence of coronavirus disease 2019 (COVID-19), neurological symptoms, syndromes, and complications associated with this multi-organ viral infection have been reported and the various aspects of neurological involvement are increasingly uncovered. As a neuro-inflammatory disorder, one would expect to observe opsoclonus-myoclonus syndrome after a prevalent viral infection in a pandemic scale, as it has been the case for many other neuro-inflammatory syndromes. We report seven cases of opsoclonus-myoclonus syndrome presumably parainfectious in nature and discuss their phenomenology, their possible pathophysiological relationship to COVID-19, and diagnostic and treatment strategy in each case. Finally, we review the relevant data in the literature regarding the opsoclonus-myoclonus syndrome and possible similar cases associated with COVID-19 and its diagnostic importance for clinicians in various fields of medicine encountering COVID-19 patients and its complications.
Asunto(s)
Ataxia/fisiopatología , COVID-19/fisiopatología , Tos/fisiopatología , Fiebre/fisiopatología , Mialgia/fisiopatología , Síndrome de Opsoclonía-Mioclonía/fisiopatología , SARS-CoV-2/patogenicidad , Adulto , Anticonvulsivantes/uso terapéutico , Ataxia/diagnóstico por imagen , Ataxia/tratamiento farmacológico , Ataxia/etiología , Azitromicina/uso terapéutico , COVID-19/complicaciones , COVID-19/diagnóstico por imagen , Clonazepam/uso terapéutico , Tos/diagnóstico por imagen , Tos/tratamiento farmacológico , Tos/etiología , Disnea/diagnóstico por imagen , Disnea/tratamiento farmacológico , Disnea/etiología , Disnea/fisiopatología , Femenino , Fiebre/diagnóstico por imagen , Fiebre/tratamiento farmacológico , Fiebre/etiología , Humanos , Hidroxicloroquina/uso terapéutico , Levetiracetam/uso terapéutico , Masculino , Persona de Mediana Edad , Mialgia/diagnóstico por imagen , Mialgia/tratamiento farmacológico , Mialgia/etiología , Síndrome de Opsoclonía-Mioclonía/diagnóstico por imagen , Síndrome de Opsoclonía-Mioclonía/tratamiento farmacológico , Síndrome de Opsoclonía-Mioclonía/etiología , Oseltamivir/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Ácido Valproico/uso terapéutico , Tratamiento Farmacológico de COVID-19RESUMEN
The severe acute respiratory syndrome novel coronavirus-2 pandemic has established a new set of challenges to health care delivery. Remotely monitored physiologic sensors on implantable cardiac devices can provide insight into the differential diagnosis of dyspnea in the heart failure population. We report on a unique pattern of sensor deviations that seem to occur specifically with severe acute respiratory syndrome novel coronavirus-2 infection.
Asunto(s)
COVID-19/fisiopatología , Insuficiencia Cardíaca/fisiopatología , Monitoreo Fisiológico/instrumentación , Transductores , Anciano , Disnea/fisiopatología , Fiebre/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Frecuencia Respiratoria/fisiologíaRESUMEN
BACKGROUND: Currently, we remain uncertain about which patients are at increased risk for recurrent pericarditis. We developed a risk score for pericarditis recurrence in patients with acute pericarditis. MATERIALS AND METHODS: We prospectively recruited 262 patients with a first episode of acute pericarditis. Baseline patients' demographics, clinical, imaging and laboratory data were collected. Patients were followed up for a median of 51 months (interquartile range 21-71) for recurrence. Variables with <10% missingness were entered into multivariable logistic regression models with stepwise elimination to explore independent predictors of recurrence. The final model performance was assessed by the c-index whereas model's calibration and optimism-corrected c-index were evaluated after 10-fold cross-validation. RESULTS: We identified six independent predictors for pericarditis recurrence, that is age, effusion size, platelet count (negative predictors) and reduced inferior vena cava collapse, in-hospital use of corticosteroids and heart rate (positive predictors). The final model had good performance for recurrence, c-index 0.783 (95% CI 0.725-0.842), while the optimism-corrected c-index after cross-validation was 0.752. Based on these variables, we developed a risk score point system for recurrence (0-22 points) with equally good performance (c-index 0.740, 95% CI 0.677-0.803). Patients with a low score (0-7 points) had 21.3% risk for recurrence, while those with high score (≥12 points) had a 69.8% risk for recurrence. The score was predictive of recurrence among most patient subgroups. CONCLUSIONS: A simple risk score point system based on 6 variables can be used to predict the individualized risk for pericarditis recurrence among patients with a first episode of acute pericarditis.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Glucocorticoides/uso terapéutico , Pericardiocentesis , Pericarditis/terapia , Adulto , Factores de Edad , Anciano , Aspirina/uso terapéutico , Dolor en el Pecho/fisiopatología , Colchicina/uso terapéutico , Femenino , Fiebre/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Ibuprofeno/uso terapéutico , Masculino , Persona de Mediana Edad , Pericarditis/sangre , Pericarditis/fisiopatología , Recuento de Plaquetas , Recurrencia , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: Although the incidence of co-existent pulmonary tuberculosis (PTB) and lung cancer in China is increasing, risk factors related to its development are still poorly understood. We aimed to investigate which clinical factors were associated with the odds of co-existent PTB and lung cancer (PTB-lung cancer) cases in a case-control study. METHOD: A total of 125 PTB-lung cancer patients were enrolled by Beijing Chest Hospital as the case group between January 2012 and December 2016. Age- and sex-matched PTB-only (N = 125) and lung cancer-only (N = 125) patients were selected as the control groups. Data were collected from the medical records and computed tomography (CT) reports. The case group was further categorized into three sub-groups according to the diagnosis intervals between previous PTB and lung cancer (<1 year, 1-10 years, and > 10 years). RESULT: Compared with both controls of PTB-only and lung cancer-only patients, the PTB-lung cancer case group had significantly higher proportions of patients with irritant cough, expectoration, hemoptysis, fever and CT features of irregular mass and pleural thickening. For PTB patients, fibrous calcification (OR, 2.193; 95%CI, 1.168-4.117) was associated with higher odds of lung cancer (P-value < .05). CONCLUSION: Distinct clinical symptoms and CT tests may help with the early diagnosis of PTB-lung cancer cases. PTB patients with fibrous calcification may have a higher risk of lung cancer. Further multicenter prospective studies are required to validate our findings.
Asunto(s)
Neoplasias Pulmonares/fisiopatología , Tuberculosis Pulmonar/fisiopatología , Anciano , Anciano de 80 o más Años , Calcinosis/diagnóstico por imagen , Estudios de Casos y Controles , Dolor en el Pecho/fisiopatología , Tos/fisiopatología , Femenino , Fiebre/fisiopatología , Hemoptisis/fisiopatología , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Linfadenopatía/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Enfermedades Pleurales/diagnóstico por imagen , Derrame Pleural/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico por imagenRESUMEN
NEW FINDINGS: What is the central question of this study? We hypothesized that prior illness would increase the susceptibility to and severity of heat stroke (HS). What is the main finding and its importance? We provide the first experimental evidence, using a mouse model of HS, that recent viral illness increases the severity of HS. Our data indicate that this effect is not attributable to the exacerbation of hyperthermia but is a consequence of ongoing coagulation and systemic inflammatory reactions. Our data suggest that measurement of platelets, cytokines and chemokines before heat exposure might be indicative of susceptibility to HS, with coagulation and inflammation being potential targets for intervention that could improve recovery. ABSTRACT: It is hypothesized that prior illness exacerbates heat stroke (HS) in otherwise healthy organisms by augmenting hyperthermia during heat exposure or deactivating cellular pathways that protect against organ injury. To test these hypotheses, we injected telemetered male C57BL/6J mice with lipopolysaccharide (LPS; 50 µg kg-1 i.p.) or polyinosinic:polycytidylic acid (PIC; 100 µg i.p.) as a bacterial or a viral mimic, respectively, with saline (SAL; equivalent volume) as a control. Mice recovered for 48 or 72 h before HS (maximal core temperature = 42.4°C). Platelet counts, cytokines, chemokines and organ injury were determined 48 or 72 h after injection (without heating) or at maximal core temperature and at 1 day of recovery from HS. In the absence of heat, PIC induced more robust signs of sickness and increased cytokines and chemokines (TNF-α, RANTES, IP-10 and MIP-1ß) at 48 h, which was not observed with LPS (P < 0.05). Responses of both groups recovered by 72 h, although low platelet counts persisted after PIC (P < 0.05). Heat-induced hyperthermia was similar among mice injected with SAL, LPS and PIC; however, PIC-injected mice displayed more severe responses during recovery from HS, with reduced survival (48 h, 70 versus 100%; P < 0.05), deeper and longer post-HS hypothermia, greater reductions in platelets, elevated RANTES, IP-10, IL-6 and TNF-α and greater duodenal injury (P < 0.05). By 72 h, survival from HS was no longer reduced in PIC-injected mice, although hypothermia, the reduction in platelets and elevated cytokines persisted. Our data indicate that prior illness exacerbates the severity of HS in the absence of signs of illness at the time of heat exposure and suggest that this is attributable to persistent coagulation and inflammatory reactions that might be targets for intervention to improve recovery.
Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Citocinas/metabolismo , Golpe de Calor/sangre , Calor , Inflamación/fisiopatología , Animales , Quimiocinas/metabolismo , Modelos Animales de Enfermedad , Fiebre/fisiopatología , Hipotermia/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
PURPOSE: The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 patients with COVID-19 pneumonia. RESULTS: At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). CONCLUSION: These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.
Asunto(s)
COVID-19/fisiopatología , Tos/fisiopatología , Disnea/fisiopatología , Fiebre/fisiopatología , Pulmón/fisiopatología , SARS-CoV-2/patogenicidad , Adulto , Anciano , COVID-19/diagnóstico , COVID-19/patología , COVID-19/virología , Tos/diagnóstico , Tos/patología , Tos/virología , Disnea/diagnóstico , Disnea/patología , Disnea/virología , Femenino , Fiebre/diagnóstico , Fiebre/patología , Fiebre/virología , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Pulmón/virología , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Espirometría , Tomografía Computarizada por Rayos XRESUMEN
Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.
Asunto(s)
Atención Ambulatoria , Prueba de COVID-19/métodos , COVID-19/diagnóstico , Dolor Abdominal/fisiopatología , Adolescente , Adulto , COVID-19/fisiopatología , Estudios de Casos y Controles , Reglas de Decisión Clínica , Tos/fisiopatología , Diarrea/fisiopatología , Progresión de la Enfermedad , Disnea/fisiopatología , Femenino , Fiebre/fisiopatología , Cefalea/fisiopatología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mialgia/fisiopatología , Oportunidad Relativa , Selección de Paciente , Faringitis/fisiopatología , Rinorrea/fisiopatología , SARS-CoV-2 , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Compelling evidence indicates that status epilepticus is a prevalent cause of rhabdomyolysis. However, cases of rhabdomyolysis induced by a single seizure accompanied by viral encephalitis are rarely reported. Herein, we present a case of adult Herpes Simplex Encephalitis complicated with rhabdomyolysis. CASE PRESENTATION: A 32-year-old male was patient presented with fever accompanied by episodes of convulsions, myalgia, and oliguria, which exacerbated the delirium. Routine blood examination showed impaired kidney function and elevated myoglobin (Mb) and creatine phosphokinase (CK) levels. MRI scanning revealed a damaged frontotemporal lobe and limbic system. In addition, herpes simplex virus (HSV) pathogen was identified in the cerebrospinal fluid thus indicating HSV infection. Therefore, a diagnosis of rhabdomyolysis triggered by HSV infection accompanied by epilepsy was made. Notably, the patient recovered well after early intervention and treatment. CONCLUSION: The case presented here calls for careful analysis of rhabdomyolysis cases with unknown causes, minor seizures, and without status epilepticus. This case also indicates that HSV virus infection might contribute to the rhabdomyolysis.
Asunto(s)
Encefalitis por Herpes Simple/complicaciones , Encefalitis por Herpes Simple/diagnóstico , Rabdomiólisis/diagnóstico , Rabdomiólisis/etiología , Adulto , Fiebre/diagnóstico , Fiebre/etiología , Fiebre/patología , Fiebre/fisiopatología , Humanos , Masculino , Rabdomiólisis/patología , Rabdomiólisis/fisiopatología , Convulsiones/diagnóstico , Convulsiones/etiología , Convulsiones/patología , Convulsiones/fisiopatología , Simplexvirus/aislamiento & purificaciónRESUMEN
BACKGROUND: Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. METHODS: To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. RESULTS: Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. CONCLUSIONS: SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.