RESUMO
Sepsis is a complex condition of inflammatory and immune dysregulation, triggered by severe infection. In survivors, chronic inflammation and immune dysregulation linger, facilitating the emergence of infections. CD8 dysfunction contributes to immunosuppression in sepsis survivors. We devised an animal model that enabled us to identify and analyze CD8-intrinsic defects induced by sepsis. We adoptively transferred CD45.1 CD8 OT-I T cells into CD45.2 congenic mice and subjected them to cecal ligature and puncture, to induce abdominal sepsis. One month later, we isolated the transferred CD8 cells. Surface marker expression confirmed they had not been activated through the TCR. CD8 OT-I T cells isolated from septic (or sham-operated) mice were transferred to second recipients, which were challenged with OVA-expressing Listeria monocytogenes. We compared effector capacities between OT-I cells exposed to sepsis and control cells. Naive mice that received OT-I cells exposed to sepsis had higher bacterial burden and a shorter survival when challenged with OVA-expressing L. monocytogenes. OT-I cells isolated from septic mice produced less IFN-γ but had conserved activation, expansion potential, and cytotoxic function. We observed lower transcript levels of IFN-γ and of the long noncoding RNA Ifng-as1, a local regulator of the epigenetic landscape, in cells exposed to sepsis. Accordingly, local abundance of a histone modification characteristic of active promoter regions was reduced in sepsis-exposed CD8 T cells. Our results identify a mechanism through which inflammation in the context of sepsis affects CD8 T cell function intrinsically.
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Linfócitos T CD8-Positivos , Cromatina , Interferon gama , Listeria monocytogenes , Sepse , Animais , Sepse/imunologia , Linfócitos T CD8-Positivos/imunologia , Camundongos , Interferon gama/imunologia , Cromatina/imunologia , Cromatina/metabolismo , Listeria monocytogenes/imunologia , Camundongos Endogâmicos C57BL , Transferência Adotiva , Modelos Animais de Doenças , Listeriose/imunologia , Ativação Linfocitária/imunologiaRESUMO
Background and aim: With an ever-increasing population of patients recovering form severe coronavirus disease 2019 (COVID-19), recognizing long-standing and delayed neurologic manifestations is crucial. Here, we present a patient developing posterior reversible encephalopathy syndrome (PRES) in the convalescence form severe coronavirus disease 2019 (COVID-19).Case presentation: A 61-year-old woman with severe (COVID-19) confirmed by nasopharyngeal real-time reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) required invasive mechanical ventilation 24-hours after admission. During her intensive care unit stay, she developed transient acute kidney injury and septic shock. She was extubated after 22 days. On day 25, she developed generalized tonic-clonic seizures. Magnetic resonance imaging (MRI) of the brain showed bilateral subcortical lesions on the parietal and occipital lobes and multiple micro-and macro-bleeds, consistent with PRES. At this point, RT-PCR for SARS-CoV-2 in a respiratory specimen and cerebrospinal fluid was negative. She was discharged home 35 days after admission on oral levetiracetam. Control MRI five months after discharge showed bilateral focal gliosis. On follow-up, she remains seizure-free on levetiracetam.Conclusions: PRES has been observed before as a neurological manifestation of acute COVID-19; to our knowledge, this is the first PRES case occurring in a hospitalized patient already recovered from COVID-19. A persistent proinflammatory/prothrombotic state triggered by SARS-CoV-2 infection may lead to long-standing endothelial dysfunction, resulting in delayed PRES in patients recovering from COVID-19. With a rapid and exponential increase in survivors of acute COVID-19, clinicians should be aware of delayed (post-acute) neurological damage, including PRES.
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COVID-19 , Síndrome da Leucoencefalopatia Posterior , Humanos , Feminino , Pessoa de Meia-Idade , COVID-19/complicações , SARS-CoV-2 , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/etiologia , Síndrome da Leucoencefalopatia Posterior/patologia , Convalescença , LevetiracetamRESUMO
5-HT7 receptors (5-HT7R) are the most recently identified among the family of serotonin receptors. Their role in health and disease, particularly as mediators of, and druggable targets for, neurodegenerative diseases, is incompletely understood. Unlike other serotonin receptors, for which abundant preclinical and clinical data evaluating their effect on neurodegenerative conditions exist, the available information on the role of the 5-HT7R receptor is limited. In this review, we describe the signaling pathways and cellular mechanisms implicated in the activation of the 5-HT7R; also, we analyze different mechanisms of neurodegeneration and the potential therapeutic implications of pharmacological interventions for 5-HT7R signaling.
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Doenças Neurodegenerativas , Receptores de Serotonina , Sistema Nervoso Central/metabolismo , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Receptores de Serotonina/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Brometo de Piridostigmina/uso terapêutico , SARS-CoV-2 , Respiração Artificial , Inflamação , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), can trigger a myriad of neuropsychiatric manifestations. As a 2-year-old disease (at the writing of this manuscript), its long-term cognitive and neuropsychiatric implications, known as post-COVID-19 conditions, are incompletely recognized and mechanistically obscure. RECENT FINDINGS: Fatigue, anxiety, depression, posttraumatic stress disorder, and cognitive dysfunction are reported more frequently in COVID-19 survivors than in matching, non-COVID-19 population. Risk factors are unclear, including comorbidities, age at COVID-19 onset, or disease severity; women, however, have been reported to be at increased risk than men. Although the frequency of these symptoms decreases over time, at least one in five will have persistent cognitive and neuropsychiatric manifestations one year after recovering from COVID-19. SUMMARY: Neurocognitive and psychiatric post-COVID-19 long-term conditions are frequent and complex multifactorial sequelae. Several acute and chronic factors such as hypoxemia, cerebral thrombotic and inflammatory endothelial damage, and disruption of the blood-brain barrier (leading to parenchymal translocation of pro-inflammatory molecules, cytokines, and cytotoxic T lymphocytes) are involved, leading to microglial activation and astrogliosis. As an evolving topic, evidence derived from prospective studies will expand our understanding of post-COVID-19 these long-term outcomes.
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Encefalopatias , COVID-19 , Doenças Neuromusculares , Ansiedade/psicologia , Encéfalo , COVID-19/complicações , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Prospectivos , SARS-CoV-2RESUMO
BACKGROUND: Information on anaphylaxis among recipients of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains scarce. OBJECTIVE: To identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. METHODS: A nationwide observational study among recipients of 61,414,803 doses of seven different anti-SARS-CoV-2 vaccines, describing the incidence and characteristics of adult patients (age ≥ 18 years) who developed anaphylaxis as an adverse event following immunization (AEFI) against SARS-CoV-2 vaccines between December 24, 2020, and October 15, 2021, in Mexico. RESULTS: Sixty-six patients developed anaphylaxis as an AEFI, for an overall observed incidence of 1.07 cases per 1,000,000 (95% CI 0.84-1.37) administered doses. Eighty-six percent of the patients were female, consistent with previous reports of AEFI to COVID-19 vaccines. mRNA-based vaccine recipients had the highest frequency of anaphylaxis, followed by adenovirus-vectored vaccines and inactivated virus recipients, with an observed incidence of 2.5, 0.7, and 0.2 cases per 1,000,000 doses administered, respectively. Only 46% of the patients received correct treatment with epinephrine as the first-line treatment through the appropriate route and dose. We detected one case of anaphylactic reaction-related death occurring 5 min following immunization with ChAdOx1 nCov-19 for a mortality rate of 1.5% among those who developed this AEFI. CONCLUSIONS: In our population, anaphylactic reactions were infrequent. Our study provides further evidence supporting the security of these newly developed vaccines.
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Anafilaxia , Vacinas contra COVID-19 , COVID-19 , Adolescente , Adulto , Feminino , Humanos , Masculino , Anafilaxia/induzido quimicamente , Anafilaxia/epidemiologia , ChAdOx1 nCoV-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , México/epidemiologiaRESUMO
The COVID-19 pandemic led to the development and emergency approval of an array of effective vaccines against SARS-CoV-2. Given the relatively small number of patients included in vaccine trials, postapproval epidemiological surveillance is crucial to detect infrequent vaccine-related adverse events. We conducted a nationwide retrospective descriptive study evaluating the incidence of seizures among recipients of SARS-CoV-2 vaccines in Mexico from December 24, 2020 (date of administration of first doses nationwide) to October 29, 2021. Among 81 916 351 doses of any vaccine that were administered, we documented seizures in 53 patients, of which 31 (60%) were new onset seizures. The incidence rate of seizures per million doses was highest for mRNA-1273 (Moderna) with 2.73 per million, followed by BNT162b2 (Pfizer-BioNTech) with 1.02 per million, and Ad5-nCoV (CanSino) with 1.01 per million. Thus, we found that seizures following SARS-CoV-2 vaccination are exceedingly rare events.
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COVID-19 , Vacinas , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Humanos , México/epidemiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Convulsões/induzido quimicamente , Convulsões/etiologia , Vacinação/efeitos adversos , Vacinas/efeitos adversosRESUMO
OBJECTIVES: The antiphospholipid syndrome (APS) is an autoimmune disease associated with thrombotic and non-thrombotic neurologic manifestations. APS is classified as primary (PAPS) or secondary (SAPS) when it co-exists with another autoimmune disease. We aim to describe the spectrum of acute cerebrovascular disease among patients with APS, their differences between stroke subtypes, and long-term functional outcomes. METHODS: Retrospective cohort study including adult (≥18 years) patients with APS followed in the stroke clinic of a tertiary-care reference center for autoimmune diseases in Mexico from 2009 to 2019. RESULTS: We studied 120 cases; 99 (82.5%) women; median age 43 years (interquartile range 35-52); 63.3% with SAPS. Demographics, comorbidities, and antiphospholipid antibodies (aPL) positivity were similar between APS type and stroke subtypes. Amongst index events, we observed 84 (70%) acute ischemic strokes (AIS), 19 (15.8%) cerebral venous thromboses (CVT), 11 (9.2%) intracerebral hemorrhages (ICH), and six (5%) subarachnoid hemorrhages (SAH). Sixty-seven (55.8%) were known patients with APS; the median time from APS diagnosis to index stroke was 46 months (interquartile range 12-96); 64.7% of intracranial hemorrhages (ICH or SAH) occurred ≥4 years after APS was diagnosed (23.5% anticoagulation-related); 63.2% of CVT cases developed before APS was diagnosed or simultaneously. Recurrences occurred in 26 (22.8%) patients, AIS, in 18 (69.2%); intracranial hemorrhage, in eight (30.8%). Long-term functional outcomes were good (modified Rankin Scale ≤2) in 63.2% of cases, during follow-up, the all-cause mortality rate was 19.2%. CONCLUSION: We found no differences between stroke subtypes and APS types. aPL profiles were not associated with any of the acute cerebrovascular diseases described in this cohort. CVT may be an initial thrombotic manifestation of APS with low mortality and good long-term functional outcome.
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Síndrome Antifosfolipídica , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Trombose , Adulto , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Hemorragia Cerebral/patologia , Feminino , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Trombose/epidemiologia , Trombose/etiologiaRESUMO
BACKGROUND AND PURPOSE: Information on Guillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 remains scarce. We aimed to report GBS incidence as an AEFI among adult (≥18 years) recipients of 81,842,426 doses of seven anti-SARS-CoV-2 vaccines between December 24, 2020, and October 29, 2021, in Mexico. METHODS: Cases were retrospectively collected through passive epidemiological surveillance. The overall observed incidence was calculated according to the total number of administered doses. Vaccines were analyzed individually and by vector as mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), and inactivated whole-virion-vectored (CoronaVac) vaccines. RESULTS: We identified 97 patients (52 males [53.6%]; median [interquartile range] age 44 [33-60] years), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97-1.45), with incidence higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50-9.93) and BNT162b2 recipients (1.92/1,00,000 doses, 95% CI 1.36-2.71). The interval (interquartile range) from vaccination to GBS symptom onset was 10 (3-17) days. Preceding diarrhea was reported in 21 patients (21.6%) and mild COVID-19 in four more (4.1%). Only 18 patients were tested for Campylobacter jejuni (positive in 16 [88.9%]). Electrophysiological examinations were performed in 76 patients (78.4%; axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar across the platforms. On admission, 91.8% had a GBS disability score ≥3. Seventy-five patients (77.3%) received intravenous immunoglobulin, received seven plasma exchange (7.2%), and 15 (15.5%) were treated conservatively. Ten patients (10.3%) died, and 79.1% of survivors were unable to walk independently. CONCLUSIONS: Guillain-Barré syndrome was an extremely infrequent AEFI against SARS-CoV-2. The protection provided by these vaccines outweighs the risk of developing GBS.
Assuntos
Vacina BNT162 , COVID-19 , ChAdOx1 nCoV-19 , Síndrome de Guillain-Barré , Adulto , Humanos , Masculino , Vacina BNT162/efeitos adversos , ChAdOx1 nCoV-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/epidemiologia , Imunoglobulinas Intravenosas/uso terapêutico , Incidência , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2 , Vacinação/efeitos adversos , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A high proportion of coronavirus disease 2019 (COVID-19) survivors may develop long-term cognitive impairment. We aimed to develop a multivariate causal model exposing the links between COVID-19-associated biomarkers, illness-related variables, and their effects on cognitive performance. METHODS: In this prospective study, we assess the potential drivers for the development of cognitive impairment in patients with severe COVID-19 pneumonia aged ≥ 18 years at 6-month follow-up after hospital discharge, using the Montreal Cognitive Assessment (MoCA). Patients with pre-existing cognitive impairment were excluded. Laboratory results at hospital admission were clustered by principal component analysis (PCA) and included in a path analysis model evaluating the causal relationship between age, comorbidities, hypoxemia, invasive mechanical ventilation (IMV) requirement, in-hospital delirium, and cognitive performance. RESULTS: We studied 92 patients: 54 (58.7%) men and 38 (41.3%) women, with median age of 50 years (interquartile range 42-55), among whom 50 (54.4%) tested positive for cognitive impairment at 6-month follow-up. Path analysis revealed a direct link between the thrombo-inflammatory component of PCA (C-reactive protein, fibrinogen, and neutrophils) and hypoxemia severity at hospital admission. Our model showed that low PaO2/FiO2 ratio values, unlike the thrombo-inflammatory component, had a direct effect on cognitive performance, independent from age, in-hospital delirium, and invasive mechanical ventilation. CONCLUSION: In this study, biomarkers of thrombo-inflammation in COVID-19 and low PaO2/FiO2 had a negative effect on cognitive performance 6 months after hospital discharge. These results highlight the critical role of hypoxemia as a driver for impaired cognition in the mid-term.
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COVID-19 , Disfunção Cognitiva , Adolescente , COVID-19/complicações , Disfunção Cognitiva/etiologia , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2RESUMO
COVID-19 can range from asymptomatic to life-threatening. Early identification of patients who will develop severe disease is crucial. A number of scores and indexes have been developed to predict severity. However, most rely on measurements not readily available. We evaluated hematological and biochemical markers taken on admission and determined how predictive they were of development of critical illness or death. We observed that higher values of readily available tests, including neutrophil:lymphocyte ratio; derived neutrophil index; and troponin I were associated with a higher risk of death or critical care admission (P < 0.001). We show that common hematological tests can be helpful in determining early in the course of illness which patients are likely to develop severe forms, as well as allocating resources to those patients early, while avoiding overuse of limited resources in patients with reduced risk of progression to severe disease.
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Biomarcadores/sangue , COVID-19/sangue , COVID-19/virologia , SARS-CoV-2 , Adulto , Contagem de Células Sanguíneas , COVID-19/diagnóstico , COVID-19/mortalidade , Estudos de Coortes , Progressão da Doença , Feminino , Testes Hematológicos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , SARS-CoV-2/genética , Índice de Gravidade de DoençaRESUMO
Vaccines are the most effective strategy to mitigate the global impact of COVID-19. However, vaccine hesitancy is common, particularly among minorities. Guillain-Barré syndrome (GBS) is the most common autoimmune illness of the peripheral nervous system, occurring at an incidence of 1.1/100,000 worldwide. A causal link between mRNA vaccines and GBS has not been previously evaluated. We analyzed a cohort of 3,890,250 Hispanic/Latinx recipients of the BNT162b2 mRNA vaccine (613,780 of whom had already received both doses) for incident GBS occurring within 30 days from vaccine administration. Seven cases of GBS were detected among first-dose recipients, for an observed incidence of 0.18/100,000 administered doses during the prespecified timeframe of 30 days. No cases were reported after second-dose administration. Our data suggest that, among recipients of the BNT162b2 mRNA vaccine, GBS may occur at the expected community-based rate; however, this should be taken with caution as the current incidence of GBS among the unvaccinated population against COVID-19 is still undetermined. We hope that this preliminary data will increase the public perception of safety toward mRNA-based vaccines and reduce vaccine hesitancy.
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Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Síndrome de Guillain-Barré/etiologia , SARS-CoV-2 , Estudos de Coortes , Humanos , Estudos RetrospectivosRESUMO
mRNA vaccines against SARS-CoV-2 are remarkably effective. Limited information exists about the incidence of adverse events following immunization (AEFI) with their use. We conducted a prospective observational study including data from 704,003 first-doses recipients; 6536 AEFI were reported, of whom 65.1% had at least one neurologic AEFI (non-serious 99.6%). Thirty-three serious events were reported; 17 (51.5%) were neurologic (observed frequency, 2.4/100,000 doses). At the time of writing this report, 16/17 cases had been discharged without deaths. Our data suggest that the BNT162b2 mRNA COVID-19 vaccine is safe; its individual and societal benefits outweigh the low percentage of serious neurologic AEFI. This information should help to dissipate hesitancy towards this new vaccine platform.
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Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Doenças do Sistema Nervoso/etiologia , SARS-CoV-2 , Adulto , Vacina BNT162 , COVID-19/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Estudos Prospectivos , Vacinas Sintéticas/imunologia , Vacinas de mRNARESUMO
In mammalians, serotonin (5-HT) has critical roles in the central nervous system (CNS), including mood stability, pain tolerance, or sleep patterns. However, the vast majority of serotonin is produced by intestinal enterochromaffin cells of the gastrointestinal tract and circulating blood platelets, also acting outside of the CNS. Serotonin effects are mediated through its interaction with 5-HT receptors (5-HTRs), a superfamily with a repertoire of at least fourteen well-characterized members. 5-HT7 receptors are the last 5-HTR member to be identified, with well-defined functions in the nervous, gastrointestinal, and vascular systems. The effects of serotonin on the immune response are less well understood. Mast cells are known to produce serotonin, while T cells, dendritic cells, monocytes, macrophages and microglia express 5-HT7 receptor. Here, we review the known roles of 5-HT7 receptors in the immune system, as well as their potential therapeutic implication in inflammatory and immune-mediated disorders.
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Sistema Imunitário/metabolismo , Receptores de Serotonina/metabolismo , Serotonina/metabolismo , Animais , Humanos , Isoformas de Proteínas/metabolismo , Receptores de Serotonina/genética , Transdução de Sinais , Distribuição TecidualRESUMO
The nervous system both monitors and modulates body metabolism to maintain homoeostasis. In disease states such as obesity and diabetes, the neurometabolic interface is dysfunctional and contributes to clinical illness. The vagus nerve, in particular, with both sensory and motor fibres, provides an anatomical substrate for this interface. Its sensory fibres contain receptors for important circulating metabolic mediators, including leptin and cholecystokinin, and provide real-time information about these mediators to the central nervous system. In turn, efferent fibres within the vagus nerve participate in a brain-gut axis to regulate metabolism. In this review, we describe these vagus nerve-mediated metabolic pathways and recent clinical trials of vagus nerve stimulation for the management of obesity. These early studies suggest that neuromodulation approaches that employ electricity to tune neurometabolic circuits may represent a new tool in the clinical armamentarium directed against obesity.
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Vias Aferentes/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Neurônios Aferentes/fisiologia , Neurotransmissores , Obesidade/fisiopatologia , Estimulação do Nervo Vago , Nervo Vago/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Humanos , Neurorretroalimentação , Neurotransmissores/uso terapêutico , Obesidade/metabolismo , Obesidade/terapia , Nervo Vago/anatomia & histologiaRESUMO
The term acquired immunodeficiency syndrome (AIDS) was coined to describe a condition marked by weakened cell-mediated immunity in the absence of a clear cause. Due to unfortunate messaging during the early days of the HIV epidemic, this term became loaded with stigma. After the discovery of HIV, the term AIDS became redundant, but its use has persisted and has come to embody negative connotations in the current landscape of the HIV epidemic. People commonly associate AIDS with a terminal illness. This misconception promotes stigma by others, including health-care workers, but also self-stigma, which can prevent individuals from accessing health care. Also, the link between AIDS and gay men generated during the early epidemic with use of the term gay-related immune disorder is misleading regarding which populations are at risk, which can delay diagnosis. The use of the term AIDS is now discouraged by several professional associations, some of which ironically have the word as part of their name. Ending use of the term AIDS would not eradicate stigma. However, this term has outlasted its usefulness, and we should transition towards more descriptive language that aligns with contemporary challenges in HIV.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Masculino , Humanos , Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Estigma Social , Pessoal de Saúde , Acessibilidade aos Serviços de SaúdeRESUMO
BACKGROUND: People who live with HIV (PWLH) have been one of the most affected groups during the current mpox outbreak. They are hypothesized to have a more severe clinical course than people without HIV but comparative data is scarce. We aimed to compare clinical features and outcomes of mpox in people with and without HIV in Mexico. SETTING: Country-wide study in Mexico. METHODS: We performed an observational study using nation-wide epidemiological data. We included all people with confirmed mpox diagnosed between May and November 2022 in Mexico. Clinical and sociodemographic characteristics were compared between people with and without HIV. Multivariable logistic regression models were preformed to determine the association between HIV, clinical features, and outcomes and reported with odds ratios (ORs) and 95% confidence intervals (95% CI). ORs for rare outcomes were interpreted as risk ratios. RESULTS: Among 3291 people with mpox, 59% were PWLH. PWLH had an increased risk of severe mpox (OR 2.6, 2.4-2.9) and death (OR 10.8, 9.7-11.9). They also had a higher risk of otalgia, proctitis, and urethritis. Eleven individuals died, of whom ten were PWLH. All deaths were directly attributed to mpox. CONCLUSION: People with HIV have a higher risk of severe mpox and death due to mpox.
RESUMO
OBJECTIVES: We aimed to identify predictors of confirmed monkeypox (mpox) among people with mpox-like illness and to develop a multivariable model for confirmed mpox. METHODS: We performed an observational study using national epidemiologic surveillance data in Mexico from May to November 2022. People with mpox-like illness were reported to the Mexican Ministry of Health and real-time polymerase chain reaction was performed in clinical samples to confirm mpox. Sociodemographic and clinical data were collected with a case report form. We performed univariable logistic regressions to estimate the predictive capability of individual characteristics, reported with ORs and 95% CIs. Variables of interest were included in multivariable logistic regression models and Akaike information criterion was used to retain variables for the final model. Discrimination and calibration of the model were estimated in bootstrap resamples. RESULTS: A total of 5078 people were reported with mpox-like illness. Of 5078 people, 3291 (64.8%) had confirmed mpox. The strongest clinical predictors of confirmed mpox in univariable models were proctitis (OR 6.54, 5.93-7.21), inguinal adenopathy (OR 5.91, 5.36-6.52), and anogenital lesions (OR 5.45, 4.94-6.02). The final model included being a man who has sex with men (8.75, 7.37-10.38), HIV diagnosis (3.04, 2.51-3.69), inguinal adenopathy (2.24, 1.81-2.77), anogenital lesions (2.32, 1.97-2.74), and pustules (1.55, 1.32-1.81). Discrimination capability was excellent (c-statistic 0.88, 95% CI 0.87-0.89) and it was well calibrated (calibration slope 1, 95% CI 0.95-1.05). DISCUSSION: A third of people with mpox-like illness do not have mpox. Factors such as being a man who has sex with men, HIV diagnosis, inguinal adenopathy, pustules, and anogenital lesions are associated with confirmed mpox.