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1.
Artigo em Inglês | MEDLINE | ID: mdl-34629415

RESUMO

INTRODUCTION: Early systemic and central nervous system viral replication and inflammation may impact brain integrity in people with HIV (PWH), leading to chronic cognitive symptoms not fully reversed by antiretroviral therapy (ART). This study examined associations between cognitive performance and markers of CNS injury associated with acute HIV infection and ART. METHODS: HIV-infected MSM and transgender women (average age: 27 and education: 13 years) enrolled within 100 days from estimated date of detectable infection [EDDI]. A cognitive performance (NP) protocol was administered at enrollment (before ART initiation) and every 24 weeks until week 192. An overall index of cognitive performance (NPZ) was created using local normative data. Blood (n=87) and cerebrospinal fluid (CSF; n=29) biomarkers of inflammation and neuronal injury were examined before ART initiation. Regression analyses assessed relationships between time since EDDI, pre-ART biomarkers, and NPZ. RESULTS: Adjusting for multiple comparisons, shorter time since EDDI was associated with higher pre-ART VL and multiple biomarkers in plasma and CSF. NPZ scores were within the normative range at baseline (NPZ=.52) and at each follow-up visit, with a modest increase through week 192. Plasma or CSF biomarkers were not correlated with NP scores at baseline or after ART. CONCLUSIONS: Biomarkers of CNS inflammation, immune activation and neuronal injury peak early and then decline during acute HIV infection, confirming and extending results of other studies. Neither plasma nor CSF biomarkers during acute infection corresponded to NP scores before or after sustained ART in this cohort with few psychosocial risk factors for cognitive impairment.

2.
PLoS Pathog ; 17(8): e1009785, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388205

RESUMO

HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine. Trial Registration: NCT00782808 and NCT00796146.

3.
BMJ Case Rep ; 14(6)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187795

RESUMO

A 52-year-old woman with HIV and recent antiretroviral therapy non-adherence presented with a 5-day history of widespread painful vesicular skin lesions. Direct fluorescent antibody testing of the skin lesions was positive for varicella zoster virus (VZV). On day 3, she developed profound right upper extremity weakness. MRI of the brain and cervical spine was suggestive of VZV myelitis. Lumbar puncture was positive for VZV PCR in the cerebrospinal fluid (CSF) and CSF HIV viral load was detected at 1030 copies/mL, indicating 'secondary' HIV CSF escape. She was treated with intravenous acyclovir for 4 weeks and subsequent oral therapy with famciclovir then valacyclovir for 6 weeks. She also received dexamethasone. The patient had an almost full recovery at 6 months. Myelitis is a rare complication of reactivated VZV infection that can have atypical presentation in immunocompromised patients. Such 'secondary' HIV CSF escape should be considered in immunosuppressed patients with concomitant central nervous system infection.


Assuntos
Infecções do Sistema Nervoso Central , Infecções por HIV , Herpes Zoster , Mielite , Aciclovir/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 3 , Humanos , Pessoa de Meia-Idade , Mielite/diagnóstico , Mielite/tratamento farmacológico , Mielite/etiologia
5.
PLoS One ; 16(5): e0250987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33983973

RESUMO

OBJECTIVE: To characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control. METHODS: This is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau. FINDINGS: HIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200-350 blood CD4+ T cells/µL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.

7.
Cell Rep Med ; : 100288, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33969321

RESUMO

COVID-19 patients frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single cell RNA-seq and cytokine analyses of CSF and blood from COVID-19 patients with neurological symptoms, we find compartmentalized, CNS specific T cell activation and B cell responses. All COVID-19 cases had CSF anti-SARS-CoV-2 antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are found only during brain infection, and are not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from a COVID-19 patient, and find that these mAbs target both anti-viral and anti-neural antigens-including one mAb that reacted to both spike protein and neural tissue. Overall, CSF IgG from 5/7 patients contains anti-neural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of COVID-19 patients and suggests a role for autoimmunity in neurologic sequelae of COVID-19.

8.
Clin Infect Dis ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34050746

RESUMO

BACKGROUND: Synaptic injury is a pathological hallmark of neurological impairment in people living with HIV (PLWH), a common complication despite viral suppression with antiretroviral therapy (ART). Measurement of synaptic density in living humans may allow better understanding of HIV neuropathogenesis and provide a dynamic biomarker for therapeutic studies. We applied novel synaptic vesical protein 2A (SV2A) positron emission tomographic (PET) imaging to investigate synaptic density in the frontostriatalthalamic region in PLWH and HIV-uninfected (HIV-) participants. METHODS: In this cross-sectional pilot study,13 older male PLWH on ART underwent MRI and PET scanning with the SV2A ligand [ 11C]UCB-J with partial volume correction, and had neurocognitive assessments. SV2A binding potential (BPND) in the frontostriatalthalamic circuit was compared to 13 age-matched HIV- participants, and assessed with respect to neurocognitive performance in PLWH. RESULTS: PLWH had 14% lower frontostriatalthalamic SV2A synaptic density compared to HIV- (PLWH: mean [SD], 3.93 [0.80]; HIV-: 4.59 [0.43]; P = .02, effect size 1.02). Differences were observed in widespread additional regions in exploratory analyses. Higher frontostriatalthalamic SV2A BPND associated with better grooved pegboard performance, a measure of motor coordination, in PLWH (r = 0.61, P = .03). CONCLUSIONS: In a pilot study, SV2A PET imaging reveals reduced synaptic density in older male PLWH on ART compared to HIV- in the frontostriatalthalamic circuit and other cortical areas. Larger studies controlling for factors in addition to age are needed to determine whether differences are attributable to HIV or comorbidities in PLWH. SV2A imaging is a promising biomarker for studies of neuropathogenesis and therapeutic interventions in HIV.

9.
Curr Opin Neurol ; 34(3): 417-422, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852526

RESUMO

PURPOSE OF REVIEW: Over the course of the coronavirus disease (COVID-19) pandemic, it has become increasingly clear that there is a high prevalence of neurological complications in people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RECENT FINDINGS: Studies of central nervous system (CNS) tissue in brain model systems and from adults with acute SARS-CoV-2 infection have begun to uncover potential mechanisms for neurological damage during COVID-19. These studies suggest that direct viral invasion of the CNS occurs in a subset of cases but does not frequently cause overt viral meningoencephalitis. Vascular abnormalities including microvascular thrombi and endothelial activation, as well as parainfectious processes, including CNS specific immune responses, may contribute to neurological symptoms during acute SARS-CoV-2 infection. SUMMARY: Neuroimmune perturbations and vascular inflammation observed in people with COVID-19 may warrant investigation of immune-modulating interventions to ameliorate neurological complications associated with acute SARS-CoV-2 infection. These therapies may also impact the trajectory of potential long-term complications of COVID-19.


Assuntos
COVID-19/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/patologia , Humanos , Imunoterapia , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/terapia , Vasculite/etiologia , Vasculite/imunologia
11.
AIDS ; 35(6): 883-888, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534200

RESUMO

OBJECTIVE: People with HIV continue to exhibit cognitive symptoms after suppressive antiretroviral therapy (ART). It remains unclear if initiating ART during acute HIV-1 infection (AHI) uniformly improves cognitive outcomes. METHODS: Sixty-seven individuals (96% men, median age 28 years) initiated ART immediately after AHI diagnosis and maintained viral suppression for 6 years. They underwent a four-test neuropsychological battery that measured fine motor speed and dexterity, psychomotor speed, and executive functioning at baseline (pre-ART AHI), weeks 12, 24 and 96, and annually thereafter through week 288. Performances were standardized to calculate an overall (NPZ-4) score and frequencies of impaired cognitive performance (≤-1 SD on at least two tests, or ≤-2 SD on at least one test). Group-based trajectory analysis (GBTA) was applied to identify distinct neuropsychological trajectories modelled from baseline to week 288. Posthoc analyses examined HIV-1 and demographic factors that differed between trajectory subgroups. RESULTS: NPZ-4 scores improved from baseline to week 96 (P < 0.001) and from weeks 96 to 288 (P < 0.001), with frequencies of impaired performance of 30, 6 and 2% at the respective time-points. The amplitude of NPZ-4 improvement throughout the period was more than 0.5 SD and beyond practice effects. GBTA identified three NPZ-4 trajectory subgroups that all showed improvement over-time. The subgroup with lowest baseline performance exhibited worse depressive symptoms at baseline (P = 0.04) and the largest improvement among the three. HIV-1 indices did not differ between the subgroups. CONCLUSION: Cognitive performance improved in a sustained and stable manner after initiating ART during AHI. Largest improvements were seen in participants with worst baseline cognitive performance.


Assuntos
Disfunção Cognitiva , Infecções por HIV , Soropositividade para HIV , HIV-1 , Adulto , Cognição , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Testes Neuropsicológicos
12.
Curr Opin Psychiatry ; 34(2): 177-185, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395100

RESUMO

PURPOSE OF REVIEW: Over 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals. RECENT FINDINGS: Based on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients have good outcomes and disease modifying therapies do not increase the risk for severe disease. Viral infections and attendant neuroinflammation have been associated with the pathogenesis of Alzheimer's disease, Parkinson's disease, and MS, suggesting that COVID-19 may have the potential to incite or accelerate neurodegeneration. SUMMARY: Since patients with Alzheimer's disease are at higher risk for hospitalization and death in the setting of COVID-19, additional precautions and protective measures should be put in place to prevent infections and optimize management of comorbidities in this vulnerable population. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.


Assuntos
COVID-19/complicações , Demência/complicações , Hospitalização , Esclerose Múltipla/complicações , Doença de Parkinson/complicações , Humanos , Prognóstico , Fatores de Risco
13.
AIDS ; 35(5): 777-782, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306551

RESUMO

OBJECTIVE: Despite suppression of HIV-1 replication in the periphery by antiretroviral therapy (ART), up to 10% of treated individuals have quantifiable HIV-1 in the CSF, termed CSF escape. CSF escape may be asymptomatic but has also been linked to progressive neurological disease, and may indicate persistence of HIV in the central nervous system (CNS). CSF escape has not yet been assessed after initiation of ART during acute HIV-1 infection (AHI). DESIGN: Prospective cohort study. SETTING: Major voluntary counseling and testing site in Bangkok, Thailand. PARTICIPANTS: Participants identified and initiated on ART during AHI who received an optional study lumbar puncture at pre-ART baseline or after 24 or 96 weeks of ART. MAIN OUTCOME MEASURES: Paired levels of CSF and plasma HIV-1 RNA, with CSF greater than plasma HIV-1 RNA defined as CSF escape. RESULTS: Two hundred and four participants had paired blood and CSF sampling in at least one visit at baseline, week 24, or week 96. Twenty-nine participants had CSF sampling at all three visits. CSF escape was detected in 1/90 at week 24 (CSF HIV-1 RNA 2.50 log10 copies/ml, plasma HIV-1 RNA <50 copies/ml), and 0/55 at week 96. CONCLUSION: Although levels of CSF HIV-1 RNA in untreated AHI are high, initiating treatment during AHI results in a very low rate of CSF escape in the first 2 years of treatment. Early treatment may improve control of HIV-1 within the CNS compared with treatment during chronic infection, which may have implications for long-term neurological outcomes and CNS HIV-1 persistence.


Assuntos
Infecções por HIV , HIV-1 , Antirretrovirais/uso terapêutico , Líquido Cefalorraquidiano , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Estudos Prospectivos , RNA Viral , Tailândia , Carga Viral
14.
J Virus Erad ; 6(3): 100004, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33251022

RESUMO

Objective and Design: A randomized, open-label pilot study in individuals treated with antiretroviral therapy (ART) since acute HIV infection (AHI) with a regimen including a histone deacetylase inhibitor to induce HIV from latency and control HIV replication during subsequent treatment interruption (TI). Methods: Fifteen participants who initiated ART at AHI were randomized to vorinostat/hydroxychloroquine/maraviroc (VHM) plus ART (n â€‹= â€‹10) or ART alone (n â€‹= â€‹5). The VHM arm received three 14-day vorinostat cycles within 10 weeks before TI. ART was resumed for plasma viral load (VL) â€‹> â€‹1,000 HIV RNA copies/mL. Primary outcome was proportion of participants on VHM â€‹+ â€‹ART versus ART only with VL â€‹< â€‹50 copies/mL for 24 weeks after TI. Results: Fifteen participants on ART (median: 178 weeks: range 79-295) enrolled. Two on VHM â€‹+ â€‹ART experienced serious adverse events. Fourteen participants underwent TI; all experienced VL rebound with no difference in time between arms: VHM â€‹+ â€‹ART (n â€‹= â€‹9) median: 4 weeks and ART only (n â€‹= â€‹5) median: 5 weeks. VHM induced a 2.2-fold increase in VL (p â€‹= â€‹0.008) by single-copy HIV RNA assay after the first cycle. Neopterin levels increased significantly following the first two cycles. After VHM treatment, the frequencies of peripheral blood mononuclear cells harboring total HIV DNA and cell-associated RNA were unchanged. All participants achieved VL suppression following ART re-initiation. Conclusions: Administration of VHM increased HIV VL in plasma, but this was not sustained. VHM did not impact time to viral rebound following TI and had no impact on the size of the HIV reservoir, suggesting that HIV reservoir elimination will require alternative treatment strategies.

15.
J Int AIDS Soc ; 23(9): e25585, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32949118

RESUMO

INTRODUCTION: Up to 30% of individuals treated with antiretroviral therapy (ART) during chronic HIV fail to recover CD4 counts to >500 cells/mm3 despite plasma viral suppression. We investigated the frequency and associations of suboptimal CD4 recovery after ART started during acute HIV infection (AHI). METHODS: Participants who started ART in Fiebig I to V AHI with ≥48 weeks of continuous documented HIV-RNA < 50 copies/mL were stratified by CD4 count at latest study visit to suboptimal immune recovery (SIR; CD4 < 350 cells/mm3 ), intermediate immune recovery (IIR; 350 ≤ CD4 < 500) and complete immune recovery (CIR; CD4 ≥ 500). Clinical and laboratory parameters were assessed at pre-ART baseline and latest study visit. Additional inflammatory and neurobehavioral endpoints were examined at baseline and 96 weeks. RESULTS: Of 304 participants (96% male, median 26 years old) evaluated after median 144 (range 60 to 420) weeks of ART initiated at median 19 days (range 1 to 62) post-exposure, 3.6% (n = 11) had SIR and 14.5% (n = 44) had IIR. Pre-ART CD4 count in SIR compared to CIR participants was 265 versus 411 cells/mm3 (p = 0.002). Individuals with SIR or IIR had a slower CD4 rate of recovery compared to those with CIR. Timing of ART initiation by Fiebig stage did not affect CD4 count during treatment. Following ART, the CD8+ T cell count (p = 0.001) and CD4/CD8 ratio (p = 0.047) were lower in SIR compared to CIR participants. Compared to the CIR group at week 96, the combined SIR and IIR groups had higher sCD14 (p = 0.008) and lower IL-6 (p = 0.04) in plasma, without differences in neuropsychological or psychiatric indices. CONCLUSIONS: Despite immediate and sustained treatment in AHI, suboptimal CD4 recovery occurs uncommonly and is associated with low pre-ART CD4 count as well as persistent low CD8 count and CD4/CD8 ratio during treatment.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , HIV-1/imunologia , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Infecções por HIV/sangue , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
17.
bioRxiv ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32935102

RESUMO

A subset of patients with COVID-19 display neurologic symptoms but it remains unknown whether SARS-CoV-2 damages the central nervous system (CNS) directly through neuroinvasion, or if neurological symptoms are due to secondary mechanisms, including immune-mediated effects. Here, we examined the immune milieu in the CNS through the analysis of cerebrospinal fluid (CSF) and in circulation through analysis of peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with neurological symptoms. Single cell sequencing with paired repertoire sequencing of PBMCs and CSF cells show evidence for unique immune response to SARS-CoV-2 in the CNS. Strikingly, anti-SARS-CoV-2 antibodies are present in the CSF of all patients studied, but the antibody epitope specificity in the CSF and relative prevalence of B cell receptor sequences markedly differed when compared to those found in paired serum. Finally, using a mouse model of SARS-CoV-2 infection, we demonstrate that localized CNS immune responses occur following viral neuroinvasion, and that the CSF is a faithful surrogate for responses occurring uniquely in the CNS. These results illuminate CNS compartment-specific immune responses to SARS-CoV-2, forming the basis for informed treatment of neurological symptoms associated with COVID-19.

18.
JAMA Neurol ; 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897296

RESUMO

Importance: Neuroimaging is a key step in the clinical evaluation of brain injury. Conventional magnetic resonance imaging (MRI) systems operate at high-strength magnetic fields (1.5-3 T) that require strict, access-controlled environments. Limited access to timely neuroimaging remains a key structural barrier to effectively monitor the occurrence and progression of neurological injury in intensive care settings. Recent advances in low-field MRI technology have allowed for the acquisition of clinically meaningful imaging outside of radiology suites and in the presence of ferromagnetic materials at the bedside. Objective: To perform an assessment of brain injury in critically ill patients in intensive care unit settings, using a portable, low-field MRI device at the bedside. Design, Setting, and Participants: This was a prospective, single-center cohort study of 50 patients admitted to the neuroscience or coronavirus disease 2019 (COVID-19) intensive care units at Yale New Haven Hospital in New Haven, Connecticut, from October 30, 2019, to May 20, 2020. Patients were eligible if they presented with neurological injury or alteration, no contraindications for conventional MRI, and a body habitus not exceeding the scanner's 30-cm vertical opening. Diagnosis of COVID-19 was determined by positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction nasopharyngeal swab result. Exposures: Portable MRI in an intensive care unit room. Main Outcomes and Measures: Demographic, clinical, radiological, and treatment data were collected and analyzed. Brain imaging findings are described. Results: Point-of-care MRI examinations were performed on 50 patients (16 women [32%]; mean [SD] age, 59 [12] years [range, 20-89 years]). Patients presented with ischemic stroke (n = 9), hemorrhagic stroke (n = 12), subarachnoid hemorrhage (n = 2), traumatic brain injury (n = 3), brain tumor (n = 4), and COVID-19 with altered mental status (n = 20). Examinations were acquired at a median of 5 (range, 0-37) days after intensive care unit admission. Diagnostic-grade T1-weighted, T2-weighted, T2 fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences were obtained for 37, 48, 45, and 32 patients, respectively. Neuroimaging findings were detected in 29 of 30 patients who did not have COVID-19 (97%), and 8 of 20 patients with COVID-19 (40%) demonstrated abnormalities. There were no adverse events or complications during deployment of the portable MRI or scanning in an intensive care unit room. Conclusions and Relevance: This single-center series of patients with critical illness in an intensive care setting demonstrated the feasibility of low-field, portable MRI. These findings demonstrate the potential role of portable MRI to obtain neuroimaging in complex clinical care settings.

19.
Clin Infect Dis ; 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32916708

RESUMO

BACKGROUND: The central nervous system (CNS) is a likely reservoir of HIV, vulnerable to viral rebound, inflammation, and clinical changes upon stopping antiretroviral therapy (ART). It is critical to evaluate the CNS safety of studies using analytic treatment interruption (ATI) to assess HIV remission. METHODS: Thirty participants who started ART during acute HIV infection underwent CNS assessments across four ATI remission trials. ART resumption occurred with plasma viral load >1000 copies/mL. CNS measures included paired pre- vs. post-ATI measures of mood, cognitive performance, and neurologic examination, with elective cerebrospinal fluid (CSF) sampling, brain diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). RESULTS: Median participant age was 30 years old and 29/30 were male. Participants' median time on ART prior to ATI was 3 years, and ATI lasted a median of 35 days. Post-ATI, there were no differences in median mood scores or neurologic findings and cognitive performance improved modestly. During ATI, a low level of CSF HIV-1 RNA was detectable in six of 20 participants with plasma viremia, with no group changes in CSF immune activation markers or brain DTI measures. Mild worsening was identified in post-ATI basal ganglia total choline MRS, suggesting an alteration in neuronal membranes. CONCLUSION: No adverse CNS effects were observed with brief, closely-monitored ATI in participants with acutely treated HIV, except a MRS alteration in basal ganglia choline. Further studies are needed to assess CNS ATI safety in HIV remission trials, particularly for studies using higher thresholds to restart ART and longer ATI durations.

20.
Stroke ; 51(9): 2664-2673, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32755347

RESUMO

BACKGROUND: Anecdotal reports suggest fewer patients with stroke symptoms are presenting to hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We quantify trends in stroke code calls and treatments at 3 Connecticut hospitals during the local emergence of COVID-19 and examine patient characteristics and stroke process measures at a Comprehensive Stroke Center (CSC) before and during the pandemic. METHODS: Stroke code activity was analyzed from January 1 to April 28, 2020, and corresponding dates in 2019. Piecewise linear regression and spline models identified when stroke codes in 2020 began to decline and when they fell below 2019 levels. Patient-level data were analyzed in February versus March and April 2020 at the CSC to identify differences in patient characteristics during the pandemic. RESULTS: A total of 822 stroke codes were activated at 3 hospitals from January 1 to April 28, 2020. The number of stroke codes/wk decreased by 12.8/wk from February 18 to March 16 (P=0.0360) with nadir of 39.6% of expected stroke codes called from March 10 to 16 (30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019). There was no commensurate increase in within-network telestroke utilization. Compared with before the pandemic (n=167), pandemic-epoch stroke code patients at the CSC (n=211) were more likely to have histories of hypertension, dyslipidemia, coronary artery disease, and substance abuse; no or public health insurance; lower median household income; and to live in the CSC city (P<0.05). There was no difference in age, sex, race/ethnicity, stroke severity, time to presentation, door-to-needle/door-to-reperfusion times, or discharge modified Rankin Scale. CONCLUSIONS: Hospital presentation for stroke-like symptoms decreased during the COVID-19 pandemic, without differences in stroke severity or early outcomes. Individuals living outside of the CSC city were less likely to present for stroke codes at the CSC during the pandemic. Public health initiatives to increase awareness of presenting for non-COVID-19 medical emergencies such as stroke during the pandemic are critical.


Assuntos
Isquemia Encefálica/epidemiologia , Hemorragias Intracranianas/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/terapia , COVID-19 , Estudos de Coortes , Comorbidade , Connecticut/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Infecções por Coronavirus/epidemiologia , Dislipidemias/epidemiologia , Serviços Médicos de Emergência , Grupos Étnicos , Feminino , Humanos , Hipertensão/epidemiologia , Renda , Seguro Saúde , Hemorragias Intracranianas/diagnóstico , Hemorragias Intracranianas/fisiopatologia , Hemorragias Intracranianas/terapia , Masculino , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Telemedicina , Trombectomia , Terapia Trombolítica
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