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1.
Arthritis Care Res (Hoboken) ; 76(8): 1051-1069, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38973731

RESUMEN

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades Pulmonares Intersticiales , Enfermedades Reumáticas , Reumatología , Humanos , Enfermedades Pulmonares Intersticiales/terapia , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/terapia , Reumatología/normas , Glucocorticoides/uso terapéutico , Medicina Basada en la Evidencia/normas
2.
Arthritis Rheumatol ; 76(8): 1201-1213, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38973714

RESUMEN

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades Pulmonares Intersticiales , Enfermedades Reumáticas , Reumatología , Enfermedades Pulmonares Intersticiales/diagnóstico , Humanos , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/diagnóstico , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/complicaciones , Reumatología/normas , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Artritis Reumatoide/complicaciones , Sociedades Médicas , Estados Unidos , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Enfermedad Mixta del Tejido Conjuntivo/diagnóstico , Miositis/diagnóstico , Miositis/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/complicaciones , Prueba de Paso
3.
Arthritis Care Res (Hoboken) ; 76(8): 1070-1082, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38973729

RESUMEN

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades Pulmonares Intersticiales , Enfermedades Reumáticas , Humanos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/diagnóstico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Reumatología/normas , Tamizaje Masivo/normas , Tamizaje Masivo/métodos
4.
Arthritis Rheumatol ; 76(8): 1182-1200, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38978310

RESUMEN

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.


Asunto(s)
Enfermedades Autoinmunes , Glucocorticoides , Enfermedades Pulmonares Intersticiales , Enfermedades Reumáticas , Reumatología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Humanos , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Reumatología/normas , Esclerodermia Sistémica/complicaciones , Estados Unidos , Progresión de la Enfermedad , Sociedades Médicas
5.
J Clin Rheumatol ; 30(6): 219-222, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38980171

RESUMEN

BACKGROUND AND OBJECTIVES: Renal involvement in systemic sclerosis remains a significant concern with the focus often centered on scleroderma renal crisis (SRC). However, the broader spectrum of renal manifestations, beyond SRC, remains underrecognized. In our case-control analysis, we describe other causes, risk factors, and renal outcomes of acute kidney injury (AKI) in systemic sclerosis other than SRC. METHODS: Patients diagnosed with SSC, with and without AKI, between 2017 and 2023 at Albany Medical Center, were included in the case-control study using International Classification of Diseases , 10th Revision codes and electronic medical records. Patients with SRC were carefully excluded. Data were collected and compared between AKI and non-AKI groups for patients' demographics, clinical characteristics, and baseline treatment. Additionally, data were collected for baseline, peak, and follow-up creatinine, etiology of AKI, treatment, and outcomes. Statistical analysis was performed using R (version 4.3.0) and Minitab (V19). Categorical variables were presented as frequencies/percentages, and continuous variables as means/standard deviations. Associations between categorical variables were assessed by χ 2 test and Fisher exact test. Odds ratios and 95% confidence intervals were calculated using binary logistic regression to separately assess the effect of each independent variable on the odds of AKI. Statistical significance was set at p < 0.05. RESULTS: A total of 74 cases were identified. Out of these 74 cases, 27 had AKI and 47 did not have AKI. Out of the 27 AKI cases, 4 with SRC were excluded. Advanced age, chronic kidney disease, and heart failure were identified as risk factors for AKI development. The predominant cause of AKI was prerenal etiology, accounting for 47.8% (n = 11) of cases. This was followed by cardiorenal syndrome and acute tubular necrosis, accounting for 21.7% and 17.3% of the cases, respectively. Most of the cases with AKI had complete renal recovery 78% (n = 18), whereas 17% (n = 4) had progression of the underlying chronic kidney disease. One patient progressed to end-stage renal disease requiring hemodialysis. CONCLUSIONS: This analysis highlights the risk factors and variable clinicopathological courses of renal involvement in patients with scleroderma. This may range from mild AKI with good prognosis to life-threatening SRC.


Asunto(s)
Lesión Renal Aguda , Esclerodermia Sistémica , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Estudios de Casos y Controles , Factores de Riesgo , Anciano , Adulto , Creatinina/sangre
6.
J Neuroinflammation ; 21(1): 165, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937750

RESUMEN

BACKGROUND: Traumatic brain injury (TBI) is a significant risk factor for Alzheimer's disease (AD), and accumulating evidence supports a role for adaptive immune B and T cells in both TBI and AD pathogenesis. We previously identified B cell and major histocompatibility complex class II (MHCII)-associated invariant chain peptide (CLIP)-positive B cell expansion after TBI. We also showed that antagonizing CLIP binding to the antigen presenting groove of MHCII after TBI acutely reduced CLIP + splenic B cells and was neuroprotective. The current study investigated the chronic effects of antagonizing CLIP in the 5xFAD Alzheimer's mouse model, with and without TBI. METHODS: 12-week-old male wild type (WT) and 5xFAD mice were administered either CLIP antagonist peptide (CAP) or vehicle, once at 30 min after either sham or a lateral fluid percussion injury (FPI). Analyses included flow cytometric analysis of immune cells in dural meninges and spleen, histopathological analysis of the brain, magnetic resonance diffusion tensor imaging, cerebrovascular analysis, and assessment of motor and neurobehavioral function over the ensuing 6 months. RESULTS: 9-month-old 5xFAD mice had significantly more CLIP + B cells in the meninges compared to age-matched WT mice. A one-time treatment with CAP significantly reduced this population in 5xFAD mice. Importantly, CAP also improved some of the immune, histopathological, and neurobehavioral impairments in 5xFAD mice over the ensuing six months. Although FPI did not further elevate meningeal CLIP + B cells, it did negate the ability of CAP to reduce meningeal CLIP + B cells in the 5xFAD mice. FPI at 3 months of age exacerbated some aspects of AD pathology in 5xFAD mice, including further reducing hippocampal neurogenesis, increasing plaque deposition in CA3, altering microgliosis, and disrupting the cerebrovascular structure. CAP treatment after injury ameliorated some but not all of these FPI effects.


Asunto(s)
Antígenos de Diferenciación de Linfocitos B , Linfocitos B , Lesiones Traumáticas del Encéfalo , Antígenos de Histocompatibilidad Clase II , Ratones Transgénicos , Animales , Ratones , Masculino , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Antígenos de Histocompatibilidad Clase II/metabolismo , Linfocitos B/efectos de los fármacos , Meninges/patología , Meninges/efectos de los fármacos , Precursor de Proteína beta-Amiloide/genética , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Modelos Animales de Enfermedad , Presenilina-1/genética , Ratones Endogámicos C57BL
7.
Clin Nephrol ; 102(2): 97-106, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38699985

RESUMEN

BACKGROUND: Systemic sclerosis (SSc) is a multi-system rheumatic disease characterized by vascular and fibrotic manifestations that can affect practically every organ. Scleroderma renal crisis (SRC) is the most common renal manifestation of SSc. However, with the use of angiotensin-converting enzyme inhibitors (ACEi), the morbidity and mortality associated with SRC has significantly reduced. Renal manifestations in SSc other than SRC have been generally under-recognized and can be left untreated, which can lead to grave consequences in this patient population. In this article, we will describe the spectrum of renal disease in SSc besides SRC. MATERIALS AND METHODS: A literature search was conducted on PubMed and Cochrane from inception to December 2022 using medical subject headings (MeSH) terms for "scleroderma", "systemic sclerosis" combined with "renal injury", and "renal dysfunction". We included case reports, case series, observational studies, and literature reviews. RESULTS: The initial search revealed 393 articles. After the exclusion of duplicates and non-relevant articles, data was included from 30 articles and 45 patients. The mean age was 55.2 years, 9 males (20%) and 36 females (80%). The most reported renal manifestations included: ANCA-associated vasculitis (n = 22), penicillamine-induced renal injury (n = 8), oxalate nephropathy (n = 5), Goodpasture syndrome (n = 4), nephrotic range proteinuria (n = 2), renal artery stenosis (n = 2), membranous glomerulonephritis (n = 1), and Evans syndrome (n = 1). CONCLUSION: The spectrum of kidney involvement in SSc can range from asymptomatic reduction of the glomerular filtration rate to life-threatening scleroderma renal crisis. Therefore, it is essential that physicians closely monitor renal function in these patients for any emerging renal dysfunction.


Asunto(s)
Esclerodermia Sistémica , Humanos , Esclerodermia Sistémica/complicaciones , Enfermedades Renales/etiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis , Hemorragia , Enfermedades Pulmonares
8.
Int J Mol Sci ; 24(22)2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-38003274

RESUMEN

Traumatic brain injury (TBI) is a major health concern. Each year, over 50 million individuals worldwide suffer from TBI, and this leads to a number of acute and chronic health issues. These include affective and cognitive impairment, as well as an increased risk of alcohol and drug use. The dopaminergic system, a key component of reward circuitry, has been linked to alcohol and other substance use disorders, and previous research indicates that TBI can induce plasticity within this system. Understanding how TBI modifies the dopaminergic system may offer insights into the heightened substance use and reward-seeking behavior following TBI. The hippocampus, a critical component of the reward circuit, is responsible for encoding and integrating the spatial and salient aspects of rewarding stimuli. This study explored TBI-related changes in neuronal D2 receptor expression within the hippocampus, examining the hypothesis that sex differences exist in both baseline hippocampal D2 receptor expression and its response to TBI. Utilizing D2-expressing tdTomato transgenic male and female mice, we implemented either a sham injury or the lateral fluid percussion injury (FPI) model of TBI and subsequently performed a region-specific quantification of D2 expression in the hippocampus. The results show that male mice exhibit higher baseline hippocampal D2 expression compared to female mice. Additionally, there was a significant interaction effect between sex and injury on the expression of D2 in the hippocampus, particularly in regions of the dentate gyrus. Furthermore, TBI led to significant reductions in hippocampal D2 expression in male mice, while female mice remained mostly unaffected. These results suggest that hippocampal D2 expression varies between male and female mice, with the female dopaminergic system demonstrating less susceptibility to TBI-induced plasticity.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Dopamina , Femenino , Masculino , Ratones , Animales , Dopamina/metabolismo , Lesiones Traumáticas del Encéfalo/metabolismo , Hipocampo/metabolismo , Neuronas/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo
9.
Semin Arthritis Rheum ; 63: 152256, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37689027

RESUMEN

BACKGROUND: The pathogenesis of scleroderma renal crisis (SRC) remains poorly understood but a growing body of evidence suggests that activation of the complement system may be involved in the disease. Recent studies have shown that Eculizumab (monoclonal antibody directed against the complement component C5) is effective in treating patients with SRC who present with symptoms of thrombotic microangiopathy (SRC-TMA). OBJECTIVES: In this study, we conducted a systematic review to characterize the published experience of the presentation and outcome of patients with SRC who were treated with C5 inhibitor, Eculizumab. METHODS: A literature search was conducted from inception to December 2022 using Medical Subject Headings (MeSH) terms for 'scleroderma', 'scleroderma renal crisis, and 'Eculizumab'. We included case reports, case series, and observational studies which reported the use of Eculizumab with or without Angiotensin-converting enzyme inhibitors (ACE-I) for the treatment of scleroderma renal crisis (SRC) in patients with systemic sclerosis. RESULTS: The study included 17 patients, all of whom were treated with Eculizumab. Additionally, the use of ACE-I was reported in 11/17 (64.7%) patients. Further, plasmapheresis was used in 9/17 (52.9%), steroids in 5/17 (29.4%), cyclophosphamide in 3/17 (17.6%), calcium channel blockers in 3/17 (17.6%), and Rituximab in 3/17 (17.6%) patients. Renal replacement therapy was required in 11/17 (64.7%) patients. 14/17 patients (82.3%) were reported to have clinical (renal or hematologic) improvement with Eculizumab therapy (Table 1). CONCLUSION: These findings should prompt testing on a larger cohort of SRC-TMA patients. This would help us determine whether aggressive treatment combining ACE-I and Eculizumab can target the various underlying endothelial, inflammatory, and immunologic mechanisms involved in SRC-TMA, and improve patient outcomes.


Asunto(s)
Lesión Renal Aguda , Esclerodermia Sistémica , Microangiopatías Trombóticas , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Riñón/patología , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/etiología , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/patología
11.
Nat Commun ; 14(1): 2186, 2023 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-37069258

RESUMEN

Despite extensive research on astrocytic Ca2+ in synaptic transmission, its contribution to the modulation of sensory transmission during different brain states remains largely unknown. Here, by using two-photon microscopy and whole-cell recordings, we show two distinct astrocytic Ca2+ signals in the murine barrel cortex: a small, long-lasting Ca2+ increase during sleep and a large, widespread but short-lasting Ca2+ spike when aroused. The large Ca2+ wave in aroused mice was inositol trisphosphate (IP3)-dependent, evoked by the locus coeruleus-norepinephrine system, and enhanced sensory input, contributing to reliable sensory transmission. However, the small Ca2+ transient was IP3-independent and contributed to decreased extracellular K+, hyperpolarization of the neurons, and suppression of sensory transmission. These events respond to different pharmacological inputs and contribute to distinct sleep and arousal functions by modulating the efficacy of sensory transmission. Together, our data demonstrate an important function for astrocytes in sleep and arousal states via astrocytic Ca2+ waves.


Asunto(s)
Astrocitos , Vigilia , Ratones , Animales , Astrocitos/fisiología , Señalización del Calcio/fisiología , Nivel de Alerta/fisiología , Sueño
12.
Front Pharmacol ; 13: 979788, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36313333

RESUMEN

Background: The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of environmental and personal factors (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs. Interstitial lung diseases (ILDs), are generally progressive, with restrictive physiology sometimes occurring in the context of multi-organ autoimmunity/inflammatory conditions such as connective tissue diseases (CTDs). In spite of significant associated morbidity and potential disability, ILD has yet to be linked to the ICF. Methods: Each instrument and their question-items within the consensus-recommended core sets for clinical trials in ILD were deconstructed to single concept units, and then linked per updated ICF linkage rules. Inter-linker agreement was established. Three additional subsequently validated measures were also included. Results: One-hundred-eleven ICF categories were identified for ten PROMs and three traditional objective measures that were amenable to ICF linkage. The proportion of agreement ranged from 0.79 (95% CI: 0.62, 0.91) to 0.93 (0.76, 0.99) with the overall proportion of inter-linker agreement being very high 0.86 (0.82, 0.89) for the initial instruments, with 94-100% for the three additional PROMs. Thirty-four new 'Personal Factors' emerged to capture disease-specific qualities not elsewhere described in ICF, e.g. 'pf_embarrassed by cough' or 'pf_panic/afraid when can't get a breath'. Conclusion: This first known effort in ICF linkage of ILD has provided important revelations on the current utility of the ICF in lung disease. Results have indicated areas for meaningful assessment of ICF descriptors for lung impairment. The mapping across PROMs provides insight into possibilities of developing more streamline and precise instrumentation. Finally, familiarity with the ICF in ILD may enable clinicians to experience a smoother transition with the imminent harmonization of ICD and ICF, ICD-11.

13.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36077246

RESUMEN

TBI induces splenic B and T cell expansion that contributes to neuroinflammation and neurodegeneration. The vagus nerve, the longest of the cranial nerves, is the predominant parasympathetic pathway allowing the central nervous system (CNS) control over peripheral organs, including regulation of inflammatory responses. One way this is accomplished is by vagus innervation of the celiac ganglion, from which the splenic nerve innervates the spleen. This splenic innervation enables modulation of the splenic immune response, including splenocyte selection, activation, and downstream signaling. Considering that the left and right vagus nerves have distinct courses, it is possible that they differentially influence the splenic immune response following a CNS injury. To test this possibility, immune cell subsets were profiled and quantified following either a left or a right unilateral vagotomy. Both unilateral vagotomies caused similar effects with respect to the percentage of B cells and in the decreased percentage of macrophages and T cells following vagotomy. We next tested the hypothesis that a left unilateral vagotomy would modulate the splenic immune response to a traumatic brain injury (TBI). Mice received a left cervical vagotomy or a sham vagotomy 3 days prior to a fluid percussion injury (FPI), a well-characterized mouse model of TBI that consistently elicits an immune and neuroimmune response. Flow cytometric analysis showed that vagotomy prior to FPI resulted in fewer CLIP+ B cells, and CD4+, CD25+, and CD8+ T cells. Vagotomy followed by FPI also resulted in an altered distribution of CD11bhigh and CD11blow macrophages. Thus, transduction of immune signals from the CNS to the periphery via the vagus nerve can be targeted to modulate the immune response following TBI.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Vagotomía , Animales , Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/cirugía , Modelos Animales de Enfermedad , Ratones , Bazo , Nervio Vago/metabolismo
14.
Ann Diagn Pathol ; 59: 151943, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35588602

RESUMEN

Kohlmeier-Degos Disease is a unique thrombotic microvascular and arteriopathic vasculopathy that is highly selective in the organs it targets. It invariably involves the skin and can be a purely cutaneous process. It affects both the microvasculature and the arterial system ranging from a thrombogenic microangiopathy to a fibrointimal obliterative arteriopathy with an accompanying background of extravascular fibrosis. A potentially lethal complication of Kohlmeier-Degos disease is constrictive pericarditis and pleuritis. We present three male patients, ages 26 years, 46 years and 58 years of age with established cutaneous and gastrointestinal Kohlmeier-Degos disease who developed progressive pericarditis which in two necessitated a pericardiectomy. There are 6 other reported cases, 5 in men, with restrictive symptoms developing on average 6 years following the onset of skin disease and all with gastrointestinal involvement. Half of the patients died within one year following the diagnosis of cardiopulmonary restrictive disease. The restrictive symptoms developed within 12 months, 2 years and 11 years following the initial skin presentation. In one patient this complication developed despite receiving eculizumab, indicative that this extravascular fibrosing reaction was not complement mediated as opposed to the thrombotic microvascular component of the disease which is C5b-9 mediated. Two of the three patients had evidence of right ventricular dysfunction. Two of our patients died within 1 year of developing constrictive pericarditis due to progressive cardiopulmonary failure. A profibrogenic process resembling scleroderma was seen given the degree of smooth muscle actin staining along with a mirror image reduction in CD34 expression within the fibrotic pleura and pericardium. There was significant upregulation in type I interferon signaling in cases tested as revealed by the degree of staining for MXA, the surrogate type I interferon marker. We propose that excessive type I interferon signaling results in the influx of monocyte derived dendritic cells with subsequent transdifferentiation into potent collagen producing myofibroblasts. We believe that targeting and suppressing type I interferon signaling should be a cornerstone of early therapy in patients with Kohlmeier- Degos disease to prevent pleural and pericardial fibrosis.


Asunto(s)
Interferón Tipo I , Papulosis Atrófica Maligna , Pericarditis Constrictiva , Enfermedades de la Piel , Trombosis , Adulto , Fibrosis , Humanos , Masculino , Papulosis Atrófica Maligna/complicaciones , Persona de Mediana Edad , Pericarditis Constrictiva/complicaciones
15.
Orphanet J Rare Dis ; 17(1): 172, 2022 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-35443671

RESUMEN

INTRODUCTION: Kohlmeier-Degos (K-D) disease is a rare obliterative vasculopathy that can present as a benign cutaneous form or with potentially malignant systemic involvement. The gastrointestinal tract is most frequently involved in systemic disease and mortality is often related to bowel perforations. Herein, we provide information to providers and patients regarding gastrointestinal K-D symptomology, pathology, treatment, and diagnosis, with a focus on the importance of timely diagnostic laparoscopy. We present three new cases of gastrointestinal K-D to highlight varying disease presentations and outcomes. BODY: Based on reviewed reports, perforation is preceded by at least one gastrointestinal symptom: abdominal pain/cramping, anorexia/weight loss, vomiting, diarrhea, nausea, gastrointestinal bleeding, obstipation, constipation, and abdominal fullness. Perforation most commonly occurs in the small intestine and often results in sepsis and death. Although underutilized, laparoscopy is the most sensitive and specific diagnostic technique, demonstrating serosal porcelain plaques similar to those on the skin and characteristic for K-D. The combination of eculizumab and treprostinil is presently the most effective treatment option for gastrointestinal K-D. The pathology of gastrointestinal K-D is characterized by an obliterative intimal arteriopathy eventuating in occlusive acellular deposits of mucin and collagen along with an extravascular pauci-cellular sclerosing process resembling scleroderma confined to the subserosal fat. C5b-9 and interferon-alpha are both expressed in all caliber of vessels in the affected intestine. While C5b-9 blockade does not prevent the intimal expansion, enhanced type I interferon signaling is likely a key determinant to intimal expansion by, causing an influx of monocytes which transdifferentiate into procollagen-producing myofibroblast-like cells. CONCLUSION: Prompt laparoscopic evaluation is necessary in any K-D patient with an abdominal symptom to facilitate diagnosis and treatment initiation, as well as to hopefully decrease mortality. Those with gastrointestinal K-D should start on eculizumab as soon as possible, as onset of action is immediate.


Asunto(s)
Enfermedades Gastrointestinales , Papulosis Atrófica Maligna , Complejo de Ataque a Membrana del Sistema Complemento , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/patología , Humanos , Papulosis Atrófica Maligna/diagnóstico , Papulosis Atrófica Maligna/patología , Piel/patología
16.
Neurotoxicology ; 90: 205-215, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35421512

RESUMEN

Gulf War illness (GWI) is a chronic, multi-symptom disorder that has impacted approximately one third of Gulf War veterans. GWI and its symptoms have been linked to the exposure to neurological chemicals, including the anti-nerve gas drug pyridostigmine bromide (PB) and the insecticide permethrin (PER), among others. Mouse models utilizing these chemicals have reported symptomology analogous to human GWI. These changes include behavioral and cognitive impairment, neuroinflammation and hippocampal pathogenesis. Disease modifying interventions that target these pathological components are desperately needed. Vagus nerve stimulation (VNS) is FDA approved for drug-resistant epilepsy and depression. VNS has also been used off-label to target a myriad of symptoms, some of which are encompassed within the Kansas and CDC definitions of clinical GWI symptomology. A GWI animal model in which mice are exposed to a daily injection of PB and PER for 10 consecutive days has been shown to exhibit cognitive impairment and hippocampal pathology. The purpose of this study was to determine if 2-4 weeks of continuous vagus nerve stimulation initiated at 32 weeks after exposure to PB and PER would improve cognitive performance and hippocampal pathology. The results of the study revealed that exposure to PB and PER produces long-term cognitive deficits and reduced hippocampal neurogenesis. The results also showed that the VNS treatment was anxiolytic, improved some aspects of pattern separation deficits, and mitigated the reduced hippocampal neurogenesis. Thus, VNS improves outcomes in a mouse model of GWI and should be examined as a potential therapeutic strategy for mitigating some symptomology associated with GWI.


Asunto(s)
Síndrome del Golfo Pérsico , Estimulación del Nervio Vago , Animales , Modelos Animales de Enfermedad , Guerra del Golfo , Ratones , Neurogénesis , Permetrina , Síndrome del Golfo Pérsico/tratamiento farmacológico , Síndrome del Golfo Pérsico/terapia , Bromuro de Piridostigmina/uso terapéutico , Bromuro de Piridostigmina/toxicidad
17.
Neurol India ; 70(1): 5-10, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35263846

RESUMEN

Malignant atrophic papulosis (MAP), or systemic Degos disease, is an obliterative vasculopathy of unknown origin, characterized by erythematous papules found on the skin, central nervous system (Neuro-MAP) and gastrointestinal tract. Neurological involvement occurs in approximately 20% of systemic cases, is progressive and largely fatal. It can be described in two forms: 1) the parenchymal presenting with meningoencephalitis and meningomyelitis and 2) the neurovascular presenting with large cerebral infarcts, intracranial and subarachnoid hemorrhage, subdural hematoma and venous sinus thrombosis. Predilection to subdural hematoma or hygroma is characteristic for neurological involvement in MAP in comparison to other vasculpathies and vasculitides. Peripheral nervous system manifestations are less common and include polyradiculopathy, neuropathy, and myopathy. CSF analysis usually shows mild to moderate pleocytosis, increased protein content, and normal glucose. Brain MRI may reveal cortical, subcortical and deep white matter ischemic lesions with possible nodular, leptomeningeal, dural, or ependymal enhancement. Spinal cord MRI may reveal patchy lesions from the periphery to the center or cord atrophy in progressive course. Neurological involvement in MAP has a grave prognosis. The interval from onset of papulosis to death averages two years in patients with neurological involvement. There is no confirmed treatment for MAP but there are promising reports with eculizumab and treprostinil.


Asunto(s)
Papulosis Atrófica Maligna , Atrofia/patología , Hematoma Subdural , Humanos , Papulosis Atrófica Maligna/complicaciones , Papulosis Atrófica Maligna/patología , Pronóstico , Piel/patología
18.
Arthritis Care Res (Hoboken) ; 74(11): 1806-1812, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-38662853

RESUMEN

OBJECTIVE: Diffuse cutaneous systemic sclerosis (SSc) is a highly heterogeneous disease. A provisionally approved Composite Response Index in diffuse cutaneous SSc (CRISS) was developed as a 1-year outcome measure for clinical trials. Our goal was to further validate the CRISS by examining agreement between CRISS definitions for improved/non-improved with physicians' evaluation of disease. METHODS: Patient profiles from a large observational cohort were created for 50 random diffuse cutaneous SSc patients of <5 years disease duration with improved CRISS scores after 1 year and 50 with non-improved CRISS scores. Profiles described disease features used during the initial CRISS development at baseline and at 1 year. Each profile was independently rated by 3 expert physicians. Majority opinion determined whether a patient was improved or not improved, and kappa agreement with the CRISS cutoff of 0.6 was calculated. RESULTS: Patients had mean ± SD disease duration of 2.2 ± 1.3 years. There was substantial agreement between the physician majority opinion about each case and the CRISS (κ = 0.76 [95% confidence interval (95% CI) 0.64-0.88]). The agreement between each individual physician opinion and the CRISS was also substantial (κ = 0.70 [95% CI 0.62-0.78]). All CRISS non-improvers were also rated as non-improved by physician majority; however, 12 CRISS improvers were rated as non-improved by physicians. CONCLUSION: There was substantial agreement between the dichotomous CRISS rating and physician assessment of diffuse cutaneous SSc patients after 1 year. This supports the use of a CRISS cutoff at 0.6 for improvement versus non-improvement, although the CRISS tended to rate more patients as improved than did physicians.


Asunto(s)
Esclerodermia Difusa , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Esclerodermia Difusa/diagnóstico , Índice de Severidad de la Enfermedad
19.
Brain Behav Immun Health ; 14: 100258, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34589764

RESUMEN

Following spinal cord injury, 18-26% of patients are diagnosed with depressive disorders, compared to 8-12% in the general population. As increased inflammation strongly correlates with depression in both animal and human studies, we hypothesized that the immune activation inherent to SCI could increase depression-like behavior. Thus, we proposed that reducing immune activation with minocycline, a microglial inhibitor, would decrease depression-like behavior following injury. Male Sprague-Dawley rats were given minocycline in their drinking water for 14 days following a moderate, mid-thoracic (T12) spinal contusion. An array of depression-like behaviors (social activity, sucrose preference, forced swim, open field activity) were examined prior to injury as well as on days 9-10, 19-20, and 29-30 post-injury. Peripheral cytokine levels were analyzed in serum collected prior to injury and 10 days post-injury. Hierarchical cluster analysis divided subjects into two groups based on behavior: depressed and not-depressed. Depressed subjects displayed lower levels of open field activity and social interaction relative to their not-depressed counterparts. Depressed subjects also showed significantly greater expression of pro-inflammatory cytokines both before and after injury and displayed lower levels of hippocampal neurogenesis than not-depressed subjects. Intriguingly, subjects who later showed depressive behaviors had higher baseline levels of the pro-inflammatory cytokine IL-6, which persisted throughout the duration of the experiment. Minocycline, however, did not affect serum cytokine levels and did not block the development of depression; equal numbers of minocycline versus vehicle-treated subjects appeared in both phenotypic groups. Despite this, these data overall suggest that molecular correlates of inflammation prior to injury could predict the development of depression after a physical stressor.

20.
World J Gastroenterol ; 27(31): 5201-5218, 2021 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-34497445

RESUMEN

Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia. The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition, as well as by xerostomia. In the pharyngeal phase of swallowing, pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance. The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility. However, it can also be affected by obstruction from chronic reflux changes, pill-induced esophagitis, or Candida esophagitis. Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis. Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.


Asunto(s)
Trastornos de Deglución , Esofagitis Péptica , Esclerodermia Sistémica , Trastornos de Deglución/etiología , Humanos , Manometría , Calidad de Vida , Esclerodermia Sistémica/complicaciones
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