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RATIONALE: Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a successful treatment for B-cell malignancies associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cardiovascular toxicities have also been reported in this setting. However, there is scarce data regarding development of autonomic disorders after CAR-T cell therapy. PATIENT CONCERNS: We report a case with a patient with non-Hodgkin B-cell lymphoma, refractory to 2 prior lines of immunochemotherapy, treated with CAR-T therapy. DIAGNOSES: Orthostatic hypotension secondary to autonomic dysfunction was diagnosed as manifestation of ICANS. INTERVENTIONS: The patient received metilprednisolone 1000 mg IV daily for 3 days and anakinra 100 mg IV every 6h. OUTCOMES: The vast majority of autonomic symptoms ceased and 4 months after CAR-T therapy, autonomic dysfunction was resolved. LESSONS: New-onset autonomic dysfunction can occur as manifestation of ICANS in patients who experience persistent neurologic and cardiovascular symptoms after resolution of acute neurotoxicity and should be early recognized. Differences in differential diagnosis, mechanisms and treatment approaches are discussed.
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Enfermedades del Sistema Nervioso Autónomo , Humanos , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Inmunoterapia Adoptiva/efectos adversos , Masculino , Síndrome de Liberación de Citoquinas/etiología , Persona de Mediana Edad , Linfoma de Células B/complicaciones , Linfoma de Células B/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/diagnóstico , Hipotensión Ortostática/etiología , Hipotensión Ortostática/diagnóstico , Metilprednisolona/uso terapéuticoRESUMEN
OBJECTIVES: Nocardia is an opportunistic infection among renal transplant recipients with an incidence of <1% but high mortality. Data from Pakistan are scarce. Our aim was to find the risk factors, clinical and radiographic findings, antimicrobial sensitivity, and outcomes of Nocardia infection among renal transplant recipients in Pakistan. MATERIALS AND METHODS: All adult renal transplant recipients diagnosed with nocardiosis between 2013 and 2020 were included. The cases were matched 1:2 with controls based on sex, age (±1 year), and transplant date (±1 year). Risk factors, clinical features, antibiotic sensitivities and outcomes were analyzed. RESULTS: A total of 48 patients developed nocardiosis. Around 25% of patients presented with disseminated disease. Median time from transplant to disease development was 2.68 years. High-dose methylprednisolone and presence of cytomegalovirus infection within 90 days of disease development were independent risk factors for Nocardia infection. The mortality rate was 20%. Central nervous system disease and cytomegalovirus infection within 90 days were significantly associated with mortality. The most susceptible drugs were co-trimoxazole and linezolid. Imipenem susceptibility was only 20%. CONCLUSIONS: High-dose methylprednisolone and cytomegalovirus infection were independent risk factors for Nocardia infection. Central nervous system disease was associated with mortality. Nocardia species were highly resistant to ceftriaxone and imipenem in our patient population.
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Antibacterianos , Huésped Inmunocomprometido , Trasplante de Riñón , Nocardiosis , Infecciones Oportunistas , Humanos , Nocardiosis/diagnóstico , Nocardiosis/mortalidad , Nocardiosis/epidemiología , Nocardiosis/tratamiento farmacológico , Nocardiosis/microbiología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Factores de Riesgo , Pakistán/epidemiología , Masculino , Femenino , Adulto , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/tratamiento farmacológico , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Factores de Tiempo , Estudios Retrospectivos , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/mortalidad , Infecciones por Citomegalovirus/epidemiología , Medición de Riesgo , Metilprednisolona/administración & dosificación , Inmunosupresores/efectos adversosRESUMEN
BACKGROUND: Intra-articular (IA) injections of plateletrich plasma (PRP) have been increasingly used in the nonoperative treatment of knee osteoarthritis (OA) but have considerable heterogeneity in both formulation and clinical results. Alpha-2-macroglobulin (A2M) is a large plasma protein found in PRP that inhibits cartilage-degrading enzymes and could be an efficacious OA treatment independently. The purpose of this study was to compare the short-term clinical efficacy of IA injection of A2M-rich PRP concentrate to conventionally prepared PRP and corticosteroids in the management of symptomatic knee OA. METHODS: This double-blinded, randomized, controlled clinical trial was conducted at a single medical center with enrollment from June 2018 to May 2019. Subjects with symptomatic Kellgren-Lawrence (KL) grade 2 or 3 knee OA were randomized to IA injection with A2M, PRP, or methylprednisolone (MP) and followed for 12 weeks post-injection. Knee pain and function were assessed at pre-treatment baseline and at 6-week and 12-week followup with patient-reported outcome (PRO) surveys including the visual analog scale (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, and Tegner score. RESULTS: Seventy-five subjects were enrolled in the trial, of whom 68 (90.7%) completed the 12-week follow-up. The majority of subjects (73%) were female with a mean age of 59 years (range: 37 to 75 years). There were no significant differences in age (p = 0.30), sex (p = 0.44), or KL grade (p = 0.73) between treatment groups. By 12 weeks postinjection, the A2M group showed significant improvement in VAS, WOMAC, KOOS, and Tegner (p < 0.05), the PRP group showed no significant improvement in any PROs (p > 0.05), and the MP group showed significant improvement in Lysholm only (p = 0.01). However, the changes in PRO scores between baseline and 12-week follow-up did not significantly differ between the three groups (p > 0.05). CONCLUSIONS: Alpha-2-macroglobulin IA injection shows comparable efficacy to PRP and corticosteroids in the treatment of mild-to-moderate knee OA. Alpha-2-macroglobulin treatment resulted in modest improvement in knee pain and function at 6-week follow-up, albeit inconsistently across PRO measures and to a similar degree as PRP and corticosteroids. Given its non-superior short-term efficacy compared to established IA injections, as well as its increased cost of preparation, A2M may not be a justifiable option for routine treatment of knee OA.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/fisiopatología , Femenino , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Método Doble Ciego , Resultado del Tratamiento , Anciano , Metilprednisolona/administración & dosificación , Dimensión del Dolor , Plasma Rico en Plaquetas , alfa-Macroglobulinas/metabolismo , alfa 2-Macroglobulinas Asociadas al Embarazo , Adulto , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/fisiopatologíaRESUMEN
Although COVID-19 infection is an immunosuppressant disease, many immunosuppressant agents, such as pulse methylprednisolone (PMP), dexamethasone (DXM), and tocilizumab (TCZ), were used during the pandemic. Secondary infections in patients with COVID-19 have been reported recently. This study investigated these agents' effects on secondary infections and outcomes in patients with COVID-19 in intensive care units (ICUs). This study was designed retrospectively, and all data were collected from the tertiary intensive care units of six hospitals between March 2020 and October 2021. All patients were divided into three groups: Group I [GI, PMP (-), DXM (-) and TCZ (-)], Group II [GII, PMP (+), DXM (+)], and Group III [GIII, PMP (+), DXM (+), TCZ (+)]. Demographic data, PaO/FiO2 ratio, laboratory parameters, culture results, and outcomes were recorded. To compare GI-GII and GI-GIII, propensity score matching (PSM) was used by matching 14 parameters. Four hundred twelve patients with COVID-19 in the ICU were included in the study. The number of patients with microorganisms ≥ 2 was 279 (67.7%). After PSM, in GII and GIII, the number of (+) tracheal cultures and (+) bloodstream cultures detected different microorganisms ≥ 2 during the ICU period, neuropathy, tracheotomized patients, duration of IMV, and length of ICU stay were significantly higher than GI. The mortality rate was similar in GI and GII, whereas it was significantly higher in GIII than in GI. The use of immunosuppressant agents in COVID-19 patients may lead to an increase in secondary infections. In addition, increased secondary infections may lead to prolonged ICU stay, prolonged IMV duration, and increased mortality.
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COVID-19 , Inmunosupresores , Unidades de Cuidados Intensivos , Humanos , Masculino , Femenino , Estudios Retrospectivos , COVID-19/mortalidad , COVID-19/complicaciones , COVID-19/epidemiología , Persona de Mediana Edad , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Anciano , Dexametasona/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Metilprednisolona/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , AdultoRESUMEN
We present a case of a woman in her 20s with inadequately treated systemic lupus erythematosus (SLE). She presented with heavy menstrual bleeding, along with nasal and gum bleeding worsening over 3 months. There was no bleeding history in her family, childhood, dental procedures or childbirth. Evaluation ruled out structural causes, revealing prolonged activated partial thromboplastin time (incomplete correction on mixing studies), normal prothrombin time, moderate thrombocytopenia, and lupus anticoagulant and anti-phosphatidylserine/prothrombin antibody positivity twice, 12 weeks apart. Further evaluation showed very low von Willebrand factor (vWF) levels (<5%). She was treated with pulse methylprednisolone for 3 days, resulting in complete symptom resolution and improvement in vWF levels to 130%. The absence of bleeding history, family history, presence of very low vWF and its response to corticosteroids led to a diagnosis of acquired vWF syndrome as the cause of mucosal bleeding in an SLE patient with concomitant positive antiphospholipid antibody. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering oral corticosteroids.
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Anticuerpos Antifosfolípidos , Lupus Eritematoso Sistémico , Enfermedades de von Willebrand , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/diagnóstico , Anticuerpos Antifosfolípidos/sangre , Enfermedades de von Willebrand/complicaciones , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/tratamiento farmacológico , Enfermedades de von Willebrand/etiología , Adulto , Menorragia/etiología , Menorragia/tratamiento farmacológico , Metilprednisolona/uso terapéuticoRESUMEN
INTRODUCTION: Intratympanic corticosteroids are commonly used in the treatment of Menière's disease (MD). However, few and small randomised controlled trials (RCT) on the effectiveness of intratympanic corticosteroids have been performed. A recent Cochrane review suggested that a well-conducted placebo-controlled RCT with a large study population is required to evaluate the effectiveness of the use of intratympanic corticosteroids in MD. The following protocol describes a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial to compare the effectiveness of methylprednisolone (62.5 mg/mL) to a placebo (sodium chloride 0.9%). METHODS AND ANALYSIS: We aim to recruit 148 patients with unilateral MD from six hospitals in the Netherlands. Patients will be randomly assigned to either the methylprednisolone or the placebo group. Two injections will be given, one at baseline and one after 2 weeks. Follow-up assessments will be done at 3, 6, 9 and 12 months. The primary outcome will be the frequency of vertigo attacks. Attacks will be evaluated daily with the DizzyQuest app. Secondary outcomes include hearing loss, tinnitus, health-related quality of life, use of co-interventions and escape medication, (serious) adverse events and cost-effectiveness. These will be evaluated with audiometry and multiple commonly used, validated questionnaires. For the primary and secondary outcomes mixed model analysis, generalised estimating equation analysis and logistic regression analysis will be used. ETHICS AND DISSEMINATION: This study was submitted via the Clinical Trials Information System, reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft and the local institutional review board of each participating centre. All data will be presented ensuring the integrity and anonymity of patients. Results will be published in scientific journals and presented on (inter)national conferences. TRIAL REGISTRATION NUMBER: This study is registered at ClinicalTrials.gov Protocol Registration and Results System, with the registration ID: NCT05851508.
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Inyección Intratimpánica , Enfermedad de Meniere , Metilprednisolona , Vértigo , Humanos , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Enfermedad de Meniere/tratamiento farmacológico , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéutico , Estudios Multicéntricos como Asunto , Países Bajos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Vértigo/tratamiento farmacológicoRESUMEN
The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-ß1 (TGF-ß1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-ß1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-ß1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects.
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Budesonida , Transición Epitelial-Mesenquimal , Fibrosis , Enfermedades Inflamatorias del Intestino , Factor de Crecimiento Transformador beta1 , Humanos , Células CACO-2 , Transición Epitelial-Mesenquimal/efectos de los fármacos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Enfermedades Inflamatorias del Intestino/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Budesonida/farmacología , Adalimumab/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Metilprednisolona/farmacología , Mesalamina/farmacología , Prednisona/farmacología , Miofibroblastos/efectos de los fármacos , Miofibroblastos/metabolismo , Antiinflamatorios/farmacología , Infliximab/farmacología , Infliximab/uso terapéutico , Azatioprina/farmacología , Metotrexato/farmacología , Intestinos/efectos de los fármacos , Intestinos/patología , Diferenciación Celular/efectos de los fármacosRESUMEN
RATIONALE: Myelin oligodendrocyte glycoprotein (MOG) antibody-related disease is a relatively recent entity in inflammatory demyelinating disease. Its clinical presentation varies in severity and the lack of specific imaging features makes it easy to misdiagnose. We now report the case of a MOG antibody-positive patient who presented with diplopia and dizziness, and whose brain magnetic resonance imaging (MRI) showed abnormal signals in the bilateral pontine brachium. PATIENT CONCERNS: A previously healthy 52-year-old woman presented with diplopia and dizziness, and was hospitalized 4 days after onset. DIAGNOSES: Brain MRI demonstrated abnormal hyperintense signals in the bilateral pontine brachium on T2-weighted fluid attenuated inversion recovery imaging. MRI enhancement showed abnormal enhancement foci in bilateral pontine brachium and pons. Cerebrospinal fluid examination showed Oligoclonal IgG bands were negative. The IgG index was normal, and serum aquaporin-4 antibody was negative, while serum MOG-Ab was positive (1:100). In conjunction with a positive serum MOG antibody and exclusion of other diseases, diagnosis of MOG antibody-related disease was made. INTERVENTIONS: Intravenous methylprednisolone followed by oral corticosteroids. OUTCOMES: Symptoms resolved completely. At 4-month follow-up. Follow-up after 4 months showed disappearance of the abnormal signal in the left pontine brachium and diminution of abnormal high signal in the right compared to the previous one, and there was no recurrence 1 year after the onset of the disease. LESSONS: If brain MRI indicating bilateral, multiple, and diffuse abnormal signals in the pontine brachium, and a discrepancy between the clinical symptoms and the imaging severity, a diagnosis of demyelinating disease should be considered highly probable. In such cases, anti-MOG antibody testing is essential for further defining the etiology. The clinical phenotype and imaging manifestations of MOG antibody-positive brainstem encephalitis may lack sufficient specificity to be readily identifiable. Timely diagnosis and early glucocorticoid therapy are beneficial in improving prognosis and preventing recurrence.
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Autoanticuerpos , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Puente , Humanos , Femenino , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Puente/diagnóstico por imagen , Puente/patología , Metilprednisolona/uso terapéuticoAsunto(s)
Erupciones por Medicamentos , Pruebas Intradérmicas , Metilprednisolona , Humanos , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Inyecciones Intraarticulares , Femenino , Masculino , Persona de Mediana EdadRESUMEN
AIM: To evaluate the effects of methylprednisolone and vitamin B12 injection on the regeneration of the nerves after a mental nerve crush injury. MATERIAL AND METHODS: A total of 40 albino Wistar rats have been randomly divided into four groups: group 1 (n=10): crushlike nerve damage was created by pinching the left mental nerve for 60 s with an aneurysm clip and intraperitoneally administered 1 ml of saline for 14 days; group 2 (n=10): the left mental nerve was pinched for 60 s with an aneurysm clip and intraperitoneally administered 2 mg/kg of methylprednisolone for 14 days; group 3, experimental group (n=10): the left mental nerve was pinched for 60 s with an aneurysm clip and intraperitoneally administered 2 mg/kg of vitamin B12 for 14 days; and group 4, experimental group (n=10): the left mental nerve was pinched for 60 s and intraperitoneally administered 2 mg/kg of methylprednisolone and 2 mg/kg of vitamin B12 for 14 days. All rats were sacrificed on the 28th postoperative day, and histopathological evaluation was performed. RESULTS: Nerve damage was higher in the control group than in other groups (p < 0.05). When Neural Cell Adhesion Molecule (NCAM) expression levels were compared, no major differences were observed between the methylprednisolone and control groups (p > 0.05). The B12 and B12+methylprednisolone groups reached significantly higher NCAM expression levels compared to the control and methylprednisolone groups. When the myelin basic protein (MBP) expression levels were compared (p < 0.05), the MBP expression was significantly higher in all experimental groups than in the control group (p < 0.05). CONCLUSION: Systemic vitamin B12 and methylprednisolone administration effectively supported remyelination in the crushed mental nerve by increasing Schwann cell proliferation and differentiation.
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Metilprednisolona , Regeneración Nerviosa , Ratas Wistar , Vitamina B 12 , Animales , Metilprednisolona/administración & dosificación , Metilprednisolona/farmacología , Vitamina B 12/administración & dosificación , Vitamina B 12/farmacología , Regeneración Nerviosa/efectos de los fármacos , Ratas , Masculino , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Compresión Nerviosa , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: Spinal cord infarction (SCI) is a rare disease representing nearly 1% of all strokes with a wide variety of symptoms at presentation. SCI diagnosis is very challenging owing to its low incidence and the variety of symptoms, and could be misdiagnosed with neuromyelitis optica spectrum disorders (NMOSD). CASE PRESENTATION: We describe the case of an 18-year-old girl who presented to the emergency department with acute neck pain and flaccid paralysis of the left upper and lower extremities. Few hours later, she developed apnea and was endotracheally intubated. Brain MRI was normal but spinal cord MRI revealed non-enhancing longitudinal abnormal high T2 signal intensity extending from C1 to C5. The patient underwent steroid therapy with methylprednisolone (1 g daily for 7 consecutive days) combined with physiotherapy. She was extubated after 3 weeks and discharged after 30 days of hospitalization with a muscle force of 4/5 in her left extremities. DISCUSSION: Idiopathic SCI in adolescence is a rare but often devastating disorder with unknown pathophysiology, however, some specific conditions in adolescent such as mechanical stresses on the immature spine can be considered as risk factors for SCI development. Early diagnosis and treatment can improve outcomes in SCI.
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Médula Cervical , Infarto , Dolor de Cuello , Humanos , Femenino , Adolescente , Infarto/diagnóstico , Infarto/complicaciones , Infarto/diagnóstico por imagen , Médula Cervical/diagnóstico por imagen , Dolor de Cuello/etiología , Parálisis/etiología , Parálisis/diagnóstico , Metilprednisolona/uso terapéuticoRESUMEN
RATIONALE: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis. PATIENT CONCERNS: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies. DIAGNOSIS: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum. INTERVENTIONS AND OUTCOMES: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable. LESSONS: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner.
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Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica , Receptor del Glutamato Metabotropico 5 , Humanos , Femenino , Neuritis Óptica/diagnóstico , Neuritis Óptica/inmunología , Neuritis Óptica/tratamiento farmacológico , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Encefalitis/diagnóstico , Encefalitis/inmunología , Encefalitis/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Imagen por Resonancia Magnética , SíndromeRESUMEN
BACKGROUND: The post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized "STERoid for OHCA" (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission. METHODS: The STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences. RESULTS: The 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49-5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03-0.10), p < 0.001), IL-8 (ratio 0.53 (0.38-0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13-0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18-0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4-0.8), p = 0.01). CONCLUSION: Administering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h. TRIAL REGISTRATION: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT04624776.
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Reanimación Cardiopulmonar , Servicios Médicos de Urgencia , Glucocorticoides , Metilprednisolona , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/sangre , Paro Cardíaco Extrahospitalario/tratamiento farmacológico , Masculino , Femenino , Anciano , Persona de Mediana Edad , Metilprednisolona/administración & dosificación , Glucocorticoides/administración & dosificación , Reanimación Cardiopulmonar/métodos , Servicios Médicos de Urgencia/métodos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Citocinas/sangre , Proteína C-Reactiva/análisis , Biomarcadores/sangre , Método Doble Ciego , Interleucina-6/sangreRESUMEN
The reportedly poor outcome of late-onset idiopathic pneumonia syndrome (IPS) necessitates new approaches to its treatment. A 55-year-old man who had undergone allogeneic hematopoietic cell transplantation (allo-HCT) for myelodysplastic syndrome 1 year ago developed dyspnea with acute skin graft-versus-host disease (GVHD) flare-up while tapering immunosuppressive agents. He presented with acute respiratory distress syndrome with ground-glass opacities in the right upper and left lower lobes. All infectious tests, including multiplex polymerase chain reaction of nasal wash, were negative, and broad-spectrum antibiotic therapy was refractory. The patient was diagnosed with late-onset IPS and was refractory to methylprednisolone pulse therapy. He then showed a favorable response to mesenchymal stem cell (MSC) infusion. After eight infusions of MSCs, he had no IPS recurrence for over one year. Recently, preclinical studies have reported the potential therapeutic utility of MSC infusion for treating IPS, and our case supports its potential for treating late-onset IPS.
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Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Trasplante Homólogo , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/terapia , Enfermedad Injerto contra Huésped , Células Madre Mesenquimatosas , Metilprednisolona/uso terapéutico , Neumonía/etiología , Neumonía/terapia , SíndromeRESUMEN
A rare subtype of autoimmune encephalitis consists of antibodies targetting the alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid receptor in the central nervous system. We describe the clinical presentation and autoimmune profile of the first case of alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid receptor encephalitis with concurrent anti-acetylcholine receptor antibodies in Pakistan. The patient was a 58-year-old male who presented with the characteristic symptoms of limbic encephalitis with memory loss, irritability, agitation, and confusion. Antibodies against the alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptor were detected in both serum and cerebrospinal fluid by indirect immunofluorescence. Computerised tomography of the chest showed an anterior mediastinal mass. The patient was treated with high dose Methylprednisolone and five sessions of plasma exchange. There was a short period of improvement; however, the patient now continues to exhibit irritability, aphasia, confusion, and memory loss. Video-assisted thoracoscopic surgery for mediastinal mass resection and histological testing was planned, however after review by the interventional radiologist the associated risks were deemed too high to proceed with the procedure and biopsy was not done.
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Miastenia Gravis , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/diagnóstico , Miastenia Gravis/complicaciones , Receptores AMPA/inmunología , Autoanticuerpos/sangre , Encefalitis/inmunología , Encefalitis/diagnóstico , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Encefalitis Límbica/inmunologíaRESUMEN
A woman in her 20s presented with 6 weeks of fever, persistent vomiting and 28% loss of body weight. Symptoms were refractory to treatment with antiemetics and broad spectrum antibiotics.Further investigation via oesophageogastroduedenoscopy revealed a large gastric ulcer and pyloric stricture, causing gastric outlet obstruction (GOO). Biopsies of the stomach and duodenum showed plasma cell infiltration with a large proportion being IgG4 positive.Treatment with methylprednisolone, and later prednisolone, quickly improved inflammatory markers and symptoms. Balloon dilatation of the pyloric stricture also improved vomiting, allowing eventual re-establishment of oral nutrition. The patient made a full recovery with maintenance treatment on mycophenolate mofetil.IgG4-related disease (IgG4-RD) is a multisystem disorder with unpredictable presentation. The case highlights diagnostic challenges in IgG4-RD and identifies it as a rare differential in upper gastrointestinal symptoms. To our knowledge this is the first published case of IgG4-RD in the duodenum causing GOO.
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Obstrucción de la Salida Gástrica , Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Femenino , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Adulto , Diagnóstico Diferencial , Inmunoglobulina G/sangre , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Prednisolona/uso terapéutico , Úlcera Gástrica/complicaciones , Úlcera Gástrica/diagnóstico , Vómitos/etiología , Estenosis Pilórica/diagnóstico , Estenosis Pilórica/complicaciones , Duodeno/patologíaRESUMEN
BACKGROUND: Acute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD. METHODS: We conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission. RESULTS: Patients with a variety of ILD classification were included. Connective-tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA. CONCLUSIONS: mNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.
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Líquido del Lavado Bronquioalveolar , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades Pulmonares Intersticiales , Humanos , Femenino , Líquido del Lavado Bronquioalveolar/microbiología , Masculino , Persona de Mediana Edad , Anciano , Enfermedades Pulmonares Intersticiales/microbiología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Estudios Transversales , Estudios Retrospectivos , Inmunosupresores/administración & dosificación , Metagenómica/métodos , Metilprednisolona/administración & dosificación , Progresión de la EnfermedadRESUMEN
BACKGROUND: Acute respiratory distress syndrome (ARDS), are respiratory diseases with high morbidity and mortality. Clinical trials investigating the efficacy of corticosteroids in the treatment of ARDS often yield contradictory results. We hereby conducted a systematic review and meta-analysis to investigate the efficacy of corticosteroids in ARDS management. MATERIALS AND METHODS: We conducted a search for randomized clinical trials (RCT) and observational studies that utilized corticosteroids for patients with ARDS in Web of Science, PubMed, and Embase. The primary outcome was mortality. Risk of bias was assessed using Cochrane or NOS scales. Statistical effect size was analyzed using the Mantel-Haenszel method. RESULTS: A total of 20 studies, comprising 11 observational studies and 9 RCTs, were eligible for analysis. In RCTs, corticosteroids were associated with a reduction of mortality in ARDS patients (relative risk [RR] = 0.80, 95%CI: 0.71-0.91, p = 0.001). Further subgroup analysis indicated that specific variables, such as low-dose (RR = 0.81; 95%CI: 0.67-0.98; p = 0.034), methylprednisolone (RR = 0.70; 95%CI: 0.49-0.98; p = 0.035), and dexamethasone (RR = 0.82; 95%CI: 0.69-0.98; p = 0.029) were associated with mortality among patients receiving corticosteroids. However, in observational studies, corticosteroids increased the risk of death (RR = 1.16, 95%CI: 1.04-1.29; p = 0.001). Subgroup analysis showed that the use of high-dose corticosteroids was associated with higher patient mortality (RR = 1.20; 95%CI: 1.04-1.38; p = 0.001). CONCLUSIONS: The efficacy of corticosteroids on the mortality of ARDS differed by the type and dosage of corticosteroids used, as well as the etiologies. Current data do not support routine use of corticosteroids in ARDS since protective effects were observed in RCTs but increased mortality was found in observational studies. More well designed and large clinical trials are needed to specify the favorable subgroups for corticosteroid therapy.
Corticosteroid use may reduce the risk of death in patients with acute respiratory distress syndrome (ARDS) according to randomized controlled trials.Observational studies indicate that corticosteroid use may increase the risk of death in non-COVID-19 ARDS patients but not in COVID-19 ARDS patients.Both regular and low-dose corticosteroids show benefits in reducing mortality in RCTs, but observational studies associate these doses with increased mortality.
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Corticoesteroides , Dexametasona , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Dificultad Respiratoria , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/mortalidad , Humanos , Corticoesteroides/uso terapéutico , Dexametasona/uso terapéutico , Resultado del Tratamiento , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificaciónRESUMEN
PURPOSE: The primary objective of this study was to identify predictive factors linked to the normalization of thyroid-stimulating immunoglobulin (TSI) levels in patients diagnosed with active, moderate-to-severe Graves' orbitopathy (GO). The study also tracked the longitudinal changes in TSI levels over a 36-month period following treatment. METHODS: The study population consisted of individuals who were recently diagnosed with active, moderate-to-severe GO and received a 12-week course of intravenous methylprednisolone (IVMP) treatment. A subgroup of patients who did not respond to the initial treatment received an additional 20 Gy of radiation therapy (RTx). TSI levels were monitored at the time of diagnosis, after treatment, and subsequently every 6 months for 36 months. Normalization was defined as a TSI level below 140%. Patients were divdied into two groups with success and failure group depending on whether TSI became normal or not. RESULTS: Out of 83 patients, 36 (43.4%) achieved normalized TSI levels within two years post-IVMP treatment. Lower initial TSI levels (< 425%), absence of additional RTx, and early treatment initiation were associated with a higher likelihood of TSI normalization (P = 0.035, P = 0.028, P < 0.001, respectively). Notably, significant differences in TSI level reduction were observed from 18 months post-treatment between the two groups (P = 0.031). A TSI cutoff value of 413% was identified as predictive for normalization at 24 months (P = 0.002). CONCLUSION: This study is the first to identify key factors that influence normalization of TSI levels in moderate-to-severe Graves' Orbitopathy. It highlights the importance of early treatment decisions, particularly for patients with initial TSI levels above 425%. Despite the treatment, less than half of the patients achieved TSI normalization within 24 months, underscoring the need for additional research to explore the relationship between TSI levels and the clinical manifestations of chronic GO.
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Glucocorticoides , Oftalmopatía de Graves , Inmunoglobulinas Estimulantes de la Tiroides , Metilprednisolona , Humanos , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/sangre , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Adulto , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Glucocorticoides/uso terapéutico , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Estudios Longitudinales , Estudios de Seguimiento , Anciano , Índice de Severidad de la Enfermedad , Estudios RetrospectivosRESUMEN
BACKGROUND: Particulate steroids are thought to exert their effects for long durations at injection sites. However, these types of steroids carry higher risks when used in epidural steroid injections. Catastrophic spinal cord complications, including sudden-onset paraplegia, have been reported due to intravascular particulate steroid preparations that cause embolisms and occlusion of blood vessels, resulting in spinal cord infarctions. Clinicians, therefore, recommend nonparticulate steroids to mitigate these adverse events. To our knowledge, this is the first retrospective study that addresses the effectiveness and safety of methylprednisolone, dexamethasone, and betamethasone when used in transforaminal epidural steroid injections (TFESIs) for the treatment of lumbar radiculopathy. OBJECTIVES: The primary goal of this study was to compare the proportion of patients who received injections of particulate steroids and required zero repeat injections within 12 months of their initial injection to the proportion of patients who received injections of nonparticulate steroids and also required zero repeat injections, as well as to compare the number of patients in the particulate cohort who required one or more repeat injections within 12 months of their initial injection to the number of patients in the nonparticulate cohort who required the same. The secondary goal was to evaluate the proportion of patients ultimately requiring surgery. STUDY DESIGN: This is a single-center, IRB-approved, retrospective study evaluating the safety and effectiveness of nonparticulate as compared to particulate steroid medications when used in TFESIs as minimally invasive treatments for chronic lumbar radiculopathy. SETTING: This study captured data (n = 1717) over a 4-year time frame (01/15/2018 to 01/15/2022). METHODS: The following data were collected from each patient's chart: age, gender, BMI, race, date of initial injection, number of repeat injections at the same lumbosacral level and on the same side within 12 months of the initial injection, and lumbar surgery date (if applicable). Inclusion criteria included: 1) having chronic low back pain of radicular etiology; 2) being at least 18 years old; 3) having experienced the failure of conservative therapy after 12 weeks (including physical therapy and/or medications); 4) having positive physical exam findings supporting nerve impingement (straight leg raise, slump test); and 5) showing lumbar MRI evidence of nerve impingement from disc herniation. Exclusion criteria included: 1) having received prior lumbar surgery at any level (L1-S1); 2) having been given prior TFESIs fewer than 6 months prior to initial injection; 3) having contracted a systemic infection at the proposed injection site; 4) undergoing active cancer treatment; and 5) having gotten any other spine injections. RESULTS: A significantly greater proportion of patients in the nonparticulate steroid cohort received 0 repeat injections (87.5% vs 71.4%, P < 0.001). The particulate steroid cohort demonstrated a significantly greater proportion of patients who received repeat injections within 12 months after the initial injections (12.5% vs 29.6%, P < 0.001). There were no significant differences among patients requiring surgery between the 2 cohorts. Other outcome measures included the identification of risk factors significantly associated with repeat injections. There was a statistically significant weak positive correlation between age and repeat injections (Pearson corr = 0.102; P < 0.001) and a weak negative correlation between ethnicity/race and repeat injections (point-biserial corr = -0.093; P < 0.001). No adverse events were reported. LIMITATIONS: Not all clinicians included in this study used each of the 3 steroid types, and all clinicians used either particulate or nonparticulate steroids exclusively. CONCLUSIONS: Our study demonstrates that the clinical outcomes associated with TFESIs of nonparticulate steroids are superior to those associated with TFESIs of particulate steroids when either variety of medication is used to treat lumbar radiculopathy. This is the first study to include a clinically useful predictive model using information on laterality, age, and steroid type.