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1.
Anticancer Res ; 41(11): 5333-5342, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732403

RESUMO

BACKGROUND/AIM: Leptomeningeal disease (LMD) is a debilitating complication of advanced malignancies. Immune-checkpoint inhibitors (ICIs) may alter disease course. We analyzed the role and toxicity of ICIs in LMD. MATERIALS AND METHODS: We systematically reviewed the literature reporting on outcome data of patients with LMD treated with ICIs. RESULTS: We included 14 studies encompassing 61 patients. Lung-cancer (44.3%), breast-cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Median duration of ICI-treatment was 7-months (range=0.5-58.0): pembrolizumab (49.2%), nivolumab (32.8%), ipilimumab (18.0%). Radiological responses included complete response (33.3%), partial response (12.5%), stable disease (33.3%), progressive disease (20.8%). Twenty-two patients developed ICI-related adverse-events, mild (100%) and/or severe (15.6%). Median progression-free and overall survival were 5.1 and 6.3 months, and 12-month survival was 32.1%. Survival correlated with ICI agents (p=0.042), but not with primary tumors (p=0.144). Patients receiving concurrent steroids showed worse survival (p=0.040). CONCLUSION: ICI therapy is well-tolerated in patients with LMD, but concurrent steroids may worsen survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Meníngeas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Neoplasias Meníngeas/imunologia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Medição de Risco , Fatores de Risco , Esteroides/efeitos adversos , Fatores de Tempo , Microambiente Tumoral
2.
Medicine (Baltimore) ; 100(39): e27391, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596164

RESUMO

RATIONALE: Several reports have described retinal pigment epithelial (RPE) tears in central serous chorioretinopathy (CSC). However, there have been no reports of spontaneously large RPE tears in acute CSC without bullous retinal detachment (RD). Herein, we report and provide sequential images of a case of bilateral spontaneous large RPE tears in patient with acute CSC without bullous RD. PATIENT CONCERNS: An 88-year-old female patient was admitted with impaired vision in both eyes, which began 10 days prior. The visual acuity was 0.4 and 0.5 in the right and left eye, respectively. She had started taking oral steroids 2 weeks prior for polymyalgia. DIAGNOSIS: Ophthalmologic examinations, including fundus photography, optical coherence tomography, and fluorescence angiography, were performed, and she was diagnosed with steroid-induced acute CSC in both eyes with large pigment epithelial detachment (PED) of approximately 4-disc diameter. Discontinuation of steroids and follow-up ophthalmic examinations were performed. However, a spontaneous large RPE tear occurred in the right eye. INTERVENTIONS: We performed follow-ups more frequently and CSC treatment such as laser photocoagulation, photodynamic therapy, and anti-vascular endothelial growth factor injections were not performed. OUTCOMES: Nine months later, a spontaneous large RPE tear occurred sequentially in the left eye. Her final visual acuity was 0.3 and 0.15 in the right and left eye, respectively. LESSONS: Patients may spontaneously develop large RPE tears in both eyes, despite no treatment for acute CSC with non-bullous RD. Large PED and old age may affect this. Therefore, for a CSC patient with a large PED and advanced age, attention must be paid when determining treatment.


Assuntos
Coriorretinopatia Serosa Central/complicações , Perfurações Retinianas/etiologia , Idoso de 80 Anos ou mais , Coriorretinopatia Serosa Central/induzido quimicamente , Coriorretinopatia Serosa Central/diagnóstico , Feminino , Angiofluoresceinografia , Humanos , Descolamento Retiniano/etiologia , Perfurações Retinianas/diagnóstico por imagem , Perfurações Retinianas/patologia , Esteroides/administração & dosagem , Esteroides/efeitos adversos , Tomografia de Coerência Óptica , Acuidade Visual
4.
G Ital Nefrol ; 38(Suppl 77)2021 Sep 07.
Artigo em Italiano | MEDLINE | ID: mdl-34669312

RESUMO

Steroid minimization has always been one of the most desired goals regarding immunosuppressive therapy after renal transplantation. Following the introduction of cyclosporine different steroid-free protocols became available, but their implementation was limited due to the high risk of acute rejection. In the last few years, the use of a very low dose of prednisone (5 mg/day) has been deemed to guarantee a good balance between steroid toxicity and efficacy. However, high interpatient variability in prednisolone exposure prevented the standard low dose to be as safe as expected in all patients. Therefore, steroid side effects can still be observed in a variable percentage of patients. In this setting, the personalization of steroid dosage might prevent an over exposure to the drug, but this strategy is not available yet. Thus, steroid withdrawal remains the only available strategy to limit side effects. In the last 40 years, we learned that steroid free protocols are associated with a higher risk of acute rejection, but they do not reduce graft survival. Hence, patients at higher risk for acute rejection or recurrence of their primary renal disease are usually excluded from these protocols. Early steroid withdrawal (within 7 days after transplantation) has been widely used and also suggested by American guidelines. However, steroid withdrawal 3-4 months after transplantation has been preferred by many Authors and deemed equally efficient. In addition, early but not late steroid withdrawal should always be associated to induction therapy. Lastly, Tacrolimus plus Mycophenolic Acid has become the most used association in steroid minimization protocols.


Assuntos
Rejeição de Enxerto , Imunossupressores , Esteroides , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico , Prednisona , Esteroides/efeitos adversos , Tacrolimo
5.
Environ Toxicol ; 36(11): 2123-2137, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34310007

RESUMO

Glucocorticoid (GC; dexamethasone, DEX) -induced osteonecrosis of the femoral head (GIOFH) is a challenging orthopedic disease, and its underlying mechanism remains not clear. This study exposed murine long bone osteocyte-Y4 (MLO-Y4) cells to DEX below normoxic or hypoxic circumstances and found that cell autophagy have been reduced. At the same time, flow cytometry analysis showed increased apoptosis, which was more pronounced in hypoxic environments. Recent research also claimed that GC induces osteoporosis after osteocyte apoptosis, and subsequent microfractures lead to ischemia and hypoxia of the femoral head, resulted in GIOFH. Presently, we found that both mitophagy-related protein hypoxia-inducible factor-1α (HIF-1α) and BNIP3 were up-regulated in the hypoxic environment, and their expression was down-regulated when exposed to DEX. Besides, we demonstrated that overexpressing HIF-1α resisted DEX-induced apoptosis in a hypoxic environment. Here, we demonstrated that overexpression of HIF-1α, through its downstream marker BNIP3, reduced the suppression of DEX on mitophagy induced by hypoxia and protected bone cells from apoptosis. Also, these findings may provide a direction of the promising application for better GIOFH treatment shortly.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Mitofagia , Osteócitos , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Camundongos , Esteroides/efeitos adversos
6.
Clin J Pain ; 37(9): 707-717, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34265792

RESUMO

OBJECTIVE: Epidural steroid injections (ESIs) are a commonly utilized treatment for lumbosacral radicular pain caused by intervertebral disc herniation or stenosis. Although effective in certain patient populations, ESIs have been associated with serious complications, including paralysis and death. In 2014, the US Food and Drug Administration (FDA) issued a safety warning on the risk of injecting corticosteroids into the epidural space. The aims of this article were to review the neurological complications associated with ESIs and to compare the formulations, safety, and effectiveness of commercially available corticosteroids given by transforaminal, interlaminar, or caudal injection. METHODS: Serious adverse events associated with ESIs were identified by a search of the FDA Adverse Event Reporting System (FAERS) database. A MEDLINE search of the literature was conducted to identify clinical trials comparing the safety and effectiveness of nonparticulate and particulate corticosteroid formulations. RESULTS: Neurological complications with ESIs were rare and more often associated with the use of particulate corticosteroids administered by transforaminal injection. Among the 10 comparative-effectiveness studies reviewed, 7 found nonparticulate steroids had comparable efficacy to particulate steroids, and 3 studies suggested reduced efficacy or shorter duration of effect for nonparticulate steroids. DISCUSSION: The risk of complications for transforaminal ESI is greater with particulate corticosteroids. Nonparticulate corticosteroids, which are often recommended as first-line therapy, may have a short duration of effect, and many commercial formulations contain neurotoxic preservatives. The safety profile of ESIs may continue to improve with the development of safer, sterile formulations that reduce the risk of complications while maintaining efficacy.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Radiculopatia , Dor nas Costas , Humanos , Injeções Epidurais , Região Lombossacral , Radiculopatia/tratamento farmacológico , Esteroides/efeitos adversos
8.
BMC Musculoskelet Disord ; 22(1): 599, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187427

RESUMO

BACKGROUND: Dysregulation of the OPG/RANK/RANKL signalling pathway is a key step in the occurrence of steroid-induced osteonecrosis of the femoral head (ONFH). This study aims to understand the degree of methylation of the OPG, RANK, and RANKL genes in steroid-related ONFH. METHODS: A case-control study was designed, including 50 patients (25 males and 25 females) and 50 matched controls. The European Molecular Biology Open Software Suite (EMBOSS) was used to predict the existence and location of CpG islands in the OPG, RANK, and RANKL genes. The Agena MassARRAY platform was used to detect the methylation status of the above genes in the blood of subjects. The relationship between the methylation level of CpG sites in each gene and steroid-related ONFH was analysed by the chi-square test, logistic regression analysis, and other statistical methods. RESULTS: In the CpG islands of the OPG, RANK, and RANKL genes in patients with steroid-related ONFH, several CpG sites with high methylation rates and high methylation levels were found. Some hypermethylated CpG sites increase the risk of steroid-related ONFH. In addition, a few hypermethylated CpG sites have predictive value for the early diagnosis of steroid-related ONFH. CONCLUSION: Methylation of certain sites in the OPG/RANK/RANKL signalling pathway increases the risk of steroid-related ONFH. Some hypermethylated CpG sites may be used as early prediction and diagnostic targets for steroid-related ONFH.


Assuntos
Metilação de DNA , Necrose da Cabeça do Fêmur , Estudos de Casos e Controles , Feminino , Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Humanos , Masculino , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , Esteroides/efeitos adversos
9.
Laryngoscope ; 131(9): 2088-2090, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33973652

RESUMO

Intratympanic (IT) steroid therapy is a mainstay treatment for sudden sensorineural hearing loss (SSNHL) for both initial therapy and salvage therapy. We report a rare case of iatrogenic perilymphatic fistula that resulted from trauma during an IT steroid injection for SSNHL. We discuss the diagnosis and treatment in the current case and compare it with previous reports from the literature. Laryngoscope, 131:2088-2090, 2021.


Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Súbita/tratamento farmacológico , Canais Semicirculares/patologia , Esteroides/efeitos adversos , Idoso de 80 Anos ou mais , Audiometria de Tons Puros/métodos , Feminino , Fístula/etiologia , Humanos , Doença Iatrogênica , Injeção Intratimpânica , Perilinfa , Terapia de Salvação , Canais Semicirculares/lesões , Cirurgia do Estribo/efeitos adversos , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Resultado do Tratamento , Vertigem/diagnóstico , Vertigem/etiologia , Doenças Vestibulares/complicações
11.
Nephrol Ther ; 17(6): 463-465, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33985919

RESUMO

Cat scratch disease, usually a benign infectious disease, may develop as multisystem disease with multiorgan involvement, particularly in immunocompromised patients. We report on a patient who developed disseminated bartonellosis while receiving mycophenolate mofetil monotherapy treating steroid-dependent nephrotic syndrome, highlighting that severe infection can be observed in those patients. Therefore, this category of patients should be cautious when having contact with kittens and receives proper prevention advice.


Assuntos
Infecções por Bartonella , Síndrome Nefrótica , Animais , Gatos , Criança , Feminino , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Esteroides/efeitos adversos , Resultado do Tratamento
14.
J Laryngol Otol ; 135(5): 442-447, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33827722

RESUMO

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.


Assuntos
COVID-19/microbiologia , Mucorales/isolamento & purificação , Mucormicose/microbiologia , Seios Paranasais/microbiologia , Administração Intravenosa , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Infecções Fúngicas Invasivas/diagnóstico , Infecções Fúngicas Invasivas/epidemiologia , Infecções Fúngicas Invasivas/microbiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Mucorales/efeitos dos fármacos , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/etiologia , Pandemias , Seios Paranasais/diagnóstico por imagem , Estudos Prospectivos , SARS-CoV-2 , Sinusite/diagnóstico , Sinusite/microbiologia , Esteroides/efeitos adversos , Esteroides/uso terapêutico
15.
Biomed Res Int ; 2021: 6655225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928159

RESUMO

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.


Assuntos
Exossomos/metabolismo , Necrose da Cabeça do Fêmur/prevenção & controle , Necrose da Cabeça do Fêmur/terapia , Cabeça do Fêmur/irrigação sanguínea , Células-Tronco Mesenquimais/metabolismo , Neovascularização Fisiológica , Esteroides/efeitos adversos , Animais , Osso e Ossos/patologia , Hipóxia Celular , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Exossomos/ultraestrutura , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ratos Sprague-Dawley , Microtomografia por Raio-X
18.
BMC Pulm Med ; 21(1): 76, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663455

RESUMO

BACKGROUND: Cryptococcus is one of the major fungal pathogens infecting the lungs. Pulmonary cryptococcal infection is generally considered a community-acquired condition caused by inhalation of dust contaminated with fungal cells from the environment. Here, we report a case developing pulmonary cryptococcosis 3 months after hospital admission, which has rarely been reported before. CASE PRESENTATION: A 73-year-old female patient who was previously immunocompetent experienced persistent dry cough for 2 weeks, 3 months after admission. Chest computed tomography (CT) showed a new solitary pulmonary nodule developed in the upper lobe of the left lung. Staining and culture of expectorated sputum smears were negative for bacteria, acid-fast bacilli, or fungus. The patient then underwent biopsy of the lesion. Histopathology findings and a positive serum cryptococcal antigen titer (1:8) indicated pulmonary cryptococcosis. Daily intravenous 400 mg fluconazole was administered initially followed by oral fluconazole therapy. Follow-up chest CT after 3 months of antifungal therapy showed complete disappearance of the pulmonary nodule. Respiratory symptoms of the patient also resolved. A complete investigation excluded the possibility of a patient-to-patient transmission or primarily acquiring the infection from the hospital environment. Based on the patient's history of exposure to pigeons before admission and recent steroid and azathioprine use after admission for the treatment of myasthenic crisis, reactivation of a latent pulmonary cryptococcal infection acquired before admission, in this case, is impressed. CONCLUSIONS: Although rarely reported, pulmonary cryptococcal infection should be included in the differential diagnosis of hospitalized patients with respiratory symptoms, especially in those with predisposing risk factors. Chest image studies and further surgical biopsy are needed for confirmation.


Assuntos
Azatioprina/efeitos adversos , Criptococose/diagnóstico , Pneumopatias Fúngicas/diagnóstico , Pulmão/patologia , Esteroides/efeitos adversos , Idoso , Antígenos de Fungos/sangue , Biópsia , Criptococose/etiologia , Criptococose/patologia , Diagnóstico Tardio , Diagnóstico Diferencial , Feminino , Humanos , Imunocompetência , Pneumopatias Fúngicas/etiologia , Pneumopatias Fúngicas/patologia , Tomografia Computadorizada por Raios X
19.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760114

RESUMO

Steroid­induced avascular necrosis of the femoral head (SANFH) is a common orthopaedic disease that is difficult to treat. The present study investigated the effects of total flavonoids of Rhizoma drynariae (TFRD) on SANFH and explored its underlying mechanisms. The SANFH rat model was induced by intramuscular injection of lipopolysaccharides and methylprednisolone. Osteoblasts were isolated from the calvariae of neonatal rats and then cultured with dexamethasone (Dex). TFRD was used in vitro and in vivo, respectively. Haematoxylin and eosin staining was used to assess the pathological changes in the femoral head. Terminal deoxynucleotidyl transferase­mediated deoxyuridine triphosphate nick end labelling assay and flow cytometry were conducted to detect apoptosis of osteoblasts. The 2',7'­dichlorofluorescein­diacetate staining method was used to detect reactive oxygen species (ROS) levels in osteoblasts and the 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay was used to detect osteoblast proliferation. The expression of caspase­3, Bax, Bcl­2, VEGF, runt­related transcription factor 2 (RUNX2), osteoprotegerin (OPG), osteocalcin (OCN), receptor activator of nuclear factor κB ligand (RANKL) and phosphoinositide 3­kinase (PI3K)/AKT pathway related­proteins were detected via western blotting. It was found that TFRD reduced the pathological changes, inhibited apoptosis, increased the expression of VEGF, RUNX2, OPG and OCN, decreased RANKL expression and activated the PI3K/AKT pathway in SANFH rats. TFRD promoted proliferation, inhibited apoptosis and reduced ROS levels by activating the PI3K/AKT pathway in osteoblasts. In conclusion, TFRD protected against SANFH in a rat model. In addition, TFRD protected osteoblasts from Dex­induced damage through the PI3K/AKT pathway. The findings of the present study may contribute to find an effective treatment for the management of SANFH.


Assuntos
Flavonoides/farmacologia , Osteonecrose/tratamento farmacológico , Extratos Vegetais/farmacologia , Polypodiaceae/química , Animais , Proliferação de Células/efeitos dos fármacos , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Modelos Animais de Doenças , Cabeça do Fêmur/patologia , Flavonoides/química , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Osteoblastos/efeitos dos fármacos , Osteogênese por Distração/métodos , Osteonecrose/induzido quimicamente , Osteonecrose/patologia , Osteoprotegerina/genética , Fosfatidilinositol 3-Quinases/genética , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-akt/genética , Ligante RANK/genética , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Esteroides/efeitos adversos
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