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Internal Medicine (Tokyo, Japan) Feb 2024Tuberculous meningitis is an infectious disease with high mortality. Literature describing intrathecal therapy for tuberculous meningitis is scarce. We herein report a...
Tuberculous meningitis is an infectious disease with high mortality. Literature describing intrathecal therapy for tuberculous meningitis is scarce. We herein report a case of refractory tuberculous meningitis in a 52-year-old woman with underlying neuropsychiatric systemic lupus erythematosus. Despite systemic treatment with anti-tuberculosis drugs and dexamethasone, her meningeal irritation deteriorated. Intrathecal isoniazid and prednisolone administration was therefore initiated, and the symptoms of severe meningeal irritation improved along with head magnetic resonance imaging and cerebrospinal fluid findings. This case report highlights the efficacy of intrathecal isoniazid and steroid injections for refractory tuberculous meningitis, particularly in patients with severe meningeal irritation.
Topics: Female; Humans; Middle Aged; Isoniazid; Tuberculosis, Meningeal; Antitubercular Agents; Prednisolone; Lupus Vasculitis, Central Nervous System
PubMed: 37344431
DOI: 10.2169/internalmedicine.1917-23 -
Scientific Reports Oct 2023Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted,...
Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO/FiO ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO/FiO ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype.
Topics: Animals; Anti-Inflammatory Agents; Erythromycin; Methylprednisolone; Oleic Acid; Respiration; Respiratory Distress Syndrome; Sheep; Random Allocation; Disease Models, Animal
PubMed: 37863994
DOI: 10.1038/s41598-023-45081-8 -
Medicine Jan 2024Osimertinib is the third-generation, pyrimidine-based, irreversible epidermal growth factor receptor-tyrosine kinase inhibitor that received approval from the FDA in...
RATIONALE
Osimertinib is the third-generation, pyrimidine-based, irreversible epidermal growth factor receptor-tyrosine kinase inhibitor that received approval from the FDA in November 2015 and has become the standard approach in patients with advanced, epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC), especially with brain metastases. Osimertinib is beneficial in terms of progression-free and overall survival in patients with EGFR-mutated NSCLC. However, the rarity of bilateral pneumothorax among adverse events necessitates further research on its potential fatality rate.
PATIENT CONCERNS
A 72-year-old man diagnosed with stage IV (T2NxM1) NSCLC with the 21L858R mutation of the EGFR gene received osimertinib treatment. Unfortunately, 10 weeks after osimertinib treatment, the patient developed severe interstitial lung disease and pneumothorax. Thus, osimertinib treatment was discontinued, and prednisolone (160 mg/day) and supportive treatment were administered.
DIAGNOSES
Osimertinib-induced severe interstitial lung disease and pneumothorax.
INTERVENTIONS
Osimertinib treatment was discontinued, and prednisolone (160 mg/day) and supportive treatment were administered.
OUTCOMES
The bilateral pneumothorax was difficult to correct and the patient eventually died.
LESSONS
Osimertinib-induced pneumothorax occurred approximately 10 weeks after receiving the drug and had severe cough and chest tightness as initial symptoms. In addition, the incidence of drug-induced pneumothorax increases in patients treated with osimertinib when combined with underlying respiratory diseases.
Topics: Male; Humans; Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pneumothorax; Protein Kinase Inhibitors; Aniline Compounds; ErbB Receptors; Prednisolone; Mutation; Lung Diseases, Interstitial; Acrylamides; Indoles; Pyrimidines
PubMed: 38241563
DOI: 10.1097/MD.0000000000036994 -
Lupus Science & Medicine Dec 2023Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to...
Methylprednisolone pulse-enhanced neutrophil extracellular trap formation in mice with imiquimod-induced lupus-like disease, resulting in ischaemia of the femoral head cartilage.
OBJECTIVES
Methylprednisolone (mPSL) pulse therapy is an essential option for patients with active systemic lupus erythematosus, but there is a risk of adverse events related to microcirculation disorders, including idiopathic osteonecrosis of the femoral head (ONFH). Recent studies have revealed that excessive neutrophil extracellular traps (NETs) are involved in microcirculation disorders. This study aimed to demonstrate that mPSL pulse could induce NETs in lupus mice and identify the factors contributing to this induction.
METHODS
Six mice with imiquimod (IMQ)-induced lupus-like disease and six normal mice were intraperitoneally injected with mPSL on days 39 to 41, and five mice with IMQ-induced lupus-like disease and six normal mice were injected with phosphate-buffered saline. Pathological examinations were conducted to evaluate the ischaemic state of the femoral head and tissue infiltration of NET-forming neutrophils. Proteome analysis was performed to extract plasma proteins specifically elevated in mPSL-administered mice with IMQ-induced lupus-like disease, and their effects on NET formation were assessed in vitro.
RESULTS
Mice with IMQ-induced lupus-like disease that received mPSL pulse demonstrated ischaemia of the femoral head cartilage with tissue infiltration of NET-forming neutrophils. Proteome analysis suggested that prenylcysteine oxidase 1 (PCYOX1) played a role in this phenomenon. The reaction of PCYOX1-containing very low-density lipoproteins (VLDL) with its substrate farnesylcysteine (FC) induced NETs in vitro. The combined addition of IMQ and mPSL synergistically enhanced VLDL-plus-FC-induced NET formation.
CONCLUSION
PCYOX1 and related factors are worthy of attention to understand the underlying mechanisms and create novel therapeutic strategies for mPSL-mediated microcirculation disorders, including ONFH.
Topics: Mice; Humans; Animals; Methylprednisolone; Extracellular Traps; Femur Head; Imiquimod; Lupus Erythematosus, Systemic; Proteome; Cartilage; Ischemia
PubMed: 38154828
DOI: 10.1136/lupus-2023-001042 -
Archives of Iranian Medicine Sep 2023It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek...
BACKGROUND
It is unknown if the clinical manifestations and phenotype of disease are comparable between early- and elderly-onset inflammatory bowel disease (IBD). We aimed to seek differences in disease phenotype, course, complications, and treatment between early- and elderly-onset IBD patients.
METHODS
This retrospective cohort study on registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) compared demographics, disease phenotype, disease activity, IBD-related surgery and medications between early- and elderly-onset IBD. A generalized linear regression model was used to investigate the relative risk of age at diagnosis adjusted for gender and disease duration for the outcomes.
RESULTS
From 10048 IBD patients, 749 with early-onset (7.5%), and 472 (4.7%) elderly-onset IBD were enrolled: 855 (63.1%) ulcerative colitis (UC) and 366 (26.9%) Crohn's disease (CD). Left-sided colitis was more frequent among elderly-onset UC patients (<0.001). Ileum and ileocolonic locations were the most common types in elderly-onset and early-onset CD patients, respectively. In comparison with elderly-onset UC, early-onset cases more often used prednisolone (22.1% vs. 11.4%, =0.001), immunomodulators (44.9% vs 25.2%, <0.001) and anti-tumor necrosis factors (TNF) (20.1% vs 11.9%, =0.002). Elderly-onset UC patients had 0.7 times lower risk of aggressive phenotype (95%CI:0.6‒0.9, =0.005). Early-onset CD was associated with higher use of prednisolone (27.7% vs 8.1%, <0.001), immunomodulators (58.7% vs 41.8%, =0.005) and anti-TNF (49.6% vs 35.4%, =0.006).
CONCLUSION
Early-onset IBD was associated with a more aggressive phenotype and higher prednisolone, immunomodulators, and anti-TNF use.
Topics: Humans; Aged; Retrospective Studies; Iran; Tumor Necrosis Factor Inhibitors; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Immunologic Factors; Prednisolone; Phenotype
PubMed: 38310403
DOI: 10.34172/aim.2023.73 -
Internal Medicine (Tokyo, Japan) Jan 2024We herein report the first case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy after coronavirus disease 2019 (COVID-19). A 23-year-old man...
We herein report the first case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy after coronavirus disease 2019 (COVID-19). A 23-year-old man experienced fatigue, a fever, and headache 14 days after the resolution of COVID-19. He was severely disoriented and admitted to our hospital. On admission, the patient exhibited disorientation, headache, neck stiffness, myoclonus of both upper limbs, dysuria, and pyramidal signs. A blood examination revealed hyponatremia, and a cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis. The CSF test results were positive for anti-GFAPα antibodies. The patient was treated with methylprednisolone pulse therapy, followed by oral prednisolone, which quickly ameliorated his neurological abnormalities.
Topics: Humans; Male; Young Adult; Autoantibodies; Behavior Therapy; COVID-19; Glial Fibrillary Acidic Protein; Headache; SARS-CoV-2
PubMed: 37952950
DOI: 10.2169/internalmedicine.2751-23 -
Turkish Journal of Pharmaceutical... Jan 2024Oral steroids are commonly prescribed to children. Steroids have a strong bitter taste that limits their oral acceptance in children. The objective of this study was to...
OBJECTIVES
Oral steroids are commonly prescribed to children. Steroids have a strong bitter taste that limits their oral acceptance in children. The objective of this study was to formulate a pediatric-friendly and palatable oral dosage form of steroids.
MATERIALS AND METHODS
Solid dispersions of dexamethasone were prepared using polyethylene glycol, pectin, and Eudragit as carrier polymers, and chocolate as a flavoring agent. Taste masking efficiency was evaluated by healthy volunteers to select the best formula. The selected formula was pressed into chewable tablets with varying amounts of sweeteners. Chewable tablets were evaluated for palatability, hardness, and chewing index. The typical application of the taste masking approach was confirmed using prednisolone.
RESULTS
Eudragit-based solid dispersions were effective in dexamethasone taste masking. Using 40% mannitol resulted in palatable tablets with acceptable hardness and chewing difficulty. The effectiveness of the taste masking approach was successfully used to prepare prednisolone chewable tablets. However, an increase in the carrier: drug ratio and a change in the flavor to pineapple were necessary to achieve maximum palatability of prednisolone chewable tablets.
CONCLUSION
Eudragit solid dispersion is an effective method for the taste masking highly bitter steroids. The solid dispersion was successfully pressed into a palatable, easy-to-chew, and pediatric-friendly chewable tablet dosage form. The carrier: drug ratio and the choice of flavoring agent are crucial factors in improving tablet palatability.
PubMed: 38254331
DOI: 10.4274/tjps.galenos.2023.24968 -
The Journal of Veterinary Medical... Nov 2023Cold agglutinin disease, one of the serological classifications of immune-mediated hemolytic anemia, is caused by the production of autoantibodies that react with...
Cold agglutinin disease, one of the serological classifications of immune-mediated hemolytic anemia, is caused by the production of autoantibodies that react with erythrocytes at low temperatures. A captive bottlenose dolphin presented with regenerative and hemolytic anemia. Anticoagulated whole blood was agglutinated at room temperature (approximately 18°C), with reversal of agglutination on warming to 37°C, indicating the presence of cold agglutinin. Based on these findings, this animal was diagnosed with cold agglutinin disease. Clindamycin, doxycycline, and prednisolone were administered orally to treat the infection and immune-mediated hemolytic anemia. Anemia gradually improved after initiation of pharmacotherapy, and erythrogenesis slowed as erythroblasts disappeared and reticulocyte count decreased in peripheral blood. This represents the first report of cold agglutinin disease in a cetacean.
Topics: Animals; Bottle-Nosed Dolphin; Anemia, Hemolytic, Autoimmune; Cetacea; Erythrocytes; Autoantibodies
PubMed: 37779092
DOI: 10.1292/jvms.23-0037 -
Endocrine Dec 2023Weekly treatment with the intravenous glucocorticoid methylprednisolone for 12 weeks is mainstay in the treatment of Graves' orbitopathy but may decrease bone mass and...
PURPOSE
Weekly treatment with the intravenous glucocorticoid methylprednisolone for 12 weeks is mainstay in the treatment of Graves' orbitopathy but may decrease bone mass and impair bone structure. We therefore investigated bone turnover, -mass and -structure during the treatment cause in these patients.
METHODS
We included 32 patients with Graves' orbitopathy scheduled for treatment with methylprednisolone. Bone turnover and thyroid function was measured at baseline and after 3, 9, 12, and 24 weeks, bone mineral density (BMD) was measured using dual x-ray absorptiometry at baseline and after 12 and 24 weeks, and bone structure was measured using high-resolution peripheral quantitative computed tomography at baseline and after 12 weeks.
RESULTS
Bone turnover and tri-iodothyronine decreased throughout the study. Cortical volumetric BMD at both the radius and tibia increased significantly by 0.98 ± 0.38% (p = 0.01) and 1.35 ± 0.50% (p = 0.01), respectively and cortical porosity at both the radius and tibia decreased significantly by -7.67 ± 3.13% (p = 0.04) and -3.30 ± 2.17% (p = 0.04), respectively. Bone mineral density was stable during the first 12 weeks but increased significantly by 2.26 ± 3.61% at the femoral neck (p < 0.01) and by 2.24 ± 4.24% at the total hip towards week 24 (p = 0.02). Stratified analyses suggested that remission of hyperthyroidism was the most important determinant of changes in bone turnover, bone mass and structure.
CONCLUSION
During a 12-week course of high-dose intravenous methylprednisolone bone turnover and cortical porosity decreased and during 24 weeks follow up bone mineral density increased. In terms of bone, methylprednisolone therefore is a safe treatment for Graves' orbitopathy.
Topics: Humans; Methylprednisolone; Graves Ophthalmopathy; Glucocorticoids; Bone Density; Bone Remodeling
PubMed: 37676399
DOI: 10.1007/s12020-023-03494-5 -
DEN Open Apr 2024A 26-year-old man with a history of ulcerative colitis treatment presented to our clinic with abdominal pain and fever. He had a history of bloody stools and abdominal...
A 26-year-old man with a history of ulcerative colitis treatment presented to our clinic with abdominal pain and fever. He had a history of bloody stools and abdominal pain at 19 years of age. A thorough examination by a medical practitioner, including lower gastrointestinal endoscopy, resulted in the diagnosis of ulcerative colitis. After induction of remission with prednisolone (PSL), the patient was treated with 5-aminosalicylate. One year ago in September, his symptoms flared up again, and he was administered 30 mg/day of PSL until November of the same year. However, he was transferred to another hospital and referred to his previous doctor. During the follow-up in December of the same year, flare-ups of abdominal pain and diarrhea were reported. Upon review of the patient's medical history, familial Mediterranean fever was suspected because the patient had periodic fevers ≥38°C and symptoms that persisted even after oral steroid administration and were sometimes accompanied by joint pain. However, he was transferred again, and PSL was administered once more. The patient was referred to our hospital for further treatment. At the time of arrival, his symptoms did not improve with 40 mg/day of PSL, and endoscopy and computed tomography revealed thickening of the colon, with no abnormality in the small intestine. Suspecting familial Mediterranean fever-associated enteritis, the patient was administered colchicine, resulting in an improvement in symptoms. Furthermore, an examination of the MEFV gene showed a mutation in Exon5 (S503C), and atypical familial Mediterranean fever was diagnosed. Endoscopy after colchicine treatment revealed that the ulcers improved remarkably.
PubMed: 37206860
DOI: 10.1002/deo2.246