Administration Of Prednisone Research Articles

CORTICOIDES: UM ESTUDO SOBRE OS EFEITOS ADVERSOS NA SAÚDE HUMANA EM RELAÇÃO AO USO PROLONGADO E O PAPEL DO FARMACÊUTICO

Glucocorticoids are currently used in medicine to cure or treat a variety of diseases, as they have antiinflammatory and immunosuppressive effects that relieve various symptoms. Corticosteroids are hormones naturally synthesized by the human body, the main one being cortisol. These hormones perform important functions, such as controlling the metabolism of nutrients, including carbohydrates, proteins and lipids, which helps the body's energy balance. This research aims to examine the risks related to the prolonged use of corticosteroids, specifically the administration of prednisone in a group at risk of corticosteroid administration. The methodology applied addresses the assessment of risks associated with corticosteroid treatment and highlights the role of the pharmacist in guiding the rational use of these drugs. The study is a critical review of the literature, adopting a descriptive and comparative approach, based on scientific sources.

Glucocorticoid chrono-pharmacology promotes glucose metabolism in heart through a cardiomyocyte-autonomous transactivation program.

Circadian time-of-intake gates the cardioprotective effects of glucocorticoid administration in both healthy and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) and its co-factor, Krüppel-like factor (Klf15), play critical roles in maintaining normal heart function in the long-term and serve as pleiotropic regulators of cardiac metabolism. Despite this understanding, the cardiomyocyte-autonomous metabolic targets influenced by the concerted epigenetic action of GR-Klf15 axis remain undefined. Here, we demonstrate the critical roles of the cardiomyocyte-specific GR and Klf15 in orchestrating a circadian-dependent glucose oxidation program within the heart. Combining integrated transcriptomics and epigenomics with cardiomyocyte-specific inducible ablation of GR or Klf15, we identified their synergistic role in the activation of adiponectin receptor expression (Adipor1) and the mitochondrial pyruvate complex (Mpc1/2), thereby enhancing insulin-stimulated glucose uptake and pyruvate oxidation. Furthermore, in obese diabetic (db/db) mice exhibiting insulin resistance and impaired glucose oxidation, light-phase prednisone administration, as opposed to dark-phase prednisone dosing, effectively restored cardiomyocyte glucose oxidation and improved diastolic function towards control-like levels in a sex-independent manner. Collectively, our findings uncover novel cardiomyocyte-autonomous metabolic targets of the GR-Klf15 axis. This study highlights the circadian-dependent cardioprotective effects of glucocorticoids on cardiomyocyte glucose metabolism, providing critical insights into chrono-pharmacological strategies for glucocorticoid therapy in cardiovascular disease.

IgG4-related sclerosing cholangitis associated with essential thrombocythemia: A case report

BACKGROUND The complexity of immunoglobulin G4 (IgG4)-related diseases and their potential connection to hematologic malignancies remains unclear. This article provided a review of the diagnosis and treatment of a patient with IgG4-related sclerosing cholangitis (SC) and essential thrombocythemia (ET), along with an analysis of relevant literature to enhance comprehension of this disease. CASE SUMMARY A 56-year-old male was admitted to two hospitals with deteriorating jaundice and pruritus prior to hospitalization. Beyond our expectations, the patient was first diagnosed with IgG4-SC and ET with the Janus kinase 2 V617F mutation. Interestingly, the administration of acetate prednisone significantly resulted in improvements in both IgG4-SC and ET. Clinicians need to pay attention to immune disorders and inflammation as they contribute to the development of various disease phenotypes. CONCLUSION When IgG4-SC is suspected without histopathological evidence, diagnostic therapy and long-term regular follow-up can lead to positive treatment outcomes. Clinicians should be mindful of the potential presence of concurrent hematologic diseases in patients with immune disorders.

Transmembrane protein 53 craniotubular dysplasia (OMIM # 619727): The skeletal disease and consequent blindness of this new disorder

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad calvarial and facial bones, skeletal modeling errors, vertebral body flattening, wide ribs, and osteopenia of expanded bones. DXA areal bone density (gm/cm2) Z-scores were low. His optic, auditory, and spinal canals were narrow. Mineral metabolism was intact. Serum alkaline phosphatase and osteocalcin levels were normal yet CTX was high. Iliac crest histomorphometry documented accelerated bone formation. His acute vision loss briefly improved following prednisone administration, optic canal decompression, and optic nerve sheath fenestration, but then progressed despite further surgeries and zoledronate treatment aimed to suppress bone turnover. Next generation sequencing of genes associated with elevated skeletal mass, including from high bone turnover, did not suggest an etiology. Whole genome sequencing then revealed within TMEM53: i) a paternally transmitted 54-base deletion, which included the mRNA splice acceptor site for exon 2 as well as 31 bases of exonic sequence (c. 62-23_92del), and ii) a maternally transmitted missense variant (c.650C > T, p.Ser217Leu: NM_024587.4/NP_078863.2) which is extremely rare in gnomAD (frequency = 0.000036), replaces Ser217 highly conserved across species, and is scored as damaging by SIFT and Mutation Taster. We call this new osteopathy TMEM53 craniotubular dysplasia.

Serial evaluation of liver enzyme activities in dogs with pulmonary coccidioidomycosis administered per os fluconazole.

Pulmonary coccidioidomycosis is a relatively common fungal disorder in dogs that have lived in or traveled to endemic regions and fluconazole is a common antifungal treatment. Liver enzymopathy can occur with fluconazole administration, but the frequency of occurrence nor potentially associative factors have been explored in dogs with pulmonary coccidioidomycosis. Therefore, our objectives were to describe the occurrence and magnitude of liver enzyme activity (LEA) elevation in dogs with pulmonary coccidioidomycosis during treatment with per os fluconazole and identify variables associated with liver enzymopathy. This was a retrospective observational study that analyzed serum biochemical data obtained from a separate prospective study that included 32 client-owned dogs with newly diagnosed pulmonary coccidioidomycosis from October 2020 to February 2021. Per os fluconazole administration (median dosage: 16.2 mg/kg/day) was initiated after diagnosis and dogs were evaluated once every 3 months thereafter until remission or for a maximum of 12 months. Recorded biochemical parameters at each visit (including baseline) included alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Magnitude of increased LEA was based on the fold increase above the upper limit of the reference interval and defined as mild (<5×), moderate (5-10×) or severe (>10×). Forty-seven percent (15/32) of dogs were documented to have elevations in one or more LEAs after initiation of fluconazole administration during the study period. Thirty-four percent and 25% of dogs had elevated ALP and ALT activities, respectively, at some point during treatment. Elevations in AST and GGT activities were rare. The magnitude of LEA elevation was mild in all cases. Logistic regression models did not identify associations between age, weight, sex, neutered status, prednisone administration, fluconazole dose or duration of treatment with the occurrence of liver enzymopathy. Approximately half of dogs with pulmonary coccidioidomycosis are expected to develop mild increases in activities of ALP and/or ALT with rare involvement of AST or GGT at some point during treatment with fluconazole up to 12 months.

Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab

Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to Aspergillus spp. ABPA diagnosis may be challenging due to its non-specific presentation. Standard ABPA treatment consists of systemic corticosteroids and antifungal agents. Mepolizumab, a monoclonal antibody against interleukin-5 seems to be a promising treatment for ABPA. Data about ABPA following lung transplantation (LuTx) are scarce. LuTx recipients are at higher risk for adverse effects of ABPA treatment compared to the general population.Here we present a case of a LuTx recipient who was successfully treated with mepolizumab for ABPA following LuTx. Prolonged administration of high dose prednisone was thus avoided. To our knowledge, this is the first case describing mepolizumab administration following LuTx. Mepolizumab seems particularly attractive as a corticosteroid-sparing agent or as an alternative option to antifungal treatments, because of its excellent safety profile and low risk of drug interactions.

Adrenal insufficiency in pediatric kidney transplantation recipients.

Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients. This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects. AI risk was assessed using morning cortisol (MC) and diagnosis confirmed by an ACTH stimulation test. Potential risk factors and adverse effects were tested for associations with MC levels and AI diagnosis. Fifty-one patients (60.8% male, age 7.4 (IQR 3.8, 13.1) years; 1 patient counted twice for repeat transplant) were included. Patients at risk for AI (MC < 240 nmol/L) underwent definitive ACTH stimulation testing, confirming AI in 13/51 (25.5%) patients. Identified risk factors for AI included current prednisone dosage (p = .001), 6-month prednisone exposure (p = .02), daily prednisone administration (p = .002), and rejection episodes since transplant (p = .001). MC level (2.5 years (IQR 1.1, 5.1) post-transplant) was associated with current prednisone dosage (p < .001), 6-month prednisone exposure (p = .001), daily prednisone administration (p = .006), rejection episodes since transplant (p = .003), greater number of medications (β = -16.3, p < .001), 6-month hospitalization days (β = -3.3, p = .013), creatinine variability (β = -2.4, p = .025), and occurrence of acute kidney injury (β = -70.6, p = .01). Greater corticosteroid exposure was associated with a lower MC level and confirmatory diagnosis of AI noted with an ACTH stimulation test. Adverse clinical findings with AI included greater medical complexity and kidney function lability. These data support systematic clinical surveillance for AI in PKT recipients treated with corticosteroids.

Leucemia linfocítica crônica em cão Shih-Tzu

Chronic Lymphocytic Leukemia (CLL) is defined as a malignant neoplasm originating from hematopoietic stem cells in the bone marrow, where the lymphocytes found in the circulation are mature and well-differentiated. The disease is rare in dogs and cats, and when it occurs, it typically affects elderly animals. This study presents an atypical clinical case of a two-years-old Shih Tzu diagnosed with chronic lymphocytic leukemia. The clinical presentation of the patient included characteristic signs of CLL, such as lymphocytosis, lymphadenomegaly, splenomegaly, and hepatomegaly. Observed symptoms included lethargy, fatigue, panting, and enlargement of the mandibular lymph nodes. Additionally, anemia and thrombocytopenia were identified, aligning with common patterns in dogs with CLL. The diagnosis was achieved through various examinations, including ultrasound, radiography, complete blood count, serum biochemistry, cytology, and parasitological tests (4DX and leishmaniasis). However, definitive confirmation of CLL was obtained through bone marrow examination. In response to the diagnosis, therapeutic intervention followed the protocol established in the literature, involving the administration of Chlorambucil and Prednisone. The results of the applied treatments reflected positively on the patient, demonstrating clinical improvement and stability. The adopted therapeutic protocol aimed to control symptoms and prolong the life of the affected animal. The objective of this study is to contribute to epidemiological data, elucidate the pathogenic course, and seek more effective diagnostic and therapeutic approaches for CLL in dogs. The detailed investigation of this case and the dissemination of results aim to provide a solid foundation for future research, with the goal of improving the quality of life for dogs affected by chronic lymphocytic leukemia.

(074) Safety and Efficacy Varying Doses of Prednisone Post Vasectomy Reversal: Results from a Randomized, Controlled Trials

Abstract Introduction There has been significant ongoing debate on the role and utility of prednisone post-vasectomy reversal to improve sperm counts and long-term patency. However, there are relatively limited data available on the efficacy, with essentially no data available on pregnancy outcomes. Objective To report outcomes of randomized, clinical trial evaluating varying protocols for prednisone administration post vasectomy reversal. Methods A randomized, controlled trial was performed (NCT04788823) with an anticipated 100 men randomized to one of four prednisone protocols post vasectomy reversal: no treatment (Control), prednisone 20 mg taper over 1 month beginning the first month post-op and then every other month x 6 months (High Dose), prednisone 20 mg taper over 1 month if declining sperm counts or a 0 count were identified (PRN), and prednisone 5 mg daily x 1 week, followed by no treatment x 1 week, continued for 6 months (Low Dose). Randomization tables were created a priori to ensure an equal representation of differing durations of time since the original vasectomy as well as an equal distribution of VV/VV vs VV/EV vs EV/EV procedures. All men had semen analyses obtained monthly for a first 12 months. Surveys were sent periodically to follow-up on subsequent pregnancies. Inclusion criteria included having a female partner &amp;lt;36 years of age with no known fertility factors. Results A total of 75 men were ultimately enrolled due to interim findings suggesting inferiority of the High Dose and PRN treatment arms and decision to close those arms before completing full enrollment. Final enrollment included: Control (n=25), High Dose (n=14), PRN (n=11), and Low Dose (n=25). The mean patient age was 38.5 years, mean partner age 29.6, and mean time since vasectomy 6.3 years (SD 5.0). 82% of men underwent VV/VV, while 15% VV/EV, and 3% EV/EV. All men underwent successful anastomosis bilaterally with no cases of one-sided or no anastomosis performed. At a mean follow-up of 16.5 months (range 7.6 to 25.1), an overall patency (sperm observed on sample) rate of 93% was noted (Control 96%, High Dose 93%, PRN 100%, Low Dose 88%, p=0.41). The mean sperm concentration post-op was 34.4 million/ml (Control 24.0, High Dose 38.4, PRN 21.0, Low Dose 49.8, p=0.33). Patency rates at 6- and 12-months were: 6-months (Control 88%, High Dose 80%, PRN 83%, Low Dose 94%, p=0.75); 12-months (Control 75%, High Dose 71%, PRN 75%, Low Dose 91%). Mean sperm concentrations at 6- and 12-months were: 6-months (Control 15.7, High Dose 21.5, PRN 6.9, Low Dose 25.7, p=0.50); 12-months (Control 12.6 million/ml, High Dose 17.1, PRN 36.1, Low Dose 50.4, p=0.64) At the 6-month post-op time point, the overall rate of pregnancy was 47%, with notable differences between cohorts: Control 57%, High Dose 10%, PRN 38%, and Low Dose 67%, p=0.02. No patients discontinued prednisone due to side effects. Conclusions Prednisone taper protocols appear to reduce the likelihood for pregnancy following vasectomy reversal. Use of low-dose prednisone results in non-statistically higher rates of patency at 6- and 12-months, mean sperm concentration at 6- and 12-months, and pregnancy at 6-months. Overall results suggest superiority of either no prednisone post-vasectomy reversal or a low dose protocol but argue against the use of higher dosages at any time due to its negative impacts on pregnancy rates despite maintained sperm counts. Disclosure No.

Feasibility of apalutamide combined with androgen deprivation therapy and short-course low-dose prednisone in treating metastatic hormone-sensitive prostate cancer: a pilot randomized controlled trial.

The role of prednisone in the prevention of androgen receptor antagonist-related rash and treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. This pilot trial (ChiCTR2200060388) aimed to investigate the feasibility of apalutamide combined with androgen deprivation therapy (ADT) and short-course low-dose prednisone in the treatment of mHSPC. All patients received apalutamide and ADT and were randomly divided into two groups based on the administration of oral prednisone or not (control group). The primary endpoint was the incidence of rash. The secondary endpoint included the proportions of patients with a decline in PSA ≥50% from baseline, PSA ≥90% from baseline, and decreased to PSA ≤0.2 ng/mL. Between June 2021 and March 2022, a total of 83 patients were enrolled (41 in the prednisone group and 42 in the control group). During the 6-month follow-up, the incidence of rash was significantly lower in the prednisone group compared with the control group (17.1% vs. 38.1%, P=0.049). There were no significant differences in the incidence of other adverse events, the number of patients who required dose adjustment (reduction, interruption, or discontinuation) of apalutamide due to rash, the number of patients with prostate-specific antigen (PSA) decreased by ≥50%, the number of patients with PSA decrease ≥90%, and the number of patients with PSA ≤0.2 ng/mL between the two groups. All patients with diabetes had stable glycemic control with no glucose-related adverse events. In patients with mHSPC, the addition of short-course low-dose prednisolone to apalutamide plus ADT can reduce the incidence of rash without risk of other adverse events.

Three-dimensional facial swelling evaluation of pre-operative single-dose of prednisone in third molar surgery: a split-mouth randomized controlled trial

BackgroundFacial swelling, pain, and trismus are the most common postoperative sequelae after mandibular third molar (M3M) surgery. Corticosteroids are the most used drugs to reduce the severity of inflammatory symptoms after M3M surgery. This study aimed to evaluate the effect of a single pre-operative dose of prednisone on pain, trismus, and swelling after M3M surgery.MethodsThis study was designed as a split-mouth randomized, controlled, triple-blind trial with two treatment groups, prednisone (PG) and control (CG). All the parameters were assessed before the extraction (T0), two days (T1), and seven days after surgery (T2). Three-dimensional evaluation of facial swelling was performed with Bellus 3D Face App. A visual analogue scale (VAS) was used to assess pain. The maximum incisal distance was recorded with a calibrated rule to evaluate the trismus. The Shapiro–Wilk test was used to evaluate the normal distribution of each variable. To compare the two study groups, the analysis of variance was performed using a two-tailed Student t-test for normal distributions. The level of significance was set at a = 0.05. Statistical analysis was conducted using the software STATA (STATA 11, StataCorp, College Station, TX).ResultsThirty-two patients were recruited with a mean age of 23.6 ± 3.7 years, with a male-to-female ratio of 1:3. A total of 64 M3Ms (32 right and 32 left) were randomly assigned to PG or CG.Surgery time recorded a mean value of 15.6 ± 3.7 min, without statistically significant difference between the groups. At T1, PG showed a significantly lower facial swelling compared to CG (PG: 3.3 ± 2.1 mm; CG: 4.2 ± 1.7 mm; p = 0.02). Similar results were recorded comparing the groups one week after surgery (PG: 1.2 ± 1.2; CG: 2.1 ± 1.3; p = 0.0005). All patients reported a decrease in facial swelling from T1 to T2 without differences between the two groups.At T1, the maximum buccal opening was significantly reduced than T0, and no difference between PG (35.6 ± 8.2 mm) and CG (33.7 ± 7.3 mm) (p > 0.05) was shown. Similar results were reported one week after surgery (PG: 33.2 ± 14.4 mm; CG: 33.7 ± 13.1 mm; p > 0.05). PG showed significantly lower pain values compared to CG, both at T1 (PG: 3.1 ± 1.5; CG: 4.6 ± 1.8; p = 0.0006) and T2 (PG: 1.0 ± 0.8; CG: 1.9 ± 1.4; p = 0.0063).ConclusionOur results showed that pre-operative low-dose prednisone administration could reduce postoperative sequelae by improving patient comfort after M3M surgery and reducing facial swelling two days and one week after surgical procedures.Trial registrationwww.clinicaltrials.gov — NCT05830747 retrospectively recorded—Date of registration: 26/04/2023.

Prophylactic effect of chronic immunosuppression in a mouse model of CSF-1 receptor-related leukoencephalopathy.

Mutations leading to colony-stimulating factor-1 receptor (CSF-1R) loss-of-function or haploinsufficiency cause CSF1R-related leukoencephalopathy (CRL), an adult-onset disease characterized by loss of myelin and neurodegeneration, for which there is no effective therapy. Symptom onset usually occurs in the fourth decade of life and the penetrance of disease in carriers is high. However, familial studies have identified a few carriers of pathogenic CSF1R mutations that remain asymptomatic even in their seventh decade of life, raising the possibility that the development and severity of disease might be influenced by environmental factors. Here we report new cases in which long-term glucocorticoid treatment is associated with asymptomatic status in elder carriers of pathogenic CSF-1R mutations. The main objective of the present study was to investigate the link between chronic immunosuppression initiated pre-symptomatically and resistance to the development of symptomatic CRL, in the Csf1r+/- mouse model. We show that chronic prednisone administration prevents the development of memory, motor coordination and social interaction deficits, as well as the demyelination, neurodegeneration and microgliosis associated with these deficits. These findings are in agreement with the preliminary clinical observations and support the concept that pre-symptomatic immunosuppression is protective in patients carrying pathogenic CSF1R variants associated with CRL. Proteomic analysis of microglia and oligodendrocytes indicates that prednisone suppresses processes involved in microglial activation and alleviates senescence and improves fitness of oligodendrocytes. This analysis also identifies new potential targets for therapeutic intervention.

A case of hypocomplementemic urticarial vasculitis syndrome complicated by eosinophilic pneumonia: a case report and review of the literature.

The primary symptom of urticarial vasculitis (UV), which is a histopathological leukocytoclastic vasculitis disease, is an eruption that resembles urticaria. Other organs may also experience accompanying symptoms. Lung lesions with UV are mostly obstructive pulmonary disease with smoking. However, the coexistence of eosinophilic pneumonia (EP) and complicated UV remains unclear. We report a man in his 70s with chronic obstructive pulmonary disease who attended our department with ring-shaped erythema, marginal edema, and pigmentation. Additionally, a skin histological analysis showed nuclear dust and perivascular neutrophil infiltration, while a blood sample showed a decrease in C3 and C1q concentrations. Administration of prednisone temporarily improved the eruption. However, he developed a cough and a new UV eruption 1 year later. Computed tomography revealed infiltration in the right upper lobe of the lungs, and a blood sample showed a high eosinophil count. He was finally diagnosed with hypocomplementemic urticarial vasculitis syndrome and idiopathic chronic EP. A previous study showed that serum C1q concentrations in patients with EP were lower when this disease was active. Whether a decline in C1q concentrations can cause EP is unclear. However, our case is unique owing to the co-onset of EP with low complement concentrations and recurrence of UV.

Clinical Features, Treatment, and Prognostic Factors of Childhood-Onset Myasthenia Gravis in a Large Chinese Cohort

BackgroundTo describe the clinical features of patients with childhood-onset myasthenia gravis (MG) (CMG) and explore predictors affecting the treatment outcomes. MethodsA retrospective observational cohort analysis of 859 patients with CMG with disease onset before age 14 years was performed at Tongji Hospital. ResultsPatients in the pubertal-onset group (n = 148) had a worse disease course than those in the prepubertal group (n = 711), including a higher incidence of generalized MG (GMG) at presentation, generalization of ocular MG (OMG), and more severe Myasthenia Gravis Foundation of America (MGFA) classification. All patients were initially treated with pyridostigmine, 657 with prednisone, and 196 with immunosuppressants (ISs). However, 226 patients were resistant to prednisone treatment. Multivariate analysis revealed that thymic hyperplasia, higher MGFA class, disease duration before prednisone administration, and thymectomy before prednisone administration were independent predictors of prednisone resistance. At the last visit, 121 of the 840 patients with OMG had developed GMG after a median of 10.0 years from symptom onset and 186 patients (21.7%) achieved complete stable remission (CSR). In multivariable analysis, age at onset, thymic hyperplasia, prednisone, and IS treatment were associated with generalization, whereas age at onset, disease duration, anti-acetylcholine receptor antibodies (AChR-ab), MGFA class II, short-term prednisone treatment, and IS treatment were associated with CSR. ConclusionsThe majority of patients with CMG have mild clinical symptoms and favorable outcomes, especially those with earlier onset age, shorter disease duration, and negative AChR-ab. In addition, early prednisone and ISs are shown to be effective and safe for most patients with CMG.

AAV induces hepatic necroptosis and carcinoma in diabetic and obese mice dependent on Pebp1 pathway

Obesity and diabetes are risk factors for hepatocellular carcinoma (HCC); however, the underlying mechanisms are yet to be elucidated. Adeno‐associated virus (AAV) frequently infects humans and has been widely used in gene therapy, but the risk of AAV infection such as HCC should be further evaluated. Here, we show that recombinant AAV injection caused liver injury, hepatic necroptosis, and HCC in db/db or high‐fat diet‐induced hyperglycemic and obese mice, but not in mice with only hyperglycemia or obesity. Prednisone administration or knockdown of Pebp1, highly expressed in db/db mice, alleviated hepatic injury and necroptosis induced by recombinant AAV in mice with diabetes and obesity. Inhibition of Pebp1 pathway also attenuated inflammation and necroptosis in vitro. Our findings show that AAV infection is a critical risk factor for HCC in patients with diabetes and obesity, and AAV gene therapy for these patients should be carefully evaluated. Both prednisone treatment and targeting Pebp1 pathway are promising strategies to alleviate inflammation and necroptosis that occurred in AAV gene therapy or related diseases.

Comparative Analysis of Rapid vs Standard Premedication Protocols for Contrast Allergy

Contrast reaction rates have been poorly studied with nonionic low osmolar agents. Premedication protocols to prevent contrast reactions to ionic high osmolar contrast have been studied in the past; however, protocol outcomes for the currently used nonionic low osmolar contrast is less clear. The purpose of this study was to evaluate the rate of contrast reactions with nonionic low osmolar using the standard premedication protocol as well as the effect of using a rapid premedication protocol. Retrospective single institution review of computed tomography (CT) scans from May 2011 through January 2022 was performed by searching the Cerner Soarian medical records system for patients with documented contrast allergies who received contrasted CT scans. The patients were then divided into groups depending on whether they received the 13-hour premedication protocol vs the 4-hour rapid protocol. Contrast reaction was extrapolated from administration of prednisone, hydrocortisone, diphenhydramine, or epinephrine outside of protocol within one hour with corresponding indication in the ordering system. Basic statistical analysis including χ2 testing was performed on acquired data. We performed 2588 premedicated contrasted CT cans during the study period, 2102 (81.2%) of which underwent the 13-hour premedication protocol and 486 (18.7%) underwent 4-hour premedication protocol. The average age of the 13-hour group was 62 years (range, 11-92) years and 1345 (64%) were female and the 4-hour protocol had an average age of 61 years (range, 5-92 years) and 277 (57%) were female. In the 13-hour group, there was an overall contrast reaction rate of 29% (613): 124 patients received prednisone, 107 hydrocortisone, 388 diphenhydramine, and 3 epinephrine. In the 4-hour group, 44% (214) patients had a contrast reaction: 78 received prednisone, 89 hydrocortisone, 41 diphenhydramine, and 6 epinephrine. There was significantly more treatment for contrast reaction in the 4-hour protocol group (P < .01). Protocols for premedication to prevent contrast allergy reactions have been based on ionic high osmolar contrast usage and have not been separately validated for use with nonionic low osmolar contrast agents. This study demonstrates that the preexisting protocols appear only partially effective in preventing contrast reactions and the outcomes for the rapid 4-hour protocol performed significantly worse than the standard protocol. These outcomes show the need for further study and protocol refinement as well as continued vigilance for contrast reactions while using the current protocols.

Dried blood spots for doping controls-Development of a comprehensive initial testing procedure with fully automated sample preparation.

Currently, primarily urine, whole blood and serum samples are analyzed for doping-relevant substances in professional sports, but recently dried blood spots (DBS) have been introduced as complementary matrix, offering advantageous features, e.g. a minimally invasive sampling procedure. In order to cope with the increased application of DBS, a comprehensive initial testing procedure (ITP) was developed, optimized and validated, comprising a total of 233 substances representing all groups on the World Anti-Doping Agency's (WADA's) Prohibited List. The sample preparation was conducted by employing a fully automated system using an efficient flow-through extraction of a 4mm diameter spot followed by LC-HRMS/MS analysis. The procedure was successfully validated in terms of selectivity, limit of detection, reproducibility, carryover and robustness with respect to an alternative manual sample preparation, an alternative dried blood collection device and the sample extract stability, and was thus found to meet the required criteria of the relevant guidelines published by WADA for routine application. As a proof-of-concept, DBS samples were analyzed after the administration of the glucocorticoids prednisone and dexamethasone, as well as the stimulant pseudoephedrine and the beta-blocker propranolol. All substances were detected in post-administration samples for at least 4h and up to 24 h after intake, depending on the collection time period, using the developed testing procedure. In particular, for substances that are only banned in-competition, data obtained from DBS samples can be useful for the interpretation of adverse analytical findings. In conclusion, the developed ITP accounts for the anticipated increasing relevance of DBS in anti-doping analysis in the future and provides a foundation for optimized approaches for specific substance classes.

Low-dose administration of prednisone has a good effect on the treatment of prolonged hematologic toxicity post-CD19 CAR-T cell therapy.

Hematologic toxicity (HT) is a joint adverse event after CAR-T cells infusion. Some patients experience prolonged hematologic toxicity (PHT), which is challenging to treat. We collected clinical data from patients with relapsed refractory B-ALL treated with CD19 CAR-T cells. Patients with PHT who did not respond to erythropoietin, platelet receptor agonists, transfusion, or G-CSF and eventually received low-dose prednisone therapy were included in the analysis. We retrospectively analyzed the efficacy and safety of low-dose prednisone on PHT. Among 109 patients treated with CD19 CAR-T cells, 78.9% (86/109) of patients were evaluated as PHT. Of these, 15 patients had persistent hematological toxicity after infusion (12 were grade 3/4 cytopenia, 12 were trilineage cytopenia and 3 were bilineage cytopenia), 2 developed cytopenia without apparent cause after D28. The initial prednisone dose was 0.5 mg/kg/day, and the median response time was 21 days (7-40 days). The recovery rate of blood count was 100%, and the complete recovery rate ranged from 60% to 66.67%. Especially exciting was that HT recurred in 6 patients after stopping prednisone. They were relieved again after the administration of prednisone. The median follow-up time was 14.97 months (4.1-31.2 months). Twelve-month duration of PFS and OS rates were 58.8% (±11.9%) and 64.7% (±11.6%). We did not observe any other side effects of prednisone apart from drug-controllable hyperglycemia and hypertension. We suggest that low-dose prednisone is a beneficial and tolerable therapy for PHT after CAR-T cells. The trials have been registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).

Clinicopathologic and gastrointestinal effects of administration of prednisone, prednisone with omeprazole, or prednisone with probiotics to dogs: A double-blind randomized trial.

The efffect of administering of probiotics or twice-daily omeprazole on glucocorticoid-induced gastric bleeding in dogs is unknown. Compare gastrointestinal bleeding among dogs administered placebo, prednisone (2mg/kg q24h), prednisone with omeprazole (1mg/kg q12h), or prednisone with probiotics (Visbiome, 11.2-22.5 billion CFU/kg q24h) for 28 days. Twenty-four healthy research dogs. Double-blinded, placebo-controlled randomized trial. Clinical signs and endoscopic gastrointestinal mucosal lesion scores at baseline (t1 ), day 14 (t2 ), and day 28 (t3 ) were compared using split-plot repeated-measures mixed-model ANOVAs. Fecal score differed by treatment-by-time (F[6,40] = 2.65, P < .03), with higher scores in groups receiving prednisone at t3 than t1 . Nineteen of thirty-three episodes of diarrhea occurred in the prednisone with omeprazole group. Gastric mucosal lesion scores differed by treatment-by-time (F[6,60] = 2.86, P=.05), among treatment groups (F[3,60] = 4.9, P=.004), and over time (F[2,60] = 16.5, P < .001). Post hoc analysis revealed lesion scores increased over time for all groups receiving prednisone. At t3 , scores for the prednisone (8.7 ± 4.9) and prednisone with probiotics (8.7 ± 4.9) groups differed significantly from placebo (1.8 ± 1.8; P ≤ .04), whereas scores for the prednisone with omeprazole (6.5 ± 5.5) group did not differ from placebo (P=.7). Ulcers occurred only in dogs receiving prednisone. Prednisone-induced gastric bleeding. Co-administration of omeprazole partially mitigated bleeding, but a similar protective benefit was not demonstrated by co-administration of the evaluated probiotic.

Prednisolone pharmacokinetics after oral prednisone administration in paediatric patients with kidney transplant.

Glucocorticoids are 1 of the primary treatments in paediatric kidney transplantation. The aims of this study were: (i) to build a population pharmacokinetics (PPK) model of free prednisolone, which is the active form of prednisone, in paediatric kidney transplant recipients; (ii) to identify covariates accounting for interindividual variability (IIV) of pharmacokinetics (PK) parameters; and (iii) to investigate drug exposure-safety relationships. Ninety-seven samples were obtained from 39 paediatric kidney transplant recipients (aged 3.4-17.2years) in order to investigate prednisone PPK. We selected children receiving oral prednisone as part of their immunosuppressive regimen. A PPK analysis was performed using Monolix. A 1-compartment model best described prednisolone concentrations. Large IIV was observed as prednisolone was undetectable at H12 in some patients but could still be detected at H24 in others. Both bodyweight and ciclosporin cotreatment influenced the PK. The clearance (CLU ) and volume of distribution of free prednisolone allometrically scaled to 70 kg were 27.6L/h and 101 L. Ciclosporin cotreatment decreased CLU by 67%. High blood pressure and new onset diabetes after transplantation were associated with daily free prednisolone exposure. This study is the first analysis of prednisolone PPK in kidney-transplanted children. Some of the IIV in the PK parameters was explained by bodyweight and ciclosporin cotreatment. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy and limit side effects. The use of therapeutic drug monitoring in kidney-transplanted children may be useful, especially with respect to safety issues.