Prolonged Use Of Corticosteroids Research Articles

Approach to the patient with eosinophilia in the era of tyrosine kinase inhibitors and biologicals.

In this review, we aim to explore the optimal approach to patients presenting with eosinophilia, considering recent advances in diagnostic and therapeutic strategies. Specifically, we focus on the integration of novel therapies into clinical practice to improve patient outcomes. Advanced insights into the clinical and genetic features of eosinophilic disorders have prompted revisions in diagnostic criteria by the World Health Organization classification (WHO-HAEM5) and the International Consensus Classification (ICC). These changes reflect a growing understanding of disease pathogenesis and the development of targeted treatment options. The therapeutic landscape now encompasses a range of established and novel therapies. For reactive conditions, drugs targeting the eosinophilopoiesis, such as those aimed at interleukin-5 or its receptor, have demonstrated significant potential in decreasing blood eosinophil levels and minimizing disease flare-ups and relapse. These therapies have the potential to mitigate the side effects commonly associated with prolonged use of oral corticosteroids or immunosuppressants. Myeloid and lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusions are managed by various TK inhibitors with variable efficacy. Diagnosis and treatment rely on a multidisciplinary approach. By incorporating novel treatment options into clinical practice, physicians across different disciplines involved in the management of eosinophilic disorders can offer more personalized and effective care to patients. However, challenges remain in accurately diagnosing and risk-stratifying patients, as well as in navigating the complexities of treatment selection.

Gene replacement therapy for spinal muscular atrophy: safety and preliminary efficacy in a Brazilian cohort.

Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness, ventilatory failure, and reduced survival. Onasemnogene abeparvovec is the first gene replacement therapy (GT) approved to treat this condition. An observational retrospective study was conducted to assess adverse events and efficacy of GT in SMA patients. Forty-one patients with SMA (58.5% females and 80.1% SMA type 1) were included. The mean age at GT dosing was 18 (±6.4) months. Thirty-six patients (87.8%) were under previous treatment with nusinersen, and 10 (24.4%) continued nusinersen after GT. Mean CHOP-INTEND increased 13 points after 6 months and this finding did not differ between groups according to nusinersen maintenance after GT (p = 0.949). Among SMA type 1 patients, 14 (46.6%) reached the ability to sit alone. Liver transaminases elevation at least two times higher than the upper limit of normal value occurred in 29 (70.7%) patients. Thrombocytopenia occurred in 13 (31.7%) patients, and one presented thrombotic microangiopathy. Older age (>2 years) was associated with more prolonged use of corticosteroids (p = 0.021). GT is effective in SMA patients, combined nusinersen after GT did not appear to add gain in motor function and older age is associated with prolonged corticosteroid use.

Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials.

Prolonged use of corticosteroids induced complicated course in children with steroid-dependent nephrotic syndrome (SDNS), and the use of tacrolimus, a first-line alternative calcineurin inhibitor (CNI) agent was related to some unwanted adverse effects. Rituximab, a second alternative treatment has been proven to reliably reduce the number of relapses within 12 months with minimal adverse effects. Our review follows Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. All the databases were derived from MEDLINE, Proquest, EBSCOhost, Wiley, and Google Scholar within the past 11 years. The risk of bias was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions. Meta-analysis used Review Manager (version 5.4) with a random effect model to obtain a pooled mean difference (MD) and odds ratio with 95% confidence intervals (CIs). Four studies were included based on our eligibility criteria, and only three were included in the quantitative analysis. Three studies had low and one study had a moderate risk of bias. Pooled data results indicated that Rituximab was superior to tacrolimus in reducing the number of patients with 1-2 relapses (MD = 0.44, [95% CI: 0.21-0.91]) and had higher eGFR values (MD = 6.67; [CI - 2.92-10.61]). However, Rituximab showed insignificant superiority compared to tacrolimus in reducing the number of patients with 3 relapses, sustained remission, cumulative steroid use, serum cholesterol, and serum albumin concentrations. Rituximab exhibits more advantages in treating SDNS compared to tacrolimus, although the treatment options are highly individualized. Both regimens must also be weighed against their potential side effects to achieve a better overall health status.

Taurine activates the AKT-mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy.

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.

Through Indian Eyes: A Case Series on Steroid-induced Secondary Cataract

Lichen planus, a chronic autoimmune dermatological disorder, often necessitates the use of topical corticosteroids for symptom management. However, this case series highlights the emergence of topical steroid-induced secondary cataracts in two patients, emphasizing a previously underrecognized complication. Both patients, females aged 36 and 43, presented with gradual vision loss in their left eyes, attributed to prolonged corticosteroid use for lichen planus and skin allergies, respectively. Ophthalmological examinations confirmed the diagnosis, leading to cataract surgeries. The pathogenesis involves complex cellular and molecular mechanisms, emphasizing the need for vigilant monitoring during corticosteroid therapy. Moreover, the lack of stringent reporting systems for adverse drug reactions in India underscores the necessity for comprehensive monitoring to mitigate economic and quality of life burdens. The study emphasizes the importance of judicious corticosteroid use, tapering regimens, and patient education to minimize complications while effectively managing dermatological conditions. This underscores the critical need for heightened awareness, surveillance, and patient-centred approaches to mitigate the risk of corticosteroid-induced secondary cataracts, ensuring optimal therapeutic outcomes and long-term ocular health.

Factors associated with corticosteroid use in Crohn's disease and ulcerative colitis patients in Israel: A multicenter cross-sectional study

BackgroundWe examined corticosteroid use among Israeli patients with Inflammatory Bowel Disease (IBD), focusing on demographic, disease-related, and psychosocial factors. The objective was to contribute to the development of strategies minimizing corticosteroid dependence and improving patient outcomes, given the adverse effects associated with prolonged corticosteroid use. MethodsA comprehensive analysis was conducted on data collected from adult IBD patients attending six gastroenterological outpatient clinics in Israel. The data collected encompassed disease characteristics, demographic information, service level characteristics, social data, and steroid use. Statistical analyses were performed to associate these variables with steroid use. ResultsOut of 402 patients, 26 % had been treated with corticosteroids in the previous year, with a majority of these having only one treatment course. Of patients treated with steroids, 57% (n-44) met steroid dependent/excess criteria. Steroid use was more common in patients diagnosed with ulcerative colitis (UC) compared to those with Crohn's disease. Factors such as a diagnosis of UC, male gender, elevated C-reactive protein and fecal calprotectin, and decreased albumin and hemoglobin were associated with steroid use. ConclusionCorticosteroid use among Israeli IBD patients was associated with disease-related factors and some demographic characteristics. The results highlight the need for continued research to inform strategies aimed at reducing corticosteroid dependence in managing IBD, thereby improving patient outcomes.

DOP03 Gaps between ECCO quality standards of care and the real world: the E-QUALITY survey on processes and outcomes

Abstract Background The European Crohn’s and Colitis Organisation (ECCO) Position Paper on Quality-of-Care (QoC) proposed essential standards on process and outcomes for units that manage patients with inflammatory bowel disease (IBD). The E-QUALITY taskforce investigated whether gaps between these standards and real-world practice exist. Methods A 74-question web survey accessible to all institutions affiliated with ECCO was developed. One delegate per institution was requested to respond. A descriptive analysis was done. Results From March to October 2023, 166 centres from 28 different countries replied to the survey (Fig.1). At diagnosis, disease extent is assessed by colonoscopy in 96% and completed by small bowel (SB) evaluation in 43%. At least 2 biopsies from each segment are obtained in 55%. SB investigation for Crohn’s disease (CD) takes place in 60%. 54% of centres provide access to endoscopy with deep sedation for the majority of patients. To assess treatment response, faecal calprotectin is used in 65%, endoscopy in 54%, cross-sectional imaging for CD in 36%. In the case of primary failure of any drug, therapeutic decisions are based on objective measures of inflammation in 98%. A scheduled monitoring protocol for asymptomatic patients is followed in 42%. Patients with prolonged use of corticosteroids are being switched to a steroid-sparing treatment in 84%, but there is no protocol to track or act upon high steroid exposure in 43% of centres. 72% centres monitor metabolic bone health. Only 51% of units screen IBD patients for colorectal cancer, but screening is done with high-definition endoscopy in 92%. Chromoendoscopy with targeted biopsies is performed in only 47% units. Patients with perianal fistula are managed by combined medical and surgical approach in 67%, and reassessment by clinical and endoscopy and/or pelvic MRI is done in 62%. Laparoscopic approach for intra-abdominal surgery is used in 76%, and preoperative nutritional assessment in 62%. Patients receive therapies to prevent post-operative recurrence based on risk factors in 70%, standard endoscopy within 6-12 months after surgery is done only in 52% of centres. Although only 8% of centres lack a defined protocol to manage acute severe ulcerative colitis flares, 13% lack a standard algorithm, and 36% do not involve the surgeon in this setting from day 1. 38% of centres have a paediatric to adult transition clinic. The main reason for not adhering to ECCO standards are difficulty of providing tests in a timely fashion in up to 83% of centres. Conclusion Our survey has revealed significant gaps between ECCO standards and real-world practice. These results will help ECCO improve initiatives to help institutions to provide standard QoC. 1) Fiorino et al. JCC 2020;14:1037-48

A case report of association between canine iatrogenic hyperadrenocorticism and hypothyroidism

The canine hypothyroidism corresponds to a hormonal disorder, mainly caused by destruction of the thyroid gland, followed by idiopathic thyroid degeneration or idiopathic follicular atrophy, leading to a low production of the hormones thyroxine (T4) and triiodothyronine (T3). The canine iatrogenic hyperadrenocorticism consists of a disorder caused by the prolonged use of corticosteroids for therapeutic purposes, in most cases in allergic processes, such as canine atopy. In this case report, a twelve-year-old female Schnauzer was presented to the clinical facility with signs of apathy, polyphagia and non-pruritic bilateral symmetric alopecia that extended to the tip of the tail but sparing the head and limbs. Other clinical manifestations included polyuria, polydipsia, and bilateral keratoconjunctivitis sicca. The animal was submitted to the blood count, T4, T3, TSH dosage, dexamethasone suppression test, biochemical tests, and imaging tests. Exam results demonstrate the presence of hyperadrenocorticism and hypothyroidism. Since the use of corticosteroids in canine allergic diseases can lead to the development of hyperadrenocorticism, and hypothyroidism corresponds to the most common endocrinopathy in dogs, it is essential that the clinical veterinarian is able to identify these diseases early.

Steroid induced glaucoma in the paediatric population

Aims/Purpose: Steroid induced glaucoma is an iatrogenic pathology secondary to the prolonged use of corticosteroids, it is a serious pathology with a high risk of blindness. The aim of this study is to evaluate the epidemiological, clinical, therapeutic and evolutionary profile of steroid induced glaucoma in children.Methods: It is a retrospective study of cases treated between November 2007 and February 2022, including patients followed in the paediatric ophthalmology department of Casablanca for steroid induced glaucoma.Results: Our study involved́ 35 children (60 eyes), including 20 boys and 15 girls, with an average age of 12 years. The involvement was bilateral in 25 eyes. All the patients had a history of discontinuous self‐medication with local corticosteroids for a mean period of 5 years. The initial condition that led to the use of steroids was in 19 cases allergic conjunctivitis, in 10 cases it was used for recurrent meibomian cysts, 3 cases of uveitis, 2 cases of blepharitis and one episcleritis. 60% eyes had visual acuity raging between 0.1 to 0.3. Mean Intraocular pressure was 36 ± 1 2 mmHg. Mean vertical cup disc ratio was 0.68 ± 0.25. all our patients had an open angle on gonioscopy and severe perimetric deficits were noted in all our patients. 19 eyes (32%) had an associated cataract. IOP was controlled after the withdrawal of steroids in 8 eyes, associated to antiglaucoma treatment in 22 eyes. The surgical management consisted of a Trabeculectomy + IP + 5 F.U in 30 eyes. Cyclophotocoagulation was not required in any of the patients. On a follow up of 24 months, the average final visual acuity was <2/10th and the tonometric results were globally good with a stabilization of the papillary excavation and visual field in 82% of the cases.Conclusions: Steroid induced glaucoma is a condition in which the functional prognosis is at risk, especially in young patients. It shows the importance of regular monitoring of the IOP in patients undergoing corticosteroid treatment. The first line of treatment consist of the prevention: awareness of the risks of self‐medication by steroids.

Inhibitory Effect of Mistletoe Ointment on DNCB-Induced Atopic Dermatitis in BALB/c Mice

Atopic dermatitis (AD) is increasingly prevalent globally. However, the frequent and prolonged use of corticosteroids, which are commonly employed for AD treatment, carries potential side effects. Korean mistletoe (Viscum album L. var. coloratum), a perennial parasitic plant, has demonstrated various biological effects. In this study, we conducted in vivo investigations to determine whether Korean mistletoe possesses anti-inflammatory effects that play pivotal roles in regulating the pathological mechanisms of AD. BALB/c mice with AD-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) were utilized to explore the therapeutic effects of 1% and 2% Korean mistletoe extract (KME) ointments. The KME ointment was topically applied to the dorsal surface of the BALB/c mice, and they were categorized into four distinct groups: normal, DNCB-induced, DNCB-induced with 1% KME ointment, and DNCB-induced with 2% KME ointment. Each assessment parameter employed to evaluate the curative impact of the KME ointment displayed improvement with the application of the 1% KME ointment. While the effects observed were less pronounced than those of the 1% KME ointment, the overall therapeutic outcomes were also evident with the utilization of the 2% KME ointment. The results suggest the potential of Korean mistletoe as a viable therapeutic agent for AD. Further investigations are warranted to elucidate the underlying mechanisms of action.

A Retrospective Study on Mucormycosis and Other Fungal Infections Associated With COVID-19

A drastic increase in mucormycosis and other opportunistic infections was observed during the Covid-19 pandemic owing to multisystem involvement and related Immunosuppression. This retrospective study was carried out among SARS-COV-2 infected patients having invasive fungal infections [IFI] admitted to a tertiary care hospital in the southern part of India, for one year from August 2020. Among a total of 115 suspected cases, 54 patients were diagnosed to have IFI, during or immediately after Covid 19 disease. The most common fungal pathogens isolated were Mucorales (57.4%) followed by Aspergillus spp. (20.3%), Candida spp. (9.2%) and mixed infections (13.1%). Important predisposing factors identified were diabetes mellitus (70.7%), prolonged use of corticosteroids (85%), and administration of broad-spectrum antibiotics (90%). The predominant species identified among the diagnosed mucormycosis cases were Rhizopus spp. (54%) and Mucor spp. (25%); the site of involvement was paranasal sinus (70.1%), and rhino-orbital in 48.7% of the cases. Increased incidence of invasive Aspergillus infection in COVID-19 was seen mainly among ICU patients on ventilators, with Covid-19 induced lung damage. Common presentations were Chronic Pulmonary Aspergillosis, Rhino sinusitis, and Asthma. Of the total IFI, 9.2 % were caused by Candida spp. Of which 75% were due to Non- albicans candida species. Candidemia was the major presentation observed (90%). Of the patients with IFI, 90 % of them recovered, and the rest of them (7.4%) succumbed to infection. Of the patients with rhino-orbital mucormycosis who survived, 10 (39 %) had facial disfigurement and 11 (45 %) had a loss of vision.

Invasive fungal infections in pediatric patients with central nervous system tumors: novel insights for prophylactic treatments?

Invasive fungal disease (IFD) poses significant morbidity and mortality risks, especially in pediatric patients with neoplastic diseases. However, there is a notable lack of data concerning patients with central nervous system (CNS) tumors. Considering vulnerability factors to infections such as neutropenia, corticosteroids, chemotherapy, surgical interventions, and others, this study aims to evaluate the incidence of IFD in pediatric patients with CNS tumors and determine appropriate indications for prophylactic measures. This is a single-center, retrospective study conducted between 2011 and 2022 at the Pediatric Institute of Oncology (IOP-GRAACC-UNIFESP). A total of 38 cases of IFD were diagnosed in 818 children with CNS malignancies (4,6%). The mean age was 3.5 years (0.4-28y), with 22 (57.9%) male patients. Embryonal tumors (18/38, 47.3%) were the most prevalent CNS tumors, followed by low-grade gliomas (13/38, 34.2%). All episodes met the EORTC IFD criteria, and 36/38 (94.7%) were proven. Invasive yeast infections (33/36, 91.6%), predominantly Candida (30/33, 90.9%), were the most common diagnosis. In total, 25 patients (25/38, 65.8%) were receiving chemotherapy, with 13 of them having embryonal tumors. A total of 11 infants were in the Head Start scheme, resulting in a high prevalence of IFD in these group of patients (11/58, 18.9%). In total, 13 (13/38, 34.2%) patients underwent neurosurgery, mostly ventricular-peritoneal shunts revisions (10/13, 76.9%). Nine (9/38, 23.7%) were with prolonged use of corticosteroids, eight of them associated with neurosurgery. Routine systemic antifungal prophylaxis based solely on diagnosis is not recommended for low-risk cases. Evaluating patient- and treatment-specific risk factors is crucial in infants undergoing high-dose chemotherapy with expected neutropenia and in patients requiring prolonged corticosteroid therapy alongside neurosurgical procedures.

Efficacy of panthenol- and bisabolol-containing lip care as monotherapy for mild-to-moderate cheilitis.

Cheilitis is a chronic inflammatory condition of the lips, and frequent or prolonged use of topical corticosteroids may lead to various adverse events. Therefore, alternative therapies with fewer side effects are beneficial for the treatment of this condition. To evaluate the efficacy of a lip care formulation containing both panthenol and bisabolol as a monotherapy for mild-to-moderate cheilitis. This single-centre prospective pilot open-label study included 20 patients with mild-to-moderate cheilitis who were treated with the tested lip care for 8 weeks and evaluated by physician and patient assessments before the final efficacy was determined using the Visioscan score. Of the 20 patients, 13 (65.0%) presented with moderate cheilitis with dry and chapped lips. All parameters, including physician and patient clinical scores and bioengineering measurements, showed significant improvements as early as week 2 and sustained until week 8 following the application of the tested lip care. The frequency of cheilitis flareups also decreased significantly. The tested product was well tolerated without any adverse effects. Lip care with panthenol and bisabolol was safe and effective. It can be used as monotherapy for the treatment of mild-to-moderate cheilitis.

Supramolecular self-assembly of EGCG-selenomethionine nanodrug for treating osteoarthritis

Osteoarthritis (OA) has emerged as a significant health concern among the elderly population, with increasing attention paid to ferroptosis-induced OA in recent years. However, the prolonged use of nonsteroidal anti-inflammatory drugs or corticosteroids can lead to a series of side effects and limited therapeutic efficacy. This study aimed to employ the Mannich condensation reaction between epigallocatechin-3-gallate (EGCG) and selenomethionine (SeMet) to efficiently synthesize polyphenol-based nanodrugs in aqueous media for treating OA. Molecular biology experiments demonstrated that EGCG-based nanodrugs (ES NDs) could effectively reduce glutathione peroxidase 4 (GPX4) inactivation, abnormal Fe2+ accumulation, and lipid peroxidation induced by oxidative stress, which ameliorated the metabolic disorder of chondrocytes and other multiple pathological processes triggered by ferroptosis. Moreover, imaging and histopathological analysis of the destabilization of the medial meniscus model in mice confirmed that ES NDs exhibiting significant therapeutic effects in relieving OA. The intra-articular delivery of ES NDs represents a promising approach for treating OA and other joint inflammatory diseases.

Analysis of factors complicating the course of acne

Acne is among the most common conditions encountered in dermatological practice. In recent decades, there has been an increase in severe, complicated forms of acne. Objective — to analyze the factors that affect the deterioration of the clinical course of acne and stimulate the development of moderate and severe forms of acne. Materials and methods. For 3 years (2020—2023) we monitored 95 patients aged 18 to 35 years (45 men and 50 women), suffering from moderate to severe forms of acne. Before starting treatment, all patients completed a special questionnaire developed by us and taking into account known trigger factors. Results and discussion. Factors stimulating the transformation of mild acne into moderate and severe forms of the disease differ in groups of men and women. Among men, stress worsened the clinical course of dermatosis in 5 (11.1 %) cases, in women — in 9 (18 %). Among the factors that influenced the course of acne in women, we can distinguish the use of contraceptives 2 (4 %) and dysmenorrhea in 4 (8 %) people. 2 (4 %) patients clearly noted an improvement in the course of acne after withdrawal of contraceptives. Alcohol stimulated exacerbation of acne in 3 (6.7 %) men. Not sticking to the diet more often contributed to the exacerbation of acne in women — 9 (18 %), compared to only 6 (13.3 %) in men. A significant role in the stimulation of acne activity was played by irrational antibacterial topical therapy: 2 (4.4 %) men and 4 (8 %) women used topical drugs with clindamycin and erythromycin for a long time. There were cases of prolonged use of topical corticosteroids (for more than 3 months), which significantly worsened the clinical course of acne, in one case led to the development of steroid rosacea. 7 (14 %) women and 3 (6.7 %) men associated exacerbation of the disease with the intervention of a cosmetologist who did mechanical cleaning during the activation of acne. 5 (11.1 %) men and 3 (6 %) women were associated with worsening of the course of acne after SARS-CoV-2 infection. Also, the most common factor in acne exacerbation was self-medication: 7 (15.5 %) men and 6 (12 %) women. Some patients were unable to isolate any of the known trigger factors of acne: 9 (20 %) men, 3 (6 %) women. Conclusions. The study made it possible to identify a number of factors that affect the severity of the clinical course of acne. The most common triggers were psycho-emotional stress (18.0 % of women and 11.1 % of men), diet disorders (18 % of women and 13.3 % of men), self-treatment (15.5 % of men and 12 % of women), the COVID-19 pandemic (11.1 % of men and 6.0% of women), the intervention of cosmetologists with irrational aesthetic procedures (6.7 % of men and 14.0 % of women). Thus, the identified trigger factors of acne have gender, nutritional, behavioral characteristics, which requires further study and development of algorithms for their elimination and correction.

Prevalence, Risk Factors, Clinical Features, and Outcome of Influenza-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Systematic Review and Meta-Analysis

Influenza-associated pulmonary aspergillosis (IAPA) increasingly is being reported in critically ill patients. We conducted this systematic review and meta-analysis to examine the prevalence, risk factors, clinical features, and outcomes of IAPA. What are the prevalence, risk factors, clinical features, and outcomes of IAPA in critically ill patients? Studies reporting IAPA were searched in the following databases: PubMed MEDLINE, CINAHL, Cochrane Library, Embase, Scopus, Cochrane Trials, and ClinicalTrials.gov. We performed one-group meta-analysis on risk factors, clinical features, morbidity, and mortality using random effects models. We included 10 observational studies with 1,720 critically ill patients with influenza, resulting in an IAPA prevalence of 19.2%(331 of 1,720). Patients who had undergone organ transplantation (OR, 4.8; 95%CI, 1.7-13.8; I2= 45%), harbored a hematogenous malignancy (OR, 2.5; 95%CI, 1.5-4.1; I2= 0%), were immunocompromised (OR, 2.2; 95%CI, 1.6-3.1; I2= 0%), and underwent prolonged corticosteroid use before admission (OR, 2.4; 95%CI, 1.4-4.3; I2= 51%) were found to be at a higher risk of IAPA developing. Commonly reported clinical and imaging features were not particularly associated with IAPA. However, IAPA was associated with more severe disease progression, a higher complication rate, and longer ICU stays and required more organ supports. Overall, IAPA was associated with a significantly elevated ICU mortality rate (OR, 2.6; 95%CI, 1.8-3.8; I2= 0%). IAPA is a common complication of severe influenza and is associated with increased mortality. Early diagnosis of IAPA and initiation of antifungal treatment are essential, and future research should focus on developing a clinical algorithm. International Prospective Register of Systematic Reviews; No.: CRD42022284536; URL: https://www.crd.york.ac.uk/prospero/.

Rare Case of Chronic Limb-Threatening Ischemia in a 32-Year-Old Patient with Nephrotic Syndrome: A Case Report

AbstractChronic limb-threatening ischemia represents the end stage of peripheral artery disease (PAD), primarily affecting individuals over 60 years old. While quite rare, nephrotic syndrome (NS) is recognized for increasing the susceptibility to arterial thromboembolism (ATE). A 32-year-old male complained of resting pain in his left leg and pain after walking 50 meters with his right leg. He had a 9-year history of NS confirmed through biopsy and was on a daily regimen of 2 × 360 mg mycophenolic acid and 1 × 8 mg methylprednisolone. He had no history of hypertension, diabetes, or smoking. Atrophy and ulcers were observed on his left leg. Laboratory tests revealed elevated D-dimer and borderline high cholesterol levels. The right ankle-brachial index was 0.5, and for the left, it was 0.33. Computed tomography angiography identified occlusion in the left external iliac artery and right superficial femoral artery (SFA). The patient underwent percutaneous transluminal angioplasty with a plain balloon on both legs and an additional drug-eluting stent on the left SFA. He was discharged on rivaroxaban, clopidogrel, aspirin, simvastatin, mycophenolic acid, and methylprednisolone, with no complaints. The mechanism behind NS-caused ATE remains unclear, although it is associated with the loss of anticoagulants in urine, increased procoagulant activity, altered fibrinolytic systems, thrombocytosis, and enhanced platelet activation. Prolonged corticosteroid therapy in NS management also amplifies the risk of thromboembolism by promoting a hypercoagulable state. We suspected NS and the prolonged use of corticosteroids as risk factors for ATE, manifested as PAD in our patient. While optimal NS therapy may reduce the risk of PAD, prolonged corticosteroid use should be closely monitored.

Topical Corticosteroid-Induced Iatrogenic Cushing Syndrome in an Adolescent: A Case Report

Cushing syndrome (CS) is an endocrinological disorder characterized by increased blood cortisol level. It is either due to an excessive endogenous release of steroids (e.g., pituitary adenoma or adrenal hyperplasia) or exogenous administration of steroids. Iatrogenic Cushing syndrome is the most common form of Cushing syndrome. The vast majority of cases are due to oral or parenteral steroid preparations, which are commonly prescribed for pulmonary, renal, hematological or autoimmune diseases. Prolonged use of topical corticosteroids, particularly in children, may cause Cushing syndrome and suppression of the hypothalamo-pituitory-adrenal (HPA) axis, which is less common than that of oral or parenteral route. Iatrogenic CS due to the overuse of topical corticosteroids is rarely reported. There are only few cases that reported young children having Cushing syndrome secondary to misuse of topical corticosteroids.

Avacopan, a Novel Competitive C5a Receptor Antagonist, for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Avacopan is a relatively novel drug with complement antagonizing properties, and it has demonstrated promising outcomes in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. This review article seeks to investigate the current standard of care for ANCA vasculitis with the combination of avacopan. The current standard therapy involves the usage of daily corticosteroids in addition to either cyclophosphamide or rituximab; however, prolonged use of corticosteroids is known to be associated with various adverse effects. Avacopan was introduced as a possible substitution to alleviate high-corticosteroid dosages. It functions through competitive inhibition of the C5a receptor in the complement system and results in the reduction of neutrophil activation and migration to sites of inflammation. Clinical trials have observed the efficacy of avacopan both in conjunction with standard therapy with corticosteroids and without corticosteroids. The use of avacopan was able to achieve disease remission and improve renal function in patients with ANCA-associated vasculitis. Additionally, the novel treatment did not increase the risk of adverse events during treatment, while also lowering the toxic effects associated with corticosteroid usage. In summary, current evidence supports the success and safety of administering avacopan to treat patients with ANCA-associated vasculitis. Additional clinical trials are warranted to identify optimal dosage and method in using avacopan in the clinical setting.

Pharmacological approaches to pulmonary fibrosis following COVID-19.

Background: In the past few years, COVID-19 became the leading cause of morbidity and mortality worldwide. Although the World Health Organization has declared an end to COVID-19 as a public health emergency, it can be expected, that the emerging new cases at the top of previous ones will result in an increasing number of patients with post-COVID-19 sequelae. Despite the fact that the majority of patients recover, severe acute lung tissue injury can in susceptible individuals progress to interstitial pulmonary involvement. Our goal is to provide an overview of various aspects associated with the Post-COVID-19 pulmonary fibrosis with a focus on its potential pharmacological treatment options. Areas covered: We discuss epidemiology, underlying pathobiological mechanisms, and possible risk and predictive factors that were found to be associated with the development of fibrotic lung tissue remodelling. Several pharmacotherapeutic approaches are currently being applied and include anti-fibrotic drugs, prolonged use or pulses of systemic corticosteroids and non-steroidal anti-inflammatory and immunosuppressive drugs. In addition, several repurposed or novel compounds are being investigated. Fortunately, clinical trials focused on pharmacological treatment regimens for post-COVID-19 pulmonary fibrosis have been either designed, completed or are already in progress. However, the results are contrasting so far. High quality randomised clinical trials are urgently needed with respect to the heterogeneity of disease behaviour, patient characteristics and treatable traits. Conclusion: The Post-COVID-19 pulmonary fibrosis contributes to the burden of chronic respiratory consequences among survivors. Currently available pharmacotherapeutic approaches mostly comprise repurposed drugs with a proven efficacy and safety profile, namely, corticosteroids, immunosuppressants and antifibrotics. The role of nintedanib and pirfenidone is promising in this area. However, we still need to verify conditions under which the potential to prevent, slow or stop progression of lung damage will be fulfilled.