Long-term Corticosteroid Treatment Research Articles

Long-term Corticosteroid Treatment Patterns and Steroid-sparing Effects of Approved Treatments for Generalized Myasthenia Gravis in the United States

Long-term Corticosteroid Treatment Patterns and Steroid-sparing Effects of Approved Treatments for Generalized Myasthenia Gravis in the United States

Long-term topical corticosteroid treatment for atopic dermatitis: an in-depth analysis of safety, efficacy, withdrawal, and patient experiences

Long-term topical corticosteroid treatment for atopic dermatitis: an in-depth analysis of safety, efficacy, withdrawal, and patient experiences

Clinical Characteristics and the Prognostic Impact of Acute Kidney Injury in Critically Ill Patients with Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Retrospective, Single-Center Study

Introduction: The incidence and impact of acute kidney injury (AKI) in patients with invasive pulmonary aspergillosis (IPA) admitted to the intensive care unit (ICU) are unknown. Methods: This retrospective study included 140 patients who were diagnosed with IPA and admitted to the medical ICU of China-Japan Friendship Hospital in Beijing, China. AKI was defined according to the Kidney Disease: Improving Global Outcomes guidelines. Data on demographic characteristics, comorbidities, laboratory tests, treatments, and prognosis at ICU admission were collected. Results: The rate of AKI was 71.4% (n = 100), and approximately 30% of the patients had preadmission acute kidney dysfunction. Of the 100 patients with AKI, 19, 8, and 73 patients had stage I, II, and III AKI, respectively, and 64 (87.6%) patients required continuous renal replacement therapy. Overall ICU mortality rate was 52.1%. Irreversible AKI was a strong independent risk factor for ICU mortality (odds ratio 13.36, 95% confidence interval 4.52–39.48, p < 0.001), followed by chronic lung disease, use of intermittent positive-pressure ventilation, and long-term corticosteroid treatment within 1 year prior to ICU admission. Higher cardiac troponin I levels at admission and worse volume control during the first 7 days of ICU stay were potential predictive factors of irreversible kidney dysfunction. Patients with irreversible AKI and those who died during the ICU stay had greater volume overload during the first 14 days of ICU stay. Patients who survived received earlier renal replacement therapy support after ICU admission compared to those who died (median, 2 vs. 5 days; p = 0.026). Conclusion: Compared to the patients with IPA in the absence of AKI, those with AKI presented with more volume overload, worse disease burden, and required stronger respiratory support, while experiencing worse prognosis. Irreversible AKI was a strong predictor of mortality in patients with critical IPA. Better volume control and earlier CRRT initiation should be considered key points in AKI management and prognostic improvement.

Factors Affecting the Ability to Discontinue Oral Corticosteroid Use in Patients with EGPA Treated with Anti-Interleukin-5 Therapy

Introduction: Patients with eosinophilic granulomatosis with polyangiitis (EGPA) and some with severe eosinophilic asthma require continuous long-term oral corticosteroid (OCS) treatment for disease control. The anti-interleukin-5 agent, mepolizumab, has recently become available for the treatment of severe eosinophilic asthma and EGPA, with promising results and safety profiles. The proportion of patients with EGPA who discontinued oral steroids was 18% in the MIRRA trial. To compare patients with EGPA who were able to discontinue steroids with mepolizumab with those who could not. Methods: Twenty patients with EGPA treated with mepolizumab were evaluated at Osaka Habikino Medical Center. The OCS dose, asthma control test score, fractional exhaled nitric oxide levels, peripheral eosinophil count, and spirometric parameters were evaluated before and after treatment. Results: There was a significant reduction in the mean OCS dose from a prednisolone equivalent of 8.88 ± 4.99 mg/day to 3.18 ± 3.47 mg/day (p < 0.001). In this study, 40% of patients discontinued oral steroids. The most common reason for the failure to discontinue steroids in patients was poor asthma control. The percentage of predicted forced expiratory volume in 1 s significantly improved in patients with EGPA who could discontinue steroids after receiving mepolizumab. Conclusion: In this real-world study, treatment with mepolizumab for EGPA was associated with a significant reduction in OCS use; however, poor asthma control was identified as an inhibiting factor for steroid reduction.

Clinical and microbiological characteristics ofnocardiosis: A 5-year single-center study inCrete, Greece.

Nocardiosis is a rare disease affecting both immunocompromised and immunocompetent hosts, presented in various clinical forms ranging from localized to disseminated infection. Aim of the present study was to investigate the clinical and microbiological characteristics of nocardiosis, antimicrobial resistance profiles, treatment, and outcomes of Nocardia infection over the last 5 years at our institution. The medical records and microbiological data of patients affected by nocardiosis and treated at the university hospital of Heraklion, Crete, Greece, between 2018 and 2022, were retrospectively analyzed. The isolates were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and through sequencing of 16S rRNA. Antimicrobial susceptibility for 17 agents was determined by E-test and results were interpreted according to CLSI guidelines. Among the 28 Nocardia isolates, eight species were identified, with Nocardia brasiliensis being the most prevalent (32.1%), followed by Nocardia otitidiscaviarum (25%), and Nocardia farcinica (14.3%). Skin and soft tissue infections were the most common presentations, noted in 13 (50%) patients, followed by pulmonaryinfection presented in 10 (38.5%) patients. Fifteen patients (57.7%) had at least one underlying disease, and 11 (42.3%) were on immunosuppressive or long-term corticosteroid treatment. Susceptibility rates of linezolid, tigecycline, amikacin, trimethoprim-sulfamethoxazole, moxifloxacin, and imipenem were 100, 100, 96.4, 92.9, 82.1, and 42.9%, respectively. The 26 patients in this study were treated with various antibiotics. Mortality rate was 3.8%, and the patient who died had disseminated infection. Since epidemiology and antimicrobial susceptibility are evolving, continuous surveillance is mandatory in order to initiate appropriate treatment in a timely manner.

The Long-Term Efficacy of a Moisturizer Containing 4-T-Butylcyclohexanol and Licochalcone a as Adjunctive Therapy for Facial Seborrheic Dermatitis

Background: Facial seborrheic dermatitis (FSD) is a chronic relapsing skin disease caused by multifactorial factors. Longterm or frequent topical corticosteroid treatment may lead to adverse effects. Aims: To determine the long-term efficacy of a trial moisturizer containing 4-t-butylcyclohexanol and licochalcone A as an adjunctive treatment and its effectiveness in extending the disease-free period in FSD patients. Patients/Methods: Twenty patients with FSD aged ≥ 18 years were enrolled. They individually received a trial moisturizer to apply to their faces twice daily for 20 weeks. Clinical assessment by a physician, patient assessments, and bioengineering measurements were performed periodically. Results: Clinical severity assessment showed a significant improvement after 1 to 2 weeks of treatment compared with the baseline. The trial moisturizer promoted skin hydration and reduced transepidermal water loss. The number of patients with disease exacerbations and frequency of relapses significantly decreased after the first week and during the remainder of the study period. No participants needed rescue by topical corticosteroid therapy. Conclusion: The moisturizer containing 4-t-butylcyclohexanol and licochalcone A showed excellent efficacy without unwanted effects. It is endorsed for use as an adjunctive treatment or maintenance therapy to control the relapse of mild to moderate FSD.

Brittle bones

The use of corticosteroids is common in our clinical practice. Cortico-induced osteoporosis should be taken into consideration when using a dosage higher than 7.5 mg/d of prednisone or equivalent for a minimum of 3 months. We describe the case of a 69-year-old female patient who received long-term corticosteroid treatment for low back pain and developed secondary vertebral compression fractures. This case illustrates the importance of assessing fracture risk when prescribing corticosteroids, in order to offer preventive measures and introduce (in subjects with high risk) prophylactic treatments aiming to reduce the risk of irreversible consequences.

Nivolumab and AVD in Early-Stage Unfavorable Hodgkin Lymphoma: Follow-up Analysis of the Randomized GHSG Phase II Nivahl Trial

Background Anti-PD1 inhibition is increasingly investigated as first-line treatment of classical Hodgkin lymphoma (HL), usually either in sequential or concomitant combination with other therapeutics. While impressive response rates and short-term progression-free survival are observed, long-term efficacy and safety as well as quality-of-life (QoL) remain unknown. Herein we present the preplanned 3-year follow-up (FU) analysis of the GHSG phase II NIVAHL trial in early-stage unfavorable HL. Methods NIVAHL is an investigator-sponsored randomized phase II trial (NCT03004833) financially supported by Bristol-Myers Squibb which was conducted at 28 GHSG trial centers and enrolled 109 patients aged 18-60 years with centrally confirmed first diagnosis of early-stage unfavorable HL. Patients received either fully concomitant (4xnivo-AVD; arm A) or sequential (4xnivolumab, 2xnivo-AVD, 2xAVD; arm B) nivolumab-based 1st-line treatment, each followed by 30Gy involved-site radiotherapy (IS-RT). The primary analysis showed feasibility with a favorable safety profile and outstanding 1-year efficacy (Bröckelmann JAMA Oncol 2020). During FU, patients were monitored regularly for signs of HL relapse, persisting or late toxicities and QoL by the EORTC QLQ-C30 questionnaire. This FU analysis of key secondary endpoints including progression-free (PFS) and overall survival (OS), long-term safety and QoL was preplanned at three years after the registration of the last patient. Results With a median FU of 40 months, no PFS or OS events were observed since the NIVAHL primary analysis. Importantly, no patient with a partial remission by central response assessment required further treatment and all 7 patients converted to a complete remission during FU. With no deaths recorded, 3-year OS is 100% in both arms and 3-year PFS estimates are 98% and 100% in arm A and B, respectively (Figure 1). No second primary malignancies were reported and overall, no new safety signals were identified: While any treatment for potentially treatment-associated morbidities was required in 13% of patients, no patient required long-term corticosteroid treatment at last FU. Mean forced expiratory pressure in one second (FEV1) at baseline and 3 years after enrollment was 91.1% (standard deviation (SD) 13.6%) and 94.7% (SD 13%), respectively. Mean diffusion capacity for carbon monoxide adjusted for hemoglobin (DLCOc) at baseline and 3 years after enrollment was 86.2% (SD 16.5%) and 81.0% (SD 22.6%), respectively. No cardiac events >°1 were reported during FU and left ventricular ejection fraction (LVEF) was in the normal range in 93% of patients at last FU. The median global health score and global QoL by EORTC QLQ-C30 improved over time and were 64 (SD 22) and 80 (SD 16) at baseline, 76 (SD 17) and 87 (SD 15) 1 year after enrollment and 82 (SD 15) and 92 (SD 11) 3 years after enrollment, respectively. Relevant fatigue existed prior to treatment (mean fatigue score difference from age- and sex-adjusted German population reference value: 22 (SD 30)), briefly worsened on-treatment (after chemotherapy: 38 (SD 27), after radiotherapy: 27 (SD 23)) but resolved over time (1 year after enrollment: 10 (SD23), 3 years after enrollment: -3 (SD 18); Figure 2). Conclusion This preplanned FU analysis of the largest anti-PD1 HL first-line trial to date confirms the outstanding efficacy and favorable safety profile of this therapeutic approach. Additionally, QoL and fatigue appear relevantly improved compared to baseline during prolonged FU. Building on NIVAHL, the upcoming GHSG phase II INDIE trial (NCT04837859) will investigate an individualized immunotherapy with tislelizumab in early-stage unfavorable HL patients. Since likely not all patients require the full course of chemoimmunotherapy and consolidative IS-RT, INDIE will be the first trial investigating a chemo- and radiotherapy-free 1st-line HL treatment in optimally responding patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

PSAT224 Endocrine Manifestations in Diamond Blackfan Anemia

Abstract Introduction Diamond Blackfan anemia (DBA) is a form of pure red cell aplasia characterized by erythroid hypoplasia, congenital deformities, and increased risk of malignancy. It is typically diagnosed in first year of life. Treatments include chronic corticosteroids and frequent blood transfusions, which can result in significant endocrine complications. Case Presentation A 39 year-old African American male with DBA presented to the hospital with decompensated heart failure secondary to hemosiderosis, with ferritin level of 14,054 ng/ml (22-322). He complained of muscle cramps and weakness but denied paresthesias. He was diagnosed with DBA at 1 month of age, which required blood transfusions every 2 weeks and dual chelation therapy. He had previously tried corticosteroids for 6 months with poor response. Endocrine service was consulted to manage his multiple endocrine issues. He was diagnosed with primary hypothyroidism at age 1 and was on levothyroxine 175 mcg daily. At age 19, he was diagnosed with hypogonadotropic hypogonadism and was on testosterone cypionate 200 mg weekly. He received growth hormone injections from age 19 to 21 due to his delayed bone age and short stature. At age 23, he was diagnosed with adrenal insufficiency due to pituitary iron overload and was on prednisone 2.5mg daily. Physical exam was remarkable for short stature with height 152 cm, weight 46.4 kg, BMI 21.9 kg/m2, blood pressure 90/54 mm Hg and heart rate 93 bpm. He had positive Chvostek sign, pedal edema, jugular venous distension and bilateral lung crackles. There were no skeletal deformities, no hyper-pigmented skin, no surgical neck scars, negative Trousseau sign, and normal deep tendon reflexes. His lab work up was remarkable for TSH 80 mcIU/ml (0.4-4.7) and HbA1c in the prediabetes range. He had ionized calcium 3.1 mg/dl (4.5-5.2), phosphorus 6.9 mg/dl (2.4-5.1), PTH 27 pg/ml (11.1-79.5), eGFR &amp;gt;90 ml/min/m2 (&amp;gt;90), and 25-hydroxy vitamin 19.7 ng/ml (25-80), therefore he was newly diagnosed with primary hypoparathyroidism, most likely attributed to iron infiltration of the parathyroid glands. He was started on calcium carbonate 500 mg BID, calcitriol 0.5 mcg daily, sevelamer 2400 mg TID and ergocalciferol 50,000 IU/week with variable compliance. He was subsequently approved for teriparatide, as a substitute for Natpara (parathyroid hormone). Unfortunately, he expired before he could receive teriparatide. Discussion Endocrine complications in DBA are common with a prevalence in the American DBA registry of 53% having one or more endocrinopathy. These complications are related to long-term corticosteroid treatment or iron related deposition from transfusions. Our patient had transfusion related endocrinopathies including newly diagnosed primary hypoparathyroidism and history of hypopituitarism with resultant hypogonadism, adrenal insufficiency and growth hormone deficiency. Given the frequency of endocrine complications associated with DBA treatment, it is important to screen for these conditions starting in childhood. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Treatment-Associated Side Effects in Patients with Steroid-Dependent Nephrotic Syndrome.

Introduction:Nephrotic syndrome is one of the most extensively studied pediatric diseases for a nephrologist. Treatment for patients suffering from it has greatly improved the prognosis and reduced the mortality rate to 3% or less. Steroid medication is the first line, but non-steroid immunosuppressive drugs are useful in limiting steroid side effects and maintaining long-term remission. Objective: The aim of the study is to choose the best treatment for each patient in order to minimize long-term effects of corticosteroid therapy, taking into account the child's age, gender and other factors to optimize the quality of life. Materials and methods:Materials and methods: This is a retrospective study of pediatric patients older than one year and younger than 18 years of age diagnosed with idiopathic corticosteroid nephrotic syndrome. Study participants were treated in the Department of Pediatric Nephrology of "M. S. Curie" Emergency Clinical Hospital for Children, Bucharest, Romania, between January 2013 and December 2020. Thirty-seven subjects with steroid-dependent nephrotic syndrome from a total of 125 patients diagnosed with nephrotic syndrome were included in the present study. All study participants underwent clinical examination and laboratory tests and were regularly monitored. Results and discussion: Long-term corticosteroid therapy can lead to unwanted complications such as hypertension, short stature, behavior disturbances, or osteopenia. To minimize certain side effects, a second line steroid-sparing agents can be used due to their ability to induce complete remission and maintain it in patients with steroid-dependent nephrotic syndrome. Conclusion: Our study describes the most frequent side effects encountered in the Department of Nephrology in patients with steroid-dependent nephrotic syndrome. The purpose was to emphasize that pediatric patients' quality of life depends on limiting long-term corticosteroid treatment and preventing adverse reactions or complications.

The correlation between VitD3 levels and the disease activity of childhood-onset systemic lupus erythematosus.

There is growing evidence linking low levels of vitamin D3 to an increased risk of many autoimmune diseases. Compared to the general population, hypovitaminosis D is more prevalent among children with systemic lupus erythematosus (SLE), which can be associated with sun exposure avoidance, long-term corticosteroid treatment, and renal disease. Therefore, we launched this study to assess the correlation between 25 (OH) D3 (VitD3) levels and the disease activity of children with SLE (cSLE) in Taiwan. From September to December 2018, we recruited 31 cSLE patients from the Pediatric Out-patient Department of Taichung Veterans General Hospital. Their basic data, including SLE disease index 2000 (SLEDAI-2K) score, laboratory values, prescribed drugs and VitD3 levels were collected and analyzed statistically. The mean serum VitD3 concentration was 19.7 ± 7.9 ng/mL and SLEDAI-2K 6.2 ± 5.0. Those patients (N = 16) with an SLEDAI-2K≦4 had higher VitD3 levels when compared to those (N = 15) with an SLEDAI-2K>4 (22.9 ± 7.7 vs 16.3 ± 6.7 points, p = 0.020). Five patients not taking systemic corticosteroids (SCS) had significantly higher VitD3 levels and lower SLEDAI-2K than those who took SCS (N = 26). Additionally, we found VitD3 levels to be negatively correlated to SLEDAI-2K (rs = -0.55, p = 0.001) and daily SCS dosages (rs = -0.49, p = 0.005). This study shows that VitD3 deficiency is common in patients with cSLE. It was also noted that serum VitD3 levels negatively correlate to SLEDAI-2K, which can be partially explained by less usage of SCS.

Steroid-Resistant Central Nervous System Sarcoidosis: The Selections of Multi-Agent Combination as the Initial Treatment

Sarcoidosis is a granulomatous multiorgan disease of unknown etiology that commonly affects the respiratory system, eyes, and skin, and less commonly affects the nervous system. Because of its rarity, a standard treatment for central nervous system (CNS) sarcoidosis has not yet been established. Corticosteroids remain the cornerstone of CNS sarcoidosis treatment. However, CNS sarcoidosis, other than isolated facial nerve paralysis, is often refractory to treatment and requires long-term corticosteroid treatment. In particular, patients with hydrocephalus have a high mortality rate and a lack of response to this treatment. Therefore, immunosuppressants, including TNF-α inhibitors and corticosteroids, should be considered as the initial treatment. For older patients, it is important to pay attention to infection as an adverse event and to the toxicity of the therapeutic agents. Because steroid-related adverse events are more common in the older patient group, the lowest effective dose should be used, and the treatment duration should be kept as short as possible after careful evaluation of disease activity. Corticosteroid-sparing agents are effective at reducing the cumulative toxicity of corticosteroids. Recently, various new potential agents have emerged and their efficacy has been assessed. It is expected that more treatment options will be available for CNS sarcoidosis in future.

The occurrence timeline of steroid-induced ocular hypertension and cataract in children with systemic autoimmune diseases.

Steroid-induced ocular hypertension (SIOH) and cataract can result in visual loss. This study evaluated the timetable of SIOH and steroid-induced posterior subcapsular cataract (SI-PSC) occurrences in children with systemic autoimmune diseases (SAD) undergoing long-term systemic corticosteroid treatment. Thirty-seven children with SAD treated with long-term oral corticosteroids were enrolled in this study. Intraocular pressure (IOP), SI-PSC occurrences, visual field and peripapillary retinal nerve fibre layer (pRNFL) thicknesses were recorded every 3months for at least 6months. Of the 37 children, with average age 11.0 ± 2.9years, 22 patients (59.5%) had SIOH, 2 progressed as glaucoma at the 18-month and 3-year follow-up, respectively, and 12 (32.4%) patients had SI-PSC. Among patients with SIOH, 45.5% (10/22) of them had SI-PSC occurrence, and among patients with normal IOP, 13.3% (2/15) of them had SI-PSC. Seventeen patients participated in a longitudinal study with a follow-up period of at least 18months. The incidence of SIOH started at 1month 52.9% (9/17) and gradually increased to 70.6% (12/17) at 6months, then decreased to 35.3% (6/17). SI-PSC onset started at 6months (17.6%, 3/17), and its occurrence increased to 35.3% (6/17) at 12months and reached to 41.2% (7/17) at 18months. The pRNFL was thicker in the children with SIOH than the healthy controls (p = 0.01). SIOH and SI-PSC are common coexistent complications in children with long-term corticosteroids treatment, and the occurrence time is during the first month and 6months, respectively. Patients with SIOH have a higher probability of cataract.

A Case of Type 2 Diabetes Mellitus Ｗith Insulin Antibody Induced by Exogenous Insulin Therapy: Serial Changes in Antibody Characteristics under Long-term Corticosteroid Treatment

A Case of Type 2 Diabetes Mellitus Ｗith Insulin Antibody Induced by Exogenous Insulin Therapy: Serial Changes in Antibody Characteristics under Long-term Corticosteroid Treatment

Efficacy of Severe Acute Respiratory Syndrome Coronavirus-2 Vaccine in Patients With Thoracic Cancer: A Prospective Study Supporting a Third Dose in Patients With Minimal Serologic Response After Two Vaccine Doses

IntroductionCoronavirus disease 2019 resulted in a 30% mortality rate in patients with thoracic cancer. Given that patients with cancer were excluded from serum antisevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine registration trials, it is still unknown whether they would develop a protective antispike antibody response after vaccination. This prospective vaccine monitoring study primarily aimed to assess humoral responses to the SARS-CoV-2 vaccine in patients with thoracic cancer. MethodsSARS-CoV-2–spike antibodies were measured using the Abbot Architect SARS-CoV-2 immunoglobulin G immunoassay before the first injection of BNT162b2 mRNA vaccine, at week 4, and 2 to 16 weeks after the second vaccine dose administration. The factors associated with antibody response were analyzed. ResultsOverall, 306 patients, with a median age of 67.0 years (interquartile range: 58–74), were vaccinated. Of these, 283 patients received two vaccine doses at 28-day intervals. After a 6.7-month median follow-up, eight patients (2.6%) contracted proven symptomatic SARS-CoV-2 infection, with rapid favorable evolution. Of the 269 serologic results available beyond day 14 after the second vaccine dose administration, 17 patients (6.3%) were still negative (<50 arbitrary units/mL, whereas 34 (11%) were less than 300 arbitrary units/mL (12.5th percentile). In multivariate analysis, only age (p < 0.01) and long-term corticosteroid treatment (p = 0.01) were significantly associated with a lack of immunization. A total of 30 patients received a third vaccine dose, with only three patients showing persistently negative serology thereafter, whereas the others exhibited clear seroconversion. ConclusionsSARS-CoV2 vaccines were found to be efficient in patients with thoracic cancer, most of them being immunized after two doses. A third shot given to 1% of patients with persistent low antibody titers resulted in an 88% immunization rate.

Comparing the clinical characteristics and outcomes of COVID-19-associate pulmonary aspergillosis (CAPA): a systematic review and meta-analysis.

PurposeInvasive pulmonary aspergillosis has been increasingly recognized in COVID-19 patients, termed COVID-19-associate pulmonary aspergillosis (CAPA). Our meta-analysis aims to assess the clinical characteristics and outcomes of patients diagnosed with CAPA compared to those without CAPA.MethodsWe searched the Pubmed, Cochrane Library, SCOPUS, and Web of Science databases for studies published between January 1, 2020 and August 1, 2021, containing comparative data of patients diagnosed with CAPA and those without CAPA.ResultsEight cohort studies involving 729 critically ill COVID-19 patients with comparative data were included. CAPA patients were older (mean age 66.58 vs. 59.25 years; P = 0.007) and had underlying chronic obstructive pulmonary disease (COPD) (13.7 vs. 6.1%; OR 2.75; P = 0.05). No differences in gender, body mass index (BMI), and comorbidities of diabetes and cancer were observed. CAPA patients were more likely to receive long-term corticosteroid treatment (15.0 vs. 5.3%; OR 3.53; P = 0.03). CAPA patients had greater severity of illness based on sequential organ failure assessment (SOFA) score with a higher all-cause in-hospital mortality rate (42.6 vs. 26.5%; OR 3.39; P < 0.001) and earlier ICU admission from illness onset (mean 11.00 vs. 12.00 days; P = 0.003). ICU length of stay (LOS), invasive mechanical ventilation (IMV) duration, the requirement of inotropic support and renal replacement therapy were comparable between the two groups.ConclusionsCAPA patients are typically older with underlying COPD and received long-term corticosteroid treatment. Furthermore, CAPA is associated with higher SOFA scores, mortality, and earlier onset of ICU admission from illness onset.

Risk factors for nontuberculous mycobacterial pulmonary disease (NTM-PD) in Croatia

The incidence, geographical distribution and clinical relevance of different nontuberculous mycobacteria (NTM) in Croatia are well described. There are few data on the risk factors for developing NTM pulmonary disease (NTM-PD) in this setting. We conducted aretrospective cohort study on all Croatian residents with NTM isolated from respiratory samples in the period from 2006 to 2015 with follow-up to 2018. The American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines were used to establish NTM-PD diagnosis. Clinical, radiological and treatment data were collected from hospital records. Risk analysis calculations were made on the 439 isolation episodes that were classified as definitive NTM-PD (n = 137) or no disease (n = 302). Female gender, presence of bronchiectasis, low BMI and long-term systemic corticosteroid treatment were independent risk factors associated with NTM-PD. Hemoptysis and malaise were presenting symptoms independently associated with NTM-PD. Chronic obstructive pulmonary disease (COPD) and low/moderate dose inhaled corticosteroid (ICS) treatment were not associated with NTM-PD. High dose ICS treatment was asignificant risk factor for developing NTM-PD (aOR = 4.73, CI 1.69-13.23 p = 0.003). The NTM-PD patients in Croatia are similar to those in other published cohorts in terms of their characteristics and risk factors. The significant dose-dependent association between ICS use and NTM-PD adds to the body of evidence suggesting that high dose ICS use is associated with NTM-PD.

Predictive factors for a severe course of COVID-19 infection in myasthenia gravis patients with an overall impact on myasthenic outcome status and survival.

Background and purposeMyasthenia gravis (MG) patients could be a vulnerable group in the pandemic era of coronavirus 2019 (COVID‐19) mainly due to respiratory muscle weakness, older age and long‐term immunosuppressive treatment. We aimed to define factors predicting the severity of COVID‐19 in MG patients and risk of MG exacerbation during COVID‐19.MethodsWe evaluated clinical features and outcomes after COVID‐19 in 93 MG patients.ResultsThirty‐five patients (38%) had severe pneumonia and we recorded 10 deaths (11%) due to COVID‐19. Higher forced vital capacity (FVC) values tested before COVID‐19 were shown to be protective against severe infection (95% CI 0.934–0.98) as well as good control of MG measured by the quantified myasthenia gravis score (95% CI 1.047–1.232). Long‐term chronic corticosteroid treatment worsened the course of COVID‐19 in MG patients (95% CI 1.784–111.43) and this impact was positively associated with dosage (p = 0.005). Treatment using azathioprine (95% CI 0.448–2.935), mycophenolate mofetil (95% CI 0.91–12.515) and ciclosporin (95% CI 0.029–2.212) did not influence the course of COVID‐19. MG patients treated with rituximab had a high risk of death caused by COVID‐19 (95% CI 3.216–383.971). Exacerbation of MG during infection was relatively rare (15%) and was not caused by remdesivir, convalescent plasma or favipiravir (95% CI 0.885–10.87).ConclusionsAs the most important predictors of severe COVID‐19 in MG patients we identified unsatisfied condition of MG with lower FVC, previous long‐term corticosteroid treatment especially in higher doses, older age, the presence of cancer, and recent rituximab treatment.

Therapeutic Challenges in Systemic Lupus Erythematosus Patient with Pregnancy, Osteoporosis, and Severe Thrombocytopenia: A Case Report and Review of Literature

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease that requires long-term corticosteroid treatment that may lead to osteoporosis characterized by low bone mass and microarchitectural deterioration of the trabecular and cortical skeletal. This study presents a severe case of thrombocytopenia in a 25-year old woman with SLE and osteoporosis who underwent routine therapy and was pregnant for the first time. The complexity of pregnancy and autoimmune conditions create therapeutic challenges that need to be considered in SLE patients with pregnancy, osteoporosis, and severe thrombocytopenia.

Dexamethasone Promotes Aspergillus fumigatus Growth in Macrophages by Triggering M2 Repolarization via Targeting PKM2.

Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on Aspergillus fumigatus-related immune modulation. We found by high content screening and flow cytometric analyses that during monocyte-to-macrophage differentiation, as little as 0.1 µg/mL Dex resulted in a shift in macrophage polarization from M1 to M2-like macrophages. This macrophage repolarization mediated via Dex was characterized by significant upregulation of the M2 marker CD163 and downmodulation of M1 markers CD40 and CD86 as well as changes in phenotypic properties and adherence. These Dex-mediated phenotypic alterations were furthermore associated with a metabolic switch in macrophages orchestrated via PKM2. Such treated macrophages lost their ability to prevent Aspergillus fumigatus germination, which was correlated with accelerated fungal growth, destruction of macrophages, and induction of an anti-inflammatory cytokine profile. Taken together, repolarization of macrophages following corticosteroid treatment and concomitant switch to an anti-inflammatory phenotype might play a prominent role in triggering invasive aspergillosis (IA) due to suppression of innate immunological responses necessary to combat extensive fungal outgrowth.