Use Of Corticosteroids Research Articles

Plasma collagen neoepitopes are associated with multiorgan disease in the ACCESS and GRADS sarcoidosis cohorts

IntroductionThe pathogenesis of sarcoidosis involves tissue remodelling mediated by the accumulation of abnormal extracellular matrix, which is partly the result of an imbalance in collagen synthesis, cross-linking and degradation. During...

Influence of severity biomarkers on the functional profile of COVID-19 survivors as assessed by the PCFS scale

Objective: To evaluate the relationship between laboratory biomarkers of severity and functional limitations analyzed by the PCFS (Post COVID Functional Scale) in COVID-19 survivors. Methods: ambispective, quantitative and longitudinal cohort study. Data collection took place in two moments: initially during hospitalization, recording the percentage of lung impairment, D-dimer, CRP (C Reative Protein), BMI (Body Mass Index), age, smoking time, mechanical ventilation (MV), MV time, lenght of hospitalization, thrombosis, use of vasoactive drugs, anticoagulants and corticosteroids. The second by applying the PCFS scale. Results: 80 individuals were included. 46 (57.5%) were female with a mean age of 52.3 years (SD 14.5) and a BMI of 27.5 kg/m2 (SD 4.4). Of these, 64 (80%) had limitations. Comparing the groups by dependent factor, functional profile, smoking time (12 vs. 28 years, p=0.041), BMI (25 vs. 28 kg/m2, p=0.036), age (43 vs. 54 years, p=0.008), D-dimer (421 vs 788 mg/L p=0.012) and CRP (2 vs 12mg/L, p=0.047) were higher in the group with limitations. In logistic regression, D-dimer and BMI remain as independent predictors of worse functional profile. Conclusion: D-dimer and BMI changes during hospital stay can modify the post-COVID-19 functional profile. Therefore, the early inclusion of individuals with changes in these markers in rehabilitation programs is an assertive strategy for COVID-19 survivors.

Management of Primary Immune Thrombocytopenia: Turkish Modified Delphi-Based Consensus Statement for Special Considerations

Primary immune thrombocytopenia (ITP) is an acquired disorder of platelets with a complex and unclear mechanism of increased immune destruction or impaired production of platelets. While the management of ITP is evolving, there is still a need for guidance, particularly in certain circumstances such as pregnancy, emergencies, or patients requiring co-medications. We aimed to determine the tendencies of hematologists in Türkiye in the event of such special considerations. Applying a modified Delphi method, the Turkish National ITP Working Group, founded under the auspices of the Turkish Society of Hematology, developed a questionnaire consisting of statements regarding pregnancy, emergencies, and circumstances requiring co-treatment with antiaggregants or anticoagulants. A total of 107 hematologists working in university or state hospitals voted for their agreement or disagreement with the statements for two sequential rounds. The participating hematologists reached an agreement on starting treatment for pregnant patients with platelets of less than 30x109/L and delivery either vaginally or by cesarean section being safe at platelet counts above 50x109/L. For emergencies and the rescue management of ITP, the panel agreed against the use of high-dose corticosteroids alone, preferring combinations with transfusions or intravenous immunoglobulin. For patients who require interventions, platelet counts of >50x109/L were regarded as safe for low-risk procedures as well as co-treatment with antiplatelets or anticoagulants. As the National ITP Study Group, we have observed the need to increase the practice guidance regarding patients with primary ITP requiring additional treatments including invasive interventions and co-treatments for coagulation. Decisions on the management of ITP during pregnancy should be individualized. There is a lack of consensus on the thresholds of platelet counts as well as co-morbidities and co-medications. This lack of consensus may be due to variations in practices.

Preventive Paradox? Postoperative Outcomes After Risk-Reducing Mastectomy and Direct-to-Implant Breast Reconstruction

BackgroundRisk-reducing mastectomy (RRM) with direct-to-implant (DTI) breast reconstruction is becoming increasingly important in breast cancer prevention. While the oncological benefits of RRM-DTI are well documented, there is a paucity of studies investigating its perioperative safety. MethodsThe ACS-NSQIP database (2008-2022) was queried to identify all patients who underwent RRM-DTI. Outcomes of interest included 30-day occurrence of reoperation, readmission, and surgical and medical complications. Multivariate logistic regression was used to determine factors associated with postoperative complications. ResultsA total of 1019 patients were included, with a mean age and BMI of 42.8 ± 10.9 years and 25.7 ± 5.8 kg/m², respectively. Complications occurred in 142 (14.0%) cases, with 103 (10.1%) reoperations and 51 (5.0%) readmissions. 62 (6.3%) surgical complications were recorded, the majority of which were superficial incisional infection (n = 19; 1.9%) and organ space infections (n = 19; 1.9%). Medical complications were rare (n = 13; 1.3%). Multivariable analyses revealed that higher BMI was significantly associated with any (OR:1.06, P < .0001), surgical (OR:1.08, P < .0001), and medical complications (OR:1.08, P = .04). Patients with bleeding disorders were at a significantly higher risk of any complications (OR:5.5, P = .03), while outpatient setting (OR:1.9, P = .03) and corticosteroid use (OR:6.6, P = .01) were identified as independent predictors of surgical complications. ConclusionThe risk of adverse events following RRM-DTI should not be underestimated, with a 30-day complication rate of 14%. Higher BMI, bleeding disorders, outpatient setting, and corticosteroid use were identified as risk factors. These findings underscore the need for thorough preoperative risk stratification, patient counseling, and health optimization to optimize surgical outcomes.

Osteonecrosis as a manifestation of Long-COVID Syndrome: a systematic review.

Purpose SARS-CoV-2 is an RNA virus responsible for COVID-19 pandemic. Some authors described the set of persistent symptoms COVID-related as "Long-COVID Syndrome." Several cases of post-COVID-19 osteonecrosis (ON) are described. Our primary aim was to study the hypothetical correlation between SARS-CoV-2 infection and ON; our secondary aim was to understand if ON can be considered part of Long-COVID. Materials and methods We performed a systematic review following the Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines. Because COVID-19 is a recently described disease, we included all levels of evidence studies. We excluded studies lacking specification regarding the use of corticosteroids (CCS) and studies not related to COVID-19. The variables extracted were age, sex, risk factors, affected joints, signs and symptoms, magnetic resonance imaging (MRI) and X-ray features, histology, treatment of COVID-19, dose and duration of treatment with CCS, treatment of ON, follow-up, and treatment outcome. Results A total of 13 studies were included, involving 95 patients and 159 joints. Time between the diagnosis of COVID-19 and the onset of symptoms related to ON was 16weeks on average. Time between the onset of symptoms and the MRI was 6weeks. An average of 926.4mg of prednisolone equivalent per patient were administered. On average, CCS were administered for 20.6days. Conclusions Patients with a history of COVID-19 infection developed osteonecrosis prematurely and with a lower dose of CCS than usually reported in the literature. Symptoms of osteonecrosis occur within the interval of the period described as Long-COVID. Surgeons should not underestimate the persistence of arthralgia when a history of SARS-CoV-2 infection and use of CCS is reported.

Anifrolumab treatment improves patient-reported quality of life and decreases disease activity and corticosteroid use in patients with systemic lupus erythematosus: A qualitative study in Denmark.

Anifrolumab is a new therapeutic approach for individuals with systemic lupus erythematosus (SLE) directed at blocking the type 1 interferon pathway. Despite the expanding body of literature on Anifrolumab, an essential aspect remains absent: the subjective patient experience of treatment effects and implications on patients' health-related quality of life (HRQoL). The present study aimed to fill this void by elucidating the nuanced perspectives of SLE patients receiving Anifrolumab treatment by conducting qualitative in-depth interviews (IDIs). SLE patients at Aarhus University Hospital who had received at least three infusions of Anifrolumab were approached for inclusion in the study, which comprised two main elements: (1) qualitative IDIs and (2) collection of patient data from electronic medical records (EMRs). The IDIs were semi-structured and based on a discussion guide that included open-ended and close-ended questions. Verbatim transcripts were coded and analysed using qualitative software to understand concepts important to patients and to understand patients' own experiences before and after Anifrolumab therapy. A clinical chart review was conducted using EMR data at baseline, 3months, and 6months after Anifrolumab initiation. IDIs were completed with 14 patients, and EMR data was collected from 16 patients (treatment days range: 62-474). Of the 23 symptoms spontaneously reported by patients prior to Anifrolumab treatment, fatigue, joint pain, sun sensitivity, joint stiffness, skin rashes, and hair loss were the most common. Most symptoms improved, and none worsened during treatment. Patients reported significant impacts of disease on daily life before treatment: day-to-day activities, social life, emotional aspects, physical activity, concentration/memory, work/employment, and family/romantic relationships. Patients reported improvements in all aspects after treatment but were still impacted. From the EMR data, we observed a fall in disease activity after treatment initiation with a concomitant reduction in the use of corticosteroids. This study provides valuable insights into the subjective experiences of SLE patients treated with Anifrolumab, and the findings collectively contribute to a comprehensive understanding of the treatment's efficacy from the patients' perspective and its tangible effects on both subjective and objective parameters in SLE patients.

Efficacy of Corticosteroids for Sore Throat Management in Adults: A Systematic Review and Meta-Analysis of Randomized Trials.

Sore throat (acute pharyngitis) is among the most common complaints among adults and is a reason for seeking healthcare globally. Antibiotics are widely used among patients with infectious sore throat. Previous research has indicated that corticosteroids could offer an alternative symptomatic treatment for sore throats.To estimate the corticosteroid efficacy as an additional therapy for sore throat adult patients, the literature search included PubMed, Medline, OVID, Cochrane CENTRAL, and Scopus for articles published until July 1st, 2024. The outcomes included the onset of pain relief (average time), complete resolution of pain (average time), absolute reduction of pain at 24 and 48 hours, requirement of antibiotics, and adverse effects related to treatment. Standardized mean difference (SMD) and risk difference were used to report numerical and dichotomous results. Five studies were included. Among the five included studies, corticosteroids showed significant effectiveness in resolving pain at 24 hours (average risk difference: 0.2200, 95% CI: 0.0500 to 0.3899, p = 0.0112) but with notable heterogeneity (I² = 82.4255%). At 48 hours, the benefit was not statistically significant (average risk difference: 0.4063, 95% CI: -0.1857 to 0.9984, p = 0.1786, I² = 98.9219%). Corticosteroids also decreased the average time to onset of pain relief (average SMD: -0.6590, 95% CI: -1.2857 to -0.0323, p = 0.0393, I² = 89.7914%), although with high heterogeneity. Other findings indicated a possible reduction in antibiotic use and fewer days missed from work. Adverse effects were minimal and occurred at similar rates in both corticosteroid and placebo arms. Corticosteroids can decrease pain intensity and duration in adults with acute sore throats. However, significant heterogeneity among studies and methodological limitations render the overall evidence inconclusive. While some studies noted reduced antibiotic use and lower symptom recurrence, high-quality RCTs are needed to address these limitations and provide more definitive guidelines for corticosteroid use in treating acute pharyngitis.

Epidemiology of Elderly Onset IBD: A Nationwide Population-Based Cohort Study

We examined the incidence and natural history of patients with very elderly onset (herein referred to as very late-onset) inflammatory bowel diseases (IBDs) (≥ 70 years of age at diagnosis), compared with patients diagnosed between 60 and 69 years of age in Denmark. In the Danish National Patient Register, between 1980 and 2018, we identified all individuals ≥ 60 years of age with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) and examined trends in incidence, cumulative risk of hospitalization, treatment patterns, IBD-related surgery, serious infection, cancer and cardiovascular and venous thromboembolic risks among very late-onset (70-79 years of age or 80+ years) vs late-onset (60-69 years of age) IBD, using nonparametric competing risk analysis treating death as competing risk. We identified 3459 patients with onset of CD at ≥60 years of age (47% ≥ 70 years of age) and 10,774 patients with onset of UC ≥60 years of age (51% ≥ 70 years of age). Over the last 3 decades, incidence changes for very late-onset and late-onset IBD have followed the same patterns. Also, both for CD and UC, cumulative incidence of IBD-related hospitalization and corticosteroid use was comparable in very late-onset vs late-onset patients. However, the burden of disease-modifying therapy, either immunomodulator or tumor necrosis factor antagonist use, and major IBD-related surgery was significantly lower in patients with very late-onset than in late-onset IBD. On the other hand, the 5-year risk of serious infections and cardiovascular events was higher in patients with very late-onset IBD. This nationwide cohort study shows that patients diagnosed with very late-onset (≥ 70 years of age) IBD have a higher relative burden of disease- and aging-related complications, with limited use of steroid-sparing strategies and surgery, compared with late-onset IBD.

Intraocular Pressure Response in the Untreated Contralateral Eye After Selective Laser Trabeculoplasty.

To examine the impact of selective laser trabeculoplasty (SLT) on intraocular pressure (IOP) in the untreated contralateral eye within 12 months after the procedure. A retrospective chart review was conducted on patients with primary open-angle, normal-tension, pigmentary, or pseudoexfoliation glaucoma who received 360-degree SLT at George Washington University. Exclusion criteria included prior or subsequent laser or glaucoma surgery within 12 months of SLT, other glaucoma types, or corticosteroid use during follow-up. Primary outcomes were IOP and medication reduction, and SLT success, defined as reducing IOP by ≥20% without additional IOP-lowering procedures or medications. Follow-up occurred at six weeks, six months, and 12 months. Demographic and clinical data were analyzed using ANOVA, paired t-tests, and chi-squared tests. A total of 125 patients were included, representing a range of backgrounds: African American (57.6%), Caucasian (31.2%), Asian (5.6%), and Hispanic/Latino (4%), and 1.6% did not report their background. Significant reductions in mean IOP and medication numbers were observed in the contralateral eye at six weeks and six months (p<0.05) but not at 12 months. The contralateral eye success rates were 24% at six weeks and six months and 20.8% at 12 months. The contralateral eye was more likely to achieve success if the ipsilateral eye was successful at six weeks (odds ratio (95% confidence interval): 5.05 (1.89-13.48)), six months (16.1 (4.56-57.17)), and 12 months (5.94 (2.07-17.04)) (p<0.001 for all). First-time SLT results in statistically significant IOP and medication reductions in the contralateral eye at six weeks and six months. The contralateral eye was 5.05-16.1 times more likely to achieve success if the ipsilateral eye was successful within 12 months.

Clinical characteristics and outcomes of patients with candidemia during the COVID-19 pandemic: Insights from experience in the Omicron era

BackgroundIn Taiwan, COVID-19 outbreaks caused by the Omicron variant occurred in 2022. We investigated the incidence of candidemia during COVID-19 pandemic and the mortality of candidemia patients with COVID-19 in Taiwan. MethodsThe incidence of candidemia and fluconazole susceptibility of Candida species before (2015–2019) and during COVID-19 pandemic (2020–2023) at Kaohsiung Chang Gung Memorial Hospital were investigated. The associated factors with mortality in candidemia patients during COVID-19 pandemic were analyzed. Candidemia patients who had COVID-19 within the prior 90 days (case group, n = 34) were propensity-score matched for age, ICU admission, and abdominal surgery in a 1:4 ratio with candidemia patients without COVID-19 (control group, n = 136). ResultsAge (adjusted odds ratio [AOR] = 1.02, 95% CI: 1.01–1.03), ICU stay (AOR = 1.84, 95% CI: 1.29–2.62), higher Charlson comorbidity index (AOR = 1.08, 95% CI: 1.03–1.13), corticosteroid use (AOR = 1.50, 95% CI: 1.04–2.17) were associated with increased risk of mortality; abdominal surgery (AOR = 0.47, 95% CI: 0.29–0.74) and infected by Candida parapsilosis (AOR = 0.61, 95% CI: 0.38–0.98) were associated with decreased risk of mortality. After matching, there was no significant difference in mortality rates between the case and control groups. The incidence of candidemia increased from 196 to 278 patients/100,000 admissions during COVID-19 pandemic, while the causative species of candidemia and fluconazole susceptibility rates were similar. ConclusionWhile the incidence of candidemia increased during COVID-19 pandemic, there was no significant difference in mortality between candidemia patients with and without COVID-19 in the Omicron era.

Lower skeletal muscle density and airway structure on computed tomography in asthma

BackgroundLower skeletal muscle density may reflect muscle adiposity and metabolic dysregulation that potentially impair disease control and lung function independent of high body mass index (BMI) in patients with asthma. ObjectiveTo investigate whether the lower density of pectoralis muscles (PMs) and erector spinae muscles (ESMs) on chest computed tomography was associated with airway structural changes in patients with asthma. MethodsConsecutive patients with asthma and healthy controls undergoing chest computed tomography were retrospectively analyzed. The ESM and PM density, areas of subcutaneous adipose tissue near the PM and epicardial adipose tissue, wall area percent of the airways, and airway fractal dimension (AFD) were quantified on computed tomography. ResultsThe study included 179 patients with asthma (52% women) and 88 controls (47% women). All the controls were 60 years old or younger. The PM and ESM density in female patients with asthma who were 60 years old or younger were significantly lower than those in controls after adjustment for BMI. In female patients with asthma at all ages, lower PM and ESM density (but not subcutaneous or epicardial adipose tissue area) was associated with greater wall area percent of the airways and lower AFD after adjusting for age, height, BMI, smoking status, blood eosinophil count, and oral corticosteroid use. The only association between ESM density and AFD was found in male patients with asthma. ConclusionLower skeletal muscle density may be associated with airway wall thickening and less complexity of the airway luminal tree in female patients with asthma.

Application of Drug Repurposing Approach for Therapeutic Intervention of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract (GIT) characterized by chronic relapsing intestinal inflammation, abdominal pain, cramping, loss of appetite, fatigue, diarrhoea, and weight loss. Although the etiology of IBD remains unclear, it is believed to be an interaction between genes, and environmental factors, such as an imbalance of the intestinal microbiota, changing food habits, an ultra-hygiene environment, and an inappropriate immune system. The development of novel effective therapies is stymied by a lack of understanding of the aetiology of IBD. The current therapy involves the use of aminosalicylates, immunosuppressants, and corticosteroids that can effectively manage symptoms, induce and sustain remission, prevent complications, modify the course of the disease, provide diverse treatment options, showcase advancements in biologic therapies, and enhance the overall quality of life. However, the efficacy of current therapy is overshadowed by a plethora of adverse effects, such as loss of weight, mood swings, skin issues, loss of bone density, higher vulnerability to infections, and elevated blood pressure. Biologicals, like anti-tumour necrosis factor agents, can stimulate an autoimmune response in certain individuals that may diminish the effectiveness of the medication over time, necessitating a switch to alternative treatments. The response of IBD patients to current drug therapy is quite varied, which can lead to disease flares that underlines the urgent need to explore alternative treatment option to address the unmet need of developing new treatment strategies for IBD with high efficacy and fewer adverse effects. Drug repurposing is a novel strategy where existing drugs that have already been validated safe in patients for the management of certain diseases are redeployed to treat other, unindicated diseases. The present narrative review focuses on potential drug candidates that could be repurposed for the management of IBD using on-target and off-target strategies. It covers their preclinical, clinical assessment, mechanism of action, and safety profiles, and forecasts their appropriateness in the management of IBD. The review presents useful insights into the most promising candidates for repurposing, like anti-inflammatory and anti-apoptotic troxerutin, which has been found to improve the DSS-induced colitis in rats, an antiosteoarthritic drug diacetylrhein that has been found to have remarkable ameliorating effects on DSS-induced colitis via anti-oxidant and anti- inflammatory properties and by influencing both apoptosis and pyroptosis. Topiramate, an antiepileptic and anticonvulsant drug, has remarkably decreased overall pathophysiological and histopathological events in the experimental model of IBD in rodents by its cytokine inhibitory action.

Long-Term Clinical and Sustained REMIssion in Severe Eosinophilic Asthma Treated With Mepolizumab: The REMI-M Study

Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. While mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission. To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months. The REMI-M is a retrospective, real-world, multicenter study that analyzed 303 severe eosinophilic asthma patients who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroids (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period. Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months, based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% to 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastro-esophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent. This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics.

Clinical and radiological effects of Bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy

PurposeThe purpose of this multicenter retrospective study was to analyze the clinical and radiological effects of bevacizumab (BV) on radionecrosis (RN) that developed after stereotactic radiotherapy (SRT) for brain metastasis.MethodsForty patients with SRT related symptomatic brain RN treated in 10 radiation oncology centers were analyzed. The clinical response to BV treatment was categorized as follows: complete (no additional treatment required), partial (requiring either steroids or repeat BV), and unresponsive (requiring surgery). The radiological features of brain RN were analyzed in 10 patients whose serial MRI scans were available after corticosteroid and BV treatments.ResultsBV was used as a first line treatment in 11 (27.5%) and as a second line treatment in 29 (72.5%) of patients. The neurological symptoms regressed in 77.5% of patients after treatment with BV (45% complete response, 32.5% partial response). The median edema volume increased from 75.9 cc (range: 5.9-125.8 cc) at RN to 113.65 cc (range: 1.5-382.1 cc) after use of corticosteroids, representing a rate of 39.8% increase (p = 0.074). However, after BV treatment the median volume of edema decreased to 19.5 cc (range: 0-163.3 cc) which represents a difference of 62.2% (p = 0.041) from RN.ConclusionThe use of BV caused clinical response rate of 77.5% and a good radiological response in corticosteroid unresponsive patients. The role of BV should be further investigated in prospective studies.

A rare clinical course of seronegative of diffuse alveolar hemorrhage coexisting with extra-capillary glomerular

Some disorders can cause concomitant kidney dysfunction with lung involvement. The diagnosis of diffuse alveolar hemorrhage (DAH) is considered in patients who develop progressive dyspnea with alveolar opacities on chest imaging and acute renal failure with proteinuria and hematuria occurs due to rapidly progressive glomerulonephritis (RPGN). These syndromes are caused by variable disorders the most frequent are ANCA associated vascularitis or goodpasture syndrome. DAH diagnosed by the presence of blood on bronchoscopic alveolar lavage, and RPGN by the presence of specific glomerular lesions on the renal biospy. Treatment should target the underlying disorder. Here, we describe in detail the clinical manifestations, diagnostic approach, and treatment of DHA in a 39-year-old male who presented an alveolar hemorrhage, with acute renal failure. Treatment involved the use of high-dose corticosteroids to suppress the autoimmune response. Finally, we discuss the striking response to corticosteroid treatment and emphasize the importance of early initiation of treatment.

Dupilumab improved objective and patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and complete nasal obstruction

Aim: The impact of complete bilateral nasal obstruction [nasal polyp score (NPS) = 8/8] on treatment outcomes in chronic rhinosinusitis with nasal polyps (CRSwNP) is unclear. This post hoc analysis assessed disease burden and dupilumab efficacy in patients with severe CRSwNP and baseline NPS = 8 in SINUS-24/-52 (NCT02912468/NCT02898454). Methods: Efficacy outcomes assessed: NPS, peak nasal inspiratory flow (PNIF), Lund-Mackay computed tomography (LMK-CT), nasal congestion/obstruction (NC), loss of smell (LoS), rhinosinusitis visual analog scale (rhino-VAS), University of Pennsylvania Smell Identification Test (UPSIT), 22-item Sinonasal Outcome Test (SNOT-22) in patients receiving dupilumab 300 mg or placebo every 2 weeks. Responder analyses evaluated clinically meaningful improvements [≥ 1 (NPS, NC, LoS); ≥ 5 (LMK-CT); ≥ 8 (UPSIT); ≥ 8.9 (SNOT-22); ≥ 20 L/min (PNIF)]. Results: Ninety-eight patients were included [59% prior NP surgery, 84% systemic corticosteroids (SCS) use in the previous 2 years, 60% coexisting asthma, 91% anosmic, 97% impaired nasal airflow]. Least squares (LS) mean differences [dupilumab vs. placebo (95% CI)] in change from baseline at week (W) 24: NPS, −2.04 (−2.67, −1.40); PNIF, 65.9 (39.4, 92.4) L/min; LMK-CT, −4.97 (−6.50, −3.44); NC, −1.30 (−1.72, −0.89); LoS, −0.96 (−1.39, −0.54); Rhino-VAS, −3.37 (−4.67, −2.07); UPSIT, 8.55 (4.91, 12.20); SNOT-22, −25.3 (−34.1, −16.4) (all P &lt; 0.0001). For all outcomes, significantly greater proportions of dupilumab vs. placebo patients achieved clinically meaningful improvements at W24. Fewer dupilumab vs. placebo patients required SCS and/or surgery through W24 (11.8% vs. 36.7%; P = 0.0005). Efficacy outcomes were similar at W52 (SINUS-52; n = 39) with P values vs. placebo of &lt; 0.0001 for NPS and NC; 0.0002 for LMK-CT; 0.0031 for LoS; 0.0014 for rhino-VAS; 0.0013 for UPSIT; 0.0012 for SNOT-22. Conclusions: In patients with CRSwNP with complete bilateral nasal obstruction, dupilumab treatment resulted in clinically significant improvements in NPS, LMK-CT, PNIF, symptoms, and health-related quality of life.

Cytoprotective Effect of Growth Factors Derived From Platelets on Corticosteroid-Treated Primary Anterior Cruciate Ligament-Derived Stromal Cells and Chondrocytes.

Background The use of corticosteroids, such as methylprednisolone, for pain management is a common clinical practice. However, it is well known that corticosteroids induce toxicity in anterior cruciate ligament (ACL)-derived stromal cells and chondrocytes. Growth factors from platelets have anti-inflammatory effects that can potentially limit the cytotoxic effects of corticosteroids. In this study, we explored the role of growth factors obtained from the OssinextTM kit (commercially available Wockhardt growth factor concentrate (GFC) kit) in recovering methylprednisolone-induced cell damage. Methodology Primary ACL-derived stromal cells and chondrocytes were isolated from human ligament tissue and articular cartilage, respectively, and characterized by immunophenotyping, gene expression analysis, and immunostaining. GFC obtained from OssinextTM kit was used for the experiments. The ACL-derived stromal cells and chondrocytes were treated with methylprednisolone, alone or in combination with GFC. Cell viability was measured by the neutral red uptake assay. Changes in cell morphology and collagen pattern were observed microscopically by H&E staining and immunostaining, respectively. Cell proliferation was assessed by cell migration assay, and the cell ultra-structure was analyzed using transmission electron microscopy. Results Methylprednisolone was found to induce cytotoxicity, altered cell morphology, reduced cell proliferation, and organelle damage in both ACL-derived stromal cells and chondrocytes. GFC obtained from the OssinextTM kit was able to restore cell viability and reverse the cell structure damages induced by methylprednisolone. GFC was found to recover and protect the cells, both when used in combination with steroids and when used after the steroid treatment. Conclusions The results indicate that GFC may be clinically beneficial when used in combination with steroids to mitigate their adverse effects.

Efficacy and safety of risankizumab by baseline corticosteroid use and achievement of corticosteroid-free clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease.

Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD). To evaluate the corticosteroid-sparing effect of risankizumab in CD. During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent. At week 0 of maintenance, a mandatory corticosteroid taper was started. This post hoc analysis evaluated corticosteroid-free clinical and endoscopic outcomes at week 52 of maintenance; safety was also assessed. Of 889 patients randomised to induction with risankizumab 600 mg or placebo, 285 (32.1%) were taking baseline concomitant corticosteroids. Week 12 clinical remission and endoscopic response rates were greater for risankizumab 600 mg versus placebo, regardless of concomitant corticosteroid use. At week 52, 66.7%, 50.0% and 41.2% of patients taking risankizumab 180 mg, risankizumab 360 mg and (withdrawal) placebo, respectively, discontinued corticosteroids. Week 52 corticosteroid-free clinical remission per stool frequency/abdominal pain score (risankizumab 180 mg [42.7%] or 360 mg [49.8%]; [withdrawal] placebo [39.0%]), corticosteroid-free clinical remission per Crohn's Disease Activity Index (risankizumab 180 mg [51.0%] or 360 mg [49.5%]; [withdrawal] placebo [40.2%]), and corticosteroid-free endoscopic response (risankizumab 180 mg [44.6%] or 360 mg [44.7%]; [withdrawal] placebo [20.7%]) rates were greater for risankizumab than placebo. Adverse event rates were generally similar,regardless of baseline corticosteroid use. Efficacy of risankizumab 600 mg induction therapy was independent of concomitant corticosteroid use. Risankizumab 180 and 360 mg maintenance therapy yielded high rates of corticosteroid-free clinical and endoscopic outcomes at week 52.

Risk Factors for Pulmonary Mycosis in Immunocompromised Patients in Surakarta, Indonesia

&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Recent evidence shows that there is an increase in the incidence of pulmonary mycosis globally. In clinical settings, pulmonary mycosis is commonly misdiagnosed as pulmonary tuberculosis (PTB). Identifying risk factors can ease the diagnosis of pulmonary mycosis. This study aimed to determine the risk factors for pulmonary mycosis in immunocompromised patients in Surakarta.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was an analytic observational study with a retrospective cohort study method. This study used purposive sampling technique on 218 medical records of immunocompromised patients during January 2019–September 2022 at a referral hospital in Surakarta. The correlation of sociodemographic, health status, health behavior, history of diseases, medications, and transplantations with the incidence of pulmonary mycosis was analyzed using Chi-Square test or Fisher’s exact test as its alternative.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There was a significant correlation between educational level (p=0.018), nutritional status (p=0.001), smoking habit (p=0.000), history of corticosteroid use (p=0.031), history of antibiotic use (p=0.006), history of chemotherapy (p=0.003), history of PTB (p=0.047), and history of chronic obstructive pulmonary disease (COPD) (p=0.001) with the incidence of pulmonary mycosis. Meanwhile, there was no significant correlation between occupation (p=0.057), neutrophil level (p=1.000), history of human immunodeficiency virus (HIV) infection (p=1.000), history of diabetes mellitus (DM) (p=0.070), and history of organ transplantation (p=1.000) with the incidence of pulmonary mycosis.&lt;/p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Low educational level, malnutrition, smoking habit, history of pulmonary diseases, and medications are the risk factors for pulmonary mycosis in immunocompromised patients in Surakarta. It is important to identify these risk factors when examining patients with respiratory disorder symptoms.

The Natural History of Crohn's Disease Leading to Intestinal Failure: A Longitudinal Cohort Study from 1973 to 2018.

The natural history of Crohn's disease leading to intestinal failure is not well characterised. This study aims to describe the clinical course of Crohn's disease preceding intestinal failure and compare disease course and burden between Crohn's disease patients with and without intestinal failure. Patients with Crohn's disease complicated by intestinal failure from Rigshospitalet, Copenhagen (n=182) and a nationwide Danish Crohn's disease cohort without intestinal failure (n=22,845) were included. Using nationwide registries in Denmark, disease course was determined from hospitalisations, surgeries and outpatient medications, and disease burden was determined from employment and mortality data. The 10-year cumulative incidence of intestinal failure following Crohn's disease diagnosis declined from 2.7% prior to 1980 to 0.2% after 2000. Compared to Crohn's disease patients without intestinal failure, those with intestinal failure experienced significantly longer duration of severe disease (50 vs. 19 years per 100 patient-years, p<0.01), secondary to greater corticosteroid use (71% vs. 60%, p=0.02), inpatient contacts (98% vs. 55%, p<0.01), and abdominal surgeries (99% vs. 48%, p<0.01). However, exposure to biologics was not different between the two groups (20.4% vs. 21%, p=0.95), and duration on biologics was shorter in Crohn's disease patients with intestinal failure (2,068 vs. 4,126 days per 100 patient-years, p=0.02). Standard mortality ratio in Crohn's disease patients with intestinal failure was 3.66 [97.5% CI 2.79,4.72]. Patients with Crohn's disease complicated by intestinal failure experienced a more persistently severe preceding course of Crohn's disease but were not more likely to be treated with biological therapy.