Systemic Corticosteroids Research Articles

Neoadjuvant adebrelimab plus dalpiciclib in HPV-negative locally advanced head and neck squamous cell carcinoma: A phase II clinical trial.

TPS6129 Background: The efficacy and safety of neoadjuvant immunotherapy (NAI) for treating resectable locally advanced head and neck squamous cell carcinoma (LAHNSCC) remain uncertain, and the comprehensive protocol of NAI needs further explored. The tumor suppressor gene CDKN2A plays a pivotal role in cell cycle regulation by modulating cyclin-dependent kinase (CDK) activity. Mutations in CDKN2A lead to continuous activation of CDK4/6, resulting in uncontrolled cell proliferation and tumor growth. Approximately 35.7% of HNSCC patients exhibit CDKN2A mutations, with the incidence rising to 58% among HPV-negative LAHNSCC patients. Studies have shown that combining immunotherapy with a CDK4/6 inhibitor produces a synergistic anti-tumor effect. This study aims to assess the efficacy and safety of combining anti-PD-L1 (adebrelimab) with a CDK4/6 inhibitor (dalpiciclib) as NAI in resectable LAHNSCC patients. Methods: This open-label, single-arm, prospective phase II trial will enroll LAHNSCC patients eligible for surgery. Inclusion criteria include: being 18 to 75 years old at study entry; pathologically confirmed HPV-negative HNSCC (oral, laryngeal, hypopharyngeal, and HPV-negative oropharyngeal carcinoma), determined via p16 immunohistochemistry or HPV DNA tests; with CDKN2A mutation; resectable LAHNSCC, staged III-IVB according to the UICC/AJCC 8th edition TNM system; an ECOG Performance Status score of 0 or 1; no prior relevant anti-tumor treatments; intent for curative treatment; and adequate organ function. Key exclusion criteria are active autoimmune diseases, use of immunosuppressive drugs, or systemic corticosteroids. Eligible patients receive 3 cycles of adebrelimab (1200 mg intravenously every 3 weeks, Day 1, 22 and 43) and 2 cycles of dalpiciclib (150 mg, po, every 4 weeks, day 1-21 and 29-49) before surgery. Dose adjustments are allowed based on toxicity. Surgery will follow 2-4 weeks post-NAI, with subsequent adjuvant radiotherapy or chemoradiotherapy based on risk factors after surgery. The primary endpoints are 1-year disease-free survival (defined as the time from surgical resection to local recurrence) and major pathological response (MPR, defined as ≤10% residual viable tumor cells), with secondary endpoints focusing on safety and predictive biomarkers. Clinical trial information: NCT06199271 .

Continuous glucose monitoring and rates of hyperglycemia during chemotherapy for early-stage breast cancer.

e24134 Background: Diabetes (DM) and hyperglycemia (HG) during chemotherapy increase the risk of treatment-related toxicities. The prevalence of HG and daily patterns of HG over the course of chemotherapy in patients with early-stage breast cancer (ESBC) are currently unknown. Methods: We conducted a prospective single-arm pilot study of continuous glucose monitoring in patients with ESBC receiving chemotherapy from 12/2020 – 2/2022. Eligibility criteria included: diagnosis of Stage I-III BC, age ≥18, and planned chemotherapy with concurrent corticosteroid supportive care use. Patients were excluded if they were receiving other systemic corticosteroids or insulin. Patients wore FreeStyle Libre Pro continuous glucose monitoring sensors from the time of chemotherapy initiation (± 7 days) through completion. The sensors detected interstitial glucose levels every 15 minutes and were reapplied by the study team every 2-3 weeks. Primary endpoints were: (1) prevalence of HG, defined as number of patients with ≥1 glucose reading ≥140 mg/dL and (2) among those who developed HG, the proportion of time spent hyperglycemic, defined as number of readings ≥140 mg/dL divided by total number of readings. Key secondary endpoints included prevalence of prediabetes (pre-DM) and diabetes (DM) at baseline and changes in A1c from baseline to weeks 12 and 24. The analysis was stratified by baseline A1c (euglycemia [A1c < 5.7%], pre-DM [A1c 5.7%-6.4%], or DM [A1c ≥6.5% and clinical diagnosis of DM prior to study enrollment]). Results: Among 20 evaluable patients, the median age at baseline was 59 (range 34-78) and median body mass index (BMI) was 29.5 kg/m2 (range 19.5-41.6). The most common chemotherapy regimens included docetaxel/cyclophosphamide (25%), weekly paclitaxel ± trastuzumab (20%), paclitaxel followed by doxorubicin/cyclophosphamide (15%), docetaxel/carboplatin/trastuzumab/pertuzumab (15%), and cyclophosphamide/methotrexate/fluorouracil (15%). All 20 patients developed HG. Of 124,165 total readings, 17% were ≥140 mg/dL and mean glucose was 112.7 mg/dL. At baseline, n = 10 were euglycemic, n = 7 had pre-DM, and n = 3 had DM. By cohort, the proportion of time spent hyperglycemic was 3.9% (euglycemia group), 10% (pre-DM group), and 73.3% (DM group) (p < .0001). Mean glucose values were 95.5 mg/dL (euglycemia group), 104.5 mg/dL (pre-DM group), and 183.0 mg/dL (DM group) (p < .0001). Change in mean A1c from baseline to weeks 12 and 24 varied significantly across groups. Conclusions: Among patients receiving chemotherapy for ESBC, we found evidence of HG in all patients, and the proportion of time spent hyperglycemic during chemotherapy varied significantly by baseline A1c. Further interventions should evaluate the benefits of improved glucose control among patients with baseline A1c > 5.7%. Clinical trial information: NCT04473378 .

Prevalence of chronic rhinosinusitis without/with nasal polyps according to severity in Spain.

The worldwide prevalence range of chronic rhinosinusitis (CRS) is 5-12%; from this, 20 % have nasal polyps. Due to the little epidemiological data about CRS in the Spanish population, this study analyses the prevalence and severity of CRS with (CRSwNP) or without (CRSsNP) nasal polyps, and their connection with other coexisting type 2 inflammatory diseases in Spain. This is a retrospective, large-scale, nationwide, epidemiological study based on the electronic medical records from the BIG-PAC® database. Patients diagnosed of CRSsNP and CRSwNP were identified using specific disease codes. The severe form of the disease was defined as patients who received at least a long course of antibiotics in CRSsNP or ≥2 short courses of systemic corticosteroids in CRSwNP in ≤12 months during the last 2 years, and/or had previous sinus surgery. Physician diagnosed prevalence, sociodemographic and clinical characteristics, and disease severity were assessed. Out of a cohort of 1,012,257 patients (≤18 years old), 42,863 and 7,550 patients with diagnosed CRSsNP and CRSwNP, respectively, were analysed. The overall prevalence of diagnosed CRS was 5.1%, being 4.3% and 0.8% for CRSsNP and CRSwNP, respectively. Patients with CRSwNP and severe forms of the disease were older and had higher levels of type 2 inflammatory biomarkers than CRSsNP patients and non-severe disease. Although CRSsNP was more prevalent than CRSwNP, the severe forms of CRS were more frequent in patients with CRSwNP. In addition, CRSwNP patients had a higher incidence of coexisting type 2 inflammatory diseases.

Binary oncolytic adenovirus in combination with HER2-specific autologous CAR VST for treatment of advanced HER2-positive solid tumors (VISTA).

TPS2679 Background: Urgent therapies are needed for patients with refractory Human Epidermal Growth Factor Receptor 2 (HER2) positive solid malignancies. Our group has previously shown potent antitumor effect of a binary oncolytic/helper-dependent adenovirus (CAdVEC) with dual expression of IL-12 and PD-L1 blocker. Initial preclinical and clinical studies with direct tumor injection of CAdVEC has shown it to be safe and result in increased infiltration of CD8 T cells into the tumor microenvironment, with antitumor effect on locoregional and distant metastatic sites.1 Based on these results, we describe an ongoing study with addition of HER2-specific autologous chimeric antigen receptor (CAR)-T cell therapy to CAdVEC. Methods: This is a single arm, dose escalation phase I clinical trial guided by Bayesian Optimal Interval Design (BOIN) for patients with advanced HER2 positive solid tumors. Patients who are deemed unsuitable for curative treatments and progressed after at least one standard first line therapy are eligible. HER2 positivity is determined by IHC and defined as ≥2+. Patients are required to have at least one tumor site appropriate for intratumor injection and radiographically measurable disease per RECIST v1.1. Patients with autoimmune disease requiring systemic corticosteroids greater than 10mg/day and those with active/untreated CNS metastasis are excluded. Patients will receive increasing doses of CAdVEC intratumor injection alone (first two dose levels) or in combination with HER2 specific autologous CAR-T cells (dose levels 3-7). A total of 45 patients are planned. The primary endpoint of the study is to evaluate safety and maximum tolerated dose as assessed by incidence of dose limiting toxicities (DLT) of CAdVEC intratumor injection in combination with HER2-specific autologous CAR T cells. Secondary endpoints include anti-tumor activity of the combination measured by overall response rate (ORR), disease control rate (DCR), median progression free survival (PFS) and median overall survival (OS). Exploratory endpoints include assessing the immunogenicity of combination therapy by determining the impact of treatment on cellular and humoral immunity, as well as assessing long-term persistence and functional status of HER2 CAR T-cells. Correlative analysis of levels of adenovirus antibodies with clinical outcomes and immunological findings are also planned. This study is currently enrolling. 1. Wang D, Porter CE, Lim B, et al: Science Advances 9, 2023. Clinical trial information: NCT03740256 .

Efficacy and toxicity of BRAF targeted therapy in elderly patients with melanoma.

e23270 Background: Melanoma is the most lethal form of skin cancer which have seen drastic improvement in patient survival over the last decade. BRAF is the most common driver mutation in melanoma, seen in ≈50% of all patients (≈30% of patients > 65). The use of BRAF & MEK inhibitors yields high response rates, though it is limited by toxicity and development of acquired resistance. Acknowledging these limitations, we aimed at assessing the efficacy and toxicity of these agents in melanoma patients > 65. Methods: We identified electronic medical records of all melanoma patients > 65 that were treated with BRAF & MEK inhibitors at our institution over the years 2017-2023. Data was retrospectively collected including demographics, disease characteristics, treatment given, response patterns and toxicity. Results: 106 patients were identified. The median age was 71 (65-89), 55% were males. The median follow up was 28.9 months. 32 (30%) patients were treated at first line, 58 (55%) at second line and 16 (15%) at third line. 88 (83%) evaluable patients received treatment for unresectable/metastatic disease of which 84% had an objective response (60% partial response, 24% complete response). Response rate (RR) was 82%, 85% and 87% for first, second and third line respectively. RR was 86% for patients with an increased serum lactate dehydrogenase. 33% of patients had active central nervous system (CNS) metastases at treatment initiation, for whom the systemic RR was 80% and the CNS RR was 39%. The median progression free survival (PFS) was 7.9 months, with a PFS of 6, 8.3 and 13.4 months for first, second and third line respectively. The median PFS was 5.7 months for patients with active CNS disease. The median overall survival (OS) from treatment initiation was 15.7 months (12.5, 14.5, 31.9 for first, second & third line respectively). The median OS for patients with CNS disease was 9.8 months. 16 patients were treated in the adjuvant setting, of which 6 (37%) finished treatment as planned, 3 stopped due to disease progression (19%) and 6 stopped due to toxicity (37%). 88% of patients experienced adverse events (AEs) of any grade, with 27% having grade 3-4 toxicity. There were no grade 5 toxicities reported. 36% of patients experienced one AE, while 52% experienced two or more. 21% of patients stopped treatment due to toxicity, 28% needed a dose reduction and 20% changed to different BRAF/MEK inhibitors. 10% of patients needed systemic corticosteroids to treat AEs. The most common toxicities seen were fever (30%), fatigue (30%), skin rash (22%), elevated liver function tests (20%), arthralgia/myalgia (15%), nausea (14%) and diarrhea (11%). 7% had decrease in cardiac ejection fraction with one grade 3 leading to treatment discontinuation. Conclusions: Treatment with BRAF & MEK inhibitors is challenging in older patients, with a high prevalence of toxicity leading to treatment modifications and discontinuation. Efficacy seems to be the same as in the general population.

HPR131 The Risk of Osteoporotic Fractures in Elderly Asthmatic Patients According to Prescribing Patterns of Systemic Corticosteroid in South Korea

HPR131 The Risk of Osteoporotic Fractures in Elderly Asthmatic Patients According to Prescribing Patterns of Systemic Corticosteroid in South Korea

Impact of immune-related adverse events (irAE) onset on disease response and survival in patients (pts) with head-neck cancer treated with immune check point inhibitors (ICI).

6028 Background: ICI or combination chemo-immunotherapy are the mainstay of therapy for metastatic head-neck squamous cell carcinoma (mHNSCC) due to durable responses in certain pts. irAEs have emerged as a new challenge in the management of these pts. Some studies suggest a positive correlation between irAE onset and ICI efficacy in other cancers, however, whether such an association exists in HNSCC remains incompletely explored. Methods: We performed a retrospective, single-center cohort study of pts ≥ 18 years of age, with histologically confirmed mHNSCC who received ≥ 1 dose of ICIs at the University of Virginia Comprehensive Cancer Center, VA, USA between 2013-2022. Demographics, disease and treatment characteristics, and clinical outcomes related to irAEs and ICI re-challenge were analyzed. IrAEs were graded using CTCAE v4.0 criteria by chart review. Independent sample t-tests and chi-square analyses were used for univariate comparisons. Median PFS and OS from ICI therapy initiation were estimated using Kaplan-Meier methodology and censored at date of last follow up. P-values <0.05 were considered statistically significant. Results: Of 1979 pts who received ICI, 110 had mHNSCC (72.7% male; 84.5% White) with a median age of 62.4 years. ICI type included pembrolizumab or nivolumab in 109 pts, and nivolumab/ipilimumab in one pt. 53 (48%) pts experienced any grade irAE and 12 pts (11%) experienced >1 irAE. The most common irAEs were hypothyroidism (30.4%), dermatitis (14.3%), and hepatitis (10.7%). CTCAE ≥G3 irAEs were seen in 22.6% pts (n=12). These included hepatitis (n=3), colitis (n=3), hypothyroidism (n=1), arthritis (n=1), pneumonitis (n=1), adrenal insufficiency (n=1), vasculitis (n=1), and cardiomyopathy (n=1). Men (62% vs 37%, p= 0.015) and pts with prior radiation therapy (83% vs 17%, p=0.047) were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% pts with irAEs. Topical/supportive therapy was required in 52.8%, and 35.8% required systemic corticosteroids, with more than half experiencing complete irAE resolution. A statistically significant association was observed between irAE onset and objective response rate (68% vs 39%, p= 0.009). 12 pts underwent ICI re-challenge, resulting in partial response in 3 (25%), stable disease in 4 (33.3%) and progressive disease in 3 (25%) pts. There was no statistically significant difference in PFS (4.9 vs 9.7 months, p = 0.731) or OS (30.5 vs 21 months, p = 0.159) in irAE vs non-irAE groups, respectively. Conclusions: irAEs onset was associated with improved best response to ICI therapy in mHNSCC. Although OS was numerically superior in the irAE group, it did not meet statistical significance. ICI re-challenge is feasible in select pts, however further studies are needed to evaluate long term benefit of ICI re-challenge.

Safety of pembrolizumab as adjuvant therapy in a pooled analysis of phase 3 clinical trials of melanoma, non–small cell lung cancer, and renal cell carcinoma

BackgroundThe safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials. MethodsPatients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non–small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment. ResultsData were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0–18.9) with pembrolizumab and 11.2 months (0.0–18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3–5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3–5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3–5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3–5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively. ConclusionsAdjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease.

Impact of comorbidities on EQ-5D quality-of-life index in severe asthma

BackgroundSevere asthma pathology encompasses a wide range of pulmonary and extra-pulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health related quality of life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities. ObjectiveTo examine the impact of pulmonary and extra-pulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centres. MethodsPatients characteristics at baseline assessment within the UK Severe Asthma Registry were compared by EQ-5D-5L utility index quartile. Patients with follow-up review data were stratified by change in EQ-5D-5L utility index from baseline to follow-up, and characteristics similarly examined. ResultsPatients in the quartiles with worst dysutility at baseline were observed to exhibit more treatable traits and in particular extra-pulmonary traits associated with cumulative systemic corticosteroids, including obesity, anxiety/depression, and osteoporosis. In those patients whose quality of life improved over follow-up, a reduction in exacerbations, uncontrolled symptoms and requirement for maintenance oral corticosteroids (OCS) was observed. ConclusionBoth pulmonary and extra-pulmonary treatable traits are important determinants of quality of life in severe asthma. Comorbidities associated with cumulative systemic corticosteroid exposure are particularly associated with worse quality of life, emphasising the importance of early identification and management of severe asthma before comorbidities develop.

Diagnosis, treatment, and long-term outcomes of pediatric pemphigus: a retrospective study at tertiary medical centers.

Pediatric pemphigus is a rare bullous disease that representsa diagnostic and therapeutic challenge; evidence on patients' response to various treatments and long-term surveillance data are lacking. We aimed to investigate pediatric pemphigus patients' characteristics, diagnosis, therapeutics, response, and long-term follow-up. This is a retrospective study of all pemphigus patients aged <18 years, diagnosed between 2000 and 2023, from three tertiary medical centers in Israel. The diagnosis was confirmed by positive immunofluorescence. Twelve pediatric pemphigus patients were included (mean age 10.7 ± 4.3 years, male:female ratio 1:1). Mean diagnostic delay was 11.1 ± 12.6 months (range 1.8-36 months). Most patients had pemphigus vulgaris with mucosal involvement (58.3%). First-line treatment for all patients included systemic corticosteroids (sCS), with a treatment duration (including tapering down) of 28 ± 18.4 months. Hospitalization did not yield better outcomes. Only three patients achieved sustained complete response with sCS treatment (25.0%), and the rest required additional therapeutics, most commonly rituximab. Rituximab showed a good safety profile and therapeutic response. Follow-up was recorded up to 18.1 years after diagnosis (mean: 5.6 years). Three of five patients with information available more than 5 years after the pemphigus diagnosis still exhibited disease symptoms. Pediatric pemphigus is associated with a significant diagnostic delay. While sCS can induce remission in most patients as a first-line treatment, long-term disease control requires additional immunomodulators. Long-term follow-up reveals a chronic yet mostly benign disease course in this population and advocates for the use of rituximab in pediatric pemphigus patients.

Evaluation of vitamin D deficiency and low bone mass in children with asthma in fars province: A case-control study.

Asthma is a chronic inflammatory pulmonary disease which affects 10%-20% of children and adolescents. Inhaled corticosteroids (ICS) is one of its most effective therapies. The effect of systemic corticosteroids on decreasing bone mineral density (BMD) was investigated and proved in children; however, the influence of ICSs on bone density has still remained unclear. This study evaluates the bone mineral density of children and adolescents with asthma in southern Iran and the associated factors, for example, amount of used inhaled steroid. This case-control study enrolled 41 children and adolescents (aged 8-18 years) with asthma and their age and gender-matched controls in 2019-2020. Serum Calcium, phosphate, vitamin D, and bone mineral density were measured. Their physical activity, sun exposure, and fracture history were evaluated subjectively. Lumbar BMD and BMD Z-score in patients showed no significant difference with controls (p = 0.23, p = 0.73). Also, it showed that there was no significant difference in biochemical studies, growth, and bone densitometry parameters between patients who used ICSs for less than 3 months/year corticosteroid therapy compared to those with equal or more than 3 months/year usage. Prevalence of vitamin D deficiency was 28% and 8% in the controls and patients, respectively (p = 0.005). The present study showed that 9.46% of children and adolescents with asthma had low bone mass for chronological age, and it is not significantly higher than normal population. Dosage of inhaled steroid did not associate with osteoporosis in these patients. Prevalence of vitamin D deficiency in patients was lower than normal population, probably due to receiving vitamin D in their routine follow-ups.

Paradoxical tuberculous reaction to anti-tnfα discontinuation: a complex case of miliary tuberculosis and macrophagic activation syndrome with hepatic manifestations

Tuberculosis reactivation during anti-TNF-alpha therapy paradoxically worsened following reconstitution of pathogen-specific immune responses after cessation of TNFα antagonist treatment and initiation of anti-bacillary therapy. We report the case of a 46-year-old woman who was prescribed a tumor necrosis factor blocker (anti-TNF) for a relapse of Behçet's disease. The patient developed pulmonary miliary tuberculosis following the reactivation of latent tuberculosis, despite a normal pre-therapeutic work-up. Discontinuation of anti-TNF and initiation of anti-bacillary drugs triggered a paradoxical tubercular reaction (PTR). The diagnosis of paradoxical reaction to anti-tuberculosis drugs was evoked by the clinical and biological deterioration and the appearance of miliary cerebral tuberculosis and cerebral venous thrombosis after a period of clinical improvement. Although this phenomenon has been documented, it represents a major challenge for clinicians. The peculiarity of this case lies in its association with a macrophagic activation syndrome (MAS) with hepatic involvement, retained on clinical-biological and histological criteria. The overlap between MAS and PTR makes it difficult to diagnose these two entities with certainty. The patient responded favorably to moderate-dose systemic corticosteroid therapy with progressive degression, and the reintroduction of anti-tuberculosis drugs.This work aims to highlight the importance of close monitoring of TB patients on anti-TNFα therapy for early diagnosis and management of complications to improve the prognosis of these complex patients.

Risk of death, major adverse cardiac events and relapse in patients with bullous pemphigoid treated with systemic or topical corticosteroids.

According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments. To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids. A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted. All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.28-1.58 (P < 0.001)]. This was consistent in time-stratified analysis (1- and 3-year mortality rates) and in analysis contrasting prednisone (equivalent) doses of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US patients with BP exposed to any dose of systemic corticosteroids vs. topical treatment was accompanied by increased risks for MACE (HR 1.33, 95% CI 1.08-1.64; P = 0.008) and infections (HR 1.33, 95% CI 1.15-1.54; P < 0.001). The risk of continued disease or relapse was decreased in patients treated with systemic vs. topical corticosteroids (HR 0.85, 95% CI 0.77-0.94; P = 0.002). Results regarding mortality and continued disease or relapse persisted in three sensitivity analyses. Potential limitations included the retrospective data collection, bias for treatment selection and miscoding. Pending validation in prospective studies, where feasible - and despite the heightened risk of relapse - topical corticosteroid treatment may be advantageous over systemic corticosteroid treatment owing to its significantly lower risk of death.

Treatments for Olfactory Dysfunction in COVID-19: A Systematic Review.

Introduction Olfactory dysfunction (OD) has emerged as a notable symptom among coronavirus disease 2019 (COVID-19) patients, with its prevalence varying among different populations. Recognizing the need to provide therapeutic solutions for these individuals, the present study seeks to comprehensively review the current evidence on potential underlying mechanisms and treatment modalities to manage OD in COVID-19 patients. Objective To review the recent evidence on treatments for OD in COVID-19. From the beginning of the study until August 2nd, 2023, we conducted a systematic search on four electronic databases, PubMed, Scopus, Embase, and Web of Science, to find relevant publications. Data Synthesis In the present study, 37 articles were selected for data extraction and included in the final review. The total number of patients was of 3,560 (2,098 female and 1,462 male subjects). The predominant disorders reported were hyposmia, anosmia, and parosmia. In most of the studies, the pre and postintervention assessments were the same, except for one study, in which the pre-intervention assessment of the disorder was through the SST, Sniffin' Sticks Test (SST), and the post-intervention assessment was through the Visual Analog Scale (VAS) and the 22-item Sinonasal Outcome Test (SNOT-22). The findings suggest olfactory training (OT), ivermectin, palmitoylethanolamide, luteolin, and systemic corticosteroids, in combination with topical corticosteroids, are potential therapies for COVID-19 patients with olfactory impairment. Conclusion Although the review suggested several medications for OD treatment, further research must delve into the specific impact of OT, a non-pharmacological modality, regarding the mitigation of OD. By continuing to investigate and refine these therapeutic approaches, we can better support COVID-19 patients and improve their quality of life while navigating the challenges posed by OD.

Association between human herpesvirus-6 encephalitis and antiviral prophylaxis after allogeneic hematopoietic stem cell transplantation in the letermovir era.

The impact of letermovir (LTV)-an anti-cytomegalovirus (CMV) drug-on human herpesvirus-6 (HHV-6) encephalitis is unclear. We hypothesized that LTV prophylaxis may increase the incidence of HHV-6 encephalitis by reducing anti-CMV therapies after allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the association between HHV-6 encephalitis and antiviral prophylaxis, 7985 adult patients from a nationwide registry who underwent their first HSCT between January 2019 and December 2021 were analyzed. The incidence of HHV-6 encephalitis on day 100 after HSCT was 3.6%; 11.5% for the broad-spectrum antiviral group (foscarnet, ganciclovir, or valganciclovir); 2.8% for the LTV group, and 3.8% for the other antiviral group (p < 0.001). These differences persisted when cord blood transplantation (CBT) was analyzed separately (14.1%, 5.9%, and 7.4%, p < 0.001). In the multivariate analysis, CBT (hazard ratio [HR]: 2.90), broad-spectrum antiviral prophylaxis (HR: 1.91), and grade II-IV acute graft-versus-host disease requiring systemic corticosteroids (HR: 2.42) were independent risk factors for encephalitis (all p < 0.001). The findings of this large modern database study indicate that broad-spectrum antiviral prophylaxis, rather than LTV prophylaxis, is paradoxically associated with HHV-6 encephalitis in the LTV era. This paradoxical finding needs to be further explored in future studies.

Clinical predictive factors and imaging biomarkers of treatment response to half dose PDT in patients with chronic central serous chorioretinopathy

PurposeTo determine the clinical and imaging biomarkers of the response to half-dose photodynamic therapy (HD-PDT) in patients with central serous chorioretinopathy (CSC) MethodsClinical records and baseline ophthalmic images of 67 chronic CSC patients who underwent HD-PDT were assessed. In addition to demographic data, optical coherence tomography (OCT), fluorescein angiography (FA) and fundus autofluorescence (FAF) images were analyzed for specific biomarkers. The patients were categorized to early responder and late responder based on the time needed for complete resolution of subretinal fluid after PDT (less than 1 month vs. more than 1 month). The baseline clinical and imaging biomarkers were compared between the two groups. ResultsSeventy-three eyes of 67 patients were included in the study. The mean response time to PDT was 1.63 ± 1.48 months with 82.2% (60/73) of eyes categorized as early responder. The mean response time to PDT in delayed-response group was 4.15±1.51 months. In multivariate analysis, delayed response to PDT was associated with lacking history of systemic corticosteroid consumption, lacking history of pretreatment with eplerenone or acetazolamide before PDT and presence of hyperreflective foci in baseline OCT images (all p values < 0.05). There was no association between final visual outcome and late response to PDT. ConclusionThe presence of inflammatory biomarkers such as hyperreflective foci in baseline OCT images might be indicative of resistance to PDT. Moreover, the effect of pretreatment with mineralocorticoid antagonist on the response to PDT in chronic CSC should be explored in future prospective studies.

Allergic bronchopulmonary aspergillosis in a lung transplant recipient treated with mepolizumab

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

Diagnosis and Treatment of Uveitis in Children: A Summary of the Latest Data from a 5-Year Literature Review (2018-2023).

Pediatric uveitis has a low incidence. It is very diverse in its presentation and is often the first sign of a severe systemic disease. The pediatric population poses a special therapeutic and diagnostic challenge due to the potentially adverse effects of therapeutic agents on the young body and difficult cooperation with the patient during the examination, as well as the increased risk of complications that can lead to severe disability. The most commonly diagnosed type of uveitis is non-infectious, with first-line therapy consisting of systemic corticosteroids followed by disease-modifying drugs (methotrexate (MTX), mycophenolate mofetil (MMF), and cyclosporin A (CsA)). In severe, refractory cases, biologic therapy is used. The authors reviewed the current literature on the etiology, diagnostic tools, and treatment of uveitis in the pediatric population covering the years 2018-2023, presenting current methods of modern diagnosis and treatment. The reason for writing this article was the need to update the knowledge on uveitis, driven by the increasing prevalence of autoimmune uveitis in the pediatric population. This trend presents significant challenges in diagnosing and treating the disease, as well as managing its complications. Correctly identifying the pathogenetic factor of uveitis can facilitate the diagnosis of the systemic disease underlying the ocular infection and enable the timely implementation of systemic treatment. Furthermore, the emergence of new diagnostic methods necessitates a revision and update of ophthalmic knowledge, essential for both ophthalmologists and other specialists involved in the treatment of uveitis.

Disseminated Intravascular Coagulation during a Course of Miliary Tuberculosis with Acute Respiratory Distress Syndrome

Abstract Miliary tuberculosis (TB) can occasionally lead to acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). In this case report, we present the case of an 18-year-old male who was diagnosed with miliary TB based on miliary shadows on X-ray and computed tomography of the chest, as well as positivity for mycobacterium TB in endotracheal aspirate by cartridge-based nucleic acid amplification. The patient’s hospital stay was complicated by ARDS and DIC, which was successfully managed with ventilatory support, administration of antitubercular treatment, systemic corticosteroids, and blood products.

#1150 Neutrophil rich infiltrate in immunotherapy induced acute interstitial nephritis

Abstract Background and Aims Acute interstitial nephritis (AIN) is a well-recognized cause of acute kidney injury (AKI) in patients treated with Immune checkpoint inhibitors (ICI). Kidney biopsy typically shows tubular interstitial infiltration with well-differentiated mononuclear cells with occasional granulomas and eosinophils. Neutrophil rich tubular interstitial infiltration is typically associated with pyelonephritis. We report a case series of neutrophil rich ICI induced AIN. Method After obtaining approval from the institutional review board, medical records of the nephrology service at a large cancer center were reviewed. Patients were included in the study if they underwent a kidney biopsy for the diagnosis of ICI associated AKI, the biopsy was consistent with atypical AIN with neutrophil rich infiltrate, there was no glomerular involvement, they exhibited no symptoms of pyelonephritis including but not limited to fever, nausea, vomiting, flank pain and dysuria and had a negative urine culture. Results Forty eight patients who had a biopsy proven ICI associated AIN were identified from the medical records. Four (8.3%) patients met the study criteria (Table 1). There were three males and one female. The mean age was 75.5 years. One patient had a history of pre-existing CKD stage 3. Mean number of ICI therapy cycles prior to the development of AIN was seven with two patients treated with pembrolizumab (2 and 14 cycles), one patient treated with nivolumab (1 cycle) and one patient treated with the combination of nivolumab and ipilimumab (2 cycles). All patients presented with asymptomatic rise in serum creatinine (sCr). Kidney biopsy showed neutrophil rich infiltrate and neutrophilic tubulitis in all patients. Neutrophilic casts were present in three biopsies. One patient had evidence of granulomatous inflammation. All patients had mild to moderate interstitial fibrosis. Three patients were initially treated with flat dose prednisone 60 mg daily and one was treated with weight adjusted dose of prednisone 1 mg/kg at 75 mg/day. Three patients had complete renal recovery (sCr &amp;lt; 0.5 mg/dl above baseline) after steroid taper. One patient developed a relapse but achieved partial recovery (sCr &amp;lt; 2x baseline) after the second taper. Two patients remain alive three and 12 months after the kidney biopsy. Two patients died due to the progression of cancer two and 10 months after the biopsy. Conclusion AIN with neutrophil rich infiltrate likely represents a subset of ICI induced AIN. In the absence of clinical signs of pyelonephritis and with evidence of negative urine cultures the treatment should be geared towards addressing inflammation with systemic corticosteroids which have been shown to be effective in management of ICU induced AIN. Avoidance of antibiotics in this setting would lead to better antibiotic stewardship.