Chronic Steroid Therapy Research Articles

Abstract CT286: TILVANCE-301, a phase 3 study of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab vs pembrolizumab alone in treatment-naive unresectable or metastatic melanoma

Abstract Introduction: Novel early-line therapies for advanced (unresectable or metastatic) melanoma are needed to improve the rate of deep and durable responses and increase the proportion of patients with long-term benefit. TILVANCE-301 will evaluate the efficacy and safety of lifileucel autologous TIL cell therapy plus pembrolizumab in patients with untreated advanced melanoma. Methods: TILVANCE-301 (NCT05727904) is a phase 3, multicenter, randomized, open-label, parallel group study that will randomize ~670 patients (1:1; Day 0) to Arm A: lifileucel plus pembrolizumab (Day 3: tumor tissue resection for TIL manufacturing; Day 5: pembrolizumab 200 mg; Day 26: pembrolizumab 400 mg; Day 28-29: cyclophosphamide 60 mg/kg; Day 28-32: fludarabine 25 mg/m2; Day 33: lifileucel; Day 34-37: ≤6 doses of high-dose IL-2; Week 10: pembrolizumab 400 mg Q6W) or Arm B: pembrolizumab alone (same pembrolizumab dosing as Arm A). Patients in Arm B with confirmed progressive disease verified by blinded independent review committee (BIRC) have the option to receive lifileucel monotherapy as immediate next treatment and may continue pembrolizumab until start of nonmyeloablative lymphodepletion. Eligible adults have histologically confirmed advanced melanoma, Eastern Cooperative Oncology Group performance status of 0-1, estimated life expectancy >6 months, ≥1 resectable lesion to generate lifileucel, and ≥1 remaining measurable lesion. Prior neoadjuvant or adjuvant treatment including immune checkpoint inhibitors may be allowed. Prior therapy for metastatic disease, symptomatic untreated brain metastases, organ allograft or prior cell therapy, uveal/ocular melanoma, and chronic systemic steroid therapy are not permitted. The dual primary efficacy endpoints are BIRC-assessed (RECIST v1.1) objective response rate (ORR) and progression-free survival (PFS). Key secondary efficacy endpoint is overall survival. Additional secondary efficacy endpoints include BIRC-assessed complete response (CR) rate, duration of response (DOR), and event-free survival (EFS); investigator-assessed ORR, PFS, CR rate, DOR, EFS, and PFS2; and safety as characterized by severity and seriousness of treatment-emergent adverse events and relationship to study drug. Exploratory endpoints include in vivo T-cell persistence (unique CDR3 sequences in peripheral blood mononuclear cell [PBMC] over time) and correlative biomarkers (eg, lifileucel phenotypic and functional characteristics; lifileucel, tumor, and PBMC gene expression profiles; tumor mutational landscape). The study will enroll globally, with initial sites in Europe, North America, and Australia. Trial registration: NCT05727904 Citation Format: Sajeve Thomas, Young Ki Hong, Yazan Samhouri, James Larkin, David J. Olson, Gino K. In, Victoria Atkinson, Philip Lammers, Andrew J. Furness, Juan Martin-Liberal, Patrick Terheyden, Andrew S. Poklepovic, Ryan H. Nguyen, Idit Peretz, Marcus Butler, Adnan Khattak, Lavinia Spain, E.M. Gaughan, Melissa Wilson, John W. Dubay, Anja Williams, Stephanie Goff, Gary C. Doolittle, Jason Chesney, Friedrich Graf Finckenstein, Jeffrey Chou, Xiao Wu, Giri Sulur, Wen Shi, John Haanen. TILVANCE-301, a phase 3 study of lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab vs pembrolizumab alone in treatment-naive unresectable or metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT286.

Vascular complications and outcomes following transcatheter aortic valve replacement in patients on chronic steroid therapy: a meta-analysis.

Chronic steroid (CS) therapy was reportedly linked to increased vascular complications following percutaneous coronary intervention. However, its association with vascular complications after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported. The authors aimed to compare the rate of vascular complications and outcomes between patients with and without CS use after TAVR. The authors conducted a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until 18th April 2022 for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions. Effect sizes were pooled using DerSimonian and Laird random-effects model as risk ratio (RR) with 95% CI. Five studies with 6136 patients undergoing TAVR were included in the analysis. The included studies were published between 2015 and 2022. The mean ages of patients in both study groups were similar, with the CS group averaging 80 years and the nonsteroid group averaging 82 years. Notably, a higher proportion of patients in the CS group were female (56%) compared to the nonsteroid group (54%). CS use was associated with a significantly higher risk of major vascular complications (12.5 vs. 6.7%, RR 2.32, 95% CI: 1.73-3.11, P <0.001), major bleeding (16.8 vs. 13.1%, RR 1.61, 95% CI: 1.27-2.05, P <0.001), and aortic annulus rupture (2.3 vs. 0.6%, RR 4.66, 95% CI: 1.67-13.01, P <0.001). There was no significant difference in terms of minor vascular complications (RR 1.43, 95% CI: 1.00-2.04, P =0.05), in-hospital mortality (2.3 vs. 1.4%, RR 1.86, 95% CI: 0.74-4.70, P =0.19), and 30-day mortality (2.9 vs. 3.1%, RR 1.14, 95% CI: 0.53-2.46, P =0.74) between both groups. Our study showed that CS therapy is associated with increased major vascular complications, major bleeding, and annulus rupture following TAVR. Further large multicenter studies or randomized controlled trials are warranted to validate these findings.

Preoperative Chronic Steroid Use is Associated with Increased Incidence of Postoperative Mortality and Limb Loss following Peripheral Arterial Bypass Surgery for Chronic Limb Threatening Ischemia

Steroids are a commonly prescribed medication in the United States and have been associated with poor surgical and treatment outcomes. The objective of this study is to assess the relationship between chronic steroid use and surgical outcomes of femoropopliteal and femoral-distal bypasses in patients suffering from chronic limb threatening ischemia (CLTI). All adult patients undergoing femoropopliteal and femoral-distal bypasses with single segment autologous vein with an indication of CLTI in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2012 and 2021 were stratified between chronic preoperative steroid use (Group I) and no preoperative use (Group II). Primary outcomes of the study included 30-day mortality, amputation, and combined outcome of mortality and/or limb loss. Secondary outcomes included specific bypass related, cardiovascular, respiratory and renal outcomes. A total of 8,324 patients (66.8% Male, 33.2% Females) underwent peripheral arterial bypass operations for the indication of chronic limb threatening ischemia. The median age was 68 years. Group I included 408 patients (4.9%) and Group II included 7,916 patients (95.1%). As compared to patients in Group II, those in Group I were more likely to be females (Group I: 42.2% vs. Group II: 32.8%), more likely to have co-existing COPD (Group I: 20.6% vs. Group II: 11.8%), less likely to be diabetic (Group I: 45.9% vs. Group II: 48%), less likely to be smokers (Group I: 30.6% vs. Group II: 45.4%) and more likely to be in ASA III or IV Classes (Group I: 98% vs. Group II: 96.5%) (all p<0.05). Primary outcomes were as follows: 30-day mortality (Group I: 3.3% vs. Group II: 1.7%), amputation (Group I: 5.9% vs. Group II: 2.8%), 30-day mortality and/or amputation (Group I: 9.1% vs. Group II: 4.5%) (all p<0.05). Among secondary outcomes, the following were found to be statistically significant: untreated loss of patency (Group I: 4.2% vs. Group II: 1.7%), significant bleeding (Group I: 26.2% Vs. Group II: 16.5%), wound infection/complication (Group I: 18.6% vs. Group II: 15%), and return to OR (Group I: 21.8% vs. Group II: 16.7%) (all p<0.05). As compared to patients with an indication of tissue loss (Rutherford's class V and VI), patients in Group I with an indication of rest pain (Rutherford's class IV) were more likely to experience 30-day mortality, major amputation and a composite of mortality and amputation. Risk adjusted analysis showed that chronic steroid use has a statistically significant effect on 30-day mortality (AOR 1.7, p=0.05), amputation (AOR 2.05, p<0.001), composite outcomes of mortality and amputation (AOR 1.959, p<0.001), untreated loss of patency (AOR 2.31, p=0.002), bleeding (AOR 1.33, p<0.011) and unplanned return to the OR (AOR 1.36, p=0.014). Chronic steroid use in patients undergoing femoropopliteal or femoral-distal bypass is associated with a higher risk of 30-day mortality, major amputation, readmission, bleeding, return to operating room, and untreated loss of patency. No significant difference in outcomes were appreciated in patients with chronic steroid use and with Rutherford class V or VI disease (tissue loss), suggesting that the effects of steroids may be less prominent in those with the most advanced peripheral arterial disease. These findings may aid physicians with risk stratification and preoperative discussions regarding open revascularization in patients receiving chronic steroid therapy. More studies including randomized trials are needed to guide perioperative management of steroids in this cohort.

Outcomes of initially nonoperative management of diverticulitis with abscess formation in immunosuppressed patients. DIPLICAB study COLLABORATIVE group.

Management of diverticulitis with abscess formation in immunosuppressed patients (IMS) remains unclear. The main objective of the study was to assess short- and long-term outcomes between IMS and immunocompetent patients (IC). The secondary aim was to identify risk factors for emergency surgery. A nationwide retrospective cohort study was performed at 29 Spanish referral centres between 2015-2019 including consecutive patients with first episode of diverticulitis classified as modified Hinchey Ib or II. IMS included immunosuppressive therapy, biologic therapy, malignant neoplasm with active chemotherapy and chronic steroid therapy. A multivariate analysis was performed to identify independent risk factors to emergency surgery in IMS. A total of 1395 patients were included; 118 IMS and 1277 IC. There were no significant differences in emergency surgery between IMS and IC (19.5% and 13.5%, p = 0.075) but IMS was associated with higher mortality (15.1% vs. 0.6%, p < 0.001). Similar recurrent episodes were found between IMS and IC (28% vs. 28.2%, p = 0.963). Following multivariate analysis, immunosuppressive treatment, p = 0.002; OR: 3.35 (1.57-7.15), free gas bubbles, p < 0.001; OR: 2.91 (2.01-4.21), Hinchey II, p = 0.002; OR: 1.88 (1.26-2.83), use of morphine, p < 0.001; OR: 3.08 (1.98-4.80), abscess size ≥5 cm, p = 0.001; OR: 1.97 (1.33-2.93) and leucocytosis at third day, p < 0.001; OR: 1.001 (1.001-1.002) were independently associated with emergency surgery in IMS. Nonoperative management in IMS has been shown to be safe with similar treatment failure than IC. IMS presented higher mortality in emergency surgery and similar rate of recurrent diverticulitis than IC. Identifying risk factors to emergency surgery may anticipate emergency surgery.

A phase 3 study (TILVANCE-301) to assess the efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte cell therapy, in combination with pembrolizumab compared with pembrolizumab alone in patients with untreated unresectable or metastatic melanoma.

TPS9607 Background: Most patients (pts) with advanced (unresectable or metastatic) melanoma receiving front-line immune checkpoint inhibitor (ICI) therapy progress within a year (Robert Lancet Oncol 2019; Larkin NEJM 2019; Tawbi NEJM 2022). Early-line therapies are needed to improve the rate of deep and durable responses and increase the proportion of pts with long-term benefit. Lifileucel demonstrated an ORR of 31.4% and median DOR not reached (median 36.5 mo follow-up) in pts with post-ICI advanced melanoma (Sarnaik SITC 2022). Earlier-line treatment with lifileucel plus pembrolizumab (pembro) in pts with ICI-naïve advanced melanoma demonstrated an ORR of 67%, including a CR rate of 25% (Iovance Press Release, April 5, 2022; O’Malley JITC 2021). TILVANCE-301 will evaluate the efficacy and safety of lifileucel plus pembro compared with pembro alone in pts with untreated advanced melanoma. Methods: TILVANCE-301 (NCT05727904) is a phase 3, multicenter, randomized, open-label, parallel group, treatment study that will randomize ~670 pts (1:1) to either Arm A: lifileucel plus pembro (study intervention includes tumor tissue resection, pembro, nonmyeloablative lymphodepletion [NMA-LD], lifileucel infusion, an abbreviated course of high-dose IL-2, and thereafter, continued pembro) or Arm B: pembro alone. Pts in Arm B who receive pembro and experience confirmed progressive disease verified by blinded independent review committee (BIRC) have the option to receive lifileucel as the immediate next line of treatment. Eligible adults have histologically confirmed advanced melanoma (Stage IIIC, IIID, or IV); ECOG PS of 0 or 1; estimated life expectancy &gt; 6 mo; ≥1 resectable lesion ~1.5 cm in diameter postresection to generate lifileucel and ≥1 measurable lesion (RECIST v1.1); and adequate hematologic parameters and organ function. Neoadjuvant or adjuvant treatment including ICI meeting protocol-specified criteria may be allowed. Exclusion criteria include prior therapy for metastatic disease; symptomatic untreated brain metastases; organ allograft or prior cell transfer therapy; uveal/ocular melanoma; chronic systemic steroid therapy; active systemic infections; cardiovascular, respiratory, or immune system illnesses; primary/acquired immunodeficiency; or other primary malignancy in the last 3 y. The dual primary efficacy endpoints are BIRC-assessed (RECIST v1.1) ORR and PFS. Key secondary efficacy endpoint is OS. Additional secondary efficacy endpoints include BIRC-assessed CR rate, DOR, and EFS; investigator-assessed ORR, PFS, CR rate, DOR, EFS, and PFS2; and safety as characterized by severity and seriousness of TEAEs, and relationship to study drug. The study will enroll globally. Clinical trial information: NCT05727904 .

A Clinical Trial to Evaluate the Efficacy of Topical Application of Modified Vijaya Oil in the Management of Vicharchika (Eczema)

Skin disorders have become a major threat in the present era due to the modern lifestyle and stressful living. References to skin diseases in Ayurveda are mostly seen under Kushtha. Vicharchika (Eczema) is one among them with Kapha predominance. The commonly used steroid therapy might lead to side effects. Thus, new topical treatments, such as Modified Vijaya oil, may be useful in reducing the requirement for chronic topical steroid therapy. Aim: To assess the efficacy of topical application of modified Vijaya oil in the management of Vicharchika (Eczema). Materials and Methods: An open-label clinical trial was conducted on 40 patients clinically diagnosed with Vicharchika (Eczema) and the oil was given for topical application for 30 days. The efficacy was evaluated in terms of changes in parameters like EASI (Eczema Area Severity Index), SCORAD (Scoring of Atopic Dermatitis), VAS (Visual Analogue Scale), and SIGA (Static Investigator Global Assessment) before and after the intervention, between Day 0 and 30. The data were collected and analyzed with Wilcoxon Test. Results: The topical application of modified Vijaya oil was found to be highly effective in reducing the symptoms of Vicharchika (Eczema). Conclusion: Modified Vijaya oil could be used in symptomatic relief of Vicharchika (Eczema), and also repairs and enhances the damaged skin.

Impact of Long-Term Steroid Use on the Disposition of Patients Undergoing Transcatheter Aortic Valve Replacement: A Retrospective Nationwide Sample Analysis.

Background Chronic steroid use is debilitating to health, but, in some cases, it is necessary. We examined the effect of chronic steroid use on the discharge disposition of people undergoing transcatheter aortic valve replacement (TAVR). Methods We queried the National Inpatient Sample Database (NIS) from 2016 to 2019. We identified patients with current chronic steroid use with the International Classification of Diseases for the Tenth(ICD-10) code Z7952. Furthermore, we used the ICD-10 procedure codes for TAVR 02RF3. Outcomes were the length of hospitalization (LOS), Charlson Comorbidity Index (CCI), disposition, in-hospital mortality, and total hospital charges (THC). Results Between 2016 and 2019, we identified 44,200 TAVR hospitalizations, and 382,497 were on current long-term steroid therapy. Of these, 934 had current chronic steroid use and underwent TAVR (STEROID) with a mean age of 78 (SD=8.4). About 50% were female, 89% were Whites, 3.7% were Blacks, 4.2% were Hispanics, and 1.3% were Asians. Disposition was 'home,' 'home with home health' (HWHH), 'skilled nursing home' (SNF), 'short-term inpatient therapy' (SIT), 'discharged against medical advice' (AMA), and 'died.' A total of 602 (65.5%) were discharged home, 206 ( 22%) were discharged to HWHH, 109 (11.7%) to SNF, and 12 (1.28%) died. In the SIT and AMA groups, there were only three and two patients, respectively, p=0.23. The group that underwent TAVR and was not on chronic steroid therapy (NOSTEROID) had a mean age of 79 (SD=8.5), with 28731 (66.4%) being discharged home, 8399 (19.4%) to HWHH, 5319 (12.3%) to SNF, and 617 (1.43%) died p=0.17. Comparing the STEROID vs. NONSTEROID group, according to the CCI, the STEROID group scored higher than the NOSTEROID group; 3.5 (SD=2) vs. 3 (SD=2) p=0.0001, while for LOS, it was 3.7 days (SD=4.3) vs. 4.1 days (SD=5.3), p=0.28, and the THC was $203,213 (SD=$110,476) vs. $215,858 (SD=$138,540), p=0.15. Conclusion The comorbidity burden of individuals on long-term steroids undergoing TAVR was slightly higher than those not on steroids undergoing TAVR. Despite this, there was no statistically significant difference in their hospital outcomes following TAVR with respect to dispositions.

Tumefactive multiple sclerosis – a diagnostic and therapeutic challenge

Tumefactive multiple sclerosis with the presence of tumefactive demyelinating lesions (TDL) is an infrequent manifestation of multiple sclerosis. It poses a diagnostic challenge, especially in attempts to differentiate it from a central nervous system neoplasm or other demyelinating disorders, such as neuromyelitis optica spectrum disorder (NMOSD). The article reports a case of a 40-year-old female during chronic steroid therapy administered due to an episode of idiopathic transverse myelitis. The patient developed tumour-like brain lesions in the left hemispheric parietal-occipital region. The diagnostic process was hindered by extended steroid treatment and a lack of patient compliance. This case is an example of insufficient knowledge about rare forms of multiple sclerosis and the need for a holistic approach involving a through analysis of medical history and previous medical records.

IL-1β and IL-6 as predictors of ypN and early response to neoadjuvant chemotherapy in patients with locally advanced GC and GEJ cancer.

454 Background: Perioperative chemotherapy remains a standard of care in locally advanced gastric cancer. About 10-15% patients do not respond to such therapy and there are currently no biomarkers which could be used to predict early response to the neoadjuvant treatment. Methods: This prospective biomarker study aimed at identification of serum biomarkers of early response to neoadjuvant chemotherapy. Here we report only the results for serum cytokine assessments. It was an academic, nonrandomized, prospective study, conducted in MSCNRIO. Between January 2018 and November 2019 we analysed 42 patients aged 30-77 (median 63 years, 52.5% male and 47.5% female) with histologically confirmed GC or GEJ cancer qualified by MDT for perioperative FLOT. Exclusion criteria were: inflammatory and autoimmune diseases, other cancers, chronic steroid and immunosuppressive therapy. Blood sample was collected a.c. prior to the administration of cycle one (C1), two (C2) and three (C3) FLOT regimen. Serum levels of IL-1β and IL-6 were measured twice using ELISA. Results: All patients with pre-treatment IL-1β levels above 0.5 ng/ml on the postoperative histopathological report had positive lymph nodes (ypN+). There was a statistically significant difference in the level of IL-1β in the blood serum of patients before the start of treatment in the subgroups ypN0 vs ypN+ vs unresectable tumor (p = 0.003), ypN0 vs ypN+ (p = 0.002) as well as ypN+ vs unresectable tumor (p = 0.075). There was a trend for change in IL-1β level between cycles C1 and C3 in the ypN0 vs ypN+ subgroups (p = 0.056). The difference in IL-1β level before C1 between the groups TGR-G1-2/ypN0 vs TGR-G1-2/ypN+ vs TGR-G3/ypN0 vs TGR-G3/ypN+ was statistically significant (p = 0.017). The difference in IL-6 level between C3 and C1 in the subgroups TGR-G1-2/ypN0 vs TGR-G1-2 / ypN + vs TGR-G3 / ypN0 vs TGR-G3 / ypN + vs unresectable tumor was statistically significant (p = 0.009). Among the analyzed factors, only the difference in serum IL-6 level between C3 and C1 may be a predictor of ypN+ response to preoperative FLOT regimen. Among ypN0 patients, 76% had an IL-6 difference between C3 and C1&gt; 1.1, i.e. C3 greater than C1 by at least 1.1 (specificity), and among ypN+ patients 83% had an IL-6 difference between C3 and C1 &lt;1.1 (specificity). Conclusions: Low IL-1β levels before starting treatment is a prognostic factor while an early decrease in IL-6 could be considered a predictive marker of response to FLOT.

Association of Comorbidities and Functional Level With Mortality in Geriatric Bowel Perforation

IntroductionSpontaneous bowel perforation is associated with high morbidity and mortality. This entity remains understudied in the geriatric patient. We sought to use a national surgical sample to uncover independent predictors of mortality in elderly patients undergoing emergent operation for perforated bowel. MethodsUsing the American College of Surgeons National Surgical Quality Improvement database, years 2007 to 2017, all geriatric patients (age ≥65 y) who underwent emergency surgery and who had a postoperative diagnosis of bowel perforation were included. Univariate and multivariable analyses were used to identify independent predictors of 30-d mortality. ResultsA total of 8981 patients were included. The median (interquartile range) age was 75 y (69, 82), and 59.0% were female. Twenty-one percent of patients were partially or totally dependent, and 25.2% were admitted from sources other than home. Overall, 30-d mortality rate was 22.1%. Independent predictors of mortality included the following: age 70-79 y (odds ratio [OR]: 1.59, P < 0.001), age ≥80 y (OR: 3.23, P < 0.001), American Society of Anesthesiologists ≥3 (OR: 4.74, P < 0.001), admission from chronic care facility (OR: 1.61, P < 0.001), being partially or totally dependent (OR: 1.50, P < 0.001), chronic steroid use (OR: 1.36, P < 0.001), and preoperative septic shock (OR: 3.74, P < 0.001). Having immediate fascial closure was protective against mortality (immediate fascial closure only, OR: 0.55, P < 0.001; -immediate closure of all surgical site layers, OR: 0.44, P < 0.001). ConclusionsIn geriatric patients, functional status and chronic steroid therapy play an important role in determining survival following surgery for bowel perforation. These factors should be considered during preoperative counseling and decision-making.

The effect of preoperative steroids for at least 10 days on complications following craniotomy for tumor resection: A database, retrospective cohort study

IntroductionThe effect of chronic steroid therapy on postoperative outcomes after craniotomy for tumor resection remains understudied. Research questionThis study aimed to fill this gap and to identify risk factors of postoperative morbidity and mortality among patients on chronic steroid use undergoing craniotomy for tumor resection. Materials and methodsData from the American College of Surgeons National Surgical Quality Improvement Program were used. Patients who underwent craniotomy for tumor resection between 2011 and 2019 were included. Perioperative characteristics and complications were compared among patients with and without chronic steroid therapy, defined as steroid use for at least 10 days. Multivariable regression analyses were conducted to assess the impact of steroid therapy on postoperative outcomes. Subgroup analyses involving patients on steroid therapy were conducted to explore risk factors of postoperative morbidity and mortality. ResultsOf 27,037 patients, 16.2% were on steroid therapy. On regression analyses, steroid use was significantly associated with any postoperative complication, infectious complication, urinary tract infection, septic shock, wound dehiscence, pneumonia, non-infectious, pulmonary, and thromboembolic complications, cardiac arrest, blood transfusion, unplanned reoperation, readmission, and mortality. On subgroup analysis, risk factors for postoperative morbidity and mortality among patients on steroid therapy included older age, higher American Society of Anesthesiology physical status, functional dependence, pulmonary and cardiovascular comorbidities, anemia, dirty/infected wounds, prolonged operative time, disseminated cancer, and a diagnosis of meningioma. Discussion and conclusionPreoperative brain tumor patients on steroids for 10 or more days are at a relatively high risk of postoperative complications. We recommend a judicious use of steroids in brain tumor patients, both in terms of dosage and duration of treatment.

Oral Antiviral Therapy and Monoclonal Antibody for the Treatment of COVID-19 Infection in Outpatients Receiving Anti-Cancer Treatment for Hematological Malignancies: A Multicenter Prospective Study Exploring Efficacy, Safety and Predictors of COVID-19 Lung Failure

Background: Serious complications during SARS-CoV2 infection were reported in onco-haematological patients; in addition, COVID-19 can also indirectly force the interruption or delay of cancer treatment. Early administration of oral antivirals [molnupiravir (MOL) and nirmatrelvir/ritonavir (NIR/r)] or monoclonal antibody (Sotrovimab) may reduce hospitalization and death risk. However, data in hematological patients are lacking. Methods: Outpatients diagnosed with onco-hematologic malignancy presenting COVID-19 were treated with oral antivirals. Hospitalization and lung failure rate, overall mortality, and safety were analyzed. Results: Overall, 83 outpatients were prospectively enrolled in the study [median (q1-q3) age of 61 (48 - 72) years; males in 52% of cases]. All subjects were affected by B.1.1.529 (omicron) SARS-CoV2 variant. Notably, 75 (90%) were fully vaccinated against SARS-CoV2. A total of 33 (40%) was affected by HL/NHL, 21 (25%) by AML/MDS, 14 (17%) by CLL, 15 (18%) by other malignancies, including 4 ALL, 9 MM, and 2 CML. At the time of COVID-19, 11 (13%) were hematopoietic-stem-cell transplant recipients, 19 (23%) were treated with anti-CD20, 7 (8%) were under chronic steroid therapy. After multidisciplinary evaluation, 44 (53%) and 39 (47%) were treated with NIR/r and MOL, respectively; in addition, 14 (17%) patients underwent a combination therapy with Sotrovimab. Median (q1-q3) time from diagnosis of COVID-19 to therapy was of 1 (1-2) days. No grade 3-4 adverse events related to antiviral or Sotrovimab were reported. Overall, 7 (8%) patients were hospitalized for COVID-19 despite therapy. By performing a univariate and multivariate logistic regression, predictors of hospitalization were: recent administration of anti-CD20 (aOR=13.03, 95%CI=1.86-91.3), chronic steroid therapy (aOR=21.37, 95%CI=1.86-244), incomplete/lack of vaccination (aOR=16.07, 95%CI=1.45-177). Interestingly, the subgroup of patients affected by HL/NHL and CLL presented a longer viral shedding, if compared with AML/MDS and other malignancies groups (14 vs 14 vs 8 vs 8 days respectively, p=.031); similarly, persisting COVID-19 symptoms (>21 days) was significantly more frequent in HL/NHL group vs others (18% vs 0% in other groups, p=.020). Conclusions: The early administration of oral antivirals may be safe in onco-hematologic outpatients and could reduce the risk of hospitalization and death due to SARS-COV2 infection. Nevertheless, some groups of patients are still at higher risk and need further attention. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 14335: Vascular Complications and Outcomes Following Transcatheter Aortic Valve Replacement in Patients on Chronic Steroids Therapy. A Meta-Analysis

Introduction: Chronic steroids therapy was reportedly linked to increased vascular complications (VC) following invasive vascular procedures. However, its association with VC after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported. We aimed to compare the rate of vascular complications and outcomes between patients with and without chronic steroid use after TAVR. Methods: We conducted a comprehensive literature search in PubMed, Embase and Cochrane databases for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions and were assessed within 30 days of TAVR. Effect sizes were pooled using the DerSimonian and Laird random-effects model as risk ratio (RR) with 95% confidence intervals (CI). Results: 5 studies with 6136 patients undergoing TAVR (328 steroids, 5808 non-steroids) were included in the analysis. Patients on chronic steroids were younger (mean age 80.2 vs 82.3 years) and were more likely to be female (56% vs 54%). Patients on chronic steroids had a higher risk of major vascular complications (RR 2.32, 95% CI 1.73-3.11, p&lt;0.001), major bleeding (RR 1.61, 95% CI 1.27-2.05, p&lt;0.001) and aortic annulus rupture (RR 4.66, 95% CI 1.67-13.01, p&lt;0.001). There was no significant difference in terms of minor vascular complications (RR 1.43, 95% CI 1.00-2.04, p=0.05), in-hospital mortality (RR 1.86, 95% CI 0.74-4.70, p=0.19) and 30-day mortality (RR 1.14, 95% CI 0.53-2.46, p=0.74) between both groups. Conclusion: Chronic steroid therapy is associated with increased rate of major VCs, major bleeding and aortic annulus rupture following TAVR. Further randomized controlled trials were encouraged to confirm these findings.

LBMON140 Central Diabetes Insipidus Manifesting After Vasopressin Withdrawal In A Critically Ill Patient

Abstract Introduction Central diabetes insipidus is a rare clinical entity characterized by a lack of vasopressin secretion from the posterior pituitary. We present a case of central diabetes insipidus manifesting after the withdrawal of vasopressin in a critically ill patient. Case presentation A 19 year old female with a history of Hodgkin's Lymphoma treated with chemotherapy was transferred from another medical facility while intubated and sedated for management of severe ARDS. She had undergone extensive infectious workup and the etiology was attributed to COVID-19 pneumonia and or bleomycin toxicity. She was started on Methylprednisolone for management of bleomycin toxicity and suspected organizing pneumonia. During her hospitalization, she developed septic shock for which she received broad spectrum antibiotics and pressor support. On day 12 of her hospitalization, vasopressin was discontinued and within 12 hours, there was a rise in serum sodium from 134 to 146 along with polyuria with dilute urine (daily urine output of ∼6-7 liters, urine osmolality decreased from 771 to 279 and urine specific gravity decreased from 1. 037 to 1. 026). No diuretics were administered and serum glucose was without excursions. With administration of 2 mcg DDAVP, urine osmolality increased by more than 50% from 279 to 497, serum sodium decreased from 146 to 141 and urine specific gravity increased from 1. 004 to 1. 026 confirming the diagnosis of central DI. CT head was negative. MRI brain could not be done due to hemodynamic instability. Endocrinology was consulted and concomitant adrenal insufficiency testing was not sought due to chronic steroid therapy. The dose of DDAVP was titrated to ∼1-2 mcg per day based on serum sodium levels and daily urine output. Approximately 10 days later, Vasopressin was restarted due to hemodynamic instability and with ongoing DDAVP therapy, hyponatremia was noted. Thus, DDAVP was discontinued while on vasopressin. She was continued on vasopressin for the remainder of her hospitalization ∼ 11 more days until she unfortunately passed away. Discussion Our patient developed central diabetes insipidus after withdrawal of vasopressin. She continued to require DDAVP for ∼10 days before Vasopressin had to be restarted due to hemodynamic instability, after which DDAVP had to be discontinued due to concern of SIADH. Central diabetes has been linked to critical illness in a transient state driven by depletion of endogenous stores, negative feedback repression and posterior pituitary hypoperfusion. However, our patient continued to require exogenous supplementation. More research is needed in this regard to elucidate the differing etiologies and characteristics of transient versus permanent DI. Critical illness is a rare but extremely important cause of central DI and can quickly prove to be life threatening without timely diagnosis and treatment. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Circulating Anti-Rituximab Antibodies Do Not Affect Response to Rituximab in Steroid-Dependent Nephrotic Syndrome

Nephrotic syndrome (NS) is the most common cause of proteinuria in children and young adults.1 Steroids still represent the cornerstone of therapy for pediatric NS, achieving remission in 80% to 90% of the cases.S1 However, half of the patients develop relapses and require chronic steroid therapy to maintain remission (steroid-dependent NS, [SDNS]).S2

DP16: Scarring alopecia masquerading as follicular mucinosis as a side‐effect of chronic topical steroid therapy: a case report

DP16: Scarring alopecia masquerading as follicular mucinosis as a side‐effect of chronic topical steroid therapy: a case report

Risks of chronic steroid or immunosuppressive therapy on total shoulder arthroplasty patients.

Patients on chronic corticosteroids/immunosuppressants (SI) undergoing orthopaedic surgery are at an increased risk for surgical complications and worse outcomes. However, whether or not chronic preoperative SI use increases the risk for 30-day complications in patients undergoing primary total shoulder arthroplasty (SA) has yet to be explored. From 2006 to 2019, the National Surgical Quality Improvement Program (NSQIP) database was used to identify all patients who underwent primary SA (anatomic TSA and reverse TSA). Patients were stratified into two cohorts: chronic preoperative SI users and those without use. Bivariate and multivariate analyses were utilized in this study. Of the 26,979 patients who underwent primary SA, 25,656 (95.1%) patients did not have SI usage whereas 1323 (4.9%) patients had chronic preoperative SI usage. Following adjustment on multivariate analyses, compared to the non-SI usage cohort, patients who used SI had an increased risk of urinary tract infections (UTIs) (OR 1.87; p = 0.009) and septic shock (OR 7.14; p = 0.002). There were no differences in mortality between the two cohorts (p = 0.058). Chronic pre-operative SI use is an independent risk factor for septic shock and UTIs following primary SA. Surgeons and patients should be aware of these risks to better inform patient counseling and surgical decision making.

Abstract 113: Impact of COVID-19 on arterial stiffness

Background: Arterial Stiffness is a manifestation of endothelial dysfunction and it can be used as a prediction parameter and a target for therapies aimed at ameliorating endothelial cell dysfunction which is raised after Covid 19 infection.Aims and Objectives: To evaluate arterial stiffness using carotid-femoral Pulse Wave Velocity (cfPWV) and to compare the difference in different groups among the study subjects.Methods and Results: Observational single centre study was done after randomly selecting 170 subjects from Telangana State Police Department after excluding subjects with chronic inflammatory diseases on chronic steroid therapy and pregnant/lactating subjects. Analysis after dividing them into 4 groups based on the presence or absence of past history of COVID-19 infection and the presence or absence of Comorbidities (Diabetes Mellitus, Systemic Hypertension, CAD, CVA or CKD) showed mean increase in cfPWV was 76.21 cm/s in Group-A (Covid-ve & Comorbidity-ve), 126.5 cm/s in Group-B (Covid+ve & Comorbidity-ve), 210.1 cm/s in Group-C (Covid-ve & Comorbidity+ve) and 263.9 cm/s in Group-D (Covid+ve & Comorbidity+ve). Significant p values were obtained for intergroup differences in cfPWV.Conclusions: The Arterial stiffness values of prior COVID-19 positive subjects were higher than the group of subjects without prior COVID-19 infection. Comorbidities also independently added to the risk. Pulse wave velocity can be considered as an easy non-invasive screening tool in post-COVID patients to identify possible high-risk candidates.

OUTCOMES OF TOTAL PROCTOCOLECTOMY (TPC) WITH ILEAL POUCH ANAL ANASTOMOSIS (IPAA)

Abstract BACKGROUND Total proctocolectomy (TPC) followed by ileal pouch anal anastomosis (IPAA) is the surgery of choice for eligible ulcerative colitis patients who are refractory to medical therapy or develop complications such as adenocarcinoma or dysplasia. Although associated with excellent quality of life, IPAA can lead to complications including chronic antibiotic-refractory pouchitis, anatomical complications, and development of Crohn’s disease. These outcomes remain a clinical challenge. The aim of this study was to evaluate the rate of complications and their treatment following TPC with IPAA to assess for predictors of adverse postoperative outcomes. METHODS This was a single center, retrospective study from January 1,2010 to December 31, 2020. We included patients who underwent TPC with IPAA and reported at least one episode of pouchitis, some of whom also had additional complications. Chronic pouchitis was defined as recurrent episodes of biopsy-proven inflammation or as reported in the patient record based on clinical presentation and responsiveness to treatment. Crohn’s disease of the pouch was defined as pre-pouch ileitis or development of a fistula more than 6 months post-operatively. Data is presented as number of cases and proportions. RESULTS A total of 44 subjects who underwent IPAA (52% female, mean age 46.4 ± 11.3 years) were included. The rate of acute pouchitis was 9%, the rate of chronic pouchitis was 75%. In the chronic pouchitis group, 45% were antibiotic-dependent and 7% were antibiotic-refractory. We found that 70% of subjects required the initiation of medical therapy to treat symptoms of pouchitis, with the majority requiring chronic antibiotics (73%) (Table). A total of 10 subjects (23%) required biologics and 10 subjects (23%) required chronic steroid therapy. Anatomic complications were noted in 23 subjects (52%), the most common being abscess/fistula formation (30%), followed by stricture formation (27%). Anatomic complications appeared more likely to occur when more time had elapsed since the original surgery. 10 subjects (23%) needed repeat surgery and 9 subjects (20%) developed Crohn’s disease of the pouch. CONCLUSIONS In our cohort, we found that nearly two thirds of subjects required medical therapy to treat pouchitis following IPAA including 25% requiring treatment biologic/immunosuppressant therapy. In addition, one quarter required repeat surgery for treatment of complications. Limitations of this study include a tertiary patient population and small sample size. We found a lack of standardized characterization of pouchitis with respect to symptoms and lab abnormalities. In future work, we plan to use this data to develop a prospective, multi-center study to establish a standardized database of patients who underwent IPAA. This will help better understand factors that influence outcomes and guide management.

Outcomes of Transcatheter Aortic Valve Replacement in Patients Treated With Systemic Steroids.

Chronic steroid therapy is associated with higher vascular complication rates in patients undergoing transcatheter aortic valve replacement (TAVR). The effect of corticosteroids on aortic annular complications has not been directly assessed in this population. A retrospective analysis of 1095 patients undergoing transfemoral TAVR was performed. Patients treated with chronic steroids at the time of the procedure (n = 99) were compared with those who received no steroids (n = 992). The primary outcome included a composite of aortic annular complications, defined as a combination of aortic annular rupture, aortic dissection/perforation, and left ventricular perforation. The primary outcome was significantly higher in the steroid group (4.0% vs 0.5%; P<.01). This finding was primarily driven by higher rates of acute annular rupture in the steroid group (2.0% vs 0.2%; P=.04). Steroid use was associated with higher rates of intraoperative cardiac arrest (5.1% vs 1.5%; P=.03), device capture/retrieval (4.0% vs 0.8%; P=.01), and emergent conversion to open heart surgery (4.0% vs 0.6%; P<.01). There were no differences with respect to in-hospital mortality, stroke, myocardial infarction, need for permanent pacemaker, bleeding complications, minor vascular complications, hospital length of stay, hospital 30-day readmission, or 30-day echocardiographic findings. Additionally, within the steroid group, there were no significant differences between balloon-expandable vs self-expanding TAVR prostheses with respect to composite aortic annular complications. Chronic steroid therapy increases the risk of aortic annular complications in patients undergoing TAVR, with detrimental consequences including intraoperative cardiac arrest and conversion to open heart surgery. Steroid use should be considered in patient selection and determination of procedural technique for TAVR.