Lower Progression Rate Research Articles

MP62-20 THE DETECTION OF A PI-RADS 4-5 LESION AT MULTIPARAMETRIC MRI BEFORE CONFIRMATORY BIOPSY IS THE STRONGEST PREDICTOR OF DISEASE PROGRESSION AMONG MEN WITH LOW-RISK PROSTATE CANCER INCLUDED IN AN ACTIVE SURVEILLANCE PROSPECTIVE PROTOCOL

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II (MP62)1 Sep 2021MP62-20 THE DETECTION OF A PI-RADS 4-5 LESION AT MULTIPARAMETRIC MRI BEFORE CONFIRMATORY BIOPSY IS THE STRONGEST PREDICTOR OF DISEASE PROGRESSION AMONG MEN WITH LOW-RISK PROSTATE CANCER INCLUDED IN AN ACTIVE SURVEILLANCE PROSPECTIVE PROTOCOL Luigi Nocera, Giorgio Gandaglia, Riccardo Leni, Armando Stabile, Elio Mazzone, Carlo Andrea Bravi, Giuseppe Rosiello, Giuseppe Cirulli, Donato Cannoletta, Lorenzo Toneatto, Simone Scuderi, Francesco Barletta, Francesco Pellegrino, Francesco De Cobelli, Francesco Montorsi, and Alberto Briganti Luigi NoceraLuigi Nocera More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Riccardo LeniRiccardo Leni More articles by this author , Armando StabileArmando Stabile More articles by this author , Elio MazzoneElio Mazzone More articles by this author , Carlo Andrea BraviCarlo Andrea Bravi More articles by this author , Giuseppe RosielloGiuseppe Rosiello More articles by this author , Giuseppe CirulliGiuseppe Cirulli More articles by this author , Donato CannolettaDonato Cannoletta More articles by this author , Lorenzo ToneattoLorenzo Toneatto More articles by this author , Simone ScuderiSimone Scuderi More articles by this author , Francesco BarlettaFrancesco Barletta More articles by this author , Francesco PellegrinoFrancesco Pellegrino More articles by this author , Francesco De CobelliFrancesco De Cobelli More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002102.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although multiparametric magnetic resonance imaging (mpMRI) is commonly used in the diagnosis and staging of prostate cancer (PCa), its implications for patient selection and follow-up of active surveillance (AS) candidates is still controversial. METHODS: Patients with localized PCa enrolled in an AS protocol at a single tertiary referral center between 2010 and 2019 were identified. All underwent mpMRI before confirmatory biopsy (cBx) (n=294). AS was proposed to pts with grade group (GG) 1 PCa, all received a cBx within 12 months. Patients referred from other institutions underwent central pathology review. mpMRIs were evaluated according to PI-RADS v.2 criteria. The primary endpoint was disease progression, defined as GG >1 at follow-up Bx. Kaplan-Meier analyses assessed the impact of negative or equivocal mpMRI (PIRADS <4) performed before cBx on risk of progression. Uni- and multivariable Cox regression tested the effect of negative or equivocal mpMRI on progression after adjusting for confounders. Multivariable Cox models tested which characteristics were associated with progression in pts with positive mpMRI. RESULTS: Median age was 65.1 y (58.6–69.3), PSA 5.7 ng/mL (4.3–7.7), PSA density (PSAD) 0.11 ng/mL2 (0.07–0.15). Median follow-up was 22 months (8–47). Overall, 115 pts (36%) had a positive (PI-RADS ≥4) mpMRI before enrollment or during follow-up. Patients with negative or equivocal mpMRI scan were younger (64.5 vs 66.5 yrs, p=0.007), had lower PSA values (5.3 vs 6.1 ng/ml, p=0.01), larger prostate volumes (55 vs 45 ml, p=0.007) and lower PSAD (0.10 vs 0.13, p<0.001). No significant differences were recorded with respect to number of positive Bx cores at enrollment (median 1 vs 1, p=0.3). Men with negative or equivocal mpMRI scan had lower progression rates compared to pts with positive baseline or follow-up mpMRI (HR 0.35, p<0.001). This finding was corroborated in multivariable regression, after adjusting for age, PSA, prostate volume and number of positive cores (p<0.001). In subgroup analyses, among patients with positive mpMRI, those with a number of cores >16 exhibited lower risk of progression (HR: 0.5, p=0.02). CONCLUSIONS: Individuals with a PI-RADS 4-5 managed with AS should be considered at increased risk of progression and should receive a more stringent follow-up. In this scenario, a number of collected cores >16 appears to be key to reduce such risk given better assessment by more extensive Bx sampling. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1100-e1100 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luigi Nocera More articles by this author Giorgio Gandaglia More articles by this author Riccardo Leni More articles by this author Armando Stabile More articles by this author Elio Mazzone More articles by this author Carlo Andrea Bravi More articles by this author Giuseppe Rosiello More articles by this author Giuseppe Cirulli More articles by this author Donato Cannoletta More articles by this author Lorenzo Toneatto More articles by this author Simone Scuderi More articles by this author Francesco Barletta More articles by this author Francesco Pellegrino More articles by this author Francesco De Cobelli More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Loading ...

Role of ivermectin in prophylaxis and treatment of Covid-19 patients: A systematic review

For a systematic review, the present study made an extensive review around the formulated question by identifying, selecting and critically appraising data based on a comprehensive and reproducible search strategy. It was found that there exists a significant literature which speaks positively about the role of Ivermectin in prophylaxis. The drug has been found statistically significant in mortality reduction, clinical recovery time and viral clearance. Contrary to what the WHO has claimed, Ivermectin prophylaxis was associated with a very low rate of disease progression.

N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study

Background N-acetyl-cysteine (NAC) has been previously shown to exert beneficial effects in diverse respiratory diseases, through antioxidant and anti-inflammatory actions. Our aim was to evaluate NAC potential impact in hospitalised patients with COVID-19 pneumonia, in terms of progression to severe respiratory failure (SRF) and mortality. Patients and Methods This retrospective, two-centre cohort study included consecutive patients hospitalised with moderate or severe COVID-19 pneumonia. Patients who received standard of care were compared with patients who additionally received NAC 600 mg bid orally for 14 days. Patients’ clinical course was recorded regarding (i) the development of SRF (PO2/FiO2 <150) requiring mechanical ventilation support and (ii) mortality at 14 and 28 days. Results A total of 82 patients were included, 42 in the NAC group and 40 in the control group. Treatment with oral NAC led to significantly lower rates of progression to SRF as compared to the control group (p < .01). Patients in the NAC group presented significantly lower 14- and 28-day mortality as compared to controls (p < .001 and p < .01 respectively). NAC treatment significantly reduced 14- and 28-day mortality in patients with severe disease (p < .001, respectively). NAC improved over time the PO2/FiO2 ratio and decreased the white blood cell, CRP, D-dimers and LDH levels. In the multivariable logistic regression analysis, non-severe illness and NAC administration were independent predictors of 28-days survival. Conclusion Oral NAC administration (1200 mg/d) in patients with COVID-19 pneumonia reduces the risk for mechanical ventilation and mortality. Our findings need to be confirmed by properly designed prospective clinical trials.

Clinical Characteristics and Treatment of Patients with Multiple Myeloma Using the Japan Medical Data Center Database

Background: The incidence of Multiple Myeloma (MM) is increasing in Asia, although it's still less common compared to the incidence in Western countries. Information on clinical characteristics and current treatments is important to inform future clinical research.Purpose: To describe the clinical characteristics and treatment patterns of patients aged ≥18 years with MM in Japan.Methods: We conducted a retrospective cohort study using the Japan Medical Data Center (JMDC) database, an employment insurance claims database covering approximately 3.78 million patients (non-government employees and their family members, <75 years of age) from July 1, 2009-December 31, 2016. Adult patients with a confirmed diagnosis of MM as well as at least one treatment for MM after the initial diagnosis were included in the analysis. Patients with any existing primary cancer other than MM were excluded. Eligible patients were followed up until death, or study end, whichever came first.Results: A total of 164 confirmed MM patients were include in the analyses, of which 73% were employees, 27% were family members, and 65% were male. 77% of patients were aged 36-65 years, reflecting the characteristics of the employment database. The median follow up period after the diagnosis was 26 months (range 1-75). The most common co-morbidities at diagnosis were hypertension (36%), bone fracture (21%), peripheral neuropathy (15%), renal failure (11%) and anemia (10%). The median time from diagnosis until commencing treatment was 27 days (range 0-1937), with 66% of patients commencing treatment within 0-90 days after diagnosis. 43% of patients (47% of employees versus 32% of family members) commenced initial MM treatment with bortezomib: most frequently bortezomib + dexamethasone without (21%, 33/160) or with (22%, 35/160) chemotherapy. Three patients received radiotherapy and one received autologous stem cell transplant as initial treatment. Median duration of treatment with a bortezomib-based regimen was 156 days (range 18-1270). Almost half (49%) of all patients received initial treatment with steroids alone. Median duration of non-bortezomib based initial treatment was 120 days (range 1-1837). By the end of the study period, 34% of patients were still using first-line treatment, 32% received no further treatment, 15% began second-line therapy, 12% received an autologous stem cell transplant, 4% commenced radiotherapy, 2% were re-treated and 1% died. Second-line treatment was with bortezomib-based therapies in 46% (11/24) of patients. A total of 23% of all patients received an autologous stem cell transplant over the study period. 20% (34/164) of patients developed at least one second tumor over the observation period: 17 patients developed a hematologic malignancy and 22 developed a solid tumor.Conclusion: The JDMC database covers approximately 1% of the Japanese population and all members are <75 years of age. Patients with MM are therefore likely to be younger with less advanced disease than the general population. Half of MM patients were initially treated with steroids, with 43% receiving bortezomib. The study suggests a relatively low rate of progression to advanced line treatment or retreatment in this young cohort of Japanese patients with MM. DisclosuresSiggins:Janssen Research & Development: Employment. Qiu:Janssen Research & Development: Employment, Other: holds shares in Janssen Research & Development . Zhang:Janssen Research & Development: Employment. Huang:Janssen Research & Development: Employment. Rothwell:Janssen Research & Development: Employment. Liu:Janssen Research & Development: Employment, Other: hold shares in Janssen Research & Development .

Multifocality and Progression of Papillary Thyroid Microcarcinoma During Active Surveillance.

Prospective trials of active surveillance (AS) have shown low rates of progression in low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0). However, the significance of multifocality as a prognostic factor remains controversial. Data from 571 patients (mean age, 53.1years; 495 females) who underwent AS were reviewed. PTMC was unifocal in 457 patients (80.0%) and multifocal in 114 patients (20.0%), with 2-5 lesions each (261 tumors in total). Tumor progression was defined as tumor size enlargement ≥ 3mm and/or development of clinically evident lymph node metastasis (LNM). After a mean duration of AS of 7.6years, 53 patients (9.3%) showed tumor enlargement and 8 patients (1.4%) developed LNM. The 10-year progression rate was 13.1%. Age, sex, and calcification pattern did not differ significantly between uni- and multifocal diseases. However, anti-thyroglobulin antibody and/or anti-thyroid peroxidase antibody was more frequently positive with multifocal PTMCs (46.7%) than with unifocal disease (34.4%, p = 0.024). Patients with uni- and multifocal disease showed no significant differences in 10-year rate of tumor enlargement (11.4% vs. 14.8%), LNM development (1.1% vs. 2.4%), or progression (12.4% vs 15.9%). Multivariate analysis of predictors for progression showed multifocality was not a significant risk factor (odds ratio, 1.45; 95% confidence interval, 0.79-2.54; p = 0.22). Eventually, 9 patients (7.9%) with multifocal PTMCs underwent surgery and 7 needed total thyroidectomy, although 7 still showed T1N0M0 low-risk cancer. Even patients with multiple PTMCs (T1amN0M0) are good candidates for AS. Many patients can avoid total thyroidectomy and subsequent surgical complications.

Making a difference: insights into effective HE progression practices in further education colleges

Further education colleges (FECs) are significant providers of level 3 (higher education (HE) entry) courses. Yet, their role in preparing students, including those from widening participation backgrounds, for HE is often overlooked. Indeed, recent reports from the Office for Students have focused on the low HE progression rates returned by colleges. However, this focus overlooks the reality that students educated in FECs do progress and that in many instances colleges are very successful in this endeavour, given that those studying with them are more likely to come from educationally and economically disadvantaged backgrounds. This paper reports on the findings from a recent study that sought to identify the effective progression practices being pursued in two FECs. These include institution-wide activities as well as initiatives adopted at subject level. Whilst the latter have received less attention in the literature, the qualitative approach adopted in this study, which involved drawing on the insights of students as well as teaching staff, was able to detail the application of these subject-level practices. The article concludes by arguing for the wider adoption of subject-level as well as institution-wide practices, and for their potential to be recognised by those working in the HE sector more generally.

LGG-07. IS BRAF ALTERATION OR A HISTOLOGIC ‘QUALIFIER’ A PREDICTOR OF OUTCOME IN PEDIATRIC PILOCYTIC ASTROCYTOMA?

IntroductionPediatric pilocytic astrocytomas (PA) are the most common pediatric central nervous system tumor. Surgical resection is the primary treatment for PA with five-year survival rates up to 95%. Despite a favorable prognosis, our understanding about the prognostic value of histopathological findings, such as histopathologic qualifier* or BRAF alterations is evolving. MethodsPatients treated for a WHO grade 1 PA at Washington University in St. Louis/St. Louis Children’s Hospital were analyzed for clinical details, including pathology diagnosis (*histopathologic qualifier refers to designations in the diagnosis such as “WHO Grade I pilocytic astrocytoma with increased proliferative index”). BRAF alterations include gene fusions and point mutations. Results224 patients were analyzed (51% female, mean age 9.6 years). Tumors were located in the cerebellum/fourth ventricle (50%), optic pathway/hypothalamus (15%), brainstem (12%), and cerebral cortex (11%). BRAF alterations were identified in 55/77 patients (71.4%) and additional histopathologic qualifiers were present in 27/220 patients (12.3%). 196 patients (87.5%) underwent surgical treatment and 22 (9.8%) had biopsy alone. 45 patients (22%) displayed tumor progression or recurrence after resection. The presence of a histopathologic ‘qualifier’ in the topline or BRAF alteration was not associated with tumor progression or recurrence (p=0.36, p=0.77). Ki-67 proliferative indices were not predictive of progression or recurrence (p=0.94), including when controlling for extent of resection and adjuvant therapy. BRAF alterations, specifically KIAA1549 fusions, were associated with cerebellar/fourth ventricular tumor location (p<0.001) and younger patient age (p=0.03). Extent of resection was the only predictor of outcome identified in this study; patients with gross total resection had significantly lower rates of progression and recurrence (p<0.0001). Conclusion BRAF alterations and histopathologic qualifiers were not associated with tumor progression or recurrence in pediatric PA, although BRAF fusions were more common in tumors located in the cerebellum/fourth ventricle and in younger patients.

Impact of BRAF mutations on outcomes in metastatic melanoma with central nervous system metastases treated with immune checkpoint inhibitors.

e21500 Background: Half of patients (pts) with melanoma (mel) develop central nervous system (CNS) metastases (mets), leading to death in over 90% in the pre-immune checkpoint inhibitor (ICI) era. Overall survival (OS) has improved in the ICI era for those with CNS mets, yet the association of survival with ICI treatment for those with tumors harboring genomic variants (var) remains unclear. Methods: We retrospectively reviewed our electronic medical records to identify pts with mel and CNS mets who received ICI from 2010 to 2018. Treatment history, systemic and CNS responses, and genomic data were recorded. Genomic var were categorized as BRAFV600E (BRAF), NRAS, cKIT, other var, and no var. Concurrent RT (CRT) was defined as RT to CNS mets within 30 days of ICI. OS was calculated from date of first ICI or RT to date of death or last follow up, and comparison analyses made using Kaplan-Meier estimate. Fisher's exact or Chi-squared tests were used to compare categorical variables and Wilcoxon or Kruskal-Wallis tests to compare continuous variables. A two-sided p-value of &lt; 0.05 was considered statistically significant. Results: A total of 49 pts were identified; 37 had var results available. BRAFV600E was the most common var identified (32%), followed by NRAS (19%), cKIT (5%), and other (5%); 38% had no var. BRAFV600K was not identified. Pts with BRAF had lower rates of CNS progression on ICI at 3 and 6 months than all other pts (17% vs 50%, p&lt; 0.01 and 12.5% vs 40%, p&lt; 0.01, respectively). Of 38 pts (10 BRAF) who had CNS mets at the start of ICI, 6-month OS was 50% in pts with BRAF, compared to 0% in pts with non-BRAF var ( p= 0.01) and 36% in pts with no var ( p= 0.7). 4 of the 10 pts with BRAF who had CNS mets at start of ICI received BRAF-targeted therapy after ICI. On ICI, only 30% of pts with BRAF developed new CNS mets, compared to 57% of all other pts ( p= 0.08). Pts who developed new CNS mets on ICI had worse OS than pts who did not (median OS (mOS) 314 days vs 662 days, p= 0.04). A majority of pts (55%) received anti-CTLA4 monotherapy as first ICI, and 39% received anti-CTLA4 plus anti-PD1. Pts with BRAF were just as likely to receive dual anti-CTLA4/PD-1 as pts without BRAF (33% vs 40%, p= 0.74). 40 pts underwent RT for CNS mets, of whom 22 received CRT. There was no difference in mOS between pts who received CRT and non-concurrent RT/no RT (468 days vs 314 days, p= 0.8). Rates of CRT between pts with BRAF and pts without BRAF were similar ( p&gt; 0.9), and there was no difference in mOS between these groups (400 days vs 536 days, p= 0.9). Conclusions: Pts with BRAF-mutated mel with CNS mets receiving ICI had lower rates of progression in CNS and improved OS compared to other var. CRT was not associated with improved survival over non-concurrent RT. There has been significant improvement in OS of pts with mel CNS mets in the era of ICI and additional studies are warranted to understand the biology of BRAF var and the host immune system response in the CNS.

POS1027 EFFICACY AND SAFETY OF GUSELKUMAB, A MONOCLONAL ANTIBODY SPECIFIC TO THE p19-SUBUNIT OF INTERLEUKIN-23, THROUGH 2 YEARS: RESULTS FROM A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY CONDUCTED IN BIOLOGIC-NAÏVE PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

Background:Guselkumab (GUS), a selective IL-23 inhibitor dosed every 4 or 8 weeks (Q4W or Q8W), demonstrated efficacy for joint and skin symptoms, inhibition of structural damage progression (Q4W), and safety vs. placebo (PBO) through Week 24 (W24) of the Ph3, double-blind, PBO-controlled trial in biologic-naïve pts with PsA (DISCOVER-2).1 Favorable benefit-risk was also seen through 1 year.2Objectives:To assess GUS efficacy and safety through 2 years.Methods:Biologic-naïve adults with active PsA (≥5 swollen joint count [SJC] + ≥5 tender joint count [TJC]; CRP ≥0.6 mg/dL) were randomized (1:1:1) to GUS 100 mg Q4W; GUS 100 mg at W0, W4, Q8W; or PBO with crossover to GUS 100 mg Q4W (PBO→Q4W) at W24. Clinical efficacy (ACR/PASI/IGA/HAQ-DI) was assessed in the modified intention to treat (mITT) population through W100 with missing data imputation (nonresponse for categorical endpoints; no change/multiple imputation for continuous endpoints). Observed PsA-modified van der Heijde Sharp (vdH-S) scores derived from blinded radiographic images collected at W0, W24, W52, W100 (or at discontinuation [d/c]) and adverse events (AEs) through W112 were collected.Results:712/739 (96%) randomized pts continued study agent at W24; 687/739 (93%) continued at W52; 652/739 (88%) completed W100. ACR20 response rates in the mITT population continued to increase after W24, and at W100 were 76% for Q4W and 74% for Q8W (Figure 1). Similar response patterns were seen for ACR50/70, HAQ-DI and PASI90/100 (Table 1), and IGA0/1 and PASI75 response rates were consistent through W100 in pts randomized to Q4W and Q8W; W100 data for PBO→Q4W pts were consistent with pts treated with Q4W and Q8W (Table 1). GUS improvements in SF-36 PCS/MCS at W52 also persisted through W100 (data not shown). Low rates of radiographic progression (as measured by PsA-modified vdH-S scores) were observed during W52-100 for Q4W (n=227; 0.75) and Q8W (n=232; 0.46). In the PBO→Q4W group (n=228), radiographic progression was 1.12 during W0-24 (while on PBO), 0.51 during W24-100 (while on Q4W), and 0.13 during W52-100. Through W112, the incidences of AEs, serious AEs (SAEs), AEs leading to d/c, infections, serious infections, and injection site reactions were generally consistent with the PBO-controlled period and through 1 year. Of the pts in the Q4W (n=245), Q8W (n=248), and PBO→Q4W (n=238) groups, 9%, 9% and 7% had ≥1 SAE; 2%, 3% and 3% had ≥1 serious infection; 2 Q8W pts (fungal esophagitis, disseminated herpes zoster) and 1 PBO→Q4W pt (listeria meningitis) had opportunistic infections; 1 PBO→Q4W pt died (road traffic accident); 1 PBO-randomized pt had IBD; no pt had anaphylactic or serum sickness reaction, or active TB.Conclusion:In biologic-naïve PsA pts, GUS improvements in joint and skin symptoms, physical function, and low rates of radiographic progression persisted through 2 years. GUS safety in PsA through 2 years was comparable with safety at 6 months and 1 year, similar between Q4W and Q8W, and consistent with GUS safety in psoriasis.

PCV chemotherapy alone for WHO grade 2 oligodendroglioma: prolonged disease control with low risk of malignant progression

IntroductionThe role of chemotherapy alone in newly diagnosed WHO grade 2 oligodendroglioma after biopsy, incomplete or gross total resection remains controversial. We here analyze the clinical outcome of four patient cohorts being treated with either procarbazine, CCNU and vincristine (PCV) or temozolomide (TMZ) after biopsy, resection only, or wait-and-scan after biopsy.MethodsPatients (n = 142) with molecularly defined oligodendroglioma (WHO 2016) were assigned to four cohorts: W&S, wait-and-scan after stereotactic biopsy (n = 59); RES, surgical resection only (n = 27); TMZ, temozolomide after biopsy (n = 26) or PCV (n = 30) after biopsy. Presurgical MRI T2 tumor volumes were obtained by manual segmentation. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of histological progression to grade 3 were analyzed.ResultsPFS was longest after PCV (9.1 years), compared to 5.1 years after W&S, 4.4 years after RES and 3.6 years after TMZ. The rate of histological progression from grade 2 to 3 within 10 years was 9% for the PCV, 29% for the W&S, 67% for the RES and 75% for the TMZ group (p = 0.01). In the W&S group, patients treated with PCV at first relapse had a longer PFS from intervention than those treated with TMZ (7.2 vs 4.0 years, p = 0.04). Multivariate analysis identified smaller tumor volume prior to any intervention (p = 0.02) to be prognostic for PFS.ConclusionsPCV chemotherapy alone is an effective treatment for WHO grade 2 oligodendroglioma, with long PFS and low rate of histological progression.

P134 Radiographic progression of structural joint damage over 5 years of baricitinib treatment in patients with RA: results from RA-BEYOND

Abstract Background/Aims Baricitinib (BARI) is an oral, reversible, selective JAK1/2 inhibitor. Treatment with once-daily oral BARI resulted in low rates of radiographic progression for up to 2 years in patients with rheumatoid arthritis (RA). Here, we evaluate the radiographic progression of structural joint damage in patients with RA over 5 years of treatment with BARI. Methods This included patients who completed three Phase 3 trials, RA-BEGIN (DMARD-naive), RA-BUILD (csDMARD-IR), or RA-BEAM (MTX-IR), and enrolled in long-term extension study, RA-BEYOND. Patients receiving blinded BARI at the conclusion of Phase 3 trials remained on that dose (2mg/4mg, once daily) in RA-BEYOND. At 52 weeks, DMARD-naive patients receiving methotrexate(MTX) or combination therapy(BARI 4mg+MTX) were switched to BARI 4mg monotherapy; MTX-IR patients receiving adalimumab(ADA) were switched to BARI 4mg on background MTX. At 24 weeks, csDMARD-IR patients receiving placebo(PBO) were switched to BARI 4mg on background csDMARD. Analysis population included patients who had baseline and at least one radiograph collected after 2 years. Radiographic progression of structural joint damage (Years 3-5) was determined by changes from baseline in van der Heijdemodified Total Sharp Score(ΔmTSS), erosion score, and joint space narrowing. Proportion of patients showing no progression was assessed based on change from baseline mTSS(ΔmTSS) from originating study, using thresholds of 0.5 or smallest detectable change(SDC). Mixedmodel repeatedmeasures and logistic regression models were used to analyze continuous variables and categorical variables, respectively; linear extrapolation was used for imputation of missing data(maximum of 1 year). Results 82.6% (2125/2573) of patients entered long-term extension study. Among DMARD-naive patients, those on initial BARI monotherapy or in combination with MTX had significantly slower radiographic progression(ΔmTSS) versus those on initial MTX at Years 3, 4, 5 (p ≤ 0.05). They had significantly fewer erosions at these time points (p ≤ 0.05). A greater proportion of patients who received initial BARI therapy and BARI+MTX had no radiographic progression versus initial MTX monotherapy using thresholds of 0.5 (p ≤ 0.05). Among MTX-IR patients, those on initial BARI treatment had slower radiographic progression compared to PBO and results were comparable to those on initial ADA treatment at Years 3, 4, 5. A greater proportion of patients who received initial BARI therapy had no radiographic progression versus initial PBO using thresholds of SDC (p ≤ 0.05). Among csDMARD-IR patients, although differences between groups were small, patients on initial BARI 4mg had slowest radiographic progression compared to initial PBO and initial BARI 2mg. At least 74% of the structure data used in the analyses are based on observed data. Conclusion Treatment with once-daily oral BARI maintained low rates of radiographic progression for up to 5 years in different patient populations with RA. Disclosure D.M.F.M. van der Heijde: Consultancies; AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daiichi Sankyo, Eli Lilly and Company, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma. C.E. Kartman: Shareholder/stock ownership; Eli Lilly and Company. L. Xie: Shareholder/stock ownership; Eli Lilly and Company. S. Beattie: Shareholder/stock ownership; Eli Lilly and Company. D.E. Schlichting: Shareholder/stock ownership; Eli Lilly and Company. P. Durez: Member of speakers’ bureau; Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, and Sanofi. Y. Tanaka: Member of speakers’ bureau; AbbVie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, Takeda, UCB, and YL Biologics. Grants/research support; AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, and Taisho-Toyama and Takeda. R. Fleischmann: Consultancies; AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Roche, Sanofi-Aventis, and UCB.

Placental growth factor testing in the management of late preterm preeclampsia without severe features: a multicenter, randomized, controlled trial

In women with late preterm preeclampsia, the optimal time for delivery remains a controversial topic, because of the fine balance between the maternal benefits from early delivery and the risks for prematurity. It remains challenging to define prognostic markers to identify women at highest risk for complications, in which case a selective, planned delivery may reduce the adverse maternal and perinatal outcomes. This trial aimed to determine whether using an algorithm based on the maternal levels of placental growth factor in women with late preterm preeclampsia to evaluate the best time for delivery reduced the progression to preeclampsia with severe features without increasing the adverse perinatal outcomes. This parallel-group, open-label, multicenter, randomized controlled trial was conducted at 7 maternity units across Spain. We compared selective planned deliveries based on maternal levels of placental growth factor at admission (revealed group) and expectant management under usual care (concealed group) with individual randomization in singleton pregnancies with late preterm preeclampsia from 34 to 36+6 weeks' gestation. The coprimary maternal outcome was the progression to preeclampsia with severe features. The coprimary neonatal outcome was morbidity at infant hospital discharge with a noninferiority hypothesis (noninferiority margin of 10% difference in incidence). Analyses were conducted according to intention-to-treat. Between January 1, 2016, and December 31, 2019, 178 women were recruited. Of those women, 88 were assigned to the revealed group and 90 were assigned to the concealed group. The data analysis was performed before the completion of the required sample size. The proportion of women with progression to preeclampsia with severe features was significantly lower in the revealed group than in the concealed group (adjusted relative risk, 0.5; 95% confidence interval, 0.33-0.76; P=.001). The proportion of infants with neonatal morbidity was not significantly different between groups (adjusted relative risk, 0.77; 95% confidence interval, 0.39-1.53; P=.45). There is evidence to suggest that the use of an algorithm based on placental growth factor levels in women with late preterm preeclampsia leads to a lower rate of progression to preeclampsia with severe features and reduces maternal complications without worsening the neonatal outcomes. This trade-off should be discussed with women with late preterm preeclampsia to allow shared decision making about the timing of delivery.

Laboratory, Clinical, and Survival Outcomes Associated With Peptide Receptor Radionuclide Therapy in Patients With Gastroenteropancreatic Neuroendocrine Tumors

Peptide receptor radionuclide therapy (PRRT) is approved in the US for treatment of gastroenteropancreatic neuroendocrine tumors (NETs), but data on PRRT outcomes within US populations remain scarce. To analyze the first 2 years of PRRT implementation at a US-based NET referral center. This cohort study was conducted using medical records of patients with metastatic NET receiving PRRT from 2018 through 2020 in a NET program at a tertiary referral center. Included patients were those at the center with metastatic NETs who received at least 1 dose of PRRT over the study period. Laboratory toxic effects were assessed using Common Terminology Criteria for Adverse Events version 5.0. Tumor response was determined using Response Evaluation Criteria in Solid Tumors 1.1. Survival analysis was conducted to identify factors associated with progression-free survival (PFS) and overall survival. Data were analyzed from August 2018 through August 2020. Receiving 4 cycles of lutetium-177-dotatate infusion, separated by 8-week intervals targeted to 7.4 GBq (200 mCi) per dose. Data were compared from before and after PRRT to determine hematologic, liver, and kidney toxic effects and to assess tumor progression and patient survival. Among 78 patients receiving at least 1 dose of PRRT, median (interquartile range) age at PRRT initiation was 59.8 (53.5-69.2) years and 39 (50.0%) were men. The most common primary NET sites included small bowel, occurring in 34 patients (43.6%), and pancreas, occurring in 22 patients (28.2%). World Health Organization grade 1 or 2 tumors occurred in 62 patients (79.5%). Among all patients, 56 patients underwent pretreatment with tumor resection (71.8%), 49 patients received nonsomatostatin analogue systemic therapy (62.8%), and 49 patients received liver-directed therapy (62.8%). At least 1 grade 2 or greater toxic effect was found in 47 patients (60.3%). Median PFS was 21.6 months for the study group, was not reached by 22 months for patients with small bowel primary tumors, and was 13.3 months for patients with pancreatic primary tumors. Having a small bowel primary tumor was associated with a lower rate of progression compared with having a pancreatic primary tumor (hazard ratio, 0.19; 95% CI, 0.07-0.55; P = .01). Median overall survival was not reached. This cohort study of patients with metastatic NETs found that PRRT was associated with laboratory-measured toxic effects during treatment for most patients and an overall median PFS of 21.6 months. Patients with small bowel NETs had longer PFS after PRRT compared with patients with pancreatic NETs.

Secukinumab: A Review in Psoriatic Arthritis.

Secukinumab (Cosentyx®) is a fully human monoclonal antibody that selectively targets interleukin (IL)-17A, a proinflammatory cytokine involved in the pathogenesis of psoriatic arthritis (PsA). Administered subcutaneously, the first-in-class anti-IL-17 agent is approved in numerous countries worldwide for the treatment of adults with active PsA. In the phase III FUTURE trials, secukinumab 150 or 300 mg improved the clinical signs and symptoms of PsA versus placebo in patients with active disease despite previous treatment with NSAIDs, biological disease-modifying anti-rheumatic drugs (bDMARDs) and/or tumour necrosis factor inhibitors (TNFi). The benefits of secukinumab were seen regardless of whether or not patients had received previous TNFi therapy, and were maintained during longer term (up to 5 years) treatment. In FUTURE 1 and 5, secukinumab inhibited structural joint damage and was associated with sustained low rates of radiographic progression through 1–3 years of treatment. Treatment with secukinumab improved physical function and health-related quality of life (HR-QOL) and was generally well tolerated, both in the short- and longer-term. In the head-to-head EXCEED trial, secukinumab did not quite attain statistical significance for superiority versus adalimumab in the joint domain. In conclusion, secukinumab is effective across all key PsA domains and is generally well tolerated, and thus represents a useful treatment alternative to TNFi and other bDMARDs in adult patients with active PsA.

A Systematic Review of Radiolunate and Radioscapholunate Arthrodesis

PurposeThe aims of this systematic review were to examine the use of radiolunate (RL) or radioscapholunate (RSL) arthrodesis as surgical management for patients with advanced radiocarpal arthritis that failed conservative management and to assess postoperative outcomes.MethodsWe reviewed articles from PubMed, EMBASE, and Web of Science from inception through December 2019. We identified complete manuscripts written in English reporting on RL or RSL arthrodesis for treatment of wrist pathology that included the primary outcomes (pain or grip strength) and at least 2 secondary outcomes (range of motion, patient-reported outcomes, or nonunion). Data pooling was used to calculate weighted averages.ResultsWe identified 2,252 articles and selected 13 for inclusion. Across all studies, RSL arthrodesis was performed for 180 patients (49% female; 45 years old) and RL for 94 (87% female; 50 years old). Both procedures exhibited improvements in pain score and grip strength. Both cohorts demonstrated postoperative changes in flexion-extension arc, flexion, extension, ulnar deviation, supination, and pronation after data pooling. The nonunion rate for RSL was 15% versus 2% for RL, whereas the rate of progression to total wrist arthrodesis for RSL and RL was 4% and 0%, respectively.ConclusionsBoth RL and RSL arthrodesis can be successfully used to manage debilitating radiocarpal arthritis by affording patients with pain reduction. Each has its own benefits, in which RSL arthrodesis provides a total arc of motion within the functional demands of most activities of daily living, and RL arthrodesis has low rates of nonunion and progression to total wrist arthrodesis. Further research is needed to compare the 2 surgeries directly and prospectively in comparable patient groups.Type of study/level of evidenceTherapeutic III.

Leukemia Cutis as an Early Presentation or Relapsing Manifestation of Chronic Lymphocytic Leukemia (CLL).

Background and Objective:Cutaneous infiltration by Chronic Lymphocytic Leukemia (CLL) is a rare complication. The clinical presentation, impact of it on disease prognosis, and the proper treatment choice are not clear. Here in our review, we try to answer these questions.Acquisition of evidences:A systematic search of PubMed, and Google Scholar for English language articles published from Jan 2000 to June 2019.Synthesis of evidences:A total of 56 cases were identified, with a median age of 66 years. Of these cases 43 were males and 12 were females, and one missing data, with a ratio of 3,6:1. Head and neck were most commonly involved. The commonest clinical presentation was papulonodular lesions, and the majority were diagnosed at an early stage. CLL skin involvement at the site of old herpetic lesions was common. Because of the rarity of the disease, treatment modalities varied widely, and there are no consensus on treatment. The majority were treated with chemotherapy. In general, 35 (77.8% - of the non-missing data) patients responded to treatment (25 patients had a complete remission and 10 a partial remission). All patients ≤60 years had an early-stage disease, on the other hand, all patients with advanced-stage were >60 years.Conclusion:Patients with early-stage and localized leukemia cutis can benefit from observation alone strategy, while intervention in young patients with advanced disease is warranted. Skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with a very low progression rate.

71. Use of Intravenous Immunoglobulin Therapy Reduces Progression to Mechanical Ventilation in COVID-19 Patients with Moderate to Severe Hypoxia

BackgroundThe majority of COVID-19 morbidity and mortality occurs in patients who progress to mechanical ventilation. Therefore, therapeutic interventions targeting the mitigation of this complication would markedly improve outcomes and reduce healthcare utilization.MethodsPatients with COVID-19 from two hospitals in San Diego, California were randomized at a 1:1 ratio to receive standard of care (SOC) plus intravenous immunoglobulin (IVIG) at 0.5 g/kg/day x 3 days with solumedrol 40 mg 30 minutes before infusion (IVIG group) versus SOC alone. The primary composite endpoint was receipt of mechanical ventilation or death before receiving ventilation. Patients were followed until discharge to home or up to 30 days from time of enrollment.ResultsSixteen patients received IVIG plus SOC and 17 SOC alone. The median age was 54 years for SOC and 57 years for IVIG. Median time from hospital admission to study enrollment was 1 day (range 0–4) for SOC and 2 days (range 0–8) for IVIG. APACHE II scores and Charlson comorbidity indices were similar for IVIG and SOC (median 8 vs 7 and 2 for both, respectively). Seven SOC patients achieved the composite endpoint (6 ventilated, 1 death) versus 2 IVIG patients (2 ventilated), p=0.12, Fisher exact test. Among the subgroup with an estimated A-a gradient of >200 mm Hg at time of enrollment, the IVIG group showed a lower rate of progression to the composite endpoint (2/14 vs 7/12, p=0.04 Fisher exact test), shorter median hospital length (11 vs 24 days, p=0.001 Mann Whitney U), and shorter median intensive care unit (ICU) stay (3 vs 13 days, p=0.005 Mann Whitey U).ConclusionThis small, prospective, randomized, open-label study showed that when administered to hypoxic non-ventilated COVID-19 patients with an A-a gradient of >200 mm Hg (corresponding to a requirement of 6 liters O2 via nasal cannula to achieve an SpO2 of 92%), IVIG significantly decreased the rates of progression to mechanical ventilation, ICU length of stay, and total hospital length of stay. A Phase 3 prospective, randomized, placebo-controlled, multicenter trial is underway to further validate these findings.Disclosures George Sakoulas, MD, Octapharma (Grant/Research Support, Scientific Research Study Investigator)

Pharmacological Myopia Control Influence on Quality of Life and Psyche among Adolescents.

Myopia is a global problem affecting all aspects of patients’ lives. Objectives: The aim of the study was to evaluate the influence of low dose atropine (LDA) myopia control on the quality of life in patients with myopia. Material and Methods: A self-constructed questionnaire, including eight questions, was distributed among 40 patients. The questionnaire was divided into two subsections: (1) influence of LDA on visual functions and (2) influence of LDA on self-esteem. Answers were collected separately for boys (18 patients) and girls (22 patients) and compared considering spherical equivalent (SE) and myopia progression rate. Results: Girls reported more issues with near activities and pupil size. Boys and girls complained similarly, regarding the sun glare. We found a high level of certainty about the efficacy of LDA therapy among both examined groups and a little improvement in self-esteem. Girls recommended LDA therapy more often than boys, especially when the progression rate was low. There was no statistically significant difference in answer scores between groups with different myopia progression rates for boys. Girls with lower progression rates reported more issues with near work and sun glare and less trust in LDA therapy’s effectiveness than girls with a higher progression rate. There was no statistically significant correlation between SE and the total answer score for both genders. Conclusions: Findings concerning childrens’ and adolescents’ psyche are a new aspect of myopia control. We prove that patients during pharmacological myopia control did not report significant problems caused by LDA therapy and they were convinced about its efficacy, had greater self-esteem, and recommended it to peers.

Microsurgical Treatment and Follow-Up of KOOS Grade IV Vestibular Schwannoma: Therapeutic Concept and Future Perspective.

PurposeSurgery of KOOS IV vestibular schwannoma remains challenging regarding the balance of extent of tumor resection (EoR) and functional outcome. Our aim was to evaluate the outcome of surgical resection and define a cut-off value for safe resection with low risk for tumor regrowth of KOOS IV vestibular schwannoma.MethodsAll patients presenting at the authors’ institution between 2000 and 2019 with surgically treated KOOS IV vestibular schwannoma were included. Outcome measures included EoR, facial/hearing nerve function, surgical complications and progression of residual tumor during the median follow-up period of 28 months.ResultsIn 58 patients, mean tumor volume was 17.1 ± 9.2 cm3, and mean EoR of 81.6 ± 16.8% could be achieved. Fifty-one patients were available for the follow-up analysis. Growth of residual tumor was observed in 11 patients (21.6%) followed by adjuvant treatment with stereotactic radiosurgery or repeat surgery in 15 patients (29.4%). Overall serviceable hearing preservation was achieved in 38 patients (74.5%) and good facial outcome at discharge was observed in 66.7% of patients, significantly increasing to 82.4% at follow-up. Independent predictors for residual tumor growth was EoR ≤ 87% (OR11.1) with a higher EoR being associated with a very low number of residual tumor progression amounting to 7.1% at follow-up (p=0.008).ConclusionsSubtotal tumor resection is a good therapeutic concept in patients with KOOS IV vestibular schwannoma resulting in a high rate of good hearing and facial nerve function and a very low rate of subsequent tumor progression. The goal of surgery should be to achieve more than 87% of tumor resection to keep residual tumor progression low.

Surgery results in low relapse and progression rates in extramedullary plasmacytoma of the head and neck: A case cohort and review of the literature.

Extramedullary plasmacytoma of the head and neck is a rare indolent neoplasm. Radiotherapy is often the preferred treatment option with excellent local control and survival. The risk of local recurrence or transformation to multiple myeloma is 10-30%. In our case-cohort, thorough, sensitive initial evaluation for disseminated clonal disease and the incorporation of surgery led to excellent results with no recurrences or systemic progression.