Repeat Courses Research Articles

Potential Missed Opportunities for Antenatal Corticosteroid Exposure and Outcomes Among Periviable Births: Observational Cohort Study

ABSTRACT Antenatal corticosteroid (ANCS) exposure reduces preterm infant death and morbidities, such as intracranial hemorrhage. Although observational studies suggest periviable infants may benefit from this treatment, many eligible women do not receive ANCSs due to unclear policies, lack of opportunity, or inconsistent care. Professional societies and the Eunice Kennedy Shriver National Institute of Child Health and Human Development recommend administering ANCSs at 24 weeks' gestation for all at-risk pregnancies and as early as 22 weeks with planned postnatal treatment. The aim of this study was to assess whether potential missed opportunities for ANCSs increase as gestational age decreases and are associated with higher rates of hospital mortality or severe brain injury. This was an observational cohort study of infants born at 24 National Institute of Child Health and Human Development Neonatal Research Network centers from 2006 to 2018. Included were infants at 220/7 to 256/7 weeks of gestation, without major birth defects, and a birth weight of 401 to 1000 g. Data were collected prospectively from birth to discharge, transfer, death, or 120 days. Antenatal corticosteroid exposure was defined as infants who received partial, complete, or repeat courses of the treatment. Potential missed opportunities for exposure were defined as infants who received no ANCSs, despite potentially having sufficient time to receive prenatal antibiotics, were administered magnesium sulfate, or experience prolonged rupture of membranes. Severe brain injury was defined as intracranial hemorrhage or periventricular leukomalacia on cranial imaging. The primary outcome was the rate of ANCS exposure and potential missed opportunities at each gestational age. Secondary outcomes included death and severe brain injury. A total of 7957 infants who were actively treated postnatally were included in the primary analysis. Of these, 87.6% had ANCS exposure, 5.7% had no exposure but potential missed opportunities for exposure, and 6.7% had no exposure and no potential missed opportunities. Potential missed opportunities for exposure were more common in infants born at 22 and 23 weeks versus 25 weeks (22 weeks: adjusted risk ratio [aRR], 11.06; 95% confidence interval [CI], 7.52–16.27; P < 0.001); 23 weeks: aRR, 3.24; 95% CI, 2.44–4.29; P < 0.001). No difference was observed between 24 and 25 weeks (24 weeks: aRR, 1.08; 95% CI, 0.82–1.42). From 2006 to 2018, infants at 22 weeks saw the largest increase in exposure to ANCSs (12.5%–87.2%) and a decrease in the rate of potential missed opportunities (68.8%–2.6%). Overall, the rate of mortality was 23% lower among infants in the exposure group than for those in the missed opportunities group (31% vs 54.8%; aRR, 0.77; 95% CI, 0.70–0.84; P < 0.001). Infants in the exposure group had lower risk of severe brain injury than those in the missed opportunities group (25% vs 44.5%; aRR, 0.64; 95% CI, 0.55–0.73; P < 0.001), with no significant variation by gestational age. In conclusion, the potential for missed opportunities for ANCS exposure was more common among periviable infants at 22 and 23 weeks compared with those at 25 weeks of gestation. Moreover, exposure to ANCSs was associated with lower rates of mortality and severe brain injury.

Repeat stereotactic body radiotherapy for oligometastatic disease

BackgroundPatients with oligometastatic disease (OMD) treated with metastasis-directed definitive local therapy such as stereotactic body radiotherapy (SBRT) are at risk of developing new metastases. Here, we compare characteristics and outcomes of patients treated with a single course and repeat SBRT. Materials/MethodsOMD patients treated with SBRT to 1–5 metastases were included in this retrospective study, and classified as single course or repeat SBRT. Progression-free survival (PFS), widespread failure-free survival (WFFS), overall survival (OS), systemic therapy-free survival (STFS) and cumulative incidence of different first failures were analyzed. Patient and treatment characteristics predicting the use of repeat SBRT were investigated using univariable and multivariable logistic regression. ResultsAmong the 385 patients included, 129 and 256 received repeat or single course SBRT, respectively. The most common primary tumor and OMD state in both groups were lung cancer and metachronous oligorecurrence. Patients treated with repeat SBRT had shorter PFS (p < 0.0001), while WFFS (p = 0.47) and STFS (p = 0.22) were comparable. Distant failure, particularly with a single metastasis, was more frequently observed in repeat SBRT patients. Repeat SBRT patients had longer median OS (p = 0.01). On multivariable logistic regression, low distant metastases velocity and more previous lines of systemic therapy significantly predicted the use of repeat SBRT. ConclusionDespite shorter PFS and comparable WFFS and STFS, repeat SBRT patients had longer OS. The role of repeat SBRT for OMD patients warrants further prospective investigation, focussing on predictive factors to select patients that might derive a benefit.

Biological Effective Radiation Dose for Multiple Myeloma Palliation

Various radiation therapy (RT) dose/fractionation schedules are acceptable for palliation in multiple myeloma. Nine years of single-institution RT experience were reviewed to determine the influence of dose/fractionation and other factors pertinent to individualizing therapy. In total, 152 items were identified from Current Procedural Terminology codes for multiple myeloma treatment from 2012 through June 30, 2021. After exclusions, 205 sites of radiation in 94 patients were reviewed. Data were captured from treatment planning and clinical records. To statistically assess the association between biological effective dose (BED10) and variables of interest, BED was first dichotomized to <24 Gy versus ≥24 Gy. Multivariate analysis used SAS software and a generalized estimating equation approach to account for multiple observations per patient. Fractions of 1.8 to 8 Gy were used in 1 to 25 fractions. Most patients had no significant toxicity. Grade 1 toxicity was more likely with greater BED radiation courses, as expected (20% vs 12% for BED <24 Gy). Pain relief was complete or very good for most sites, with <3% reporting no pain relief. Eleven sites in 9 patients required retreatment. All retreatment sites had palliation that was lasting, with a median of 22 months to last follow-up or death after repeat course (range, 0.5-106 months). There was a trend for better pain control and less risk of fracture retreatment with BED ≥24 Gy. Most patients had good palliation without toxicity. BED ≥24 Gy caused 8% greater risk of grade 1 toxicity and trended toward better pain control plus reduced risk of fracture retreatment.

Proton beam therapy in repeat irradiation of recurrent head and neck tumors: analysis of short-term results

Introduction. Recurrence of head and neck tumors occurs in 50 % of cases and usually has locoregional character. Due to the characteristics of dose distribution, proton beam therapy is a promising treatment option for patients with recurrences of tumors in this location who previously underwent radiation therapy.Aim. To evaluate the effectiveness and tolerability of repeat irradiation using active scanning proton beam therapy in patients with recurrent head and neck tumors who previously underwent radiation therapy.Materials and methods. Between November of 2015 and December of 2020, 40 patients with locoregional recurrence of head and neck tumors underwent treatment using active scanning proton beam therapy at the A. F . Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center. Median cumulative dose of primary irradiation was 64.5 Gy. Median time between primary and repeat irradiation was 35.7 months, mean irradiated volume of the repeat course was 94.5 cm3. Proton beam therapy was performed using standard mode (2 isoGy) and accelerated hypofractionation (2.4 isoGy / 3 isoGy) with mean equivalent cumulative dose of 56.4 Gy (α / β = 10). Radiation toxicity was evaluated using the Radiation Therapy Oncology Group European (RTOG) / Organization for Research and Treatment of Cancer (EORTC) scale.Results. Treatment response was achieved in 34 (85 %) patients: in 17 (42.5 %) patients, stable disease was observed; in 10 (25 %) patients, partial response was observed; and in 7 (17.5 %) patients, complete response was observed. In 6 (15 %) cases, disease progression was diagnosed at first follow-up examination. One- and two-year locoregional control, progression-free survival and overall survival were 58.4 / 19.8; 44.5 / 19.8 and 82.3 / 38.8 % respectively with median follow-up duration of 14.2 months. Median survival was 19.5 months. Grade III and above early radiation toxicity was observed in 3 (7.5 %) patients. In total, 6 (15 %) cases of grade III complications and 2 (5 %) episodes of carotid artery rupture leading to death were observed. Overall frequency of complications of grade III and higher was 20 %.Conclusion. Repeat irradiation using proton beam therapy can be considered an effective and safe treatment method for patients with recurrent head and neck tumors. Dosimetric and radiobiological benefits of proton beams allow to achieve balance between high doses and radiation exposure in previously irradiated tissues.

Online Credit Recovery as an Intervention for High School Students Who Fail Courses

Online credit recovery (OCR) refers to online courses that high school students take after previously failing the course. Many have suggested that OCR courses are helping students to graduate from high school without corresponding increases in academic skills. This study analyzes administrative data from the state of North Carolina to evaluate the efficacy of OCR using full data from public and private OCR providers. Findings indicate that students who fail courses and enroll in OCR are 20 percentage points more likely to earn course credit, have lower test scores of up to two tenths of a standard deviation, and are about eight percentage points more likely to graduate high school within 4 years than students who repeat courses traditionally. Test score differences are particularly large for Biology compared to Math I and English II. Hispanic and economically disadvantaged OCR students are more likely to graduate high school than their peers.

The role of antenatal corticosteroids in twin pregnancy.

Twin pregnancy was associated with significantly higher rates of adverse neonatal and perinatal outcomes. One of the underlying causes is that twins are prone to preterm birth. Antenatal corticosteroids are widely used for reducing the incidence of neonatal respiratory distress syndrome initially and other neonatal mortality and morbidities subsequently. As it is widely used as a prophylactic treatment for potential premature births, there remain controversies of issues relating to twin gestations, including window for opportunity, timing of use, repeat course, optimal administration-to-delivery intervals, dosage, and type of corticosteroid. Thus, we present a thorough review of antenatal corticosteroids usage in twin gestation, emphasizing the aforementioned issues and attempting to offer direction for future investigation and clinical practice.

Three Weekly Intra-Articular Injections of Hylan G-F 20 vs Arthrocentesis in Patients with Chronic Idiopathic Knee Osteoarthritis: A Multicenter, Evaluator- and Patient-Blinded, Randomized Controlled Trial

Knee osteoarthritis is a leading cause of disability worldwide. Symptoms can vary over time, leading to episodes of worsened symptoms known as flares. Intra-articular injection of hyaluronic acid has demonstrated long-term symptomatic relief in the broader knee osteoarthritis population, although its use in the flare population has not been extensively examined. To assess the efficacy and safety of 3 once-weekly intra-articular injections of hylan G-F 20 (as single and repeat courses) in patients with chronic knee osteoarthritis, including a subpopulation that experienced flare. Prospective randomized controlled, evaluator- and patient-blinded, multicenter trial with 2 phases: hylan G-F 20 vs arthrocentesis only (control) and 2 courses vs single-course hylan G-F 20. Primary outcomes were visual analog scale (0-100 mm) pain scores. Secondary outcomes included safety and synovial fluid analysis. Ninety-four patients (104 knees) were enrolled in Phase I, with 31 knees representing flare patients. Seventy-six patients (82 knees) were enrolled in Phase II. Long-term follow-up was 26 to 34 weeks. In flare patients, hylan G-F 20 showed significantly more improvement than the controls for all primary outcomes except pain at night (P = 0.063). Both 1 and 2 courses of hylan G-F 20 showed significant improvements from baseline for primary outcomes with no differences in efficacy between groups in the intention-to-treat population at the end of Phase II. Two courses of hylan G-F 20 showed better improvement in pain with motion (P = 0.0471) at long-term follow-up. No general side effects were reported, and local reactions (pain/swelling of the injected joint) resolved within 1 to 2 weeks. Hylan G-F 20 was also associated with reduced effusion volume and protein concentration. Hylan G-F 20 significantly improves pain scores vs arthrocentesis in flare patients with no safety concerns. A repeat course of hylan G-F 20 was found to be well tolerated and efficacious.

Эффективность ритуксимаба в терапии системного ювенильного идиопатического артрита

Эффективность ритуксимаба в терапии системного ювенильного идиопатического артрита

Predictability of response to rTMS in repeated treatment courses for patients with Major Depressive Disorder

Predictability of response to rTMS in repeated treatment courses for patients with Major Depressive Disorder

Optimal Treatment Interval of Viscosupplementation for Osteoarthritic Knee Pain: Real-world Evidence from a Retrospective Study

Background: The evidence supporting multiple courses of viscosupplementation for knee osteoarthritis continues to grow; however, the optimal treatment interval for repeat courses is not well understood. To address this, we compared baseline pain and disability scores in patients returning for subsequent treatment with their prior discharge scores. Methods: We retrospectively collected data from patients at 16 rehabilitation clinics who presented for repeated courses of viscosupplementation treatment for knee OA. Primary outcomes were pain (visual analog scale, VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores, which were collected following the initial treatment course and compared with scores upon return for treatment. The proportion of patients who fulfilled a minimal clinically important difference in each outcome was calculated. Results: 61 patients (81 knees) were included in our analysis. After a 6-month treatment interval, no significant differences were noted between post-discharge and returning scores for either VAS (p=0.73) or WOMAC (Pain: p=0.42; Function: p=0.54; Stiffness: p=0.29). Patients waiting 9 months to return for treatment saw a 45% increase in their pain scores (p=0.10) and significant worsening in WOMAC scores (Pain: p=0.007; Function: p=0.03; Stiffness: p=0.04). At 12 months, pain (p=0.01), WOMAC Pain (p=0.05), and WOMAC Stiffness (p=0.02) had all worsened significantly compared to discharge following the initial course. Conclusion: Our data indicate that patients who return for treatment within a 6-month treatment interval maintain their improvements, but that when the interval increases to 9 months or more, patients present as significantly worsened, having lost the benefit of their initial course of treatment.

428: A PERSISTENT CASE OF COVID-19 IN A PATIENT WITH COMPLETE DIGEORGE SYNDROME

Introduction: DiGeorge Syndrome is a relatively common microdeletion syndrome defined by a deletion in chromosome 22 at position 22q11.2 and clinically characterized by T-cell deficiency, unique facial features, congenital heart disease and hypocalcemia. Complete DiGeorge Syndrome refers to a subset that is athymic (< 1%) without any T cell function. The adaptive immune response is then disturbed leading to an increased susceptibility to infections given the lack of cytotoxic response to infected cells. In this population, pathogens can persist and have unique presentations due to the lack of an adaptive immune response. Description: We present a case of persistent COVID-19 in a 3-year-old male with complete DiGeorge syndrome. Two months prior to presentation, he was treated with remdesivir for a symptomatic COVID-19 infection. He later represented with severe persistent hypocalcemia despite aggressive IV electrolyte repletion as well as a new acute hemolytic anemia with positive Coombs and concern for Graft vs Host disease. During his hospital course, he had worsening respiratory status leading to re-intubation. Bronchoscopy with BAL showed significant SARS-CoV-2 viral load and he was started on a repeat course of remdesivir and convalescent plasma. Two weeks after initial bronchoscopy, repeat BAL samples showed unchanged SARS-CoV-2 viral load leading to another course of remdesivir and convalescent plasma. After a month of invasive ventilation, he was able to be successfully extubated and eventually discharged from the hospital, despite having persistently an elevated SARS-CoV-2 viral load and polymerase chain reaction testing positivity. Discussion: This case illustrates a unique situation of COVID-19 in a patient without an adaptive immune response due to complete DiGeorge Syndrome. This patient population is athymic without any T cell function leading to a lack of cytotoxic response and a susceptibility to infections due to the inability to clear infected cells. With COVID’s high mutation rate leading to multiple new strains, we present a case illustrating the possibility of new strain mutations developing due to persistent COVID in a patient with an inability to clear the viral infection.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) as a novel presentation of CNS autoimmunity in a pediatric patient with Wiskott-Aldrich syndrome (WAS)

Objective Report a novel case of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) presenting as relapsing bilateral optic neuritis in a pediatric patient with Wiskott-Aldrich syndrome (WAS). Background WAS is a rare X-linked primary immunodeficiency caused by mutations in the WAS gene that leads to increased susceptibility to infections, thrombocytopenia, eczema, malignancies, and autoimmunity. Known CNS autoimmune manifestations include cerebral vasculitis, but optic neuritis, CNS demyelination, and MOGAD have not been previously reported. Design/Methods Chart review Results A 5-year-old boy with a history of chronic immune thrombocytopenia, hypogammaglobulinemia, anemia, and focal epilepsy developed binocular vision loss. MRI of the brain demonstrated enlargement of bilateral optic nerves with marked enhancement of the nerve sheaths consistent with optic neuritis, as well as multiple small enhancing supratentorial lesions. He was treated with pulse methylprednisolone followed by oral steroid taper, and he returned to baseline with no reported residual visual deficits. Five months later, he experienced a relapse of bilateral vision loss, and repeat MRI re-demonstrated bilateral optic neuritis as well as resolution of prior brain lesions. He was treated with repeat course of steroids and experienced moderate improvement in his vision. Rituximab was then initiated to prevent further relapses of optic neuritis while treating his chronic suspected immune-mediated thrombocytopenia. Myelin oligodendrocyte glycoprotein antibody (MOG-IgG) via serum fluorescence-activated cell sorting assay was positive (titer 1:100), confirming a diagnosis of MOGAD. At age six, molecular panel testing for genes associated with primary immunodeficiency identified a missense WAS gene variant. He was subsequently found to have decreased WAS protein expression consistent with a diagnosis of WAS. Conclusions We describe a case of pediatric MOGAD presenting with multiphasic bilateral optic neuritis in a patient with WAS. This case expands the reported spectrum of CNS autoimmunity associated with WAS and may help to inform indications for therapeutic options such as bone marrow transplant.

Efficacy and Safety of Long-Term Romiplostim Use for Refractory Aplastic Anemia

Introduction: Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome characterized by pancytopenia and hypocellular bone marrow caused by the destruction of hematopoietic stem cells by lymphocytes. About one-third of patients with severe AA who cannot undergo allogeneic hematopoietic stem cell transplantation from a matched sibling donor are refractory to single or repeated immunosuppressive therapy courses. Romiplostim (ROMI), a thrombopoietin receptor agonist, signals and activates intracellular transcriptional pathways via the thrombopoietin receptor, resulting in stimulation of hematopoietic stem and progenitor cells. Our previous research, a phase II/III, multicenter, open-label interventional study, showed that ROMI induced the recovery of at least one lineage of blood cells in >80% of patients with refractory AA. However, data on the long-term efficacy and safety of ROMI in refractory AA beyond 52 weeks are scarce. Additionally, the pretreatment baseline factors of patients who achieve hematological response during treatment and maintain response after discontinuing ROMI are unclear. To address these issues, we report the results at the end of the extension phase (June 2020) of the aforementioned phase II/III study. Methods: We conducted a long-term follow-up analysis of the efficacy and safety of ROMI 10 μg/kg administered subcutaneously once weekly for 4 weeks (Weeks 1-4), followed by 1-step titration to 5, 10, 15, and 20 μg/kg once weekly up to 52 weeks (Weeks 5-52) depending on platelet response. The extension study was started from Week 56 after a 4-week suspension period. The patients continued to receive the same dose of ROMI they received on Week 52 until its commercially available date for the treatment of AA in the study country or the end of June 2020 (end of the extension phase), whichever occurred first. Results: Of the 31 patients enrolled in the phase II/III study, 27 completed the 53-week assessment. Twenty-five hematological responders (any cell lineage) and 2 non-responders entered the extension phase. ROMI was administered for 2 years in 23 patients, 3 years in 7 patients, and 3.5 years in 6 patients in this extension study. The median dose of ROMI was 20 μg/kg at Week 53, which was reduced to 15 μg/kg at 2 years, and 7.5 μg/kg at 3.5 years (Figure 1). Of the 2 non-responders, 1 patient showed platelet response at 2 years, which was sustained thereafter, while the other failed to respond by the end of the extension study at 103 weeks. Of the patients who failed to achieve the platelet (n=7) and erythrocyte (n=6) responses at 1 year, 3 (43%) and 1 (17%) showed responses at 2 years; the mean platelet count increased from 38.3 to 76.7 ×109/L in the 3 platelet responders, and the hemoglobin level increased from 8.0 to 9.2 g/dL in the erythrocyte responder (Figure 2). Of the 23 patients who needed blood transfusions at baseline, 4 and 2 of them still required erythrocyte and platelet transfusions at 1 year, and 4 and 5 of them did so at 2 years, respectively. Five patients remained in response after discontinuing ROMI lasting 29-111 weeks even after discontinuing treatment. These 5 patients had relatively high baseline reticulocyte counts (45.8-93.8 ×109/L, median 57.5 ×109/L) compared with the remaining 22 patients (2.7-114.7 ×109/L, median 46.5 ×109/L). The most common adverse drug reactions included headache (3 cases, 9.7%) and muscle spasms (2 cases, 6.5%); cytogenetic abnormality (-7) led to discontinuation of the study drug in 1 case. Two patients presented with chromosomal abnormalities of unknown significance, including 46,XX,t(11;17) at Week 108 and 46,XX,add(10) at Week 134. No transformation to acute myeloid leukemia or myelodysplastic syndromes occurred. Conclusions: The up to 3.5-year follow-up study of ROMI administration in adult patients with refractory AA demonstrated its safety and efficacy during the extension period. The dose of ROMI was on a downward trend during the long-term follow-up. Nearly half the patients who did not achieve platelet or erythrocyte responses to ROMI at Week 52 eventually achieved responses by continuing the administration until the end of the study, demonstrating the efficacy of prolonged ROMI administration. High reticulocyte counts at ROMI initiation may predict achievement of response after discontinuing ROMI. Further studies with larger sample sizes should confirm these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Reirradiation with Photon Radiotherapy for Recurrent or New Primary Breast Cancer after Prior Breast Irradiation

<h3>Purpose/Objective(s)</h3> Recurrent or new primary breast cancer may benefit from the local and/or regional recurrence risk reduction provided by RT, but delivery of a repeat course of RT is challenging due to risks of potential serious toxicities to organs at risk. This has led to limited use and heterogeneous practice patterns of salvage RT delivery. We hypothesize that breast cancer reirradiation (reRT) may be feasible using modern photon treatment techniques, and we present clinical outcomes and toxicities from a large single institution cohort. <h3>Materials/Methods</h3> In an IRB-approved retrospective study, all consecutive patients with recurrent or new primary non-metastatic breast cancer treated with breast or chest wall (CW) RT and photon reRT from a single institution were identified. Patient and tumor characteristics, treatment parameters, clinical outcomes and toxicities were collected. Recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) were defined from reRT start to date of any recurrence, distant recurrence, and death or last follow-up and estimated using Kaplan-Meier methodology. <h3>Results</h3> In total, 126 consecutive patients treated with reRT from 2013-2020 met criteria for analysis. Median age at reRT was 65 years (range 39-88). ReRT was delivered with 3DCRT in 47.6%, VMAT in 46.0%, and static IMRT in 6.4%. Median first, second, and cumulative prescription doses were 60.0 Gy, 46.4 Gy, and 105.0 Gy, respectively. Most received whole breast (WB) (80.2%) or partial breast (PB) (8.7%) initial RT. At reRT, 30.9% were treated to the PB, 11.1% WB/CW, 37.3% WB/CW with comprehensive regional lymph nodes (LN), and 12.8% WB/CW with partial regional LN. Median time between RT courses was 95 months (range 10-361). At a median follow-up of 26.5 months, 9 patients had died. Locoregional, distant, and any recurrence developed in 15 (11.9%), 22 (17.5%), and 28 (22.2%) patients, respectively. Estimated 3-year RFS was 80.7%, DMFS was 80.9%, and OS was 93.2%. Eleven (8.7%) patients developed grade 3 (G3) toxicities (dermatitis (n=8), acute (n=1) and late (n=1) CW pain, decreased joint range of motion (ROM) (n=1)); no G4 or G5 toxicities occurred. Five (4.0%) patients developed rib fracture. Of 23 patients retreated to a reconstructed CW, 30.4% and 34.8% developed Baker G1-2 or G3-4 implant contracture, respectively. Four patients had significant brachial plexus overlap, of whom 1 developed G2 decreased joint ROM and G2 soft tissue fibrosis and 1 developed G3 decreased joint ROM. <h3>Conclusion</h3> In the largest institutional experience to date on the use of photon reRT for recurrent or new primary breast cancer, reRT is associated with low rates of severe adverse events. In this high-risk population, locoregional and distant disease control rates are high. Further prospective study is needed to define the optimal treatment volume, prescription dose selection, and cumulative dose constraints with reRT to maximize the likelihood for successful and safe salvage therapy.

Early Imaging Characteristics Associated with Development of Future Brain Metastases in Patients Undergoing Stereotactic Radiosurgery

<h3>Purpose/Objective(s)</h3> Brain MRIs are carefully reviewed during the process of stereotactic radiosurgery (SRS) planning to select targets with radiographic characteristics typical of brain metastases (BM). Some BMs, especially ones that are small, dural-based, appear similar to blood vessels or resemble microinfarcts, are difficult to definitively identify and may go untreated initially, only to become apparent on future imaging. We hypothesized that in patients receiving multiple courses of SRS, retrospective review of the initial planning MRI would reveal early evidence of lesions that would subsequently develop into metastases requiring SRS. <h3>Materials/Methods</h3> Patients undergoing two or more courses of SRS to BMs within a 6-month interval between 2016 and 2018 were included in this single-institution, retrospective study. Exclusion criteria included small cell histology or previous whole-brain radiation therapy. Brain MRIs from the initial treatment course were reviewed for the presence of a contrast enhancing lesion at the same location as a lesion treated in a subsequent course of SRS, which was classified as a "retrospectively identified metastasis" or RIM. <h3>Results</h3> Of the 683 patients who underwent 923 courses of SRS within the study period, 98 patients met inclusion criteria. There were 120 repeat courses of SRS, with 345 treated metastases in the subsequent course, 128 of which were RIMs. 48% were within 5mm of the dura: 12% were abutting blood vessels: 8% became symptomatic. 23% of subsequent courses consisted of metastases that were all identified as RIMs. <h3>Conclusion</h3> Radiographic evidence of lesions requiring future treatment was occasionally present on brain MRIs from prior SRS treatments. RIMs are typically small, often abut blood vessels and/or the dura, and rarely become symptomatic. In some patients undergoing SRS, RIMs alone were treated, suggesting that enhanced detection of RIMs could reduce the need for additional courses of SRS.

New approach to the treatment of cancer of large duodenal papilla and extrahepatic bile ducts with photodynamic therapy

The study is based on the treatment of 79 patients with adenocarcinoma of large duodenal papilla and extrahepatic bile ducts. 29 patients received palliative bile drainage operations with PDT. 50 patients in the group of chronological control only palliative bile drainage operations had been performed. Patients in research group received from 1 to 3 PDT courses in a year. In total 29 patients received 52 PDT courses. Outcomes were assessed by determining the median survival. The treatment was well-tolerated by the patients. The median survival time was 18 months (11–60 months). In patients who had only one PDT session during the year median survival was 12,5 months; in patients who had two or more PDT sessions median survival was 29 months (15–60 months). Results of PDT treatment for cancer of this localization are comparable with the results of radical surgeries and overcome palliative surgeries. Decrease of tumor growth rate and longer survival period in patients after PDT are determined by vascular mechanisms produced by PDT (vascular thrombosis and impaired tumor blood supply), these factors provide long-term process stabilization. Repeated PDT courses signifi cantly improve treatment results.

A BENEFICIAL EFFECT OF LONG-TERM TREATMENT OF RITUXIMAB IN INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SYSTEMIC SCLEROSIS

A BENEFICIAL EFFECT OF LONG-TERM TREATMENT OF RITUXIMAB IN INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SYSTEMIC SCLEROSIS

ИССЛЕДОВАНИЕ РЕПРОДУКТИВНОЙ ТОКСИЧНОСТИ ЗЕМЛЯНИКИ САДОВОЙ ЛИСТЬЕВ ЭКСТРАКТА СУХОГО

Abstract. The growing demand for medicinal herbal preparations, the changing requirements of the regulatory system for their effectiveness and safety during the registration procedure pose certain tasks for their study. For the prevention and treatment of various diseases, along with a wide range of synthetic medicines, herbal medicines are used. At the same time, not only medicinal plants and collections are used as herbal medicines, but also various plant extracts, individual biologically active compounds isolated from plants. A preclinical study of reproductive toxicity seems necessary, since it is known that some medicinal plants have a teratogenic effect [1]. The main task of the preclinical study of the effect of potential drugs on the reproductive system is to prove or exclude the possibility of developing a teratogenic effect caused by a new pharmacological agent in an animal experiment. Mandatory testing for reproductive toxicity should be subject to new, original pharmacological agents, as well as well-known drugs recommended for use in long repeated courses, as well as for the treatment of pregnant women and when prescribed during lactation; as preventive agents and contraceptives [2, 3]. Strawberry garden leaf extract dry (strawberry garden extract) is one of the potential substances for obtaining safe medicines for the prevention and treatment of diseases of the urinary tract, as it has diuretic and anti–inflammatory activity [4]. The study of the reproductive toxicity of strawberry garden extract is a mandatory part of the preclinical safety assessment of a new pharmacological substance for obtaining safe medicines with it. In this regard, studies on the reproductive toxicity of strawberry garden leaves of dry extract are relevant in the framework of preclinical studies and substantiation of the use of the substance for the further development of medicines based on it.

A Rare Case of Guillain–Barré Syndrome with Signs of Meningeal Irritation and Treatment-Related Fluctuations/Relapse

Abstract Guillain–Barré Syndrome is an acute inflammatory demyelinating polyradiculoneuropathy that can present at any age. The presentation of Guillain–Barré syndrome may be variable as the classic symptoms of areflexia and flaccid paralysis may or may not be present. Here we reported a case of a 15-year-old male patient who presented with complaints of weakness in bilateral lower limbs with inability to sit along with slurred speech and drooling of saliva with positive meningeal signs like neck stiffness and Kernig's sign. His symptoms improved with immunoglobulin therapy. Five days later, the child again had pain and increased weakness with increased work of breathing for which repeat dose and course of immunoglobulins were given. As patients with signs of meningeal irritation may suggest other diseases such as meningitis, it is important to consider atypical cases of Guillain–Barré syndrome along with treatment-related fluctuations as observed in our patient.

The Association Between a Second Course of Cardiac Rehabilitation and Cardiovascular Outcomes Following Repeat Percutaneous Coronary Intervention Events.

Survivors of coronary artery disease (CAD) events are at risk for repeat events. Although evidence supports cardiac rehabilitation (CR) after an initial CAD event, it is unclear whether a repeat course of CR (CR × 2) is beneficial after a recurrent CAD event. The purpose of this study was to determine the association of CR × 2 with clinical outcomes in persons undergoing repeat percutaneous coronary intervention (PCI). We assessed the prevalence of CR × 2 and its impact on cardiovascular outcomes in individuals who experienced a repeat PCI at the Mayo Clinic hospitals between January 1, 1998, and December 31, 2013. Landmark analyses were used to calculate unadjusted and propensity score adjusted mortality rates and cardiovascular (CV) events rates for patients who underwent CR × 2 compared with those who did not. Among 240 individuals who had a repeat PCI and who had participated in CR after their first PCI, 97 (40%) participated in CR × 2. Outcomes were assessed for a mean follow-up time of 7.8 yr (IQR 7.1-9.0 yr). Propensity score-based inverse probability weighting analysis revealed that CR × 2 was associated with significantly lower target lesion revascularization (HR = 0.47: 95% CI, 0.26-0.86; P = .014), lower combined end point of CV death, myocardial infarction, and target lesion revascularization (HR = 0.57: 95% CI, 0.36-0.89; P = .014), and lower CV hospitalization (HR = 0.60; 95% CI, 0.43-0.84; P = .003). A second course of CR following repeat PCI is associated with a lower risk of adverse clinical outcomes. These findings support current policies that allow for repeat courses of CR following recurrent CV events.