Completed Cycle Research Articles

Do serum vitamin D levels affect assisted reproductive outcomes and perinatal outcomes in young non-PCOS patients? A retrospective study.

This study aimed to determine the influence of serum vitamin D levels on assisted reproductive and perinatal outcomes in young non-polycystic ovary syndrome (PCOS) patients. A total of 3397 non-PCOS women under 35years who underwent their first IVF/ICSI cycle at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University, from 2018 to 2019, were included. The women were categorized into two groups based on their serum 25(OH)D concentrations: deficient group [25(OH)D < 50nmol/L] and non-deficient group [25(OH)D ≥ 50nmol/L]. Ovulation induction results, clinical pregnancy rate, cumulative live birth rate (CLBR), and perinatal outcomes of both groups were compared. A total of 1113 non-PCOS women had successful pregnancies in their first completed IVF cycle. Comparison of laboratory results between the two groups revealed a significantly higher number of oocytes retrieved in the vitamin D-non-deficient group (15.2 ± 6.8 vs. 14.5 ± 6.7, p = 0.015). After controlling for confounding factors, there was no significant difference in the CLBR between the vitamin D-deficient group and the non-deficient group (71.0%, 1,973/2,778 vs. 69.0%, 427/619, p = 0.314, unadjusted). The prevalence of gestational diabetes mellitus (GDM) was higher in the vitamin D-deficient group than in the vitamin D-non-deficient group in both fresh-cycle singleton live births (3.8% vs. 1.2%) and twin live births (2.3% vs. 1.5%). This study demonstrated that vitamin D-deficient group had a lower number of oocytes retrieved than the non-deficient group and a higher prevalence of GDM, suggesting that vitamin D deficiency impacts assisted pregnancies and perinatal outcomes in infertile non-PCOS women. However, further studies are required to confirm these findings.

MPROVING STUDENTS’ WRITING SKILL ON DESCRIPTIVE PARAGRAPH THROUGH INSTAGRAM PERSONAL PHOTOGRAPHY AT THE 11th GRADE OF SMA PANGERAN ANTASARI MEDAN

This study's goal was to assess the writing skills of class XI SMA students. Regarding text descriptions, Pangeran Antasari. How does using a personal photo help students create better text descriptions? is how the issue is phrased. The purpose of this study was to teach secondary school pupils how to use real-world examples to improve their ability to create descriptive prose. Researchers employ the Classroom Action Research Methodology (CAR). 40 pupils from class XI made up the study's sample. The study's findings, which took into account both qualitative and quantitative data, showed that 90% of students could finish writing assignments once a discussion technique was applied. Data from cycles I and II were used to make this conclusion. In the pre-test, 17 students had a 42% success rate, while 23 students scored a 57.5 percent failure rate. 25 students completed cycle I with a success percentage of 62.5%, while 15 students failed with a rate of 37.5%. In cycle II, 36 students achieved a 90% success rate, while 10 students failed the post-test II with a 10% failure rate. Their writing skills greatly improved once the teaching and learning activities got going. It might be argued that using personal pictures helps pupils become better at producing descriptive text.Keywords : Personal photograph, descriptive text.

1912 Reviewing the effect of COVID pandemic on changing clinical practice of administrating Zoledronic Acid to hip fracture patients

Abstract Introduction Reduction in outpatient appointments during the COVID-19 pandemic and patient concern surrounding risk of contracting COVID-19 by attending day-case settings, resulted in delayed or cancelled medical treatments including Zoledronic Acid infusions as management for Osteoporosis. This, alongside recent research concluding that these treatments can be given safely as early as 1-2 weeks post-fracture, lead to the adaptation of protocol at Hull University Teaching Hospitals Trust in 2021, to provide rapid loading of Cholecalciferol over 6 days, prior to administration of Zoledronic Acid on day 7. However, some concerns remain surrounding the potential interference with bone remodelling and healing. This completed audit cycle evaluates the logistics and safety of this new protocol. Methods All patients over 60, admitted with neck of femur fracture who received Zoledronic Acid infusion as inpatient or outpatient in 2019 and 2021 were included in the initial and repeat audit respectively. Electronic records for the following 12 months were analysed evaluating for further fragility fracture and mortality rate. Results There was an increase in patients receiving Zoledronic Acid as an inpatient treatment from 21% in the initial audit to 97% in the repeat audit. There was a slight increase in mortality rate at one year from 14% to 19%. The percentage of a further fragility fracture within one year, remained stable at 7%. Conclusion The increase in inpatient infusions suggests more patients with significant frailty who would otherwise not have been able to attend outpatient settings, have been able to receive treatment. The mortality results reflect this frailer audit population. The absence of a substantial increase in the rate of further fragility fracture at one year; supports the earlier administration of Zoledronic Acid as a management protocol.

The number of previous implantation failures is a critical determinant of intrauterine autologous platelet-rich plasma infusion success in women with recurrent implantation failure.

We aimed to identify factors influencing the reproductive outcomes of frozen-thawed embryo transfer (FET) with intrauterine autologous platelet-rich plasma (PRP) infusion in patients with either a thin endometrium or recurrent implantation failure (RIF) despite a normal endometrial appearance. In this retrospective study of women who underwent PRP-FET, factors influencing PRP-FET outcomes were identified using multivariate logistic regression analysis. We enrolled 111 patients (70 with refractory thin endometrium and 41 with RIF but no thin endometrium). For 99 completed FET cycles, the β-hCG positivity rate was 46.7%, clinical pregnancy rate (CPR) was 41.0%, and live birth rate (LBR) was 36.2%. PRP treatment was associated with significant improvements over previous cycles, and participants with thin endometria demonstrated thickening. Multivariate logistic regression analysis showed that the number of previous implantation failures in women with RIF was a significant factor affecting the PRP-FET outcomes. The CPR and LBR of women with RIF were lower when there had been ≥3 previous implantation failures occurred. Intrauterine PRP infusion improves the pregnancy outcomes of patients with RIF or a thin endometrium. The number of previous implantation failures is a critical determinant of successful intrauterine PRP infusions in women with RIF.

W1+∞ and [formula omitted] algebras, and Ward identities

It was demonstrated recently that the W1+∞ algebra contains commutative subalgebras associated with all integer slope rays (including the vertical one). In this paper, we realize that every element of such a ray is associated with a generalized W˜ algebra. In particular, the simplest commutative subalgebra associated with the rational Calogero Hamiltonians is associated with the W˜ algebras studied earlier. We suggest a definition of the generalized W˜ algebra as differential operators in variables pk basing on the matrix realization of the W1+∞ algebra, and also suggest an unambiguous recursive definition, which, however, involves more elements of the W1+∞ algebra than is contained in its commutative subalgebras. The positive integer rays are associated with W˜ algebras that form sets of Ward identities for the WLZZ matrix models, while the vertical ray associated with the trigonometric Calogero-Sutherland model describes the hypergeometric τ-functions corresponding to the completed cycles.

Safety and Tolerability of Magrolimab Combinations in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Safety Run-in Results from a Phase 2 Study

Background Outcomes remain poor for patients (pts) with RRMM; thus, novel combinations incorporating standard-of-care (SOC) regimens with new drugs possessing unique mechanisms of action and nonoverlapping toxicity are needed. Magrolimab (Magro) is a first-in-class monoclonal immunoglobulin G4 antibody blocking CD47, an antiphagocytic signal overexpressed in cancer cells, including MM, enabling them to evade phagocytosis. In vitro, blocking CD47 resulted in elimination of MM cells, and preclinical data suggested that Magro may synergize with commonly used agents in MM. Reported here are initial safety and tolerability data from 3 safety run-in (SRI) cohorts of our phase 2, open-label, multiarm study (NCT04892446) in which Magro-based combinations were evaluated in pts with RRMM. Methods Adult pts with RRMM were eligible if they had received ≥3 prior lines of therapy for MM, including an immunomodulatory drug and a proteasome inhibitor. In the SRI cohorts, pts received Magro in the following combinations: with daratumumab (Magro + D), pomalidomide/dexamethasone (Magro + Pd), or carfilzomib/dexamethasone (Magro + Kd). At the initial dose level tested, Magro was given intravenously as a 1-mg/kg priming dose, followed by a maintenance dose of 30 mg/kg every week during the first 2 cycles and then every 2 weeks starting in cycle 3. All other therapies were administered at standard doses and schedules per clinical guidelines. Dose-limiting toxicities (DLTs) were evaluated throughout cycle 1 (35 days); cycles were 28 days thereafter. Primary end points of the SRI included incidence of adverse events (AEs) and DLTs. Pts were included in the DLT-evaluable population if they met 1 of 2 criteria: (1) experienced a DLT during cycle 1 or (2) completed cycle 1 and received ≥3 Magro infusions and ≥2 (D, d, K) or ≥10 (P) doses of the SOC agents. DLTs were generally defined as grade (gr) ≥3 AEs that worsened from baseline and were at least possibly Magro-related (with a few exceptions, including gr 3 anemia and gr 3 neutropenia resolving within 2 weeks). Dose de-escalation of Magro was planned in the event of &amp;gt;2 DLTs per 6 DLT-evaluable pts. Results Of the 25 pts treated in the SRI (Magro + D, n = 9 [6 DLT evaluable]; Magro + Pd, n = 9 [6 DLT evaluable]; Magro + Kd, n = 7 [5 DLT evaluable]), all were treated at the Magro initial dose level. Median (range) age was 59 (55-78) years for Magro + D, 69 (46-79) years for Magro + Pd, and 64 (57-82) years for Magro + Kd. The mean (range) number of prior lines of therapy received was 5.2 (3-9). Two DLTs were reported: gr 3 febrile neutropenia (Magro + D) and gr 3 dyspnea (Magro + Pd) experienced in a context of probable infusion-related reaction (IRR). No DLTs were reported in the Magro + Kd arm. All pts experienced ≥1 treatment-emergent AE (TEAE); all but 2 experienced ≥1 Magro-related TEAE ( Table 1). The most common Magro-related TEAE observed in each cohort was anemia; other common Magro-related TEAEs were headache (Magro + D), fatigue (Magro + D, Magro + Pd), and thrombocytopenia (Magro + Kd). Magro-related anemia was reported in 13 of 25 pts (gr ≥3, n = 6). There were 3 pts with Magro-related IRRs (all gr 1-2: Magro + Kd, n = 1; Magro + D, n = 2) and 1 pt with a subcutaneous D-related IRR. Gr 3-4 Magro-related TEAEs reported in &amp;gt;1 pt in any cohort were anemia (Magro + D, n = 3; Magro + Pd, n = 2), decreased neutrophil count (Magro + Pd, n = 2), and decreased platelet count (Magro + Pd, n = 2). Serious Magro-related TEAEs occurred in 3 of 9 pts in the Magro + D cohort (febrile neutropenia, a DLT, on day 12; anemia on day 21; bacteremia on day 135), 1 of 9 pts in the Magro + Pd cohort (dyspnea, a DLT, on day 9 followed by febrile neutropenia on day 22 occurring in the same pt), and 1 of 7 pts in the Magro + Kd cohort (pneumonia on day 75). One pt (in the Magro + Pd arm) discontinued treatment due to Magro-related TEAEs reported on day 15 (gr 1 fatigue, gr 3 decreased neutrophil count, gr 3 decreased white blood cell count). No TEAEs leading to death occurred. Conclusion Magro demonstrated an acceptable safety profile with minimal additive toxicity when given in combination with SOC regimens for pts with heavily pretreated RRMM.

Post Hematopoietic Cell Transplantation Maintenance Therapy with Low-Dose Azacitidine in a Pediatric Population with High-Risk Myeloid Neoplasms

Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT) remain at risk for relapse. Children with relapsed AML and high-risk features including prior HCT, early relapse, and high-risk cytomolecular features experience survival of ≈30%. Given the even more dismal survival and limited therapy options for post-HCT relapse, azacitidine (aza) has been explored as post-HCT maintenance therapy based on potential disease targeting activity and enhancement of graft versus leukemia. Studies to date suggest that this approach is safe with signals of favorable survival. A phase 3 trial in adults did not show a survival benefit, although results were confounded by a high rate of withdrawal and a minority of patients received all intended cycles. We performed a descriptive analysis of all patients with high-risk myeloid neoplasms who underwent allogeneic HCT at Seattle Children's Hospital (SCH) from November 2017 to January 2023 and received post-HCT maintenance aza. Patients were considered high-risk if they had undergone prior HCT, measurable residual disease at HCT, ≥CR2, or high-risk cytomolecular features. Patients received myeloablative conditioning according to standard protocols. All patients were in remission prior to aza initiation. Aza 36-50 mg/m 2 was administered as IV or subcutaneous infusions daily for 5 consecutive days on a 28-day cycle with intention to continue therapy with cycles beginning through 1-year post-HCT. Nineteen patients began aza therapy at a median of 109 days (range 66-263) post-HCT. Demographics and disease information plus the primary high-risk feature for consideration of post-HCT aza are reported in Table 1. Following aza initiation, 9 (47.4%) patients continued subsequent aza cycles at their referring institution with concurrent remote management by SCH as needed. Median post-HCT follow-up was 30.4 months (range 7-66). The median number of completed aza cycles was 8 (range 3-12) and 14 (73.7%) patients received all intended cycles through 1 year following HCT. In 3 patients, aza cycles were delayed &amp;gt;4 weeks due to non-neutropenic fever or infection; de-escalation to 36 mg/m 2 for subsequent courses in the 2 patients who were receiving 50 mg/m 2 led to no further delays. There were no delays due to marrow suppression, no increased transfusion needs, and no hospitalizations attributed to aza. Fourteen (73.7%) patients had grade II acute graft versus host disease (GVHD) prior to initiation of aza. Two (10.5%) of these patients subsequently developed chronic oral GVHD, 1 diagnosed incidentally during their last aza cycle and 1 diagnosed after completion of aza. Two (10.5%) patients experienced ≤ grade II acute GVHD flares while tapering systemic immunosuppressive treatment (IST) and receiving aza, prompting escalation of same systemic IST (n=1) or addition of topical IST (n=1). Seventeen of 18 patients who were in remission at 1-year post-HCT were tapering or off IST. Five (26.3%) patients discontinued aza before 1 year post-HCT: 2 due to relapse, 2 per family preference, and 1 for inflammatory process with persistent dual chimerism from double cord HCT. Three-year estimates for overall and relapse free survival were 92% (95% CI 54-99) and 76% (95% CI 46-91), respectively, and cumulative incidence of relapse was 24% (95% CI 7-48) (Figure 1). The 6 patients with history of prior HCT are all are alive with ongoing remission at ≥3 years following second HCT with aza maintenance. Our experience demonstrates that post-HCT maintenance therapy with low-dose aza for high-risk pediatric AML/ MDS is tolerable with limited toxicity and without significant impact on marrow suppression or GVHD. The ability to successfully implement a post-HCT aza regimen in partnership with local institutions allowed families to return home, potentially reducing emotional hardship and financial toxicity due to travel/ housing and supporting feasibility. Outcomes in this cohort were improved compared to historical controls; this was especially notable in patients undergoing 2 nd HCT and in patients ≥CR2. Our findings suggest a potential role for post-HCT low-dose aza in children with high-risk AML/ MDS but further prospective pediatric studies are needed to define optimal dosing and evaluate for benefit.

Outcome of Risk- and Response-Adapted Post-Remission Therapy in Patients with NPM1 AML Treated Intensively

Introduction: Molecular assessment of measurable residual disease (MRD) is a powerful prognostic tool to identify high risk of relapse. Specifically, large studies have shown that MRD negativity of NPM1 after two cycles of intensive chemotherapy (IC) predicts long term remission. The translation of MRD results to treatment decisions such as treatment augmentation (MRD erasing) and referral to an allogeneic stem cell transplant (allo-SCT) is still lacking. The purpose of this study is to report the outcome of AML patients with NPM1 mutation who received IC and achieved remission, in whom NPM1 MRD post cycle 2 of IC, combined with FLT3-ITD status, were used systematically to decide whether patients were to complete intensive consolidations or refer to alloSCT. Methods: This is a retrospective analysis from 3 large hospitals in Israel. Patients were treated with 7+3 for induction and a repeat induction based on day 14 marrow. Midostaurin was added for FLT3mut leukemia since 2018. Consolidation consisted of 3-4 HiDAC cycles at doses of 1-3 g/msqrX6. Gemtuzumab ozogamicin and maintenance with FLT3 inhibitors or CC486 could be added. NPM1 transcript levels (normalized to ABL copies) were collected at diagnosis, after 2 cycles of IC, at the end of IC cycles and during follow-up. Patients were transplanted if a donor was available and any of the following: NPM1 transcript level was not reduced by 3 logs by the end of second cycle chemotherapy, absolute level was &amp;gt;1%, poor risk AML (ELN 2017 guidelines) or high AR FLT3-ITD mutation was present. Patients were followed for relapse (type and timing) and whether a second remission was achieved, as well as for EFS and overall survival. Results: A database search yielded 90 patients with NPM1 AML who were treated according the abovementioned protocol between 5/2015 and 11/2022 and achieved remission, with a median follow-up of 872 days (range 103-2751). Forty-seven patients were to receive consolidation cycles without transplantation in CR1, based on the aforementioned criteria. All but one patient (death from sepsis) completed treatment cycles. During follow-up, 21 (45%) patients relapsed at a median of 343 days. Two patients died while in CR1 during follow-up (extensive burns; sudden death at home). In a subgroup analysis of patients &amp;lt;60y (N=28), there were 11 events (9 relapses and 2 deaths), whereas in patients &amp;gt;60y (N=19) there were 13 events (12 relapses and 1 death during follow-up). Of note, 4 patients &amp;gt;60y were treated with CC486, of whom only 1 relapsed. Of the 18 patients who relapsed and received further treatment (3 had palliative care only), only 1 patient did not enter CR2 (died during salvage). The other 17 patients entered CR2 after salvage regimen (N=7, 4 were qPCR MRDneg, 5 were subsequently transplanted in CR2) or after upfront alloSCT without any salvage regimen (N=10, 4 were qPCR MRDneg). Forty-three patients were planned for alloSCT at CR1 (27 - inadequate molecular response, 16 - ELN risk group). Only one of these patients failed to undergo alloSCT in CR1 as she relapsed. The other 42 patients underwent alloSCT at CR1. In this group of patients, the median progression-free survival was 5 years, with no difference in patients above or below the age of 60. One half of the events (9/18) were relapses and the other half were deaths in remission, almost all were GVHD associated (figure1). Discussion: NPM1 mut AML without FLT3 is still considered by the ELN to have favorable outcome and most patients are not being transplanted at CR1. Yet, many relapse. This study evaluated the outcome of AML patients according to molecular risk stratification and alloSCT consideration by the end of cycle 2 of IC. In line with previous publications, younger patients with standard-risk AML and with adequate molecular response had a favorable outcome, with &amp;gt;60% of them having a disease-free long-term survival without transplantation. Moreover, even in a case of relapse, patients can achieve CR2 with MRDneg and attain long-term remission (90% OS in long-term follow-up). Older patients have a less favorable outcome even when they achieve adequate molecular response with two thirds of them experiencing relapse. Hence, the potential long-term outcome without transplantation needs to be balanced by the high risk of relapse. Nevertheless, even these patients can be successfully treated with either a salvage regimen or immediate transplantation, and &amp;gt;40% of them can be long-term survivors.

Management of Bone Marrow Transplants in Incarcerated Patients with Plasma Cell Dyscrasias: A Case Series

Background The U.S.' incarcerated population aged 55 years or older is expected to increase to 400,000 by 2030. This aging population faces intensifying health issues, including an increase in cancer diagnosis rates without adequate healthcare infrastructure and access. Studies show that individuals who received a cancer diagnosis while incarcerated, or within one year of release, had higher rates of cancer-related and all-cause mortality, compared to the general population. Our research seeks to assess how a cohort of patients with plasma cell dyscrasias (myeloma, amyloidosis, plasma cell leukemia) were treated and managed while incarcerated. Methods We performed a retrospective chart review of three patients with plasma cell dyscrasias in the incarcerated population who have undergone bone marrow transplants. Patients' disease characteristics, treatment sequences and details, and clinical outcomes were described qualitatively. Results Case 1: a 48-year-old Black man diagnosed with multiple myeloma in 2019. He was treated with 5 cycles of CyBorD at an outside hospital and had a favorable response. Stem cells were collected but never transplanted and patient was lost to follow-up due to incarceration. In April 2021, he presented to us with bilateral lower extremity paralysis and difficulty walking while in prison. He received emergent radiation to spine, then underwent both DCEP and VDPAC. The patient was discharged for physical rehabilitation in prison with ixazomib maintenance and monthly lab work. 6 months later, he was sent to another outside hospital with acute renal failure and then transferred to us. He demonstrated relapsed myeloma, received DV-AC, and was discharged back to prison while we awaited banked stem cells from 2019. He was admitted a month later for melphalan and auto-SCT, which was well-tolerated. We were ultimately able to arrange lenalidomide maintenance with prison. Case 2: a 65-year-old Black man with abnormal cardiac imaging and lymph node biopsy concerning for amyloid in 2020 while in prison. No treatment was given at the time. In 2021, an outside hospital conducted a bone marrow biopsy showing monoclonal plasma cells consistent with primary amyloidosis. 3 months later, the patient began CyBorD but completed subsequent cycles at another outside hospital. Correctional authorities indicated transplant would ultimately need to occur at our facility. Patient began stem cell mobilization and was admitted to us for melphalan and auto-SCT in March 2022. Patient was discharged back to corrections but there was a delay in acquiring lenalidomide for maintenance therapy, which was not started until August 2022. Case 3: a 44-year-old Black man was diagnosed with plasma cell leukemia in 2009. That year, he received an auto-SCT and then an allo-SCT from his HLA-matched sister at an outside hospital. In 2016, he received radiation for a large mass in his brain, as well as lenalidomide and dexamethasone. Since then, records indicate limited follow-up until he presented to us in 2022 with leg pain and imaging showing progressing myeloma while in prison. He was given 1 cycle of DCEP, was discharged back to a correctional facility, and subsequently refused 2 nd cycle. He sought a second opinion from an outside hospital for CAR-T therapy but was told eligibility required failure of daratumumab. In January 2023, he was offered Dara-Pom-Dex-Carfilzomib though declined the pomalidomide portion. He has responded well and is continuing maintenance. The CAR-T center offered to see him for treatment if he progresses on this regimen. Discussion Our research suggests that incarcerated patients face multiple obstacles that delay or hinder treatment, including siloed care, poor record-keeping, lack of follow-up, and difficulty obtaining appropriate medications. All three patients were frequently transferred between correctional facilities, outside hospitals, and our institution, which led to incomplete records. Additionally, patients went months or even years without follow-up monitoring after initial treatment and would often re-enter the healthcare system only upon presenting with severe symptoms from relapsed disease. Correctional facilities faced issues procuring expensive medications only available through restricted distribution programs. Further analysis is warranted to understand the generalizability of our results and identify solutions to support this population.

BIOM-13. ASSOCIATION OF HAND-FOOT SKIN REACTIONS WITH SURVIVAL IN RECURRENT GLIOBLASTOMA PATIENTS TREATED WITH REGORAFENIB

Abstract INTRODUCTION The phase 2 REGOMA trial suggested a survival benefit of the multikinase inhibitor regorafenib for treating patients with glioblastoma at first recurrence. Hand-foot skin reactions (HFSR) following multikinase inhibitor therapy have been reported to predict prolonged overall survival (OS) in patients with solid tumors. The predictive value of HFSR in patients with recurrent glioblastoma undergoing regorafenib therapy remains to be investigated. METHODS Fifty-seven patients (age range, 35-77 years) with recurrent IDH-wildtype glioblastomas were retrospectively identified from five centers in Germany and Switzerland. Regorafenib was administered at 160 mg/d for the first three weeks of each 4-week cycle, with individual dose adjustments according to toxicity. Patients were stratified into two groups based on the occurrence of HFSR following regorafenib. Group differences were investigated using the Mann-Whitney rank-sum and Fisher's exact tests. Kaplan-Meier analysis was used for univariate analyses, and the Cox proportional hazards regression model for multivariate analyses. RESULTS Patients received a median of two regorafenib cycles (range, 1-14 cycles). Median follow-up after recurrence was 7.0 months (range, 0.6-35.9 months). The median number of previous treatment lines was 2 (range, 1-6 lines). At the time of data analysis, 47 patients (82%) had died. HFSR were observed in 14 out of 57 patients (25%) and associated with a significantly longer OS (10.6 vs. 6.0 months; P = 0.040). No significant group differences (HFSR compared to no HFSR) were observed regarding age, the extent of resection, MGMT promoter methylation, Karnofsky performance status, or the number of completed regorafenib cycles (all P &amp;gt; 0.05). Cox proportional hazards regression analysis confirmed that HFSR were associated with longer OS (P = 0.039; HR, 0.438), independent of age, Karnofsky performance status, and the number of previous treatment lines (all P &amp;gt; 0.05). CONCLUSION Our data suggest that the occurrence of HFSR following regorafenib is associated with longer OS in recurrent glioblastoma patients.

Efficacy of Biofeedback in Paediatric Urology Patients: A Single Centre Experience

Aim of the Study: Biofeedback assisted pelvic floor muscle training is an underutilised nonpharmacological treatment in paediatric urology. We reviewed all patients who underwent a course of treatment at our centre to evaluate its efficacy. MethodsAll patients who underwent a full cycle of biofeedback in the paediatric urology department from 2016 to 2023 were identified. Demographics and outcomes following treatment were accessed. Results42 patients (28 female) were identified who underwent 8 one-hour sessions on a weekly basis constituted a completed cycle of treatment. Patients were identified for treatment as per local lower urinary tract symptom guidelines and following discussion in a fortnightly urology MDT and including diagnoses of overactive bladder, dysfunctional voiding, and giggle incontinence.Outcomes were measured as successful 29% (continence, normal postvoid residuals, clean intermittent catherization discontinued), partially successful 19% (reduced wetting, abnormal post void residuals, ongoing CIC) and unsuccessful 52% (no change for patient). Age at time of treatment affected likelihood of success: <9 years, 0% success; ≥9 years, 57% [p < 0.05]. There was no significant difference in success for 9–11 years [60%] vs >11 years [56%]. ConclusionsBiofeedback has shown success with improvement in symptoms in 48% of patients (complete or partial), which increases to 57% success in ≥9 years group. We would advocate its use in these difficult to manage patients with LUTS.

Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial.

Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial.

174 A silver lining: the identification of silver trauma at triage for older persons (&amp;gt;65) presenting to the emergency department

Abstract Background Trauma in patients over 65 (silver trauma), can result in serious injury from lower impact mechanisms. The NOCA Major Trauma report highlights that 58% of major trauma is a result of a fall from 2 metres or less and mortality increases with age and comorbidities. Failure to identify, rapidly assess and treat older persons who have suffered silver trauma results in prolonged emergency department stays with an increase in morbidity and mortality. We therefore, performed a completed audit cycle to assess the identification of Silver Trauma in our emergency department. Methods A focus group involving key stakeholders was established, including Emergency Physicians, nurses and members of the Gerontological Emergency Department Intervention team. An audit assessed patients triaged as ‘major trauma’ from October to December 2022. We established silver trauma guidelines for triage. Teaching sessions on the recognition of silver trauma were provided, daily briefings were given, and information leaflets were placed in all triage areas. A triage discriminator of ‘Silver Trauma’ was introduced to prompt recognition and review by clinicians. A full audit cycle was completed. Results Our initial audit (October to December 2022) revealed 25 patients triaged as ‘Major Trauma’ who were aged over 65. After the completion of the initial audit and implementation of measures, 122 patients were triaged as ‘Silver Trauma’ between January 20th and March 31st. We identified that 59% (N = 72) were due to falls from 2 meters or less. Other mechanisms of injury included unwitnessed fall (21% N = 25), syncope (7% N = 8), fall from height (11% N = 13) and Major Trauma (3% N = 4). Seventy-one (58.19%) were admitted and 51 (41.80%) were discharged home. Conclusion This audit demonstrates that departmental education and implementation of a triage discriminator has significantly improved the recognition of silver trauma within the ED setting.

PENINGKATAN HASIL BELAJAR SISWA KELAS V DALAM PEMBELAJARAN IPS BERBANTUAN GAMES BOOK

This classroom action research was motivated by the low social studies learning outcomes of fifth grade students at SDN 1 Kedungdowo. In this case, researchers use the Games Book media as an improvement in learning outcomes in Class V in Social Sciences lessons. This study uses the PTK method, which consists of two cycles. Each cycle consists of stages namely planning (planning), implementation of action (acting), observation (observing) and reflection (reflecting). Data collection techniques using interviews, observation, tests and documentation. Data analysis techniques which include data reduction, presentation and drawing conclusions. The results showed that the teacher's teaching skills increased by an average of ≥75%. In the first cycle, the percentage was 72.82% and the second cycle increased with the percentage to 80.97% with good and successful criteria. Student learning outcomes increased by an average of ≥75% classical. The percentage of the completed cycle I obtained 56.67% and the completed cycle II obtained 76.67%.

Assessment of endometrial carcinoma on biopsy as a predictor of final surgical pathology: Are we doing it right? A completed audit cycle and recommendations.

Typing and grading of endometrial carcinomas (ECs) on small biopsy specimens is crucial to determine the need for full surgical staging. Histological subtype and grade are key factors available for risk stratification before surgery. However, this can be diagnostically challenging on small biopsy specimens, especially when morphologic features are subtle or overlapping. The aims of this audit were to assess concordance of endometrial carcinomas on biopsy specimens with hysterectomy specimens and to determine if the immunohistochemistry (IHC) panel being used in our practice was adequately subtyping ECs. The audit was approved by the Clinical Effectiveness Team of the Royal College of Pathologists (UK) as meeting all the criteria and standards set out by the College. Biopsies from 67 cases of EC were compared for histological subtype and grade of endometrioid carcinoma with resection specimens. A re-audit was carried out on 59 cases after implementation of changes recommended by the initial audit. Two of 35 (6%) tumours defined as G1 on biopsy were upgraded (to G2) on final pathology, as was one of 7 (14%) G2 tumours (to G3). One of these cases had solid areas just amounting to more than 6% on resection. In the second case, a comment was made that assessment had been difficult as the specimen was suboptimally fixed, but nuclei appeared atypical. Of seven G2 biopsies, one case was upgraded to grade 3 on final pathology based on proportion of solid areas. Our data show lower rates of discordance as compared to previous studies and on re-audit, the concordance between endometrioid and nonendometrioid serous carcinoma improved with the addition of immunohistochemistry (IHC) for Phosphatase and tensin homolog (PTEN) to biopsies. PTEN IHC can complement other stains and aid in the distinction of grade 3 endometrioid carcinoma from serous carcinoma on endometrial biopsies.

Evaluation of pollutant emissions from a railbus in real operating conditions during transport work

The article discusses issues related to the assessment of pollutant emissions from a railbus during transport work. The test object was a rail vehicle equipped with two diesel engines with a total power of 780 kW, Stage IIIB homologated. Measurements were carried out on the route Poznań - Wągrowiec in two directions. During the tests, the vehicle performed a transport service, where the number of passengers was counted. For the completed cycles, the average number of people was 82 and 18. On the basis of the obtained data, the vehicle operating conditions and emission indicators were analyzed, which were related to the number of passengers. A dimensionless toxicity index was also determined.

Significance of the second stage of medical rehabilitation after arthroplasty of large joints

BACKGROUND: Until recently, the three-level system of medical rehabilitation adopted in Russia assumed the implementation of each of the stages in various medical organizations. The lack of funding within the budget and the basic compulsory medical insurance program led to limited access for patients to the trajectory of the completed cycle of medical rehabilitation after surgical interventions, which reduced the effectiveness of the provision of profile high-tech medical care.&#x0D; AIM: is to demonstrate the effectiveness of the system for organizing rehabilitation care for patients after arthroplasty of large joints of the lower extremities in a stationary (second) stage in a medical rehabilitation center.&#x0D; MATERIALSAND METHODS: The data of the medical information system on patients treated for three months at the second (inpatient) stage after arthroplasty of the hip and knee joints in the conditions of the Medical Rehabilitation Center were used. The effectiveness of rehabilitation was assessed by tests and scales: rehabilitation routing scale (RRS), visual analog scale (VAS), Borg exercise tolerance scale, Hospital anxiety and depression scale (HADS), European quality of life questionnaire (EQ-5D); Medical research scale (MRS), index Leken.&#x0D; RESULTS: 308 patients (306 operated) were treated after medical rehabilitation measures at the first stage with a RRS score of 4-5 points, of which about 80% after primary and revision arthroplasty of large joints. Upon completion of rehabilitation measures, a statistically significant improvement in all functional indicators was noted. Despite the ambiguous opinion of scientists about the need for inpatient rehabilitation after arthroplasty, according to our data, arthroplasty and the subsequent stage of medical rehabilitation using modern technologies in a hospital significantly improve the clinical status, reduce or eliminate pain, increase motor activity, improve the psycho-emotional background and the patient s quality of life. Stationary (second) stage of rehabilitation was effective in 100%.&#x0D; CONCLUSIONS: The results of the work of the medical rehabilitation center proved its organizational feasibility, clinical effectiveness and advantages: continuity and phasing of rehabilitation in a single institution; continuity of observation of the patient during the interaction of multidisciplinary rehabilitation team with the participation of the operating surgeon, an anesthesiologist-resuscitator. The quality of rehabilitation is improved by the concentration of high-tech therapeutic and regenerative agents and experienced specialists, the correction of concomitant pathology, explanatory work with patients to increase compliance.

P-675 Analysis of a digitally integrated ovulation date kit to determine ovulation precisely

Abstract Study question Do digitally integrated ovulation prediction kits (OPK) predict the fertile window and the ovulation date accurately? And can this prediction be proven by sonography? Summary answer Particularly for subfertile women with irregular cycles, OPKs can help predict their fertile window and ovulation day, in accordance with vaginal sonography. What is known already The fertile window is defined as the period of five days before ovulation including the day of ovulation itself. Prediction based only on cohort observations or historical datasets may be inaccurate for women with irregular cycles, particularly when unforeseen changes of ovarian function occur during reproductive life. Urinary luteinizing hormone (LH) assays and smartphone applications are already widely used to detect the optimal time for conception, but can only predict a likelihood of ovulation without proof. Study design, size, duration 100 healthy women between the ages of 21 and 45, cycle length up to 42 days, trying to conceive and without hormone intake were to be recruited in the gynecological outpatient clinics of the Technical University of Munich (TUM) and of the University of Ulm. Each participant entered the study for up to three consecutive cycles. Two vaginal ultrasound scans were performed per cycle – before and after the ovulation date prognosis by the app. Participants/materials, setting, methods After informed consent, participants downloaded the smartphone application “Pearl Fertility” and received OPKs consisting of four different sets of lateral flow immunoassay test strips (LFIA): for luteinizing hormone, follicle-stimulating hormone, progesterone and human chorionic gonadotropin. Home measurements with LFIAs were performed with morning urine. The phone camera feed analyzed the color information of the LFIAs. Three differently prioritized algorithms calculated the ovulation date. Two questionnaires evaluated patient baseline characteristics and their perception of the app. Main results and the role of chance 89 women were recruited. Mean age was 34.6 yrs. (SD ± 4.2). On average, the included women had tried to conceive for 7.5 (±5) months before joining the study. 8% (n = 7) became pregnant before the first cycle started.140 completed cycles in 71 remaining women were analyzed so far. 46% of the recruited women completed the study after 3 cycles, the drop-out-rate was 32.4%. The app predicted ovulation for cycle day 14.3 (mean, SD ± 3.5). In 25 cycles the date of ovulation was before day 12 and in 33 cycles on day 16 or later. The first ultrasound was done on cycle day 13.5 (mean, SD ± 3), the second ultrasound on cycle day 17.6 (mean, SD ± 3.6). In several cycles at least one (up to three) corrections of the prognosis occurred by the app, resulting in the day of predicted ovulation being moved either backward (retrospectively) or forward by 2.5 (mean, SD ± 1.9) days. Urinary progesterone measured with the OPK and post-ovulatory ultrasound were in accordance in the majority of cycles. 17% (n = 12) of the women became pregnant in the current analysis (mean duration to pregnancy: 1.3 cycles). In the ITT population (after informed consent) the rate was 23%. Limitations, reasons for caution This study was performed without a control group. Therefore, as an intraindividual control, a follow-up is planned to calculate the pregnancy rates and outcomes with and after the use of the app. Wider implications of the findings Our study shows that digitally integrated OPK are able to predict the fertile window and the ovulation date in a slightly subfertile cohort unselected for mild cycle irregularities. An early and accurate prediction may help couples to conceive, particularly if the date of ovulation is divergent from standard information. Trial registration number Not applicable

Tazemetostat, a selective EZH2 inhibitor, with pembrolizumab as treatment of anti-PD-1 resistant head and neck squamous-cell carcinoma (HNSCC): A phase 1-2 trial.

6022 Background: EZH2 is the catalytic subunit of PRC2, which catalyzes H3K27me3 of target gene promotors and silences transcription of several cancer-related genes. EZH2 overexpression is common in HNSCC and correlated with methylation of several tumor suppressor genes. EZH2 siRNA downregulated EZH2 mRNA and protein and reduced colony formation in an EZH2-expressing HNSCC cell line. EZH2 inhibitors decreased H3K27me3 in HPV + and - cell lines. Tazemetostat, an EZH2 inhibitor, upregulated expression of HLA class I molecules in anti-PD-1-resistant HNSCC cell lines and mouse models, and increased antigen-specific CD8+ T cell proliferation, IFN-γ production, CXCL10 expression, and tumor cytotoxicity. In an anti-PD-1-resistant HNSCC model, tazemetostat and an anti-PD-1 suppressed tumor growth. The primary aims of this phase 1-2 trial were to establish 1) the recommended phase 2 dose (RP2D) of tazemetostat given with pembrolizumab and 2) the objective response rate of this regimen among patients (pts) with anti-PD-1 resistant, PD-L1 positive HNSCC. We report the results of Phase 1. Methods: In phase 1, eligible pts had recurrent/metastatic (RM) HNSCC, adequate performance status and organ function, and ability to swallow study drug. A 3+3 dose-escalation phase 1 design was used to assess 3 dose-levels of tazemetostat (400, 600, and 800 mg orally twice daily) with pembrolizumab (200 mg IV). Cycle 1 was 35 days, with tazemetostat given on days 1-35 and pembrolizumab on day 15. Subsequent cycles were 21 days, with tazemetostat given on days 1-21 and pembrolizumab on day 1. Dose-limiting toxicity (DLT), assessed during cycle 1, was defined as grade 4 neutropenia/thrombocytopenia, grade 3 febrile neutropenia, or study drug-related grades 3-4 non-hematologic adverse events (AEs). Pts must have completed cycle 1 to be evaluable for DLT assessment; otherwise, an equal number of additional pts were enrolled. The RP2D was defined as the highest dose level in which 0 of the first 3 or &lt;1 of 6 pts experienced a DLT. Results: 12 pts enrolled to phase 1: 3 each on the 400 and 600 mg dose-levels of tazemetostat and 6 on the 800 mg dose-level. Key tumor characteristics included primary site (larynx: 4, oral cavity: 3, oropharynx: 3, nasopharynx: 1, cutaneous: 1), HPV status (+: 1, -: 11), and number of lines of prior systemic treatment for RM disease (1-2: 6, &gt;3: 6). Nine pts were evaluable for DLT; 3 pts on the 800 mg dose-level did not complete cycle 1 and were not evaluable for DLT. DLT events and grade 4-5 AEs did not occur. Grade 3 AEs that occurred after cycle 1 included anemia (2 pts, both at 800 mg dose) and fatigue (1, at 400 mg dose). Across all cycles, the most common AEs included anemia (10 pts), fatigue (9), rash (7), and myalgia (4). Conclusions: Among pts with RM-HNSCC, the RP2D of tazemetostat was 800 mg twice daily when given with pembrolizumab. Enrollment to phase 2 is ongoing. Clinical trial information: NCT04624113 .

Regorafenib in older adults with metastatic colorectal cancer: A multi-center, single arm phase II trial.

12047 Background: Metastatic colorectal cancer (mCRC) is a leading cause of death, particularly in older adults. Regorafenib (REGO) is an FDA-approved oral multi-kinase inhibitor for refractory mCRC based on the CORRECT trial results, but older adults were underrepresented with a median age of 61 (54–67). This study aimed to evaluate REGO safety in older adults with mCRC and assess the feasibility of using geriatric assessment (GA) to predict toxicity risk. Methods: 27 subjects (PTs) enrolled (median age 73, range 65-85) and started at 120mg of REGO for 21 days of a 28-day cycle with provider discretion to escalate to full dose of 160mg after cycle 1. GA was conducted at enrollment, 4 weeks later, and then every 3 months to monitor for any deterioration. GA assessed 8 geriatric domains (comorbidity, functional status, physical performance, cognition, psychological state, nutrition, medication review, and social support) using validated tools. Primary objective was to assess grade 3-5 toxicity rate, with secondary objectives evaluating REGO efficacy and exploring baseline GA and toxicity risk associations. Kaplan-Meier method was used to estimate median overall survival (OS) and progression-free survival (PFS) from date of consent. Continuous GA measures were compared using non-parametric Wilcoxon rank-sum test, and binary GA measures were compared using Fisher’s exact test. Results: Of 27 PTs enrolled, 15 were male, 12 were female, and 19 identified as white. At baseline, 77.7% of PTs had at least 3 (1-9) GA impairments. Physical performance (80.8%), comorbidity (75%), and cognition (69.2%) were the most prevalent impaired GA domains. 40% required dose reduction by end of cycle 2, and none escalated to full dose. 55% of PTs completed cycle 3. Main reasons for drug discontinuation were disease progression (80%) and toxicity (12%). 74.1% of PTs experienced at least one treatment-related grade 3-4 toxicity. Fatigue (33%), hypertension (30%), and hand-foot syndrome (15%) were the leading grade 3-4 toxicities. Median OS was 5.6 months (95% CI: 3.6-12.2m), and median PFS was 2.8 months (95% CI: 2.5-3.4m). There was no significant difference in baseline GA measures between those who experienced toxicities and those who did not. No statistically significant toxicity risk was associated with any baseline GA impairment. The prevalence of impaired mini-nutritional assessment increased over 4 weeks (58% to 91%, p &lt; 0.01), and median Short Physical Performance Battery (SPPB) scores decreased (7 to 6, p = 0.03). Conclusions: The study found that older adults with mCRC had comparable survival with REGO but experienced high toxicity. This may be ameliorated by recently published step-wise REDOS dosing method and should be considered in older adults with mCRC. The study confirms the feasibility of implementing GA within clinical trials. More data is needed on the role of GA in predicting toxicity with targeted therapies. Clinical trial information: NCT02466009 .