bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel method for the detection of circulating tumor plasma cells in multiple myeloma.
Authors: Lee Jihyun , Kang Hoin , Kim Soee , Lee Ju Bi , Kim Hyo Yong , Kim Min Hyung , Kim Myeong-Jin , Kim Jungwon
Published: June 2024

e19520

Background: Multiple Myeloma (MM) is characterized by the proliferation of abnormal plasma cells within the bone marrow. A bone marrow examination is essential for the diagnosis of multiple myeloma. This is a test that causes great pain to patients because it requires collecting and analyzing the bone marrow fluid inside the bone. In addition, there is a disadvantage that it cannot be carried out frequently due to cost issues. Therefore, the development of new diagnostic methods is absolutely necessary. The aim of this study is to access the potential of circulating tumor plasma cells (CTPC) for the diagnosis of MM using CytoGen's Smart Biopsy platform. Methods: Spiking tests using MM cell line (RPMI8226) was conducted with the purpose of making an environment similar to the MM patient's blood. RPMI8226 cells (200 cells) stained with CellTracker were spiked into human blood sample (5mL, healthy donor). Then, spiked cells were isolated by CytoGen’s Smart Biopsy isolator, subsequently recovery rate was accessed by counting of isolated RPMI8226 or immunofluorescence (IF) staining with multiple myeloma-specific marker, CD138. Then, clinical evaluation was performed with bone marrow (3mL) and peripheral blood (5mL) samples of MM patients (n=20). The presence of CTPC in patient samples was tested by IF staining with anti-CD138 antibody. Results: In in vitro experiments to test recovery rate of CTPC using CytoGen's Smart Biopsy isolator, MM cell line’s recovery rate was validated to over 80%. CD138 expression was clearly detected by IF staining of spiking samples of multiple myeloma cell line and was not detected at all in the negative controls. In clinical evaluation study, CTPC was successfully observed after the isolation from bone marrow and peripheral blood using CytoGen's Smart Biopsy isolator by IF staining with CD138. Conclusions: This study shows a novel method for the detection of MM with liquid biopsy. CTPC from liquid biopsy of MM could be isolated using CytoGen's Smart Biopsy isolator with high recovery rate and can clearly be detected with specific marker of MM, CD138 by IF staining. These results suggested that CytoGen's Smart Biopsy platform might be an effective diagnostic tool for the detection of MM. Expanded clinical study will be performed with more MM samples for clinical validation. Clinical trial information: 2013-09-009 .
Efficacy of low-dose direct oral anticoagulants (DOACs) for venous thromboembolism prophylaxis in newly diagnosed multiple myeloma.
Authors: Basali Diana , Zureigat Hadil , Nurse Daniel Paul , Elmaleh Hassan , Batah Heya , Adcock Bridget , Wei Wei , Dima Danai , Valent Jason Neil , Anwer Faiz , Samaras Christy Joy , Khouri Jack , Williams Louis , Raza Shahzad , van Heeckeren Willem Jan , Mazzoni Sandra Ann
Published: June 2024

e19521

Background: The venous thromboembolism (VTE) risk is high in newly diagnosed multiple myeloma (NDMM) patients, especially within 6 months of beginning treatment and with the use of immunomodulatory-drug (IMiD)-based regimens. SAVED and IMPEDE VTE scores assess risk and NCCN guidelines recommend their use. Few studies have explored optimal thromboprophylaxis agent by risk category which has led to varied treatment strategies. We share our institutional experience using DOACs vs aspirin in NDMM patients and explore incidence of VTE, utility of SAVED and IMPEDE scores, and patient safety. Methods: We retrospectively analyzed outcomes of NDMM patients aged 18 and above from January 2018 to June 2022. Patients receiving anticoagulation for other indications or unable to safely take aspirin or DOACs were excluded. The primary outcome was incidence of VTE in the first 6 months of treatment. Secondary outcomes included patient and treatment factors contributing to VTE risk, comparison of VTE scoring calculators: SAVED vs IMPEDE VTE, and safety of low dose DOAC therapy. Fisher’s exact and Wilcoxon rank sum tests were used to compare patient characteristics between 6-month VTE status. Results: Of 347 NDMM patients that were included, 21% experienced VTE within 6 months. Of those who took aspirin, 20.2% had 6-month VTE. For DOACs, 21.4% taking apixaban and 21.7% taking rivaroxaban had 6-month VTE. There was no significant difference in VTE rate between DOAC or ASA groups (p=0.90). Patients with SAVED score ≥2 (p<0.0006) or prior VTE history (p<0.0001) had significantly higher 6-month VTE rates . Characteristics including age>80, sex, race, BMI>25, IMPEDE score, presence of high-risk cytogenetics, existing use of aspirin or low molecular weight heparin, or transplant status showed no significant difference in VTE rate. Conclusions: This is one of the largest retrospective studies examining efficacy and safety of DOACs in NDMM. Initial analysis showed no significant difference in 6-month VTE rate between NDMM patients treated with aspirin or DOAC therapy. SAVED score appears to delineate high risk VTE patients vs IMPEDE. Follow-up will assess 12-month, 18-month, and overall VTE rates. Bleeding events and analysis for additional high-risk correlates, such as choice of induction regimen, will be presented. This highlights the need for ongoing trials evaluating risk-assigned thromboprophylaxis in patients with MM. [Table: see text]
Clinical outcomes and resource utilization in patients with multiple myeloma admitted with gastrointestinal bleeding.
Authors: Khan Fayaz , Rahima Kenan
Published: June 2024

e19522

Background: In multiple myeloma (MM) patients, GIB can be due to factors such as abnormal proteins affecting the GI tract, coagulation issues, or secondary conditions like amyloidosis. There's limited scientific evidence examining outcomes among patients presenting with both GIB and MM. Thus, our objective was to assess clinical outcomes in this specific population. Methods: We accessed the National Inpatient Sample from 2017-2020 to identify adult patients with MM hospitalized due to GIB. The primary endpoint was inpatient mortality, with secondary endpoints including length of stay and total hospital charges. We utilized multivariable logistic regression analysis to estimate clinical outcomes, considering a significance threshold of P < 0.05. Results: We identified 4,067,364 hospitalizations with GIB, among which 22,000 (5.9%) presented with MM. Comparing MM and Non-MM cohorts, the mean age was 71.9 vs 67.8 years, males constituted 58% vs 52.2%, and White ethnicity accounted for 55.6% vs 66.1%. The prevalence of obesity was 10.6% vs 14.5%, diabetes mellitus was 32.1% vs 33.8%, chronic obstructive pulmonary disease was 16.9% vs 20.4%, dyslipidemia was 38.5% vs 40.7%, atrial fibrillation was 27.7% vs 25.6%, hypertension was 22.9% vs 34.7%, heart failure (HF) was 30.7% vs 26.4%, peripheral vascular disease (PVD) was 2.9% vs 4.1%, acute kidney injury was 45.6% vs 29.4%, anemia was 26.3% vs 27.7% and chronic kidney disease (CKD) was 51.9% vs 28.6%. Clinical outcomes revealed stark differences between MM and Non-MM cohorts: in-hospital mortality rates were 10.9% vs 6.3% with an odds ratio (OR) of 1.5 (CI 1.4-1.7); LOS was 9.6 days vs 6.7 days (IRR 1.26, CI 1.21-1.32); and hospital charges were $30,006 vs $20,172 (IRR 1.34, CI 1.26-1.42). All data demonstrated a p-value < 0.001 and were adjusted for various factors including age, sex, race, comorbidity indices, obesity, atrial fibrillation, diabetes mellitus, hypertension, peripheral vascular disease, acute kidney injury, chronic kidney disease, nicotine and alcohol use, stroke, acute respiratory failure, and inflation during 2017-2020. Conclusions: Patients hospitalized for GIB and MM were comparatively older, with a larger male population and fewer Caucasians. They exhibited higher Afib, HF, AKI, and CKD rates with lower occurrences of obesity, DM, COPD, dyslipidemia, HTN, anemia and PVD. This group showed a significantly worse mortality rate with prolonged hospital stays and resource utilization. This entails to have prompt medical attention, appropriate management of bleeding, and addressing the underlying causes are crucial in improving outcomes and reducing mortality rates. Treatment strategies often involve a multidisciplinary approach involving oncologists, hematologists, gastroenterologists, and other specialists to provide comprehensive care tailored to the individual's condition.
Phase 3 randomized double-blind study evaluating selinexor, an XPO1 inhibitor, plus ruxolitinib in JAKi-naïve myelofibrosis.
Authors: Mascarenhas John , Maher Keri Renee , Rampal Raajit , Bose Prithviraj , Podoltsev Nikolai Alexandrovich , Hong Junshik , Wang Xulong , Kye Steve , Harrison Claire
Published: June 2024

TPS6594

Background: Myelofibrosis (MF) is a myeloproliferative neoplasm with common somatic gene driver mutations in JAK2, CALR, and MPL. Selinexor, an investigational oral XPO1 inhibitor, may inhibit MF-relevant JAK/STAT and non-JAK/STAT pathways. Preclinical studies have shown potential synergy with ruxolitinib treatment. In the phase 1 portion of XPORT-MF-034 evaluating selinexor plus ruxolitinib in JAKi-naïve patients with MF, the most common AEs in the 60 mg cohort were nausea (79%), anemia (64%), thrombocytopenia (64%), and fatigue (57%). Nausea was predominantly Grade 1 and transient in nature. Treatment-related AEs leading to treatment discontinuation were thrombocytopenia (n=1) and neuropathy (n=1). SVR35 and TSS50 was achieved by 79% and 58% of the 60 mg cohort intent-to-treat population at Week 24, respectively. Response rates were consistent across subgroups, including sex and regardless of ruxolitinib starting dose. These data provide strong support to further evaluate selinexor (60 mg) and ruxolitinib in patients with JAKi-naïve MF. Methods: The XPORT-MF-034 (NCT04562389) trial includes a global, Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate selinexor and ruxolitinib. JAKi-naïve patients with MF will be randomized 2:1 to receive oral selinexor 60 mg or placebo once weekly (28-day cycle) and twice daily ruxolitinib. Randomization will be stratified by DIPSS risk category (int-1 vs int-2 or high-risk), spleen volume (<1800 cm3 vs >1800 cm3 by MRI/CT scan), and baseline platelet counts (100-200x109/L vs >200x109/L). Dual anti-emetics for nausea prophylaxis will be required for the first two cycles. Select eligibility criteria include ≥18 years of age, spleen volume ≥450 cm3 by MRI or CT, DIPSS intermediate-1, intermediate-2, or high-risk, active symptoms of MF (MFSAF v4.0), currently not eligible for stem cell transplantation, ECOG≤2, and platelet count ≥100 x 109/L. Select exclusion criteria include >10% blasts in peripheral blood or bone marrow; previous treatment with JAKi for MF, or previous treatment with selinexor or other XPO1 inhibitors. The co-primary study endpoints are SVR35 and TSS50 at Week 24 and will be tested hierarchically. The key secondary endpoint is anemia response at Week 24 per the IWG-MRT and ELN criteria. The XPORT-MF-034 Phase 3 trial is currently open for enrollment; a total of 306 JAKi-naïve MF patients will be enrolled and the study was initiated on June 28, 2023. Clinical trial information: NCT04562389 .
EPCORE FL-2: Phase 3 trial of epcoritamab with rituximab and lenalidomide (R2) vs chemoimmunotherapy or R2 in previously untreated follicular lymphoma.
Authors: Linton Kim M. , Thompson Philip , Luminari Stefano , Casulo Carla , Patah Poliana , Zeng Lingmin , Mei JP , Dixit Neha , Hoehn Daniela , Bachy Emmanuel
Published: June 2024

TPS7084

Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma. Most patients with advanced-stage FL in need of systemic therapy are treated with an anti-CD20 monoclonal antibody (eg, rituximab [R] or obinutuzumab [G]) with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] or bendamustine [benda]). Recent studies have shown R plus lenalidomide (R2) is a potent FL treatment in the 1L and relapsed or refractory (R/R) settings and is a promising backbone for combination therapies. Epcoritamab, a subcutaneous CD3xCD20 bispecific antibody, received breakthrough therapy designation by the FDA for R/R FL after ≥2 lines of systemic therapy. In the phase 1/2 trial (NCT04663347), epcoritamab plus R2 demonstrated high complete response (CR) rates in the 1L and R/R settings. The objective of this trial is to evaluate the safety and efficacy of 1L epcoritamab plus R2 vs CIT in patients with FL. Methods: EPCORE FL-2 (NCT06191744) is a global, randomized, open-label phase 3 trial. Eligible adult patients must have CD20+ histologically confirmed classic FL (previously grade 1–3A), stage III or IV disease (or bulky stage II), and in need of systemic treatment by meeting GELF criteria. Approximately 1080 patients will be randomized to 3 treatment arms (Table). Patients achieving CR or PR upon 6 cycles will move to epcoritamab on day 1 of cycles 7–12 (28-day cycles) and 13–21 (56-day cycles). After 120 weeks of treatment, patients will be followed for progression and survival. Dual primary endpoints will be CR rate at 30 months and progression-free survival in arm A vs arm B. Key secondary efficacy endpoints include overall survival, minimal residual disease negativity, and changes in patient-reported outcomes on the physical functioning scale of the European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire from baseline to week 25. Safety endpoints include incidence and severity of adverse events (AEs), including AEs of special interest (cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome). The study is open for enrollment. Clinical trial information: NCT06191744 . [Table: see text]
CELESTIAL-TNCLL: An ongoing, open-label, multiregional, phase 3 study of sonrotoclax (BGB-11417) + zanubrutinib vs venetoclax + obinutuzumab for treatment-naïve (TN) CLL.
Authors: Shadman Mazyar , Kater Arnon P. , Woyach Jennifer Ann , Li Jianyong , Munir Talha , Salmi Tommi , Phuong Patrick , Tian Tian , Patten Piers
Published: June 2024

TPS7087

Background: The combination of venetoclax (ven), the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with CLL (Wierda et al. J Clin Oncol. 2021); however, the toxicity profile of this regimen suggests a need for a more tolerable BTK/BCL2 inhibitor combination. Sonrotoclax, a next generation BCL2 inhibitor, is a more selective and more pharmacologically potent inhibitor of BCL2 than venetoclax. In a phase 1 study in patients with TN CLL treated with sonrotoclax + zanubrutinib, efficacy data was promising with ORR and 1-year progression-free survival (PFS) rates of 100% and deep responses based on undetectable measurable residual disease at <10-4 sensitivity (uMRD4). The most common grade ≥3 TEAE was neutropenia, and no tumor lysis syndrome or cardiac toxicity was observed (Tam et al. Blood. 2023). Zanubrutinib, a next-generation BTK inhibitor, significantly improved PFS and had a more tolerable safety profile, including fewer cardiac adverse events vs ibrutinib in a randomized, head-to-head study of patients with CLL/SLL (Brown et al. N Engl J Med. 2023). Presented here is the design of a phase 3 trial aimed at comparing the efficacy of sonrotoclax + zanubrutinib vs ven + obinutuzumab (obi) in patients with TN CLL. Methods: CELESTIAL-TNCLL (BGB-11417-301; NCT06073821) is a randomized, open-label, phase 3 study. Eligible patients must have previously untreated CLL that requires treatment per 2018 iwCLL criteria, measurable disease by CT/MRI, an ECOG performance score of 0-2, and adequate hematologic and organ function. Approximately 640 patients will be randomized 1:1 to receive either 3 cycles of zanubrutinib monotherapy (320 mg total daily dose, orally), followed by zanubrutinib + sonrotoclax for 12 cycles, or standard ven + obi treatment for 12 cycles. Randomization will be stratified by age (<65 vs ≥65 years) and IGHV and del(17p)/ TP53 mutation status. The primary endpoint is PFS as assessed by independent review committee (IRC) according to 2018 iwCLL guidelines with modifications for treatment-related lymphocytosis for patients with CLL (Cheson et al. 2012). Key secondary endpoints include complete response rate (CRR), defined as CR or CR with incomplete hematopoietic recovery, assessed by IRC; rates of uMRD4 in bone marrow and peripheral blood at the first post-treatment follow-up visit based on next-generation sequencing by clonoSEQ; and overall survival. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing. Clinical trial information: NCT06073821 .
First-line treatment of follicular lymphoma (FL) with golcadamide, rituximab +/- nivolumab: An umbrella randomised phase 2 investigator-led study.
Authors: Chong Geoffrey , Palmer Jodie , Barraclough Allison , Churilov Leonid , Keane Colm , Lee Sze Ting , Lee Denise , Ratnasingam Sumita , Smith Charmaine , Hawkes Eliza Anne
Published: June 2024

TPS7092

Background: The most common therapy FL pts receive remains chemotherapy which yields high efficacy but also significant toxicity.(Marcus 2017, Rummel 2013). FL pts are largely aged over 65 and may require treatment multiple times over their disease course thus novel regimens which enhance efficacy and minimise toxicity are highly desirable. FL patient (pt) outcomes are influenced by tumor microenvironment composition and manipulation with immunotherapy. Ikaros and Aiolos, key cell development and homeostasis transcription factors are upregulated in FL. Cereblon-modulating compounds (CELMoDs) such as golcadomide (G) promote degradation of these with demonstrated efficacy alone or with rituximab (R) in FL (responses-ORR- upto 75% in heavily pre-treated FL pts) (Morschhauser 2018, Michot 2021). We reported favourable efficacy of nivolumab (N) a PD1 inhibitor plus R in 1L treatment of FL (ORR 92% complete response CR 54%). (Hawkes 2021).This study (‘TOP-FLOR’; NCT05788081) builds on these findings and potential immunomodulatory synergy to explore the efficacy and safety of R + G, a novel CELMoD +/- N in treatment-naïve advanced stage FL pts. Methods: This is an open label multicentre umbrella Bayesian Optimal randomised Phase 2 trial (n=40). Eligibility includes: age >18 years, treatment-naïve, stage II-IV, low grade FL, ECOG 0-2. Pts from 5 Australian sites are randomised 1:1 to receive 8 cycles of R-G +/-N 8 cycles of 28 days (D) each as follows: Arm A; R 375 mg/m2 IV D1 + G 0.4 mg orally D1- 14; Arm B; R-G as above +N 480mg IV D1. All pts in partial response (PR) or CR post cycle 8 receive 8 doses of 12-weekly R maintenance. The primary endpoint (EP) is CR rate post induction in the absence of prohibitive toxicity (CTCAE V5.0). Secondary EP are overall toxicity, ORR (as per Lugano criteria), time to treatment failure, progression free survival, overall survival. Exploratory EP include: pt reported outcomes, PET radiomics, laboratory biomarkers. Study assessments include safety assessments every cycle until D28 post final study drug delivery. Response assessments (PET/CT), pt reported outcomes & biomarker bloods are performed at baseline, post cycles 2, 5 & 8, then 6 monthly during R maintenance. Futility analysis occurs after 11 pts are recruited to each arm with < 7 pts achieve the primary EP. Treatment arms will not be formally compared. Kaplan-Meier analysis will be used to report survival probabilities. This trial received IRB approval on 14 July 2023 (HREC/88597/Austin-2023). To date 15 pts have been randomised. Clinical trial information: NCT05788081 .
A phase 1/2, open-label, multicenter trial investigating the safety, tolerability, and preliminary antineoplastic activity of IPH6501, a first-in-class NK cell engager, in patients with relapsed and/or refractory CD20-expressing non-Hodgkin lymphoma.
Authors: Falchi Lorenzo , Walker Patricia , Presgrave Peter , Gregory Gareth P. , Marie Delphine , Leyco A.J. , Demaria Olivier , Le Floch François , Hanekom Wouter , Bonin Cecile , Paturel Carine , Quaratino Sonia
Published: June 2024

TPS7095

Background: The therapeutic landscape for relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL) is evolving to include targeted T-cell based immunotherapies. However, there remains an unmet medical need for patients who are refractory to, relapsing from, or are ineligible for these therapies. Leveraging natural killer (NK) cells emerges as a promising strategy, as demonstrated in a Phase 1 study with IPH6101/SAR’579 in R/R AML (Stein, ASCO 2023; Bajel, ASH 2023), and offers a novel approach that could complement or provide an alternative to T-cell therapies. IPH6501 is a first-in-class tetraspecific antibody-based NK cell engager that simultaneously targets the CD16a and NKp46 receptors on NK cells and CD20 on B-NHL cells. It also includes an engineered IL-2 variant designed with mutations to avoid binding to CD25 (IL-2Rα), limiting Treg activation and potential IL-2 related side effects, whilst inducing NK proliferation. In preclinical animal models, IPH6501 boosted NK cell proliferation and activation, and CD20+ target cell elimination in peripheral blood and tissues, at well-tolerated doses. In samples obtained from R/R B-NHL patients, IPH6501 demonstrated greater killing efficacy compared to a CD3xCD20 T-cell engager, and yet lower cytokine secretion, suggesting a potentially safer profile. Methods: This is a global first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety profile (DLTs and MTD), tolerability according to NCI-CTCAE v5.0 and to determine the RP2D of IPH6501 for patients with B-NHL (NCT06088654). Secondary objectives are to characterize the pharmacokinetic profile and evaluate the immunogenicity of IPH6501. Eligible subjects are aged ≥18 years with advanced, histologically confirmed, CD20+ B-NHL with an ECOG PS ≤2, and without established alternative therapy. Subjects must have received ≥2 prior systemic therapies which may have included astem cell transplant or CAR-T cell therapy. The Phase 1 part of the study will consist of a dose escalation part which will follow a3+3 design to determine the MTD or the highest dose to be tested as defined in protocol if the MTD has not been reached, and a dose assessment part to randomize ≥2 dose levels to determine the RP2D. The Phase 2 part will enroll one or more cohorts of selected B-cell NHL subtypes to be determined at a later stage. Up to 184 subjects will be enrolled, and the study is open in the United States, Australia and Europe. Clinical trial information: NCT06088654 .
Ο Theodore Stephanides (1896-1983) ως μεταφραστής της ελληνικής ποίησης και ως αγγλόφωνος ποιητής και απομνημονευματογράφος
Authors: Κονιδάρη Βαρβάρα-Ειρήνη
Published: June 2024

Η παρούσα διδακτορική διατριβή στόχο έχει την παρουσίαση, μελέτη και ανάλυση του πολύπλευρου μεταφραστικού και συγγραφικού έργου του λογίου, μεταφραστή και συγγραφέα Θεόδωρου Στεφανίδη. Ο Θεόδωρος Στεφανίδης (1896-1983), άνθρωπος ευρύτατης μόρφωσης, μετέφρασε έναν τεράστιο όγκο ποιημάτων του Κωστή Παλαμά, με συνεργάτη του τον ενορχηστρωτή της Γενιάς του ’30, Γιώργο Κατσίμπαλη (1899-1978). Έφερε εις πέρας και πολλές άλλες σημαντικές μεταφραστικές εργασίες από την ελληνική στην αγγλική γλώσσα, όπως για παράδειγμα, τη μετάφραση του Ερωτόκριτου του Βιτσέντζου Κορνάρου σε έμμετρο στίχο, και τη μετάφραση αρχαίων ελλήνων ποιητών. Επιπλέον, συνέγραψε και ο ίδιος και μελέτησε σε βάθος την ελληνική και βρετανική πολιτιστική παράδοση, αφήνοντας ένα αξιόλογο συγγραφικό έργο, στο οποίο συνυπάρχουν, μεταξύ άλλων, ποιητικές συλλογές, τόμοι απομνημονευμάτων, θεατρικά κείμενα και αλληλογραφία.Θα αναλυθεί διεξοδικά το πολυσχιδές αλλά ελάχιστα καταχωρημένο στην νεότερη ελληνική γραμματεία μεταφραστικό και συγγραφικό έργο του, με στόχο την ουσιαστική κατανόηση και συμπερίληψή του στις μεταφραστικές και ανθρωπιστικές σπουδές.
Απόψεις των φοιτητών, του διοικητικού και ειδικού τεχνικού εργαστηριακού προσωπικού (ΕΤΕΠ) για τη διαχείριση κίνδυνων – κρίσεων στον εργασιακό χώρο των Ανώτατων Εκπαιδευτικών Ιδρυμάτων (Α.Ε.Ι.)
Authors: Σκουλιδάς Νικόλαος
Published: June 2024

Τα πανεπιστήμια, ως κοινωνικές οργανώσεις, αποτελούν τόπους στους οποίους ο κίνδυνος είναι αυξημένος, και συντελούνται κρίσεις με ολοένα αυξανόμενο ρυθμό και ένταση. Ως εκ τούτου, οι διοικήσεις τους καλούνται να είναι κατάλληλα προετοιμασμένες για κάθε ενδεχόμενο, ανεξάρτητα από το πόσο ακραία ή υπερβολική μπορεί να θεωρηθεί υπόθεση και η πιθανότητα εμφάνισής του. Για την καταλληλότερη αυτή προετοιμασία θεωρούνται αναγκαία μεταξύ άλλων η διαμόρφωση θετικών αντιλήψεων και στάσεων των μελών της πανεπιστημιακής κοινότητας απέναντι στον κίνδυνο και στη διαχείριση των κρίσεων. Με βάση το έλλειμμα σχετικών ερευνών στη βιβλιογραφία σκοπός της εργασίας αυτής είναι να διερευνήσει τις αντιλήψεις των φοιτητών, του Διοικητικού Προσωπικού και ΕΤΕΠ, του Πανεπιστημίου Αιγαίου και του Πανεπιστημίου Δυτικής Αττικής ως προς τη διαχείριση των κινδύνων και την αντιμετώπιση κρίσεων στο ευρύτερο περιβάλλον (εκπαιδευτικό, ερευνητικό, κοινωνικό, εργασιακό) των Ανώτατων Εκπαιδευτικών Ιδρυμάτων (ΑΕΙ). Τα ερευνητικά εργαλεία της έρευνας αποτέλεσαν δύο ερωτηματολόγια. Το «Ερωτηματολόγιο φοιτητών» και το «Ερωτηματολόγιο Διοικητικού Προσωπικού και ΕΤΕΠ» (κατασκευασμένα από τον ερευνητή). Τα ερωτηματολόγια διανεμήθηκαν και συμπληρώθηκαν από τους φοιτητές, το Διοικητικό Προσωπικό και ΕΤΕΠ των Πανεπιστήμιων Αιγαίου και Δυτικής Αττικής και είχαν ως στόχο να αποτυπώσουν τις απόψεις τους, για τη διαχείριση κινδύνων –κρίσεων στον εργασιακό χώρο των Α.Ε.Ι. Για τη στατιστική επεξεργασία των δεδομένων της έρευνας χρησιμοποιήθηκε το πρόγραμμα SPSS 20 και υπολογίσθηκε ο δείκτης εσωτερικής αξιοπιστίας Cronbach΄s a. Τα κυριότερα αποτελέσματα της παρούσας έρευνας δείχνουν ότι παρόλο που η λειτουργία του πανεπιστήμιου λαμβάνει χώρα σε ένα προστατευμένο σχετικά περιβάλλον οι κίνδυνοι σε αυτόν υφίστανται και τα κρίσιμα συμβάντα λαμβάνουν χώρα συχνά. Ωστόσο ο βαθμός ετοιμότητάς της πανεπιστημιακής κοινότητας στον τομέα της διαχείρισης κινδύνου και κρίσεων κρίνεται ότι είναι χαμηλός.
Χορήγηση αντιβιοτικών σε υποψία λοίμωξης καθοδηγούμενη από βιοδείκτες
Authors: Αδάμη Μαρία-Ευαγγελία
Published: June 2024

Σκοπός: Οι πρόσφατες κατευθυντήριες γραμμές για τη σήψη προτείνουν άμεση έναρξη αναζωογόνησης για τους ασθενείς με λοίμωξη που παρουσιάζουν 2 ή 3 βαθμούς της κλίμακας Quick Sequential Organ Failure Assessment (qSOFA). Ωστόσο, η αντιμετώπιση των ασθενών με ένα βαθμό παραμένει αμφιλεγόμενη. Σκοπός της μελέτης ήταν η απόδειξη πως η χρήση του βιοδείκτη soluble urokinase plasminogen activator receptor (suPAR), μπορεί να βελτιώσει την πρόγνωση του κινδύνου και να αποτρέψει την δυσμενή έκβαση των ασθενών με qSOFA 1 με την εφαρμογή έγκαιρης θεραπευτικής παρέμβασης. Μεθοδολογία: Η μελέτη αποτελούνταν από δύο μέρη. Στο πρώτο μέρος, αναλύθηκαν δεδομένα προοπτικής κοορτής ως προς την προγνωστική ικανότητα του συνδυασμού qSOFA/suPAR. Στο δεύτερο μέρος, διεξήχθη μια διπλά τυφλή, τυχαιοποιημένη, ελεγχόμενη κλινική δοκιμή με το ακρωνύμιο SUPERIOR που αξιολόγησε την αποτελεσματικότητα της καθοδηγούμενης από τον βιοδείκτη suPAR ιατρικής παρέμβασης. Η μελέτη αυτή πραγματοποιήθηκε από τον Νοέμβριο του 2018 έως τον Δεκέμβριο του 2020. Στο πρώτο μέρος χρησιμοποιήθηκε πολυπαραγοντική αναλογική εξάρτηση, ενώ στο δεύτερο μοντέλα μονοπαραγοντικής και πολυπαραγοντικής αναλογικής εξάρτησης. Ασθενείς του τμήματος επειγόντων περιστατικών (ΤΕΠ) με υποψία λοίμωξης και τιμές qSOFA 1 και suPAR≥12 ng/mL κατανεμήθηκαν είτε στην ομάδα μεροπενέμης είτε εικονικού φαρμάκου. Ως πρωτογενές καταληκτικό σημείο θεωρήθηκε η πρώιμη επιδείνωση που ορίστηκε ως η αύξηση κατά τουλάχιστον ένα βαθμό της κλίμακας Sequential Organ Failure Assessment (SOFA) κατά τις πρώτες 24 ώρες της εισαγωγής. Αποτελέσματα: Τον υψηλότερο κίνδυνο θνητότητας διέτρεχαν οι ασθενείς με qSOFA 2 και 3. Λαμβάνοντας ως αναφορά τον σχετικό κίνδυνο (HR) θνητότητας των ασθενών με qSOFA=1 και suPAR <12 ng/mL, ο HR για τη θνητότητα μετά από 28 ημέρες για τους ασθενείς με qSOFA=1 και suPAR ≥12 ng/mL ήταν 2.98 [95% Διάστημα Εμπιστοσύνης (ΔΕ) 2,11-3,96]. Η μελέτη SUPERIOR τερματίστηκε πρόωρα λόγω της πανδημίας COVID-19 με αποτέλεσμα την εγγραφή 91 ασθενών. 47 κατανεμήθηκαν στην ομάδα εικονικού φαρμάκου και 44 στην ομάδα μεροπενέμης. Το πρωτογενές καταληκτικό σημείο επετεύχθη στο 40,4% (ν=19) και στο 15,9% (ν=7), αντίστοιχα [διαφορά 24,5% (5,9-40,8); συμπληρωματικός λόγος πιθανοτήτων (OR) 0,28 (0,10-0,76)]. Post-hoc ανάλυση έδειξε σημαντικές διάμεσες αλλαγές της βαθμολογίας SOFA μετά από 72 και 96 ώρες ίσες με 0 και -1, αντίστοιχα.Συμπεράσματα: Η συνδυαστική χρήση του qSOFA 1 με το βιοδείκτη suPAR βελτιώνει την ικανότητα πρόγνωσης δυσμενούς έκβασης αυτής της ομάδας ασθενών και προτείνει την έγκαιρη έναρξη θεραπευτικής αντιμετώπισης.
Financialization and Dynamics of Currency Futures Market during COVID-19: Evidence from India
Authors: Kumar Adish , Gupta Kapil
Published: June 2024

This study examines inter-relationship and impact of COVID-19 on Indian currency and equity futures markets during the period of financial crisis. In such period, investors look for alternative asset classes to hedge against risk as observed during Global Financial Crisis. This study examines whether same phenomenon was observed after COVID-19 in India considering currency futures as an alternate asset class. For this purpose daily exchange rate of Indian Rupee with British Pound Sterling, Japanese Yen, Euro and United States Dollar and for equity futures, near-month NIFTY 50 futures contracts are used. After examining stationarity of data, Co integration test, Granger causality and Bi-variate correlation is applied. ARCH and DCC-GARCH model is employed to allow for heteroscedasticity and time variation in correlation. It is observed that YEN, JPY and USD display significantly negative correlation with Nifty futures. Currency futures is causing Nifty futures during COVID-19 period and leads Nifty futures by one day. However, it is other way around during pre-COVID-19 period. Long-run co-integration is not evident. ARCH effect is present in both time series and except for insignificant short-run shock persistence during COVID-19 period, there exists time varying correlation between currency returns and Nifty.
Guía de género y salud. Innovaciones y propuestas para trabajar en grupos pequeños
Authors: García-Carpintero Muñoz Mª Ángeles
Published: June 2024

Esta guía, cuya primera edición obtuvo en 2015 el IX Premio Rosa Regás, presenta un conjunto de propuestas dirigido fundamentalmente a los estudiantes universitarios. Surge a raíz de la experiencia y reflexión docente desarrollada en la asignatura Género y Salud, impartida en el grado de Enfermería desde 2009. Constituye, pues, una herramienta para trabajar en seminarios y grupos reducidos temas que abordan, entre otros aspectos, la salud de hombres y mujeres, las identidades sexuales, el impacto de la construcción cultural del género, las características específicas del maltrato y su abordaje desde la atención sanitaria, así como otras formas de violencias invisibilizadas en la sociedad. Asimismo, se reflexiona sobre la construcción de la identidad de género, identificando mitos, estereotipos y creencias. Para desarrollar las propuestas, se emplean diversas estrategias metodológicas, entre las que se incluyen ejercicios vivenciales, grupos de discusión o videofórum.
Selling Bonus Actions in Video Games
Authors: Sheng Lifei , Zhao Xuying , Thomas Ryan Christopher
Published: June 2024

In the mobile video games industry, a common in-app purchase is for additional “moves” or “time” in single-player puzzle games. We call these in-app purchases bonus actions. In some games, bonus actions can only be purchased in advance of attempting a level of the game (pure advance sales (PAS)), yet in other games, bonus actions can only be purchased in a “spot” market that appears when an initial attempt to pass the level fails (pure spot sales). Some games offer both advance and spot purchases (hybrid advance sales). This paper studies these selling strategies for bonus actions in video games. Such a question is novel to in-app tools selling in video games, and it cannot be answered by previous advance selling studies focusing on end goods. We model the selling of bonus actions as a stochastic extensive form game. We show how the distribution of skill among players (i.e., their inherent ability to pass the level) and the inherent randomness of the game influence selling strategies. For casual games, where low-skill players have a sufficiently high probability of success in each attempt, if the proportion of high-skill players is either sufficiently large or sufficiently small, firms should adopt PAS and shut down the “spot” market. Furthermore, the player welfare-maximizing selling strategy is to sell only in the spot market. Hence, no “win-win” strategy exists for casual games. However, PAS can be a win-win for hardcore games, where low-skill players have a sufficiently low success probability for each attempt.

This paper was accepted by Hemant Bhargava, information systems.

Funding: C. T. Ryan received funding from NSERC Discovery [Grant RGPIN-2020-06488].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2022.02348 .
How to Design a Stable Serial Knockout Competition
Authors: Lambers Roel , Pendavingh Rudi , Spieksma Frits
Published: June 2024

We investigate a new tournament format that consists of a series of individual knockout tournaments; we call this new format a serial knockout competition (SKC). This format has recently been adopted by the Professional Darts Corporation. Depending on the seedings of the players used for each of the knockout tournaments, players can meet in the various rounds (e.g., first round, second round … semifinal, final) of the knockout tournaments. Following a fairness principle of treating all players equal, we identify an attractive property of an SKCl each pair of players should potentially meet equally often in each of the rounds of the SKC. If the seedings are such that this property is indeed present, we call the resulting SKC stable. In this note, we formalize this notion, and we address the following question. Do there exist seedings for each of the knockout tournaments such that the resulting SKC is stable? We show using a connection to the Fano plane that the answer is yes for eight players, and we prove that the resulting SKC is unique up to permutations of the players. We further prove that stable SKCs exist for any numbers of players that are a power of two, and we provide stable schedules for competitions on 16 and 32 players.

Funding: The research of F. Spieksma was partly funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek [Grant 024.002.003].
ECG of the month
Authors: Bloe Charles
Published: June 2024

In this issue's ECG of the month, Charles Bloe presents the case of a 94-year-old male care home resident with a recent history of frequent hospital admissions, who was experiencing shortness of breath at rest.
INCIDENCE, DEMOGRAPHICS, CHARACTERISTICS, AND MANAGEMENT OF ACUTE ACHILLES TENDON RUPTURE
Authors: Briggs-Price S. , O'Neill S. , Houchen-Wolloff L. , Modha G. , Fitzpatrick E. , Faizi M. , Shepherd J. , Mangwani J.
Published: June 2024

Introduction

Achilles tendon rupture (ATR) account for 10.7% of all tendon and ligament injuries and causes lasting muscular deficits and have a profound impact on patients’ quality of life1,2. The incidence, characteristics and management of ATR in the United Kingdom is poorly understood.

Method

Data was collected prospectively from University Hospitals of Leicester Emergency Department (ED) between January 2016 and December 2020 and analysed retrospectively. The medical records were reviewed to determine management protocols (surgical/non-surgical) and limited mobilisation (VACOped™ boot) duration. Leicestershire population data was taken from Leicestershire County Council demography report.

Findings

277 individuals were diagnosed with an ATR during the 4-year period. The mean (SD) annual incidence was 56 (±6) ATR. An incidence rate of 8.02 per 100,000 people per annum. The average characteristics of those experiencing an ATR is male (78.3%), 46.8yrs old (±14.4), body mass index 29.1 (±6.3). Median (IQR) number of comorbidities 1 (2) and duration to present to ED was 0 days (1). The main mechanism of rupture was sporting activity (62.1%).

97.4% were non-surgically managed using a limited mobilisation boot (VACOped). The boot was worn for an average of 62.6 days (±8.9). 94 participants provided pre-ATR Achilles symptoms data. 16% (n=15/94) of participants reported a previous contralateral ATR. 7.4% reported a re-rupture (n=7/94). 15.4% (n=14/91) reported an Achilles tendinopathy on the ipsilateral side prior to ATR. 7.7% (n=7/91) reported bilateral Achilles tendinopathy and 1.1% (n=1/91) reported contralateral Achilles tendinopathy prior to ATR.

Conclusion

The incidence of ATR is 8.02 cases per 100,000 people per annum. This is the first UK data on ATR incidence. Most ATR were managed non-surgically in this cohort. The majority of ruptures occurred during sporting activity. Those that had previous Achilles symptoms (24.2%) indicate tendons are not always asymptomatic prior to ATR.
EFFECT OF FIBULA SHORTENING ON MEDIAL CLEAR SPACE AND LATERAL TRANSLATION OF THE TALUS: AN ANATOMICAL CADAVERIC STUDY
Authors: Gomaa A. , Heeran N. , Roper L. , Airey G. , Gangadharan R. , Mason L. , Bond A.
Published: June 2024

Introduction

Fibula shortening with an intact anterior tibiofibular ligament (ATFL) and medial ligament instability causes lateral translation of the talus. Our hypothesis was that the interaction of the AITFL tubercle of the fibular with the tibial incisura would propagate lateral translation due to the size differential.

Aim

To assess what degree of shortening of the fibular would cause the lateral translation of the talus.

Methodology

Twelve cadaveric ankle specimens were dissected removing all soft tissue except for ligaments. They were fixed on a specially-designed platform within an augmented ankle cage allowing tibial fixation and free movement of the talus. The fibula was progressively shortened in 5mm increments until complete ankle dislocation. The medial clear space was measured with each increment of shortening.

Results

The larger AITFL tubercle interaction with the smaller tibial incisura caused a significant increase in lateral translation of the talus. This occurred in most ankles between 5–10mm of fibular shortening. The medial clear space widened following 5mm of shortening in 5 specimens (mean=2.0725, SD=±2.5338). All 12 specimens experienced widening by 10mm fibula shortening (Mean=7.2133mm, SD=±2.2061). All specimens reached complete dislocation by 35mm fibula shortening. Results of ANOVA analysis found the data statistically significant (p<0.0001).

Conclusion

This study shows that shortening of the fibula causes a significant lateral translation of the talus provided the ATFL remains intact. Furthermore, the interaction of the fibula notch with the ATFL tubercle of the tibia appears to cause a disproportionate widening of the medial clear space due to its differential in size. Knowledge of the extent of fibula shortening can guide further intervention when presented with a patient experiencing medial clear space widening following treatment of an ankle fracture.
THE ACUTE MANAGEMENT OF PILON FRACTURES (ENFORCE) STUDY: A TRAINEE-LED NATIONAL COLLABORATIVE EVALUATION OF PRACTICE
Authors: Hill D. , Davis J.
Published: June 2024

Introduction

Tibial Pilon fractures are potentially limb threatening, yet standards of care are lacking from BOFAS and the BOA. The mantra of “span, scan, plan” describes staged management with external fixation to allow soft tissue resuscitation, followed by a planning CT-scan. Our aim was to evaluate how Tibial Pilon fractures are acutely managed.

Methods

ENFORCE was a multi-centre retrospective observational study of the acute management of partial and complete articular Tibial Pilon fractures over a three-year period. Mechanism, imaging, fracture classification, time to fracture reduction and cast, and soft tissue damage control details were determined.

Results

656 patients (670 fractures) across 27 centres were reported. AO fracture classifications were: partial articular (n=294) and complete articular (n=376). Initial diagnostic imaging mobilities were: plain radiographs (n=602) and CT-scan (n=54), with all but 38 cases having a planning CT-scan. 526 fractures had a cast applied in the Emergency Department (91 before radiological diagnosis), with the times taken to obtain post cast imaging being: mean 2.7 hours, median 2.3 hours, range 28 mins – 14 hours). 35% (102/294) of partial articular and 57% (216/376) of complete articular (length unstable) fractures had an external fixator applied, all of which underwent a planning CT-scan. Definitive management consisted of: open reduction internal fixation (n=495), fine wire frame (n=86), spanning external fixator (n=25), intramedullary nail (n=25), other (n=18).

Conclusion

The management of Tibial Pilon fractures is variable, with prolonged delays in obtaining post cast reduction radiographs, and just over half of length unstable complete articular fractures being managed with the gold standard “span, scan, plan” staged soft tissue resuscitation. A BOFAS endorsed BOAST (British Orthopaedic Association Standard for Trauma) for Tibial Pilon fractures is suggested for standardisation of the acute management of these potentially limb threatening injuries, together with setting them apart from more straightforward ankle fractures.
WHAT DO BOFAS MEMBERS PERCEIVE TO BE THE BARRIERS AND FACILITATORS OF DAY-CASE SURGERY FOR MAJOR FOOT AND ANKLE PROCEDURES? A SCOPING SURVEY OF SURGEONS
Authors: Houchen-Wolloff L. , Berry A. , Crane N. , Townsend D. , Clayton R. , Mangwani J.
Published: June 2024

Introduction

Recent advances in minimally invasive surgery and improved post-operative pain management make it possible to perform major foot/ankle operations as day-case. This could have significant impact on length of stay, saving resources and is in keeping with government policy. However, there are theoretical concerns about complications and low patient satisfaction due to pain.

Methods

The survey was developed following review of the literature and was approved for distribution by the BOFAS (British Orthopaedic Foot & Ankle Society) scientific committee. An online survey (19 questions) was sent to UK foot and ankle surgeons via the BOFAS membership list. Major foot/ ankle procedures were defined as surgery that is usually performed as an inpatient in majority of centres and day-case as same day discharge, with day surgery as the intended pathway.

Results

A total of 132 surgeons responded, 80% from Acute NHS Trusts. The majority (78%) thought that more procedures could be performed as day-case at their centre. Currently 45% of respondents perform less than 100 day-case surgeries per year for these procedures. Despite post-operative pain and patient satisfaction being theoretical concerns for day-case surgery in this population; these outcomes were only measured by 34% and 10% of respondents respectively. The top perceived barriers to performing more major foot and ankle procedures as day-case were: Lack of physiotherapy input pre/post-operatively (23%), Lack of out of hours support (21%).

Conclusions

There is consensus among surgeons to do more major foot/ ankle procedures as day-case. Despite theoretical concerns about post-operative pain and satisfaction this was only measured by a third of those surveyed. Out of hours support and physiotherapy input pre/ post-op were perceived as the main barriers. There is a need to scope the provision of physiotherapy pre/post-operatively and out of hours support at sites where this is a perceived barrier.
TOWARDS UNDERSTANDING MÜLLER-WEISS DISEASE: A UNIVERSAL PLATFORM
Authors: Wong-Chung J. , McKenna R. , Lynch-Wong M. , Walls A. , Wilson A.
Published: June 2024

Background

The only existing classification of Müller-Weiss Disease (MWD), based solely on Méary's angle, serves neither as guide for prognosis nor treatment. This accounts for lack of gold standard in its management.

Methods

Navicular compression, medial extrusion, Kite's angle and metatarsal lengths were measured on all radiographs of 95 feet with MWD. Joints involved, presence and location of navicular fracture were recorded.

Results

We identified three distinct groups. Group 1 comprises 11 “early-onset” MWD feet, aged 9 to 29 years. These had the greatest compression and medial extrusion, and lowest Kite's angles. All except 1 were index minus and had a lateral navicular fracture. None has required surgery to date. Only 1 has moderate talonavicular joint (TNJ) degeneration.

Group 2 comprises 23 “Müller-Weissoid” feet with radiologically normal navicular in their fifties and developing MWD, on average, 4.5 years later. These had the lowest compression and extrusion, and highest Kite's angles. None had complete fracture. All had TNJ arthritis, with early changes at lateral naviculocuneiform joint (NCJ) in 43%. Group 3 “late-onset” MWD, presenting in the sixth decade, is subdivided into 3 sub-groups. Only TNJ is involved in group 3A (16). Group 3B denotes affection of TNJ more than NCJ (20). In group 3C “reverse Müller-Weiss disease”, which affects NCJ more than TNJ (25), second metatarsal overlength is highest of all groups. No difference in age, compression, extrusion and Kite's angle exists among the 3 subgroups. No fracture occurred in group 3A compared to 65% and 32% in groups 3B and 3C, respectively.

Conclusions

With a need to compare like-for-like pathology, the proposed classification provides a common platform for reporting outcomes of different treatment modalities, operative or nonoperative. We theorize pathogenetic pathways in the different groups and propose systematic surgical approaches for each category.
OUTCOMES OF TENOSYNOVIAL GIANT CELL TUMOUR OF THE FOOT AND ANKLE
Authors: Barnett J. , Rudran B. , Patel S. , Aston W. , Welck M. , Cullen N.
Published: June 2024

Background

Tenosynovial giant cell tumour (TGCT) is a benign proliferative disease affecting synovial membranes. There are two forms, localised and diffuse, which although histologically similar are managed differently. It is locally invasive and is treated in most cases by operative excision. The aim of this study was to assess outcomes from the largest single-centre experience to date in patients with this condition.

Methods

A retrospective analysis of 123 cases was performed in patients treated between 2003 and 2019 with TGCT of the foot and/or ankle. Data was collected on age at presentation, radiological pattern of disease, location of disease, treatment provided and recurrence rates. The minimum follow-up was 2 years with a mean of 7.7 years.

Results

47 male and 76 female patients with a mean age at diagnosis of 39 (range, 11–76) years were identified. 85 (69.1%) cases were categorised as localised and 38 (30.9%) were diffuse. Half of the cases presented in the ankle (62/123, 50.4%). 89% (110) of patients underwent open operative excision of the lesion. Radiotherapy was used in 2 cases for recurrent disease. Pain was the most common postoperative symptom which developed in 20% (22/110) of cases). 13 cases were managed nonoperatively where symptoms were minimal, with one case requiring surgery at a later date. Disease recurrence was 3.5% (3/85) in localised disease and 36.8% (14/38) in diffuse disease giving an overall recurrence rate of 13.8% (17/123).

Conclusion

The outcomes of TGCT management are dependent on the type of disease, the extent of preoperative erosive changes and the presence of pre-operative pain. We present a summary of recommended management based on the experience from this single tertiary centre.