Consolidation Phase Research Articles

Vitamin D status in healing of distal humeral fractures: Clinical observations.

Fracture healing is a complex biological process that begins soon after a fracture has occurred. Whereas the role of vitamin D status on the maintenance of bone health is well established, the clinical effects of vitamin D deficiency in the healing of distal humeral fractures are less well explored. This study examines the role of vitamin D serum levels in distal humeral fractures (C2, C3) managed with open reduction and double plate fixation, by comparing its concentration in patients with or without radiographic signs of fracture healing and in control subjects. Our hypothesis is that 6 months from treatment vitamin D levels will be different between the groups of patients. We measured the vitamin D serum level in a cohort of consecutive adult patients aged 30 to 60 years. They included a group of subjects without fractures who were admitted to our clinic in the 6 months preceding the study (controls) and two groups of patients with humeral fractures who at 6-month follow-up showed or failed to show radiological signs of fracture healing. The mean vitamin D concentration was 23.03 μg/L (±5.8) in the group with radiographic signs of fracture healing, 9.30 μg/L (±2.60) in the group with radiographic signs of delayed union and 26.15 μg/L (±11.76 μg/L) in the control group. Significantly different (p < 0.05) concentrations were measured between the fracture groups, between the group with radiographic signs of fracture healing and the control group and between the group with radiographic signs of delayed union and the control group. Vitamin D is primarily involved in the stages of hard callus formation and remodelling. It also has several functions that affect the early stages of fracture healing. Vitamin D influences the cellular process of bone healing, although the underlying mechanism is still partly unclear. It would be useful to determine the vitamin D status of fracture patients at admission and to start supplementation, with periodic checks, to foster the consolidation phase. Although vitamin D is clearly not the only factor influencing the consolidation of a surgically treated distal humerus fracture, its concentration can easily be determined and managed. Our data suggest that vitamin D levels should be determined at admission and that fracture patients with low concentrations should be started on vitamin D supplementation.

Blinatumomab in the Therapy of Acute B-Lymphoid Leukemia.

Blinatumomab, a CD19-CD3 bispecific T cell engager (BiTE), has two recombinant single-chain variable fragments that temporarily link CD3+ T cells and CD19+ B cells, leading to the T cell-mediated lysis of neoplastic B cells. Improved minimal residual disease (MRD)-negative response rates and long-term overall survival have been observed in B-ALL patients who received this drug. These therapeutic successes have led to FDA approval for refractory/relapsed and MRD-positive B-ALL patients. Furthermore, recent studies in newly diagnosed B-ALL patients have led in Philadelphia chromosome-positive patients to the development of chemotherapy-free regimens based on tyrosine kinase inhibitors plus Blinatumomab and in Philadelphia chromosome-negative patients to improvement in outcomes using chemotherapy regimens that have incorporated Blinatumomab in the consolidation phase of treatment.

Assessing Sustainability Performance of Community-based Fish Farming Cooperatives: A Comprehensive Checklist

Cooperative fisheries are increasingly recognized as a promising approach for small-scale fisheries management. However, there is a lack of empirical evidence on the key elements that drive sustainability within these cooperatives. This survey study aims to develop a sustainability performance checklist tailored for fisheries cooperatives throughout their lifecycle. Initially, a preliminary list of five-point Likert scale sustainability factors was created and reviewed through interviews with experts from both fisheries academic and executive sectors. Their feedback contributed to refining the checklist, ensuring its relevance, clarity, and simplicity. Experts from both the academic and executive sectors of fisheries cooperatives have confirmed the content validity of the economic, social, and environmental criteria included in the checklist. The data collected across 61 cooperatives. To identify the key factors influencing the sustainability performance of fisheries cooperatives throughout their lifecycle, a factor analysis was performed, employing the Varimax rotation method. The findings indicate that economic considerations are the primary focus during the initial establishment of fisheries cooperatives. As these cooperatives evolve through the growth and consolidation phases, social factors become increasingly significant. Additionally, the study highlights the essential role of environmental aspects in maintaining the stability and balance of these cooperatives. The research underscores the interdependence of economic, social, and environmental elements in fostering the sustainability of fisheries cooperatives. These insights are particularly relevant for policymakers, managers, and stakeholders in fisheries management. Furthermore, the developed sustainability performance checklist and weighting system can effectively assist in assessing and enhancing the sustainability of fisheries cooperatives.

The impact of immune recovery and treatment duration on disseminated histoplasmosis consolidation therapy in AIDS patients

IntroductionThe present study investigated the impact of immune recovery and the duration of antifungal adherence in the consolidation phase of disseminated histoplasmosis (DH) in acquired immune deficiency syndrome (AIDS) patients living in a hyperendemic area in northeastern Brazil. Material and MethodsSixty-nine patients with DH/AIDS, admitted to the São José Hospital between 2010 and 2015, who continued histoplasmosis consolidation therapy at the outpatient clinic were studied. The follow-up duration was at least 24 months. ResultsSixty-eight patients used itraconazole 200–400 mg/day or amphotericin B deoxycholate weekly during the consolidation phase, and six patients relapsed during follow-up. The overall median duration of consolidation antifungal use was 250 days [IQR 101 - 372]. Antifungal withdrawal by medical decision occurred in 41 patients (70.7 %) after a median of 293 days [IQR 128 - 372] of use; 16 patients discontinued by their own decision, with a median of 106 days [IQR 37 - 244] of therapy; three patients had no information available, and nine continued on AF therapy. The median CD4+ T-cell count in the group without relapse was 248 cells/µL [IQR 115–355] within 6 months after admission; conversely, in the relapse group, the median cell count remained below 100 cells/µL. Irregular adherence to highly active antiretroviral therapy (HAART) was the leading risk factor associated with relapse and death (p< 0.01). DiscussionThe regular use of HAART, combined with immune recovery, proved to be highly effective in preventing relapses in DH/AIDS patients, suggesting that long-term antifungal therapy may not be necessary.

Systematic review: genetic polymorphisms in the pharmacokinetics of high-dose methotrexate in pediatric acute lymphoblastic leukemia patients.

Variations in pharmacokinetic responses to high-dose methotrexate are essential for the prognosis and management of toxicity in the treatment of pediatric acute lymphoblastic leukemia (ALL) patients. This systematic review aimed to identify and evaluate genetic polymorphisms that are significantly associated with the pharmacokinetic parameters of methotrexate during the consolidation phase of pediatric ALL treatment. Using the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, we systematically reviewed the literature from 2013 to 2023. The databases used were PubMed and Scopus. The outcomes of interest are the study design, patient characteristics, sample size, chemotherapy protocol utilized, pharmacokinetic parameters identified, and genetic polymorphisms implicated. We included 31 articles in the qualitative synthesis and found that the SLCO1B1, ABCB1, ABCC2, and MTHFR genes appear to play significant roles in MTX metabolism and clearance. Among these, variations in SLCO1B1 have the most significant and consistent impact on methotrexate clearance. These implicated variants may contribute to the precision and tailoring of HD-MTX treatment in pediatric ALL patients.

Symptom Clusters in Children With Leukemia Receiving Chemotherapy: A Scoping Review.

Leukemia represents the most prevalent childhood malignancy. Understanding the symptom clusters (SCs) associated with leukemia may help develop an effective care plan for affected children. The aims of this study were to summarize the methods of identifying SCs; ascertain the types, attributes, and changing patterns of SCs during different chemotherapy phases; and provide a point of reference for the subsequent improvement of symptom management in pediatric leukemia. The methodological framework employed was the Joanna Briggs Institute Scoping Review Guide. A comprehensive search was conducted across various databases, including PubMed, EMBASE, CINAHL, Web of Science, MEDLINE, Scopus, and China National Knowledge Infrastructure from inception until July 15, 2023. A total of 14 articles were included in this review, 6 in English and 8 in Chinese. The Memorial Symptom Assessment Scale 10-18 is the most commonly used instrument, whereas factor analysis is the most common statistical method for SC identification. The SCs were classified into 12 categories. The most severe SCs varied across different phases. Specifically, the emotional cluster dominated the prechemotherapy phase, the gastrointestinal cluster surfaced during postinduction therapy, and the consolidation and maintenance therapy phases revealed the self-image disorder cluster. Various consistent and dynamic SCs manifest among pediatric patients with leukemia undergoing chemotherapy. Future research endeavors should formulate clear criteria to determine the stability and consistency of SCs, validate SC composition and characteristics, and devise precise symptom management protocols based on SC characteristics in the distinct chemotherapy phases.

EEG subject-dependent neurofeedback training selectively impairs declarative memories consolidation process

The process of stabilization and storage of memories, known as consolidation, can be modulated by different interventions. Research has shown that self-regulation of brain activity through Neurofeedback (NFB) during the consolidation phase significantly impacts memory stabilization. While some studies have successfully modulated the consolidation phase using traditional EEG-based Neurofeedback (NFB) that focuses on general parameters, such as training a specific frequency band at particular electrodes, they often overlook the unique and complex neurodynamics that underlie each memory content in different individuals, potentially limiting the selective modulation of memories.The main objective of this study is to investigate the effects of a Subject-Dependent NFB (SD-NFB), based on individual models created from the brain activity of each participant, on long-term declarative memories. Participants underwent an experimental protocol involving three sessions. In the first session, they learned images of faces and houses while their brain activity was recorded. This EEG data was used to create individualized models to identify brain patterns related to learning these images. Participants were then divided into three groups, with one group receiving SD-NFB to enhance brain activity linked to faces, another to houses, and a CONTROL sham group that did not receive SD-NFB.Memory performance was evaluated 24 h and seven days later using an ‘old-new’ recognition task, where participants distinguished between ‘old’ and ‘new’ images. The results showed that memory contents (faces or houses) whose brain patterns were trained via SD-NFB scored lower in recognition compared to untrained contents, as evidenced 24 h and seven days post-training.In summary, this study demonstrates that SD-NFB can selectively impact the consolidation of specific declarative memories. This technique could hold significant implications for clinical applications, potentially aiding in the modulation of declarative memory strength in neuropsychiatric disorders where memories are pathologically exacerbated.

Feasibility of adaptive teaching with technology: Which implementation conditions matter?

Adaptive teaching is regarded to address students' heterogeneity in schools and to individually support their learning. Technology may help to teach adaptively. However, it is still unclear whether realizing adaptive teaching with technology is a feasible teaching practice in real-world classrooms. More importantly, it is an open question which boundary conditions constrain the feasibility of adaptive teaching with technology. We realized a four-year co-design-project in which researchers and teachers co-constructively developed adaptive teaching units (duration: 3–4 weeks) by deliberately integrating technology across secondary education. To assess the feasibility of technology-enhanced adaptive teaching, we followed a sequential-explanatory mixed-methods approach during the co-design-process. We combined a quantitative study (N = 183), investigating students' learning gains and potential moderators, and a qualitative study by means of semi-structured teacher interviews (N = 3) on implementation conditions of the adaptive teaching units. We observed that the teaching units were particularly beneficial for students with low prior knowledge and when they were highly adaptive to students’ needs. Fine-grained qualitative findings indicated that formative assessments and consolidation phases were crucial for the feasibility of technology-enhanced adaptive teaching, as well as a parsimonious use of technologies. These findings indicate that the feasibility of adaptive teaching with technology depends on boundary conditions, highlighting the need for further support to unfold the potential of adaptive teaching.

Austria: Private foundations in Austria—between consolidation and reform

Abstract Austrian private foundation law, which was 30 years old in 2023, is currently going through a phase of consolidation. Private foundations are also a constant concern for the Austrian courts in conflict situations. In this article the authors take a closer look at the Austrian private foundation as an instrument of asset protection in case of divorce, the interpretation of foundation documents, and the composition of a possible council. They also make an assessment of the way ahead.

Gap Volume Based on Computed Tomography Measurement Is a Strong Risk Factor for Delayed Gap Healing After Open-Wedge High Tibial Osteotomy

To identify factors that affect delayed gap healing after open-wedge high tibial osteotomy (OWHTO) and to determine whether large gap volume is a predictor of delayed gap healing. This retrospective study analyzed biplane OWHTO performed between 2019 and 2023 for knee osteoarthritis or osteonecrosis. The minimum follow-up period was 1 year. Delayed gap healing was defined when the medial half of the osteotomy gap area had not reached the consolidation phase by 6 months after surgery based on anteroposterior knee radiographs. Gap volume was calculated from computed tomography images. Logistic regression was performed using body height, smoking, correction angle, hinge fracture, flange thickness, and gap volume. A gap volume cutoff value for delayed gap healing was determined with receiver operating characteristic curve analysis. Gap volume was predicted with multiple linear regression. There were 80 knees in 71 patients (36 men and 44 women). The mean gap volume was 7.6 cm3. Gap healing rates at 3, 6, 9, and 12 months after surgery were 26%, 65%, 89%, and 100%, respectively. There were 25 knees with delayed gap healing. Male sex was not a significant risk factor when adjusted for body height. Multivariate logistic regression revealed that only larger gap volume was a significant risk factor (odds ratio, 1.45; P= .006). The gap volume cutoff value was 7.6 cm3, with an area under the curve of 0.74. Tall body height and a large correction angle (both P < .001) were associated with a significantly larger gap volume (R2= 0.73). Large gap volume is the most important risk factor for delayed gap healing after OWHTO. Gap volume can be predicted based on body height and correction angle. When OWHTO with substantial correction is planned for tall men, surgeons should be aware of possibly delayed gap healing. Level IV, retrospective case-control study.

Internationalisation of science and technology parks and the stage of their life: The Central European perspective

Research background: A science and technology park (STP) is an important tool of innovation policy. In order to carry out new tasks in the field of internationalisation of innovative processes, parks have to incorporate completely new ones into their classic roles and activities. There is still a low level of knowledge about the factors that limit this process. The identified research gap provided the rationale for addressing the issue of the internationalisation of parks in Poland, which is an original treatment of the issue and probably one of the first such studies in Central Europe. Purpose of the article: The purpose of the article is to diagnose the stages through which the internationalisation of science and technology parks takes place in the context of the phases of the life cycle of these organisations, as well as to identify and assess the importance of obstacles limiting the internationalisation process. Methods: A critical analysis of the literature and direct research was carried out using the survey method, according to the author's questionnaire. The research was carried out in 2022 among 18 STPs in Poland (55% of all Polish parks). The diagnosis of internationalisation was made on an institutional level. Three phases of the park life cycle were defined and operationalised based on the criteria identified by J. Allen (2007): creation, consolidation and maturity phase. Ward’s agglomeration method (Ward, 1963) was utilised to group the parks based on the level of actions realised in their life cycle and their degree of internationalisation. In the identification of the number of groups, the Duda-Hart (Duda et al., 2000) Je(2)/Je(1) index-stopping rule was used. Thirteen of the most important obstacles to the internationalisation process were identified. In order to examine the internal consistency of variables describing the internationalisation of parks, Cronbach’s Alpha reliability index was calculated. In order to find out the strength and direction of the existing relationship between obstacles and the internationalisation index of the studied parks, Kendall’s τ test was used. Findings &amp; value added: The sequential development of parks at the national level is in line with the assumptions indicated in the literature. The problem, however, is the internationalisation of parks. Not only is it characterised by a low level, but its course also does not indicate that it is the result of the successive implementation of previously assumed activities. The processes of development and internationalisation are interrelated, but this is not a significant interdependence. The problem is also indicated by the results of studies relating to obstacles to the internationalisation process. This is because the most significant ones are diagnosed only at an advanced level of internationalisation. Such an important activity of parks is undertaken without a prior in-depth diagnosis of the international situation. This can result in limited effectiveness of the activities undertaken in the direction of internationalisation and generate related problems. The results of the study provide a basis for indicating the type of activities aimed at activating parks in the international arena. Such activities should be undertaken at a higher level than the parks themselves since they do not have sufficient procedures and resources to guarantee increased internationalisation. One desirable course of action could also be the creation of cooperation networks at different territorial and entity levels.

Female political discourse in the Albanian parliament in democracy and communism

This study delves into the transformation of women’s political discourse in Albania amidst significant political and technological shifts in recent decades. Its objective is to systematize the understanding of women’s political discourse within the Albanian parliament, examining its evolution across various historical-political periods and the influence of modern information processes in democratic Albania. Utilizing theoretical methodologies, the research scrutinizes political discourse as a dynamic facet of political communication, with a particular focus on its gender dimensions and its impact on political engagement. The analysis spans several eras: the communist regime, the initial formation of democracy, and the current democratic consolidation phase. It employs a comparative approach to highlight distinct and common features of women’s political discourse across these periods. The study identifies contemporary challenges in female political communication within the Albanian parliament and proposes strategies for their improvement, emphasizing the need to enhance the role of women in Albania’s socio-political sphere. Key lexemes indicative of different historical and political contexts are analyzed to understand the influence of regime shifts on political discourse. The study differentiates between the concepts of political discourse and political communication, offering nuanced insights into these areas. This material reveals the intersection of political, social, and cultural changes in Albania as seen through women’s political discourse. It demonstrates how shifts in political regimes and societal norms have redefined political communication, particularly for women, highlighting their growing involvement and impact in Albania’s political arena. The conclusions provide a comprehensive view of Albania’s evolving socio-political landscape, underlining the increasing significance of women in shaping the nation’s future.

Evaluation of post-activation mandibular remodelling in children with craniofacial microsomia treated with distraction osteogenesis.

Patients with type IIA craniofacial microsomia (CFM) may benefit from mandibular distraction osteogenesis (MDO) treatment during childhood; however, remodelling of the mandible during the consolidation phase, which may affect the short-term outcomes of MDO, has not yet been quantitatively analysed using computed tomography. Therefore, we aimed to investigate bone remodelling of the mandible in children with type IIA CFM treated with MDO before distractor removal and the factors that influence ramus vertical elongation efficiency. Twenty-three children with unilateral CFM were studied between 2020 and 2024. Longitudinal computed tomography data (preoperative, end of active phase and at pre-distractor removal) were analysed. Condyle positions and the mandibular cant were analysed using a paired-sample t test. The relapse rates of vertical lengthening and mandibular cant were calculated. The correlation between distraction efficiency and preoperative craniofacial morphology was analysed. The condyle on the affected side moved upwards and backwards by 28.84 ± 4.08 and 2.85 ± 4.33 mm, respectively during the active phase but lost 7.66 ± 2.64 mm of vertical extension during the consolidation phase. The relapse rates for vertical extension of the condyle and occlusal plane were 27% and 35%, respectively. The ratio of mandibular ramus height was positively related to EV. In children with CFM, attention should be paid to vertical elongation instability and relapse of mandibular inclination during consolidation. Severe mandibular ramus hypoplasia is a preoperative risk factor for vertical skeletal relapse during consolidation. Further efforts are required to reduce the stress that leads to relapse.

Differential metabolomic pathway analysis in Malaysian childhood acute lymphoblastic leukemia patients treated with high-dose methotrexate

BackgroundMethotrexate (MTX) is the mainstay of the consolidation and maintenance phase of chemotherapy protocol for childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the altered metabolism associated with high dose-MTX and determine the potential of the metabolic markers and differential pathways involved in MTX therapy. MethodsSerum samples were collected from 38 children with ALL at 2 time points: p-MTX; before induction chemotherapy was initiated, and post-MTX; after completion of the first high-dose MTX. The samples were analyzed using HPLC/MS-QTOF. Data acquisition was performed using Agilent MassHunterTMB.05.00 software for subsequent metabolomics analysis. Differential expressions of metabolites were analyzed using univariate Welch's t-test unequal variance. Compounds were identified using the METLIN Database. Pathways and network analyses were performed using Metaboanalyst 4.0. Potential biomarkers were analyzed using the Receiving Operator Characteristic curve. ResultsMetabolites with AUC between 0.7 and 0.9 include xanthine (0.889), oxoglutaric acid (0.770), and alpha-linolenic acid (ALA) (0.741). Alpha-linolenic acid abundance was detected in ALL patients with remission status, corresponding to a test sensitivity and specificity of 0.77 and 0.87, respectively. ALA has an antineoplastic effect that potentially inhibits the proliferation of leukemic cells by inhibiting caspase activation in the phosphatidylinositol 3-kinase (PI3K) pathway and Bcl-2 inhibition. ConclusionIn this study, ALA was found to be significantly higher in patients treated with high-dose MTX and associated with remission status than in pre-MTX treatment.

MDB-51. PHASE II INTERVENTIONAL STUDY TO EVALUATE THE SAFETY AND EFFICACY OF STANDARD AND HIGH-DOSE CHEMOTHERAPY COMBINED WITH CRANIOSPINAL IRRADIATION WITH PROTON THERAPY IN PATIENTS WITH METASTATIC MEDULLOBLASTOMA AND OTHER EMBRYONIC CANCERS: PRELIMINARY RESULTS

Abstract BACKGROUND The high risk medulloblastoma remains a leading cause of cancer-related death in children. METHODS A total of 18 patients have been enrolled from February 2018 to May 2022.The median age was 7,5 years (range; 12 males and 6 female). The protocol predicted the first phase of induction with 4 cycles of chemotherapy. After induction patients with favorable histology without evidence of disease were enrolled to proton therapy (with concomitant vinorelbine biweekly). The maintenance phase with Lomustine repeated every 9 weeks and vinorelbine every 3 weeks for overall 12-18 months (PR). Conversely LC/A MB, were subjected to consolidation phase with high dose of chemotherapy with tiothepa followed by autologous HSC transplant and successive maintenance phase of 6 months. RESULTS At October 2023, the median follow up was 24 months. After the induction phase 14 patients showed CR, 2 PR, 1PD, 1SD. At subsequent re-evaluations two with PR, showed disease control, one CR and the other SD and the patient with PD showed CR. Patient with SD showed an unchanged state of the disease. During the reporting period two patient died for progression of the underlying disease. At 24 months from the start of treatment the PFS was 75,4 % (95% CI: 34.1% - 87.6%) and at 15 months the OS was 86,1% (95% CI: 68.1% - 99.2%). The principal expected side effects of chemotherapy were hematology toxicity and 58% rate of GH deficiency. Among the unexpected side effect was CMV retinopathy with complete blindness and leukoencephalopathy after high dose of thiotepa and proton irradiation. We reported only one case of ototoxicity. CONCLUSIONS The use of proton therapy combined with intensive chemotherapy and myeloablative chemotherapy only in selected cases and always before irradiation has proven feasible and effective in the treatment of high-risk patients medulloblastomas and other embryonic tumors.

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial

CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383. Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001). The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma. Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development.

Osteotomy Site Venting Enhances Femoral Bone Consolidation With Magnetic Intramedullary Lengthening Nails.

Magnetic intramedullary lengthening nailing has demonstrated benefits over external fixation devices for femoral bone lengthening. These include avoiding uncomfortable external fixation and associated pin site infections, scarring, and inhibition of muscle or joint function. Despite this, little has changed in the field of biologically enhanced bone regeneration. Venting the femoral intramedullary canal at the osteotomy site before reaming creates egress for bone marrow during reaming. The reamings that are extruded from vent holes may function as a prepositioned bone graft at the distraction gap. The relationship between venting and the consolidation of regenerating bone remains unclear. (1) Do bone marrow reamings extruded through venting holes enhance the quality of bone regeneration and improve healing indices and consolidation times? (2) Is venting associated with a higher proportion of complications than nonventing? We performed a retrospective study of femoral lengthening performed at one hospital from December 2012 to February 2022 using a magnetic intramedullary lengthening nail with or without venting at the osteotomy site before reaming. This was a generally sequential series, in which the study groups were assembled as follows: Venting was performed between July 2012 and August 2016 and again from November 2021 onward. Nonventing was used between October 2016 and October 2021 because the senior author opted to create drill holes after the reaming procedure to avoid commitment to the osteotomy level before completing the reaming procedure. Outcomes were evaluated based on bone healing time, time to achieve full weightbearing, and complications. Sixty-one femoral lengthening procedures were studied (in 33 male and 28 female patients); two patients were excluded because of implant breakage. The mean age was 17 ± 5 years. The mean amount of lengthening was 55 ± 13 mm in the venting group and 48 ± 16 mm in the nonventing group (mean difference 7 ± 21 [95% CI 2 to 12]; p = 0.07). The healing index was defined as the time (in days) required for three cortices to bridge with new bone formation divided by the length (in cm) lengthened during the clinical protocol. This index signifies the bone formation rate achieved under the specific conditions of the protocol. Full weightbearing was allowed upon bridging the regenerated gap on three sides. Consolidation time was defined as the total number of days from the completion of the lengthening phase until adequate bone union (all three cortices healed) was achieved and full weightbearing was permitted. This time frame represents the entire healing process after the lengthening is complete divided by the amount of lengthening achieved (in cm). Patient follow-up was conducted meticulously at our institution, and we adhered to a precise schedule, occurring every 2 weeks during the distraction phase and every 4 weeks during the consolidation phase. There were no instances of loss to follow-up. Every patient completed the treatment successfully, reaching the specified milestones of weightbearing and achieving three cortexes of bone bridging. The mean healing index time in the venting group was faster than that in the nonventing group (21 ± 6 days/cm versus 31 ± 22 days/cm, mean difference 10 ± 23 [95% CI 4 to 16]; p = 0.02). The mean consolidation time was faster in the venting group than the nonventing group (10 ± 6 days/cm versus 20 ± 22 days/cm; mean difference 10 ± 23 [95% CI 4 to 15]; p = 0.02). No medical complications such as deep vein thrombosis or fat or pulmonary embolism were seen. Two patients had lengthy delays in regenerate union, both of whom were in the nonventing group (healing indexes were 74 and 62 days/cm; consolidation time was 52 and 40 days/cm). Femoral lengthening with a magnetic intramedullary lengthening nail healed more quickly with prereaming venting than with nonventing, and it allowed earlier full weightbearing without any major associated complications. Future studies should evaluate whether there is a correlation between the number of venting holes and improvement in the healing index and consolidation time. Level III, therapeutic study.

National wealth in the context of the transformation of the socio-economic system

The subject of the research is the functions of national wealth, considered in the context of the transformation of the socio-economic system. National wealth in the context of the transformation of the socio-economic system is one of the fundamental indicators that reflects the totality of tangible and intangible resources at the disposal of the nation. During the transformation of the socio-economic system, there is a redistribution of national wealth between sectors of the economy. Transformation requires reforming state institutions, legal systems and management structures - this can affect the efficiency of using national wealth, increasing or decreasing economic stability, national security and investment attractiveness of the country. In modern conditions, special attention is paid to sustainable development, which involves the rational use of natural resources and minimization of environmental risks. Transformation of the system aimed at sustainable development contributes to the preservation and increase of national wealth in the long term. The purpose of the work is to determine the content and structure of national wealth in the context of the transformation of the socio-economic system. The research methodology is based on the generalization of information from domestic and foreign sources, statistical data on the issues considered in the work. The scientific novelty of the study consists in identifying qualitative changes in the characteristics of national wealth in the modern conditions of transformation of the socio-economic system. The article highlights the following stages (phases) in the development of the socio-economic system: crisis phase (destabilization phase), phase of awareness of the need for change, reform base (transformation phase), phase of adaptation and stabilization, phase of growth and development, phase of consolidation and institutionalization. The results of the study can be considered as an increase in scientific knowledge in economic theory.

High-dose furmonertinib in combination with intraventricular chemotherapy for EGFR exon 20 insertion mutated lung adenocarcinoma with leptomeningeal metastasis.

e20555 Background: Leptomeningeal metastasis (LM) is a severe complication of advanced lung adenocarcinoma (LUAD) and always has a dismal prognosis. EGFR exon 20 insertion ( EGFR 20ins) is the third most common EGFR mutations; however, there are currently no reports focusing on LM with EGFR 20ins, and the optimal therapy for these patients remains unclear. This retrospective study aimed to evaluate the efficacy and safety of high-dose furmonertinib in combination with intraventricular chemotherapy in EGFR 20ins mutated LUAD patients with LM. Methods: Weretrospectively enrolled 10 LUAD patients with LM who had failed multiline treatment between May 2021 and June 2023 at Nanjing Chest Hospital. All of them had confirmed EGFR 20ins by next generation sequencing. All patients received furmonertinib in combination with intraventricular chemotherapy via the Ommaya reservoir. Furmonertinib was taken at 160 mg once daily. The chemotherapy regimen consisted of 30mg pemetrexed and 5 mg dexamethasone administered twice weekly for 2 weeks during the consolidation phase, followed by a maintenance phase every 3-4 weeks until disease progression or unacceptable toxicity, or patient refusal. Results: The median age was 53.5 years (range: 39-66), and six (60%) were males. Four patients (40%) had an ECOG of 3, and six patients (60%) had an ECOG of 4. The intracranial ORR (iORR) was 60% (6/10) and intracranial DCR (iDCR) was 90% (9/10). The ECOG PS improved in 80% patients after treatment. With a median follow-up of 9.3 months, the median intracranial progression-free survival (iPFS) was 7.3 months (95% CI, 3.3-NR) and the median overall survival (OS) was 8.8 months (95% CI, 4.9-NR), respectively. Treatment related adverse events of ≥ grade 3 occurred in only 2 patients, which were nausea and rash. Conclusions: Furmonertinib in combination with intraventricular chemotherapy is a tolerable treatment with breakthrough clinical efficacy for LUAD patients with LM harboring EGFR 20ins.

Distraction Osteogenesis: Changing Lives

Background: A method of generating new bone following a corticotomy or an osteotomy and gradual distraction based on the tension-stress principle proposed by Ilizarov is called distraction osteogenesis. DO works in following phases: Osteotomy or surgical phase - Latency period - Distraction phase - Consolidation phase - Appliance removal - Remodeling period. Case report: A 21 years old female patient reported to the department of orthodontic with the chief complaint of forwardly placed upper front teeth. Her past medical, dental, post natal and family history did not show any relevant reporting. Material and method: The osteotomy was prepared by extending the line from medial aspect of posterior border of ramus till the buccal cortical plate between first and second molar and the intraoral bidirectional distractors (figure 3) were secured in place and the distraction was done twice a day at a rate of 1mm/day. The distraction was initiated five days after the surgery and then continued till 11 days. Conclusion: DO can effectively treat facial ............