Search Results (82)

Background: Treatment options for recurrent ovarian cancer (OC) are limited, leading to poor prognosis. Targeting tumor-promoting signaling transduction pathways (STPs), such as Hedgehog (HH) and Phosphoinositide-3-kinase (PI3K) STPs, might be an option for treatment. This study evaluates the efficacy of itraconazole as a targeted treatment in HH and/or PI3K active recurrent OC. Methods: We assessed HH and PI3K STP activity in recurrent OC patients. If activity was aberrantly high in either STP, patients received itraconazole treatment, which has been shown to inhibit both HH and PI3K pathways. The primary objective is to compare progression-free survival (PFS) on itraconazole therapy (PFS2) to the PFS on therapy prior to enrolment (PFS1). A PFS2/PFS1 ≥ 1.0 was considered successful. Secondary objectives included side effects, best overall response, one-year survival, and CA125 levels, though this was not a secondary endpoint. Results: Of sixteen patients with successful STP analysis, 93% were eligible for itraconazole therapy. Nine patients started treatment, with a mean duration of 55 days. None achieved a PFS2/PFS1 ratio ≥ 1.0 (mean 0.26, range 0.1–0.7). One patient had radiologically stable disease, while the others experienced disease progression. Side effects were mostly limited to grade 1–2, including fatigue, nausea, dysgeusia, dyspnea, cough, vertigo, and edema. No grade ≥ 3 adverse effects were linked to treatment. One-year survival was 22%. CA125 levels did not correlate with the treatment outcome, but increased rapidly after ceasing treatment. Conclusions: Itraconazole monotherapy for recurrent HH and/or PI3K aberrantly active OC is an ineffective treatment. While CA125 did not correlate with treatment outcome, the rapid increase in CA125 after therapy cessation suggests tumor inhibitory effects. Full article

Background/Objectives: Radiation therapy is a common treatment modality for non-small-cell and small-cell lung cancer that can be associated with considerable side effects, mainly reactions of healthy tissues in the radiation field. Radiation therapy may lead to significant fatigue, which can potentially be mitigated by maintaining or increasing physical activity during treatment. Since achieving this goal may be a challenge for patients, they may benefit from a mobile application reminding them daily to perform a predefined number of steps. Such a reminder app will be investigated prospectively in a phase 2 trial. The current APART-LUNG study (NCT07380815) is a mandatory study for designing the prospective trial. Methods: The main objective of the APART-LUNG (exploratory non-interventional) study is to report patterns of physical activity during radiation therapy for lung cancer patients and generate hypotheses based on our findings. Our primary endpoint is the within-patient difference in weekly average steps per wear hour of the smartphone (week 5 minus week 1 of radiation therapy), and our secondary aim is to estimate differences in operational measures (wear time of the smartphone) between week 5 and week 1. The sample size of approximately 20 patients (full analysis set) allows us to detect a moderate-to-large standardized within-patient difference and is driven by feasibility and the intent to obtain preliminary estimates of effect size and variability. The results of the APART-LUNG study will be very important for appropriately designing a phase 2 trial. Full article

Background: Primary malignant brain tumors (PBT) impose substantial burdens on patients and caregivers. Caregivers are essential in the delivery of outpatient care for patients with PBT but experience high levels of fatigue, distress, and health decline. Although exercise is known to improve outcomes in cancer patients, interventions tailored specifically to the PBT patient–caregiver dyad remain limited. Dyadic intervention, as well as exercise oncology, are emerging areas of active research in neuro-oncology. This scoping review incorporates both principles to evaluate the existing literature on exercise interventions on primary brain tumor patient–caregiver dyads. Methods: We conducted a comprehensive search of MEDLINE (PubMed), Embase, CINAHL (EBSCO), Rehabilitation & Sports Medicine (EBSCO), and Cochrane Central (Ovid) in December 2025 for studies involving exercise interventions that included adult PBT patients and caregivers. Results: Of the 1126 records screened, eight studies were included: four yoga-based interventions (three feasibility trials and one ongoing multicenter RCT), one pilot ski-based intervention, and three aerobic and resistance training-based interventions (two qualitative and one ongoing trial). The interventions were safe and feasible, with high adherence and retention. The preliminary reported benefits included improvements in fatigue, sleep, quality of life, and caregiver distress for the dyads. Videoconference delivery was effective, particularly during the COVID-19 pandemic. The eight included studies comprised 5–67 dyads, with four being single-arm feasibility studies. Conclusions: Current literature on dyadic exercise intervention in neuro-oncology consists primarily of small-scale feasibility and pilot studies. Initial findings have demonstrated that such interventions are safe. However, preliminary efficacy remains limited due to the risk of bias and lack of statistical power. Larger randomized clinical trials with objective endpoints are needed to define efficacy and guide evidence-based protocols. Full article

Background: In the context of long COVID, persistent fatigue is among the most prevalent symptoms that can develop after SARS-CoV-2 infection. Mitochondrial myopathy and endothelial dysfunction, which are triggers of inflammation, have emerged as prominent causes of long COVID-induced fatigue. Interestingly, the intake of flavanols, particularly (−)-epicatechin (EC), has been associated with the positive modulation of endothelial and mitochondrial structure and function. Methods: In this work, we conducted a randomized, double-blind, placebo-controlled clinical trial to determine whether an EC-enriched supplement (ECES) improves plasma markers of inflammation, endothelial structure, and fatigue-related endpoints in patients with long COVID-19. Results: The study included 46 subjects (mean age 52 years) who were instructed to consume two capsules/day for 90 days of either ECES (n = 23) or placebo (n = 23). Endpoints assessed included mean changes in plasma inflammatory markers (IL-1β, IL-6, and TNF-α) and endothelial dysfunction markers (syndecan-1), handgrip strength, fatigue scale, and quality of life (QoL). The results showed significant improvements in the ECES group for inflammatory markers, syndecan-1, and fatigue compared with the placebo group. Conclusions: The results yield intriguing positive findings for EC and open a new avenue for treating long COVID. Full article

This first part of a two-part review examines how Computed Tomography(CT)-based, additively manufactured (AM) porous implants are used to reconstruct large segmental defects of the femur and tibia. We focus on lightweight patient-specific lattice implants, architected cages, and modular porous constructs that incorporate engineered porosity into the load-bearing structure and are deployed with plate-, nail-, or external-fixator-based stabilization. We show how defects are described and classified by size, morphology, and anatomical subsegment; how these descriptors influence fixation choice and the resulting mechanical environment; and where along the femur and tibia porous implants have been applied in clinical and preclinical settings. Across the literature, outcomes appear to depend most strongly on defect morphology and local biology, while fixation feasibility and construct behavior vary by subregional anatomy. Most reported constructs use Ti6Al4V porous architectures intended to share load with fixation, reduce stress shielding, and provide a regenerative space for graft and tissue ingrowth. Finite element analyses (FEA) and bench-top studies consistently indicate that lattice architecture, relative density (RD), and fixation concept jointly control stiffness, micromotion, and fatigue-sensitive regions, whereas early animal and human reports describe promising incorporation and functional recovery in selected cases. However, defect descriptors, fixation reporting, boundary conditions, and outcome metrics remain diverse, and explicit quantitative validation of simulations against mechanical or in vivo measurements is uncommon. Most published work relies on simulation and bench testing, with limited reporting of biological endpoints, leaving a validation gap that prevents direct translation. We emphasize the need for standardized defect and fixation descriptors, harmonized mechanical and modeling protocols, and defect-centered datasets that integrate anatomy, mechanics, and longitudinal outcomes. Across the 27 included studies (may be counted in more than one group), simulation and mechanical testing are reported in 19/27 (70%) and 15/27 (56%), respectively, while in vivo studies (preclinical or clinical) account for 9/27 (33%), highlighting a validation gap that limits translation. Part 2 (under review); of these two series review paper; Patient-Specific Lattice Implants for Segmental Femoral and Tibial Reconstruction (Part 2): CT-Based Personalization, Design Workflows, and Validation-A Review; extends this work by detailing CT-to-implant workflows, lattice design strategies, and methodological validation. Full article

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can develop as post-vaccination syndrome (PVS) or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). In our prior retrospective study, most patients with PVS who developed ME/CFS had vitamin D insufficiency or deficiency. We evaluated the efficacy of vitamin D replacement therapy guidance for ME/CFS symptom improvement in patients with vitamin D insufficiency or deficiency. Methods: This open-label randomized controlled trial enrolled 91 participants with ME/CFS as PVS or PASC and serum 25(OH) vitamin D < 30 ng/mL across five clinical sites. Participants were randomized 1:1 to intervention (active vitamin D preparation plus vitamin D replacement therapy guidance: 25 μg daily supplementation, dietary counseling, sun exposure, and exercise) or control (active vitamin D preparation alone) for 12 weeks. The primary endpoint was the change in ME/CFS symptom count from screening to Week 12. Results: Mean symptom change was −6.7 in the intervention group versus −1.2 in the control group (between-group difference −5.6; 95% CI: −7.2, −3.9; p < 0.001). Serum 25(OH) vitamin D improved from 18.6 to 27.1 ng/mL in the intervention group, while the control group showed a decreasing trend (between-group difference 10.2 ng/mL; 95% CI: 7.9, 12.5). Achievement of <8 symptoms (i.e., no longer meeting ME/CFS diagnostic criteria) was significantly higher in the intervention group, with 16 participants achieving this threshold compared to 1 in the control group (p < 0.001). Subgroup analyses showed consistent benefit in both PVS (n = 56) and PASC (n = 29) cohorts. Conclusions: Vitamin D replacement therapy guidance significantly reduced ME/CFS symptoms along with improvement of serum 25(OH) vitamin D levels in patients with vitamin D insufficiency or deficiency who developed ME/CFS as PVS or PASC. Full article

Background: Exercise-induced fatigue (EIF) impairs performance and recovery and may contribute to overreaching/overtraining and adverse health outcomes. Beyond classical explanations (substrate depletion, metabolite accumulation, oxidative stress), accumulating evidence indicates that the gut microbiota modulates fatigue-related physiology through metabolic, immune, barrier, and neurobehavioral pathways. Methods: We conducted a structured narrative review of PubMed and Web of Science covering 1 January 2015 to 30 November 2025 using predefined keywords related to EIF, gut microbiota, recovery, and nutritional interventions. Human studies, animal experiments, and mechanistic preclinical work (in vivo/in vitro) were included when they linked exercise load, microbial features (taxa/functions/metabolites), and fatigue-relevant outcomes. Results: Across models, high-intensity or prolonged exercise is consistently associated with disrupted gut homeostasis, including altered community structure, reduced abundance of beneficial taxa, increased intestinal permeability, and shifts in microbial metabolites (e.g., short-chain fatty acids). Evidence converges on four interconnected microbiota-mediated pathways relevant to EIF: (1) energy availability and metabolic by-product clearance; (2) redox balance and inflammation; (3) intestinal barrier integrity and endotoxemia risk; and (4) central fatigue and exercise motivation via microbiota–gut–brain signaling. Nutritional strategies—particularly targeted probiotics, prebiotics/plant polysaccharides, and selected bioactive compounds—show potential to improve fatigue biomarkers and endurance-related outcomes, although effects appear context-dependent (exercise modality, baseline fitness, diet, and baseline microbiota). Conclusions: Current evidence supports a mechanistic role of the gut microbiota in EIF and highlights microbiota-targeted nutrition as a promising adjunct for recovery optimization. Future work should prioritize causal validation (e.g., fecal microbiota transplantation and metabolite supplementation), athlete-focused randomized trials with standardized fatigue endpoints, and precision approaches that stratify individuals by baseline microbiome features and training load. Full article

Background: Data on long-term sequelae after severe imported Plasmodium falciparum malaria in adults are scarce in non-endemic settings. We aimed to quantify early and medium term renal and neurological outcomes and identify prognostic factors. Therapeutic strategies have evolved with widespread intravenous artesunate, yet survivorship data remain limited. Methods: We performed a retrospective study of cases of severe malaria at the University Hospital of Marseille (France) between January 2018 and December 2024. This study is a single-centre retrospective cohort with prospective follow-up using standardised questionnaires. Adults meeting the criteria for severe falciparum malaria were included. The primary endpoint was a composite of renal impairment and/or neurological sequelae assessed at day 28 (D28) and at remote post-discharge follow-up. Patient-reported outcomes were collected at one year. Associations with baseline features were tested using the Fisher’s exact and Wilcoxon–Mann–Whitney tests. Results: Among 474 malaria cases, 66 (13.9%) were severe; of these, 57 met inclusion criteria. Fifty-seven of them were included. All received intravenous artesunate with oral step-down; 35% required ICU care. At D28, 6/41 patients (14.6%) had sequelae (four renal, one neurological, one both). Sequelae at D28 were associated with neurological failure (66.7% vs. 14.3%; p = 0.015), severe metabolic acidosis (50.0% vs. 2.9%; p = 0.007) and renal impairment at admission (83.3% vs. 2.9%; p < 0.001). At remote follow-up, 6/33 patients (18.2%) had sequelae (two renal, three neurological, one both), associated with older age (61.0 ± 5.3 vs. 39.8 ± 15.8 years; p = 0.008), D3 blood smear positivity (66.7% vs. 11.5%; p = 0.012), neurological failure (66.7% vs. 18.5%; p = 0.034) and renal impairment (50.0% vs. 7.4%; p = 0.031). No deaths or relapses occurred. At one year, patient-reported outcomes (n = 14) showed persistent symptoms in 8/14, chiefly fatigue and cognitive complaints. Conclusions: In a high-resource, non-endemic setting, renal and neurological sequelae after severe imported malaria are frequent at D28 and persist in nearly one-fifth of cases during post-discharge follow-up. Neurological failure, metabolic acidosis, renal impairment at presentation, older age and D3 blood smear positivity identify patients at risk and support risk-stratified post-discharge follow-up. Full article

Background/Objectives: Eltrombopag, a thrombopoietin receptor agonist, is widely used in the treatment of relapsed or refractory (R/R) immune thrombocytopenia (ITP). This study aimed to compare the efficacy, safety, and tolerability of generic eltrombopag (Rompag^®) with original eltrombopag (Revolade^®) in adult patients with R/R ITP. Methods: In this prospective, multicenter study conducted at 10 centers, 104 adult ITP patients were followed for at least 3 months. A total of 35 (33.7%) patients received Rompag^® and 69 (66.3%) received Revolade^®. The primary endpoint was platelet (PLT) response, defined as achieving a PLT count ≥50 × 10⁹/L and at least a twofold increase from baseline, without the need for rescue therapy or transfusion. Secondary endpoints included bleeding rates, fatigue-related quality of life, adverse events (AEs), and rescue therapy requirements. Results: PLT response was achieved in 94.2% of patients in the Revolade^® group and 85.7% in the Rompag^® group (p = 0.16). Bleeding rates decreased significantly in both groups (Revolade^®: 56.5% to 2.9%, p < 0.001; Rompag^®: 62.9% to 2.9%, p < 0.001). Although overall AE rates were similar (30.4% in the Revolade^® group and 42.9% in the Rompag^® group; p = 0.22), arthralgia (28.6% vs. 7.2%, p = 0.01) and vomiting (11.4% vs. 0%, p = 0.008) were more frequent with Rompag^®. Conclusions: Both generic and original eltrombopag demonstrated no statistically significant difference in efficacy in achieving PLT response, reducing bleeding, and improving fatigue-related quality of life in adult patients with R/R ITP. Although minor differences in AE profiles were observed, particularly arthralgia and vomiting, both formulations showed acceptable safety and tolerability. Full article

Background/Objectives: Breast cancer is the most common malignancy among women globally, with survival rates improving due to earlier detection and better treatment. As a result, cancer survivors now constitute a growing segment of the population, and addressing their long-term health and well-being is a public health priority. Diet and nutrition represent modifiable factors that may influence recurrence, comorbidities, and quality of life (QoL), yet clear evidence-based guidance remains limited. This umbrella review thus synthesized evidence from published reviews on the effects of dietary and nutrition interventions among breast cancer survivors. Methods: Following a prospectively registered protocol in PROSPERO (CRD420251185022), six databases (PubMed, EMBASE, Scopus, Cochrane Library, PsycINFO and CINAHL) were systematically searched for systematic reviews/meta-analyses evaluating dietary or nutrition interventions in adult breast cancer survivors. Eligible reviews reported anthropometric, metabolic, psychosocial, or survival outcomes. Methodological quality was appraised using the AMSTAR-2 tool, and findings were narratively synthesized. Results: Nine systematic reviews encompassing more than 10,000 breast cancer survivors were included. Interventions ranged from general dietary counselling and structured weight-management programmes to Mediterranean-style dietary patterns, dietitian-led primary care, multiple health behaviour change interventions, mobile nutrition apps, and broader lifestyle programmes incorporating diet. Across reviews, interventions consistently improved diet quality and fruit–vegetable intake, produced modest but meaningful reductions in weight, body mass index, and body fat, and enhanced several QoL domains (e.g., fatigue, physical functioning, body image). Higher adherence to Mediterranean-style diets was associated with lower all-cause and non–breast cancer mortality, though certainty was limited by observational designs. However, evidence for long-term maintenance, survival endpoints, and ethnically diverse or low- and middle-income populations remains sparse. Conclusions: Dietary and nutrition interventions, particularly structured, dietitian-supported, and Mediterranean-style approaches, contribute to improved diet quality, sustainable weight control, and enhanced QoL among breast cancer survivors. Integrating nutrition care into survivorship pathways should be the focus of future research. Full article

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are the standard of care for first-line maintenance in advanced ovarian cancer, but their benefit varies by BRCA and homologous recombination deficiency (HRD) status, and no head-to-head comparisons are available. Methods: We conducted an indirect comparison of PARPi regimens using reconstructed individual patient data (IPD) from Kaplan–Meier curves of phase III randomized trials (SOLO1, PRIMA, PAOLA1, ATHENA, FLAMES). Progression-free survival (PFS) was the primary endpoint; overall survival (OS) was exploratory. Subgroups were defined as BRCA−mutated (BRCA+), BRCA−/HRD+, and BRCA−/HRD−. Safety outcomes were assessed through a network meta-analysis of adverse drug reactions (ADRs). Results: In BRCA+ patients, olaparib + bevacizumab achieved the largest PFS improvement (HR = 0.27; 95%CI: 0.19–0.39), followed by olaparib monotherapy, while niraparib performed significantly worse. In BRCA−/HRD+, olaparib + bevacizumab was superior to niraparib and rucaparib, with restricted mean survival time (RMST) gains of 3–4 months. In BRCA−/HRD−, PARPi produced only a modest benefit, with no advantage over bevacizumab monotherapy. Exploratory OS analysis confirmed long-term survival with olaparib in BRCA+ but not in the other subgroups. Safety analysis indicated olaparib had the most favorable hematological profile, while niraparib was associated with the highest rates of severe anemia, thrombocytopenia, and neutropenia, despite showing lower gastrointestinal toxicity and fatigue incidence. Conclusions: PARPi efficacy depends strongly on BRCA and HRD status. Olaparib-based regimens provide the greatest clinical benefit with acceptable safety in BRCA+ and HRD+ disease, whereas PARPi appear to be of limited value in HRD-negative ovarian cancer. Full article

Background: The phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with relapsed/refractory multiple myeloma (r/r MM). ADMYRE met its primary endpoint, showing a 35% reduction in the risk of progression or death. Methods: Results from a pre-planned subgroup of patients aged <75 years are shown here. This subgroup includes most of the patients evaluated in the ADMYRE study: 145/171 patients (84.8%) in the plitidepsin + DXM arm and 71/84 (84.5%) patients in the DXM alone arm. Results: Compared to the overall ADMYRE population, a higher reduction was found with plitidepsin plus DXM for the risk of progression or death in the primary endpoint: 47.7% vs. 35.0% (Hazard ratio [HR] = 0.523 vs. HR = 0.6509). Higher reduction in the risk of death was also found (28.9% vs. 20.3%; HR = 0.711 vs. HR = 0.797), with a clinically meaningful 5-month difference in median overall survival (13.0 months vs. 8.1 months; p = 0.0350). The safety profile of plitidepsin plus DXM in patients aged <75 years was similar to that observed in the overall population of patients treated in the ADMYRE study. The most common adverse events (all grades) related to the study treatment in patients < 75 years were fatigue (39.2% of patients), gastrointestinal (nausea, 39.2%; vomiting, 19.6%; diarrhea, 14.7%), and myalgia (14.0%). Conclusions: Larger differences in efficacy outcomes while maintaining a similar safety profile, together with a novel mechanism of action, suggest that this combination can be a valid option for patients with r/r MM aged <75 years. Full article

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which environmental factors modulate genetically determined immune dysregulation. Vitamin D has emerged as a plausible modifier of disease expression because its active metabolite signals through the vitamin D receptor on innate and adaptive immune cells and influences antigen presentation, cytokine balance, and lymphocyte differentiation. This narrative review synthesizes current evidence on vitamin D status and supplementation in SLE with attention to organ-specific domains. Observational studies consistently report high rates of hypovitaminosis D in SLE and associations with less favorable clinical profiles, including higher global and renal disease activity, adverse cardiometabolic features, greater infection vulnerability, and neuropsychiatric manifestations. Preclinical models demonstrate neuroprotective and barrier-stabilizing actions of vitamin D analogs, supporting biological plausibility. Interventional trials indicate that supplementation safely corrects deficiency and shows signals of benefit for selected outcomes (e.g., modest activity reductions or fatigue in specific contexts), although effects on interferon signatures, complement, and autoantibodies are heterogeneous and often limited. Overall, current evidence supports optimization of vitamin D status as a low-risk adjunct in comprehensive SLE care while highlighting the need for adequately powered, organ-focused randomized trials using standardized measurements and prespecified endpoints to define causality, therapeutic targets, and long-term safety. Full article

Palliative radiotherapy (PRT) is central to symptom control in advanced cancer, yet referrals are often late, and patients and clinicians frequently hold misconceptions about intent, benefits, and logistics. Patient education may address these gaps, but the PRT-specific evidence base has not been consolidated. We conducted a narrative review following SANRA guidance. We searched PubMed, Scopus, and the Cochrane Library for English-language studies from 1 January 2000 to 18 July 2025. Eligible articles evaluated structured patient-education interventions or characterized education or communication content, information needs, or decision processes among adults referred to or receiving PRT. Two reviewers independently screened and extracted data. Owing to heterogeneity of designs and endpoints, we performed a narrative synthesis without meta-analysis. Six studies met criteria: two randomized controlled trials, two prospective pre–post studies, one qualitative interview study, and one observational communication study, conducted in the Netherlands, the United States, Canada, and Hong Kong. Education at referral or consultation improved knowledge, reduced decisional uncertainty, and increased readiness to proceed with PRT. Education integrated with treatment improved symptom outcomes, including higher rates of pain control at 12 weeks and faster time to pain control when a nurse-led pain-education program accompanied PRT for painful bone metastases, and improvements in dyspnea, fatigue, anxiety, and function in advanced lung cancer. Observational and qualitative work showed low patient question-asking and persistent curative expectations; overall quality of life generally did not change. Although the evidence is limited and heterogeneous, targeted, standardized education appears to improve decision quality and selected symptoms in PRT pathways. Pragmatic multi-site trials and implementation studies are needed to define content, timing, personnel, and delivery models that are scalable in routine care. Full article

Interictal burden (IB), defined as the symptoms and impairments that occur between migraine attacks, including cognitive dysfunction, photophobia, and fatigue, is recognized as a significant determinant of quality of life in patients. A prospective observational study was conducted. Patients diagnosed with chronic migraine (CM) and under treatment with OnabotulinumtoxinA (OnabotA) according to the PREEMPT protocol (every 12 weeks) were assessed at baseline and at 3, 6, 9, and 12 months. The primary endpoint was to evaluate the change in the IB measured with the Migraine Interictal Burden Scale (MIBS-4) and in the monthly migraine days (MMD). The secondary endpoint was acute medication use. This single-center study included 150 patients (91.3% female; median age 44 years). MIBS-4 scores were decreased by 29.1% at 3 months (8.47 to 5.97) and by 41.6% at 12 months (to 4.86; p < 0.001). IB-free status was achieved by 16 patients (10.7%). The most disabling baseline symptoms were photophobia (37%), fatigue (20%), and allodynia (18%), which reduced by 52%, 43%, and 39% at 12 months, respectively. MMD were reduced from 18.6 to 8.3 days at 12 months and triptan and analgesic intake decreased by 58.7% and 55.4%. OnabotA significantly reduced both IB and migraine frequency over 12 months, underscoring its relevance in CM management. Full article