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Perspectives of participating neurologists and study nurses - Mixed-methods process evaluation of a web-based program for relapse management in multiple sclerosis (POWER@M2).

BACKGROUND: Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system and the leading cause of disability in young adults. In Germany, 90% of relapses are treated with high-dose intravenous glucocorticoids, despite limited evidence for long-term benefit and international preference for oral administration. Time constraints often hinder informed decision-making. The multicentre Randomized Controlled Trial (RCT) POWER@MS2 (N = 160, 2020-2023), conducted at 18 German MS-centres, aimed to promote self-determined relapse management through a complex intervention (dialogue-based decision aid, nurse-led webinar, online-chat). OBJECTIVE: While RCTs demonstrate effectiveness, process evaluations are essential to understand implementation, mechanisms of impact and contextual factors. This study explored healthcare professionals' experiences and attitudes toward implementing relapse self-management and self-medication in clinical practice. METHODS: A mixed-methods process evaluation followed the UK Medical Research Council- framework. Quantitative data were collected via validated questionnaires at up to three time points and analysed descriptively. Interview guides were developed based on these results. Qualitative data from neurologist and study nurse interviews were thematically analysed. Results were triangulated using a joint display. RESULTS: Data were collected from 55 neurologists and 17 study nurses (quantitative) and from 7 neurologists and 4 nurses (qualitative) (2020-2024). Most neurologists opposed routine steroid use, reserving it for severe relapses. Some voiced concerns about self-management, but informed patients were generally viewed as capable of safe self-medication. Study nurses gave mixed feedback on the intervention, citing overload and improved guidance. CONCLUSION: Clinicians showed openness toward implementing the intervention. Enhancing accessibility and addressing specific concerns may support broader adoption.

Humans

Relapsed rhabdomyosarcoma: treatment recommendations from the European pediatric soft tissue sarcoma study group (EpSSG).

At least one-third of patients with localized rhabdomyosarcoma (RMS) and 60-70% of patients with metastatic RMS experience progressive disease or relapse. Following relapse, outcomes generally remain poor with limited treatment options and a high risk of subsequent recurrence. Optimal treatment requires a multidisciplinary approach incorporating chemotherapy with local control. Given the complexity of managing relapsed RMS and the challenges in developing effective treatment strategies, we aim to present clear and practical recommendations on the management of these patients across Europe. These recommendations were developed collaboratively by a group of pediatric and adolescent sarcoma experts from the European paediatric Soft Tissue Sarcoma Study Group. A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Such recommendations provide a standardized approach to managing relapsed cases, improving patient outcomes and offering a framework for clinicians to make informed decisions.

Humans

Acute leukemia therapy at a crossroads: from conventional chemotherapy to the era of precision medicine.

Since the discovery of cytotoxic agents in the mid-20th century, acute leukemia has consistently served as a model for oncology research. As the Human Genome Project and subsequent genomic profiling elucidated the landscape of somatic mutations and cytogenetic aberrations driving leukemogenesis, the development of molecularly targeted therapies has dramatically accelerated, yielding significant improvements in patient outcomes. In acute myeloid leukemia (AML), the emergence of selective inhibitors targeting high-frequency alterations such as FLT3, NPM1, and IDH1/2 has redefined the standard of care, demonstrating superior efficacy when combined with conventional intensive chemotherapy or hypomethylating agents. Simultaneously, for acute lymphoblastic leukemia (ALL), in addition to the significant improvements achieved by tyrosine kinase inhibitors (TKIs) for BCR-ABL-positive ALL, the advent of CD19- or CD22-targeted monoclonal antibodies and CAR-T cell therapies has marked an epoch-making milestone, representing a major paradigm shift in the management of relapsed or refractory cases. Bridging these two distinct lineages, menin inhibitors have emerged as a novel class of agents targeting a common pathogenic mechanism in KMT2A-rearranged AML/ALL and NPM1-mutated AML, exhibiting promising antileukemic activity across these subtypes. In this review, we describe the evolution of leukemia therapy-highlighting historical trajectory across AML, APL, and ALL from uniform cytotoxic chemotherapy to molecularly targeted agents, antibody-based therapies, and chemo-free paradigms, while outlining future perspectives for precision hematology.

Acute lymphoblastic leukemia

[Therapy of peptic ulcer and chronic pancreatitis].

Medical treatment of gastric and duodenal ulcerations has recently been improved and extended by anti-aggressive and protectively acting drugs (e.g., H2-receptor antagonists and carbenoxolone sodium). However, antacids and anticholinergic treatment are still being used in modern ulcer management. The most important therapeutical measures against chronic relapsing pancreatitis are abstinence from ethanol and surgical treatment of biliary or pancreatic duct obstructions. Symptomatic management--pancreatic enzyme substitution and analgetics, antacids, anticholinergics--is adequate in pancreatic insufficiency and during acute exacerbation, respectively.

Antacids

Management of the schizophrenic patient.

Schizophrenia is a continuing and relapsing disorder that begins in early adulthood and lasts indefinitely. Effective treatment, therefore, needs to be long-term and comprehensive. The physician must be able to control disabling symptoms while minimizing the side effects of neuroleptic medication. The lifetime risk remains of depression and suicide, paranoid crisis, social distress and frequent rehospitalization. It is a medical responsibility not only to look after the schizophrenic patient's health but also to coordinate social and emergency services, improve the quality of life, support the family and anticipate problems in offspring. At the time, the physician needs to consider the welfare of the community in which the schizophrenic patient lives.

Adolescent

The role of circulating tumor DNA (ctDNA) to detect minimal residual disease in locally advanced gastroesophageal carcinoma: the BUTTERFLY study.

BACKGROUND: Despite advances in perioperative and neoadjuvant strategies, patients with locally advanced gastroesophageal cancers remain at high risk of recurrence after curative intent treatment. No validated biomarkers are available to detect minimal residual disease (MRD) or to guide post-operative risk-adapted management. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool for disease monitoring; single-parameter or tumor-informed assays, however, may lack sensitivity in low-tumor burden settings. Multimodal, tumor-agnostic approaches may overcome these limitations. METHODS: The BUTTERFLY study is a prospective, multicenter observational study enrolling patients with stage II-III gastric, gastroesophageal junction, or esophageal cancer treated with perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. It evaluates the diagnostic performance and prognostic value of an academic, tumor-agnostic, multimodal ctDNA assay for MRD detection and prognostic stratification. Serial plasma samples are collected from baseline through post-operative follow-up and at relapse. Cell-free DNA is analyzed using the Agnostic Liquid Biopsy Multimodal Advancement (ALMA) platform, integrating tumor fraction estimation, somatic copy number alterations, fragmentomic features, single-nucleotide variants, and whole-genome methylation profiling. Multimodal features are combined with clinical variables using machine learning-based models to enhance MRD detection and relapse risk stratification. The primary endpoint includes sensitivity and specificity of ALMA-defined ctDNA/MRD status at the 4-8 weeks after surgery landmark, whereas secondary endpoints assess diagnostic performance at other time points and associations between ctDNA status and dynamics with disease-free survival, overall survival, treatment response, and lead time to recurrence. FUTURE PERSPECTIVES: If validated, this tumor-agnostic, multimodal ctDNA approach may enable earlier molecular relapse detection and support personalized post-operative management strategies.

circulating tumor DNA (ctDNA)

Electroencephalographic cranial computerized tomographic correlations in brain abscess.

The authors studied 19 cases of brain abscess. The investigation included one or more EEG records from 13 patients and one or more cranial computerized tomograms in all cases. In this work the two techniques were associated to establish the diagnosis of cerebral abscess. The EEG is almost always abnormal and pronounced EEG disturbances are, in most cases, sufficient for indicating a diagnosis of a space-occupying process. On the other hand, EEG patterns suggestive of brain abscess were detected in only 38% of the patients. In brain abscess, CCT is of considerable value since the existence of 'suppurative' images was demonstrated in all cases and of these, 70% were characteristic. The association of these two techniques is thus extremely useful in the diagnosis of cerebral abscess, to follow its evolution and to detect postoperative relapse or to evaluate the efficiency of medical management alone.

Adolescent

Management of nodular sclerosis Hodgkin's disease stage I, II A and B: evidence for a beneficial effect of MOPP on the relapse rate.

85 patients with previously untreated Hodgkin's disease with stage I, II A and B nodular sclerosis were treated. 31 of them with stage I and II A were submitted to radiotherapy alone. All are alive, but 9 of them (30%) relapsed. On the contrary, 35 patients with stage I and II A, and 19 with stage I, II and IIE B were submitted to radiotherapy followed by three courses of MOPP. All 54 patients are alive and relapse-free. No severe complication related to chemotherapy was observed. The analysis of results suggests that 3 courses of MOPP can significantly (Ip < 0.00025) reduce the relapse rate in patients with stage I and II nodular sclerosis, eligible for radiotherapy, without increasing morbidity.

Adolescent

The utility of 18F-fluorodeoxyglucose PET/computed tomography in relapsing polychondritis: a systematic review and meta-analysis.

Relapsing polychondritis is a rare chronic autoimmune inflammation of the cartilage associated with life-threatening respiratory complications. Currently, no clear role of imaging modalities such as 18F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is defined in the literature. This systematic review and meta-analysis provide current evidence on the PET-positivity rate and utility in relapsing polychondritis. Prospective or retrospective studies with more than five patients of suspected relapsing polychondritis who underwent 18F-FDG PET/CT during their management and reported a PET-positivity rate were included. Low-sample-size studies describing chondritis due to other aetiologies or utilizing PET-based radiopharmaceuticals other than FDG were excluded. A systematic search using relevant keywords was conducted across four databases (PubMed, Embase, Scopus and Web of Science) to include studies up to 25 April 2025. The Joanna Briggs Institute critical appraisal tools were used for risk-of-bias analysis. Data were analysed using the R software package (v4.3.1; 2023). Out of 962 articles, three with a total of 97 patients were included. With a pooled PET-positivity rate of 94% [95% confidence interval (CI): 73-99%, I2&#x2005;=&#x2005;0%, P&#x2005;=&#x2005;0.76] and a pooled baseline SUVmax of 4.0 (95% CI: 3.5-4.6, I2&#x2005;=&#x2005;32%, P&#x2005;=&#x2005;0.23), 18F-FDG PET identified asymptomatic cartilage involvement in more than 25% patients and PET parameters correlated well with inflammatory markers. It had a higher positivity rate for inaccessible sites, such as peripheral airways, and was crucial in treatment monitoring. The pooled PET-positivity rate of 18F-FDG PET in relapsing polychondritis is high but requires prospective large-sample-size studies to explore the diagnostic accuracy and prognostic implications of 18F-FDG PET in relapsing polychondritis.

Polychondritis, Relapsing

Understanding recurrence in Mycobacterium avium complex pulmonary disease: genotypic strategies to support clinical decision-making.

Pulmonary disease caused by Mycobacterium avium complex (MAC-PD) is a chronic, recurrent disease, and its high recurrence rate after treatment makes clinical management difficult. Distinguishing whether recurrence is due to persistence of existing strains or reinfection with new strains is essential for establishing treatment strategies, preventing overuse of antimicrobials, and establishing infection control measures. According to reports, 54%-74% of MAC-PD recurrence is due to reinfection, which may be mainly related to environmental reservoirs such as household water supply. In this review, we present various clinical scenarios in which MAC-PD recurrence may occur and examine genotyping techniques as a strategy to distinguish and respond to them. From traditional methods such as IS1245-based restriction fragment length polymorphism, pulsed-field gel electrophoresis, and hsp65 and rpoB gene sequencing to high-resolution analysis techniques such as multilocus sequence testing and whole-genome sequencing, the latest molecular typing methods are comprehensively summarized. Integrating these genotype data into clinical settings, standardizing single-nucleotide polymorphism-based interpretation thresholds, and promoting the establishment of a global MAC strain database will make a substantial contribution to more accurately distinguishing the recurrence mechanisms of MAC-PD and establishing personalized treatment strategies.IMPORTANCEThe global burden of nontuberculous mycobacterial pulmonary disease (PD) is increasing, with Mycobacterium avium (MAC)-PD being the most prevalent and clinically challenging form. Its low treatment success rates, high frequency of recurrence, and persistent environmental exposure complicate both diagnosis and management. A critical clinical issue is determining whether recurrence represents true relapse, due to persistence of the original strain, or reinfection with a new strain, as this guides treatment and prevents overtreatment. Genotypic strategies capable of resolving strain-level differences can improve diagnostic accuracy, prevent misclassification, and ultimately support more informed treatment decisions. Therefore, integrating genotyping data into clinical workflows, standardizing single-nucleotide polymorphism thresholds, and establishing a global MAC strain database will not only support personalized treatment but also enhance the broader public health response to this disease.

Humans

Human vascular pythiosis: pathogenesis, diagnosis, and evidence-informed management.

SUMMARYHuman vascular pythiosis is a rare, life-threatening angioinvasive infection caused predominantly by the oomycete Pythium insidiosum. Unlike ocular or cutaneous pythiosis, the vascular form is defined by arterial wall invasion, long-segment thrombosis, limb ischemia, aneurysmal complications, and high risks of amputation and death. Although P. insidiosum is broadly distributed in freshwater environments, reported human vascular disease remains concentrated in Thailand, indicating that exposure alone is insufficient for disease development. Available evidence supports a multifactorial model centered on repeated freshwater exposure and host susceptibility, particularly hemoglobinopathies and iron dysregulation, while the rarity of comparable vascular disease elsewhere remains unexplained. Because vascular-specific mechanistic data are limited, evidence from animal pythiosis, nonvascular human disease, environmental studies, genomic analyses, and experimental models must be interpreted selectively and linked explicitly to vascular pathogenesis, diagnosis, or management. Infection usually begins at sites of skin disruption after freshwater exposure and progresses through soft tissue and perivascular planes into the arterial wall. Longitudinal intramural extension, rather than typical hematogenous dissemination, explains long-segment arterial occlusion, proximal progression, and relapse after incomplete source control. Diagnosis requires early suspicion, serology, vascular imaging, and tissue-based confirmation. Management depends on prompt and complete surgical removal of infected arterial tissue, supported by adjunctive protein-synthesis-inhibiting antibacterial therapy, particularly when residual disease is suspected. Conventional antifungals have limited activity, and Pythium antigen immunotherapy remains historically important but of uncertain independent benefit. Earlier recognition, better surgical-margin assessment, standardized diagnosis, and prospective treatment data are needed.

P. insidiosum

Chemotherapy for disseminated testicular cancer.

Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diaminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered unevaluable due to early death. This chemotherapy regimen produced 74 per cent complete and 26 per cent partial remissions. Furthermore, five patients in partial remission became disease-free following the surgical removal of residual disease, producing an overall 85 per cent disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable. Maintenance therapy with vinblastine and BCG was very well tolerated, and only two patients in complete remission have experienced a relapse on maintenance therapy, one of whom had a central nervous system relapse. Thirty eight of these patients remain alive, and 32 remain alive and disease-free 6+ to 30+ months. We feel that this regimen represents a major advance in the management of patients with disseminated testicular cancer.

Adolescent

The management of ulcerative colitis.

The modern medical and surgical treatment of ulcerative colitis has been detailed. Whilst improvements in medical management have been few in the past decade there have been advances in dietary management and in the use of new drugs such as azathioprine and disodium cromoglycate which are currently being evaluated. Sulphasalazine remains a valuable drug in treating attacks of the disease and in preventing relapses, and its mode of action is now better understood. Steroid therapy, used orally, parenterally or topically, is of value in managing acute colitic attacks. Surgery is often required and total proctocolectomy with ileostomy remains the operation of choice. Colectomy with ileorectal anastomosis still remains a controversial operation but has its enthusiastic advocates. The interesting a new operation of proctocolectomy, with the establishment of an ileal bladder and continent ileostomy, is being assessed in Sweden and in a few centres in Britain and America.

Azathioprine

Radionuclides in oncology.

Radionuclides already have a major role in the daily practice of oncology and will, undoubtedly, be of even greater importance in the future. The variety of current and potential applications is shown in tab. 1. Their major use at this time is, in the broadest sense, for 'tumour scanning', which includes the evaluation of specific organs for the presence of tumour (usually with different radiopharmaceuticals for each organ) and the entire body (generalized tumour searches with radiopharmaceuticals like 67Ga-citrate or 111In-labeled bleomycin). The clinician uses these agents in the initial evaluation of extent of tumour (staging) and in the subsequent management of the patient with cancer to assess response to treatment, to reveal early relapse, and to assist in making decisions concerning treatment. The other potential roles for radionuclides are also briefly considered in this review.

Abdominal Neoplasms

The role of radionuclides in clinical oncology.

The major role of radionuclides in clinical oncology is, in the broadest sense, "tumor scanning". This includes evaluating specific organs for the presence of tumor (usually with different radiopharmaceuticals for each organ) or the entire body (generalized tumor searches with radiopharmaceuticals with 67Ga-citrate or 111Inlabeled bleomycin). The clinician uses these agents in the initial evaluation of the extent of tumor (staging) and in the subsequent management of the patient with cancer to assess response to treatment, to detect early relapse, and to assist in making decisions concerning treatment. The uses and limitations of the agents currently available for tumor scanning are summarized in this review (by major tumor type) from the perspective of the practicing oncologist. Other potential roles for radionuclides, including use as components of combined modality treatment programs, use as labels for antibodies or as drugs for both diagnosis and treatment, and use in the prediction of response to treatment, which are of great interest now and which will become realities for the oncologist in the future, are also considered.

Bleomycin

New approach to the rehabilitation of the hard core drug addict (heroin methadone addicts) a pilot community study.

The limitation of the methadone maintenance program has pressed for a re-evaluation of our understanding of the underlying causes of addiction. Apparently, one of theunderlying causes or end result produced by the drug itself is that of depression. It explains why the addicts try to maintain to the maximum, the euphoric state and are unwilling to rehabilitate. A pilot study was conducted for the treatment of ex-methadone addicts with large dosages of antidepressants and anxiolytics. Out of 117 ex-methadone and soft drug addicts treated with antidepressants and anxiolytics, 46% ex-methadone and 46.3% soft drug abusers failed to become abstinent. The failures were basically related to the management of treatment. The study suggests a possibility for detoxification from methadone and control of relapse by antidepressants and anxiolytics.

Anti-Anxiety Agents

Combined management of malignant teratoma of the testis.

Intensive chemotherapy with bleomycin and vinblastine was used as initial treatment in patients with advanced testicular teratoma and after relapse following lymph-node irradiation in patients with early-stage disease. Between January, 1976, and March, 1978, 84 patients, 28 with early disease and 56 with advanced disease, were treated. All 28 men with early-stage disease are alive and disease-free. Patients with advanced disease were divided into two groups. Patients with bulky multiple lung metastases and those with liver involvement did poorly, only 4 of 23 (17.4%) being disease-free. Conversely, patients with bulky abdominal nodes and those with limited lung disease did well, 17 of 21 previously untreated patients (80.9%) being alive and disease-free. Within the latter group, 16 patients were managed with chemotherapy and radiotherapy and/or surgery. Of these, 15 (93.4%) are disease-free.

Abdominal Neoplasms

Risk of Relapse and Efficacy of Adjuvant Chemotherapy in Localized Appendiceal Adenocarcinoma.

IMPORTANCE: Relapse risk and benefit of adjuvant chemotherapy after resection of appendiceal adenocarcinoma (AA) are uncertain. OBJECTIVE: To identify clinicopathologic and genomic factors associated with relapse and assess efficacy of adjuvant chemotherapy in localized AA. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study (January 2000 through February 2024; median follow-up, 62.6 months) used Kaplan-Meier and Cox proportional hazards modeling. It took place at the University of Texas MD (UT MD) Anderson Cancer Center with validation from Memorial Sloan Kettering Cancer Center (MSKCC). Participants included a complete localized cohort of 439 patients with stage I to III AA from UT MD Anderson, of whom 202 underwent surgery at UT MD Anderson and also included a validation cohort of 128 patients with stage II AA from MSKCC. EXPOSURES: Surgical resection with or without adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: Rate of recurrence, recurrence-free survival (RFS), and overall survival (OS). RESULTS: There were 439 patients with localized AA (median age, 56.5 [IQR, 22.2-83.7] years; 50% female and 50% male) managed at MD Anderson between January 2000 and February 2024. Of 202 MDA surgical patients, 19 (9.4%) had a relapse including 9 (6%) patients with stage II and 8 (19.5%) of patients stage III disease. Five-year OS was 95.7% without vs 77.2% with relapse (hazard ratio [HR], 5.50; 95% CI, 3.07-9.83; P&#x2009;<&#x2009;.001). Relative to goblet cell tumors, mucinous (HR, 5.60; 95% CI, 2.1-15; P&#x2009;<&#x2009;.001) and enteric-type (HR, 6.60; 95% CI, 2.9-15; P&#x2009;<&#x2009;.001) histologies were independently associated with relapse, as was pathologic T4 (HR, 3.30; 95% CI, 1.9-5.7; P&#x2009;<&#x2009;.001). Importantly, poor differentiation, perforation, lymphovascular invasion, and perineural invasion, known risk factors in colorectal cancer, were not significantly associated with relapse. For the complete localized cohort, adjuvant chemotherapy was not associated with improved RFS (univariate HR, 2.06; 95% CI, 1.36-3.13; P&#x2009;=&#x2009;.001 and multivariable HR, 0.98; 95% CI, 0.43-2.28; P&#x2009;=&#x2009;.90) or OS (univariate HR, 1.80; 95% CI, 1.0-3.2; P&#x2009;=&#x2009;.04 and multivariable HR, 0.71; 95% CI, 0.24-2.1; P&#x2009;=&#x2009;.53). TP53 mutation in goblet cell tumors (HR, 6.93; 95% CI, 1.50-31.00; P&#x2009;=&#x2009;.01) and GNAS mutation in nongoblet tumors (HR, 17.0; 95% CI, 3.09-93.3; P&#x2009;=&#x2009;.001) were associated with greater risk of relapse. CONCLUSIONS AND RELEVANCE: These results demonstrate that relapse after resection of localized AA is uncommon. Molecular profiling and histopathologic subtype refine risk. Adjuvant chemotherapy were not associated with benefit.

Journal Article