IMPORTANCE: Belantamab mafodotin (belamaf)-containing regimens are effective treatment options for patients with relapsed and/or refractory multiple myeloma. Ocular events are a common adverse effect of belamaf treatment, which can be managed by physicians, following appropriate training, to minimize their impact on the patient. OBJECTIVE: To develop clinical recommendations for the identification, monitoring, and management of ocular events associated with belamaf therapy, and guidance for any required dose modification. EVIDENCE REVIEW: A systematic literature review was conducted and an international group of hematologists and ophthalmologists reviewed clinical trial data, real-world evidence, and published literature on belamaf-associated ocular events. This literature review and the collective experience and expertise of the panel of experts informed the recommendations. FINDINGS: Belamaf-associated ocular events are common side effects of treatment, which are managed primarily with appropriate dose modification and decreased frequency of dosing, as well as the use of artificial tears. These events affect the corneal epithelium, are mainly Grade 1 and 2 per the Keratopathy and Visual Acuity scale and are reversible in almost all patients. In general, before initiating belamaf therapy, all patients should undergo a baseline ophthalmic evaluation with an eye specialist. However, if there are delays in obtaining ophthalmic evaluation, or if a patient is rapidly progressing, treatment should be initiated, and ophthalmic evaluation should be undertaken as soon as possible. Patients should be also evaluated by an eye specialist before administering the next three belamaf doses (i.e., before Cycles 2, 3, and 4); dose modifications, as described in this paper, may apply if required. Importantly, modifying the belamaf dose in response to an ocular event is not associated with any reductions in treatment efficacy. After Cycle 4, the treating physician may use the Vision-Related Anamnestic tool, alongside clinical judgment, to decide whether to administer the next dose of belamaf or to refer the patient to an eye specialist (i.e., if the patient experiences new worsening of vision or if the ocular events have neither improved after 8\u2009weeks nor resolved after 12\u2009weeks). CONCLUSIONS AND RELEVANCE: The expert panel developed recommendations for managing belamaf-associated ocular events, with the aim of contributing to the ease of clinical use of belamaf and improving patient outcomes.
\n \n\n \n \nBACKGROUND AND PURPOSE: Patients receiving total hip arthroplasty (THA) have different expectations and concerns about their health outcomes after surgery. In this study we developed a tool based on registry data to inform patients and their clinicians about activity outcomes after THA. METHODS: We used data from the Geneva Arthroplasty Registry (GAR) on patients receiving a primary elective THA between 1996 and 2019. The information tool was developed around five activity outcomes: getting in/out of the car, getting dressed autonomously, independence in weekly tasks, interference in social activities, and activity levels. Based on baseline predictors, conditional inference trees (CITs) were used to create clusters of patients with homogeneous activity outcomes at one, five and 10 years after surgery, rather than to predict individual probabilities. RESULTS: In total, 14 CITs were generated based on 6,836 operations included in the tool. Overall, activity outcomes substantially improved at all three times points after surgery, with 1-year values mostly being the highest. While before surgery only about 10% of patients had none/slight limitations in activities of daily living, about 70% did one year after surgery. The SF12 mental component score (MCS), SF12 self-rated health (SRH), BMI, ASA score, and comorbidity count were the most recurring predictors of activity outcomes.\u00a0Predictors and their relative importance changed at different time points for the same outcome. For example, for ability to get in/out the car, whilst clusters at year 1 were generated based on WOMAC function, SRH, mental health, WOMAC difficulty walking, and SF12 physical interference, at year 5, ASA score, BMI, SF12 physical & mental health, activity level, and socio-economic status were significant. Outcome profiles varied by clusters. CONCLUSION: Distinct activity outcomes clusters based on baseline patient characteristics were identified and knowing this can help inform patients' expectation and meaningful discussions with clinicians about treatment decisions.
\n \n\n \n \nBackground: Malnutrition, prevalent in locally advanced oesophagogastric adenocarcinoma (LA-OGA), has an undetermined impact on survival. This study aimed to elucidate the association between survival and nutritional status in patients with LA-OGA undergoing perioperative 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) treatment. Materials and methods: We screened patients with LA-OGA (cT2-4 and/or N1-3) treated with FLOT from 423 patients who underwent radical resection at The Royal Marsden Hospital between 2017 and 2023. Nutritional status was assessed using body weight and prognostic nutritional index (PNI). The primary outcome was 3-year recurrence-free survival (RFS) rate. Survival time was estimated using Kaplan\u2013Meier curves and restricted mean survival time at 36 months. Multivariate analyses were carried out. Pathological response was defined as a tumour regression grade of 1-2 using the Mandard criteria. Results: A total of 210 patients met the inclusion criteria [median follow-up time, 26.5 months; 3-year RFS rate, 53% (95% confidence interval 45% to 60%)]. Weight loss and PNI at diagnosis and after neoadjuvant chemotherapy were not significant predictors of RFS. A decrease in PNI during neoadjuvant chemotherapy was associated with a significantly shorter 3-year RFS rate than a maintained or increased PNI (46% versus 69%, P < 0.01). The restricted mean survival time difference was 5.46 months (95% confidence interval 1.73-9.19 months, P < 0.001). A decreased PNI (P = 0.03) independently and negatively predicted RFS. The pathological response was not associated with PNI changes (28.2% versus 30.4%, P = 0.75). Conclusions: Our findings suggest that changes in PNI during neoadjuvant therapy may be associated with survival outcomes.
\n \n\n \n \nINTRODUCTION: Acute appendicitis is the most common emergency general surgical condition in pregnancy, affecting around 1 in 1000 pregnancies. Reaching a diagnosis is more challenging in this group because of altered clinical presentations and the limitations of diagnostic tools in pregnancy. There is limited guidance from national bodies in the UK on the management of this condition. This study aims to describe current diagnostic and treatment practices for acute appendicitis in pregnancy in the UK, and associated outcomes, to identify variations in practice and areas for improvement. METHODS AND ANALYSIS: This is a UK-wide observational study. Hospitals providing an emergency general surgical service will be eligible to participate. The study consists of two components: (1) a site resource-profile questionnaire to assess the setup of services to care for the pregnant patient requiring emergency non-obstetric abdominal surgery to be completed by a senior collaborator at each participating site, and (2) a retrospective study of patients diagnosed with appendicitis or who had an appendicectomy for suspected appendicitis during a ten-year study period (2013-2023). Data will be collected on diagnostics, radiological findings, management approach and surgical and obstetric outcomes. The main measure of interest is the management approaches (operative versus non-operative; laparoscopic versus open surgery) and their association with selected outcomes. Multivariable logistic regression analyses will be conducted to identify factors which might predict the management strategy and outcomes. ETHICS AND DISSEMINATION: The protocol for this service evaluation study has been reviewed by the University of Sheffield Research Ethics Committee. The study findings will be discussed in a multistakeholder workshop consisting of general surgeons, obstetricians and gynaecologists, radiologists, anaesthetists and patient representatives with a view to making recommendations for quality improvement work and further research. Key findings and recommendations will be disseminated through specialist societies.
\n \n\n \n \nBACKGROUND: Psoriasis is a chronic inflammatory disease associated with multiple comorbidities, including metabolic syndrome and cardiovascular disease. Although specific dietary interventions, such as intermittent fasting and caloric restriction, have been shown to ameliorate inflammation and promote weight loss, the effect of these interventions independent of weight loss remains unclear. Time-restricted eating (TRE), a type of intermittent fasting, limits the daily eating window to a fixed number of hours. Recent studies suggest TRE may improve immune function in individuals with metabolic syndrome and cardiovascular risk factors. A crucial advantage of TRE over other investigated dietary restriction strategies is its reported high adherence rate, making it a more feasible intervention for long-term use. Therefore, exploring the effects of TRE on metabolic and immunological parameters in psoriasis is warranted. OBJECTIVE: This study was designed to evaluate the effects of short-term, isocaloric TRE, independent of weight loss, on immune cell function and serum metabolite profiles of volunteers with mild-to-moderate psoriasis compared to healthy individuals. METHODS: This case-control, prospective study was performed on 10 healthy male participants and 10 age-, BMI-, and sex-matched individuals with mild-to-moderate psoriasis. All individuals with psoriasis had stable disease and were being treated with topical therapies without any exposure to immunomodulatory biologics. This study was conducted at the National Institutes of Health Clinical Center. Immune profiles, glucose handling, energy expenditure, and participants' weights were assessed at baseline and after 3 days of TRE following a daily 6-hour eating window and 18-hour fast. RESULTS: The trial commenced in June 2021 and was completed in February 2023. A total of 20 participants were enrolled-10 with mild-to-moderate psoriasis and 10 age-, BMI-, and sex-matched healthy individuals. As of the time of manuscript submission, data processing is ongoing. Multiomic datasets, including gene expression, surface and intracellular protein levels, and metabolite profiles, are being generated from peripheral blood mononuclear cells, CD4+-enriched T-cells, and serum samples. The integrated bioinformatics analyses will be reported once the data analysis is completed. CONCLUSIONS: This clinical protocol was designed to characterize the effects of short term (3-day) TRE on psoriasis, independent of weight loss, by comparing immune cell regulatory responses between healthy individuals and those with psoriasis. More specifically, we aim to map the molecular pathways activated by TRE and assess how they affect immune cell composition, activation, and metabolism. Additionally, components of the metabolic response to isocaloric TRE are being explored. Insights into how dietary interventions impact metabolism and the immune system will enhance our understanding of the pathogenesis of psoriasis and may reveal new therapeutic avenues for managing this inflammatory condition. TRIAL REGISTRATION: ClinicalTrials.gov NCT04728165; https://clinicaltrials.gov/study/NCT04728165.
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