Disease Status Research Articles

Psychological outcomes in patients with rare cancers: a systematic review and meta-analysis

Rare cancers are those that exhibit an incidence of less than six per 100,000 in a year. On average, the five-year relative survival for patients with rare cancers is worse than those with common cancers. The traumatic experience of cancer can be further intensified in patients with rare cancers due to the limited clinical evidence and the lack of empirical evidence for informed decision-making. With rare cancers cumulatively accounting for up to 25% of all cancers, coupled with the rising burden of rare cancers on societies globally, it is necessary to determine the psychological outcomes of patients with rare cancers. This PRISMA-adherent systematic review (PROSPERO: CRD42023475748) involved a systematic search of PubMed, Embase, Cochrane and PsycINFO for all peer-reviewed English language studies published since 2000 to 30th January 2024 that evaluated the prevalence, incidence and risk of depression, anxiety, suicide, and post-traumatic stress disorder (PTSD) in patients with rare cancers. Two independent reviewers appraised and extracted the summary data from published studies. Random effects meta-analyses and meta-regression were used for primary analysis. We included 32 studies with 57,470 patients with rare cancers. Meta-analyses indicated a statistically significant increased risk-ratio (RR) of depression (RR=2.61, 95% CI: 1.43-4.77, I2=97%) and anxiety (RR=2.66, 95% CI: 1.27-5.55, I2=92%) in patients with rare cancers compared to healthy controls. We identified a high suicide incidence (315 per 100,000 person-years, 95% CI: 162-609, I2=95%), prevalence of depression (17%, 95% CI: 14-22, I2=88%), anxiety (20%, 95% CI: 15-25, I2=96%) and PTSD (18%, 95% CI: 9-32, I2=25%). When compared to patients with common cancer types, suicide incidence, and PTSD prevalence were significantly higher in patients with rare cancers. Systematic review found that having advanced disease, chemotherapy treatment, lower income, and social status were risk factors for negative psychological outcomes. We highlight the need for early identification of psychological maladjustment in patients with rare cancers. Additionally, studies to identify effective interventions are imperative. This study was supported by the National Medical Research Council Transition Award, SingHealth Duke-NUS Oncology Academic Clinical Programme, the Khoo Pilot Collaborative Award, the National Medical Research Council Clinician Scientist-Individual Research Grant-New Investigator Grant, the Terry Fox Grant and the Khoo Bridge Funding Award.

Assessment of chronic rhinosinusitis with nasal polyps: Development of the Nasal Polyp Patient Assessment Scoring Sheet tool.

Chronic rhinosinusitis (CRS) is a heterogeneous disorder with a wide range of validated subjective and objective assessment tools to assess disease severity. However, a comprehensive and easy-to-use tool that integrates these measures for determining disease severity and response to treatment is still obscure. The objective of this study was to develop a standardized assessment tool that facilitates diagnosis, uniform patient monitoring, and comparison of treatment outcomes between different centers both in routine clinical practice and in research. To develop this tool, published literature on assessment tools was searched on various databases. A panel of 12 steering committee members conducted an advisory board meeting to review the findings. Specific outcome measures to be included in a comprehensive assessment tool and follow-up sheet were then collated following consensus approval from the panel. The tool was further validated for content and revised with expert recommendations to arrive at the finalized Nasal Polyp Patient Assessment Scoring Sheet (N-PASS) tool. The N-PASS tool was developed by integrating the subjective and objective measures for CRS assessment. Based on expert opinions, N-PASS was revised to be used as an easy-to-use guidance tool that captures patient-reported and physician-assessed components for comprehensively assessing disease status and response to treatment. The N-PASS tool can be used to aid in the diagnosis and management of CRS cases with nasal polyps. The tool would also aid in improved monitoring of patients and pave the way for an international disease registry. Oxford Level 3.

Responsiveness of the condition-specific OVAMA questionnaire to measure symptoms and appearance in patients with vascular malformations.

Evidence-based guidelines for the treatment of vascular malformations are not readily available, possibly due to the diversity in methods used to evaluate treatment efficacy in clinical research, complicating the aggregation and comparison of study results. The OVAMA (Outcome Measures for VAscular Malformations) questionnaire was developed to uniformly measure symptoms and appearance, i.e., condition-specific core outcome domains, in patients with vascular malformations. However, the OVAMA questionnaire needs to be responsive to changes in these constructs in order to assess whether the disease status has altered since treatment. To assess the responsiveness of the OVAMA questionnaire in patients with vascular malformations. In a prospective longitudinal study, patients completed the OVAMA questionnaire at baseline and eight weeks follow-up since treatment or watchful waiting policy. Additionally, patients completed the Global rating of change (GRC) scales at follow-up. Responsiveness was evaluated following the criterion approach of testing predefined hypotheses about expected relationships between the OVAMA questionnaire and GRC scales, measuring the same constructs. The OVAMA questionnaire was considered responsive if ≥ 75% of the hypotheses were confirmed. Between July 2020 and September 2022, 89 patients were recruited in a vascular anomaly centre in the Netherlands, of which 63 patients completed the questionnaires at baseline and follow-up. In total, fifteen constructs of the OVAMA questionnaire were assessed for five hypotheses. Of these 75 hypotheses, 63 (84%) hypotheses were confirmed and thereby providing evidence that the OVAMA questionnaire is responsive to change. Our study found convincing evidence that the OVAMA questionnaire is responsive to changes in symptoms and appearance in patients with vascular malformations. In addition to determining a baseline of symptoms and appearance, the OVAMA questionnaire can now be used to evaluate the effect of treatment from the patient's perspective. The responsive OVAMA questionnaire allows for uniform evaluation and comparison of the effects of treatment on the condition-specific core outcome domains, tackling heterogeneity in outcome measurement and improving the clinical research of vascular malformations.

Health-related quality of life in adults with hematological cancer: a 2023 cross-sectional survey from Qatar

BackgroundHematological cancers impose a complex burden on individuals, affecting their physical health and mental and emotional well-being. This study evaluated the health-related Quality of Life (HRQOL) and its determinants among adults with hematological cancers in Qatar in 2023.MethodsA cross-sectional study used a validated structured questionnaire conducted among adult patients diagnosed with hematological cancers. All adult patients who attended The National Centre for Cancer Care and Research (NCCCR) in Qatar during the Data collection period (January to March 2023) and agreed to participate were included in the study.ResultsA total of 257 participants were enrolled in the study. The highest median (IQR) score of the HRQOL domain was observed in the functionating score of 90.6 (13.8), followed by the global health score of 83.3(25. 0). The median (IQR) of the symptoms burden score was 07.4(12.3). Gender significantly affects HRQOL, with males reporting better functioning and lower symptom burden than females. Employment status is positively associated with functioning scores. Regular exercise correlates with higher global health and functioning scores and lower symptom burden, while depressive symptoms are linked to poorer HRQOL outcomes. Patients experiencing cancer recurrence or active disease report lower global health and functioning scores and higher symptom burden. Treatment modalities such as chemotherapy and bone marrow transplant (BMT) timing also influence HRQOL, with recent treatment recipients showing lower global health and higher symptom burden scores. Depressive symptoms were the primary factor, lowering the global health score by 15.2%. Regarding the low functioning score predictors, female gender, depressive symptoms, and cancer recurrence emerged as significant predictors of the low functioning score. Furthermore, Regular exercise increased the functioning score by 03.4 units (p-value=0.018). Finally, Multiple linear regression analysis reinforced the significance of depressive symptoms, active disease status, and recurrence within the past five years as substantial predictors of higher symptom scores.ConclusionsThe study emphasizes the profound impact of depressive symptoms on all aspects of Health-Related Quality of Life (HRQOL), mainly affecting global health. It highlights the positive role of regular exercise in enhancing global health, functioning, and symptom burden scores.

Effect of methotrexate hold on COVID-19 vaccine response in the patients with autoimmune inflammatory disorders: a systematic review and meta-analysis.

Immunosuppressants, such as methotrexate (MTX), can suppress the COVID-19 vaccine response in patients with autoimmune diseases. Thus, this study aims to evaluate the effects of MTX hold following COVID-19 vaccination on vaccine efficacy response. A systematic review and meta-analysis of relevant studies retrieved from Web of Science, SCOPUS, PubMed, and CENTRAL from inception until Oct 1, 2023, was conducted. Covidence was used to screenthe eligible articles, and all relevant outcomes data were synthesized using risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) in meta-analysis models within RevMan 5.4. PROSPERO ID: CRD42024511628. Four studies with a total of 762 patients with autoimmune inflammatory disorders were included. Holding MTX following the COVID-19 vaccination for approximately 2 weeks was associated with significantly higher antibody titer (SMD: 0.70,95% CI [0.54, 0.87], P < 0.00001). However, the flare rate was significantly higher in the MTX hold group based on CDAI > 10 or DAS28-CRP > 1.2 either after 1st dose (RR: 2.49 with 95% CI [1.39, 4.47], P = 0.002) or 2nd dose (RR: 2.16 with 95% CI [1.37, 3.41], P = 0.0009) and self-reported disease flare (RR: 1.71 with 95% CI [1.35, 2.17], P < 0.00001). Holding MTX for 2 weeks after the COVID-19 vaccination resulted in significantly higher antibody titer but also had a higher disease flare rate, necessitating cautious clinical monitoring during this period. There is still a need to investigate safer MTX hold duration, considering patients' vulnerability to COVID-19, disease status, and demographics while adopting this strategy.

A comparative study of blood cell count in four automated hematology analyzers: An evaluation of the impact of preanalytical factors.

Differential white blood cell counts are frequently used in diagnosis, patient stratification, and treatment selection to optimize therapy responses. Referral laboratories are often used but challenged with use of different hematology platforms, variable blood shipping times and storage conditions, and the different sensitivities of specific cell types. To extend the scientific literature and knowledge on the temporal commutability of blood samples between hematology analyzers, we performed a comparative ex-vivo study using four of the most utilized commercial platforms, focusing on the assessment of eosinophils given its importance in asthma management. Whole blood from healthy volunteers with and without atopy (n = 6+6) and participants with eosinophilic asthma (n = 6) were stored under different conditions (at 4, 20, 30, and 37°C, with or without agitation) and analyzed at different time points (3, 6, 24, 48 and 72h post-sampling) in parallel on the Abbott CELL-DYN Sapphire, Beckman Coulter DxH900, Siemens ADVIA 2120i and Sysmex XN-1000V. In the same blood samples, eosinophil-derived neurotoxin (EDN), eosinophil activation and death markers were analyzed. All platforms gave comparable measurements of cell differentials on fresh blood within the same day of sampling. However, by 24 hours, significant temporal and temperature-dependent differences were observed, most markedly for eosinophils. None of the platforms performed perfectly across all temperatures tested during the 72 hours, showing that handling conditions should be optimized depending on the cell type of interest and the hematology analyzer. Neither disease status (healthy vs. asthma) nor agitation of the sample affected the cell quantification result or EDN release. The eosinophil activation markers measured by flow cytometry increased with time, were influenced by temperature, and were higher in those with asthma versus healthy participants. In conclusion, hematology analyzer, time window from sampling until analysis, and temperature conditions must be considered when analyzing blood cell differentials, particularly for eosinophils, via central labs to obtain counts comparable to the values obtained in freshly sampled blood.

Advances in the mechanism of metformin with wide-ranging effects on regulation of the intestinal microbiota

Metformin is of great focus because of its high safety, low side effects, and various effects other than lowering blood sugar, such as anti-inflammation, anti-tumor, and anti-aging. Studies have shown that metformin has a modulating effect on the composition and function of the intestinal microbiota other than acting on the liver. However, the composition of microbiota is complex and varies to some extent between species and individuals, and the experimental design of each study is also different. Multiple factors present a major obstacle to better comprehending the effects of metformin on the gut microbiota. This paper reviews the regulatory effects of metformin on the gut microbiota, such as increasing the abundance of genus Akkermansia, enriching short-chain fatty acids (SCFAs)-producing bacterial genus, and regulating gene expression of certain genera. The intestinal microbiota is a large and vital ecosystem in the human body and is considered to be the equivalent of an “organ” of the human body, which is highly relevant to human health and disease status. There are a lot of evidences that the gut microbiota is responsible for metformin’s widespread effects. However, there are only a few systematic studies on this mechanism, and the specific mechanism is still unclear. This paper aims to summarize the possible mechanism of metformin in relation to gut microbiota.

Acute Appendicitis in Children with Hematological Malignancies: The Need for Early Diagnosis and Prompt Treatment—A Single-Center Case Series

Abstract Introduction Appendicitis in patients with hematological malignancies presents with vague symptoms, thus requiring a high degree of suspicion for early diagnosis and treatment to prevent complications. Objectives The aim of this article was to describe the demographic, clinicoradiological, operative findings, and outcomes in patients with acute appendicitis with underlying hematological malignancies. Materials and Methods A retrospective review of pediatric patients with hematological malignancy who developed acute appendicitis was conducted. Medical records of patients were reviewed for patient demographics, disease status, signs, and symptoms at the time of diagnosis of acute appendicitis, and outcome. The laboratory, radiological, and histological findings were retrieved from the hospital records. Results Six (2.4%) patients developed acute appendicitis over the past 8 years among a total of 254 patients treated for hematological malignancies in the unit. Five patients had underlying acute lymphoblastic leukemia (ALL) and one had acute myeloid leukemia (AML). Of the five patients, three were in postremission consolidation, one each in the delayed intensification and maintenance phase of chemotherapy. The child with AML was on induction chemotherapy for the first relapse at the time of diagnosis. Fever and abdominal pain were the common presenting symptoms. Diagnosis was made on ultrasound abdomen in five patients, and one patient was diagnosed on computed tomography. All patients underwent open appendectomy. Two patients had evidence of appendiceal perforation. Three patients had neutropenia at the time of developing appendicitis and underwent appendectomy regardless of the absolute neutrophil count (ANC). Five patients recovered well, and chemotherapy was restarted within 2 weeks of appendectomy. One patient developed a superficial surgical site infection. and one patient with relapsed AML expired due to refractory septic shock. Conclusion Acute appendicitis in patients with hematological malignancies can present with subtle signs and symptoms. Appendectomy can be safely performed irrespective of the ANC.

Low frequency of Vγ9Vδ2 T-cells predicts poor survival in newly diagnosed acute myeloid leukemia

In several tumor subtypes, an increased infiltration of Vγ9Vδ2 T-cells has been shown to have the highest prognostic value compared to other immune subsets. In acute myeloid leukemia (AML), similar findings have been based solely on the inference of transcriptomic data and have not been assessed with respect to confounding factors. This study aimed at determining, by immunophenotypic analysis (flow or mass cytometry) of peripheral blood from AML patients at diagnosis, the prognostic impact of Vγ9Vδ2 T-cell frequency. This was adjusted for potential confounders (age at diagnosis, disease status, European LeukemiaNet classification, leukocytosis, and allogeneic hematopoietic stem cell transplantation as a time-dependent covariate).The cohort was composed of 198 newly diagnosed AML patients.By univariate analysis, patients with lower Vγ9Vδ2 T-cells at diagnosis had significantly lower 5-year overall and relapse-free survivals. These results were confirmed in multivariate analysis (Hazard Ratio [HR]=1.55[1.04-2.30], p=0.030 and HR=1.64[1.06,2.53], p=0.025). Immunophenotypic alterations observed in patients with lower Vγ9Vδ2 T-cells included a loss of some cytotoxic Vγ9Vδ2 T-cell subsets and a decreased expression of BTN3A on the surface of blasts. Samples expanded regardless of their Vγ9Vδ2 T-cell levels and displayed similar effector functions in vitro. This study confirms the prognostic value of elevated Vγ9Vδ2 T-cells among lymphocytes, in newly diagnosed AML patients. These results provide a strong rationale to consider consolidation protocols aiming at enhancing Vγ9Vδ2 T-cell responses.

Exploring potential influencing factors of inadherence to specialist aftercare and long-term medication in patients with acromegaly.

To improve the understanding of adherence as one major factor of disease control in acromegaly patients, we systematically assessed patients' motivations to adhere to advised follow-up schedules and recommended medication for acromegaly. Cross-sectional, postal questionnaire study on adult patients with acromegaly, operated upon a growth hormone producing pituitary adenoma more than 1 year ago in two tertiary treatment centers. We assessed demographic and clinical characteristics, disease status, adherence to acromegaly medication and/or aftercare, and the five dimensions defined by the World Health Organization influencing adherence. Wherever applicable, we included validated short scales. The answers of 63 patients (33 f, 30m; mean age 56.1 y) were analyzed. Patients with problems in adherence to aftercare had a significantly lower subjective symptomload than those adherent to aftercare (p = 0.026) and a lower perceived need for treatment (p = 0.045). Patients with adherence problems to medication had a higher subjective symptomload than those without (p = 0.056). They also tended to have shorter consultations, were significantly more often dissatisfied with the duration of their medical consultations (42% vs 4.8%, p = 0.019) and tended to find that their physician explained potential difficulties with adherence less well than patients without adherence problems (p = 0.089). To our knowledge, this is the first study which explored adherence to medication and aftercare in patients with acromegaly, taking into account potential influencing factors from all areas defined by the WHO model of adherence. Of the modifiable factors of adherence, patient-doctor relationship seemed to play a crucial role and could be one leverage point to improve adherence.

Sequential analysis of cfDNA reveals clonal evolution in neuroblastoma patients receiving ALK targeted therapy.

The study of cell free DNA (cfDNA) enables sequential analysis of tumor cell-specific genetic alterations in neuroblastoma patients. Eighteen patients with relapsing neuroblastoma having received Lorlatinib, a 3rd generation ALK inhibitor, were identified (SACHA national registry and/or in the institution). cfDNA was analyzed at relapse for 9 patients, and sequentially for 5 patients (blood/bone marrow plasma) by performing WGS library construction followed by ALK-targeted ddPCR of the hotspot mutations (F1174L, R1275Q, I1170N) (variant allele fraction (VAF) detection limit 0.1%) and WES to evaluate disease burden and clonal evolution, following comparison with tumor/germline WES. Overall response rate to Lorlatinib was 33% (CI 13-59%), with response observed in 6/10 cases without versus 0/8 cases with MYCN amplification (MNA). ALK VAFs correlated with the overall clinical disease status, with a VAF<0.1% in clinical remission, versus higher VAFs (>30%) at progression. Importantly, sequential ALK ddPCR detected relapse earlier than clinical imaging. cfDNA WES revealed new SNVs, not seen in the primary tumor, in all instances of disease progression after Lorlatinib treatment, indicating clonal evolution, including alterations in genes linked to tumor aggressivity (TP53) or novel targets (EGFR). Gene pathway analysis revealed an enrichment for genes targeting cell differentiation in emerging clones, and cell adhesion in persistent clones. Evidence of clonal hematopoiesis could be observed in follow-up samples. We demonstrate the clinical utility of combining ALK cfDNA ddPCR for disease monitoring and cfDNA WES for the study of clonal evolution and resistance mechanisms in neuroblastoma patients receiving ALK targeted therapy.

Elucidating the role of T-Reg related cytokines: serum transforming growth factor beta and interleukin-35 in alopecia areata.

Previous studies demonstrated that Th1 cytokines like IL-2, IL-12 and IFN-γ have initiatory role in alopecia areata (AA) and positive correlation with disease severity. They informed that serum levels of Th17 cytokines, IL-17, IL-22, IL-23 increased in active AA patients and corelated, particularly IL-17, with disease severity. In recent reports it was showed the balance between Th17 and Treg cells is crucial for maintaining tolerance to self-antigens, and an imbalance towards Th17 may contribute to the development of autoimmune diseases like AA. But research on serum Treg markers in AA is limited. It was aimed to investigate whether the Treg cells have a role in the pathogenesis of AA analyzing the serum levels of Treg cytokines IL-35 and TGF-β in the patients with AA. 42 AA patients and 38 healthy controls were enrolled. Patient demographics, clinical data, disease severity assessed by Severity of Alopecia Tool (SALT) scores were recorded. Serum samples were collected and analyzed for TGF-β and IL-35 levels using ELISA kits. The cytokine levels in both groups were statistically compared. Their relation with parameters of demographic and severity of disease was evaluated. The patient and control groups had no statistically significant difference, there was 71.4% males and 28.6% females in patient group, while the control group had 63.2% males and 36.8% females, Severity analysis classified 18 patients with mild AA, 19 with moderate AA, and 5 with alopecia totalis/areata universalis. While TGF-β levels exhibited no significant difference between groups, IL-35 levels were significantly elevated in AA patients (p = 0.002). Logistic regression identified IL-35 as a significant parameter influencing disease status (OR = 1.055). Correlation analysis revealed a weak positive correlation between patient age and IL-35 levels (r = 0.436; p = 0.004). Notably, IL-35 levels displayed a significant decrease in individuals with antinuclear antibody (ANA) positivity. No correlations were identified between cytokine levels and disease severity, prognosis, or disease activity. Elevated IL-35 levels suggest that IL-35 and specific Treg cell subsets can play a role in AA pathogenesis. The nuanced roles of TGF-β and IL-35 highlight the need for comprehensive studies to interpret their implications in the complex immunopathogenesis of AA. These findings open avenues for further research, positioning IL-35 as a prospective target for investigating and potentially intervening in AA pathogenesis.

How group structure impacts the numbers at risk for coronary artery disease: polygenic risk scores and non-genetic risk factors in the UK Biobank cohort.

The UK Biobank is a large cohort study that recruited over 500,000 British participants aged 40-69 in 2006-2010 at 22 assessment centres from across the UK. Self-reported health outcomes and hospital admission data are two types of records that include participants' disease status. Coronary artery disease (CAD) is the most common cause of death in the UK Biobank cohort. After distinguishing between prevalence and incidence CAD events for all UK Biobank participants, we identified geographical variations in age-standardised rates of CAD between assessment centres. Significant distributional differences were found between the pooled cohort equation scores of UK Biobank participants from England and Scotland using the Mann-Whitney test. Polygenic risk scores of UK Biobank participants from England and Scotland and from different assessment centres differed significantly using permutation tests. Our aim was to discriminate between assessment centres with different disease rates by collecting data on disease-related risk factors. However, relying solely on individual-level predictions and averaging them to obtain group-level predictions proved ineffective, particularly due to the presence of correlated covariates resulting from participation bias. By using the Mundlak model, which estimates a random effects regression by including the group means of the independent variables in the model, we effectively addressed these issues. In addition, we designed a simulation experiment to demonstrate the functionality of the Mundlak model. Our findings have applications in public health funding and strategy, as our approach can be used to predict case rates in the future, as both population structure and lifestyle changes are uncertain.

The impact of the implementation of hierarchical medical system on population health: evidence from China

IntroductionThe implementation of a hierarchical medical system holds significant practical importance in advancing the Healthy China strategy and elevating the overall health status of the population of China.MethodsThis article empirically examines the influence of the implementation of a hierarchical medical system on the health of the population using the latest 2020 China Family Panel Studies database. Furthermore, it investigates the variability of this impact across distinct health insurance participation statuses and literacy groups.ResultsThe findings of the study demonstrate that the implementation of the hierarchical medical system substantially enhances the health of the population, not only in terms of self-assessed health but also through a notable positive effect on alleviating chronic diseases. These results maintain their validity even after conducting robustness tests utilizing a replacement estimation model. Heterogeneity analysis reveals that the impact of the hierarchical medical system on the population’s health status exhibits significant variation concerning health insurance participation and literacy. Specifically, regarding health insurance participation, the hierarchical medical system effectively improves both self-assessed health and chronic disease status among the insured population. However, for those not enrolled in health insurance, the hierarchical medical system only demonstrates improvement in chronic disease status, with insignificant results observed in enhancing self-assessed health status. Moreover, propensity score matching (PSM) was also used to address endogeneity problems resulting from sample selectivity bias. The findings demonstrate that endogeneity issues can be suitably addressed by the PSM model. Additionally, they point out that an overestimation of the impact of the hierarchical medical system on the population’s self-assessed health state would result from failing to take sample selectivity bias into account. On the other hand, it will lead to the underestimation of the effect of the hierarchical medical system on the status of chronic diseases.DiscussionMoving forward, steadfast efforts should be directed toward further enhancing the implementation of the hierarchical medical system. This includes the comprehensive promotion and using the pivotal role of the hierarchical medical system in improving the health of the population.

#386 Avacopan versus prednisone taper in newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis in the ADVOCATE trial

Abstract Background and Aims In granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), two types of antineutrophil cytoplasmic autoantibody-associated vasculitis, relapses are common, with 14–44% of patients experiencing a relapse at 18–36 months, depending on patient characteristics, duration of follow-up, and maintenance treatment [1]. In the phase 3 ADVOCATE trial, 69% of patients were newly diagnosed and 31% had relapsing GPA/MPA [2]. This post hoc subgroup analysis of ADVOCATE evaluates the safety and efficacy of avacopan compared with a prednisone taper in patients with newly diagnosed or relapsing GPA/MPA. Method ADVOCATE, a randomised, double-blind, double-dummy, active-controlled clinical trial, assigned eligible patients 1:1 to receive avacopan or a prednisone taper on a background of either cyclophosphamide (followed by azathioprine or mycophenolate mofetil) or rituximab. Data from patients with newly diagnosed (N = 229) or relapsing (N = 101) GPA/MPA were analysed. Key outcomes were the percentage of patients achieving remission at week 26 and sustained remission at week 52. Other outcomes included relapse rate, change in estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), glucocorticoid dose (prednisone-equivalent), Glucocorticoid Toxicity Index (GTI), health-related quality of life (HRQoL), and safety. Results Baseline characteristics were comparable between the avacopan and prednisone taper arms within each disease status group (Table 1). Efficacy outcomes are reported in Table 2. At week 26, similar proportions of patients with newly diagnosed GPA/MPA achieved remission in the avacopan and prednisone taper arms (66.1% vs 66.7%; difference [95% confidence interval (CI)]: −0.6% [−12.8, 11.7]). In the relapsed group, a numerically higher proportion of patients receiving avacopan than those receiving a prednisone taper achieved remission at week 26 (86.3% vs 78.0%; difference [95% CI]: 8.3% [−6.6, 23.1]). Compared with the prednisone taper arm, the proportion of patients who achieved sustained remission at week 52 with avacopan was similar in newly diagnosed GPA/MPA (60.9% vs 57.9%; difference [95% CI]: 3.0% [−9.7, 15.7]) and higher in relapsed GPA/MPA (76.5% vs 48.0%; difference [95% CI]: 28.5% [10.4, 46.6]). The relapse rate over 52 weeks after remission at any time was lower with avacopan than with a prednisone taper in both newly diagnosed (8.2% vs 18.2%) and relapsed (14.6% vs 27.7%) GPA/MPA. There was a larger improvement in eGFR over 52 weeks (newly diagnosed: 8.1 vs 5.3; relapsed: 5.0 vs 0.7) and earlier reduction in UACR at 4 weeks (newly diagnosed: −42% vs −1%; relapsed: −32% vs 3%) in the avacopan arm than in the prednisone taper arm. The total all-source median glucocorticoid dose was 625 mg in the avacopan arm compared with 3048 mg in the prednisone taper arm for newly diagnosed GPA/MPA, and 500 mg in the avacopan arm compared with 3139 mg in the prednisone taper arm for relapsed GPA/MPA. At week 26, the GTI cumulative worsening and aggregate improvement scores were lower (more favourable) with avacopan than with a prednisone taper in both arms. The change from baseline in both analysed HRQoL scales was numerically higher with avacopan than with a prednisone taper at week 52 in both groups (Table 2). Fewer adverse events per patient were reported with avacopan vs a prednisone taper in both disease status groups (Table 1). Conclusion In this post hoc subgroup analysis of the ADVOCATE trial, efficacy and safety outcomes in patients with newly diagnosed or relapsed GPA/MPA favoured avacopan compared with a prednisone taper, supporting the use of avacopan in these patient types. The observed clinical efficacy of avacopan especially in patients with relapsing GPA/MPA provides valuable insights into the treatment of this difficult-to-treat subgroup.

#2973 COVID-19 increased hemodialysis patients’ mortality, relation with inflammation and telomere attrition

Abstract Background and Aims An increased risk of mortality and hospitalization has been consistently demonstrated in patients with CKD who are additionally affected by corona virus disease 19 (COVID-19). In this study, we tried to identify predictive factors of mortality and hospitalizations, especially the ratio of neutrophils to lymphocytes (NLR), lactate dehydrogenase (LDH), c-reactive protein (CRP), disease status of COVID-19, telomere length in peripheral blood cells (TL) and 2-year risk score. Method A total of 130 chronic hemodialysis patients, were enrolled in the present study and followed up for 18 months. Routine laboratory parameters including LDH, were determined by standard automated methods, redox status parameters SOD and O2. - Using spectrophotometric methods.TL was determined using the modified Cawthon method and was calculated as the T/S ratio. Kaplan-Meier analysis was used to test survival predictors. Results Patients in deceased group (30%) were significantly older (p &amp;lt;0.001), with higher body mass index (BMI), (p &amp;lt; 0.01) than survived patients. Also, patients in the deceased group had higher levels of LDH, NLR index, CRP compared to survivors. Lower lymphocytes and shortened TL were characteristic of these patient groups, but the deceased group had the lowest lymphocytes (p &amp;lt; 0.005) and telomeres (p&amp;lt;0.002), and had the highest NLR (0.004). The difference in 2-years risk score also was significant (p &amp;lt; 0.001), with higher scores in the deceased group. Kaplan-Meier survival analysis showed six parameters were significant predictors in the following order of significance: COVID-19 status, 2-years risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patients’ survival in this group of parameters (Log rank=25.4, P &amp;lt; 0.001). Conclusion Independent predictors of mortality in chronic haemodialysis patients are higher NLR, CRP, LDH, Lower lymphocytes and shortened TL, and COVID -19 made the situation even worse by significantly arising these patients’ mortality rate.

Analysis of surgical margins and prognostic factors in dermatofibrosarcoma protuberans after wide local excision: Amulticenter study of 116 Japanese patients.

Cutaneous dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor characterized by a high risk of local recurrence but a low risk of metastasis. Wide local excision (WLE) has been an important treatment option, but its clinical outcomes and safety have not been thoroughly evaluated in previous reports. The aim of this study was to determine appropriate surgical margins (deep and lateral) and prognostic factors associated with recurrence-free survival (RFS) of DFSP. A database collected by two dermatology departments in Japan was retrospectively reviewed to identify 116 patients with DFSP who underwent complete resection with WLE between 1994 and 2021. Sixty-one men (53%) and 55 women (47%) were included in our cohort. The primary sites of DFSP were as follows: 11 head and neck (9%); seven face (7%); 12 upper extremities (10%); 20 lower extremities (17%); and 66 trunk (57%). There were 103 cases (89%) of primary DFSP and 13 cases (11%) of recurrent DFSP. Total 10-year RFS was 96.6%. There were significant differences in RFS by tumor size (median size: 3 cm), disease status (primary versus recurrent DFSP), and fibrosarcomatous change (positive versus negative) (all p < 0.05). Two patients (1.7%) with buccal or head lesions had positive deep margins. In all cases, the lateral margin was negative at the postoperative evaluation. Tumor size, disease status, and fibrosarcomatous change are important risk factors for recurrence. Both face and head-neck lesions were more likely to have positive deep margins than other anatomic areas in DFSP. Although this study was limited by its retrospective design, a narrow 2-cm lateral margin is especially considered for low-risk patients.

Tungiasis among children in Kenya is associated with poor nutrition status, absenteeism, poor school performance and high impact on quality of life.

Tungiasis is a highly neglected tropical skin disease caused by the sand flea, Tunga penetrans. The flea burrows into the skin inducing a strong inflammatory response, leading to pain and mobility restrictions with potential impacts on quality of life. Few countries implement control efforts and there are few data on the impact of the disease to support policy decisions. We conducted a survey to determine the impact of tungiasis among primary school children across nine counties of Kenya. A total of 10,600 pupils aged 8 to 14 years were randomly selected from 97 primary schools and examined for tungiasis. For 81 cases and 578 randomly selected controls, anthropometric measurements were made, and school attendance and exam scores were collected from school records. Of those with tungiasis, 73 were interviewed regarding their quality of life using a tungiasis-specific instrument. Mixed effect ordered logistic and linear models were used to assess associations between disease status and impact variables. Compared to uninfected pupils, those with tungiasis had lower weight-for-age z-scores (adjusted β -0.41, 95% CI: -0.75-0.06, p = 0.020), missed more days of school the previous term (adjusted Incidence Rate Ratio: 1.49, 95% CI: 1.01-2.21, p = 0.046) and were less likely to receive a high score in mathematics (aOR 0.18, 95% CI: 0.08-0.40, p<0.001) and other subjects. Pupils with severe disease (clinical score >10) were four times more likely to experience severe pain than those with mild disease (OR 3.96, 95% CI: 1.35-11.64, p = 0.012) and a higher impact on their quality of life than those with mild disease (aOR 3.57, 95% CI: 1.17-10.8, p = 0.025) when adjusted for covariates. This study has demonstrated tungiasis has a considerable impact on children's lives and academic achievement. This indicates the need for integrated disease management for school-aged children to protect their physical and cognitive development and their future prospects.

Radiotherapy for Recurrent Medulloblastoma in Children and Adolescents: Survival after Re-Irradiation and First-Time Irradiation

Background: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects. Methods: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2. Results: A total of 42 pre-irradiated patients with RT2 were matched to 42 pre-irradiated controls without RT2. RT2 improved the median PFS [21.0 (CI: 15.7–28.7) vs. 12.0 (CI: 8.1–21.0) months] and OS [31.5 (CI: 27.6–64.8) vs. 20.0 (CI: 14.0–36.7) months]. Concerning long-term survival after ten years, RT2 only lead to small improvements in OS [8% (CI: 1.4–45.3) vs. 0%]. RT2 improved survival most without (re)-resection [PFS: 17.5 (CI: 9.7–41.5) vs. 8.0 (CI: 6.6–12.2)/OS: 31.5 (CI: 27.6–NA) vs. 13.3 (CI: 8.1–20.1) months]. In the RT-naïve patients, CSI at recurrence improved their median PFS [25.0 (CI: 16.8–60.6) vs. 6.6 (CI: 1.5–NA) months] and OS [40.2 (CI: 18.7–NA) vs. 12.4 (CI: 4.4–NA) months]. Conclusions: RT2 could improve the median survival in a matched cohort but offered little benefit regarding long-term survival. In RT-naïve patients, CSI greatly improved their median and long-term survival.

Utilizing red blood cell distribution width (RDW) as a reliable biomarker to predict treatment effects after chimeric antigen receptor T cell therapy

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for B cell malignancies. A certain fraction of patients, however, experience post-CAR-T relapse, and due to the difficulty of precise relapse prediction, biomarkers that can predict the strength and duration of CAR-T efficacy are needed before CAR-T infusion. Therefore, we performed a single-center cohort study including 91 diffuse large B cell lymphoma (DLBCL) patients treated with CAR-T in order to identify such a new prognostic biomarker. After confirming that each of the already reported prognostic parameters (disease status at leukapheresis, primary refractoriness, number of treatment lines, CD3+ cell counts at leukapheresis) has only limited predictive performance, we established a new composite parameter by integrating these four variables, and found that it predicts progression-free survival (PFS) after CAR-T infusion with statistical significance. Moreover, after comprehensive correlation analyses of this new composite parameter with all individual laboratory variables, we determined that the standard deviation of red blood cell distribution width (RDW-SD) at leukapheresis shows significant correlation with the composite parameter and may be a prognostic biomarker (R2 = 0.76, p = 0.02). Validation analysis indicated that a higher RDW-SD is significantly associated with poorer PFS after CAR-T cell therapy (HR, 3.46, P = 0.03). Thus, this study suggests that a single parameter, RDW-SD at leukapheresis, is a novel, useful biomarker that can be obtained early to predict therapeutic effects of CAR-T cell therapy. Post-CAR-T maintenance or re-induction therapies should be adopted for higher risk patients, who may relapse after CAR-T therapy.