High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy.

BACKGROUND AND AIMS: Accurate biomarkers to predict outcomes following discontinuation of nucleos(t)ide analogue (NA) therapy are needed. We evaluated serum hepatitis B core-related antigen (HBcrAg) level as a biomarker for predicting outcomes after NA discontinuation. METHODS: Patients with HBeAg-negative chronic hepatitis B (CHB) without cirrhosis were enrolled in a prospective trial evaluating clinical outcomes until 96 weeks after NA discontinuation. End of treatment (EOT) and off-treatment levels of serum HBcrAg, HBsAg, HBV RNA and HBV DNA were used to predict key clinical outcomes including hepatitis flare (ALT ≥5 × ULN and HBV DNA > 2000 IU/mL). The SCALE-B score was calculated for the purposes of model validation. RESULTS: HBcrAg was tested amongst 65 participants. The median age was 54 years, 54% were male and 83% were Asian. HBcrAg was detectable in 86% patients. HBcrAg level ≥4 log U/mL at EOT was predictive of hepatitis flare [8/10 (80%) vs. 17/55 (31%), p = .001]. The presence of either HBcrAg ≥4 log U/mL or detectable HBV RNA at EOT predicted for both biochemical relapse and hepatitis flare. The SCALE-B model at EOT predicted for virological relapse, biochemical relapse, hepatitis flare and HBsAg loss in this cohort. An increase in the serum HBcrAg level off-treatment was also associated with hepatitis flare. No participant with EOT HBcrAg level ≥4 log U/mL achieved HBsAg loss. CONCLUSIONS: High levels of serum HBcrAg predict for hepatitis flare after stopping NA therapy and low likelihood of HBsAg loss at week 96. People with high levels of serum HBcrAg are not suitable candidates for NA discontinuation.

C-Reactive Protein Kinetic as a Potential Predictive and Prognostic Factor during Treatment with Checkpoint Inhibitors in R/M-HNSCC.

Introduction The kinetic of C-reactive protein (CRP) in the early phase of therapy with checkpoint inhibitors (CPI) and its prognostic value has already been investigated in several tumor entities. In particular, flare dynamics have been described as a positive prognostic parameter. The aim of this retrospective study is to examine the extent to which such an application can also be transferred to patients with recurrent or metastatic squamous cell carcinoma of the head and neck region (R/M-HNSCC). Material and Methods All patients treated with CPI for R/M-HNSCC at our clinic between 2018 and 2023 were included (n = 44). Demographic, clinical, histopathologic and laboratory data were extracted from the digital patient records and statistically analyzed. We then examined the CRP kinetic using two previously published classifications and proposed a new classification ourselves. Subsequently, correlation analyses were performed with the overall survival (OS) of the patients. Results Of the two CRP kinetic classifications previously published, only one showed a correlation with the result of the first re-staging, and neither showed a correlation with the OS of R/M-HNSCC patients. Our new CRP kinetic classification showed a significant association with OS in R/M-HNSCC patients (p = 0.05). In a multivariate analysis, our CRP kinetic classification (p = 0.007) and the outcome of the first re-staging (p = 0.002) were significant independent factors for OS. Discussion Our novel CRP kinetic classification significantly correlates with OS in R/M-HNSCC patients, indicating a potential prognostic marker. Existing classifications from other cancer entities showed limited prognostic significance, emphasizing the need for tailored markers. For validation, however, testing on larger R/M-HNSCC patient collectives is necessary.

STOPPING NUCLEOS(T)IDE ANALOGUES IN CHRONIC HEPATITIS B USING HBSAG THRESHOLDS: A META-ANALYSIS AND META-REGRESSION.

BACKGROUND AND AIMS: Recommendations for stopping nucleoside analogue(NA) therapy in HBeAg-negative Chronic Hepatitis B(CHB) are unclear. End-of-treatment quantitative HBsAg(EOTqHBsAg) thresholds<100IU/ml or <1000IU/ml have been proposed as stopping criterion. We assessed this by meta-analysis and meta-regression. DESIGN: We searched PubMed, EMBASE and conference abstracts for studies of HBeAg-negative CHB NA discontinuation. Extracted studies were analysed for risk-of-bias, pooled risk of HBsAg loss, virological(VR) and biochemical relapse(BR). Significant heterogeneity(I2) was addressed by subgroup analysis and random-effects meta-regression with known important covariables, including EOTqHBsAg thresholds, ethnicity, duration of therapy and followup. RESULTS: We found 24 papers(3732 subjects), 16 had low and 8 had moderate risk of bias. The pooled risks of HBsAg loss, VR and BR for stopping therapy at EOTqHBsAg<100IU/ml were 41.8%, 33.4% and 17.3%, versus 4.6%, 72.1% and 34.6% respectively for EOTqHBsAg≥100IU/ml. The pooled risks of HBsAg loss, VR and BR for stopping therapy at EOTqHBsAg<1000IU/ml were 22.0%, 52.7% and 15.9%, versus 3.4%, 63.8% and 26.4% respectively for EOTqHBsAg≥1000IU/ml. Multivariable analysis for HBsAg loss showed ethnicity, followup duration and EOTqHBsAg<100≥IU/ml explained 85% of the variance in heterogeneity; Asians with EOTqHBsAg<100IU/ml had 28.2%, while non-Asians with EOTqHBsAg<1000IU/ml had 38.4% HBsAg loss. Multivariable analysis showed EOTqHBsAg<100≥IU/ml and other covariables only explained 43% and 63% of the variance in heterogeneity for VR and BR respectively, suggesting that other factors are also important for relapse. CONCLUSIONS: While EOTqHBsAg thresholds, ethnicity and followup duration strongly predict HBsAg loss, this is not true for VR and BR, hence stopping NA therapy should be considered cautiously.

Sustained depression of B cell counts in lupus nephritis after treatment with rituximab and/or belimumab is associated with fewer disease flares.

OBJECTIVE: To study the risk of lupus nephritis flare (LNF) or severe lupus flare (SLF) as a function of B cell count kinetics in lupus nephritis (LN) patients after they achieve at least a partial renal response (PRR) with induction treatment that includes rituximab (RTX) and/or belimumab (BLM). METHODS: We performed a retrospective analysis of a cohort of 19 patients with severe LN that received a B cell agent (BCA), RTX and/or BLM, as part of an initial treatment regimen for an LN flare and had subsequent CD19+ B cell measurements in peripheral blood. We then characterized the follow-up periods, after B cell depressions occurred and PRR were achieved, by the corresponding trajectories of B cell counts (BCC). Time periods with sustained low BCC were type 1 (T1) episodes, while those with repletion of BCC>100 cells/µL were called type 2 (T2) episodes. Time periods with rapid BCC repletion, defined as >50 cells/µL in ≤6 months, were called T2b episodes. Corresponding C3, C4, and anti-dsDNA levels were recorded for each episode. The time from PRR until an event, either a LNF or SLF, or to censoring, either at the end of the study period or the end of available patient follow-up, was assessed for each episode type. Kaplan-Meier survival analysis was used to compare time to flare between T1 and T2 episodes. RESULTS: There were 26 episodes of B cell depression. Seventeen (65%) were T1 and 9 (35%) were T2. Compared to T1 episodes, T2 episodes were 9.0 times more likely to result in flare over the follow-up period (hazard ratio (HR) = 9.0, 95% CI for HR = 2.2-36.7); this risk was even larger for T2b vs T1 episodes. Median BCC was 14 cells/µL in T1 and 160 cells/µL in T2 episodes. Both C3 and C4 levels significantly increased over the duration of the episode in T1 episodes only. CONCLUSION: Sustained low BCC was associated with prolonged serologic and clinical response, whereas repletion, and particularly rapid repletion, of B cells after treatment with BCA was associated with subsequent disease flare.

Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study.

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan-Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan-Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

The incidence and intensity of postoperative pain and Flare-up following the use of three different intracanal medicaments in teeth with posttreatment apical periodontitis: a randomized clinical trial.

OBJECTIVES: This randomized clinical trial aimed to compare the effect of intracanal medicaments on the incidence of postoperative pain and flare-up with posttreatment apical periodontitis (PTAP) of retreatment cases. MATERIALS AND METHODS: One hundred twenty patients diagnosed with PTAP with single-rooted teeth with single-canal without spontaneous pain or swellings were included and randomly divided into three groups according to the intracanal medicament used. Intracanal medicaments were placed into the root canals following the removal of previous root canal fillings and re-instrumentation. Calcium hydroxide (Ca (OH)2), chlorhexidine gel (CHX), calcium hydroxide and chlorhexidine gel combinations were used as intracanal medicaments. Postoperative pain scores were recorded at 6 and 12 h and 1, 2, 3, 4, 5, 6, and 7 days using a visual analog scale (VAS). Sensitivity on percussion, spontaneous pain, swelling, antibiotic and analgesic requirements of the patients were evaluated during clinical examinations performed postoperatively after 2 and 7 days. RESULTS: There were no statistically significant differences between groups in terms of VAS scores following the intracanal medicament application (p > 0.05). However, compared to the patients of 20-34 and 50-65 age groups, greater VAS scores were observed in patients of 35-49 age groups at 12 h, and 3, 4, 7 days (p < 0.05). Flare-up was observed in only one patient in the CHX gel group, and no flare-up was observed in other groups. CONCLUSIONS: Similar postoperative pain incidence in all experimental groups indicates that all three medicaments are clinically acceptable in inter-appointment management of retreatment cases in terms of post-endodontic pain and flare-up. CLINICAL RELEVANCE: In this randomized clinical trial, three different intracanal medicaments were utilized in nonsurgical endodontic retreatment and their effect on postoperative pain and flare-up incidence was examined. Thus, this study will be a significant contribution in the decision-making during clinical practice; since there are a limited number of prospective clinical trials in the literature about the severity of pain following retreatment procedures including intracanal medicament use.

Risk Factors for Periprosthetic Femoral Fractures After Cementless Total Hip Arthroplasty.

BACKGROUND: The present study aimed to identify the risk factors of periprosthetic femoral fracture (PFF) after cementless total hip arthroplasty and rank them based on importance. METHODS: The age, sex, body mass index (BMI), osteoporosis, canal flare index (CFI), canal bone ratio (CBR), canal calcar ratio (CCR), stem design, and stem canal fill ratio (P1, P2, P3, and P4) of the proximal femoral medullary cavity of 111 total hip arthroplasty patients who had PFF and 388 who did not have PFF were analyzed. Independent-samples student t-tests were used for continuous variables, and Chi-square tests were used for categorical variables. The importance rankings of influencing factors were assessed using a random forest algorithm. Dimensionally reduced variables were then incorporated into a binary logistic regression model to determine the PFF-related risk factors. RESULTS: The mean age, BMI, CBR, CCR, and incidence of osteoporosis were higher in cases of PFF (all P < .001), while the mean CFI, P1, P2, P3, and P4 were lower in cases of PFF (P < .001, P = .033, P = .008, P < .001, and P < .001, respectively). Additionally, the stem design was also statistically associated with PFF (P < .001). Multivariate logistic regression revealed that advanced age, higher BMI, osteoporosis, stem design, lower CFI, higher CBR, higher CCR, lower P1, lower P2, lower P3, and lower P4 were the risk factors of PFF (P < .001, P < .001, P < .001, P < .001, P < .001, P = .010, P < .001, P = .002, P < .001, P < .001, and P = .007, respectively). The ranked importance of the risk factors for PFF was P3, CFI, osteoporosis, CBR, age, P4, P1, stem design, CCR, BMI, and P2. CONCLUSIONS: Lower P3, lower CFI, osteoporosis, higher CBR, advanced age, lower P4, lower P1, stem design, higher CCR, higher BMI, and lower P2 increased the risk of PFF.

The Impact of Bronchiectasis on the Clinical Characteristics of Non-Severe Asthma.

Current literature primarily delves into the relationship between bronchiectasis and severe asthma, and only a few studies have evaluated the impact of bronchiectasis in patients with non-severe asthma. Therefore, this study investigated the clinical impact of bronchiectasis in patients with non-severe asthma. A prospective observational study of 140 non-severe asthmatic patients with (bronchiectasis group) and without bronchiectasis (control group) was conducted between September 2012 and February 2022. The bronchiectasis and control groups were compared in terms of demographics, lung function, asthma control test (ACT) results, exacerbation history, and respiratory medications. Among 140 non-severe asthmatic subjects, approximately 15.7% (n = 22) had bronchiectasis. The most common type of bronchiectasis was cylindrical type (90.7%). The left lingular division was the most frequently involved lung lobe (20.4%). There were no significant differences in the demographics (age, sex, body mass index, smoking history, and comorbidities) or ACT results between the 2 groups. The bronchiectasis group used inhaled corticosteroids/long-acting ß2-agonists (P = 0.074) and mucolytics (P < 0.001) more frequently than the control group. Compared to the control group, the bronchiectasis group had lower forced expiratory volume in 1 second (FEV1) (L) (1.9 ± 0.7 L vs. 2.3 ± 0.9 L, P = 0.039) and FEV1%predicted (67.2 ± 22.2%predicted vs. 77.1 ± 20.0%predicted, P = 0.038). The rate of hospital admission to a general ward in the preceding year was significantly higher in the bronchiectasis group compared to those of the control group (23.8% vs. 3.5%, P = 0.005) with an adjusted odds ratio of 6.308 (95% confidence interval, 1.401-28.392). Patients with non-severe asthma and bronchiectasis had lower lung function and more frequent exacerbations requiring hospitalization than those without bronchiectasis. More attention is needed for asthmatic patients with bronchiectasis, even if the asthma is not severe.

Risk Factors for Psoriasis Flares: A Narrative Review.

Psoriasis is a chronic inflammatory cutaneous disease with multifactorial pathogenesis involving both genetic and environmental factors as well as the innate and acquired immune response. Several triggering factors may exacerbate or worsen the disease. In this context, we performed a review manuscript with the aim of investigating current literature on psoriasis risk factors, also showing possible mechanisms by which they act on psoriasis. Globally, risk factors can be divided in classic risk factors (eg, mechanical stress, infections and dysbiosis of the skin, common drugs, environment and pollution, lifestyle, psychological stress, hormonal and metabolic alterations) which have long been known to be responsible for worsening and/or reoccurrence of psoriatic manifestations, and emerging risk factors (eg, biological drugs, immunotherapy for oncologic disease, Covid-19, and vaccines) defined as those newly identified risk factors. Accurate patient information and monitoring of risk factors as well as planned follow-ups may help to prevent and treat the worsening of psoriasis and consequently improve the quality of life of psoriatic patients.

Impact of COVID-19 Pandemic on Patients With Rheumatic Diseases in Medina, Saudi Arabia: An Observational Cross-Sectional Study.

INTRODUCTION: The Coronavirus disease of 2019 (COVID-19) pandemic undoubtedly ranks among the most health-impacting pandemics throughout medical history. Although the COVID-19 global public health emergency has ended, lessons need to be learned to be more ready to face similar pandemics in the future. Few studies in Saudi Arabia discuss the impact of the COVID-19 pandemic on autoimmune rheumatic disease (AIRD) patients. Thus, this study was conducted to elaborate on the effects of the COVID-19 pandemic on AIRD patients and rheumatology practices in Saudi Arabia.  Methods: This observational cross-sectional study was conducted among patients aged over 14 with AIRD using a pre-designed validated survey questionnaire. Data were collected from AIRD patients who were following up between November 2021 to April 2022 at the Rheumatology Clinic of King Fahad General Hospital in Madinah City, Saudi Arabia. This center was chosen as being the main hospital in the city following patients of AIRD. RESULTS: A total of 324 patients were included in our study, with the majority (n=264, 81.5%) being females. The mean age was 44.42±14.4 years. Clinical data revealed that 115 (35.5%) of our patients experienced mild COVID-19 infection, 19 (5.9%) suffered from respiratory insufficiency, and seven (2.2%) required admission to the intensive care unit (ICU). Non-compliance to medication was recorded at 25.2%. There were 115 (35.5%) patients who had an AIRD flare that was significantly higher among those who were not adherent to the medications (p<0.001). Disease flare was also significantly seen among patients who were not on prednisone or were on low doses of prednisone (p<0.001). The majority (n=33, 97.1%) of the 34 infected patients who had an AIRD flare had their flare-up at the same time as their COVID-19 infection (p<0.001). COVID-19 vaccination rate was 87.7% (n=284). The most common reason for non-vaccination in 40 (12.3%) patients was the patients' concern about disease flare-ups by the vaccine or interference of the vaccine with their medication (n=16, 4.9%). CONCLUSION: Our study showed a 35.5% (n=115) COVID-19 infection rate. The majority of our AIRD patients sustained minor infections that did not require hospitalization or ICU admission. The majority of the patients who underwent a severe COVID-19 infection course were not on prednisolone or were on low-dose prednisone. Due to COVID-19 restrictions and drug shortages, one in four patients (25.3%) stopped taking their medications and was significantly found to have a high prevalence of underlying AIRD flare. Despite the high vaccination rate, disease flare was the biggest concern for those who were not immunized. Although the COVID-19 pandemic has ended, doctors should be aware of risk factors associated with severe AIRD outcomes that should be balanced based on the infection severity, underlying disease flares, and patient-centered education about medication adherence and vaccination.

Gas flaring: technicalities, challenges, and the economic potentials.

Gas flaring has been identified as a major contributor to global warming and climate change. It is used either as a safety measure or as a means of disposal for technical or economic reasons. Over 250 toxins have been directly/indirectly associated with gas flaring and its associated emissions. Most of these toxins have been known to have significant inimical impacts on humans' health, plant biodiversity, and the environment. With the recent rise in global energy insecurity, several EU countries have either returned to coal power generation or extended the lifetime of their coal-fired plants thereby increasing anthropogenic carbon emissions. This increase in carbon emission has necessitated the re-evaluate of gas flare practices vis-à-vis the environmental challenges and the financial potentials. This paper presents a holistic review of gas flaring, its types, composition, systems design, estimation methods, social and environmental challenges, the abatement measures, and the re-utilization strategies. It identified the potential to save a minimum of US$10.4 billion globally if more stringent gas flare abatement measures were pursued. Furthermore, the paper highlights the recent trends in flare gas re-utilization technologies such as the production of bioproducts which has been reported to hold a potential for an annual production of about 148 million bbl of biocrude and 67 million metrics of algae protein from 140 bcm of globally flared gas. Finally, it explored the possible way forward and stringent measures that can be pursued to disincentivize gas flare and also increase investments in gas processing technologies.

Impact of Psychosocial Factors on the Activity of Crohn's Disease: A Cross-Sectional Analysis of Social Support, Stress, and Flare-Up Incidence.

Background/Objectives: Crohn's disease is a chronic and debilitating intestinal disorder that alternates between remission and active flare-ups, often leading to hospitalization. Social support is known to enhance adaptation to the disease and modulate stress perception in patients, while stress may exacerbate symptoms. The aim of this study was to examine the roles of perceived stress and social support in Crohn's disease and their impact on the frequency of flare-ups. Methods: A cross-sectional observational study was conducted, assessing stress and social support in a cohort of 91 patients with Crohn's disease during flare-up and remission phases. The Perceived Stress Scale (PSS-14) and a Social Support Questionnaire were utilized for evaluation. We examined the relationship between stress and social support in Crohn's disease. The interaction between the variables studied was also observed, considering the stage of the disease. Finally, we carried out an analysis of the influence of these two variables on the development of flare-ups in Crohn's disease. Results: The study revealed that patients experience higher stress levels during flare-ups and that these levels are amplified by a lack of social support. A significant relationship was identified between the levels of social support and the occurrence of flare-ups, indicating that better social support is associated with fewer flare-ups. Conclusions: Patients with Crohn's disease in the flare-up phase are subject to considerable stress. A deficit in social support is linked to an increase in stress levels. The interaction between social support and stress plays a critical role in the development of flare-ups.

Prolonged Disease Control Despite ALK Inhibitor Discontinuation in Advanced ALK-Positive NSCLC.

Introduction: EML4-ALK is an oncogenic driver, seen in around five per cent of advanced non-small-cell lung cancer (NSCLC) patients, which can be targeted with anaplastic lymphoma kinase tyrosine kinase inhibitors with great response rates. Disease flare refers to sudden rapid disease worsening on tyrosine kinase inhibitors (TKI) discontinuation, which is associated with shorter survival and worse outcomes. Here, we review cases previously published in the literature where patients developed disease flares, and contrast this with our patients who had prolonged survival despite TKI discontinuation. Case description: We report three different patients with advanced ALK-positive NSCLC seen at our institute, who had EML4-ALK translocation variant 1 oncogenic driver on next-generation sequencing. They received treatment with several different ALK inhibitors before opting to discontinue TKI. They were able to come off TKI safely without developing disease flare and had prolonged survival. Discussion: Shorter time to progression on TKI, presence of symptoms with disease progression or central nervous system/pleural metastasis have been previously linked with development of flare, although this was not seen in our case series. Tumour response at the time of treatment discontinuation, line of therapy, overall disease burden, fusion variant and co-alteration status can affect the prognosis of these patients after ALK TKI cessation. In particular, variant 1 and wild-type TP53 status may be a suitable patient population for dose optimisation strategies. Intermittent TKI dosing strategies may help to avoid acquiring resistance mutations and prevent long-term treatment toxicities. Conclusion: It is important for clinicians to identify patients at risk for developing disease flare on TKI discontinuation to improve outcomes. Intermittent TKI dosing strategies require further investigation. LEARNING POINTS: Patients who develop disease flare after cessation have poor survival and worse outcomes.Certain phenotypic and molecular characteristics of the tumour may help clinicians identify which patients are likely and which are unlikely to develop disease flare on TKI discontinuation.Advanced ALK-positive NSCLC with variant 1 and wild-type TP53 may be a suitable patient population for intermittent TKI dosing investigations.

The Contribution of Sleep Quality and Psychological Factors to the Experience of Within-Day Pain Fluctuations Among Individuals With Temporomandibular Disorders.

We assessed the impact of day-to-day sleep quality and psychological variables (catastrophizing, negative affect, and positive affect) to within-day pain fluctuations in 42 females with painful temporomandibular disorders (TMD) using electronic diaries. More specifically, we examined the contribution of these variables to the likelihood of experiencing pain exacerbations defined as 1) an increase of 20 points (or more) in pain intensity on a 0 to 100 visual analog scale from morning to evening, and/or 2) a transition from mild-to-moderate pain over the course of the day; and pain decreases defined as 3) a decrease of 20 points (or more) in pain intensity (visual analog scale) from morning to evening, and/or 4) a reduction from moderate-to-mild pain over the day. The results indicated significantly main effects of sleep on both pain exacerbation outcomes (both P's < .05), indicating that nights with better sleep quality were less likely to be followed by clinically meaningful pain exacerbations on the next day. The results also indicated that days characterized by higher levels of catastrophizing were associated with a greater likelihood of pain exacerbations on the same day (both P's < .05). Daily catastrophizing was the only variable significantly associated with within-day pain decrease indices (both P's < .05). None of the other variables were associated with these outcomes (all P's > .05). These results underscore the importance of addressing patients' sleep quality and psychological states in the management of painful TMD. PERSPECTIVES: These findings highlight the significance of sleep quality and pain catastrophizing in the experience of within-day pain fluctuations among individuals with TMD. Addressing these components through tailored interventions may help to alleviate the impact of pain fluctuations and enhance the overall well-being of TMD patients.

Hyperuricemia and intravenous fat emulsion are risk factors for gout flares during active gastrointestinal bleeding: a case control study.

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

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 screen the 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.

Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review.

T-cell engagers (TCE) are cancer immunotherapies that have recently demonstrated meaningful benefit for patients with hematological malignancies and solid tumors. The anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events. By mobilizing T-cells directly at the contact of tumor cells, TCE mount an obligatory and immediate anti-tumor immune response that could result in diverse reactions and adverse events. Cytokine release syndrome (CRS) is the most common reaction and is largely confined to the first drug administrations during step-up dosage. Cytokine release syndrome should be distinguished from infusion related reaction by clinical symptoms, timing to occurrence, pathophysiological aspects, and clinical management. Other common reactions and adverse events with TCE are immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), infections, tumor flare reaction and cytopenias. The toxicity profiles of TCE and CAR-T cells have commonalities and distinctions that we sum-up in this review. As compared with CAR-T cells, TCE are responsible for less frequently severe CRS or ICANS. This review recapitulates terminology, pathophysiology, severity grading system and management of reactions and adverse events related to TCE.

Definitions of rheumatoid arthritis flare and how they relate to patients' perspectives: A scoping review of qualitative and quantitative evidence.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by intermittent flares of disease activity with a significant impact on patients' lives. However, distinguishing flare from daily symptom variation may be approached differently by patients and healthcare providers, potentially hampering shared decision-making when treating RA. OBJECTIVES: To provide a comprehensive overview of RA flare definitions reported in the published literature, and to compare these with patients' perceptions of the flare concept according to qualitative evidence. METHODS: A systematic search was conducted on August 30th, 2022, and updated on September 30th, 2023, for both quantitative and qualitative studies reporting "flare" or related terms in the context of RA. We searched the following databases: Pubmed, EMBASE, Web of Science, Cochrane Library, and CINAHL. Definitions of RA flare reported in quantitative studies were summarized descriptively. In parallel, a thematic synthesis of qualitative studies was performed to outline patients' views on the concept of flare, and to compare these with the currently used definitions. RESULTS: Among 32,864 potentially eligible records, 304 studies were included, 5 of which used qualitative/mixed methods to study patients' perceptions of flare. Remarkably, 62 different definitions for RA flare were reported, with many studies reporting more than one. The most commonly used definitions (54 %) were based on disease activity indices, with DAS28-based definitions the most widely applied (84 %). For each of the disease activity indices, several different cutoffs to define flares were used. Various definitions based on physician report were applied in 24 % of cases, while patient-reported criteria represented only 15 % of the applied definitions. Thematic synthesis of the qualitative/mixed-methods studies highlighted the multidimensional impact of flares on patients' lives, resulting in five sequential overarching themes: "Living with RA: a balancing act", "Flare: a disturbance of this balance", "The biopsychosocial impact of flares", "Self-management: the first line of defense", and "Medical help: the last resort". In turn, these five themes were underpinned by a central theme of "Uncertainty and variability". CONCLUSION: We found a striking heterogeneity regarding the conceptualization and measurement of RA flare in the published literature. Although qualitative evidence highlighted the considerable impact of flares on patients' wellbeing, the majority of reported flare definitions were not based on patient report. There is a need to bridge this gap by aligning patients' and healthcare professionals' views on what distinguishes a flare from acceptable symptom variability when living with RA.