The prescription and monitoring of conventional synthetic disease-modifying anti-rheumatic drugs: British Society for Rheumatology guideline scope.

This guideline will provide up-to-date, evidence-based recommendations on the safe use of non-biologic DMARDs, also called conventional synthetic DMARDs (csDMARD), across the full spectrum of autoimmune rheumatic diseases. The guideline will update the guideline published in 2017 and will be expanded to include people of all ages. Updated information on the monitoring of DMARDs and vaccinations will be included. The guideline will be developed using the methods and processes described in the British Society for Rheumatology's 'Creating clinical guidelines: our protocol', updated 2023.

Effectiveness of digital health interventions on adherence and control of hypertension: a systematic review and meta-analysis.

BACKGROUND: Hypertension, a risk factor for developing cardiovascular disease, is becoming increasingly prevalent worldwide. Digital health is now widely utilized for hypertension management, and numerous studies have assessed its effectiveness. OBJECTIVE: The review aims to analyse the effectiveness of digital health (i.e., mobile health (mHealth), telehealth, and the combination of mHealth & telehealth) on hypertensive patients, concerning three key areas: clinical outcomes, medication adherence, and adherence to lifestyle changes, as compared to standard care. METHODS: The review followed the PRISMA framework. Eight electronic databases were scanned for randomized control trials focusing on the effects of mHealth or telehealth on hypertensive patients, published between 2010 and 2023. All processes were conducted by the first two authors independently. A meta-analysis was conducted for quantitative data, while a narrative synthesis was conducted for qualitative data. RESULTS: In total, 74 studies involving 92 686 participants were identified. The meta-analysis favoured the interventions, revealing a significant decrease in systolic blood pressure and diastolic blood pressure for mHealth, telehealth and mHealth & telehealth groups. Nevertheless, medication adherence showed improvement only in the mHealth group, while blood pressure control showed improvement in both mHealth and mHealth & telehealth groups, and BMI showed improvement only in the mHealth group. Evidence for adherence to physical activity and DASH diet/salt intake remained inconclusive. CONCLUSION: In general, mHealth and telehealth have demonstrated their merits in improving the clinical outcomes of hypertensive patients.

Validating the Prognostic Utility of the ABCD-GENE Score in Asian Patients with Acute Coronary Syndrome Patients on Clopidogrel.

Background: The ABCD-GENE score, which links cytochrome P450 2C19 (CYP2C19) phenotype and high platelet reactivity (HPR) to the risk of major adverse cardiovascular events (MACE) in clopidogrel users, has been validated in white and Japanese populations. The prognostic implications of the score in other Asian cohorts, however, have been largely unchartered. The aim of this study was to validate the prognostic utility of the ABCD-GENE score in a heterogeneous Asian acute coronary syndrome (ACS) cohort. Methods and Results: In this single-centre, retrospective cohort evaluation of 423 ACS patients, the objectives were to characterise the best cut-off score for MACE prognostication by comparing the adjusted 1-year risk of MACE between groups above and below the candidate cut-off scores using Cox regression; and for on-clopidogrel HPR prediction using receiver operating characteristic (ROC) analysis and Youden's index. In the adjusted Cox model, an ABCD-GENE score cut-off at 10 points significantly predicts the 1-year risk of MACE (adjusted HR 3.771; 95% CI [1.041-13.661]). Female sex, baseline LDL, history of ACS and angiotensin receptor blocker use were additional independent predictors of MACE. On ROC analysis the ideal cut-off for HPR prediction was 7 points. However, that did not independently predict the 1-year risk of MACE (adjusted HR 1.595; 95% CI [0.425-5.989]). Conclusion: The original ABCD-GENE score 10-point cut-off moderately predicts MACE in a heterogeneous, Asian ACS population at 1 year. Additional predictors of MACE were also identified in the present cohort, and these findings should be prospectively validated in larger ACS cohorts.

CAR T-cell therapies in China: rapid evolution and a bright future.

Chimeric antigen receptor (CAR) T-cell therapies have achieved remarkable success in the treatment of haematological malignancies. Over the past 9 years, the use of CAR T-cell therapies has expanded throughout China, from the first clinical trials of CAR T cells conducted in 2013, to the world's largest number of CAR T-cell-related clinical trials in 2017, to a cumulative US$2·37 billion in funding for cell therapy companies in 2021, and a significant growth in the number of CAR T-cell-related clinical trials and basic research. This strong increase in activity is the result of a culmination of factors in China: strong government support, capital inflow, large patient demand, a unique health-care system, and the efforts of Chinese physicians and scientists. This Series paper provides an overview of the scope of CAR T-cell clinical trials in China (especially in the field of haematological malignancies), analyses the relevant policies, summarises the characteristics of corporate and capital support, and explores the achievements and challenges of CAR T-cell therapy in China to provide a better understanding for further promoting the development of cellular therapy and its clinical application.

The role of pre-treatment and mid-treatment 18F-FDG PET/CT imaging in evaluating prognosis of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS).

BACKGROUND: It has been reported the prognostic value of MTV in predicting the disease prognosis of peripheral T-cell lymphoma (PTCL) through pre-treatment PET/CT imaging. However, these are limited data on pretreatment evaluation and prognosis assessments of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS). This study aimed to determine the prognostic values of pre-treatment and mid-treatment total metabolic tumor volume (MTV), total lesion glycolysis (TLG), and Deauville 5-Point Scale (D-5PS) in accessing the prognosis of PTCL-NOS. METHODS: A retrospective analysis was conducted in 31 patients with pathologically diagnosed PTCL-NOS. These patients have undergone positron emission PET/CT scanning before and during chemotherapy. Follow-ups were also done to investigate the 2-year progression-free survival (PFS) and Overall Survival (OS) of these patients. During [Formula: see text]F-fluorodeoxyglucose ([Formula: see text]F-FDG) PET/CT scans, the MTV and TLG were recorded. Meanwhile, [Formula: see text]MTV and [Formula: see text]TLG were calculated. Furthermore, the receiver operating characteristic (ROC) curve was employed to classify and to define the threshold values. On the other hand, the mid-chemotherapy assessment and staging of these 31 patients were done by utilizing D-5PS. Subsequently, based on the D-5PS scores obtained, these patients were grouped into two categories: a group of patients with a score of <4 and another group with [Formula: see text]4 points. For these two groups of patients, the survival analysis was done by Kaplan-Meier analysis and a multivariate COX regression model. Moreover, Pearson's chi-square test ([Formula: see text] test) and Spearman rank correlation coefficient were used to comparing the collected data, respectively. RESULTS: During the 2-year follow-up period, 15 out of the 31 patients experienced disease progression. The optimal threshold values for both baseline MTV and TLG were 158.16 cm[Formula: see text] and 677.40.Additionally, the difference in 2-year PFS between the progressive and non-progressive groups was statistically significant ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text]), significant between-group difference was detected for MTV and for TLG ([Formula: see text], [Formula: see text]; [Formula: see text], [Formula: see text]). On the other hand, when these patients were classified into two groups according to the mid-chemotherapy Deauville score of <4 and [Formula: see text]4, the statistical difference of 2-year PFS between these two groups was significant, too ([Formula: see text], [Formula: see text]),but there is no significant between-group difference in OS ([Formula: see text], [Formula: see text]). COX analysis revealed that D-5PS are the independent factors influencing PFS, while MTV is the independent influencing factor of OS. CONCLUSION: The baseline total MTV obtained by PET/CT scanning, and D-5PS are crucial prognostic factors in evaluating the prognosis of PTCL-NOS.

Tumor Burden Measured by 18F-FDG PET/CT in Predicting Efficacy and Adverse Effects of Chimeric Antigen Receptor T-Cell Therapy in Non-Hodgkin Lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy has exhibited promising clinical outcomes in treating relapsed/refractory (R/R) B-cell hematologic malignancies. Current studies have shown a close correlation between baseline tumor burden and therapeutic response in CAR-T cell therapy. However, the roles of PET/CT metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), remain unclear in this setting. In this study, we retrospectively reviewed 41 R/R NHL patients. 18F-FDG PET/CT was used to measure the average standardized uptake value (SUVavg), MTV, and TLG of the lymphomatous lesions. These patients were divided into two groups according to the optimal cutoff values of respective PET/CT metabolic parameters. The multivariate analysis depicted that early post-therapy SUVavg (HR: 1.418, 95% CI: 1.029, 1.955; p = 0.033) and MTV (HR: 1.001, 95% CI: 1.000, 1.002; p = 0.041) were independent risk factors associated with OS and PFS, respectively. Patients with baseline SUVavg < 4.36 achieved a superior 1-year OS rate than the SUVavg ≥ 4.36 group (100.0% vs. 44.9%, p = 0.019). For the patients with lower values in early post-therapy SUVavg (<2.60) (51.1% vs. 0%, p < 0.001), MTV (<0.55 cm3) (53.6% vs. 0.0%, p = 0.001), and TLG (<1.54) (53.6% vs. 0.0%, p = 0.001), their 1-year PFS rates were higher than the compared groups. Moreover, patients with higher baseline tumor burdens were found to have significantly increased CRS incidence and cytokine levels. In conclusion, the PET/CT metabolic parameters are closely related to OS, PFS, and CRS in R/R NHL patients treated with CAR-T cells. This study may pave the way for building a comprehensive assessment system of tumor burden using 18F-FDG PET/CT, which can optimize therapeutic and supportive approaches in CAR-T cell therapy.

CAR-T cells: the Chinese experience.

INTRODUCTION: Chimeric antigen receptor T (CAR-T) cells are harnessed to identify and lyse malignant cells specifically, efficiently, and independently of the major histocompatibility complex (MHC). As a result, prognoses of relapsed or refractory (R/R) B cell hematological malignancies as well as limited types of solid tumors, have been ameliorated to a great extent. In China, a rising number of clinical trials that contribute to the development of novel CAR-T therapeutic strategies have been conducted on an extensive scale. AREAS COVERED: We summarize registered clinical trials related to CAR-T therapy conducted in China by evaluating various parameters such as distribution, study phase, CAR structure, target antigen, and disease. The efficacy, toxicity, and, more importantly, the new strategies for optimization of CAR-T therapy of Chinese studies and clinical trials are elaborated in detail. EXPERT OPINION: In terms of the number of CAR-T clinical trials, China is second to the USA, registering approximately 33% of trials worldwide. China's extensive explorations and breakthroughs in the search of novel target antigens, optimization of CAR structure, cocktail CAR-T therapy, combination therapy, and extension of CAR-T cell applications, imply that we are currently on the verge of a revolution in CAR-T therapy.

CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges.

The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.

Switching from Ticagrelor to Clopidogrel in Asian Patients with ST-Elevated Myocardial Infarction - A Time Dependent Analysis Study.

BACKGROUND: Ticagrelor is initially prescribed after an ST-elevated myocardial infarction (STEMI) and this may be followed by a switch to clopidogrel. However, studies involving antiplatelet switching have been conflicting and only assessed at a specific switch point. The objective of this study was to investigate switching from ticagrelor to clopidogrel in an Asian population, after accounting for various switch points as in a real-world environment. METHODS: A retrospective cohort of 349 STEMI patients started on ticagrelor and aspirin were followed-up for 1 year after a percutaneous coronary intervention that was performed between June 2014 and November 2016. Patients who switched to clopidogrel were compared with those who remained on ticagrelor. Outcomes measured were major adverse cardiac and cerebrovascular events (MACCEs) and clinically significant bleeding (CSB). Cox regression analysis with switch status as a time-dependent covariate was performed. RESULTS: The switched group was not associated with MACCEs or CSB [10.0% vs. 13.8%; hazard ratio (HR) = 0.484; 95% confidence interval (CI): 0.196-1.191; p = 0.114]. There was also no significant difference when MACCEs were analyzed alone (2.3% vs. 7.7%; HR = 0.518; 95% CI: 0.137-1.957; p = 0.332). For CSB, the switched group was less likely to have an event (7.8% vs. 8.5%; HR = 0.298; 95% CI: 0.091-0.982; p = 0.047). CONCLUSIONS: This study showed no significant difference between staying on ticagrelor and switching to clopidogrel. Switching might decrease the incidence of CSB. De-escalation from ticagrelor to clopidogrel could translate to cost savings for Asian patients without compromising safety and efficacy.

Weathering the storm: COVID-19 infection in patients with hematological malignancies.

The coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a matter of months, this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents. In patients with COVID-19, underlying chronic diseases and comorbidities are associated with dismal treatment outcomes. Owing to their immunosuppressive status, patients with hematological malignancies (HMs) are at an increased risk of infection and have a worse prognosis than patients without HMs. Accordingly, intensive attention should be paid to this cohort. In this review, we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs. Furthermore, we briefly describe customized management strategies and interventions for this susceptible cohort. This review is intended to guide clinical practice.

A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma / 医学前沿

The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy.

Weathering the storm: COVID-19 infection in patients with hematological malignancies / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within a matter of months, this highly contagious novel virus has led to a global outbreak and is still spreading rapidly across continents. In patients with COVID-19, underlying chronic diseases and comorbidities are associated with dismal treatment outcomes. Owing to their immunosuppressive status, patients with hematological malignancies (HMs) are at an increased risk of infection and have a worse prognosis than patients without HMs. Accordingly, intensive attention should be paid to this cohort. In this review, we summarize and analyze specific clinical manifestations for patients with coexisting COVID-19 and HMs. Furthermore, we briefly describe customized management strategies and interventions for this susceptible cohort. This review is intended to guide clinical practice.

Intestinal knotting: A case report and brief literature review

@#this condition, one bowel loop makes a knot with anadjacent bowel loop, resulting in mechanical obstructionand even gangrene of the bowel. We present a case of ayoung girl with ileo-ileal knotting resulting in a closed-loopobstruction and gangrene of the small bowel loop. This is adifficult condition to diagnose; a high index of suspicion andearly surgical intervention are essential to reduce morbidityand mortality.

Autophagic Degradation of Misfolded Nuclear Receptor Co-repressor (NCoR) Is Linked to the Growth of Tumor Cells in HBX Positive Hepatocellular Carcinoma (HCC).

Hepatitis B virus (HBV) is causally linked to hepatocellular injury and cell death, which are followed by hepatocellular carcinoma (HCC) after a long latent period. The HBV derived X protein (HBX) is the most potent carcinogenic factor for HCC, however, the molecular mechanism of HBX-induced transformation of hepatic cells in HCC is poorly understood. We have shown that nuclear receptor co-repressor (NCoR) is essential for the spatial repression of global transcription by the promyelocytic leukemia oncogenic domains (PODs), a frequent target of viral oncoproteins like HBX and that disintegration of PODs due to misfolded conformation dependent loss (MCDL) of NCoR is linked to promyelocytic and monocytic acute myeloid leukemia (AML). Given the key role of NCoR in cellular homeostasis across various tissue subtypes, we hypothesized that HBX-induced MCDL of NCoR might be linked to HCC through similar mechanism. Based on this hypothesis, the conformation of NCoR in HCC derived tumor cells and primary human tissue sections were analyzed and a selective MCDL of NCoR in HBX positive HCC cells was identified. HBX triggered the misfolding of NCoR through ubiquitination, followed by its degradation by autophagy, thus suggesting a cross talk between ubiquitin proteasome system (UPS) and autophagy lysosomal pathway (ALP) in MCDL of NCoR in HBX positive HCC cells. SiRNA-induced NCoR ablation selectively impaired the growth and survival of HBX positive HCC cells, suggesting a role of MCDL in the growth and survival of HBX positive HCC cells. These finding identify a possible crosstalk between UPS and ALP in the misfolding and loss of NCoR in HBX positive HCC cells and suggest a role of autophagic recycling of misfolded NCoR in the activation of oncogenic metabolic signaling in HCC. The misfolded NCoR reported in this study represents a novel conformation based molecular target which could be valuable in the design and development of tumor cell specific diagnostic and therapeutic approach for HBX positive HCC.

Crime victimization and the implications for individual health and wellbeing: A Sheffield case study.

Public health and criminology have developed largely independently of one another at the research and policy levels so that the links between crime victimization and health status are not well understood. Although it is not difficult to support the idea of crime as a threat to the health of individuals and the wider community, the difficulty lies in quantifying the impact of crime on public health, while controlling other variables, including gender and ethnicity. We report the results of a study, the goals of which were to: develop an understanding conceptually of the relationships between different types of crime (violent and non-violent) and health; explore the impact of victimization on quality of life and physical and psychological wellbeing; investigate the role of social and demographic factors in shaping any relationships. The study is based on 840 responses from a postal survey administered to 4,100 households in Sheffield, England, located primarily in deprived areas where overall crime rates were high. Non-violent crimes were more frequently reported than violent crimes and in general, inner city neighbourhoods were associated with higher violent crime rates. Out of 392 victims of crime, 27% of individuals detailed physical injuries resulting directly from a crime event and 31% had taken some medical steps to treat a crime-related injury. 86% experienced at least one psychological or behavioural change, including stress, sleeping difficulties, loss of confidence, and depression. Logistic regression models estimated victimization risk based on various social and demographic variables. Violent crimes were consistently linked with higher odds of seeking medical treatment and a higher likelihood of experiencing psychological ill health effects or behavioural changes. In comparison, victims of non-violent or property crimes were not significantly associated with mental health or behavioural/lifestyle effects.

Association between Total Daily Doses with duration of hospitalization among readmitted patients in a multi-ethnic Asian population.

Increased length of stay (LOS) in the hospital incurs substantial financial costs on the healthcare system. Multiple factors are associated with LOS. However, few studies have been done to associate the impact of Total Daily Doses (TDD) and LOS. Hence, the aim of this study is to examine the association between patients' LOS upon readmission and their TDD before readmission. A retrospective cross-sectional study of readmission cases occurring from 1st January to 31st March 2013 was conducted at a regional hospital. Demographics and clinical variables were collected using electronic medical databases. Univariable and multiple linear regressions were used. Confounders such as comorbidities and drug related problems (DRP) were controlled for in this study. There were 432 patients and 649 readmissions examined. The average TDD and LOS were 18.04 ± 8.16 and 7.63 days ± 7.08 respectively. In the univariable analysis, variables that were significantly associated with the LOS included age above 75 year-old, race, comorbidity, number of comorbidities, number of medications, TDD and thrombocytopenia as DRPs. In the multiple linear regression, there was a statistically significant association between TDD (ß = 0.0733, p = 0.030) and LOS. Variables that were found significant were age above 75 year-old (ß = 1.5477, p = 0.008), Malay (ß = -1.5123, p = 0.033), other races (ß = -2.6174, p = 0.007), depression (ß = 2.1551, p = 0.031) and thrombocytopenia as a type of DRP (ß = 7.5548, p = 0.027). When TDD was replaced with number of medications, number of medications (ß = 0.1487, p = 0.021), age of 75 year-old (ß = 1.5303, p = 0.009), Malay (ß = -1.4687, p = 0.038), race of others (ß = -2.6499, p = 0.007), depression (ß = 2.1951, p = 0.028) and thrombocytopenia as a type of DRP (ß = 7.5260, p = 0.028) were significant. In conclusion, a significant relationship between TDD and number of medications before readmission and the LOS upon readmission was established. This finding highlights the importance of optimizing patients' TDD in the attempt of reducing their LOS.

Association between number of doses per day, number of medications and patient's non-compliance, and frequency of readmissions in a multi-ethnic Asian population.

OBJECTIVE: To investigate whether number of doses per day and number of medications are significantly associated with the number of readmissions and to study the association of readmission frequency with other medical and socio-demographic variables. METHODS: Retrospective cross-sectional study involving 432 patients who were readmitted within 15 days of previous hospital discharge between January 1, 2013 and March 31, 2013. Relevant medical records were collected from the national electronic databases of every public tertiary hospital in Singapore. Significant variables (p < 0.05) were identified using forward selection and modeled using generalized linear mixed models. RESULTS: A total of 649 unplanned readmissions were reviewed. At a multivariable level, number of readmission was significantly associated with the number of medications (p = 0.002) and number of doses per day (p = 0.003) after adjusting for race, liver disease, schizophrenia and non-compliance. CONCLUSION: Complex medication regimen (i.e. multiple medications and multiple doses per day) is a statistically significant predictor of number of readmissions. Simplifying therapeutic regimens with alternatives such as longer-acting or fixed-dose combination drugs may facilitate better patient adherence and reduce costly readmissions.