Efficacy and safety of mycophenolate mofetil in patients with immune thrombocytopenic purpura: a systematic review and meta-analysis.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP. METHODS: We systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design. RESULTS: Nine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly. CONCLUSION: This systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/.

Cardiovascular Risk Among Saudi Adults with Prediabetes: A Sub-Cohort Analysis from the Heart Health Promotion (HHP) Study.

Background: This study aimed to estimate the prevalence of prediabetes among Saudi adults and to evaluate their risk of developing cardiovascular diseases. Methods: This is a cohort of 2470 Saudi adults attending employee clinics in the university hospital. WHO-STEPs approach was used to collect sociodemographic (age, gender, and education), clinical (body mass index and blood pressure) and laboratory data (HbA1c, lipid profile and vitamin D concentration). Prediabetes was defined according to HbA1c level of 5.7-6.4%. Cardiovascular risk (CVR) scores were evaluated using the Framingham Risk Score. SPSS was used for data analysis to investigate the relation between different CVR and prediabetes. Results: Prediabetes affected 25.1% of the study population. Males had higher rates of prediabetes than females (27.5% versus 23.5%). The prevalence of prediabetes increased from 11.6% among young individuals (18-29 years) to 56.0% among participants 60 years and older. Prediabetes patients exhibited considerably higher levels of all cardiovascular risk factors and nearly half of them (49.3%) had at least two risk factors. The prevalence of intermediate CVR among prediabetics was 13.2% compared to just 2.9% among the normal group, and high CVR was defined in 3.7% among prediabetics compared to only 1.7% in the normal group. Having prediabetes increased the odds to develop higher CVR of 2.64 times compared to those without prediabetes (OR = 2.64, 95% CI = 1.51-4.64) and the level of vitamin D did not affect the odds of CVR. Conclusion: Prediabetes is quite prevalent among Saudi adults, and they are at a higher risk of cardiovascular diseases. Patients with prediabetes have higher cardiac risk scores when compared to normal participants across the whole spectrum of (25(OH)D) concentrations. Additionally, no significant correlation was observed between HbA1c and (25(OH)D) levels in prediabetics or normoglycemic subjects.

Effect of the COVID-19 Pandemic on the Rate of Interventional Pain Management Therapies. Could the Application of Personal Protective Equipment Help?

BACKGROUND: Chronic pain symptoms are distressing conditions that necessitate regular visits to  pain therapists and may require interventions, however, the COVID-19 pandemic has caused patients and their therapists to limit both visits and interventions with the transition to telehealth, with little or no preparation or training. This has resulted in the extensive use of over-the counter analgesia and corticosteroids. OBJECTIVES: Our study aimed to evaluate the effect of the COVID-19 pandemic on the rates of counseling and interventional pain management therapies (IPMT), and determine the effects of implementing an infection control program (ICP) and mandating personal protective equipment (PPE) on these rates. STUDY DESIGN: Prospective multicenter survey, based on an online self-assessed questionnaire. SETTING: Departments of Anesthesia, Pain, Intensive Care Unit, Physical Medicine, Rheumatology, and  Rehabilitation at Egyptian University hospitals. METHODS: A self-assessed questionnaire was uploaded on Google forms and links were sent to enrolled therapists with an identification number to allow self-administration and privacy. Feedback was analyzed by 2 authors who were blinded to the identity of the responders. RESULTS: A total of 57.9% of responders increased their patients' contact by phone and video conference. Within 1-4 months after the outbreak began, 59% stopped in-person contact and 38.2% stopped their IPM practice. Prescriptions of analgesics and oral steroids increased by about 50%. The majority of responders complained of a shortage of ventilation appliances in their workplaces. About 50% of them always use ICP, 85% use surgical masks, 61% use gloves, and 45% wear gowns when meeting with patients. After the application of PPE, 45.5% of responders increased their consultation rate and 40% increased their rate of IPMT. LIMITATIONS: This study is limited to being a national study, and so lacked comparative data. CONCLUSION: The COVID-19 outbreak seriously affected the rates of in-person consultations and IPMT for patients with chronic pain and increased the rates of consumption of analgesia and oral steroids. Most responders reported a shortage of PPE especially ventilation appliances in workplaces. A high percentage of responders lack interest in ICP and PPE, despite the positive effects of its application on consultation and IPMT rates.

Dichotomous response to transforming growth factor ß after T cell receptor activation by naive CD4+ T cells from DBA/1 mice: enhanced retinoic acid receptor-related orphan nuclear receptor γt expression yet reduced FoxP3 expression.

OBJECTIVE: To investigate the molecular mechanism for biased interleukin-17 (IL-17) production by DBA/1 CD4+ T cells upon T cell receptor (TCR) and transforming growth factor ß (TGFß) stimulation. METHODS: Purified naive CD4+ T cells were stimulated with anti-CD3/CD28 under Th1, Th2, Th17, and induced T regulatory (iTreg) cell conditions. Cytokine production was assayed by intracellular staining and enzyme-linked immunosorbent assay. Expression of transcription factors was determined by reverse transcription-polymerase chain reaction, flow cytometry, and immunoblotting techniques. RESULTS: Naive CD4+ T cells from DBA/1 mice produced more IL-17 under Th17 cell polarizing conditions as compared with those from C57BL/6 or BALB/c mice. Further investigation revealed no difference among the strains in terms of CD4+ T cell survival, upstream TCR signaling, or CD69 expression or in the phosphorylation of STAT-3 and expression of suppressor of cytokine signaling 3 that positively or negatively regulate IL-17 cell production. However, DBA/1 CD4+ T cells expressed increased levels of retinoic acid-related orphan receptor γt (RORγt). Furthermore, under iTreg cell polarizing conditions, DBA/1 CD4+ T cells showed a strikingly reduced level of FoxP3 expression. When interferon-γ and IL-4 were blocked, FoxP3 expression increased but remained lower in DBA/1 CD4+ T cells following exposure to TGFß as compared with C57BL/6 CD4+ T cells. Moreover, DBA/1 CD4+ T cells showed reduced phosphorylation of Smad2 and Smad3 under both Th17 and iTreg cell polarizing conditions. CONCLUSION: These results indicate that naive CD4+ T cells from DBA/1 mice have a dichotomous response to TGFß: enhanced RORγt, yet reduced FoxP3, up-regulation. This observation may help to elucidate the branch point of TGFß signaling that leads to skewed Th17, but reduced iTreg, cell differentiation.