The role of BAFF and BAFF-R inhibitors in the treatment of immune thrombocytopenia; a focused review.

Immune thrombocytopenia (ITP) is an autoimmune-driven disease characterized by increased destruction and impaired platelet production resulting in an enhanced risk of bleeding. Immunosuppressant agents are the most common treatment strategies for ITP. Despite their efficacy, these medications often cause unpredictable side effects. Recent investigations revealed that patients with ITP exhibit elevated B-cell activating factor (BAFF) levels in both their spleens and serum. Belimumab, a BAFF inhibitor, illustrated a promising therapeutic avenue for managing ITP by interfering with BAFF activity and long-lived plasma cell production. Both clinical and experimental studies have yielded positive outcomes when combining rituximab with an anti-BAFF monoclonal antibody in treating ITP. In addition, ianalumab, a monoclonal antibody with a dual mechanism that targets BAFF-R and deletes peripheral BAFF-R+ B cells, is currently being used for ITP treatment [NCT05885555]. The upcoming results from novel BAFF inhibitors, such as ianalumab, could offer clinicians an additional therapeutic option for treating ITP.

Epidemiology of substance and opium use among adult residents of Tehran; a comprehensive report from Tehran cohort study (TeCS).

BACKGROUND: The prevalence and burden of substance and opium use have increased worldwide over the past decades. In light of rapid population changes in Tehran, we aimed to evaluate the prevalence of opium and other substance use among adult residents in Tehran, Iran. METHOD: From March 2016 to March 2019, we utilized data from 8 296 participants in the Tehran Cohort Study recruitment phase (TeCS). We calculated the age-sex-weighted prevalence of substance use and the geographic distribution of substance use in Tehran. We also used logistic regression analysis to determine possible determinants of opium use. RESULT: We analyzed data from 8 259 eligible participants with complete substance use data and the average age of participants was 53.7 ± 12.75 years. The prevalence of substance use was 5.6% (95% confidence interval [CI]: 4.6- 7.1%). Substance use was more common in males than females (Prevalence: 10.5% [95% CI: 8.6- 12.6%] vs. 0.5% [95% CI: 0.2- 1.2%], respectively). The age-sex weighted prevalence of substance use was 5.4% (95% CI: 4.6-7.1%). Moreover, opium was the most frequently used substance by 95.8% of substance users. Additionally, we found that male gender (Odds ratio [OR]: 12.1, P < 0.001), alcohol intake (OR: 1.3, P = 0.016), and smoking (OR: 8.5, P < 0.001) were independently associated with opium use. CONCLUSIONS: We found that the prevalence of substance use in Tehran was 5.6%, and opium was the most frequently used substance. In addition, male gender, lower levels of education, alcohol, and tobacco consumption are the main risk factors for substance use in Tehran. Healthcare providers and policymakers can utilize our results to implement preventive strategies to minimize substance use in Tehran.

Tumor necrosis factor inhibitors and janus kinase inhibitors in the treatment of cicatricial alopecia: A systematic review.

BACKGROUND: Cicatricial alopecia (CA) refers to various conditions that result in permanent hair loss. Treatment of CA has always been challenging. Regarding immune-mediated pathophysiology for many CA subtypes, the administration of Janus kinase (JAK) and tumor necrosis factor (TNF) inhibitors have potentiated the treatments of CA. METHODS: After a thorough systematic search in PubMed/Medline, Embase, Web of Science, Scopus, Google Scholar, ClinicalTrials.gov, and WHO ICTRP, a total of 3,532 relevant records were retrieved and screened. Accordingly, 56 studies met the eligibility criteria and entered the review. RESULTS: Among JAK inhibitors, oral tofacitinib was the most frequently reported and the most effective treatment in improving signs and symptoms of CA with minimal adverse effects (AEs). Baricitinib was another JAK inhibitor with sustained improvement while causing mild AEs. As a TNF inhibitor, adalimumab induced a rapid and stable improvement in signs and symptoms in most patients with rare, tolerable AEs. Thalidomide was the other frequently reported yet controversial TNF inhibitor, which caused a rapid and significant improvement in the condition. However, it may result in mild to severe AEs, particularly neuropathies. Infliximab is a TNF inhibitor with mostly favorable results, albeit in a few patients caused treatable dermatological AEs. Apremilast and certolizumab pegol caused an incomplete amelioration of signs and symptoms with no AEs. Lenalidomide is another TNF inhibitor that can induce temporary improvement in CA with probable AEs. It is noteworthy that utilizing adalimumab, infliximab, etanercept, golimumab, and an anonymous TNF inhibitor has induced paradoxical CA and other A.E.s in some patients. CONCLUSION: Recent studies have recommended JAK and TNF inhibitors, especially oral tofacitinib and adalimumab, as a new modality or adjuvant therapy to previous medications for primary CA. Nonetheless, monitoring AEs on a regular basis is suggested, and further extensive studies are required before definitive recommendations.

Microfluidic Synthesis of Ultrasmall Chitosan/Graphene Quantum Dots Particles for Intranasal Delivery in Alzheimer's Disease Treatment.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid ß (Aß) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

Evaluation of the Causes of Door-to-Balloon Time Delays in Patients with ST-Elevation Myocardial Infarction at Tehran Heart Center.

Background: Coronary artery disease (CAD) is the leading cause of cardiovascular death globally, and the most severe form of CAD, ST-elevation myocardial infarction (STEMI), needs immediate treatment. This study aimed to report patient characteristics and the causes of door-to-balloon time (D2BT) delays in STEMI patients admitted to Tehran Heart Center with a D2BT exceeding 90 minutes. Methods: This cross-sectional study was conducted at Tehran Heart Center, Iran, from March 20th, 2020, through March 20th, 2022. Variables consisted of age, sex, diabetes mellitus, hypertension, dyslipidemia, smoking, opium, family history of CAD, in-hospital mortality, primary percutaneous coronary intervention results, culprit vessels, causes of delays, the ejection fraction, triglycerides, and low and high-density lipoprotein levels. Results: The study population was composed of 363 patients (272 males [74.9]) at a mean (SD) age of 60±11.47 years. The leading causes of D2BT delays were the catheterization lab used in 95 patients (26.2) and misdiagnosis in 90 (24.8). Other causes were ST-elevation less than 2 mm in electrocardiograms in 50 patients (13.8) and referral from other hospitals in 40 (11.0). Conclusion: The catheterization lab in use and misdiagnosis were the leading causes of D2BT delays. We recommend that high-volume centers allocate an additional catheterization lab with an on-call cardiologist. Improved resident training and supervision in hospitals with many residents are also necessary.

Predictors of Five-Year Survival after EVAR: 10-Year Experience of Single-Center Cohort Study.

BACKGROUND: Endovascular abdominal aortic repair (EVAR) is the main therapeutic option for repairing abdominal aortic aneurysms (AAAs). We aimed to determine the long-term outcomes of patients who underwent EVAR at our center. METHODS: In this retrospective cohort study, patients who underwent EVAR for intact isolated AAA at Tehran Heart Center between 2007 and 2017 were included. Clinical outcomes and the frequency of mortality were analyzed for follow-up periods. We calculated the 5-year survival rate and its predictors for our patients using Kaplan-Meier estimation. RESULTS: We included the data of all patients (154 patients, mean age = 70.7 [± 8.0] years, 96.1% men) who successfully underwent EVAR at our center. The most common risk factors were coronary artery disease (70.1%), hypertension (68.2%), smoking (64.9%), and dyslipidemia (39.6%). There was no mortality during the procedure. The median follow-up was 65.5 months. An average decrease of 9.07 mm (95% confidence interval: 6.9-11.2) occurred in the size of the AAA. During follow-up, 12 patients developed some complications, 49 died, and 7 did not complete the follow-up. The 5-year survival rate was 75% (3.9%). The independent predictors for 5-year survival were age (hazard ratio [HR] = 1.06, P = 0.002) and anemia (HR = 1.91, P = 0.029). Despite not being statistically significant, dyslipidemia (HR = 0.573, P = 0.078) and long intensive care unit/cardiac care unit stays (HR = 1.08, P = 0.070) were borderline mortality predictors. CONCLUSIONS: This study depicted an acceptable survival rate for patients who underwent EVAR at our center. Age and anemia, 2 modifiable predictors of 5-year survival, can probably prolong the survival rate of patients, which requires evaluation later.

Epidemiology and prevalence of tobacco use in Tehran; a report from the recruitment phase of Tehran cohort study.

INTRODUCTION: Tobacco use is a major health concern worldwide, especially in low/middle-income countries. We aimed to assess the prevalence of cigarette smoking, waterpipe, and pipe use in Tehran, Iran. METHODS: We used data from 8272 participants of the Tehran Cohort Study recruitment phase. Tobacco use was defined as a positive answer to using cigarettes, waterpipes, or pipes. Participants who did not report tobacco use during the interview but had a previous smoking history were categorized as former users. Age- and sex-weighted prevalence rates were calculated based on the national census data, and characteristics of current and former tobacco users were analyzed. RESULTS: Age- and sex-weighted prevalence of current tobacco users, cigarette smokers, waterpipe, and pipe users in Tehran was 19.8%, 14.9%, 6.1%, and 0.5%, respectively. Current tobacco use was higher in younger individuals (35-45 years: 23.4% vs. ≥ 75 years: 10.4%, P < 0.001) and men compared to women (32.9% vs. 7.7% P < 0.001). The prevalence of tobacco use increased with more years of education (> 12 years: 19.3% vs. illiterate: 9.7%, P < 0.001), lower body mass index (< 20 kg/m2: 31.3% vs. ≥ 35 kg/m2: 13.8%, P < 0.001), higher physical activity (high: 23.0% vs. low: 16.4%, P < 0.001), opium (user: 66.6% vs. non-user: 16.5%, P < 0.001), and alcohol use (drinker: 57.5% vs. non-drinker: 15.4%, P < 0.001). Waterpipe users were younger (46.1 vs. 53.2 years) and had a narrower gender gap in prevalence than cigarette smokers (male/female ratio in waterpipe users: 2.39 vs. cigarette smokers: 5.47). Opium (OR = 5.557, P < 0.001) and alcohol consumption (OR = 4.737, P < 0.001) were strongly associated with tobacco use. Hypertension was negatively associated with tobacco use (OR = 0.774, P = 0.005). CONCLUSION: The concerning prevalence of tobacco use in Tehran and its large gender gap for cigarette and waterpipe use warrant tailored preventive policies.

The prevalence of permanent pacemaker implantation after open-heart surgeries; eight years of experience in Tehran heart center.

BACKGROUND: We aimed to evaluate the prevalence of permanent pacemaker implantation (PPI) among open-heart surgery patients. METHODS: We reviewed data from 23 461 patients undergoing open-heart surgeries between 2009 and 2016 in our heart center in Iran. A total of 18 070 patients (77%) had coronary artery bypass grafting (CABG), 3 598 (15.3%) valvular surgeries, and 1 793 (7.6%) congenital repair procedures. Finally, 125 patients who received PPI following open-heart surgeries were enrolled in our study. We defined the demographic and clinical characteristics of all these patients. RESULTS: PPI was required in 125 (0.53%) patients with an average age of 58 ± 15.3 years. The average hospitalization time after surgery and waiting time for PPI were 19.7 ± 10.2 and 11.4 ± 6.5 days, respectively. Atrial fibrillation was the dominant pre-operative cardiac conduction abnormality (29.6%). Also, the primary indication for PPI was complete heart block in 72 patients (57.6%). Patients in the CABG group were significantly older (P = 0.002) and were more likely to be male (P = 0.030). The valvular group longer bypass and cross-clamp times and had more left atrial abnormalities. In addition, the congenital defect group was younger and had longer ICU stay times. CONCLUSIONS: Based on our study findings, PPI was required in 0.53% of patients following open-heart surgery due to damage to the cardiac conduction system. The current study paves the way for future investigations to identify possible predictors of PPI in patients undergoing open-heart surgeries.

Prevalence, awareness, treatment, and control of type 2 diabetes mellitus among the adult residents of tehran: Tehran Cohort Study.

BACKGROUND: The prevalence of type 2 diabetes mellitus has increased in the past decades. We investigated the prevalence of diabetes and its awareness, treatment, and control among adult residents of Tehran. METHODS: We used the recruitment phase data of the Tehran Cohort study, enrolling a random sample of adult residents of Tehran aged ≥35 years. Diabetes was defined as self-report, current use of glucose-lowering medications, and/or fasting plasma glucose (FPG) ≥126mg/dl. Impaired fasting glucose (IFG) was defined as an FPG of 100-125mg/dl. Awareness was defined as diabetes self-report, treatment as receiving glucose-lowering medications, and glycemic control as FPG <126mg/dl. The age- and sex-weighted estimates were calculated using the 2016 national census. Logistic regression models were used to determine the factors associated with diabetes awareness, treatment, and control. RESULTS: A total of 8151 participants were included. Age- and sex-weighted prevalence of diabetes mellitus and IFG were 16.7% (95% CI: 15.1-18.4) and 25.1% (95% CI: 23.1-27.1), respectively. Diabetes was more prevalent in the eastern and central districts of Tehran. Advanced age (OR per 1-year increase: 1.026, 95% CI: 1.021-1.030), male sex (OR: 1.716, 95% CI: 1.543-1.909), higher BMI levels (OR for BMI ≥35 vs. <20 kg/m2: 4.852, 95% CI: 3.365-6.998), pre-existing hypertension (OR: 1.552, 95% CI: 1.378-1.747), dyslipidemia (OR: 1.692, 95% CI: 1.521-1.883), and chronic kidney disease (OR: 1.650, 95% CI: 1.019-2.673) were associated with an increased odds of diabetes mellitus. On the contrary, diabetes mellitus was less likely in current tobacco (OR: 0.872, 95% CI: 0.765-0.994) and alcohol users (OR: 0.836, 95% CI: 0.703-0.994) compared to non-users. Among diabetic individuals, 82.8% were aware of their condition, 71.9% received treatment, and 31.7% of treated patients had adequate glycemic control. Advanced age and pre-existing comorbidities, including hypertension and dyslipidemia, were associated with higher diabetes awareness and treatment. Furthermore, advanced age, higher levels of education, and female sex were determinants of better glycemic control among treated diabetic participants. CONCLUSION: There is a high prevalence of diabetes and IFG among adult residents of Tehran. Additionally, more than two-thirds of treated diabetics living in Tehran remain uncontrolled.

Brain Homogenate of a Rat Model of Alzheimer's Disease Modifies the Secretome of 3D Cultured Periodontal Ligament Stem Cells: A Potential Neuroregenerative Therapy.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal cell death and manifested by cognitive disorders and behavioral impairment. Mesenchymal stem cells (MSCs) are one of the most promising candidates to stimulate neuroregeneration and prevent disease progression. Optimization of MSC culturing protocols is a key strategy to increase the therapeutic potential of the secretome. Objectives: Here, we investigated the effect of brain homogenate of a rat model of AD (BH-AD) on the enhancement of protein secretion in the secretome of periodontal ligament stem cells (PDLSCs) when cultured in a 3D environment. Moreover, the effect of this modified secretome was examined on neural cells to study the impact of the conditioned medium (CM) on stimulation of regeneration or immunomodulation in AD. Methods: PDLSCs were isolated and characterized. Then, the spheroids of PDLSCs were generated in a modified 3D culture plate. PDLSCs-derived CM was prepared in the presence of BH-AD (PDLSCs-HCM) and the absence of it (PDLSCs-CM). The viability of C6 glioma cells was assessed after exposure to different concentrations of both CMs. Then, a proteomic analysis was performed on the CMs. Results: Differentiation into adipocytes and high expression of MSCs markers verified the precise isolation of PDLSCs. The PDLSC spheroids were formed after 7 days of 3D culturing, and their viability was confirmed. The effect of CMs on C6 glioma cell viability showed that both CMs at low concentrations (> 20 mg/mL) had no cytotoxic effect on C6 neural cells. The results showed that PDLSCs-HCM contains higher concentrations of proteins compared to PDLSCs-CM, including Src-homology 2 domain (SH2)-containing PTPs (SHP-1) and muscle glycogen phosphorylase (PYGM) proteins. SHP-1 has a role in nerve regeneration, and PYGM is involved in glycogen metabolism. Conclusions: The modified secretome derived from 3D cultured spheroids of PDLSCs treated by BH-AD as a reservoir of regenerating neural factors can serve as a potential source for AD treatment.

Antimicrobial Resistance among Community-Acquired Uropathogens in Mashhad, Iran.

Background: Antimicrobial resistance among community-acquired uropathogens is an emerging concern over the past decades that warrants a continuing reevaluation of the appropriateness of recommended empiric antimicrobial regimens for treatment of urinary tract infections (UTIs). Aims: To describe the microbial spectrum and resistance profile of community-acquired uropathogens and predictors of isolation of resistant strains. Methods: Between October 2017 and June 2019, individuals who visited the outpatient clinics for diagnosis of UTIs or screening of asymptomatic bacteriuria were included in the study if they were tested for urine culture in one of the three main medical diagnostic laboratories of Mashhad, Iran. The standard disk diffusion antimicrobial susceptibility testing was used, with the Clinical and Laboratory Standards Institute (CLSI) threshold cutoffs for susceptibility of isolated uropathogens. Results: Three hundred thirty cases were included with a median age of 47 years. Two hundred seventy-six (83.6%) were female. The most common isolated uropathogens were Escherichia coli in 201 (60.9%) cases and Klebsiella species in 46 (13.9%) cases. E. coli isolates showed the highest rates of susceptibility to nitrofurantoin (89.3%), cefixime (75%), and gentamicin (72.4%). Exposure to antibiotics in the past 3 months was a predictor of resistance to ciprofloxacin (OR: 2.8, 95% CI: 1.33-6.28), and older age was a predictor of resistance to TMP-SMX (OR: 2.1, 95% CI: 1.07-3.97) among E. coli isolates. Conclusion. E. coli and Klebsiella species accounted for about two-thirds of community-acquired uropathogens. In regard to the high susceptibility rates, nitrofurantoin was identified as the first-choice agent for empiric treatment of community-acquired cystitis, while cefixime and gentamicin might be the second-choice alternatives. Ciprofloxacin and TMP-SMX, on the other hand, cannot be considered appropriate agents for empiric therapy of community-acquired UTIs, particularly in those who had exposure to antibiotics in the past 3 months and the elderly.