Association of future cancer metastases with fibroblast activation protein-α: a systematic review and meta-analysis.

Introduction: Fibroblast activation protein-α (FAP-α) is a vital surface marker of cancer-associated fibroblasts, and its high expression is associated with a higher tumor grade and metastasis. A systematic review and a meta-analysis were performed to associate future metastasis with FAP-α expression in cancer. Methods: In our meta-analysis, relevant studies published before 20 February 2024 were systematically searched through online databases that included PubMed, Scopus, and Web of Science. The association between FAP-α expression and metastasis, including distant metastasis, lymph node metastasis, blood vessel invasion, vascular invasion, and neural invasion, was evaluated. A pooled odds ratio (OR) with 95% confidence intervals (CI) was reported as the measure of association. Results: A total of 28meta-analysis. The random-effects model for five parameters showed that a high FAP-α expression was associated with blood vessel invasion (OR: 3.04, 95% CI: 1.54-5.99, I 2 = 63%, P = 0.001), lymphovascular invasion (OR: 3.56, 95% CI: 2.14-5.93, I 2 = 0.00%, P < 0.001), lymph node metastasis (OR: 2.73, 95% CI: 1.96-3.81, I 2 = 65%, P < 0.001), and distant metastasis (OR: 2.59; 95% CI: 1.16-5.79, I 2 = 81%, P < 0.001). However, our analysis showed no statistically significant association between high FAP-α expression and neural invasion (OR: 1.57, 95% CI: 0.84-2.93, I 2 = 38%, P = 0.161). Conclusions: This meta-analysis indicated that cancer cells with a high FAP-α expression have a higher risk of metastasis than those with a low FAP-α expression. These findings support the potential importance of FAP-α as a biomarker for cancer metastasis prediction.

Effect of the number of negative lymph nodes removed on the survival and recurrence rate after gastrectomy in patients with gastric cancer: a multicenter retrospective cohort study.

BACKGROUND: Various factors affect the survival rate of Gastric cancer (GC) patients after gastrectomy. This study aimed to investigate the effect of the number of negative lymph nodes (NLNs) removed on GC patients' survival and recurrence rate after gastrectomy. METHODS: In this retrospective, multicenter cohort study, we reviewed the medical profile of 639 patients with a definite diagnosis of GC who underwent gastrectomy from 2010 to 2022 in one of the medical centers affiliated with the Iran University of Medical Sciences. Based on the number of NLNs removed, patients were divided into three groups, including (0-9NLNs), (10-15 NLNs), and (≥ 16 NLNs), including 155, 231, and 253 GC patients, respectively. Demographic characteristics, tumor characteristics, and pathological findings of the patients were extracted by referring to the patient's files. RESULTS: The 5-year survival rate of patients was estimated at 48.2%. The 5-year tumor recurrence rate in patients with the number of NLNs 1-9, NLNs 10-15, and ≥ 16 NLNs were 79.4%, 51.1%, and 30.8%, respectively. (Log-rank = 9.24, P 0.001) The multivariate analysis showed that the 5-year survival rate in patients with fewer NLNs removed ≥ 16 was significantly higher than in the other two groups. In addition, age, BMI, tumor size, tumor stage, metastasis, and tumor differentiation were significantly related to the survival of GC patients after gastrectomy. (p < 0.05) CONCLUSION: Paying attention to the number of NLNs removed during gastrectomy can be a key factor in improving the survival prediction of GC patients.

The use of metformin, sulfonylurea compounds and insulin and the risk of hip fractures in diabetic patients: a systematic review and meta-analysis of observational studies.

BACKGROUND: Hip fracture is a major health problem that occurs more often in the elderly, especially in diabetic patients. Some studies have been conducted regarding the effect of anti- diabetic drugs on fractures. But so far, no meta-analysis study has been conducted to investigate the effect of diabetic drugs on hip fractures. Therefore, this study investigated the relationship between anti-diabetic drugs (Metformin, Sulfonylurea, and insulin) with hip fractures. METHODS: In this systematic review and meta analysis study, PubMed, Scopus, Google Scholar, and Web of Science databases were searched with specific keywords to find relevant studies. Two researchers included related studies after screening based on the title and full text. Cochran's Q and I2 tests were used to assess heterogeneity between studies. Publication bias between studies was evaluated for each drug using Egger's test. A 95% confidence interval was used for effect size significance. Overall, 49 studies, including 6,631,297 participants, were reviewed. RESULTS: The results showed that metformin significantly reduced the risk of hip fracture (HR: 0.833, 95% CI: 0.759, 0.914, P:0.001). Consumption of sulfonylurea compounds was significantly associated with an increased risk of hip fracture. (HR: 1.175, 95% CI:1.068,1.293, P:0.001), The risk of hip fracture in patients receiving insulin was significantly higher than in diabetic patients who did not receive insulin. (HR:1.366, 95% CI:1.226,1.522, P:0.001). CONCLUSION: The results of this study showed that taking metformin reduces the risk of hip fracture, and insulin and Sulfonylurea increase the risk of hip fracture.

Total body irradiation-free haploidentical peripheral blood stem cell transplantation compared to related and unrelated donor transplantation in pediatrics with acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer under the age of 15 years. Despite the recent advances in therapeutic regimens, relapse occurs in 15%-20% of pediatric patients after chemotherapy, and hematopoietic stem cell transplantation (HSCT) is the best treatment option. However, donor availability is one of the major challenges. Over the last decade, haploidentical donor (HID) transplantation has evolved as an alternative option. Herein, we aimed to compare the transplant outcomes in pediatric patients receiving total body irradiation (TBI)-free myeloablative regimens, between non-HID and HID transplant. PATIENTS AND METHODS: The study included 60 pediatric ALL patients who had undergone HSCT from October 2016 until September 2020. Forty-three patients received non-HID HSCT, while 17 patients received HID. The sources of stem cells (SC) were peripheral blood stem cells (PBSC) for all the patients. The conditioning regimen was based on busulfan and cyclophosphamide. For graft-versus-host disease (GvHD) prophylaxis, patients received cyclosporine and methotrexate in the setting of non-HID transplantation, where HIDs received post-transplant cyclosporine and cyclophosphamide. RESULTS: The cumulative incidences of 3-year overall survival (OS) were 73.1%, 66.6%, and 69.5%, for matched sibling donor-matched related donor (MSD-MRD), matched unrelated donor-mismatched unrelated donor (MUD-MMUD), and HID groups, respectively (p = .85). The cumulative incidences of grade II-IV acute GvHD for the MRD, MUD-MMUD, and HID groups were 29%, 41%, and 49%, respectively (p = .47). Furthermore, the 3-year cumulative incidence of chronic GvHD was MSD-MRD: 70% versus MUD-MMUD: 42% versus HID: 45% (p = .64). The 3-year cumulative incidence of relapse post transplantation was 45%, 18%, and 45%, respectively, for the MSD-MRD, MUD-MMUD, and HID groups, and the differences were not statistically significant (p = .55). There was a higher risk for cytomegalovirus (CMV) infection in patients receiving HID transplants compared to those of non-HIDs (p < .01). CONCLUSION: Our results indicate that PBSC-HID transplant outcomes in the setting of non-TBI conditioning are comparable to those of non-HIDs in pediatric ALL patients.

The visceral adiposity index and lipid accumulation product as predictors of cardiovascular events in normal weight subjects.

INTRODUCTION: Visceral adipose tissue (VAT) has an important role in the incidence of cardiovascular disease (CVD) than obesity by itself. The visceral adiposity index (VAI) and lipid accumulation product (LAP) are surrogate indices for measuring VAT. The aimed of this study was to investigate the association of these markers with cardiovascular events among populations with different BMI category in Mashhad, northeast of Iran. METHOD: The present study comprised a prospective cohort of 9685 men and women (35-65 years) who were recruited from MASHAD study. BMI category was defined as normal weight (BMI <25), over weight (25 ≤ BMI<30) and obese (BMI≥30). Demographic, laboratory evaluations, anthropometric and metabolic parameters were performed. Logistic and Cox regression analyses were used to determine the association and risk of cardiovascular events with VAT and LAP. RESULTS: The mean VAI and LAP in CVD patients were significantly higher than in healthy ones in all 3 groups. In terms of CVD event prediction, VAI and LAP had significant association with the incidence of CVD in the second (RR (95% CI): 2.132 (1.047-4.342) and 2.701 (1.397-5.222), respectively) and third tertiles (RR (95% CI): 2.541 (1.163-5.556) and 2.720 (1.159-6.386), respectively) in the normal group, but this association was only found in the third tertiles (RR (95% CI): 2.448 (1.205-4.971) and 2.376 (1.086-5.199), respectively) in the overweight group. The result couldn't find this association for the obese group. CONCLUSION: In this study, we found that there was a significant association between LAP and VAI and cardiovascular events in normal weight and over-weight groups; however, no significant relationship was found in the obese group.

Protective Effects of Leukadherin1 in a Rat Model of Targeted Experimental Autoimmune Encephalomyelitis (EAE): Possible Role of P47phox and MDA Downregulation.

BACKGROUND: Reactive oxygen and nitrogen species (ROS and RNS) are involved in pathologic mechanisms underlying demyelination and exacerbation in multiple sclerosis (MS) lesions. P47phox is the most important subunit of an ROS-producing enzyme (NADPH oxidase) which is reportedly upregulated in MS plaques due to the intense activity of infiltrated immune cells and resident microglia. Leukadherin1 is a specific CD11b/CD18 agonist that inhibits signaling and transmigration of inflammatory cells to sites of injury. Based on this mechanism, we evaluated therapeutic effects of leukadherin1 in an animal model of targeted experimental autoimmune encephalomyelitis (EAE) through focal injection of inflammatory cytokines to the spinal cord. METHODS: For model induction, Lewis rats were first immunized with 15µg MOG 1-125 emulsion. Twenty days later, animals were subjected to stereotaxic injection of IFNγ and TNFα to the specific spinal area (T8). One day after injection, all animals presented EAE clinical signs, and their behaviors were monitored for eight days through open-field locomotion and grid-walking tests. Leukadherin1-treated animals received daily intraperitoneal injections of 1mg/kg of the drug. The specific spinal tissues were extracted on day 5 in order to measure nitric oxide (NO), malon di-aldehyde (MDA), and TNFα concentrations alongside P47phox real-time PCR analysis. In addition, spinal sections were prepared for immunohistochemical (IHC) observation of infiltrated leukocytes and activated microglia. RESULTS: Leukadherin1 exhibited promising improvements in EAE clinical scores and behavioral tests. Demyelination, CD45+ leukocyte infiltration, and Iba1+ microglia activation were reduced in spinal tissues of leukadherin1-treated animals. Furthermore, P47phox expression levels, MDA, and NO amounts were decreased in treated animals. However, TNFα concentrations did not differ following treatment. CONCLUSION: Based on our results, we suggest that leukadherin1 may be used as a novel therapeutic agent in tackling the clinical challenge of multiple sclerosis, especially during the acute phase of the disease. This effect was possibly mediated through decreased leukocyte infiltration and oxidative stress.