The efficacy and safety of fluvoxamine in patients with COVID-19: A systematic review and meta-analysis from randomized controlled trials.

BACKGROUND: Recently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis was to evaluate the efficacy and safety of fluvoxamine in patients with COVID-19. METHODS: MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov were searched for RCTs which were performed to evaluate fluvoxamine and placebo up to January 31, 2024. Review Manager 5.3 was used to perform meta-analysis. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model. RESULTS: We pooled 4,711 participants from six RCTs (2,382 in the fluvoxamine group and 2,329 in the placebo group). Compared to the placebo group, the fluvoxamine group had a significantly lower rate of clinical deterioration (RR, 0.73; P = 0.004; 95% CI, 0.59 to 0.90; I2 = 0%) and hospitalization (RR, 0.76; P = 0.04; 95% CI, 0.59 to 0.99; I2 = 0%). In the meantime, compared with the placebo group, fluvoxamine group did not show any higher risk of AEs (P = 0.13 and 0.91, respectively) in safety outcomes analysis. The subgroup analysis showed that fluvoxamine treatment performed more than 200 mg daily appears to be more effective than those performed less than 200 mg daily in reducing clinical deterioration and hospitalization risks, while not exhibiting higher AE and SAE risks than placebo group. CONCLUSION: Fluvoxamine for patients with COVID-19, especially those who take 200 mg or more daily, is superior to the placebo group in reducing clinical deterioration and hospitalization, and did not show any higher risk of AEs and SAEs in safety concerns, which might be a promising intervention for COVID-19.

The efficacy and safety of atogepant for the prophylactic treatment of migraine: evidence from randomized controlled trials.

BACKGROUND: Migraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efficacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies. METHODS: MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched before October 20, 2021 for any relevant literature. Eventually, three randomized clinical trials (RCTs) with 2,466 patients were included in our study. RESULTS: We pooled 2,466 patients from 3 RCTs and primary outcome was mean monthly migraine days, the secondary endpoints were monthly headache days, acute medication use days per month and ≥ 50% reduction in monthly migraine days, baseline to end of trials. It was found that atogepant (10 mg, 30 mg, 60 mg once a day) led to a significant reduction in monthly migraine days (P < 0.00001, P < 0.00001, P = 0.007), monthly headache days (P < 0.00001, P < 0.00001, P = 0.001), and monthly medication use days (P < 0.00001, P < 0.00001, P = 0.0001), and an increase in the proportion of people with ≥ 50% reduction in monthly migraine days (P = 0.0008, P = 0.02, P = 0.04) in comparison with placebo. Moreover, there were no significant differences (P > 0.05) in outcomes of adverse events between atogepant and placebo. CONCLUSIONS: Atogepant has shown good efficacy and safety in the prophylactic treatment of migraine, and further studies are expected.

Clinical and pathological analysis of 19 cases of medullary thyroid carcinoma without an increase in calcitonin.

BACKGROUND: Medullary thyroid carcinoma (MTC), defined as a malignant tumour with C-cell differentiation, is of neuroendocrine origin and is characterized by the synthesis and secretion of calcitonin (CT). MTC without CT secretion has been reported on rare occasions. The purpose of this study was to evaluate the histological, immunohistochemical, and molecular pathologic features as well as the clinical significance of non-secretory MTC (NCR-MTC). METHODS: A retrospective analysis of patients with NCR-MTC was performed. The clinical features of NCR-MTC, including age, gender, tumour size and number, clinical signs of hypocalcaemia and diarrhoea, and the presence of lymph node metastasis, as well as the pathologic features of the disease, including tumour morphology, presence of neuroendocrine structures, capsular invasion, and immunohistochemical expression and presence of mutations in the RET gene, were evaluated. RESULTS: Nineteen patients with NCR-MTC were identified among 158 patients with MTC, resulting in a prevalence rate of 12.02%. Patients with NCR-MTC typically had masses less than 1cm in size (73.7%, 14/19). Hypocalcaemia was not present in 94.7% (18/19) of patients. While 42.1% (8/19) of patients with NCR-MTC did not have amyloid deposits, only 18% (25/139) of patients with secretory MTC did not have such deposits. While 95.7% (133/139) of the control group of patients with secretory MTC had neuroendocrine tumour structure, only 84.2% (16/19) of the patients with NCR-MTC had this type of tumour structure. Patients with NCR-MTC were also less likely to have vascular tumour thrombus, lymph node metastasis or thyroid capsular invasion. With regard to immunohistochemistry, CT expression was mostly negative, and carcinoembryonic antigen (CEA) expression was positive in 21.1% (4/19) of patients with NCR-MTC, while only 5.8% (8/139) of patients in the control group had positive CEA expression. CONCLUSIONS: The prevalence of NCR-MTC was low (12.02%). This type of tumour was smaller in size and more differentiated. Compared with the control group, relatively few patients had obvious symptoms, hypocalcaemia, lymph node metastasis, thyroid capsular or vascular invasion, or tumours with amyloid or neuroendocrine tumour structure.

Roles of fibroblasts from the interface zone in invasion, migration, proliferation and apoptosis of gastric adenocarcinoma.

AIMS: Interface zone fibroblasts (INFs) are very important in the progression and metastasis of tumours but their effect on the invasion and migration of gastric cancer cells is still unclear. METHODS: Primary fibroblasts were isolated from the distal normal zone (normal zone fibroblasts, NFs), interface zone (INFs) and tumour zone (cancer-associated fibroblasts, CAFs) of 60 human gastric carcinoma tissue samples. The crosstalk between these fibroblasts and human gastric cancer MGC-803 cells was evaluated using an indirect co-culture model in vitro. RESULTS: A high level of fibroblast activation protein (FAP) in the invasion front of gastric cancer was found in the gastric cancer tissue samples and no FAP expression was found in 20 normal gastric tissue samples by immunohistochemistry. High FAP expression was associated with Lauren classification, degree of differentiation, tumour node metastasis stage and depth of tumour invasion (p<0.05 or p<0.01). INFs promoted invasion and migration of MGC-803 cells. The number of invasions in INFs, CAFs and NFs were 120.10±27.53 (95% CI 102.12 to 138.10), 63.00±14.80 (95% CI 53.33 to 72.67) and 14.22±6.20 (95% CI 10.17 to 18.27), respectively; the number of invasions in INFs were 8.45-fold and 1.89-fold higher than those in NFs and CAFs, respectively (p<0.05). The number of migrations in INFs, CAFs and NFs were 118.00±16.83 (95% CI 107.00 to 129.00), 61.00±16.36 (95% CI 50.31 to 71.69) and 24.00±11.52 (95% CI 16.47 to 31.53), respectively; the number of migration in INFs were 4.91-fold and 1.92-fold higher than those in NFs and CAFs, respectively (p<0.05). INFs also significantly promoted cell proliferation and inhibited apoptosis in MGC-803 cells compared with NFs and CAFs (p<0.05). CONCLUSIONS: These findings indicate that INFs exhibit a more robust biological modulatory activity than CAFs and NFs. INFs may be a key factor leading to tumour progression and metastasis and may be of use as a tool for post-treatment surveillance.

The role of SPARC protein expression in the progress of gastric cancer.

We aimed to investigate the expression of SPARC (secreted protein, acidic and rich in cysteine) in gastric cancer and its relationship with tumor angiogenesis and cancer cells proliferation. Protein expression of SPARC, VEGF, CD34 and Ki-67 in 80 cases of gastric cancer and 30 cases of normal gastric tissue was evaluated by immunohistochemistry. CD34 staining was used as an indicator of microvessel density (MVD). Ki-67 labeling Index (LI) indicated cancer cells proliferation. Statistical analysis was used to investigate its relationship with clinical characteristics, tumor angiogenesis and cancer cells proliferation. SPARC expression was mainly in the stromal cells surrounding the gastric cancer cells, and was statistically significant differences between gastric cancer and normal gastric tissue (P < 0.05). Both the expression of SPARC and VEGF were related to differentiation degree, clinical stage, Lauren classification and lymph node metastasis (P < 0.05). Expression of SPARC was significantly negatively correlated with the expression of VEGF and MVD in gastric cancer tissues. Expression of SPARC was also negatively correlated with Ki-67-LI. Our findings suggest that both the expression of SPARC and VEGF are closed to tumor angiogenesis in gastric cancer, SPARC inhibited tumor angiogenesis but VEGF promoted tumor angiogenesis. SPARC also inhibited cells proliferation of gastric cancer.