Managing the Adverse Events Associated with Pembrolizumab and Lenvatinib Therapy in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months.

Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study.

BACKGROUND: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. METHODS: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. RESULTS: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. CONCLUSIONS: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors.

Background and aim: Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Methods: Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Results: Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. Conclusion: The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

Case report: Sintilimab combined with anlotinib as neoadjuvant chemotherapy for metastatic bone tumor resection in patients with PSC.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small-cell lung cancer (NSCLC), which is resistant to chemotherapy and radiotherapy with a poor prognosis. PSC is highly malignant and is prone to recurrence even after surgery. The programmed death-ligand 1 (PD-L1) tumor cell proportion score (TPS) 5%, TERT and TP53 gene mutations were detected in this patient accompanied by multiple metastatic sites. The anlotinib is a novel multitarget tyrosine kinase inhibitor (TKI) that could be effective for advanced NSCLC and some sarcoma patients. Limited clinical trials and case reports have shown that PSC patients with gene mutations and PD-L1 expression have good responses to multitarget antiangiogenic drug and immune checkpoint inhibitors (ICIs). In this article, we reported a case with metastatic PSC diagnosed by Computed Tomography (CT)-guided needle biopsy treated with immunotherapy combined with antiangiogenic drugs as a neoadjuvant chemotherapy (NACT). PSC is controlled and the patient achieves successfully limb salvage treatment by surgical resection. Therefore, targeted therapy and immunotherapy can provide sufficient surgical opportunities for limb salvage in the treatment of metastatic PSC patients. Case summary: A 69-year-old male diagnosed with malignant bone tumor in the proximal femur was admitted to our hospital in June 2022 with recurrent fever as well as swelling and pain in the left thigh for twenty days. The initial computed tomography (CT) scan of the chest showed a pulmonary cavity (20 mm × 30 mm) and scattered lung masses. Subsequently, he underwent a CT-guided needle biopsy to distinguish the essence of osteolytic bone destruction and soft tissue mass in the left proximal femur which showed metastatic sarcomatoid carcinoma histology. Genetic testing revealed TERT c.-124C mutation (abundance 8.81%), TP53 p.R342 mutation (abundance 11.35%), tumor mutational burden (TMB) 7.09 muts/Mb, microsatellite stability (MSS), and PD-L1 (SP263) TPS 5% were also detected. The patient was tentatively treated with a combination of antiangiogenic drug and PD-1 inhibitor. After one course, the tumor volume significantly reduced in magnetic resonance imaging (MRI) and pathological fracture occurred in the femur after combined treatment. The patient received proximal femoral tumor resection and prosthesis replacement after defervescence. Sequentially sintilimab with anlotinib were administered for over 1 year. Finally, the local tumor was well controlled, and no obvious drug-related adverse reactions were observed. The lesions in the lung remained in partial response (PR) for more than 16 months and complete response (CR) of metastatic tumor in the proximal femur was observed through imaging examinations. Conclusion: This is the first reported case of a metastatic PSC in femur showing a favorable response to the treatment consisting of anlotinib combined with sintilimab. This case suggests that antiangiogenic therapy combined with immunotherapy may benefit patients with metastatic PSC in the preoperative adjuvant therapy for limb salvage.

Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report.

INTRODUCTION: Systemic therapy is recommended for patients with advanced hepatocellular carcinoma (aHCC). However, drug resistance occurs over time when patients receive systemic therapy, resulting in cancer progression. Due to the lack of relevant clinical trials, optimizing subsequent treatments after cancer progression remains elusive. PATIENT CONCERNS: A 52-year-old male patient presented with epigastric discomfort and fatigue for almost 1 month with a past history of chronic hepatitis B virus infection for 30 years. DIAGNOSIS: Based on the patient's performance status, tumor status assessed by computed tomography, liver function, he was diagnosed with HCC at BCLC stage C. INTERVENTIONS AND OUTCOMES: He first received transarterial chemoembolization (TACE) combined with sintilimab and lenvatinib as first-line treatment and experienced 10-month progression-free survival. After cancer progression, the patient participated in a clinical trial of ABSK-011, a novel fibroblast growth factor receptor 4 inhibitor, with a frustrating result. Then, the patient underwent TACE and received sintilimab plus lenvatinib again. Surprisingly, the tumor had a partial response, and the patient's serum alpha-fetoprotein returned to normal. LESSONS: The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.

Mixed-method evaluation study of a targeted mass drug administration of long-acting anti-malarials among children aged 3 months to 15 years in the Bossangoa sub-prefecture, Ouham, Central African Republic, during the COVID-19 pandemic.

BACKGROUND: In 2020, during the COVID-19 pandemic, Médecins Sans Frontières (MSF) initiated three cycles of dihydroartemisin-piperaquine (DHA-PQ) mass drug administration (MDA) for children aged three months to 15 years within Bossangoa sub-prefecture, Central African Republic. Coverage, clinical impact, and community members perspectives were evaluated to inform the use of MDAs in humanitarian emergencies. METHODS: A household survey was undertaken after the MDA focusing on participation, recent illness among eligible children, and household satisfaction. Using routine surveillance data, the reduction during the MDA period compared to the same period of preceding two years in consultations, malaria diagnoses, malaria rapid diagnostic test (RDT) positivity in three MSF community healthcare facilities (HFs), and the reduction in severe malaria admissions at the regional hospital were estimated. Twenty-seven focus groups discussions (FGDs) with community members were conducted. RESULTS: Overall coverage based on the MDA card or verbal report was 94.3% (95% confidence interval (CI): 86.3-97.8%). Among participants of the household survey, 2.6% (95% CI 1.6-40.3%) of round 3 MDA participants experienced illness in the preceding four weeks compared to 30.6% (95% CI 22.1-40.8%) of MDA non-participants. One community HF experienced a 54.5% (95% CI 50.8-57.9) reduction in consultations, a 73.7% (95% CI 70.5-76.5) reduction in malaria diagnoses, and 42.9% (95% CI 36.0-49.0) reduction in the proportion of positive RDTs among children under five. A second community HF experienced an increase in consultations (+ 15.1% (- 23.3 to 7.5)) and stable malaria diagnoses (4.2% (3.9-11.6)). A third community HF experienced an increase in consultations (+ 41.1% (95% CI 51.2-31.8) and malaria diagnoses (+ 37.3% (95% CI 47.4-27.9)). There were a 25.2% (95% CI 2.0-42.8) reduction in hospital admissions with severe malaria among children under five from the MDA area. FGDs revealed community members perceived less illness among children because of the MDA, as well as fewer hospitalizations. Other indirect benefits such as reduced household expenditure on healthcare were also described. CONCLUSION: The MDA achieved high coverage and community acceptance. While some positive health impact was observed, it was resource intensive, particularly in this rural context. The priority for malaria control in humanitarian contexts should remain diagnosis and treatment. MDA may be additional tool where the context supports its implementation.

A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.

Eosinophilic granulomatosis with polyangiitis and its association with montelukast: a case-based review.

The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.

Effect of cytokines on advanced hepatocellular carcinoma prognosis receiving radiotherapy and tislelizumab plus anlotinib: a single-center phase II clinical trial.

The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3-4. In addition to stage, intrahepatic metastasis and Child-Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p < 0.05). The OS (14.63 pg/mL as cutoff value) and PFS (9.85 pg/mL as cutoff value) of patients with low IL-6 levels exceeded those with high levels (21.0 and 6.9, 15.8 and 10.0 months, respectively). The risks of death and disease progression were reduced by 63.0% (HR = 0.37, 95% CI: 0.19-0.72) and 43.0% (HR = 0.57, 95% CI: 0.22-1.47), respectively. Pre-treatment IL-6 levels may be a simple and effective prognostic indicator for patients with advanced HCC treated with radiotherapy combined with immunotargeted therapy.

The later-line efficacy and safety of immune checkpoint inhibitors plus anlotinib in EGFR-mutant patients with EGFR-TKI-resistant NSCLC: a single-center retrospective study.

BACKGROUND: Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy. METHODS: A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR). RESULTS: The median follow-up period was 28.6 months (range: 2.3-54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2-7.4 months), and the median OS was 17.1 months (95% CI 12.0-22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1-2, and no increase in adverse events was observed compared to monotherapy. CONCLUSION: Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.

Efficacy of Lenvatinib in Combination With PD-1 Monoclonal Antibody and Interventional Treatment for Intermediate-Stage Hepatocellular Carcinoma: Impact on Serum Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Levels: A Retrospective Study.

Objectives: To scrutinize the therapeutic efficiency and safety profile of lenvatinib, accompanied by the programmed cell death protein-1 (PD-1) monoclonal antibody, and interventional treatment in managing intermediate-stage hepatocellular carcinoma. Methods: Retrospective analysis was performed on clinical data from 93 patients suffering from intermediate to advanced hepatocellular carcinoma, treated at our institution from May 2018 to April 2020. Patients were divided based on the therapeutic regimen: 43 cases constituted the control group receiving lenvatinib plus transhepatic artery chemoembolization (TACE), while the remaining 50 cases in the study group were managed with lenvatinib, PD-1 monoclonal antibody, and TACE. Outcome measures included therapeutic efficacy, tumor markers (carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP], α-L-fucosidase [AFU], carbohydrate antigen 199 [CA199]), immune response indices (CD3+, CD4+, CD8+, CD4+/CD8+ ratio), pertinent cytokine levels (vascular endothelial growth factor [VEGF], matrix metalloproteinase-9 [MMP-9], basic fibroblast growth factor [aFGF], acidic fibroblast growth factor [bFGF]), quality of life (as per Quality of Life Assessment Scale for Cancer Patients [QOL-LC] scores), adverse effects, and survival rates. Results: The study group exhibited a significantly enhanced total effective rate compared to the control group (74.00% vs 53.49%, P < .05). Post-treatment levels of CEA, AFP, AFU, CA199, CD8+, VEGF, MMP-9, aFGF, and bFGF were notably lower in both groups, particularly in the study group. Contrastingly, CD3+, CD4+, CD4+/CD8+ratios, and QOL-LC scores were substantially elevated in the study group (P < .05). Adverse reaction prevalence was analogous between 2 groups (27.91% vs 26.00%; P > .05). Moreover, the study group reported significantly higher 1-, 2-, and 3-year survival rates than the control group (P < .05). Conclusion: The combined use of lenvatinib, PD-1 monoclonal antibody, and interventional treatment for intermediate to advanced hepatocellular carcinoma may have a definitive therapeutic efficacy. This regimen is effective in reducing tumor marker levels, enhancing immune function, modulating VEGF, MMP-9, and other related cytokine levels, and improving patients' quality of life without significantly augmenting adverse effects. This treatment paradigm also contributes to increased survival rates and promises favorable prognosis.

Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Ameliorative potential of galangin in murine model of ovalbumin-induced allergic rhinitis: a role of PI3K-PKB pathway.

OBJECTIVE: To examine the potential of galangin in a mouse model of ovalbumin (OVA)-induced allergic rhinitis (AR), as chronic AR, induced by immunoglobulin-E (IgE), leads to histamine release and nasal inflammation, and although galangin exhibits antiasthmatic and anti-inflammatory potential, its effect on AR is yet to be investigated. ANIMALS: 126 BALB/c mice. METHODS: AR induction involved sensitizing female mice with OVA (5%, 500 µL, IP) for 14 days. Post OVA challenge, the mice were divided into 7 groups (n = 18/group), including normal, AR control, montelukast (10 mg/kg), galangin (5, 10, and 20 mg/kg), and per se (galangin [20 mg/kg] treatment. Various outcomes were evaluated, including nasal symptoms, histopathology, biochemistry, and nasal lavage fluid inflammatory cytokines and signaling pathways in nasal mucosal to assess galangin potential in AR. RESULTS: In AR mice, galangin (10 and 20 mg/kg) significantly (P < .05) reduced sneezing, rubbing, and nasal discharge post-OVA challenge. Galangin treatment attenuated (P < .05) elevated serum histamine, ß-hexosaminidase, IgE, and Immunoglobulin G1 levels in AR control mice. Additionally, galangin significantly (P < .05) decreased OVA-induced alterations in IL-4, IL-6, IL-13, and interferon-γ levels in nasal lavage fluid compared to AR control mice. Western blot analysis demonstrated that galangin lowered OVA-induced AR by significantly (P < .05) downregulating the phosphorylated protein kinase B and mammalian target of rapamycin-protein expressions while markedly (P < .05) upregulating the glycogen synthase kinase-3ß protein expressions in nasal mucosal. Galangin also significantly ameliorated (P < .05) the OVA-induced histological aberrations in the nasal mucosa, reflected by reduced eosinophil infiltration, hyperplasia, and edema. CLINICAL RELEVANCE: Galangin exhibits antihistaminic and anti-inflammatory effects in AR mice by regulating IgE-mediated histamine and inflammatory release and modulating the phosphatidylinositol 3-kinase/Ak strain transforming/mammalian target of rapamycin pathways.

Clinical Characteristics, Investigations and Treatment in Children with Chronic Urticaria: An Observational Study.

Background and Objectives: The guidelines for chronic urticaria in children contain recommendations that are often based on adult studies. The diagnostic pathway has not been standardized and the effectiveness of anti-H1, omalizumab, montelukast, and systemic glucocorticoids is rarely reported in the pediatric population. There is a wide variation in the rate of remission of chronic urticaria between studies. The aim of this study is to enhance our understanding of pediatric chronic urticaria. Materials and Methods: This study enrolled 37 children with chronic urticaria aged from 0 to 18 years. Demographic parameters, medical history, clinical features, laboratory data and treatment information were collected. Children were treated with the recommended dosage of second-generation H1-antihistamines, which was increased by up to twofold. Omalizumab was added for refractory anti-H1 patients. A three-day course with systemic glucocorticoids was administered for severe exacerbations. Montelukast was administered to some children. Results: Wheals without angioedema were common. Chronic urticaria was spontaneous in 32 children (86.48%), inducible in 2 (5.41%), induced by a parasite in 1 and vasculitic in 2. Treatment of the potential causes of chronic urticaria was of no benefit, except for eradication of Dientamoeba fragilis. Chronic urticaria was resolved within three years in 45.9% of cases. Allergic diseases were present in nine children (24.32%) and autoimmune diseases were present in three (8.11%). All children were treated with anti-H1 at the licensed dose or at a higher dose. A partial or complete response to anti-H1 was observed in 29 (78.38%) patients. Montelukast showed no benefit. All children treated with omalizumab responded. Systemic glucocorticoids were successfully used to treat exacerbations. Conclusions: Our findings indicate that laboratory tests should not be routinely performed in children with chronic urticaria without clinical suspicion. However, comorbidities such as thyroid autoimmune disease and coeliac disease are suggested to be monitored over the chronic urticaria course. These clinical conditions could be diagnosed from the diagnostic framework of chronic urticaria. Increasing the dosage of anti-H1 and omalizumab was effective in children resistant to standard treatment but we still need further studies to generate a standard patient-centered treatment.

Montelukast Influence on Lung in Experimental Diabetes.

Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.

Palliative treatment of generalized metastatic follicular carcinoma of thyroid after operation: A case report and literature review.

RATIONALE: Follicular carcinoma of thyroid is a rare pathological type of thyroid carcinoma, accounting for 4.5% of the total. At present, the main treatment methods include surgery, iodine therapy, thyroid hormone inhibitors, etc. Targeted drug therapy is very important for distant metastasis and iodine-refractory differentiated thyroid cancer. PATIENT CONCERNS: This clinical case is a 51-year-old male patient with follicular carcinoma of thyroid. DIAGNOSES: After 7 years of total thyroidectomy, multiple distant metastasis occurred to bilateral lungs, bones, multiple lymph nodes, etc. INTERVENTION: After multidisciplinary consultation in the department of oncology, thoracic surgery, nuclear medicine and other departments, he received targeted drug therapy of Lenvatinib. OUTCOMES: After 3 months, his condition was partially relieved, and his quality of life was significantly improved. After 11 months of treatment, the evaluated efficacy was still in remission. LESSON: Late metastatic thyroid cancer is faced with dilemma of radioiodine refractory after traditional treatment. This will provide further evidence for therapeutic intervention in similar patients in the future.