METHODS: Participants with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Post hoc efficacy analyses of the PD-L1 CPS < 1 and CPS 1-19 subgroups were performed.
RESULTS: Of 882 participants enrolled, 128 had PD-L1 CPS < 1 and 373 had CPS 1-19. For pembrolizumab versus cetuximab-chemotherapy, the median overall survival was 7.9 versus 11.3 months in the PD-L1 CPS < 1 subgroup (hazard ratio [HR], 1.51 [95% CI, 0.96 to 2.37]) and 10.8 versus 10.1 months in the CPS 1-19 subgroup (HR, 0.86 [95% CI, 0.66 to 1.12]). For pembrolizumab-chemotherapy versus cetuximab-chemotherapy, the median overall survival was 11.3 versus 10.7 months in the PD-L1 CPS < 1 subgroup (HR, 1.21 [95% CI, 0.76 to 1.94]) and 12.7 versus 9.9 months in the CPS 1-19 subgroup (HR, 0.71 [95% CI, 0.54 to 0.94]).
CONCLUSION: Increased efficacy of pembrolizumab or pembrolizumab-chemotherapy was observed with increasing PD-L1 expression. PD-L1 CPS < 1 subgroup analysis was limited by small participant numbers. Results from the PD-L1 CPS 1-19 subgroup support previous findings of treatment benefit with pembrolizumab monotherapy and pembrolizumab-chemotherapy in patients with PD-L1 CPS ≥ 1 tumors. Although PD-L1 expression is informative, exploration of additional predictive biomarkers is needed for low PD-L1-expressing HNSCC.
METHODS: This study evaluated Malaysian Gelam honey as a nutraceutical alternative to estrogen HRT (ERT) in alleviating VVA. A total of 24 female 8-weekold Sprague Dawley rats underwent bilateral oophorectomy. A minimum of 14 days elapsed from the time of surgery and administration of the first dose of Gelam honey to allow the female hormones to subside to a stable baseline and complete recovery from surgery. Vaginal tissues were harvested following a 2-week administration of Gelam honey, the harvested vagina tissue underwent immunohistochemistry (IHC) analysis for protein localization and qPCR for mRNA expression analysis.
RESULTS: Results indicated that Gelam honey administration had increased the localization of Aqp1, Aqp5, CFTR and Muc1 proteins in vaginal tissue compared to the menopause group. The effect of Gelam honey on the protein expressions is summarized as Aqp1>CFTR>Aqp5>Muc1.
DISCUSSION: Gene expression analysis reveals Gelam honey had no effect on Aqp1 and CFTR genes. Gelam honey had up-regulated Aqp5 gene expression. However, its expression was lower than in the ERT+Ovx group. Additionally, Gelam honey up-regulated Muc1 in the vagina, with an expression level higher than those observed either in the ERT+Ovx or SC groups. Gelam honey exhibits a weak estrogenic effect on the genes and proteins responsible for regulating water in the vaginal tissue (Aqp1, Aqp5 and CFTR). In contrast, Gelam honey exhibits a strong estrogenic ability in influencing gene and protein expression for the sialic acid Muc1. Muc1 is associated with mucous production at the vaginal epithelial layer. In conclusion, the protein and gene expression changes in the vagina by Gelam honey had reduced the occurrence of vaginal atrophy in surgically-induced menopause models.
METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH.
CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.
METHODS: The present cross-sectional analytical study was performed in normal and PE primigravidae (n = 10 in each group) who were admitted to the North Okkalapa General and Teaching Hospital from February 2019 to February 2020. Serum samples were collected immediately before delivery, and placental tissues were collected immediately after emergency or elective cesarean section. The expression of placental eNOS was measured by western blot, and the levels of ET-1 in placental tissue homogenates and in the serum were measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS: The PE group had significantly higher serum levels of ET-1 (median: 116.56 pg/mL; IQR: 89.14-159.62 pg/mL) than the normal group (median: 60.02 pg/mL; IQR: 50.89-94.37 pg/mL) (p
RECENT FINDINGS: We performed a systematic search of the PubMed, EMBASE, and Web of Science databases to evaluate the impact of inguinal and pelvic LND on the oncological outcomes of PUC and to identify indications for this procedure.
RESULTS: Three studies met the inclusion criteria. The cancer detection rate in clinically nonpalpable inguinal lymph node (cN0) was 9% in men and 25% in women. In clinically palpable lymph node (cN+), the malignancy rate was 84% and 50% in men and women, respectively. Overall cancer detection rate in pelvic lymph nodes in patients with cN0 was 29%. Based on tumor stage, the detection rate was 11% in cT1-2 N0 and 37% in cT3-4 N0. Nodal disease was associated with higher recurrence and worse survival. Pelvic LND seems to improve overall survival for patients with LND regardless of the location or stage of lymph nodes. Inguinal LND improved overall survival only in patients with palpable lymph nodes. Inguinal LND had no survival benefit in patients with nonpalpable lymph nodes.
SUMMARY: The available, albeit scarce, data suggest that inguinal LND derives the highest benefit in women and in patients with palpable inguinal nodes, whereas the benefit of pelvic LND seems to be more pronounced across all stages of invasive PUC. Prospective studies are urgently needed to further address the prognostic benefit of locoregional LND in PUC.
MATERIALS AND METHODS: We retrospectively analysed data from 157 patients who underwent FG-TBLB, with the primary outcome being procedure-related pneumothorax. We assessed several risk factors for pneumothorax following FG-TBLB: patient characteristics, location of biopsy, number of biopsies and computed tomography pattern. Univariate and multivariate logistic regression analyses were performed.
RESULTS: One-hundred fifty-seven patients were included [mean (SD) age 57.9 (16.2) years; 60.5% male]. The most common location for FG-TBLB was the right upper lobe (n=45, 28.7%). The mean (SD) number of biopsy samples was 6.7 (2.1). Radiographic evidence of pneumothorax was reported in 12 (7.6%) patients, with 11 of those requiring intercostal chest tube intervention (mean air leak time: 5.7 days and 1 had persistent air leak requiring autologous blood patch pleurodesis. None experienced pneumothorax recurrence. Female gender and upper lobe location of the biopsy were identified as predisposing factors for pneumothorax. In the multivariable analysis, upper lobe biopsies were associated with a higher risk of pneumothorax (OR 0.120; 95% CI 0.015-0.963; p = 0.046).
CONCLUSION: The overall rate of pneumothorax is low. We recognise the increased risk of pneumothorax associated with upper lobe biopsy. These findings suggest that clinicians should exercise caution when performing FGTBLB in this region and consider alternative biopsy locations whenever feasible. We suggest adequate planning and preparation should be implemented to minimise the risk of pneumothorax following FG-TBLB.