Efficacy and Safety of Different Immunosuppressive Therapies in Patients With Membranous Nephropathy and High PLA2R Antibody Titer

Background: This study aimed to evaluate clinical features and prognosis and therapy option of patients with different risk ranks based on antibody against the M-type phospholipase-A2-receptor (PLA2Rab) level in seropositive M-type phospholipase-A2-receptor (PLA2R)-associated membranous nephropathy (MN) in a large sample size, multi-center study.Method: Based on the unvalidated cut-off value of PLA2Rab above 150 RU/ml as one of the clinical criteria for high risk of progressive kidney function loss in MN according to 2020 Kidney Disease: Improving Global Outcomes (KDIGO) draft guidelines recommendation, a total of 447 patients who received cyclophosphamide (CTX) or tacrolimus (TAC) combined with corticosteroids treatment for 12 months were divided into high titer (>150 RU/ml) group and non-high titer (20–150 RU/ml) group, which were subdivided into CTX subgroup and TAC subgroup. The overall cohort was classified into CTX group and TAC group as well. Clinical parameters levels and remission rates were recorded at 3, 6, and 12 months follow-up. PLA2Rab was tested by enzyme-linked immunosorbent assay.Results: Patients with high titer PLA2Rab were associated with more severe proteinuria and hypoalbuminemia compared to those with non-high titer antibody, accompanied by lower complete remission (CR) and total remission (TR) rates at 3, 6, and 12 months, which even took longer to remission. Similar remission rates differences between the two titer groups were observed in the CTX and TAC groups, respectively. PLA2Rab level at baseline was an independent predictive factor for CR and TR. In the high titer group, CR and TR rates in the CTX subgroup were significantly higher than those in the TAC subgroup at 12 months, although serious adverse events were more frequent in the former.Conclusion: High-risk rank patients with PLA2Rab level above 150 RU/ml have higher disease activity and worse prognosis among patients with seropositive PLA2R-associated MN, even under different immunosuppressive therapeutic models; moreover, CTX combined with corticosteroids was preferred compared to TAC plus corticosteroids, although serious adverse events were more frequent in the former. Additionally, baseline PLA2Rab level was an independent predictive factor for clinical remission.

Significance of the neutrophil-to-lymphocyte ratio in predicting the response to neoadjuvant chemotherapy in extremity osteosarcoma: a multicentre retrospective study

Background At present, no predictive factor has been validated for the early efficacy of neoadjuvant chemotherapy (NACT) in osteosarcoma. The purpose of this study was to investigate the significance of the neutrophil-to-lymphocyte ratio (NLR) in predicting the response to NACT in extremity osteosarcoma. Methods Pathological complete response (pCR) was used to assess the efficacy of NACT. Receiver operating characteristic (ROC) curves and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR. Univariate and multivariate analyses using logistic regression models were conducted to confirm the independent factors affecting the efficacy of NACT. Results The optimal NLR cut-off value was 2.36 (sensitivity, 80.0%; specificity, 71.3%). Univariate analysis revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR. Multivariate analyses confirmed that the NLR before treatment was an independent risk factor for pCR. Compared to patients with a high NLR, those with a low NLR showed a more than 2-fold higher likelihood of achieving pCR (OR 2.82, 95% CI 1.36-5.17, p = 0.02). Conclusion The NLR is a novel and effective predictive factor for the response to NACT in extremity osteosarcoma patients. Patients with a higher NLR showed a lower percentage of pCR after NACT.

LYMPHEDEMA DURATION AS A PREDICTIVE FACTOR OF EFFICACY OF COMPLETE DECONGESTIVE THERAPY

Lymphedema is a common condition with global impact and a multitude of complications, however, only a few professionals specialize in its management. A retrospective analysis of 105 subjects with unilateral lymphedema upper or lower limb was performed to investigate whether the duration of lymphedema constitutes an important factor associated with the efficacy of complete decongestive therapy (CDT). Subjects were classified into two groups according to the duration of lymphedema, prior to CDT: group A (≤1 year) and group B (>1 year). Both groups were treated daily according to the same CDT protocol for four weeks. The CDT efficacy was determined based on the percent reduction of excess volume (PREV) measurements. Lymphedema was significantly reduced in both groups of subjects, but significantly more in group A (p<0.001). In subjects with upper limb lymphedema, median value of PREV was 80.8% (interquartile range, 79.1-105.0%) in group A and 62.0% (interquartile range, 56.7-66.5%) in group B (p<0.001). In subjects with lower limb lymphedema PREV was 80.7% (interquartile range, 74.9-85.2%) and 64.5% (interquartile range, 56.0-68.1%) for groups A and B, respectively (p<0.001). Duration of lymphedema was found to be a strong predictive factor that may significantly impact CDT efficacy. Therapeutic effects were increased in subjects who were detected and treated earlier for lymphedema.

Dynamin 3 Gene as a Tumor Suppressor and an Independent Predictive Factor of Poor Prognosis in Patients with Gastric Cancer

Gastric cancer is a leading cause of death from malignant tumors worldwide. With the development of genome sequencing technology, an increasing number of key driver genes and tumor suppressors have been discovered. Some studies have suggested that Dynamin 3 (DNM3) is a novel tumor suppressor; however, the role of DNM3 in malignancy remains unclear. We performed a systematic analysis using The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohorts, and 160 patients with stomach adenocarcinoma at Fujian Medical University Union Hospital (FJMUUH) (48 quantitative PCR [qPCR] and 112 immunohistochemistry). DNM3 expression was found to be downregulated in gastric cancer compared to that in paraneoplastic tissue. Low expression of DNM3 was mainly associated with DNM3 promoter hypermethylation status. Low expression of DNM3 can upregulate the tumor cell cycle and oxidative phosphorylation process and downregulate immune regulation, and Th17 and Th2 immune cell infiltration was increased in patients with lower expression of DNM3. Patients with a lower DNM3 expression had a higher rate of lymph node metastasis and poor prognosis. In summary, DNM3 is a tumor suppressor and an independent predictive factor of poor prognosis that regulates the cell cycle and immunosuppression in the tumor microenvironment in gastric cancer via methylation.

Cord Bilirubin Value as a Predictor of Significant Hyperbilirubinemia in Abo Incompatiblity

Background: Hyperbilirubinemia is a condition in which the blood contains too much bilirubin and producing jaundice (yellow coloring of the eyes and skin). Low bilirubin levels in newborns are common and do not pose any problems; they will resolve on their own within the first week of life. Studying the cord bilirubin levels in new born babies is significant to predict the risk of abo incompatiblity. Methods: A total of 129 babies born to O blood group mother were included in the study. Out of which 111 babies were with risk of ABO incompatibility. Among them 17 babies developed pathological hyperbilirubinemia. None of the 0 positive babies developed pathological hyperbilirubinemia. Results: The peak bilirubin level was attained on 3rd and 4th day for all the babies and was taken as the outcome measure and cord serum bilirubin was taken as the predictive factor. The incidence of pathological hyperbilirubinemia is 13.2%. The mode of delivery had no positive association with the development of pathological hyperbilirubinemia. Male babies had positive ociation for pathological hyperbilirubinemia without any statistical significance. Incidence of pathological hyperbilirubinemia is higher in babies with a birth weight of <3 kg. Conclusion: A cord bilirubin value of 2.65 mg/dL can be used as a cut off for predicting pathological hyperbilirubinemia. Infants with bilirubin level more than the cutoff values were subjected to early intervention with complete recovery. None of the babies had developed encephalopathy and its sequelae.