[Clinical characteristics and their influences on the survival of leptomeningeal metastasis derived from lung adenocarcinoma harboring epithelial growth factor receptor mutation].

Objective: To analyze the clinical characteristics of leptomeningeal metastasis (LM) patients from epithelial growth factor receptor (EGFR)-mutated lung adenocarcinoma, and their impacts on the survival of the patients. Methods: From July 2018 to July 2022, the clinicopathological data of 81 patients diagnosed as EGFR-mutated lung adenocarcinoma LM by cytopathology who admitted to the Department of Oncology of Xiangya Hospital of Central South University were retrospectively analyzed, including 33 males and 48 females. The age ranged from 31 to 76 years, with a median age of 54 years. All the 81 patients were followed up, with a median follow-up of 21.0 months (95%CI: 12.5 to 29.5 months). The Kaplan Meier method was used to draw survival curve. Cox proportional hazards regression model was used to analyze the impact of the factors on the survival of patients. Results: Among the 81 patients, the interval between the initial diagnosis of lung cancer and the pathological diagnosis of LM in cerebrospinal fluid (CSF) was 0-108 months, with a median interval of 14 months. Fifty-two patients (64.2%) used the third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), while 17 patients (21.0%) used EGFR-TKIs in combination with other drugs, and 12 patients (14.8%) were treated with best supportive care (BSC). Sixty patients (74.1%) had a Kanofsky performance status (KPS) score of less than 60 points, and 71 patients (87.7%) had brain parenchymal metastasis and/or spinal metastasis. Twenty-two patients (27.2%) used pemetrexed through intrathecal CSF, and 17 patients (21.0%) used pemetrexed through the Ommaya sac to the CSF of the ventricle. The incidence of adverse event related to the administration of pemetrexed through CSF was 64.1% (25/39), mainly manifested as myelosuppression, including 22 patients of leukocyte reduction, 25 patients of hemoglobin reduction, and 14 patients of platelet reduction. The median post-leptomeningeal metastasis overall survival (pLM-OS) in 81 patients was 11.0 (95%CI: 7.7-14.3) months. KPS score≥60 points (HR=0.407, 95%CI: 0.170-0.973, P=0.043), CSF cytology negative after treatment (vs persistent positive, HR=0.351, 95%CI: 0.155-0.792, P=0.012), intraventricular administration of pemetrexed (vs non intraventricular administration of pemetrexed, HR=0.319, 95%CI: 0.137-0.745, P=0.008) and the treatment with third-generation EGFR-TKIs after LM (vs EGFR-TKIs in combination with other drugs, HR=0.486, 95%CI: 0.237-0.998, P=0.049) were a factor affecting pLM-OS of patients. Conclusions: Brain parenchyma, or/and spine are the most sites where the LM patients concurrently metastasize. KPS score≥60 points and CSF cytology negative after treatment, intraventricular administration of pemetrexed and the treatment with third-generation EGFR-TKIs are indictors affecting pLM-OS of the patients.

A nomogram for predicting overall survival in patients with type II endometrial carcinoma: a retrospective analysis and multicenter validation study.

OBJECTIVE: Type II endometrial cancer (EC) is associated with high risk of metastasis and poor prognosis. We aimed to develop a nomogram for predicting survival probability in patients with type II EC. PATIENTS AND METHODS: Data from a total of 4,117 patients with confirmed type II EC were pulled from the Surveillance, Epidemiology, and End Results (SEER) database, and were randomly divided into a training set and an internal verification set. A nomogram was constructed based on the training set. The concordance index (C-index), area under the ROC curve, and calibration plots were used to evaluate the identification and calibration of the nomogram. The SEER internal validation set and the Chinese multicenter data set (74 patients) were used to verify discriminations and corrections of the model. RESULTS: Multivariate analysis indicated that age, marital status, tumor size, T stage, N stage, M stage, surgery, radiotherapy, and chemotherapy were independent factors affecting the prognosis of type II EC patients (p<0.001). The corresponding nomogram has showed excellent calibration and discrimination (C-index [95% CI], 0.752 [0.738-0.766]). The model was verified in the internal verification set (0.760 [0.739-0.781]) and the Chinese multicenter set (0.784 [0.607-0.961]). In addition, the AUC further confirmed the accuracy of the nomogram in predicting survival. The calibration curve of OS within 5 years confirmed good calibration of the nomogram. CONCLUSIONS: This model and the corresponding risk classification system may provide useful tools for clinicians to evaluate the long-term prognosis of patients and carry out personalized clinical evaluation.

Carbohydrate-specific antibodies in normal human sera. II. Structural definition of antigenic determinants.

IgG and IgM antibodies against several sugars have been characterized in sera of normal donors by passive hemagglutination and a quantitative hemagglutination inhibition test. These antibodies distinguish between the equatorial and axial OH groups at C2, C3, or C4 positions of the glycopyranose configuration, differences between the anomers, linkage types, changes in the primary alcohol group at C6, and OH substitution. In the examples of antibodies to mannose, galactose, and glucose investigated, specificities were usually directed against the beta-anomers. In disaccharides, the antibodies appeared to react only with 1 of the 2 sugar subunits, but unlike monosaccharides, the glycosidic linkages also seemed to be a part of the reaction site. Thus, the reacting moiety in gentiobiose was beta-D-glucopyranosyl with 1----6 linkage, in cellobiose with beta-D-glucopyranosyl with 1----4 linkage, in meliboise was alpha-D-galactopyranosyl with 1----6 linkage, and in lactose the reaction was directed against beta-D-galactopyranosyl with 1----4 linkage. In the maltose-dependent hemagglutination, alpha-D-glucose appeared to be the main reaction site. ManNAc exemplified the specificity determined by OH group substitution. Antibody to D-Fucose represented example of specificity evolving from substitution of the primary alcohol.

Carbohydrate-specific antibodies in normal human sera. I. Characterization of specificity for beta-D-glucose.

A glucose-dependent hemagglutinin, present in the serum of an apparently healthy donor, is shown to be a polyclonal IgM immunoglobulin with specificity for beta-D-glucopyranose configuration. The antibody did not agglutinate erythrocytes coated with hexoses differing from glucose at C2, C3, or C4 positions or lacking the primary alcohol group at C6 position. The hemagglutination reaction, quantitated in a continuous flow system, was inhibited by the addition of 6-deoxyglucose, 5-thioglucose, 2-deoxyglucose, 2-aminoglucose or 3-0 methylglucose. D-glucose, in beta- but not in alpha-configuration, attached by a glycosidic bond to another glucose or to an aglycone, was also inhibitory. A cross-reactivity was demonstrated between glucose and 6-deoxyglucose by antibody absorption and elution techniques. The donor's serum contained independent antibodies that reacted with erythrocytes coated with melibiose, gentiobiose, cellobiose, or N-acetylmannosamine. Further investigation revealed that antibodies are present in sera of all normal adults against erythrocytes coated with melibiose and N-acetylmannosamine and with high frequency against erythrocytes coated with gentiobiose, L-rhamnose, cellobiose, D-mannose, lactose, or D-galactose.

The manual polybrene test: a simple and rapid procedure for detection of red cell antibodies.

A rapid manual Polybrene test for detection of red blood cell antibodies have been devised which uses standard laboratory equipment. Red blood cells are incubated with the test sera in a low ionic medium at room temperature for one minute. Polybrene, a quaternary ammonium polymer, is then introduced to cause nonspecific red blood cell aggregation. The test tubes are centrifuged, the cell free supernatant fluid decanted, and the Polybrene effect on the cells is neutralized by adding a dilute sodium citrate-glucose solution. The hemagglutination results are evaluated macroscopically and microscopically. The entire procedure is completed in less than three minutes. In the Rh system, the test is 10--160-fold more sensitive than the antiglobulin reaction. In other systems tested, except for the Kell, a high sensitivity is achieved. The sensitivity for the Kell system is markedly increased, however, by performing a supplementary antiglobulin reaction on the sensitized, Polybrene-treated, red blood cells. The antiglobulin reagent used for this purpose should lack anti-C4 and anti-C3 activities. Sensitivity for cold reactive antibodies is augmented by cooling the cells for 30 seconds before citrate-glucose reagent is added.

Chronic autoimmune neutropenia due to anti-NA2 antibody.

In exploring the immunologic causes of chronic neutropenia, we identified a persistent neutrophil-specific antibody with NA2 specificity in the blood of a nontransfused two-year-old girl with severe neutropenia. No such antibody was detected in the maternal blood. The antibody was first studied and identified when the patient was 11 months old, but she had had clinical manifestations since the age of one month. After a trial of steroid therapy, a marked but temporary reduction in the antibody titer occurred, accompanied by the rise of the neutrophils to normal level. Neutropenia reoccurred, however, when the antibody titer began to rise, despite continuation of steroid therapy. This transient response allowed the patient's neutrophils to become available and identified as NA2-positive. Although the cause of this disorder remains obscure, the data presented indicate that the anti-NA2 autoantibody is responsible for the neutropenia observed.