Preoperative and postoperative clinical signatures of postgastrectomy venous thromboembolism in patients with gastric cancer: A retrospective cohort study.

BACKGROUND: This study aimed to identify preoperative and postoperative risk factors of venous thromboembolism (VTE) after gastrectomy in gastric cancer (GC) patients. METHODS: 757 GC patients underwent gastrectomy at our institution and 246 patients with elevated postoperative D-dimer levels who received Doppler ultrasonography of lower/upper extremity veins were enrolled. Clinicopathological factors data were collected, and the differences in clinicopathological factors between postoperative VTE (+) and VTE (-) groups were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of postgastrectomy VTE. RESULTS: Of 246 patients with elevated postgastrectomy D-dimer concentrations, 74 patients showed thrombosis in lower/upper extremity veins. Among preoperative factors, age, WBC level, D-dimer concentration, and blood glucose level were significantly higher in the postoperative VTE (+) group. Among the postoperative factors, hemoglobin level was significantly lower in the postoperative VTE (+) group. Among the pathological factors, tumor stage, depth of invasion and TNM classification indicated higher malignancy in the postoperative VTE (+) group. Univariate logistic regression analysis indicated age, preoperative blood glucose level, postoperative hemoglobin level, tumor stage, depth of invasion, and TNM classification as the independent risk factors for postgastrectomy VTE, whereas multivariate logistic regression analysis revealed age and tumor stage as independent risk factors for postgastrectomy VTE. CONCLUSION: Our study revealed that age, preoperative blood glucose level, postoperative anemia, and tumor malignancy were independent risk factors for GC patients exhibiting postgastrectomy VTE. Therefore, the perioperative monitoring, assessment and management of risk factors are important in achieving better outcomes after gastrectomy.

[Efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A].

OBJECTIVE: To investigate the efficacy of short-term full-dose prophylaxis in adult Chinese patients with severe hemophilia A. METHODS: Thirteen adult Chinese patients with severe hemophilia A receiving on-demand or low-dose prophylaxis underwent ultrasound examination of the target joints and evaluation of Hemophilia Joint Health Score (HJHS). The data of annual bleeding episodes in the period of on-demand or low-dose prophylaxis were collected retrospectively from the patients, and the changes in bleeding and joint condition (ultrasound findings of the target joints and HJHS) were observed during short-term full-dose prophylaxis. The activity intensity of the patients was assessed using the IPAQ questionnaire, and the 72 h FⅧ trough activity was measured during full-dose prophylaxis. RESULTS: The median age of the 13 patients was 26.0 (20.5-29.0) years. For full-dose prophylaxis, the patients received a median therapeutic dose of 31.0 (29.1-33.0) IU/kg, administered for 3 times per week; the median 72 h FⅧ trough activity of patients was 1.7% (1.3-3.4%). During the follow-up period for 3 months, the annual bleeding rates (ABR) and annual joint bleeding rates (AJBR) decreased significantly in all the patients (P=0.001 and 0.001, respectively), but zero bleeding was achieved in only 4 patients (30.8%) and zero joint bleeding in 7 patients (53.8%); 9 patients (69.2%) still experienced breakthrough bleeding. The damage severity of target joints assessed by ultrasound and HJHS in 6 patients (46.2%)was worse than before and no obvious progression of target joints damage was found in 7 patients (53.8%). Compared with the patients without progression, the patients with worsened joint damage had poorer baseline joint condition, higher bleeding frequencies before and during the follow-up, a higher intensity of physical activity, and a lower baseline FⅧ activity. CONCLUSIONS: At present, although short-term full-dose prophylaxis can significantly reduce the bleeding and partially prevent the progression of joint damage, it is not yet possible to achieve the goal of zero bleeding for all adult patients with severe hemophilia A in China, nor can it completely prevent further joint damage. For adult patients with different clinical bleeding phenotypes, joint conditions and physical activity intensity, individualized therapy involving additional evaluation methods should be implemented, and physiotherapy and surgical intervention can be considered when necessary.

[Prophylactic treatment with low- and intermediate-dose factor VIII in children with severe hemophilia A: comprehensive evaluation of joint outcomes and correlation analysis].

OBJECTIVE: To study the effect of low- and intermediate-dose factor VIII (FVIII) for prophylactic treatment of severe hemophilia A in children by comprehensively evaluating the outcomes of the joints. METHODS: Forty-seven children with severe hemophilia A (FVIII activity ≤2%) were enrolled in this study. Eighteen of the children received prophylactic treatment with low-dose FVIII (10 U/kg, 2-3 times a week), 20 received prophylactic treatment with intermediate-dose FVIII (15-30 U/kg, 3 times a week), and 9 received on-demand treatment with FVIII infusion when bleeding occurred according to the Chinese Expert Consensus on the Diagnosis and Treatment of Hemophilia. The children were followed up for 180 days to observe the changes in the indexes of clinical bleeding phenotype, joint structure, joint function, and joint mobility, and the correlation of these indexes were analyzed. RESULTS: Compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII significantly improved the clinical hemorrhage phenotype (P<0.01), and the improvement was significantly more conspicuous with intermediate-dose prophylactic treatment (P<0.05). Comprehensive evaluation of the joint structure and function changes showed that compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII resulted in significant improvements in the total score of Hemophilia Joint Health Score (HJHS), Functional Independence Score in Hemophilia (FISH), the single most severe target joint ultrasound and HJHS score of the target joint (P<0.05) and prophylactic treatment with intermediate-dose FVIII appeared to produce better outcomes of the joint than low-dose FVIII. No correlation was found between annual target joint bleeding rate (ATJBR) and ultrasound score, between ATJBR and HJHS change, or between annual joint bleeding rate (AJBR) and the total score of FISH (P>0.05). CONCLUSION: Compared with on-demand treatment, prophylactic treatment with low- and intermediate-dose FVIII can significantly improve the bleeding phenotype and delay the progression of joint injury, but the clinical hemorrhagic phenotype is not sufficient to monitor the disease progression.

[Breakthrough bleeding in adult patients with severe hemophilia A receiving low- and intermediate-dose FVIII for tertiary prophylaxis: characteristics and influencing factors].

OBJECTIVE: To investigate the characteristics of breakthrough bleeding in adult patients with severe hemophilia A (SHA) receiving low- and intermediate-dose FVIII for tertiary prophylaxis and explore the factors affecting the outcomes of the treatment. METHODS: Forty-nine patients (mean age 31.53∓7.33 years) with SHA receiving tertiary prophylaxis FVIII treatment were divided into low-dose group (n=15) and intermediate-dose group (n=34). The data including clinical bleeding phenotype (Pre?AJBR), 72 h FVIII trough activity, and Functional Independence Score in Hemophilia (FISH) were recorded in all the patients, and Hemophilia Steward APP was used to record the bleeding episode and the treatment data. All the patients were followed up for at least 6 months. RESULTS: In the low-dose and intermediate-dose groups, the number of joint bleeding (AJBR) episodes were 18.79∓13.03 and 9.28∓7.02 per year (P=0.016), and the proportions of spontaneous bleeding were 75.0% and 47.7%, respectively. The proportions of patients with target joint were 80% and 44%, target joint bleeding occurred in 59% and 41%, and cataract bleeding after 0-12 h of prophylactic injection occurred in 4.86% and 5.18% of the patients with a median breakthrough bleeding time of 40.08 h and 46.08 h (P=0.008), respectively. The proportions of patients with 72 h FVIII trough activity <1% were 44.4% and 34.8% in the two groups, respectively. AJBR was negatively correlated with the preventive dose consumed (r=-0.57, P=0.000, n=49) and FISH, but positively correlated with Pre-AJBR in the two groups (P<0.05). CONCLUSION: Tertiary prophylaxis with low- and intermediate-dose FVIII is not sufficient to achieve the goal of preventing progression of joint disease in Chinese adult patients with SHA. Although the prophylactic dose is the most important factor to affect the treatment efficacy, other non-factor approaches may also help to improve the efficacy of the treatment.

Pyrus pyrifolia stylar S-RNase induces alterations in the actin cytoskeleton in self-pollen and tubes in vitro.

Pears (Pyrus pyrifolia L.) have an S-RNase-based gametophytic self-incompatibility system, and S-RNases have also been implicated in self-pollen or genetically identical pollen rejection. Tip growth of the pollen tube is dependent on a functioning actin cytoskeleton. In this study, configurations of the actin cytoskeleton in P. pyrifolia pollen and effects of stylar S-RNases on its dynamics were investigated by fluorescence and confocal microscopy. Results show that actin filaments in normal pollen grains exist in fusiform or circular structures. When the pollen germinates, actin filaments assembled around one of the germination pores, and then actin bundles oriented axially throughout the shank of the growing tube. There was a lack of actin filaments 5-15 microm from the tube tip. When self-stylar S-RNase was added to the basal medium, pollen germination and tube growth were inhibited. The configuration of the actin cytoskeleton changed throughout the culturing time: during the first 20 min, the actin configurations in the self-pollen and tube were similar to the control; after 20 min of treatment, the actin filaments in the pollen tube gradually moved into a network running from the shank to the tip; finally, there was punctate actin present throughout the whole tube. Although the actin filaments of the self-pollen grain also disintegrated into punctate foci, the change was slower than in the tube. Furthermore, the alterations to the actin cytoskeleton occurred prior to the arrest of pollen tube growth. These results suggest that P. pyrifolia stylar S-RNase induces alterations in the actin cytoskeleton in self-pollen grains and tubes.

[Effects of G-protein regulators and stylar S-RNase on the growth and Ca2+ concentration of Pyrus pyrifolia pollen tube].

The effects of G protein regulators and stylar S-RNase on the growth and [Ca(2+)](i) changes of the Pyrus pyrifolia pollen tube were investigated using Laser Confocal Scanning Microscope (LCSM). The results indicated that: (1) The growth of 'Housui' pollen tube could be inhibited by its stylar S-RNase and pertussis toxin (PTX), the inhibitor of heterotrimeric G protein. While 'Kousui' stylar S-RNase had little effect on the growth of 'Housui' pollen tube; cholera toxin (CTX), the activator of heterotrimeric G protein, could promote pollen tube growth and eliminate the suppression of stylar S-RNase on the growth of self-pollen tube, but the growth of 'Housui' pollen tube could be arrested under the co-action of PTX and S-RNase from 'Kousui' Fig.1). (2) Treatments with different stylar S-RNase and G protein regulators could have different effects on the change in [Ca(2+)](i) in the tip of pollen tube (Figs.2,3). The treatment with 'Housui' stylar S-RNase could induce the decrease of fluorescence gradient of [Ca(2+)](i) along the tip of self-pollen tube (Figs.2A, 3A), and the treatment with CTX could markedly elevate [Ca(2+)](i) in the tip of pollen tube showed (Fig.3C). The way of [Ca(2+)](i) changed in 'Housui' pollen tube under the co-action of CTX and its stylar S-RNase showed the compositive effect of the two respective treatment (Fig.3A, C, E), but the effect of the co-action of PTX and 'Kousui' stylar S-RNase showed increase in [Ca(2+)](i) in the pollen tube in 18 min after treatment, and then decrease between 18-36 min (Fig.3F). These results suggest that during self or cross pollination, the control of the growth of Pyrus pyrifolia pollen tube is by the synergistic effect of stylar S-RNase, G protein and [Ca(2+)](i) in the pollen tube.

[The effect of G protein regulator on pollen germination and [Ca2+]i variation in Pyrus serotina Rehd. pollen].

The effects of the cholera toxin (CTX) and pertussis toxin (PTX), which can activate and antagonize respectively the heterotrimeric G protein, on pollen germination, pollen tube growth and the dynamic of cytosolic free calcium concentration ([Ca(2+)]i) in pear pollen were investigated using Laser Confocal Scanning Microscope (LCSM). The results show that CTX could stimulate pollen germination and tube growth while PTX had the opposite effect. CTX and PTX had marked influence on the dynamic of pollen [Ca(2+)]i. The CTX treatment had no significant effect on the changes in pollen [Ca(2+)]i during pollen germination, but induced specific signaling of "calcium transient" in pollen. Treatment with PTX caused decline of pollen [Ca(2+)]i in the first 18 min after treatment. These data suggested that the regulation of pollen germination and tube growth in Pyrus serotina may involve in heterotrimeric G protein, which can stimulate specific change of pollen [Ca(2+)]i.