PURPOSE: To summarize and analyze the early treatment of multiple injuries combined with severe pelvic fractures, especially focus on the hemostasis methods for severe pelvic fractures, so as to improve the successful rate of rescue for the fatal hemorrhagic shock caused by pelvic fractures. METHODS: A retrospective analysis was conducted in 68 cases of multiple trauma combined with severe pelvic fractures in recent 10 years (from Jan. 2006 to Dec. 2015). There were 57 males and 11 females. Their age ranged from 19 to 75 years, averaging 42 years. Causes of injury included traffic accidents in 34 cases (2 cases of truck rolling), high falling injuries in 17 cases, crashing injuries in 15 cases, steel cable wound in 1 case, and seat belt traction injury in 1 case. There were 31 cases of head injury, 11 cases of chest injury, 56 cases of abdominal and pelvic injuries, and 37 cases of spinal and limb injuries. Therapeutic methods included early anti-shock measures, surgical hemostasis based on internal iliac artery devasculization for pelvic hemorrhage, and early treatment for combined organ damage and complications included embolization and repair of the liver, spleen and kidney, splenectomy, nephrectomy, intestinal resection, colostomy, bladder ostomy, and urethral repair, etc. Patients in this series received blood transfusion volume of 1200-10,000 mL, with an average volume of 2850 mL. Postoperative follow-up ranged from 6 months to 1.5 years. RESULTS: The average score of ISS in this series was 38.6 points. 49 cases were successfully treated and the total survival rate was 72.1%. Totally 19 patients died (average ISS score 42.4), including 6 cases of hemorrhagic shock, 8 cases of brain injury, 1 case of cardiac injury, 2 cases of pulmonary infection, 1 case of pulmonary embolism, and 1 case of multiple organ failure. Postoperative complications included 1 case of urethral stricture (after secondary repair), 1 case of sexual dysfunction (combined with urethral rupture), 1 case of lower limb amputation (femoral artery thrombosis), and 18 cases of consumptive coagulopathy. CONCLUSION The early treatment of multiple injuries combined with severe pelvic fractures should focus on pelvic hemostasis. Massive bleeding-induced hemorrhagic shock is one of the main causes of poor prognosis. The technique of internal iliac artery devasculization including ligation and embolization can be used as an effective measure to stop or reduce bleeding. Consumptive coagulopathy is difficult to deal with, which should be detected and treated as soon as possible after surgical measures have been performed. The effect of using recombinant factor VII in treating consumptive coagulopathy is satisfactory.
Adult ; Embolization, Therapeutic ; methods ; Factor VII ; administration & dosage ; Female ; Fractures, Bone ; complications ; therapy ; Hemostasis, Surgical ; Humans ; Iliac Artery ; surgery ; Injury Severity Score ; Ligation ; Male ; Middle Aged ; Multiple Trauma ; complications ; therapy ; Pelvic Bones ; injuries ; Prognosis ; Recombinant Proteins ; administration & dosage ; Retrospective Studies ; Shock, Hemorrhagic ; etiology ; prevention & control ; Young Adult

PURPOSE: To compare the efficacy and safety of recombinant human bone morphogenetic protein (rhBMP) and iliac crest autograft in the fusion treatment of lumbar spondylolisthesis. METHODS: The studies using randomized controlled trials to compare the rhBMP with iliac crest autograft in the treatment of lumbar spondylolisthesis were retrieved from Embase, Pubmed, ProQuest dissertations & theses (PQDT), China national knowledge infrastructure (CNKI), Chinese Biomedical Database, Wanfang Data, Cochrane Library (from March 1998 to March 2018). Postoperative fusion rate, clinical success rate, postoperative intervertebral height, complications, operation time, blood loss and duration of hospitalization were chosen as the outcome indicators. Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical software Revman 5.3 was used for data-analysis. RESULTS: Eleven articles were included in the meta-analysis. The results showed that, comparing the efficacy of rhBMP with iliac crest autograft, statistical significance was found in the 24-month fusion rate post operation [95% CI (1.38, 24.70), p = 0.02] and operation time [95% CI (-14.22, -2.08), p = 0.008]. There is not sufficient evidence for statistical differences in the remaining indicators. CONCLUSION The current literature shows rhBMP is a safe and effective grafting material in the treatment of lumbar spondylolisthesis. Further evidence is dependent on the emergence of more randomized controlled trials with higher quality and larger sample sizes in the future.
Autografts ; Bone Morphogenetic Proteins ; administration & dosage ; Databases, Bibliographic ; Humans ; Ilium ; transplantation ; Lumbar Vertebrae ; surgery ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; administration & dosage ; Spinal Fusion ; methods ; Spondylolisthesis ; surgery ; Time Factors ; Treatment Outcome

OBJECTIVE: To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. METHODS: Mice were immunized intranasally with PBS (negative control), or H3N2 split vaccine (3 μg/mouse) alone, or CTA1-DD (5 μg/mouse) alone, or H3N2 split vaccine (3 μg/mouse) plus CTA1-DD (5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine (3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. RESULTS: H3N2 split vaccine formulated with CTA1-DD could elicit higher IgM, IgG and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory IgA titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. CONCLUSION CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.
Adjuvants, Immunologic ; Administration, Intranasal ; Animals ; Cholera Toxin ; Female ; Immunity, Humoral ; Influenza A Virus, H3N2 Subtype ; immunology ; Influenza Vaccines ; Mice, Inbred BALB C ; Nasal Mucosa ; immunology ; Random Allocation ; Recombinant Fusion Proteins

OBJECTIVETo explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with high-dose dexamethasone (DXM) in the treatment of children with refractory immune thrombocytopenic purpura (ITP).

METHODSFifty-eight ITP children who had failed first-line therapy were randomly divided into two groups: DXM treatment (n=27) and rhTPO + DXM treatment (n=31). The DXM treatment group received two continuous cycles of DXM treatment; in each cycle, patients received high-dose DXM (0.6 mg/kg daily) by intravenous drip for 4 days every 28 days. The rhTPO group received subcutaneous injection of rhTPO (300 U/kg daily) for 14 days additional to DXM treatment. The overall response rate (marked response rate + slight response rate) and adverse reactions were evaluated after 3, 7, and 14 days and 1, 2, and 3 months of treatment.

RESULTSAfter 7 and 14 days and 1 month of treatment, the rhTPO + DXM treatment group had a significantly higher marked response rate and a significantly higher overall response rate than the DXM treatment group (P<0.05). After 2 months of treatment, the rhTPO + DXM treatment group had a significantly higher overall response rate than the DXM group (P<0.05). One patient in the DXM treatment group had liver damage during the first week of treatment. There was no hypertension, fever, rash, allergy, or weakness in the two groups.

CONCLUSIONSrhTPO combined with high-dose DXM is an effective and safe approach for treating refractory ITP.

Child ; Child, Preschool ; Dexamethasone ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Infant ; Male ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; administration & dosage ; Thrombopoietin ; administration & dosage ; adverse effects ; Treatment Outcome

BACKGROUNDHepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a.

METHODSA total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months.

RESULTSBaseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss.

CONCLUSIONSPatients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.

Antiviral Agents ; administration & dosage ; therapeutic use ; Drug Administration Schedule ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B, Chronic ; drug therapy ; metabolism ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Kinetics ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

METHODSA total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment.

RESULTSThe median treatment time for HBsAg loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005).

CONCLUSIONBaseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Child ; Child, Preschool ; DNA, Viral ; blood ; Drug Administration Schedule ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Young Adult

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

OBJECTIVETo explore the formation of pre-metastatic niche in the mouse lung and to study the underlying molecular mechanisms whereby primary breast carcinoma-derived factors mediate recruitment of bone marrow-derived cells (BMDCs) and affect the formation of pre-metastatic lung environment before the arrival of tumor cells.

METHODSMammary carcinoma 4T1 cells were inoculated into the mammary gland to construct mouse model of breast cancer. Confocal microscopy was used to detect the recruitment of BMDCs in the pre-metastatic lungs. The expression of factors in the mouse sera and 4T1 cell culture media was assayed using RayBio Custom mouse cytokine antibody array kit. The mice were injected daily with recombinant VEGF for 7 consecutive days to observe the effect of VEGF on BMDCs recruitment in the mouse lung.

RESULTSNo BMDCs were observed in the lungs of control and 4T1-tumor-bearing mice on day 0. On day 7 and 14, clusters of BMDCs observed in the lungs of 4T1-tumor-bearing mice were 8.7±2.2/objective field and 48.8±3.2/objective field, respectively, significantly higher than those in the control mice (1.1±0.8/objective field and 3.1±1.7/objective field) (P<0.05 for both). Confocal microscopic observation found that metastatic breast cancer cells preferentially facilitate BMDCs recruitment sites in the pre-metastatic mouse lungs. The levels of VEGF, GM-CSF, and IL-6 in the serum of 4T1-tumor-bearing mice were significantly increased compared with those in the control group (P<0.05 for all). However, VEGF was detected only in the culture media of 4T1 cells. The amount of BMDCs in the mouse lung tissue was (22.8±3.6)/objective field in the VEGF group and (3.1±0.4)/objective field in the control group (P<0.05). There were 36.8±5.4 metastatic foci in the lung tissue of VEGF group and 12.6±2.2 in the control group (P<0.05).

CONCLUSIONSThe results of this study demonstrate that primary breast cancer cells can alter the lung microenvironment during the pre-metastatic phase and induce the formation of pre-metastatic niche. Primary tumor cell-derived VEGF may be a crucial factor responsible for the formation of pre-metastatic niche.

Animals ; Bone Marrow Cells ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; blood ; Humans ; Interleukin-6 ; blood ; Lung ; pathology ; Lung Neoplasms ; secondary ; Mice ; Recombinant Proteins ; administration & dosage ; Time Factors ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A ; administration & dosage ; physiology ; secretion

OBJECTIVETo evaluate the efficacy and safety of high dose dexamethasone combined with recombinant human thrombopoietin (rhTPO) in adults with severe newly diagnosed immune thrombocytopenia (ITP).

METHODSForty-eight adult patients with severe ITP were randomized into two groups, experimental group and control group. The patients in experimental group were given high-dose dexamethasone combined with rhTPO treatment, the patients in control group were given single high-dose dexamethasone treatment. Platelet count, platelet increase, as well as the overall response rate were strictly observed in the process. At the same time, the patient's drug tolerance and any adverse drug reactions were observed.

RESULTSThe platelet counts and platelet increase of the patients in experimental group were significantly higher than that in control group (P<0.05) at day 3, 7, 14, 30. There was no significant difference in overall response rates between the two groups (34.8% vs 36.0%, 56.5% vs 48.0%, P>0.05) at day 3, 7. The overall response rates of experimental group at day 14, 30 were significantly higher than that of control group (91.3% vs 68.0%, 82.6% vs 52.0%, P<0.05). The muscle aches occurred in one patient in experimental group which was self-recovery without special treatment.

CONCLUSIONrhTPO combined with high-dose dexamethasone could rapidly increase the platelet count, reduce the risk of bleeding, and prolonge the effect with a low incidence of tolerable adverse events compared to single high-dose dexamethasone. rhTPO combined with high-dose dexamethasone could be a new therapeutic choice for severe primary ITP.

Adult ; Blood Platelets ; Dexamethasone ; administration & dosage ; therapeutic use ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombopoietin ; administration & dosage ; therapeutic use ; Treatment Outcome

PURPOSE: To report the results of switching treatment to vascular endothelial growth factor (VEGF) Trap-Eye (aflibercept) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to anti-VEGF (ranibizumab and bevacizumab). METHODS: This is a retrospective study involving 32 eyes from 29 patients; 18 were cases of neovascular AMD and 14 were cases of PCV. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) of spectral-domain optical coherence tomography were evaluated. RESULTS: BCVA and CMT improved from 0.58 to 0.55 (p = 0.005) and from 404 to 321 microm (p < 0.001), respectively, after switching to aflibercept. The 14 eyes that received 6 or more aflibercept injections remained stable at 0.81 to 0.81 and 321 to 327 microm (p = 1.0, 0.29), respectively, after 3 aflibercept injections. The 10 eyes that received 3 or more bevacizumab injections after 3 or more aflibercept injections worsened, from 0.44 to 0.47 and from 332 to 346 microm (p = 0.06, 0.05), respectively. The results showed similar improvement of BCVA and CMT in neovascular AMD and PCV. CONCLUSIONS: Aflibercept seems to be effective for improvement and maintenance of BCVA and CMT for neovascular AMD and PCV refractory to anti-VEGF. Switching from aflibercept back to bevacizumab treatment may not be a proper strategy.
Angiogenesis Inhibitors/administration & dosage ; Bevacizumab/administration & dosage ; Choroid/*blood supply ; Choroid Diseases/complications/diagnosis/*drug therapy ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Intravitreal Injections ; Male ; Ranibizumab/administration & dosage ; Receptors, Vascular Endothelial Growth Factor/*administration & dosage ; Recombinant Fusion Proteins/*administration & dosage ; Retinal Neovascularization/complications/diagnosis/*drug therapy ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; Vascular Endothelial Growth Factor A/*antagonists & inhibitors ; *Visual Acuity ; Wet Macular Degeneration/diagnosis/*drug therapy/etiology