[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Long-term observation of the effect of atlantoaxial fusion on the growth and development of children's cervical spine].

Objective: To explore the effect of atlantoaxial fusion on the growth and development of children's cervical spine. Methods: The clinical data of 12 children with atlantoaxial dislocation who underwent posterior atlantoaxial fusion at Department of Orthopaedics,the 909th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from June 2002 to September 2013 were retrospective analyzed. There were 7 males and 5 females,with age of (8.1±3.1)years (range:3 to 13 years).Nine cases were traumatic and 3 cases were congenital malformations,1 of the children had Down syndrome. All children underwent posterior atlantoaxial fusion. Furthermore,the information of the height and anteroposterior width of the cervical vertebral bodies and vertical growth rate of the fusion mass were collected from all patients immediately postoperatively and during the follow-up.The range of motion in cervical spine were collected preoperatively and during follow-up period. Data were compared using independent sample t test, paired sample t test and repeated-measurement. Results: All 12 children had regular follow-up within (122.4±25.3)months(range:65 to 163 months). The height and anteroposterior width of the cervical vertebral bodies were similar to these results with those in published reports of growth in normal children of the same age(all P<0.01). At the last follow-up,atlantoaxial fusion of 11 cases had substantial growth (vertical growth rate of the fusion mass:11 cases ≥10%, 1 case <10%);the range of motion in cervical spine was close to the normal level (flexion(55.2±5.0)°,extension (65.3±4.9)°,left bending (41.7±4.5)°,right bending (42.4±4.4)°,left rotation (66.4±5.6)°,right rotation (68.5±5.8)°). Conclusions: Atlantoaxial fusion surgery is satisfactory in the treatment of pediatric atlantoaxial dislocation.During the follow-up,the growth and development of the cervical spine is close to that of normal children of the same age.In long-term observation,it has been found that the operation has no negative effect on the growth and development of the children's cervical spine.

Positron emission tomography (18)F-fluorodeoxyglucose uptake and prognosis in patients with bone and soft tissue sarcoma: A meta-analysis.

PURPOSE: To investigate the prognostic significance of (18)F-FDG PET imaging in patients with bone and soft tissue sarcoma, a meta-analysis was conducted. METHODS: Comprehensive literature searches were performed in PubMed, Embase, Web of Science and Cochrane Library. Pooled hazard ratio (HR) values were calculated to assess the correlations of pre-chemotherapy SUV (SUV1), post-chemotherapy SUV (SUV2), SUV Ratio, total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with event-free survival (EFS) and overall survival (OS). RESULTS: Twenty-three studies with 1261 patients were identified. The combined HRs for EFS were 1.84 (95% CI: 1.54-2.20) for SUV1, 2.92 (95% CI: 2.15-3.97) for SUV2, 1.90 (95% CI: 1.43-2.52) for SUV Ratio, 3.01 (95% CI: 1.36-6.67) for TLG and 2.32 (95% CI: 1.44-3.75) for MTV. The pooled HRs for OS were 1.85 (95% CI: 1.49-2.30) for SUV1, 2.00 (95% CI: 1.39-2.88) for SUV2, 2.20 (95% CI: 1.18-4.10) for SUV Ratio, 6.19 (95% CI: 2.17-17.66) for TLG and 2.67 (95% CI: 1.52-4.68) for MTV. Besides, high SUV1 was found to be significantly associated with higher rate of metastasis (RR 5.55, 95% CI: 2.75-11.18) and local recurrence (RR 1.87 95% CI: 1.28-2.72). CONCLUSION: (18)F-FDG PET parameters of SUV1, SUV2, SUV Ratio, TLG and MTV may have effective prognostic significance for patients with bone and soft tissue sarcoma. (18)F-FDG PET imaging may be a promising tool to help predict survival outcomes of these patients.

Experience of interstitial permanent i(125) brachytherapy for extremity soft tissue sarcomas.

AIMS: Soft tissue sarcomas are uncommon, but relatively aggressive tumours. Although surgical resection remains the primary therapeutic modality for all localised tumours, brachytherapy combined with function-preserving excision is a popular treatment for extremity soft tissue sarcomas. The objective of this study was to evaluate the effect of interstitial permanent brachytherapy using I(125) seeds in patients undergoing the combined modality in the management of soft tissue sarcomas at our institution. MATERIALS AND METHODS: Between January 2007 and January 2012, 110 adult patients aged 18-86 years (median = 44 years) with extremity soft tissue sarcomas and who underwent interstitial permanent brachytherapy as part of the local treatment were included in this study. Treatment included wide local excision of the tumour and brachytherapy using a permanent I(125) implantation. Complications were assessed in terms of wound complication and peripheral nerve damage. RESULTS: After a median follow-up of 43.7 months, the local control, disease-free survival and overall survival for the entire cohort studied were 74, 54 and 77%, respectively. The actual rates of wound complications requiring reoperation and nerve damage were 4.5 and 1.8%, respectively. CONCLUSIONS: We conclude that interstitial permanent brachytherapy with I(125) after function-preserving surgery results in a satisfactory outcome in patients with extremity soft tissue sarcomas and the complication rate is low.

Beta-CTX and ICTP act as indicators of skeletal metastasis status in male patients with non-small cell lung cancer.

Bone metastasis is common in lung cancer patients and associated with reduced quality of life and reduced overall and median survival, so the early detection of bone metastasis and monitoring of its status is very important for clinicians. Serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), beta isomer of C-terminal telopeptide of type I collagen (beta-CTX) and cross-linked C-terminal telopeptide of type I collagen (ICTP) were compared with regard to their usefulness as indicators of bone metastasis in lung cancer. The serum concentrations of the 4 markers were measured by commercially available tests in 96 male patients with non-small cell lung cancer and 30 male patients with other pulmonary diseases. The levels of both â-CTX and ICTP were significantly higher in 61 lung cancer patients with bone metastases than in 35 lung cancer patients without bone metastases (both p<0.001), and significantly correlated with the extent of bone disease. Although ICTP had a better sensitivity and accuracy than beta-CTX (75.4% vs 65.6% and 72.9% vs 68.8%, respectively), they had a similar area under the receiver operating characteristic curve (0.85 vs 0.83). These results support the use of beta-CTX and ICTP as an adjunct tool for the diagnosis and screening of bone metastasis in lung cancer.

Species distribution of polymeric aluminium-ferrum--timed complexation colorimetric analysis method of Al-Fe-ferron.

The effects of the colorimetric buffer solutions were investigated while the two colorimetric reactions of Al-ferron complex and Fe-ferron complex occurred individually, and the effects of the testing wavelength and the pH of the solutions were also investigated. A timed complexation colorimetric analysis method of Al-Fe-ferron in view of the total concentration of (Al + Fe) was then established to determine the species distribution of polymeric Al-Fe. The testing wavelength was recommended at 362 nm and the testing pH value was 5. With a comparison of the ratios of nAl/nFe, the standard adsorption curves of the polymeric Al-Fe solutions were derived from the experimental results. Furthermore, the solutions' composition were various in both the molar nAl/nFe ratios, i.e. 0/0, 5/5, 9/1 and 0/10, and the concentrations associated with the total [Al + Fe] which ranged from 10(-5) to 10(-4) mol/L.

The subsequent effect of interaction between Co(2+) and human serum albumin or bovine serum albumin.

A notable hysteretic effect has been observed in the interaction of Co(II) with human serum albumin (HSA) or bovine serum albumin (BSA) using UV-Visible spectrometry at physiological pH (7.43), which shows that the binding between Co(II) and HSA or BSA may induce a slow transition of HSA or BSA from the conformation of weaker affinity for Co(II) to one of stronger affinity (A-B transition). The rate constants and activation parameters of this transition were measured and are discussed. It is inferred that such a conformation transition may occur due to the binding of the first Co(II) ion with the peptide segment of N-terminal residues 1-3, which results in a 'hinged movement' of the relatively hydrophobic 'valley' in the IA subdomain. This process leads to a slow conformational transition in the albumins, makes the other binding sites of Co(II) exposed, and shows a positive cooperativity effect. The LMCT (ligand-to-metal charge transition) bands of the Co(II)-HSA and Co(II)-BSA systems also show a kind of hypochromic effect featuring a dipole-dipole interaction mechanism. This phenomenon is rarely reported.

[Experimental study on stimulation of guided bone regeneration by acid fibroblast growth factor].

OBJECTIVE: To investigate the effect of acid fibroblast growth factor (aFGF) on guided bone regeneration (GBR), to study whether aFGF can promote the repairing ability of GBR in bone defect. METHODS: 10 mm long segmental defects were created in the diaphyses of both radii in 16 New Zealand rabbits. The defect was bridged with a silicon tube. Human recombinant aFGF was instilled into the tube on the experimental side, while the contralateral tube was instilled with saline as control group. The radiographic, gross and histologic examination of the samples were analyzed at 2, 4, 6 and 8 weeks after operation. RESULTS: On the experimental side, there was new bone formation in the bone medullary cavity, the endosteum and the section surface of the cortex at 2 weeks. At 4 weeks, at the center of the blood clot in the tube there was new bone formation and bone defect was completely healed at 8 weeks. On the control side, new bone formation was less in every period compared with that of the experimental side. At 8 weeks, there was only partial healing of the bone defect. CONCLUSION: It can be concluded that aFGF can promote new bone formation and facilitate GBR in bone defect.

[Reconstruction of hip joint function: old fracture-dislocation of hip joint complicated with deformed healing of upper 1/3 of fractured femur--a case report].

OBJECTIVE: To explore a method of reconstruction of hip joint function after deformed healing of the upper 1/3 of fractured femur as a complication of old fracture dislocation of hip joint. METHODS: A patient with loss of function in hip joint and fusion of knee joint was treated with lock for femur intra-medullary fixation in April 1997. RESULTS: Before operation, the diseased hip joint lost its most functions and the entire lower extremity was disabled because the knee joint had been fused. One year after operation, the follow-up examination revealed that the patient could walk by crutches without discomfort, his daily life and work recovered to normal. CONCLUSION: It is effective to treat a patient suffering old fracture-dislocation of hip joint complicated with deformed healing of the upper 1/3 of fractured femur by means of individualized artificial joint replacement and a prosthesis body with lock for femur intra-medullary fixation, and it is helpful for the development of a new clinical idea to reconstruct functions in the management of some particular cases.