Similarities and Differences between Clavicular Bacterial Osteomyelitis and Nonbacterial Osteitis: Comparisons of 327 Reported Cases.

BACKGROUND: Currently, both clavicular bacterial osteomyelitis (BO) and nonbacterial osteitis (NBO) remain not well understood owing to their much lower incidences. This study is aimed at summarizing similarities and differences between clavicular BO and NBO based on comparisons of literature-reported cases. METHODS: We searched the PubMed and Embase databases to identify English published literature between January 1st, 1980, and December 31st, 2018. Inclusion criteria were studies evaluating clinical features, diagnosis, and treatment of clavicular BO and NBO, with eligible data for synthesis analysis. RESULTS: Altogether, 129 studies with 327 patients were included. Compared with BO, clavicular NBO favored females (P < 0.001) and age below 20 years (P < 0.001) and mostly presented in a chronic phase (disease term exceeding 2 months) (P < 0.001). Although local pain and swelling were the top two symptoms for both disorders, fever, erythema, and a sinus tract were more frequently found in BO patients (P < 0.01). Although they both favored the medial side, lesions in the clavicular lateral side mostly occurred in BO patients (P = 0.002). However, no significant differences were identified regarding the serological levels of white blood cell count (P = 0.06), erythrocyte sedimentation rate (P = 0.27), or C-reactive protein (P = 0.33) between BO and NBO patients before therapy. Overall, the BO patients achieved a statistically higher cure rate than that of the NBO patients (P = 0.018). CONCLUSIONS: Females, age below 20 years, and a long duration of clavicular pain and swelling may imply NBO. While the occurrence of a sinus tract and lesions in the lateral side may be clues of BO, inflammatory biomarkers revealed limited values for differential diagnosis. BO patients could achieve a better efficacy than the NBO patients based on current evidence.

[Analysis of Clinical Characteristics of Acute B Lymphoblastic Leukemia with EP300-ZNF384 Fusion Gene Positive].

OBJECTIVE: To investigate the clinical manifestations and laboratory features of B-ALL patients with EP300-ZNF384 fusion gene positive, so as to improve the understanding of this subtype disease. METHODS: The clinical data of 3 B-ALL patients with EP300-ZNF384 fusion gene positive admitted in Department of Hematology, the first medical center of Chinese PLA general hospital from February 2017 to February 2018 were collected and analyzed retrospectively. The clinical and laboratory characteristics as well as the therapentic outcome in B-ALL patients with EP300-ZNF384 fusion gene positive were analyzed. RESULTS: The fusion gene of EP300-ZNF384 was detected in 8.1%(3/37) of B-ALL patients. All cases showed the normal karyotype and aberrant CD13 and/or CD33 expression for immunophenotype. 3 patients were sensitive to traditional chemotherapy. CONCLUSION: The B-ALL with EEP300-ZNF384 fusion gene positive may be a subgroup of B-ALL with a uniqe clinical characteristis and laboatorial features. EP300-ZNF384 positive patients show a good response to conventional chemotherapy, suggesting a favorable prognosis.

Aucubin Protects Chondrocytes Against IL-1ß-Induced Apoptosis In Vitro And Inhibits Osteoarthritis In Mice Model.

OBJECTIVE: Chondrocyte apoptosis has also been strongly correlated with the severity of cartilage damage and matrix depletion in an osteoarthritis (OA) joint. Therefore, pharmacological inhibitors of apoptosis may provide a novel treatment option for patients with OA. Aucubin, a natural compound isolated from Eucommia ulmoides, has been proved to possess antioxidative and anti-apoptotic properties. However, anti-osteoarthritis effect of aucubin in animal model and anti-apoptotic response of aucubin in OA chondrocytes remain unclear. This study aimed to determine whether aucubin could slow progression of OA in a mouse model and inhibit the IL-1ß-induced chondrocyte apoptosis. METHODS: OA severity and articular cartilage degradation were evaluated by Safranin-O staining, Hematoxylin-eosin (H&E) staining, and Osteoarthritis Research Society International (OARSI) standards. Chondrocyte viability was observed by Cell Counting Kit-8 (CCK8) and live/dead cells assay; the apoptotic rate of chondrocytes was evaluated by flow cytometry (FCM) with Annexin V-FITC/PI kit. Mediators of apoptosis were tested by Western blot of Bax, caspase-3, caspase-9, and Bcl-2 expression. The intracellular levels of Reactive oxygen species (ROS) were assessed by the probe of 2,7-Dichlorofluorescin diacetate (DCFH-DA). RESULTS: The articular cartilage in the limb with destabilization of the medial meniscus (DMM) exhibited early OA-like manifestations characterized by proteoglycan loss, cartilage fibrillation, and erosion, with lower OARSI score. Oral administration of aucubin remarkably attenuated the loss of proteoglycan and the articular cartilage erosion and decreased the OARSI scores underwent DMM surgery. Aucubin treatment significantly reverses IL-1ß-induced cytotoxicity and attenuated the IL-1ß-induced chondrocyte apoptosis. In addition, aucubin can significantly inhibit mediators of apoptosis in rat primary chondrocytes. Furthermore, aucubin remarkably attenuated the IL-1ß-induced intracellular ROS production. CONCLUSION: Our findings suggest that aucubin has a protective effect on articular cartilage and slowing progression of OA in a mouse model. This protective effect may result from inhibiting chondrocyte apoptosis and excessive ROS production.

[Clinical Retrospective Analysis of Chronic Myeloid Leukemia in Myeloid Blast Crisis].

OBJECTIVE: To retrospectively analyze the clinical manifestation, laboratorial test features and prognosis of patients with CML in myeloid blast crisis. METHODS: The clinical data of 10 patients with CML in myeloid blast crisis admitted in Chinese PLA General Hospital from June 2011 to May 2018 were collected, and their clinical features, laboratorial data and long-term survival were analyzed. RESULTS: The median age of these 10 cases was 32.5 (23-73) years old. Nine cases had chronic phase history. The median chronic phase was 17(4-84) months. All the 10 cases had splenomegaly; B-ultrasonography showed that the median spleen size was 5.2 (4-7.8) cm in thickness, and 14.6 (11.4-19.8) in length. When chronic myeloid leukemia was in blast crisis, the median WBC count was 41.705（11.9-344.41）×109 /L and the median platelet count was 159 (13-2326) ×109 /L. The Ph+ chromosome and BCR-ABL1 fusion gene coulld be detected in all the cases. The chromosome karyotyping showed that additional chromosome abnormalities were found in 5 cases. One case was of low diploid, and two cases were with complex karyotype. ABL1 mutation was detected in 6 out of these 10 cases. ABL1 T315I mutation was detected in 2 of them and one was with deletion of combined P53 in genetic tests. The median follow-up time was 10.5(0.2-78) months. There were 5 cases treated sequentially by chemotheraphy with or without TKI and allo-HSCT. Three cases reached CP2 before transplantation. Among them, two cases still survived without progression for 67 months and 69 months after the transplantation respectively. One case died of transplantation-related mortality (suffered from cerebral hemorrhage 7 months after the transplantation). Two cases were NR before the transplantation, and both died of disease relapse or progression at the time points of one or three months after the transplantation. Five cases treated by TKI ± chemotheraphy and without HSCT succumbed to disease progression. The median time was 6(0.2-22) months. CONCLUSION: CML patients in myeloid blast crisis treated by chemotheraphy combined with TKI gain CP2, the survival time of patients treated by sequential allo-HSCT is prolonged.

SDF-1/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis.

Crosstalk between subchondral bone and articular cartilage is considered a central feature of osteoarthritis (OA) initiation and progression, but its underlying molecular mechanism remains elusive. Meanwhile, specific administration of drugs in subchondral bone is also a great challenge during investigation of the process. We here explore the role of stromal cell-derived factor 1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis in the crosstalk between subchondral bone and articular cartilage in OA pathogenesis, using osmotic infusion pumps implanted in tibial subchondral bone directly to ensure quantitative, continuous and steady drug delivery over the entire experiment. We found that increased SDF-1 in subchondral bone firstly induced subchondral bone deterioration by erroneous Mesenchymal Stem Cells (MSCs) recruitment and excessive bone resorption in anterior cruciate ligament transection (ACLT) mice. Deterioration of subchondral bone then led to the traverse of SDF-1 from subchondral bone to overlying cartilage. Finally, SDF-1 from underlying subchondral bone combined with CXCR4 in chondrocytes to induce articular cartilage degradation by promoting the shift of transforming growth factor-ß receptor type I (TßRI) in chondrocytes from activin receptor-like kinase 5 (ALK5) to activin receptor-like kinase 1 (ALK1). More importantly, specific inhibition of SDF-1/CXCR4 axis in ACLT rats attenuated OA by stabilizing subchondral bone microarchitecture, reducing SDF-1 in cartilage and abrogating the shift of TßRI in chondrocytes. Our data demonstrate that the SDF-1/CXCR4 axis may coordinate the crosstalk between subchondral bone and articular cartilage in OA pathogenesis. Therefore, specific inhibition of SDF-1/CXCR4 axis in subchondral bone or intervention in SDF-1 traverse may be therapeutic targets for OA.

Interleukin-1 Beta Gene Polymorphism rs16944 May Associate with Increased Susceptibility to Extremity Chronic Osteomyelitis in Chinese Han Population.

BACKGROUND: Previous studies had indicated that interleukin-1 beta (IL-1ß) gene single nucleotide polymorphisms (SNPs) associate with different inflammatory diseases. However, potential links between these polymorphisms and susceptibility to extremity chronic osteomyelitis (COM) remain unclear. This study aimed to investigate relationships between IL-1ß gene polymorphisms (rs16944, rs1143627, rs1143634, and rs2853550) and risks of developing extremity COM in Chinese Han population. METHODS: Altogether 233 extremity COM patients and 200 healthy controls were genotyped for the four tag SNPs of the IL-1ß gene using the SNapShot genotyping method. Comparisons were performed regarding genotype distribution, mutant allele frequency, and four genetic models (dominant, recessive, homozygous, and heterozygous models) of the four SNPs between the two groups. RESULTS: Significant associations were identified between rs16944 polymorphism and the risk of developing COM by dominant model (P = 0.026, OR = 1.698, 95% CI 1.065-2.707) and heterozygous model (P = 0.030, OR = 1.733, 95% CI 1.055-2.847). Although no statistical differences were found of rs1143627 polymorphism between the two groups, there existed a trend that rs1143627 may be linked to an elevated risk of developing COM by outcomes of dominant (P = 0.061), homozygous (P = 0.080) and heterozygous (P = 0.095) models. However, no statistical correlations were found between rs1143634 and rs2853550 polymorphisms and susceptibility to COM in Chinese Han population. CONCLUSIONS: To our knowledge, we reported for the first time that IL-1ß gene rs16944 polymorphism may contribute to the increased susceptibility to extremity COM in Chinese Han population, with genotype of AG as a risk factor.

Clinical characteristics and treatment of clavicular osteomyelitis: a systematic review with pooled analysis of 294 reported cases.

BACKGROUND: It is usually difficult to diagnose clavicular osteomyelitis (OM), and treatment is delayed because of its rarity. This study aimed to summarize clinical characteristics and treatment of this disease. METHODS: We searched the PubMed and Embase databases to identify English studies that reported on clavicular OM from January 1980 through December 2016. Effective data were pooled for analysis. RESULTS: In total, 111 studies comprising 294 cases (bacterial OM, 146; nonbacterial OM, 148) were included, with a sex ratio of 1.89:1 indicating female predilection. Overall, the median age at diagnosis was 16 years. The acute to chronic phase ratio was 0.30, with a median symptom duration of 4 months. The most frequently reported symptom was pain (192 cases), followed by swelling (151 cases) and fever (52 cases). Altogether, 86.94% cases of single-site involvement were reported, with the medial side being the most common site (69.95%). The erythrocyte sedimentation rate achieved the highest positive rate (74.44%) before treatment. The total positive rate of culture for bacterial OM was 81.82%, with Staphylococcus aureus being the most frequently detected pathogen (44.70%). The average cure rate was 83.52%, with no significant difference between surgical (89.70%) and nonsurgical (79.63%) cases (P = .079). CONCLUSIONS: Clavicular OM, predominant in female patients and young people, usually occurred at a chronic stage. Pain was the most frequent symptom, with the medial side being the most involved site. The erythrocyte sedimentation rate may be a helpful indicator for diagnosis. Regardless of surgery or nonsurgery, most patients achieved a favorable prognosis.

Lateral Subcutaneous Locking Compression Plate and Small Incision Reduction for Distal-third Diaphyseal Humerus Fractures.

OBJECTIVE: Iatrogenic radial nerve injury is a great challenge for orthopaedic surgeons who deal with distal-third diaphyseal humerus fractures. Conventional open reduction and internal fixation (ORIF) remains the gold standard, but complications such as nonunion and iatrogenic radial nerve injury still occur. We fixed the fractures with a lateral locking compression plate (LCP) subcutaneously after small incision reduction to protect the radial nerve. This study reports the clinical and radiographic outcomes of our modified method. METHODS: Thirty-eight patients with distal-third diaphyseal humerus fractures were treated with lateral subcutaneous LCP and small incision reduction at our department between September 2013 and August 2016. There were 33 males and 5 females, with an average age of 30.3 years (range, 17 to 49 years). All the cases were types A or B (AO/OTA classification, type A, 24 cases; type B, 14 cases). Among them, 6 cases were combined with preoperative radial nerve palsy. All patients were diagnosed with closed humeral fractures after X-ray examination, and had typical upper limb pain, swelling, and movement disorders. The operations were performed by a single surgeons' team. Union time, range of motion (ROM), University of California, Los Angeles (UCLA) shoulder rating scale, and Mayo Elbow Performance Index (MEPI) scores were assessed to evaluate the postoperative results. RESULTS: All patients were followed up for an average of 11.4 months (range, 3 to 36 months). The average operation time was 75.5 min (range, 60 to 150 min) and average intraoperative radiation exposure was 10.5 s (range, 8 to 18 s). Bony union was achieved in all cases after an average of 16.2 weeks (range, 12 to 25 weeks). No complications such as infection or screw and plate fracture occurred, and no iatrogenic radial nerve injury was observed. According to the UCLA shoulder rating scale, the average score was 33.7 (range, 31 to 35), with 33 excellent (86.8%) and 5 good cases (13.2%). They were all excellent according to their MEPI scores (ranging, 94 to 100, with an average of 97.4). The average operation time for secondary removal of the plate was 15.2 min (range, 10 to 20 min), and no complications such as infection or secondary radial nerve injury occurred. CONCLUSIONS: Lateral subcutaneous LCP and small incision reduction may reduce the risk of iatrogenic radial nerve injury significantly in the treatment of distal-third diaphyseal humerus fractures. It also leads to solid fixation, good postoperative function, and convenient removal of the plate without injuring the radial nerve.

[Safety and Effectiveness of High Dose Tigecycline for Treating Patients with Acute Leukemia after Ineffctiveness of Carbapenems Chemotherapy Combinating with Febrile Neutropenia: Retrospective study].

OBJECTIVE: To investigate the safety and efficacy of high dose tigecycline for treatment of fibric neutrope-nia in acute leukemia patients after ineffectiveness of carbapenems chemotherapy of acute leukemia. METHODS: The clinical data of 41 acute leukemia patients with febrile ncutropenia received high dose tigecycline (100 mg q12h), who showed ineffectiveness of treatment with carbapenems, from 20151.30-2017.1. 29 in our hospital were collected and analyzed retrospectively. The temperature, inflammatory indicators as well as hepatic and renal function before and after treatment with tigecycline were compared. RESULTS: Among 41 patients treated with tigecycline due to ineffectiveness of treatment with carbapenems, the infection had been controled in 34 cases, 7 patients died due to ineffectiveness of anti-infective treatment, these patients all were patients with relapse/refractory leukemia. 41 patients were examined etialogically, as a result, 22 patients showed possitive, among them the gram-negative bacill was found in 11(11/22) cases. The average deferves counce time of tigecycline was 28.2±12.0 hours. The temperature of patients treated with tigecycline for 48 hours decreased significantly (P<0.05). There were no significant differences in calcitonin and C-reactive protein levels after treatment with tigecycline (P>0.05), but cacitonin level displayed decrease tread. There was no hepatic and renal impairment after treatment with tigecycline, but levels of as partate aminotransferase, total bilirubin and blood area nitrogen in blood significantly increased as compared with levels before treatment with tigecycline (P<0.05). CONCLUSION: The application of high dose tigecycline for treatment of febrile neutropenia is safety and effective. The high dose tigecycline can decrease the temperature, calcitonin and C-reactive protein levels, and can control infection without the hepatic and renal impairment, but it needs to be confimed by more prospective studies.

Serum TNF-α, erythrocyte sedimentation rate and IL-6 are more valuable biomarkers for assisted diagnosis of extremity chronic osteomyelitis.

AIM: This study aimed to investigate the values of preoperative serum levels of white blood cell, erythrocyte sedimentation rate (ESR), C-reactive protein, procalcitonin, IL-6, TNF-α and serum amyloid A for diagnosis of chronic osteomyelitis (COM) in Chinese patients. METHODS: All 586 eligible patients were included for analysis. RESULTS: Outcomes revealed that positive ratios of TNF-α, ESR and IL-6 lied in top three. Taken predicted probability and detection cost into consideration, combination of ESR, IL-6 and TNF-α might be the optimal model due to its high predicted probability for COM (91.02%) with an acceptable cost (CN¥161). CONCLUSION: Combination of preoperative serum TNF-α, ESR and IL-6 can help a reliable predication of COM.