Objective To explore clinical distribution characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP), analyze enzyme production of strains and verify the in vitro antimicrobial activity of tigecycline.Methods Antimicrobial susceptibility testing results of 53 strains of CRKP isolated from clinical specimens of patients in a hospital from January to December 2015 were analyzed, carbapenemase production of target strains was detected by modified Hodge test, metallo-β-lactamase was detected by EDTA synergy test, minimum inhibitory concentration(MIC) of tigecycline susceptibility testing result detected by instrument was confirmed by MIC test strip(MTS method).Results 53 CRKP strains were mainly isolated from patients in intensive care unit (n=14, 26.42％) and burn unit(n=13, 24.53％);sputum(n=23, 43.40％) and wound secretion(n=15, 28.30％) were the main specimen sources;isolation rate of CRKB was highest in the elderly≥60 years old, 35 strains(66.04％)of CRKP were isolated.CRKP was most sensitive to tigecycline(96.2％).The modified Hodge test showed that 48 strains(90.6％) produced carbapenemases and 15 strains produced metallo-β-lactamase.MICs of tigecycline-resistant strains detected by instrument were all confirmed as susceptibility by MTS.Conclusion CRKP mainly produce carbapenems in this hospital, some strains can produce two types of different β-lactamases;antimicrobial susceptibility testing showed that tigecycline has good antimicrobial activity against CRKP, tigecycline-resistant strains detected by instrument must be confirmed by MTS method.

Objective To report two cases of severe pulmonary complication after bortezomib treatment for multiple myeloma. Methods Two cases of severe pulmonary complication after bortezomib treatment patients with relapsed multiple myeloma wereas discussed with review of literature. Results Two relapsed MM patients were treated with bortezomib and thalidomide or dexametbasone. Cough, dyspnea, fever and hypoxia developed after completion of bortezomib. Chest X-ray revealed bilateral pulmonary infiltrates,but infection was not identified with sputum cultures, and broad-spectrum antibiotics were ineffective.Conclusion Severe pulmonary injury was rare complication in patients receiving treatment for multiple myeloma, however, it was a life-threatening disorder. Prophylaxis corticosteroids maybe effective. Although corticosteroids are effective, but the mechanism of lung injury associated with bortezomib is unclear, and further evaluation of this potential toxicity is appropriate.

ObjectiveTo investigate the value of prothrombin time-international normalized ratio to albumin ratio (PTAR) in evaluating the prognosis of patients with decompensated cirrhosis. MethodsA retrospective analysis was performed for the clinical data of 172 patients with decompensated cirrhosis who were admitted to The Second Affiliated Hospital of Kunming Medical University from April 2016 to April 2017, including sex, age, etiology, complications, and first examination of laboratory markers after admission. With death as the outcome event, the patients were divided into survival group with 98 patients and death group with 74 patients according to the outcome of the disease after 2 years of follow-up. The influencing factors for prognosis were analyzed, and the value of PTAR in predicting the prognosis of patients with decompensated cirrhosis were evaluated. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. Univariate and multivariate Cox regression analyses were performed for related variables. The receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated, and the optimal cut-off value was determined according to the sensitivity and specificity of the ROC curve. The Kaplan-Meier survival curve analysis was performed to compare 2-year survival rate between patients with different values of PTAR, indocyanine green retention rate at 15 minutes (ICGR15), and Model for End-Stage Liver Disease (MELD) score, and the log-rank test was used for comparison between groups. ResultsCompared with the survival group, the death group had significantly higher PTAR (Z=-7.823, P＜0.001), ICGR15 (t=3.458, P=0.001), and MELD score (t=5.921, P＜0.001). PTAR, ICGR15, and MELD score had optimal cut-off values of 0.05, 41.00%, and 37.25, respectively, in predicting 2-year prognosis, with AUCs of 0849, 0.651, and 0.724, respectively. The survival analysis showed that the high-PTAR (PTAR≥0.05) group had a significantly lower survival rate than the low-PTAR (PTAR＜0.05) group (χ2=60.07, P＜0.001). The multivariate Cox regression analysis showed that PTAR ≥0.05 was an independent risk factor for death within 2 years (hazard ratio = 2.564, 95% confidence interval: 1.276-5.151, P=0.008). ConclusionPTAR ≥0.05 can be used as an independent predictive factor for death within 2 years in patients with decompensated cirrhosis, and PTAR has a relatively high value in predicting the prognosis of patients with decompensated cirrhosis.

Objective: To explore the prognostic factors in newly diagnosed multiple myeloma (NDMM) patients with 1q21 amplification/gain treated with bortezomib-based regimens followed by autologous hematopoietic stem cell transplantation (ASCT) . Methods: We retrospectively assayed 35 NDMM patients with 1q21 amplification/gain who received bortezomib-based chemotherapy followed by ASCT and maintenance therapy between January 2008 and August 2015. Results: ①The median age of 35 patients were 49(33-63)years old. Ratio of male to female was 22∶13. Monosomy1q21 amplification/gain was only seen in 3(8.6%) patients, the other 32 patients were with additional cytogenetic abnormalities including 13q14 deletion, t(11,14), t(4,14), t(14,16), 17p deletion and complex karyotype aberrations. ②The complete remission (CR) rate was 57.0% (20/35), the very good partial remission(VGPR) rate was 37.1%(13/35) and the partial remission (PR) rate was 5.7%(2/35) after ASCT. At a median follow-up of 24 (8-85) months, 3-year estimated progression free survival (PFS) and overall survival (OS) rate were (66.5±9.7)% and (69.6±9.9)%, respectively. ③As 13 patients with high-risk cytogenetic abnormalities, the median PFS and OS time was 26 and 28 months. The 3-year estimated PFS and OS was (28.0±15.9)% and (36.5±16.4)%, respectively. Another 22 patients without other high-risk cytogenetic abnormalities, the median PFS and OS time was 54 months and not reached. The 3-year estimated PFS and OS was (71.5±12.7)% and (92.3±7.4)% in this group, respectively. The presence of additional other high-risk cytogenetic abnormalities resulted in significantly shortened PFS (χ²=5.404, P=0.020) and OS (χ²=7.596, P=0.006) compared with no high-risk cytogenetic patients. Conclusion NDMM patients with isolated1q21 amplification/gain were rarely and usually had additional other cytogenetic abnormalities. The outcomes in this group treated with bortezomib-based chemotherapy followed by ASCT and maintenance therapy were satisfied, additional other high-risk cytogenetic abnormalities made PFS and OS further shortened.

Objective: To investigate the clinical efficacy and safety of lenalidomide (Revlimid, R) -based chemotherapy in the treatment of relapsed/refractory multiple myeloma (MM) patients. Methods: 57 consecutively relapsed/refractory MM patients were retrospectively analyzed from June 2013 to February 2016. All the patients received lenalidomide-based chemotherapy. Results: ① 60.4% patients had international staging system (ISS) stage Ⅲ, 37.9% patients had revised international staging system (R-ISS) stage Ⅲ, and 53.3% patients harbored at least one of the high-risk cytogenetic abnormalities[del (17p) and/or t (4;14) and/or t (14;16) ]. ②The patients received median 6 cycles of R (range: 1-32). The overall response rate (ORR) was 58.9% (33/56) , among which 8.9% was complete response (CR) , 19.8% was very good partial response (VGPR) , and 30.4% was partial response (PR). In addition, 10.7% patients attained minor response (MR). Total clinical benefit was 69.6%. Patients with more than 1 line of prior therapy, or previously thalidomide-resistance, or R-ISS stage Ⅲ disease showed significantly lower ORR. ③With a median follow-up of 27 months, the median progression free survival (PFS) , the median interval to PR, the median duration of response (DOR) , and the median overall survival (OS) was 8 months, 2 months, 8 months, and 19 months, respectively. Univariate prognostic analysis showed that abnormal karyotype, R-ISS stage Ⅲ and response inferior to PR were negative prognostic factors for PFS and OS. While the multivariate prognostic analysis showed that abnormal karyotype and R-ISS stage Ⅲ were independent prognostic factors. ④In the safety aspect, the most common grade 3-4 non-hematology adverse events (AEs) were infection (17.5%) , rash (1.8%) and thromboembolism (1.8%) , and the most common grade 3-4 hematology AEs were neutropenia (7.0%) and thrombocytopenia (3.5%). Totally 3 patients (5.3%) discontinued R because of AEs, and 2 cases (3.5%) of secondary primary malignancies were observed. Conclusion The R-based treatment is effective and safe in the treatment of relapsed/refractory MM patients in China. Abnormal karyotype and R-ISS stage Ⅲ were independent negative prognosis factors in this cohort.

Objective To study the clinical management way for HPV+/papanicolaou (Pap)-during cervical cancer screening.Methods To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN)Ⅱ in Peking University People's Hospital from Jan.2010 to Dec.2014.Results (1) For biopsy confirmed CINⅡ,HPV positive rate was 98.5％ (135/137),Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3％ (95/137),there was significant difference between them (x5=43.32,P＜0.01).(2) For the 42 patients with HPV+/Pap-,whose cytology slides were reviewed again.Among them,the interpretations of there were 16 cases confirmed as the same before,while 26 cases were changed to abnormal (≥ASCUS).Cytology be misdiagnosed was 19.0％ (26/137) at the first review.Among the 26 cases,13 (50.0％) cases were missed for the little amount of abnormal cells,8 (30.8％) cases for mild atypical morphology changed;the other 5 (19.2％) cases missed for stain problems.(3) For the cervical LEEP samples,37 cases of the pathology diagnosis were upgrade to CIN Ⅲ+,among them,2 cases of microinvasive cervical carcinoma,1 case of invasive cancer,34 cases of CIN Ⅲ;37 cases were CINⅠ or no lesion found;63 cases were still CIN Ⅱ.Four to six months later after LEEP,the cytology abnormal rate was 11.7％ (16/137),and the HR-HPV positive rate was 34.3％ (47/137).Conclusions Compared with cytology alone,cytology combined with HPV testing increase the sensitivity of cervical high grade lesion.For the cases of HPV+/Pap-cases,the cytology slides should be reviewed.The quality control of cervical exfoliate sample collection and interpretation should be strengthened.LEEP procedure is not only a treatment method,but also it could provide samples to confirm the diagnosis.

Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% vs 36.2%, χ²=6.536, P=0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (P<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (P<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[HR=0.133 (95% CI 0.062-0.288) , P<0.001] and OS[HR=0.156 (95% CI 0.050-0.484) , P=0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. Conclusions MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.

Objective: To evaluate the efficacy and long-term outcome of a combined protocol for multiple myeloma (MM) , including induction therapy, autologous hematopoietic stem cell transplantation (ASCT) and consolidation and maintenance therapy. Methods: Clinical records of 144 patients with MM from January 1, 2005 to February 1, 2016 were retrospectively analyzed. Results: The overall response rate (ORR) after ASCT was 100.0%, in which the complete remission (CR) was 64.1% and the best treatment response rate of superior to PR was 89.4%. During a median follow-up of 47 months, patients with an overall survival (OS) and progression free survival (PFS) was 120.9 and 56.9 months respectively. 5y-OS (73.7±4.7) %, 7y-OS (60.5±6.3) %; 3y-PFS (69.2±4.2) %, 5y-PFS (47.8±5.3) %. The median OS and PFS between the first line transplantation group and salvage transplantation group were 120.9 months vs 50.1 months and 60.2 months vs 16.7 months (all P=0.000). In 127 patients with R-ISS staging, the median survival of Ⅰ, Ⅱ, Ⅲ stage was 120.9 months (n=43) , 88.4 months (n=64) , 35.6 months (n=20) , respectively (P=0.000). For subgroup analysis of survival in early and late ASCT, the median OS of patients with R-ISS stage Ⅲ (35.6 months vs 15.8 months, P=0.031) and the median PFS of two groups (phase Ⅰ: 72.1 months vs 18.9 months, P=0.000; Ⅱ: 53.4 months vs 16.7 months, P=0.012; Ⅲ: 28.5 months vs 5.9 months, P=0.001) were different. Multivariate analysis showed that only R-ISS and the degree of remission before transplantation had impact on OS (HR=8.486, 95% CI 2.549-28.255, P=0.003) and PFS (HR=2.412, 95% CI 1.364-4.266, P=0.002) , respectively. Conclusion The combined protocol containing ASCT is effective for MM patients, improving remission rate and remission depth, prolonging PFS and OS. First line transplantation could significantly prolong the OS and PFS as compared with salvage transplantation. R-ISS and pre-transplantation remission depth are prognostic factors for survival.

OBJECTIVETo investigate the clinical characteristics and prognosis of very young patients with multiple myeloma (MM).

METHODSWe retrospectively analyzed the clinical characteristics and outcome of 35 newly diagnosed MM patients 40 years old or younger during a period of 15 years and compared with published data from western countries.

RESULTSOur study demonstrated that these very young patients were more likely to be in advanced stage of International staging system, IgD isotype, hemoglobin<100 g/L, decreased platelets and deletion of 17p13. With a median follow-up of 17 months (1- 89 months), the median overall survival (OS) of this cohort was 33 months and progression-free survival (PFS) was 13 months, moreover 8 of 17 deaths occurred in the first year after diagnosis. In the univariate analysis, extramedullary infiltration, del (17p13）and renal impairment were associated with reduced PFS (P=0.031, P=0.015, P=000, respectively), while the last two factors also predicted inferior OS (P=0.015, P=0.001), but multivariate analysis showed that only renal impairment independently associated with inferior survival in COX model（PFS: HR=3.953, 95% CI 1.263-12.371, P=0.018; OS: HR=5.769, 95% CI 1.602- 20.771, P=0.007).

CONCLUSIONOur research showed for the first time that the clinical characteristics and survival of MM patients ≤ 40 years old in China were different from that in western countries. The special attention should be paid to the patients with their diagnosis and treatment.

Adult ; China ; epidemiology ; Chromosome Deletion ; Disease-Free Survival ; Humans ; Multiple Myeloma ; diagnosis ; epidemiology ; Prognosis ; Retrospective Studies

OBJECTIVETo study the association between the level of serum DKK1 and disease course of multiple myeloma（MM）as well as myeloma bone disease.

METHODSThis study enrolled 145 cases of MM（including 79 newly diagnosed MM, 19 responded MM, 47 relapsed or progressive MM） whose lytic bone disease were evaluated by conventional radiography, ELISA was used to detect the concentration of serum DKK1.

RESULTSSerum DKK-1 elevated in newly diagnosed MM compared with normal donors［2 155（646-35 251）vs 1 487（646-2 577） ng/L, P=0.000］, those responded［1 136（431- 3 582） ng/L, P=0.001］and relapsed/progressive MM［1 695（431-3 582） ng/L, P=0.037］, and the level of relapsed/progressive MM was marginally higher than the responded ones. Moreover, MM patients without lytic lesions in conventional radiography had significantly lower DKK- 1 levels than those with lytic bone disease［1 910（660-26 925）vs 2 519（646-35 251） ng/L, P=0.005］. Notably serum DKK-1 correlated with the number of bone lesions［0 vs 1-3 vs >3 lesions: 1 910（660-26 925）vs 2 155（1 369-5 974）vs 2 547（646-35 251）ng/L, P=0.018].

CONCLUSIONDKK-1 serum concentration correlated with disease course of MM and myeloma bone disease, indicating that DKK-1 was an important factor for the extent of bone disease, which supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

Bone Neoplasms ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multiple Myeloma