With the development of the aging of domestic and foreign populations, patients placed in Cied (Cardiac Implanted Electronic Devices), the patients in which the electronic device) increased year by year, and the clinical situation of complicated symptoms Characteristics  . CIED-related infections have also become a common tricky problem. CIED clinical infection is ultimately likely to cause serious consequences of overall or partial devices, even infective endocarditis, surgical surgery  , early prevention and identification. The case definition of the case definition of the case definition of CIED pocket microbial culture positive but does not merge any clinical infection symptoms (redness and heat pain, crash, crack, crack, and supplementation, hydraulic pus can confirm Infection in symptoms, i.e., subclinical pocket infection. There have been many clinical experiments to show that the early detection rate of asymptomatic subclinical pockets is low, but the probability of CIED clinical infection occurs during subsequent follow-up , so early recognition of no symptoms infection, become clinical Practical concerns. Patients infected with subclinical pockets currently lack effective non-invasive inspection methods, while pockets are cultured in wound . Therefore, looking for reliable non-invasive testing methods, early identification of CIED-related infections, is also critical to improving CIED infection, and is also a hot problem of current research.
2. Instruments and reagents
Vitek-2 Compact bacterial automatic identification / drug sensitizer (French Merrier); electric thermostat incubator ( Shanghai Bo Xun Industrial Co., Ltd. Medical Equipment Factory; TQZ-312 Type Heavy Water Club (Shanghai Jinghong Experiment Equipment Co., Ltd.).
Agarose, anhydrous calcium chloride, ampicillin, bromine, bromophenol blue, etc. Common molecular biology reagents (Shanghai Sangon).
3.1. Research object
January 2011 ~ October 2014 during the Ministry of Health Beijing Hospital and Fuwai Hospital line CIED replacement Patient. Selection criteria: 1.Years; 2. Previously implanted CIED, currently need to be replaced; 3. Expected survival time for more than 1 year; 4. Patients who fully understand the study and obtain informed consent. Exclusion criteria: 1. Patients refuse; 2. Clinical symptoms can be confirmed by patients with pockets; 3. Patients with CIED-related infective endocarditis can be diagnosed.
3.2.1. Clinical data collection
For patients who meet the selected standards, record their clinical data: age, gender, pacemaker implantation Loosing, pacemaker replacement reasons, pacemaker implant time, replacement frequency, temporary pacemaker usage, pacemaker type, clinical complications and past history: Whether chronic heart disease (coronary heart disease or heart function, NYHA Hierarchical III, IV level; three kinds of drug controls for long-term hypertensive diseases), ventricular fibrillation, diabetes, whether thereof is incomplete in renal insufficiency (EGFR
), chronic obstructive pulmonary disease, immunosuppression state (Use hormone or immunosuppressive drug), combined with malignant tumors, anticoagulant anti-blood plate drugs, recent antibiotic use (various reasons for various reasons for more than 10 days in March before surgery). Regular follow-up to 5 years after surgery, follow-up mode is outpatient follow-up or telephone consultation, recording whether the patient has a clinical pocket infection symbol or CIED-related infective endocarditis, whether it is cleared by CIED infection, wire removal, surgical surgery, Or dies due to CIED infection.
3.2.2. Specimen collection and detection
< 60 ml/min/1.73 m Extracted 10 ml of the selection of the subject, immediately transmit microbiological examination laboratory line bacterial culture test. The selected subject is 4 mL, and the biopsy of the biopsy is selected. During CEID replacement, leave the bag specimen 5 g and immediately sent to the microbial examination laboratory for bacterial culture: the pocket specimen was ground after grinding blood agar medium, China blue medium and chocolate medium, At the same time, the broth was simultaneously inoculated, and the incubation of 35 ° C was observed for 24 hours, and the blood agar of the meat soup was transformed into blood agar medium, and the incubation tank was incubated in the incubation of 24 hours after observation. 3.2.3. Statistical Method
Data is carried out using SPSS18.0 software package for statistical analysis, measurement data (x ±S), the single factor analysis is tested by the independent sample T. The multi-sample number is compared to the single-factor variance analysis and H test; the count data is compared with χ
inspection; multi-factor analysis adopts Logistic regression analysis, P
4.1. Research object Basic characteristics of the patient: This test has selected 179 cases of pacemakers to change patients, 101 cases of male In 78 women, age 21 to 96 years old, the average age (74.10 ± 12.46), the pacemaker implant time is 4 months, up to 372 months, the average implant time (114.78 ± 47.22) month. The replacement of CIEDs mainly includes: 171 (95.5%) of the battery, 6 cases (3.4%) (3.4%), 2 cases of electrode adjustment (1.1%). 47 cases of single cavity pacemakers (26.3%), double cavity pacifier example 129 (72.1%), ICD (Implanted Cardiac Defibrillator) 2 cases (1.1%), CRT (Cardiac Resynchronization Tharapy Heart resynchronous therapist) 1 case (0.6%). In the first time, 145 patients (81.0%), 25 cases (14.0%) (14.0%), 9 cases (5%). 8 patients with temporary pacemakers (4.5%) were used. Other basic features < 0.05认为差异有统计学意义。
4.2. Seakophotogenic microbial culture results
Among the 179-selected patients, 25 cases (13.9%) were tissue culture positive. The highest detection rate is the patient with a solidisolase auretics, a total of 19 cases (76.0%), including 5 cases of epithelis Sapoccus (20.0%), 2 cases of Staphylococcus aureus (8.0%), Humo Staphylococcus 2 Example (8.0%), 1 case of Staphylococcus Staphylococcus (4.0%), 2 cases (8.0%) (8.0%), 7 cases of unparalleled solidifier pocochococci (28.0). Other pathogenic bacteria include: 1 case of S. aureus (4.0%), 1 case of vine-yellow micronori (4.0%), hemp1 case of rash twisher (4.0%), 1 case of Krebia pneumoniae (4.0%), 1 case of Cook bacterium (4.0%), 1 case of Swingshaloni (4.0%).
. Result of Pockets Microbial CultiVation
4.3. Single factors and multivariate Logistic regression analysis of pocket culture positive regression
Single factor Logistic regression analysis Male (P = 0.001), the number of surgical times (P = 0.013), the application of antibiotics in the first three months (P = 0.024), long-term use of anti-platelet drugs (P = 0.010), positive in the pocket culture and The two groups of pockets were statistically significant (P Multi-factor Logistic regression analysis results, gender is male (P = 0.001, OR = 14.001, 95% CI: 2.825 ~ 69.401), preoperative Antibiotics in March are more than 10 days (P = 0.002, OR = 27.935, 95% CI: 3.446 ~ 226.437), taking antiplatelet drugs (P = 0.008, OR = 3.761, 95% CI: 1.406 ~ 10.058) is asymptomatic The independent risk factor of subclinical pocket infection. See Table 2
Table 3 .
. Multi-Variable Logistic Regression of Pockets Subclinical Infections in Patients Undergoing Cied Replacement
25 people in the positive group culture positive group and the pocket culture positive group and the pockets were cultured in the positive group. There were 1 person (4%) After the discharge, the cutting electrode was fixed after the pocket infection returning, and the patient’s pocket culture was a Staphylococcus. Six patients died within 60 months of follow-up and the cause of death was non-CIED. 7 people have lost their visit (no returning or reporting CIED infection). The pockets cultivating the negative group unattended CIED-related infection, 14 were died in the period of 60 months, and the cause of death was non-CIED. There are 84 people who are moving (not returning to the hospital or reporting CIED infection). 4.5. Pacemaker Replacement Patients Inflammatory Factor Measurement
108 routine of 5 inflammatory factors were randomly selected from the above patient. Basic information on patients involved in inflammatory factors, such as Table 4 .
. Basic Information and Culture Result in Patients Undergoing Inflammatory Factors Tests
. Basic data and culture results of patients involved in inflammatory factors
4.6. Correlation between inflammatory factors and pouch culture results of Pacemaker
108 patients with pockets were cultured in 10 cases, and 13 cases were positive in pocket culture. There was no significant difference between the pocket culture positive group and the pockets culture negative group. See Table 5
Table 5 . Correlation Between Five Inflammatory Factors and Pocket Culture Result in Patients Undergoing Cied Replacement . CIED replaces the correlation between 5 inflammatory factors and pockets of patients
Exhaute the combined basic disease, including atrial fibrillation, diabetes, renal dysfunction, chronic heart disease, chronic obstructive pulmonary disease, immunosuppressive state (use Hormones or immunosuppressive drugs), malignant disease (various malignant tumors), after infection, 22 cases without the above complications were screened, and the correlation analysis of the culture result line culture results. The results show that even if the impact of the combined disease is excluded, the inflammatory factor value between the positive positive group and the pocket culture negative group is not statistically different. See
4.8. Normal human control group Inflammatory factor and pacemaker replaces patients with inflammatory factor 40 cases of normal people (age 50 ~ 60 years old, 20 cases of men and women ), The five kinds of inflammatory factors are significantly different from those of the five kinds of inflammatory factors to determine the five kinds of inflammatory factors. See in Table 7 .
. Contrast Of Inflammatory Factors Between Control Group and patients undergoing CIED Replacement
. Contrast of Inflammatory Factors Between Patients WITHOUT COMPLICATIONS AND CONTROL GROUP
Table 8 . Inflammatory factors with the comparative patient and the control group
China CIED implanted patients without clinical infection, the positive probability of pocket culture is about 15% to 33%  , and the main pathogenic bacteria is a solidishanococcus aureus  . Among the 179 patients selected in this study, the positive results were positive in 25 cases (14.0%), and the results of other studies.Nearly, suggesting that there is no symptoms of pocket infections, accounting for considerable proportion of clinical, should be concerned. The bacteria in which the bloody bag culture in this study is the most probe, which accounted for 76.0% of the total number, which is basically consistent with other studies  , and further clarify the negative grapes of solidiffesease The main pathogenic effects of Sococcus in infection in subclinical pockets. This study believes that gender is male, long-term application of antiplatelet drugs, using antibiotics in the first three months of 10 days for independent risk factors for non-symptoms infection. Male patients more prone to CIED-related infections have been made to clinical research. , Johanson et al., The large-scale clinical study of Johanson, and the male is independent risk factors for CIED infection. Research on Lekkerkerker , etc., the oral anti-condensant increased the chance of infection after CIED surgery, and it was speculated that the probability of postoperative pockets was increased. In the study of Ammar Habid, , anti-platelery drug applications can reduce the probability of fracturing biomass in pacemaker wires. Therefore, the use of anti-platelet drugs on the effects of asymptomatic bladder infection is still to be discussed. This research statistically applied antibiotics in the first three months to increase the probability of no symptoms infection infection. Domestic research  has also reported that there is a postal use of antibiotics to increase pockets without symptom infection. However, the reason is not clear, and it is speculated that it may be related to the disorder of the flora. Pichlmaier  uses bacterial DNA detection technology to sequencing CIED devices, and draws the inclusion of the detection rate of bacterial DNA that is a bacterial DNA for the surface of CIED. The influence of long-range antibiotics in the long-range antibiotic infection in the operation, there is still a major study to confirm.
Inflammatory factors such as CRP (C-Reactive Protein, C-reactive protein) , PCT (PCALCITONININ Calcugin) , IL-6 / IL-1 (Interleukin-6/1, Interleukin 6/1) , MCP-1 (Monocyte Chemoattractant Protein serum monocyte driven protein-1) as a predictive indicator of infection, locally infection in urinary system, respiratory system, etc. It is more widely used, and the clinical common bacteria include solid Staphylococcus aureus, also shows good correlation  . Therefore, this study tried to explore its application in the infection of the pacemaker without symptoms. Inflammatory factors have their own unique advantages in judging infections due to their economic, simple, non-invasive. This study showed that patients with CIED replacement, regardless of positive pockets, its inflammation has significantly increased, suggesting that patients may be in a state of inflammatory response. But unfortunately, patients with patent patients with pockets and positive patients with patent positive, the above five inflammation factors have not seen different. In order to eliminate the inflammatory factor of clinical basic diseases, this study will have subgroup analysis after removal of patients with merger, and the patients who remove merger have increased significantly, but patients with non-comorbite. There is no statistical difference between the inflammatory factor value between the pocket culture positive group and the pocket culture negative group. In speculative reasons may be small in subgroup analysis, and whether or not the basic disease is combined, the surgery has caused the activation of inflammatory response, resulting in the factors of subclinical infection in inflammation factors.The contribution is reduced. In Zou  and other scholars, the microbial detection method for high-throughput sequencing was used to detect the pocket and blood specimens, and 16SRNA sequencing patients were found, and the inflammatory factors were increased, and the cause of the study was excluded. Patients with basic diseases, and high-throughput sequencing methods have better sensitivity and specificity than bacterial culture.
In most cases, the increase in inflammatory factors is related to infection, but the inflammatory factors do not have good specificity. CRP can rise under the infection, or in surgery, it is high in autoimmune disease, not strong . Cell factors such as IL-1, IL-6 Although plasma concentrations in patients with bacterial infection increase, but also received regulation of systemic immune status . In contrast, PCT shows better specificity of bacterial infection   , its negative predictive value is high, there are a number of patients who believe that PCT negative patients, bacterial infections are not large, However, in patients with cirrhosis, cardiogenic shock and low blood pressure and wounded bleeding shock, PCT is also observed  , which has a certain effect on its specificity. CIED replacement patients inevitably in stress, so inflammatory response activation, integral inflammatory factor level increase is understandable. Elevated inflammatory factors, there is no difference between the pocket culture and the negative group, suggesting that the application of inflammatory factors predicting the infection infection infection infection. In order to solve this problem, it has been studied  to associate the multi-gene sequencing of blood and pouch specimens with inflammatory factor detection, suggesting that gene sequencing means and inflammatory factors can be combined in the future, screening CIED-related subclinical infections. For patients with delayed CIED infection between follow-up, new clinical studies can be designed in the future, and the inflammatory factors can continue to monitor inflammatory factors during long-term follow-up period after surgery, assess whether the inflammatory factor level after the surgery stress has retired. Delayed pocket infection. Fund Project Project Name: Capital Characteristic Clinical Application Research Achievements and Promotion. Quest ID: Z171100001017203. Ethical license statement
The study has obtained the corresponding ethical license. NOTES
Cabell, CH, Heidenreich, Pa, CHU, VH, Moore, CM, Stryjewski, ME, COREY, GR AND FOWLER, VG (2004) Infections Among Medicare Beneficiaes: 1990 -1999. American Heart Journal, https://doi.org/10.1016/j.ahj.2003.06.005
Voigt, A., Shalaby, A., SABA, S., ET Al. (2006) Rising Rates of Cardiac Rhythm Management Device Infections in The United States: 1996 THROUGH 2003. Journal of Thane American college of Cardiology, 48, 590-591.
Baddour, LM, Bettmann, MA, BOLGER, AF, ET Al. (2003) NonvalVular Cardiovascular Device-Related Infections. Circulation, 108, 2015-2031.
TARAKJI, KG, CHAN, EJ, Cantillon, DJ, Doonan, Al, Hu, T., Schmitt, S., Fraser, TG, KIM, A., Gordon, Sm and Wilkoff, BL (2010) Cardiac Implantable Electronic Device Infections: Presentation, Management, And Patient Outcomes. Heart Rhythm, 7, 1043-1047.
https://doi.org/ 10.1016 / j.hrtHM.2010.05.016
Chua, JD, Abdul-Karim, A., Mawhorter, S., Procop, GW, Tchou, P., Niebauer, M., Saliba, W., . Schweikert, R. and Wilkoff, BL (2005) The Role of Swab and Tissue Culture in the Diagnosis of Implantable Cardiac Device Infection Pacing and Clinical Electrophysiology, 28, 1276-1281
https:. // doi. ORG / 10.1111 / J.1540-8159.2005.00268.X