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1.
Surg Endosc ; 37(12): 9062-9069, 2023 12.
Article in English | MEDLINE | ID: mdl-37964092

ABSTRACT

OBJECTIVE: Sphincter of Oddi dysfunction (SOD) has been used to describe patients with RUQ abdominal pain without an etiology. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of ES (endoscopic sphincterotomy) for SOD. METHODS: The study methodology follows the PRISMA guidelines. A comprehensive search was conducted using MEDLINE and EMBASE databases for RCTs with ES in patients with SOD. The primary outcome assessed was the improvement of abdominal pain after ES/sham. A random effects model was used to calculate pooled estimates for each outcome of interest. RESULTS: Of the initial 55 studies, 23 were screened and thoroughly reviewed. The final analysis included 3 studies. 340 patients (89.7% women) with SOD were included. All patients had a cholecystectomy. Most included patients had SOD type II and III. The pooled rate of technical success of ERCP was 100%. The average clinical success rate was 50%. The pooled cumulative rate of overall AEs related to all ERCP procedures was 14.6%. In the sensitivity analysis, only one study significantly affected the outcome or the heterogeneity. CONCLUSION: ES appears no better than placebo in patients with SOD type III. Sphincterotomy could be considered in patients with SOD type II and elevated SO basal pressure.


Subject(s)
Sphincter of Oddi Dysfunction , Sphincter of Oddi , Humans , Female , Male , Sphincterotomy, Endoscopic/adverse effects , Sphincterotomy, Endoscopic/methods , Sphincter of Oddi Dysfunction/surgery , Sphincter of Oddi Dysfunction/etiology , Sphincter of Oddi/surgery , Cholangiopancreatography, Endoscopic Retrograde/methods , Manometry , Abdominal Pain/etiology
2.
Surg Laparosc Endosc Percutan Tech ; 33(2): 147-151, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36977323

ABSTRACT

BACKGROUND: Up to 70% of the cases of biliary strictures are cholangiocarcinoma. Cholangiocarcinoma has a late diagnosis and poor outcomes; therefore, effective biomarkers are needed for malignant lesions detection at earlier stages. AIM: The aim was to assess the diagnostic utility of bile pyruvate kinase M2 (PKM2) as a biomarker for the detection of malignant biliary strictures in patients with an indeterminate biliary stricture. MATERIALS AND METHODS: This is a prospective study to evaluate the diagnostic value of bile PKM2 for the diagnosis of malignant biliary strictures. Bile samples were collected during Endoscopic Retrograde Cholangio Pancreatography to quantify PKM2 levels and were used to compare their diagnostic value with biliary brush cytology, endoscopic ultrasound-guided fine needle biopsy, or clinical follow-up. RESULTS: Forty-six patients were recruited for the study; 19 patients with malignant strictures and 27 with benign biliary strictures. The bile PKM2 levels were elevated in patients with malignant biliary strictures [median 0.045 ng/mL (IQR 0.014 to 0.092)] compared with those with benign strictures [median 0.019 ng/mL (IQR 0.00 to 0.047)]. Bile PKM2 had a receiver-operating characteristic curve of 0.66 (0.49 to 0.83) with a cutoff value of bile PKM2 of 0.0017 ng/mL. The sensitivity and specificity of bile PKM2 for the diagnosis of cholangiocarcinoma were 89% and 26%; the positive and negative predictive values were 46% and 78%, respectively. CONCLUSION: In patients with indeterminate biliary strictures, bile PKM2 may be a potential biomarker for the diagnosis of malignancy.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Cholestasis , Humans , Constriction, Pathologic , Pyruvate Kinase , Bile , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/pathology , Prospective Studies , Cholangiocarcinoma/diagnosis , Cholestasis/diagnosis , Cholestasis/etiology , Cholangiopancreatography, Endoscopic Retrograde , Sensitivity and Specificity , Bile Ducts, Intrahepatic
3.
J Anesth Analg Crit Care ; 2(1): 32, 2022 Jul 19.
Article in English | MEDLINE | ID: mdl-37386573

ABSTRACT

INTRODUCTION: Significant concerns raise for the healthcare workers involved in airway management of patients diagnosed with coronavirus 2019 disease (COVID-19). Due to shortages of personal protective equipment (PPE), barrier enclosure systems such as aerosol box (AB) have been proposed worldwide. The aim of this study was to evaluate our experience using AB as protective equipment in patients with COVID-19 in a third-level center in Mexico. METHODS: A retrospective study of COVID-19 patients requiring airway management using an AB in the Hospital Central Sur de Alta Especialidad de Pemex in Mexico City from March 1 to June 1, 2020. Antropometric data, pre-intubation vital signs, and laboratory tests were recorded; the primary endpoints were intubation success rate and complications associated with AB and patients' mortality. As a secondary endpoint, AB subjective evaluation was explored by administering a survey after airway management procedures. RESULTS: Thirty-nine patients for a total of 40 intubations were documented. Thirty-one (77.5%) were men, with a mean age of 61.65 years; successful intubation occurred in 39 (97.55%) of the procedures, and AB was used in 36 (90%) of intubations, with success in 28 (70.0%); A Cormack-Lehane grade 3 view was recorded in 18 patients (46.2%), and during the procedure, the AB had to be removed in 8 (22.2%) cases, with migration documented in 91.6% of cases. The 30-day mortality was 48.71%, with 23.0% of patients discharged. 83.3% of surveyed anesthesiologists reported significant limitations in manipulating airway devices with AB used. CONCLUSION: Our data indicate that in clinical practice, the use of AB may hinder airway management and decrease the intubation success rate and may also result in patients' injury. Further studies are necessary to validate the use of AB in clinical practice, and they should not replace certified PPE.

5.
Prz Gastroenterol ; 15(1): 60-64, 2020.
Article in English | MEDLINE | ID: mdl-32215130

ABSTRACT

INTRODUCTION: Ectopic varices are those that appear in a different region of the gastroesophageal junction. Bleeding from ectopic varices is rare but is usually massive and deadly. AIM: To identify the possible factors that cause bleeding from ectopic varices in patients with portal hypertension. MATERIAL AND METHODS: A cross-sectional and retrospective study; the data were collected between January 2004 and June 2014. We included patients with portal hypertension and gastrointestinal ectopic varices diagnosed by endoscopy. RESULTS: We found 31 patients with gastrointestinal ectopic varices. Of these, 25 had liver cirrhosis, and six showed non-cirrhotic portal hypertension. There were 16 men and 15 women in the study. The median age of the patients was 60 years (range minimum-maximum of 27 to 80 years). Nineteen (61%) patients had rectal varices, 10 (32%) had duodenal varices, 1 (3%) had ileal varices, and 1 (3%) had colonic varices. We found bleeding in 4 (13%) of the 31 patients with ectopic varices; two belonged to the cirrhosis group, and the other two were from the non-cirrhotic portal hypertension group. Three of the 4 patients with bleeding from gastrointestinal ectopic varices had exhibited haemorrhage from oesophageal varices (odds ratio = 4.09, 95% CI: 0.37-44.78, p = 0.249), but none of them showed bleeding from gastric varices. CONCLUSIONS: Bleeding from gastrointestinal ectopic varices is not necessarily associated with bleeding from oesophageal or gastric varices.

6.
Postgrad Med ; 132(3): 275-281, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31922437

ABSTRACT

BACKGROUND: Burnout syndrome (BOS) is characterized by emotional exhaustion, depersonalization and reduced personal accomplishment. It affects doctors, patients and their inter-relationship. There is a lack of data on BOS in Mexico. The main objective of the present study is to evaluate the prevalence of BOS in physician members of the Mexican gastroenterological association (MGA) and Mexican association for gastrointestinal endoscopy (MAGE). MATERIALS AND METHODS: Cross sectional, prospective study through anonymous electronic survey via e-mail, sent to members of the MGA (n = 1192) and MAGE (n = 600). The survey included questions about basic sociodemographic information, Maslach Burnout Inventory, and factors potentially associated with BOS. Continuous variables were summarized as means and ANOVA or Kruskal-Wallis test were used to compare groups. Nominal variables were summarized as proportions and Fisher's exact test or Χ2 test were used, as appropriate. RESULTS: A total of 1792 e-mail invitations were delivered and 411 answers were received with a response rate of 22.9%. The prevalence of BOS according to the Maslach Burnout Inventory was 26.3% (108/411). The prevalence of BOS according to the single-item self-defined burnout question (SISDBOQ) was 32.6% (134/411). The Kappa coefficient for emotional exhaustion between the SISDBOQ and Maslach inventory was 0.48 (p = 0.0001). Factors associated with BOS included performing endoscopic procedures (OR 2.9 (1.2-6.6); p = 0.008), lack of support from colleagues upon complications (OR 0.2 (0.1-0.4); p = 0.0001), receiving frequent reprimands from superiors (OR 2.4 (1.5-3.8); p = 0.0001), work unrelated to medicine (OR 2.4 (1.4-3.9); p = 0.0001), work violence/harassment (OR 3.0 (1.9-4.9); p = 0.0001) and living in a big city (OR 1.9 (1.2-3); p = 0.005). CONCLUSION: BOS is a frequent entity in Mexican gastroenterologists and endoscopists. There are potentially modifiable factors associated with BOS.


Subject(s)
Burnout, Professional/epidemiology , Endoscopy, Gastrointestinal/psychology , Gastroenterologists/psychology , Cross-Sectional Studies , Humans , Internship and Residency , Mexico/epidemiology , Postoperative Complications/psychology , Prevalence , Prospective Studies , Social Support , Socioeconomic Factors , Workplace Violence/psychology
7.
Medicine (Baltimore) ; 98(26): e15954, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31261501

ABSTRACT

Early diagnosis of pancreatic cancer (PC) is based on endoscopic ultrasound (EUS). However, EUS is invasive and requires a high level of technical skill. Recently, liquid biopsies have achieved the same sensitivity and specificity for the diagnosis of numerous pathologies, including cancer. Insulin-promoting factor 1 (PDX1) and Msh-homeobox 2 (MSX2), 2 homeotic genes, have been confirmed to be related to pancreatic oncogenesis.The aim of this study is to establish the diagnostic utility of circulating serum levels of MSX2 and PDX1 expression in patients with PC.A prospective study was conducted from January 2014 to February 2017. Patients with a suspected diagnosis of PC who underwent fine needle aspiration biopsy guided by EUS (EUS-FNA) were included in the study, in addition to non-PC control subjects. Both tissue and blood serum samples were submitted to histopathological analysis and measurement of PDX1 and MSX2 gene expression by means of qRT-PCR.Patients were divided into non-PC, malignant pathology (MP), or benign pathology (BP) groups. Significant differences in both MSX2 [2.05 (1.66-4.60) vs 0.83 (0.49-1.60), P = .006] and PDX1 [2.59 (1.28-10.12) vs 1.02 (0.81-1.17), P = .036] gene expression were found in blood samples of PC compared with non-PC subjects. We also observed a significant increase in MSX2 transcripts in tissue biopsy samples of patients diagnosed with MP compared with those with BP [1.98 (1.44-4.61) and 0.66 (0.45-1.54), respectively, P = .012]. The ROC curves indicate a sensitivity and specificity of 80% for PDX1 and 86% for MSX2.Gene expression of MSX2 in tissue samples obtained by EUS-FNA and serum expression of MSX2 and PDX1 were higher in patients with PC.


Subject(s)
Homeodomain Proteins/metabolism , Pancreatic Neoplasms/metabolism , Trans-Activators/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Biopsy, Fine-Needle , Case-Control Studies , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Gene Expression , Gene Expression Regulation, Neoplastic , Humans , Male , Middle Aged , Pancreas/metabolism , Pancreas/pathology , Pancreatic Neoplasms/pathology , Prospective Studies , Sensitivity and Specificity
8.
Surg Endosc ; 33(7): 2349-2356, 2019 07.
Article in English | MEDLINE | ID: mdl-30820658

ABSTRACT

INTRODUCTION: Hemostatic powder (TC-325) is a new tool for treatment of gastrointestinal bleeding that allows the treatment of large surfaces with active bleeding. The aim was to describe the initial success of TC-325 for the control of GI bleeding. MATERIALS AND METHODS: We did a multicenter cohort study with patients admitted to the endoscopy service for GI bleeding. A format was generated to standardize the information obtained in each center. It was determined whether this treatment had been used as a single therapy or as a combination therapy. Descriptive statistics with medians and ranges, or averages with SD according to distribution. RESULTS: Eighty-one patients with 104 endoscopic procedures were included. The median number of endoscopic procedures was 1 (1-3). In the first procedure, the initial success rate was 98.8% (n = 80), failure rate was 1.2% (n = 1), and rebleeding rate was 20% (n = 16). The majority of rebleeding cases occurred within the first 3 days (12/16, 75%). There was no association between rebleeding and etiology (malignant or benign; P = 0.6). In first procedure, 44 (54%) cases had monotherapy with TC-325 and 37 (46%) cases had a combined endoscopic therapy. There were no differences in initial success or rebleeding rates when TC-325 was used as monotherapy versus combined therapy (P = 0.7). The mortality rate was 4% (3/81). CONCLUSION: TC-325 is effective for achieving initial control of bleeding in patients with different GI etiologies. The rate of bleeding recurrence is considerable in both patients with benign and malignant etiology.


Subject(s)
Gastrointestinal Hemorrhage/therapy , Hemostasis, Endoscopic/methods , Hemostatics/therapeutic use , Minerals/therapeutic use , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Gastrointestinal Hemorrhage/etiology , Hemostasis, Endoscopic/adverse effects , Hemostatics/adverse effects , Humans , Male , Middle Aged , Minerals/adverse effects , Recurrence , Retrospective Studies
9.
Endoscopy ; 49(11): 1061-1068, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28898920

ABSTRACT

Background and study aim Different techniques have been introduced to improve the endoscopist's view and enhance the detection of polyps. The endocuff is a polymer sleeve cap that is connected to the tip of the colonoscope in order to improve visualization of the mucosa during colonoscopy. The aim of the study was to compare adenoma detection rates (ADR) of endocuff-assisted colonoscopy and conventional colonoscopy. Patients and methods Patients 50 years or older were randomized into two groups: an endocuff-assisted colonoscopy group and a conventional colonoscopy group without the endocuff. Results A total of 337 patients were included: 174 in the endocuff group and 163 in the conventional group. The median age was 61 years (interquartile range 55 - 70 years), and 74 % were women. The ADR was higher in the endocuff group than in the conventional group (22.4 % vs. 13.5 %; P = 0.02). The mean number of adenomas was 0.30 (SD 0.25) in the endocuff group and 0.21 (SD 0.26) in the conventional group (P â€Š= 0.02). The rate of ileal intubation was lower in the endocuff group (73 % vs. 87 %; P < 0.001). No serious adverse events occurred with the use of the endocuff. Conclusions Endocuff colonoscopy achieved a greater ADR than conventional colonoscopy.Trial registered at ClinicalTrials.gov (NTC02387593).


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenoma/diagnostic imaging , Colonic Polyps/diagnostic imaging , Colonoscopy/instrumentation , Colorectal Neoplasms/diagnostic imaging , Aged , Colonoscopy/adverse effects , Early Detection of Cancer/instrumentation , Female , Humans , Ileum , Intubation, Gastrointestinal , Male , Middle Aged , Prospective Studies
10.
Endosc Ultrasound ; 4(1): 52-5, 2015.
Article in English | MEDLINE | ID: mdl-25789285

ABSTRACT

BACKGROUND AND OBJECTIVES: Noninvasive imaging techniques have shown limitations to identify insulinomas. In few studies reported so far, endoscopic ultrasound (EUS) has proven to be able to locate lesions. The aim of this study was to compare the performance of computed tomography versus EUS for the detection of insulinomas. MATERIALS AND METHODS: In a retrospective manner prospectively collected data were analyzed. Patients with hypoglucemia and hyperinsulinemia were included. Diagnostic yield was measured in relationship to sensitivity, specificity, positive predictive value, negative predictive value and accuracy. Surgical specimens were considered the gold standard. RESULTS: Sensitivity, positive predictive value, and accuracy of EUS was 100%, 95.4% and 95.4%, respectively. In the case of CT the sensitivity was 60%, specificity 100%, positive predictive value 100%, negative predictive value 7%, and accuracy were 68%. CONCLUSIONS: EUS is useful in the preoperative assessment of patients with hypoglycemia and serum hyperinsulinemia.

11.
World J Gastroenterol ; 20(26): 8612-6, 2014 Jul 14.
Article in English | MEDLINE | ID: mdl-25024616

ABSTRACT

AIM: To follow up patients with pseudotumoral chronic pancreatitis (PCP) to assess their outcome and identify an optimal surveillance interval. METHODS: Data obtained prospectively were analyzed in a retrospective manner. Patients with clinical evidence of chronic pancreatitis (abdominal pain in the epigastrium, steatorrhea, and diabetes mellitus), endoscopic ultrasound (EUS) criteria > 4, and EUS-fine needle aspiration (FNA) were included. A pseudotumor was defined as a non-neoplastic space-occupying lesion, a cause of chronic pancreatitis that may mimic changes typical of pancreatic cancer on CT or endoscopic ultrasound but without histological evidence. A real tumor was defined as a neoplastic space-occupying lesion because of pancreatic cancer confirmed by histology. RESULTS: Thirty-five patients with chronic pancreatitis were included, 26 (74.2%) of whom were men. Nine (25.7%) patients were diagnosed with pseudotumoral chronic pancreatitis and two (2/35; 5.7%) patients with pseudotumoral chronic pancreatitis were diagnosed with pancreatic cancer on follow-up. The time between the diagnosis of pseudotumoral chronic pancreatitis and pancreatic adenocarcinoma was 35 and 30 d in the two patients. Definitive diagnosis of pancreatic adenocarcinoma was made by surgery. In the remaining six patients with pseudotumoral chronic pancreatitis, the median of follow-up was 11 mo (range 1-22 mo) and they showed no evidence of malignancy on surveillance. In the follow-up of patients without pseudotumoral chronic pancreatitis but with chronic pancreatitis, none were diagnosed with pancreatic cancer. According to our data, older patients with chronic pancreatitis are at risk of pseudotumoral chronic pancreatitis. CONCLUSION: According to characteristics of patient, detection of PCP should lead a surveillance program for pancreatic cancer with EUS-FNA in < 1 mo or directly to surgical resection.


Subject(s)
Adenocarcinoma/etiology , Granuloma, Plasma Cell/etiology , Pancreatic Neoplasms/etiology , Pancreatitis, Chronic/complications , Adenocarcinoma/diagnosis , Adenocarcinoma/therapy , Adolescent , Adult , Aged , Diagnosis, Differential , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Female , Granuloma, Plasma Cell/diagnosis , Granuloma, Plasma Cell/therapy , Humans , Male , Middle Aged , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/therapy , Predictive Value of Tests , Prognosis , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Young Adult
12.
World J Gastrointest Endosc ; 5(6): 297-9, 2013 Jun 16.
Article in English | MEDLINE | ID: mdl-23772268

ABSTRACT

The development of pseudocysts in patients with chronic pancreatitis has been reported in 23%-60% of cases and drainage is indicated when they become symptomatic. Endoscopic ultrasound-guided drainage with the placement of plastic or metallic stents to create a cystogastric anastomosis has been shown to be a reliable and efficacious maneuver. Metallic stent use appears to be a safe and effective alternative that shortens the length of time of the procedure and maintains a greater diameter in the cystogastric communication. However, important migration rates have been reported. The use of new metallic stents that are specially designed to prevent migration represents a promising development in the treatment of these group of patients that appears to be safe and effective for pseudocyst drainage and could importantly reduce migration rates, while at the same time having the advantage of a single step procedure and a larger fistula diameter in the endoscopic cystogastric anastomosis.

13.
Rev. invest. clín ; 57(6): 814-819, Nov.-Dec. 2005. ilus, tab
Article in Spanish | LILACS | ID: lil-632402

ABSTRACT

The carcinoembryonic antigen (CEA) is glycoprotein localized in the apical surface of mature enterocytes. The members of the CEA gene family are clustered on chromosome 19q13.2. It is formed by 29 genes, of which 18 are expressed. Many functions of CEA have been known in healthy individuals, however its role as cell adhesion molecule is the most studied. Besides the colon, CEA is expressed in the stomach, tongue, oesophagus, cervix, and prostate. The most important clinical function is in colorectal, gastric and ovary cancer. It is used as prognosis marker, staging system, recurrence, treatment response and liver metastases. There are many no neoplasic-diseases that enhance CEA value. Actually, the CEA is being studying as target of immunotherapy.


El antígeno carcinoembrionario (ACE) es una glucoproteína localizada en el polo apical de los enterocitos. Los genes que codifican para el ACE se localizan en el cromosoma 19q13.2. El grupo total está constituido por 29 genes, divididos en tres subgrupos de los cuales se expresan sólo 18. En el individuo sano existen múltiples funciones del ACE que han sido ampliamente estudiadas, su función como molécula de adhesión ha sido la más ampliamente difundida. En pacientes sanos además de expresarse a nivel de colon el ACE se expresa en células de la lengua, esófago, estómago, cervix y próstata. Los pacientes que reciben una mayor utilidad clínica son aquellos con cáncer colorrectal (CCR), cáncer gástrico y cáncer de ovario. Su uso más amplio es en el CCR, actualmente se utiliza como marcador pronóstico, estadiaje, marcador de recurrencia, de respuesta al tratamiento y como indicador de metástasis a nivel hepático. Existen algunas patologías no neoplásicas que causan elevación de las cifras séricas de ACE. Actualmente se estudia al ACE como blanco de inmunoterapia dirigida a tumores que contengan células que expresen esta molécula.


Subject(s)
Adult , Animals , Humans , Mice , Carcinoembryonic Antigen/physiology , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/chemistry , Carcinoembryonic Antigen/genetics , Carcinoembryonic Antigen/immunology , Cell Adhesion/physiology , /genetics , Fetal Proteins/analysis , Immunotherapy , Mice, Transgenic , Organ Specificity , Prognosis , Biomarkers, Tumor/blood , Vaccines, Synthetic/therapeutic use
14.
Rev Invest Clin ; 57(6): 814-9, 2005.
Article in Spanish | MEDLINE | ID: mdl-16708907

ABSTRACT

The carcinoembryonic antigen (CEA) is glycoprotein localized in the apical surface of mature enterocytes. The members of the CEA gene family are clustered on chromosome 19q13.2. It is formed by 29 genes, of which 18 are expressed. Many functions of CEA have been known in healthy indiuiduals, however its role as cell adhesion molecule is the most studied. Besides the colon, CEA is expressed in the stomach, tongue, oesophagus, cervix, and prostate. The most important clinical function is in colorectal, gastric and ovary cancer. It is used as prognosis marker, staging system, recurrence, treatment response and liver metastases. There are many non-neoplasic diseases that enhance CEA value. Actually, CEA is being studying as target of immunotherapy.


Subject(s)
Carcinoembryonic Antigen/physiology , Adult , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Biomarkers, Tumor/blood , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Carcinoembryonic Antigen/analysis , Carcinoembryonic Antigen/chemistry , Carcinoembryonic Antigen/genetics , Carcinoembryonic Antigen/immunology , Cell Adhesion/physiology , Chromosomes, Human, Pair 19/genetics , Fetal Proteins/analysis , Humans , Immunotherapy , Mice , Mice, Transgenic , Organ Specificity , Prognosis , Vaccines, Synthetic/therapeutic use
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