National Medical Journal of China
Volume 99 · Issue 12 · 2019
Natl Med J China
Historic evolution of tissue matching in organ transplantation
Tissue matching, which is used to evaluate the degree of tissue compatibility between donors and recipients, is a necessary support for the development of organ allotransplantation. As one of the hotspots in the field of transplantation science, the establishment and improvement of its techniques and strategies are constantly undergoing follow-up and change. With the development and application of new technology platforms such as flow cytometry, liquid phase chip, high-throughput sequencing and computer-aided analysis, traditional tissue matching methods have made great progress, and the application scope has gradually expanded from early rejection risk assessment after transplantation to predicting the occurrence of antibody-mediated rejection, guiding individualized immune tolerance induction protocols and the selection of immunosuppressants, with promising prospects.
Cytomegalovirus active infection after kidney transplantation affecting the expression of activation receptor CD226 on NKT cell
To investigate the effect of active cytomegalovirus infection post kidney transplant on the expressing of receptor CD226 on NKT cell.
Case controlled study. From December 2013 to December 2014, 43 cases of kidney transplant recipient with CMV infection were collected in the Organ Transplantation Research Institute of the former 309th Hospital of PLA. The healthy control group included 15 cases. 15 cases of recipients who were stable after operation and followed up in our hospital at the same time were also collected as control. Peripheral blood specimen with EDTA as anticoagulant were used and analyzed by flow cytometry.
The population of NKT in CMV infection recipients were 5.19(1.18, 25.92)%, while in the remission stage the population were 4.89(0.68, 25.33)%, Compared with normal healthy controls and the stable recipients, the percentage of CD3+CD56+ NKT cells in periphery blood mononuclear cells did not vary among these groups(P>0.05). The CD226+ NKT population during the active CMV infection was (70±13)%, which was significantly lower than the health control [(87±10)%] and stable recipients [(80±9)%](P<0.001). Whereas in the CMV infection remission stage, the CD226+NKT population was (81±16)%, which was significantly higher than that of CMV active infection group (P<0.05), and showed no difference with the health control group and stable recipients (P>0.05). The CD226 MFI expressed on NKT in CMV infection group was 101±49, which showed no difference with health controls and stable recipients (P>0.05). However, significantly up regulation of CD226 MFI on NKT was observed in the samples obtained from the same recipients in CMV active infection (91±40) and in CMV regression stage(173±73)(P<0.001).
The CD226+ NKT cells population was down during the active CMV infection post kidney transplantation, while the expression of CD226 and the population of CD226+NKT could regression when the CMV infection regressed, which indicates the involvement of CD226 in the process of NKT cells anti-CMV infection.
Clinicopathologic features and prognosis of patients with IgA nephropathy superimposed on transplant glomerulopathy
To observe the clinicopathologic features and prognostic of patients with IgA nephropathy (IgAN) superimposed on transplant glomerulopathy (TG+ IgAN).
Electronic medical records of Jinling Hospital were searched for TG+ IgAN patients that was diagnosed during January 2004 to December 2016. Clinicopathologic features and prognoses information were retrieved and analyzed. The primary outcome was initiation of replacement therapy or an eGFR declined to<15 ml·min-1·(1.73m2)-1.
A total of 49 patients with pathologically confirmed TG+ IgAN were enrolled in this study. The median time from renal transplantation to allograft biopsy was 85 months. There were 131 patients with TG in the control group. There was no statistical difference in the age, gender, and immunosuppressive regimen during renal biopsy in the two groups. In TG+ IgAN patients, the median serum creatinine level was 175 μmol/L, the median urinary protein was 1.45 g/24 h, and 16.3% of the patients had nephrotic range proteinuria, the incidence of microscopic hematuria was 40.8%, and the average hemoglobin was 105 g/L. In terms of pathology, the degree of glomerular mesangial matrix hyperplasia in the TG+ IgAN group was significantly heavier compared with TG group ( P=0.004), and the degree of hyaline degeneration of the small arteries was lighter (P=0.043). There was no significant difference in interstitial inflammation (i), tubulitis (t), glomerulitis (g), peritubular capillaritis (ptc) and intimal arteritis (v). Calculated by Kaplan-Meier method, the median survival time of 49 patients with TG+ IgAN was 36.9 months, and there was no difference in survival rate of allografts compared with TG group.
Compared with TG patients without IgA, TG+ IgAN patients had higher incidence of microscopic hematuria, more severe glomerular mesangial matrix hyperplasia, and no significant differences in other clinicopathological features. The prognosis of TG+ IgAN patients was not significantly different from those without IgAN.
Strategy and clinical outcome of deceased donor kidney transplantation for presensitized recipients
To explore the management strategy and clinical outcome of renal transplantation in presensitized recipients using deceased donor kidneys.
From January 2011 to June 2018, twenty-one presensitized patients, including 8 with positive donor specific antibodies (DSA) and 13 with positive panel-reactive antibodies (PRA) but no DSA, received renal retransplantation from deceased donors in our center. The incidence of delayed graft function (DGF) and acute rejection (AR), changes of DSA, and the graft and patient survival were retrospectively analyzed.
None of the renal allografts had primary non-function (PNF) and DGF after transplantation. Four of the 13 recipients with PRA+/DSA-had a total of 5 episodes of acute cell-mediated rejection (CMR), while 5 of 8 recipients with pre-existing DSA+ developed AR, including 3 cases with CMR alone and 2 cases with mixed AR. All episodes of rejection were successfully reversed after targeted treatment. Interestingly, of the 8 recipients with positive preformed DSA, 4 cases with positive DR-DSA and/or class Ⅰ-DSA had their DSA disappeared after transplantation, whereas DQ-DSA remained positive in 4 of 5 recipients. After a median follow-up of 26 months, all recipients maintained normal renal allograft function, and the survival rates of both graft and recipient were 100%.
With the use of deceased donors, kidney transplantation can be successfully performed in presensitized patients by appropriate HLA-matching screening, choosing donor kidneys with good quality, and the combination of optimal perioperative treatment.
Relationship of distribution frequency of HLA antigen/antibody and PIRCHE score with DSA production and AMR occurrence
To analyze the distribution frequency of HLA antigen gene and antibody, and explore the relationship of PIRCHE score with DSA production and AMR occurrence.
Kidney transplantation cases of department Kidney transplantation, the First Hospital of Xi′an Jiaotong University from November 2013 to June 2017 were included in our study. HLA high resolution typing were detected with LAB Type TM SSO method. HLA classⅠ & Ⅱ antibody detection were tested by LAB screen Single Antigen beads with Luminex 200 technology. PIRCHE score were graded with PIRCHE score system.
HLA high resolution classification data of 798 recipients and 409 donors showed that HLA A2, A11, A24 were common in HLA A locus; HLA B46, B51 B60, B35, B62, B61 were common in HLA B locus; HLA DR9, DR4, DR15, DR12, DR7, DR11 were common in HLA DR locus; HLA DQ7, DQ6, DQ5, DQ9, DQ2 were common in HLA DQ locus. The positive cases of HLA class Ⅰ & Ⅱ antibody and DSA were 105, 40 and 32, respectively. The most common of HLA class Ⅰ antibody were A24 and B7 antibody; the most common of HLA class Ⅱ antibody was DQ antibody, including DQ2, DQ9, DQ4, DQ6, DQ7 and DQ8. PIRCHE scores of living donor transplantation recipients were significantly lower than DCD group ( P<0.01). PIRCHE score of DSA+ and DSA+AMR+ group were markedly higher than that of DSA-and DSA+AMR-group, respectively(P<0.05); analysis of ROC curve on PIRCHE scores could predict DSA production and AMR occurrence. The AUC for prediction DSA production was 0.80, and the critical value was 115.5. For prediction of AMR, the AUC was 0.89 and the critical value was 133.5.
The common HLA antigens have stronger immunogenicity, and easy to stimulate the body to produce HLA antibodies; matching of common antigen sites and HLA class Ⅱ antigen should be attached importance before kidney transplantation. PIRCHE score can predict the generation of DSA and the occurrence of AMR effectively. PIRCHE score for HLA match, is more sensitive than traditional methods, and contains more information.
Clinical application of renal autotransplantation in complex urological diseases
To summarize the experience of renal autotransplantation for severe iatrogenic proximal ureteral damage and renal artery aneurysms in eight patients and to explore the clinical application value of renal autotransplantation.
Two patients of renal artery aneurysms and six patients of severe iatrogenic proximal ureteral damage between January 2010 and March 2018 in our center were retrospectively reviewed.
The procedures of eight cases were successful, with immediate return of renal function in the patients. The warm ischemia time was (3±1) minutes, the total operation time was (340±164) min, and the estimated blood loss was (180±60) ml, respectively. For renal artery anastomosis, six patients of severe iatrogenic proximal ureteral damage received end-to-end anastomosis between the internal iliac artery and renal artery, and two patients of renal artery aneurysms were treated with renal artery and internal iliac artery for reconstruction, then end-to-side anastomosis to recipien external iliac artery. A direct ureterovesical anastomosis was performed in seven patients, one patient was received pyeloureteroplasty. No serious complications of blood vessel and ureter were found during perioperative and long-term follow-up. All cases follow-up hitherto have normal renal function and blood pressure.
Renal autotransplantation can be appropriate for patients with proximal ureteral loss and complex hilar renal artery aneurysms. In addition, it is able to protect renal functions to the most extent and provides a surgical alterative for complex renal diseases.
Molecular and clinical study on homozygous or heterozygous large deletion of CYP21A2 gene in 21-OHD patients
To explore the relationship between homozygous or heterozygous large deletion of CYP21A2 gene and clinical manifestation in 21-hydroxylase deficiency (21-OHD) patients.
The records of 100 patients with 21-OHD were collected between June 2016 and December 2017 in Peking Union Medical College Hospital. Large deletion of CYP21A2 gene was detected by multiplex ligation probe amplification (MLPA). The biochemical results and clinical symptoms of patients with homozygous or heterozygous large deletion were analyzed in order to investigate the influence of complete or single allele deletion of CYP21A2 gene on 21-OHD patients.
Large deletion of CYP21A2 gene was detected in 33 patients by MLPA, including 13 males and 20 females, with an median age of 10 (6,16) years. Two of them had simultaneous deletions of two alleles. Among 31 patients with heterozygous deletion, 16 were combined with gene mutations that severely affected 21-hydroxylase enzyme activity (I2G and Q318X), 15 with mutations that retained part enzyme activity (I172N and P30L). Two patients with complete deletion of CYP21A2 gene had no significant difference in biochemical and clinical manifestations compared with those with single allele deletion combined with another gene mutation that severely affected enzyme activity. Both kinds of patients above were manifested as severe salt-wasting type. Patients with a single allele deletion and a mutation retaining part enzyme activity were manifested as mild simple-viralizing type.
Large deletion of CYP21A2 gene could appear in 21-OHD patients and the phenotype is similar to that of salt-wasting patients with heterozygous large deletion.
Clinical features of primary tracheobronchial pulmonary amyloidosis
To analyze the clinical features of primary tracheobronchial pulmonary amyloidosis (PTBA).
The records of 11 patients with PTBA diagnosed by pathology from January 2002 to June 2018 in Xiangya Hospital of Central South University were retrospectively reviewed, including clinical manifestations, laboratory and imaging examination, bronchoscopic manifestations and therapies. Meanwhile, PTBA was staged based on the severity and extent of lesion under bronchoscopy.
The most common clinical symptoms were cough and expectoration followed by shortness of breath and hemoptysis. Chest computed tomography (CT) revealed pulmonary infection (4/11), pulmonary nodules and masses (5/11), interstitial lesions (2/11), tracheal bronchial wall thickening (5/11) or airway stenosis (4/11). Bronchoscopy showed mucosal hypertrophy (8/11), nodular bulge (3/11), and luminal stenosis (6/11). According to the lesion involvement, 1 case only involved the lungs, 10 cases involved the trachea and/or bronchus, with (8/10) or without (2/10) lung lesions. According to the bronchoscopic staging, 2 cases (2/10) in the stage Ⅰ, lesions were limited; 2 cases (2/10) in the stage Ⅱ, lesions were diffuse; 6 cases (6/10) in the stage Ⅲ, diffuse lesions with stenosis.
PTBA is a rare disease of the respiratory system, with unspecific clinical manifestations and diverse pulmonary imaging findings; airway mucosal hypertrophy and nodular bulging can be seen under bronchoscopy. Patients with advanced stage may present with airway stenosis.
Adrenal androgen measurement for assessing the selectivity of adrenal venous sampling in primary aldosteronism
To investigate the usefulness of adrenal androgens for assessing the selectivity of adrenal venous sampling (AVS).
Between January 2010 and December 2016, 37 consecutive patients [with an average age of (47±14) years, 16 males and 21 females] with primary aldosteronism (PA) who underwent AVS were enrolled. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal venous (AV) and peripheral venous (PV) samples, respectively.
The selectivity index (SI) based on androstenedione and DHEA was higher than that of cortisol (SI-left: 13.9, 13.1 vs 6.05, P=0.006, 0.035; SI-right: 30.4, 18.5 vs 11.6, P=0.028, 0.051). However, the SI based on DHEAS was lower than that of cortisol (SI-left: 1.3 vs 6.0, P=0.002; SI-right: 1.5 vs 11.6, P=0.038). Plasma androstenedione and DHEA concentrations were positively correlated with cortisol and aldosterone in AV samples (all P<0.001). Compared to cortisol, the variation ratio of AV androstenedione and DHEA was lower from t-15 to t0 (0.23, 0.43 vs 0.52, both P<0.05). Using the receiver operating characteristic curve, a SI ≥ 3.0 for androstenedione or DHEA provided optimal sensitivity(97.7%, 91.9%) and specificity (93.8%, 93.8%) in AVS.
Given the greater AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors co-secreting cortisol and aldosterone.
Correlation between serum interleukin-38 and acute exacerbation of chronic obstructive pulmonary disease with pulmonary embolism
To investigate the correlation between serum interleukin-38 (IL-38) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with pulmonary embolism (PE).
The 94 patients with AECOPD admitted to Tianjin Chest Hospital from August 2015 to April 2018 were suspected of PE. They were divided into two groups based on CT pulmonary angiography (CTPA) and color Doppler ultrasound of lower extremity veins: 39 cases in PE group and 55 cases in Non-PE group. The general data and laboratory examination results of these subjects were recorded. Serum IL-38 was measured by double antibody enzyme-linked immunosorbent assays (ELISA). The between-group differences of above parameters were analyzed. Pearson correlation or Spearman rank correlation was used to analyze the association of IL-38 with each variable in AECOPD patients. Binary Logistic regressions were conducted to determine the risk factors of AECOPD with PE. ROC curve was used to assess the value of serum IL-38 in predicting AECOPD with PE.
The serum level of IL-38 was lower in PE group than in Non-PE group [46.3 (33.1, 58.1) vs 61.5 (46.6, 72.5) ng/L, P<0.05]. Correlation analysis showed that serum IL-38 levels were negatively correlated with C reactive protein and fibrinogen in patients with AECOPD (r=-0.38,-0.29, all P<0.05). Binary Logistic regressions showed that lower serum IL-38 level was a risk factor of AECOPD with PE (OR=0.78, 95%CI: 0.61-0.94, P<0.05). The area under the ROC curve was 0.74 (95% CI: 0.63-0.84, P<0.05). When cutoff value of serum IL-38 was 52.1ng/L, the sensitivity was 70.9% and the specificity was 69.2% respectively.
IL-38 could relieve the hypercoagulability by inhibiting inflammation in patients with AECOPD and could act as a predictor of AECOPD with PE.
Relationship between angiopoietin-2 and vascular endothelial factor and vasodilation function in hypertensive patients
To analyze the relationship between angiopoietin 2 (Ang2) and vascular endothelial factor and vasodilation function in hypertensive patients.
Patients with new onset grade 1~2 hypertension (n=40) and healthy control group (n=25) wereenrolledprospectively. Serum Ang2 and nitric oxide (NO), nitric oxide synthase (eNOS), endothelin-1 (ET-1) were measured in both groups. Flow-mediated vasodilation (FMD) were measured in hypertensive patients. The above indicators were reviewed in hypertensive patients after antihypertensive treatment until blood pressure<140/90 mmHg.
Compared with the control group, serum Ang2 (P=0.049) and ET-1 (P<0.001) were significantly higher. Serum NO (P<0.001) and eNOS (P<0.001) was significantly lower in the hypertensive group. Compared with baseline, serum Ang2 (P=0.049) and ET-1 (P<0.001) were decreased significantly, meanwhile serum NO (P<0.001) and eNOS (P<0.001) were significantly increased. Serum Ang2 after antihypertensive treatment was not significantly different from that of the control group, but no statistical difference was observed in FMD after antihypertensive therapy. Correlation analysis found that serum Ang2 was positively correlated with mean arterial pressure (R=0.432, P<0.001), and negative correlated with serum NO(R=-0.374, P=0.001) and FMD (R=-0.368 0, P=0.002). Multiple linear regression found that serum Ang2 was independently associated with body mass index, mean arterial pressure, and serum NO.
Serum Ang 2 can reflect the degree of endothelial and vasodilation impairment in hypertensive patients. Antihypertensive therapy can improve endothelial function, but whether it can restore damaged vasodilation function needs further verification.
The effect of air test and methylene blue perfusion test on detecting the quality of anastomosis during laparoscopic rectal cancer excision (Dixon)
To investigate the feasibility and safety of air test (AT) and methylene blue perfusion test (MBPT) to detect the quality of the anastomosis in laparoscopic rectal cancer excision (Dixon), and compare the two approaches.
AT is performed by filling the pelvis with saline solution and insufflating the rectum with air through a size 22 G balloon catheter (Foley). MBPT is carried out by surrounding clean sponges around anastomosis and injecting methylene blue solution into the rectum as like as AT. The balloon catheter connected manometer,ensuring the pressure in rectum can reach 40 cmH2O during AT and MBPT. The presence of air bubbles and overt blue-stained spillage indicated anastomotic leaks which are were resolved during surgery. All 28 patients undergoing laparoscopic rectal excision received both AT and MBPT intraoperatively in a randomized fashion. The integrity of the anastomosis, postoperative vital signs, blood examination, drainage and postoperative imaging were analyzed.
All 28 patients received both tests successfully with no adverse event. MBPT Level 1 was detected in 15 cases, level 2 in 8 cases, level 3 in 5 cases. No MBPT level 4 was observed. AT level 1 was detected in 22 cases, level 2 in 5 cases, level 3 in 1 cases. No AT level 4 was founded. Three cases were diagnosed with postoperative anastomotic leakage (3/28, 10.71%), of which 2 cases were Grade B [definition and grading proposed by the international study group of rectal cancer (ISREC) in 2010]. One case was Grade C. The positive rate of MBPT was superior to AT (the McNemar testing, P<0.01).
The two intraoperative tests are both technically feasible and safe. Compared to AT, MBPT has the advantage of localizing the leak site with a higher positive accuracy, and represents a promising standardized approach for intraoperative test of the anastomosis quality. Intraoperative repair is absolutely helpful for the level 3 and 4 intraoperative tests.
Preliminary application of one-step hybrid operation in the treatment of carotid artery occlusion
To evaluate the prognosis and surgical complication of the recanalization treatments for internal carotid artery (ICA) occlusion by using one-step hybrid carotid endarterectomy and endovascular surgery.
Retrospective analysis was performed on the clinical data and follow-up data of 22 patients with occluded ICA treated by one-step hybrid surgery. Difference in Barthel score and occurrence of ischemic stroke were compared with surgical group and conventional group which was treated by oral taking anti-platelet drugs. Further, the complications were analyzed to evaluate the safety and effectiveness of the surgery.
The difference in ischemic event rate and Barthel scores improvement between the two groups were significant. Occlusive ICAs in 19 cases were recanalized successfully. The possibility of brain hyperperfusion related to the surgery was 10.5% (2/19) while the possibility of carotid artery cavernous fistula was 9.1% (2/22). We also observed rare dissecting ICA caused by the treatment (4.5%) and distal restenosis (5.3%).
One-step hybrid carotid endarterectomy and endovascular surgery could help recanalize the ICA, improve the blood supply and improve the prognosis. It′s a safe and effective treatment for ICA occlusion.
Surgical treatment for inflammatory myofibroblastic tumor in genito-urinary system: a study of 15 cases
To present 15 cases of inflammatory myofibroblastic tumor (IMT) in genitor-urinary system, and analyze the characteristics, diagnosis and treatment of the disease.
The diagnostic and therapeutic process of 15 confirmed cases admitted to Sun Yat-sen University Cancer Center between March 2009 and September 2017 were retrospectively analyzed. Of the total cases, 11 cases were diagnosed with cystic IMT with a maximum diameter of 1.0-4.5 cm, 8 cases underwent transurethral resection of bladder tumor(TURBT)and 4 of them underwent partial cystectomy after TURBT and 3 underwent partial cystectomy directly. Two cases were renal IMT with a maximum diameter of 4.0-9.0 cm, one underwent partial nephrectomy and the other accepted radical nephrectomy. One case who was diagnosed with prostatic IMT with a maximum diameter of 3.4 cm underwent transurethral resection of the prostate (TURP) and postoperative radiotherapy. One case who was diagnosed with perineal IMT with a maximum diameter of 2.1 cm underwent tumor resection.
The patients were followed up for 10-32 months with a median time of 27 months. No cases relapsed during the follow-up.
Surgery is the preferred method for treating IMT in genitor-urinary system. Retrospective study shows a good prognosis in IMT patients, but a long-term follow-up is still required.
Patient with atrial fibrillation after radiofrequency ablation-hemoptysis-fever-left lower lung patch
Three months after radiofrequency ablation of atrial fibrillation (referred to as atrial fibrillation), the patient repeatedly went to the department of respiratory medicine due to fatigue, fever, hemoptysis, left lower lung patches, and a small amount of bloody pleural effusion. The patient was initially diagnosed as pneumonia and tuberculosis. The etiological culture and sequencing were negative, and the anti-bacterial, fungal and tuberculosis effects were poor. Positron emission computed tomography (PET/CT) showed that the uptake rate of 18F-FDG in the left lower lung was increased, and the pathology of multiple tissue biopsies did not support the tumor. After detailed inquiry of the patient's medical history and cardiology consultation, cardiac CT + pulmonary vein reconstruction showed severe stenosis at the opening of the left lower pulmonary vein, which was diagnosed as pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation.
A case of uremia complicated with critical reversible posterior encephalopathy syndrome
Reversible posterior encephalopathy syndrome (PRES) is a group of clinical imaging syndromes caused by multiple factors with neurological abnormalities as the main manifestation. After active and effective treatment, clinical symptoms and imaging can be completely recovered. This paper reports the clinical and imaging features of a case of uremia complicated by critical PRES in order to improve the understanding of this disease.
Discussion on the choice of surgical strategies for the treatment of mitral regurgitation in young patients
Mitral valve replacement (MVR) and mitral valvuloplasty (MVP) are the two main treatments for mitral regurgitation at present. At present, the view that shaping is superior to valve replacement has become increasingly unsuitable for the current clinical situation. For patients with degenerative and rheumatic valvular disease, MVP has advantages in postoperative survival rate, but there is a high risk of early regurgitation recurrence rate, and MVR can also achieve satisfactory clinical efficacy; For patients with ischemic mitral regurgitation, the clinical decision-making is more detailed and complex, and the selection of MVP and MVR needs more in-depth clinical research to provide evidence support.
Metformin and pulmonary vascular remodeling in patients with chronic thromboembolic pulmonary hypertension
Pulmonary vascular remodeling is one of the important pathological changes in chronic thromboembolic pulmonary hypertension (CTEPH). In recent years, it has been found that metformin has a protective effect on pulmonary vascular system, which is characterized by inhibiting vascular remodeling, resisting cell proliferation and inhibiting cell mesenchymal transformation. This article will expound the research progress of pathophysiological changes and signaling pathways of CTEPH in recent years from the aspect of pulmonary vascular remodeling, and expound the possibility of prevention and treatment of CTEPH by hypoglycemic drug metformin according to pathophysiological changes and signaling pathways of CTEPH vascular remodeling.
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