Preliminary Study on the Combination Effect of Clindamycin and Low Dose Trimethoprim-Sulfamethoxazole on Severe Pneumocystis Pneumonia After Renal Transplantation.

Objective: Evaluate the effect of the combination of clindamycin with low-dose trimethoprim-sulfamethoxazole (TMP/SMX) regimen on sever Pneumocystis pneumonia (PCP) after renal transplantation. Method: 20 severe PCP patients after renal transplantation were included in this historical-control, retrospective study. A 10 patients were treated with the standard dose of TMP/SMX (T group), the other 10 patients were treated with the combination of clindamycin and low dose TMP/SMX (CT group). Results: Although there was no significant difference in the hospital survival between the two groups, the CT protocol improved the PaO2/FiO2 ratio more significantly and rapidly after the 6th ICU day (1.51 vs. 0.38, P = 0.014). CT protocol also ameliorated the pulmonary infiltration and the lactate dehydrogenase level more effectively. Moreover, the CT protocol reduced the incidence of pneumomediastinum (0 vs. 50%, P = 0.008), the length of hospital staying (26.5 vs. 39.0 days, P = 0.011) and ICU staying (12.5 vs. 22.5 days, P = 0.008). Furthermore, more thrombocytopenia (9/10 vs. 3/10, P = 0.020) was emerged in the T group than in the CT group. The total adverse reaction rate was much lower in the CT group than in the T group (8/80 vs. 27/80, P < 0.001). Consequently, the dosage of TMP/SMX was reduced in 8 patients, while only 2 patients in the CT group received TMP/SMX decrement (P = 0.023). Conclusion: The current study proposed that clindamycin combined with low-dose TMP/SMX was more effective and safer the than single use of TMP/SMX for severe PCP patients after renal transplantation (NCT04328688).

Machine learning models to predict red blood cell transfusion in patients undergoing mitral valve surgery.

BACKGROUND: Red blood cell (RBC) transfusion therapy has been widely used in surgery, and has yielded excellent treatment outcomes. However, in some instances, the demand for RBC transfusion is assessed by doctors based on their experience. In this study, we use machine learning models to predict the need for RBC transfusion during mitral valve surgery to guide the surgeon's assessment of the patient's need for intraoperative blood transfusion. METHODS: We retrospectively reviewed 698 cases of isolated mitral valve surgery with and without combined tricuspid valve operation. Seventy percent of the database was used as the training set and the remainder as the testing set for 13 machine learning algorithms to build a model to predict the need for intraoperative RBC transfusion. According to the characteristic value of model mining, we analyzed the risk-related factors to determine the main effects of variables influencing the outcome. RESULTS: A total of 166 patients of the cases considered had undergone intraoperative RBC transfusion (24.52%). Of the 13 machine learning algorithms, CatBoost delivered the best performance, with an AUC of 0.888 (95% CI: 0.845-0.909) in testing set. Further analysis using the CatBoost model revealed that hematocrit (<37.81%), age (>64 y), body weight (<59.92 kg), body mass index (BMI) (<22.56 kg/m2), hemoglobin (<122.6 g/L), type of surgery (median thoracotomy surgery), height (<160.61 cm), platelet (>194.12×109/L), RBC (<4.08×1012/L), and gender (female) were the main risk-related factors for RBC transfusion. A total of 204 patients were tested, 177 of whom were predicted accurately (86.8%). CONCLUSIONS: Machine learning models can be used to accurately predict the outcomes of RBC transfusion, and should be used to guide surgeons in clinical practice.

RETRACTED: Twist2 promotes kidney cancer cell proliferation and invasion via regulating ITGA6 and CD44 expression in the ECM-Receptor-Interaction pathway.

Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence proves that Twist2 involves in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. RT-PCR and Western blot analysis were used to detect the expression of Twist2 in kidney cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration and invasion assay was measured by the Cell Count Kit-8 (CCK8), flow cytometry, wound healing and transwell analysis, respectively. Gene set enrichment analysis (GSEA) was used to identify correlation of Twist2 with ECM-Receptor-Interaction pathway. In this report, we show that Twist2 up-regulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promotes cell proliferation, inhibits cell apoptosis, augments cell migration and invasion in human kidney cancer-derived cell in vitro, and promotes tumor growth in vivo. Moreover, we found that knockdown of Twist2 decreased the levels of ITGA6 and CD44 which contribute to cell migration and invasion correlated with ECM-Receptor-Interaction pathway. This result indicates Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 involves in kidney cancer progression. The identification of the role Twist2 on the migration and invasion of kidney cancer provides a potential appropriate treatment after radical nephrectomy to get a better prognosis that reducing recurrence.

Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway.

Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence has proven that Twist2 is involved in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of Twist2 in kidney cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration, and invasion assay were analyzed using the Cell Count Kit-8, flow cytometry, wound healing, and Transwell analysis, respectively. In this study, we showed that Twist2 was upregulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promoted cell proliferation, inhibited cell apoptosis, and augmented cell migration and invasion in human kidney-cancer-derived cells in vitro. Twist2 also promoted tumor growth in vivo. Moreover, we found that the knockdown of Twist2 decreased the levels of ITGA6 and CD44 expression. This result indicates that Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 is involved in kidney cancer progression. The identification of the role of Twist2 in the migration and invasion of kidney cancer provides a potential appropriate treatment for human kidney cancer.

Moderate-dose glucocorticoids as salvage therapy for severe pneumonia in renal transplant recipients: a single-center feasibility study.

This study aimed to assess the effectiveness and safety of moderate-dose glucocorticoids (GCs) with mechanical ventilation as salvage therapy for renal transplant recipients with severe pneumonia, which was non-responsive to conventional treatment. A retrospective study was conducted involving renal transplant recipients diagnosed with severe pneumonia and did not respond to conventional treatment. All immunosuppressants were then completely withdrawn, and the patients were initially administered with methylprednisolone at doses of 2.0-2.5 mg/kg/day once every 12 h. This dosage was continued until oxygenation improved, and the treatment was gradually tapered (by 20 mg every 2-3 days) to the previous maintenance dosage. Ten patients were recruited from year 2008 to 2012. Two patients who underwent emergency endotracheal intubation were intubated on days 3 and 8, respectively, another one died from recurrent pneumothorax. The mean PaO2/FiO2 of the nine survivors was significantly increased by the increasing treatment duration; whereas the lung injury scores (LIS) and the sequential organ failure assessment (SOFA) score were both significantly decreased. The use of moderate-dose GCs may play a role as salvage therapy for renal transplant recipients with severe pneumonia. However, further study with larger trials to is needed.

Clinical features and treatment strategies for older prostate cancer patients with bone metastasis.

To identify the clinical features and independent predictors of survival in older patients with bone metastasis from prostate cancer (PCa). We retrospectively analysed 205 older patients with bone metastases from PCa between 1997 and 2012. The Kaplan-Meier method was used with the log-rank test for survival rate calculations and to evaluate each variable. Multivariate analysis was performed with the Cox regression model. The chi-squared test was used to compare survival rates between older and younger (n=197) patients. All patients were followed up. The 1-, 2-, 3- and 5-year survival rates were 95.5%, 77.5%, 68.5% and 33.7%, respectively. Gleason score, radiotherapy of the primary tumour, the number of bone metastases, the alkaline phosphatase alkaline phosphatase (ALP) level, organ metastasis and regional lymph node metastasis were associated with the survival rates. Multivariate Cox regression analysis showed that Gleason score at diagnosis of the primary tumour was a significant predictor of overall survival following the diagnosis of bone metastases. In addition, the overall survival rates of older patients were higher compared with younger patients, but older patients who underwent radiotherapy had higher mortality. These data may serve as a guide for creating clinical prediction models in further studies.

[Clinical and serological analyses of 70 erythrocyte allo-antibodies to MNS blood group system].

OBJECTIVE: To explore the occurrence and clinical significance of erythrocyte allo-antibodies to MNS blood group system among hospitalized patients in China. METHODS: The specificity and clinical features of erythrocyte allo-antibodies detected from August 2009 to July 2012 were retrospectively analyzed. RESULTS: A total of 187 erythrocyte allo-antibodies were detected from 66 042 hospitalized patients (0.28%) among which 70 (37.4%) were specific to MNS blood group system. Antibody frequencies were as follows: anti-M, 18.2%; anti-Mi(a), 18.2%; anti-S, 1.1%. Anti-Mi(a) was more frequent among transfused patients (16/34 vs 5/34, P = 0.004), and tended to be accompanied by other allo-antibodies. CONCLUSIONS: Antibodies to MNS blood group system are second only to Rh system as the most common erythrocyte allo-antibodies in China. And anti-Mi(a) is an important transfusion-related allo-antibody among the patients of southern ancestry.

Combination of caspofungin and low-dose trimethoprim/sulfamethoxazole for the treatment of severe Pneumocystis jirovecii pneumonia in renal transplant recipients.

Pneumocystis jirovecii pneumonia (PJP) is a severe and life-threatening complication in immunocompromised patients. Trimethoprim/sulfamethoxazole (TMP-SMZ) is well known for its effectiveness as prophylaxis of PJP. However, the use of TMP-SMZ is associated with various adverse effects that may not be tolerated by critically ill patients. Caspofungin is recommended for invasive fungal infections, but the treatment of PJP after solid organ transplantation (SOT) is an off-label use of this drug. In this study, three cases of severe PJP in renal transplant recipients treated with a combination of caspofungin and low-dose TMP-SMZ were presented. Initial findings indicated that the combined treatment may be beneficial for the treatment of PJP and decrease the incidence of TMP-SMZ-related adverse effects.

[Expression of inflammation cytokines and network analysis in acute rejection of renal transplantation].

OBJECTIVE: To explore the changes of inflammation cytokines during acute renal transplantation rejection and decipher the functions of their protein-protein interaction network. METHODS: Serum samples were collected from renal transplantation patients with stable renal function or acute rejection (n = 6 each) to measure the expression level of 40 inflammatory factors by APIX protein array. The differentially expressed proteins were selected and their protein-protein interaction networks constructed. And biologic processes were analyzed by the online tools of String and Network Ontology Analysis. RESULTS: There were 8 differentially expressed cytokines in the AR group versus the stable group (M (Q(1)-Q(3)), CCL24: 700 (255 - 1157) vs 330 (100 - 610) ng/L, ICAM-1: 58 737 (8018 - 105 395) vs 22 660 (137 - 68 914) ng/L, IL-10: 120 (20 - 517) vs 298 (81 - 11 609) ng/L, IL-6sR: 11 328 (3357 - 21 251) vs 7665 (370 - 12 455) ng/L, CCL3: 1712(7002 - 32 634) vs 283 (54 - 1915) ng/L, CCL4: 554 (28 - 2355) vs 283(104 - 1915) ng/L, TIMP-1: 15 560 (13 343 - 42 481) vs 11 271 (1207 - 18 228) ng/L, CCL5: 44 547 (38 252 - 78 631) vs 27 765 (12 073 - 46 627) ng/L, all P < 0.05). The analyses of protein-protein association network showed that these proteins were correlated and involved in such biological processes as taxis, chemotaxis, inflammatory reactions, wound responses and leukocytic migration. CONCLUSIONS: Comparing the inter-group differences of inflammatory cytokines and further developing and analyzing the protein-protein interaction network may help us to explore the mechanisms of acute renal transplantation rejection. And the differential cytokines can be used as candidate diagnostic biomarkers and intervention targets.

[Specificity and clinical features of erythrocytic allo-antibodies in hospitalized patients].

OBJECTIVE: To evaluate the occurrence and clinical significance of red blood cell (RBC) allo-antibodies among hospitalized patients in China. METHODS: The specificity and clinical features of RBC allo-antibodies of hospitalized patients at our hospital from August 2009 to January 2011 were retrospectively analyzed. RESULTS: Sixty-four (0.17%) RBC allo-antibodies were detected from 37 548 hospitalized patients. The male-to-female ratio was 0.6:1 and the transfused: untransfused ratio 0.9:1. Two patients had experienced episodes of delayed hemolytic transfusion reaction (DHTR). Their antibody frequencies were as follows: anti-E 53.1% (34/64), anti-D 10.9% (7/64), anti-cE 3.1% (2/64), anti-c 1.6% (1/64), anti-M 14.1% (9/64), anti-Mi(a) 10.9% (7/64), anti-Le(a) 4.7% (3/64), anti-Di(a) 1.6% (1/64). Antibodies to Rh system were more frequent among transfused patients while antibodies to Lewis system had a male predominance (both P < 0.05). CONCLUSION: As the most common and clinically significant RBC allo-antibodies, the antibodies to Rh blood group system, especially anti-E, anti-cE and anti-c, are the main cause of DHTR.

[Analysis of microchimerism in living renal transplantation between mothers and children relationship].

OBJECTIVE: To compare the microchimerismic and rejection rates in living donor kidney transplant recipients in mother and child relations and other relations. METHODS: This retrospective single-center study enrolled 130 recipients to receive allografts from living related donors from 2004 to 2008 at our hospital. They were followed up for 1 - 5 years. The demographic data of the study population were analyzed by basic statistical methods. A total of 43 recipient blood samples were collected for the detection of microchimerism by the assays of short tandem repeat (STR) and sex-determining region-y gene (SRY) polymerase chain reaction (PCR). RESULTS: The 1-year patient/graft survival rates were 93.8% and 92.3% respectively. And there was no significant differences between mother and child group and other relative group. Forty-six biopsy samples were collected from 46 recipients. Twenty-six (20.0%) cases had the occurrences of acute rejection episodes in different Banff degrees as proven by biopsy. 53.8% (14/26) cases were mother and child renal transplantation, higher than other relative (46.2%, 12/26). The mother donor kidney transplant recipients had about a twice higher rejection rate (30.4% vs 14.3%, P = 0.028) and a twice higher microchimerismic rate (25.0% vs 14.8%) than other relative. CONCLUSION: Compared with other relations, the mother donor kidney recipients tend to have higher rates of microchimerism and acute rejection. And the special immune effect in mothers and children renal transplantation may influence its outcomes.

[Preliminary exploration in proteomic-based mechanistic analysis of patients with acute renal allograft rejection].

OBJECTIVE: To explore the application of proteomics in the mechanistic analysis of acute rejection (AR). METHODS: Quantified proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling was utilized to identify the protein profiling between the transplantation patients with (n = 5) or without AR (n = 8) from 2008 to 2010. RESULTS: Among the 179 identified proteins, 66 proteins in AR patients had at least a 2-fold change as compared with those without AR. The results demonstrated the dominant processes and responses associated with inflammation and complement activation. It was consistent with the underlying immune rejection associated with AR. Moreover, the results also indicated that high-coagulation state existed in AR patients. A number of transcription factors were identified in AR patients, including nuclear factor-κB, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3. The analysis of transcription regulation networks suggested that the cross-talks among these key transcription factors might play an important role in the acute response and activation of coagulation system. CONCLUSION: The application of proteomics provides a new strategy of mechanistic analysis in AR.

[Detection of BK virus infection in renal transplant recipients and clinical application].

OBJECTIVE: To study the detection methods of BK virus infection in kidney transplant recipients, and to explore the clinical application. METHODS: 132 cases of renal transplant recipients were undertaken BK virus detection including presence of decoy cells in urinary sediment, urine and serum BKV-DNA to demonstrate the BK virus replication. RESULT: Among 132 cases of renal transplant recipients, urinary decoy cell was found in 37 (28.0%) patients and the median time was 12 months after surgery. 32 (24.2%) patients were diagnosed as BK viruria at a median of 11 months after surgery, and 16 (12.1%) recipients were diagnosed as BK viremia at a median of 15 months after surgery, 5 patients with BK viruria were diagnosed as BK virus associated nephropathy according to allograft biopsy. CONCLUSION: To make early diagnosis of BK virus infection, detection of urine decoy cells and BKV-DNA in urine and plasma sample is important,which provides an important basis for the prevention of BK virus associated nephropathy.

[Efficacy and safety of different dosages of intravesical epirubicin instillation for prevention of primary superficial bladder carcinoma from recurrence].

OBJECTIVE: To investigate the efficiency and safety of different regimens by intravesical instillation of epirubicin, a derivative of adriamycin, for the prevention of primary superficial bladder carcinoma from recurrence. METHODS: Ninety patients supplemented with intravesical epirubicin instillation after operation were randomly divided into three groups: Group A--80 mg in one dose; Group B--repeated epirubicin 40 mg q wk x 4-8 sessions followed by q month to the end of the second year; or Group C--50 mg q month to the same duration. All patients were followed up for two years by observing the recurrence rates and side effects. RESULTS: The recurrence rate of groups A, B and C at one year was 16.7%, 13.3% and 16.7%, respectively, without any significant difference observed. However, it was 50.0%, 36.7% and 36.7% at two years, at which time the recurrence rate of group A was significantly higher than those of groups B and C. The side effects rate was 23.3%, 40.0% and 33.3% for groups A, B and C, respectively. The more instillations the patients had, the more severe side effects were. CONCLUSION: Early postoperative single high dose intravesical instillation of epirubicin combined with repeated lower doses of the same drug every month may be an efficient and safe regimen to prevent the primary superficial bladder carcinoma from recurrence.