[Preliminary clinical application of novel magnetic navigation and ultrasound-guided percutaneous transhepatic cholangiography drainage through the right liver duct for malignant obstructive jaundice].

Objective: To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice. Methods: Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People's Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group (n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group (n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results: The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35,P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81,P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion: Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

[A single-center retrospective study of percutaneous drainage clinical characteristics of grade B and C postoperative pancreatic fistula and determination of the optimal intervention time].

Objective: To classified the fluid location of of grade B and C postoperative pancreatic fistula (POPF) and propose processing flow. Methods: Data from 232 patients who underwent pancreatic surgery from January 2018 to December 2022 at Department of General Surgery & Hepato-billo-pancreatic,Beijing Hospital were collected retrospectively. Forty-six patients who suffered from grade B and C POPF underwent ultrasound-guided drainage. There were 32 males and 14 females, with an age of (60.2±13.7)years (range:18 to 85 years). The imaging data of postoperative CT were collected and the the fluid location was classified. Then analyzed the drainage status when patents were diagnosed as POPF. Machine learning was performed and a random forest model was applied to construct the relationship between intervention time and mortality. The optimal intervention time was calculated. The patients were then divided into early and late intervention groups and clinical data and outcomes were compared using the t test,Mann-Whitney U test, χ2 test or Fisher's exact test between the two groups. Results: Based on the results of the random forest model, the optimal puncture time was within 5.38 days after the diagnosis of POPF. Based on the optimal time, 21 patients were subsumed into early intervention group and 25 patients were subsumed into late intervention group. The location of fluid collection was classified into four types: peripancreatic (32.7%,15/46), extra-pancreatic and epigastric (41.3%,19/46), extra-pancreatic and hypogastic (13.0%,6/46) and diffused (13.0%,6/46). The status of the drainage included normal in 10 patients (21.8%), displaced drain in 18 patients (39.1%) and drain removed or blocked in 18 patients (39.1%). The perioperative mortality rate was 19.0% (4/21) in the early intervention group and 8.0%(2/25) in the late. The late intervention group had significantly higher rates of positive drainage fluid cultures (88.0%(22/25) vs. 42.9%(10/21), χ2=10.584, P=0.001), secondary surgery (24.0%(6/25) vs. 0(0/21), P=0.025), and readmission within 90 days(32.0%(8/25) vs. 4.8%(1/21),χ2=5.381, P=0.020) than the early group, and a significantly longer postoperative hospital stay(M(IQR))(24(20)days vs. 39(53)days,Z=3.023,P=0.003). Conclusions: The location of the POPF fluid collection is classified into four types. Early radiological evaluation can detect abdominal effusion promptly,and early puncture and drainage will be beneficial in improving outcomes in these patents.

[Effects and mechanism of diammonium glycyrrhizinate on liver injury in severely scalded rats].

Objective: To investigate the effects and mechanism of diammonium glycyrrhizinate (DG) on liver injury in severely scalded rats. Methods: The experimental research method was used. Fifty-four female Sprague-Dawley rats aged 7-9 weeks were divided into sham injury group with simulated injury on the back, and simple scald group and scald+DG group with scald of 30% total body surface area on the back, with 18 rats in each group. Rats in sham injury group were not specially treated after injury, and rats in simple scald group and scald+DG group were rehydrated for antishock. Besides, rats in scald+DG group were injected intraperitoneally with 50 mg/kg DG at post injury hour (PIH) 1, 25, and 49. Rats in the three groups were collected, the serum content of liver function injury related indexes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total protein, and albumin was measured by automatic biochemical assay analyzer, and serum content of ornithine carbamoyl transferase (OCT) was measured by enzyme-linked immunosorbent assay method at PIH 24, 48, and 72; hepatic histopathological changes at PIH 72 were observed by hematoxylin-eosin staining; the mRNA expressions of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), glucose regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and protein kinase R-like endoplasmic reticulum kinase (PERK) in liver tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction at PIH 24, 48, and 72. The protein expressions of Bcl-2, Bax, GRP78, PERK, and ATF4 in liver tissue were detected by Western blotting at PIH 72 in sham injury group and PIH 24, 48, and 72 in simple scald group and scald+DG group. The number of samples was 6 in each group at each time point. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni test. Results: Compared with that in sham injury group, the serum content of AST, ALT, and LDH was significantly increased (P<0.01), and the serum content of total protein and albumin was significantly decreased (P<0.05 or P<0.01) of rats in simple scald group at all post-injury time points. Compared with those in simple scald group, the serum AST content of rats in scald+DG group at PIH 24 was decreased significantly (P<0.05); the serum AST, ALT, and LDH content of rats in scald+DG group at PIH 48 was decreased significantly (P<0.01), and the serum total protein content was increased significantly (P<0.01); the serum AST, ALT, and LDH content of rats in scald+DG group at PIH 72 was decreased significantly (P<0.01), and the serum total protein and albumin content was increased significantly (P<0.01). At PIH 24, 48, and 72, the serum OCT content of rats in simple scald group was (48.5±3.9), (40.8±2.4), and (38.7±2.0) U/L, which was significantly higher than (15.1±2.5), (15.7±2.6), and (16.4±3.7) U/L in sham injury group (P<0.01), and (39.0±4.5), (31.8±2.0), and (22.1±2.6) U/L in scald+DG group (P<0.05 or P<0.01). At PIH 72, the cells in liver tissue of rats in sham injury group had normal morphology and regular arrangement, with no obvious inflammatory cell infiltration; the cells in liver tissue of rats in simple scald group had disordered arrangement, diffuse steatosis, and moderate inflammatory cell infiltration; the cells in liver tissue of rats in scald+DG group arranged regularly, with scattered steatosis and a small amount of inflammatory cell infiltration. Compared with those in sham injury group, the Bcl-2 mRNA (P<0.05 or P<0.01) and protein expressions of liver tissue were significantly decreased, and the mRNA (P<0.01) and protein expressions of Bax were significantly increased in rats in simple scald group at PIH 24, 48, and 72. Compared with those in simple scald group, the mRNA (P<0.05) and protein expressions of Bax in liver tissue of rats in scald+DG group were decreased significantly at PIH 48; the mRNA (P<0.01) and protein expressions of Bax in liver tissue of rats in scald+DG group were significantly decreased, and the mRNA (P<0.01) and protein expressions of Bcl-2 were significantly increased at PIH 72. Compared with those in sham injury group, the mRNA (P<0.05 or P<0.01) and protein expressions of ATF4, GRP78, and PERK in liver tissue were significantly increased in rats in simple scald group at all post-injury time points. Compared with those in simple scald group, the mRNA (P<0.01) and protein expressions of ATF4 in liver tissue of rats in scald+DG group at PIH 48 were significantly decreased, and the mRNA (P<0.05 or P<0.01) and protein expressions of ATF4, GRP78, and PERK were significantly decreased in liver tissue of rats in scald+DG group at PIH 72. Conclusions: DG can effectively reduce the degree of liver injury in rats after severe scald, and the mechanism may involve alleviating endoplasmic reticulum stress and mitigating mitochondrial damage.

[Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles].

OBJECTIVE: To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression profiles on T helper type 17 (Th17)/regulatory T cells (Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis. METHODS: Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways (PI3K-Akt and mTOR pathways) were matched. RESULTS: A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs. GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and mTOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and 15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways. CONCLUSIONS: Significant changes are found in serum miRNA expression profiles among patients with E. granulosus infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K-Akt and mTOR pathways, which facilitates the long-term parasitism of E. granulosus in hosts and causes a chronic disease.

[Efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma].

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(n=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(n=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,P=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,P=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P=0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,P=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.

Effects of CAR structure and culture conditions on memory CAR-T cells.

Adoptive CAR T cell therapy (chimeric antigen receptor T-Cell) has received increasing attention in recent years; however, its efficacy is undesirable and differs from person to person. Understanding how to overcome this obstacle is important to improve therapy. Infusion of poorly differentiated CAR-CD62L+ T cells, such as T memory stem cell populations, leads to enhanced T cell implantation, expansion, and persistence, which ultimately leads to more stable tumour regression. Here, we reviewed emerging findings demonstrating that CAR structure and cell culture conditions can influence CAR T cell differentiation and antitumour efficacy.

[The effect of standardized lymphectomy and sampling of resected lymph nodes on TNM staging of resectable pancreatic head cancer].

Objective: To examine the effect of standardized lymphectomy and sampling of resected lymph nodes (LN) on TNM staging of resectable pancreatic head cancer. Methods: Consecutive patients with resectable pancreatic head cancer who received standard pancreatoduodenctomy at Department of General Surgery in Beijing Hospital from December 2017 to November 2018 were recruited as study group. After operation, the surgeon sampled lymph nodes from the fresh specimen following the Japanese Gastric Cancer Guidelines.Thirty-three cases were recruited in the study group and the mean age was (59.8±15.2) years.Pathologic reports from December 2015 to November 2016 were taken as control group, containing 29 cases with age of (57.0±13.0) years. Number of lymph nodes, standard-reaching ratio and positive nodes ratio were compared between two groups. According to the seventh edition and eighth edition of TNM staging, the changes of N staging and TNM staging were analysed. The quantitative data conforming to normal distribution were tested by independent sample t test, the quantitative data not conforming to normal distribution were tested by rank sum test, and the enumeration data were analysed by χ(2) test. Results: The basal data of the two groups were comparable (all P>0.05) . The number of lymph nodes sampled in the study group was 23.27±8.87, significantly more than in control group (12.86±5.90, t=0.653, P=0.000) .Ratio of cases with more than 15 nodes was 81.8% (27/33) in the study group and 34.5% (10/29) in the control group with statistical significance (χ(2)=14.373, P=0.000) . In the study group, the positive lymph node ratios of No. 17a+17b, 14a+14b, 8a+8p LN were 36.4% (12/33) , 30.3% (10/33) and 9.1% (3/33) respectively. The positive lymph node ratio in No.14a+14b LN was higher than in No.8 LN (χ(2)=4.694, P=0.030) . According to the change in N staging system in the AJCC eighth edition, 2 cases (6.1%, 2/33) changed from ⅠB to ⅡA, 7 cases (21.2%, 7/33) from ⅡA to ⅠB and 5 cases (15.2%, 5/33) changed from ⅡB to Ⅲ (25.0%, 5/20) . Conclusions: No.14 LN should be treated as the first station rather than second station because of the anatomic character and higher metastatic ratio. Standardised lymphectomy and sampling may increase the number of LN resected and improve the TNM staging of resectable pancreatic head cancer.

[Mortality trend and age-period-cohort analysis of colorectal cancer among residents in Yangpu District of Shanghai from 1975 to 2014].

Objective: To describe the 40-years trend for the mortality of colorectal cancer (CRC) in Shanghai and to estimate the effect of age, period, and birth cohort with Age-Period-Cohort (APC) model. Methods: Data on tumor-releated death from 1975 Janurary 1 to 2014 December 31 was derived from the Yangpu District of Shanghai Center for Diseases Prevention and Control tumor registration system. Colonrectal cancer cases (C18.2-C18.9 and C20 in ICD10) were selected for analyses. Crude mortality, age-adjusted mortality, and Average Annual Percent Changes (AAPCs) were calculated for colon cancer and rectal cancer. The difference of AAPCs between male/female and different age groups were tested. An APC model (reference cohort and period were 1900 and 1975, respectively) was constructed to estimate the age-effect, period-effect, and cohort-effect on the colorectal cancer death. Results: During 1975-2014, 6 725 cases died of colorectal cancer (the cased of colon and rectal cancer were 3 684 and 3 041, respectively). The crude mortality and age-adjusted mortality of colon cancer was 8.83/100 000 and 6.76/100 000, respectively. The crude mortality and age-adjusted mortality of rectal cancer were 7.32/100 000 and 5.67/100 000, respectively. For population in Yangpu District, the crude mortality and age-adjusted mortality of colon cancer increased with time, and the crude mortality of rectal cancer increased with time (P<0.001). AAPC of the crude mortality rate (5.6%) and age-adjusted mortality rate (2.3%) of colon cancer were higher than those in rectal cancer (3.0% and -0.3%), respectively (both P values <0.001). AAPC of the crude mortality rate (males vs. females was 6.2% vs. 5.0%, P<0.05) and age-adjusted mortality rate (males vs. females was 2.7% vs. 1.7%, P<0.05) of colon cancer were higher in males than in females. APC model indicted that CRC-related death increased with age. During 1901 to 1941, the RR values of cohort effects for colon and rectal cancer death were 1.09-5.57 and from 1.04-2.28, respectively; During 1946 to 1991, the RR values of cohort effects for colon cancer and rectal cancer were 5.51-4.32 and 2.16-0.89. Conclusion: From 1975 to 2014, the mortality of CRC in Yangpu District increased gradually, and colon cancer mortality in males increased faster than that in females. The risk of death from colorectal cancer in the 1946-1991 birth cohort declined.

Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in ABO-Incompatible Kidney Transplantation Recipients.

BACKGROUND: Cytomegalovirus (CMV) infection can increase morbidity and mortality in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV) is recommended for ABO-incompatible (ABOi) KT patients as it significantly reduces CMV disease and infection. The recommended dose of VGCV for prevention of CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6 months. However, because it is expensive, sufficient amounts might not be administered. METHODS: We investigated whether ultralow-dose VGCV (450 mg every other day) and short dosing period (3 months) was sufficient to prevent CMV infection after ABOi KT. We retrospectively evaluated 74 adult CMV-seropositive donor/CMV-seropositive recipient (D+/R+) ABOi KT recipients from June 2009 to July 2016 who received ultralow-dose VGCV prophylaxis for 3 months. The primary outcome was occurrence of CMV infection. Secondary outcomes were leukopenia and thrombocytopenia. RESULT: All patients received intravenous rituximab 200 mg once and plasmapheresis for reduction of anti-A/B antibodies and interleukin-2 antibodies before undergoing ABOi KT. Mean prophylaxis and follow-up durations were 3 and 52 months, respectively. One patient died of bacterial pneumonia. Four patients lost graft function and were undergoing hemodialysis; 3 cases were caused by antibody-mediated rejection, and 1 was due to mechanical complication after surgery. Fortunately, CMV infection did not occur in any patient. CONCLUSION: Ultralow-dose VGCV is an effective prophylaxis for D+/R+ ABOi KT recipients. Especially, ultralow-dose VGCV CMV infection prevention protocol in Asian populations reduced the side effects and cost.

[Characteristics of scar hyperplasia after burn and the rehabilitation treatment in children].

After the wound healing of deep burn in children, there will be scar tissue proliferation in varying degrees. Burn scar seriously affects the quality of life and the psychological health during the growth and development of children, so parents of children pay more and more attention to scar treatment and functional rehabilitation after burn. The treatment of scar after burn in children has become an important issue for medical workers in burn, plastic surgery, and rehabilitation. This article analyzes and summarizes the relationship between scar hyperplasia and age, race, and position of scar hyperplasia after burn in children. The treatment and functional rehabilitation methods of scar are also discussed, so as to provide some guidance for the formulation of appropriate individualized treatment plan.

Effect of Low-Dose Vs Standard-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Kidney Transplantation Recipients: A Systemic Review and Meta-Analysis.

BACKGROUND: Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains controversial because the continuous use of this drug decreases kidney function and can induce leukopenia. OBJECTIVE: The purpose of this study was to measure the appropriate dose of valganciclovir required to prevent CMV infection. METHODS: A systematic review and meta-analysis were performed by using a random effects model. The Cochrane Central Register, MEDLINE, EMBASE, and PubMed databases were searched up to April 15, 2017. We conducted analysis on low-dose (450 mg) and standard-dose (900 mg) valganciclovir groups. RESULTS: After completion of the research, the analysis revealed that the glomerular filtration rate, graft loss, tacrolimus level, antibody-mediated rejection, and fungal and Candida infection rates did not differ between the 2 groups. However, the incidence of CMV tended to decrease in the low-dose group (0.584 [95% confidence interval [CI], 0.352-0.967]; P = .036). The biopsy-proven rejection rate decreased by 0.427 times in the low-dose group compared with the standard-dose group (95% CI, 0.274-0.667; P = .002). Furthermore, the incidence of leukopenia decreased by 0.371 times in the low-dose group compared with the standard-dose group (95% CI, 0.264-0.523; P = .001). CONCLUSIONS: The 450-mg dose of valganciclovir effectively prevented post-transplantation CMV infection and decreased drug-induced side effects such as leukopenia. In the future, the lower dose of valganciclovir should be considered to prevent CMV infection and enhance cost-effectiveness.

High-Dose Intravenous Immunoglobulin Treatment of Polyomavirus Nephropathy Developing After T Cell-Mediated Rejection Treatment: A Case Report.

BACKGROUND: Reactivation of BK polyomavirus causes destructive virus allograft nephropathy; however, treatment options are limited. Herein, we report a case in which a patient with T cell-mediated rejection was treated with steroid therapy. The patient subsequently developed BK viremia and was successfully treated by using intravenous immunoglobulin (IVIG) after failing to respond to conventional treatment. CASE PRESENTATION: A 54-year-old man had been undergoing peritoneal dialysis for 3 years before kidney transplantation. He had an elevated serum creatinine level (2.26 mg/dL; normal range, 1.2-1.4 mg/dL) and reduced urine output 2 months after transplantation. Suspecting T cell-mediated rejection, steroid pulse therapy (methylprednisolone 250 mg twice daily) was performed for 3 days. Despite treatment, there was a recurrence of increased serum creatinine, and real-time quantitative polymerase chain reaction (serum samples) indicated BK viremia (>5.5 × 105 copies/mL). Results of a kidney biopsy revealed polyomavirus nephropathy (BK virus positive and C4d negative). Thus, the patient's tacrolimus dosage was reduced (from 2.75 mg twice daily to 2 mg once daily), he discontinued mycophenolate mofetil, and he was administered ciprofloxacin and leflunomide. However, the BK viremia showed no improvement, even after 3 months of treatment. Thus, he was administered high-dose IVIG (1 g/kg, 5 times over 5 weeks). The viremia load (blood specimen) decreased to 5197 copies/mL, and the patient's graft function stabilized. His serum creatinine decreased to 2.68 mg/dL. The patient is currently being followed up. CONCLUSIONS: Optimal BK treatment methods have not been established, and IVIG treatment remains controversial. However, the present case provides an example of successful treatment using high-dose IVIG.

Graft Contrast-Induced Nephropathy Caused by Prerenal Transplant Computed Tomography: A Case Report.

BACKGROUND: We report a case of posttransplant contrast-induced nephropathy (CIN) that occurred after performing computed tomography (CT) scanning for pretransplant cardiac and vascular evaluation. CASE PRESENTATION: The patient had an 8-year history of hemodialysis and was admitted to the hospital for a kidney transplant from a deceased donor. Cardiac CT imaging and 3-dimensional low-extremity CT angiography were performed to confirm the patient's cardiac and iliac artery function. After successful transplantation surgery, the patient had a urine output of 250 mL and a reduced creatinine level from 8.8 to 2.3 mg/dL on postoperative day 4. However, urine output suddenly decreased to 30 mL and the creatinine level suddenly increased to 7.6 md/dL without any symptoms such as fever or graft tenderness. The patient tested negative for panel-reactive antibodies and donor-specific antibodies, and he was discharged 1 week later with an improvement in symptoms. Results of a graft biopsy indicated CIN, and the contrast-enhanced kidney was observed on noncontrast CT imaging that was performed immediately after transplantation to rule out vascular problems as well as other complications. CONCLUSIONS: There may be residual contrast present from pretransplant CT imaging, which could affect the functional kidney grafts after transplantation and can lead to CIN. This scenario could potentially lead to loss of graft function, suggesting that caution should be observed when ordering CT imaging in this patient population.

Efficacy and Safety of Induction Therapy in Kidney Transplantation: A Network Meta-Analysis.

BACKGROUND: Rejection and infection can occur after kidney transplantation and are important factors in preserving graft kidney function. The use of immunosuppressant agents in transplantation is therefore important, and the question of which induction therapy should be used as an immunosuppressant is controversial. OBJECTIVE: The goal of this study was to assess the comparative benefits and harms of various maintenance immunosuppressive induction agents in adults undergoing kidney transplantation by using a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy. METHODS: CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers were searched until May 2017 to identify randomized controlled trials on immunosuppression for kidney transplantation. RESULTS: Twenty-seven studies involving 4484 participants were eligible for analysis. Induction and maintenance treatments were administered for 12 months. There was no evidence of differences in outcomes between therapies on all-cause mortality, graft loss, cytomegalovirus, BK virus, neutropenia, thrombocytopenia, and biopsy-proven acute rejection. However, compared with intravenous basiliximab (an interleukin-2 receptor antagonist [IL-2RA]), the most effective treatments to decrease biopsy-proven acute rejection were intravenous alemtuzumab and rabbit antithymocyte globulin (rATG). The odds ratios were 0.45 (95% confidence interval [CI], 0.29-40.78) and 0.63 (95% CI, 0.42-0.95), respectively. As a side effect, rATG was accompanied by more bacterial infection than the IL-2RA (OR, 1.8 [95% CI, 1.01-2.8]). CONCLUSIONS: The determination of induction in kidney transplantation is important for future prognosis of the graft kidney. Alemtuzumab and rATG exhibited lower biopsy-proven acute rejection than the IL-2RA. As a side effect, rATG produced frequent bacterial infections.

A comparison of ultrasound-guided interscalene and supraclavicular blocks for post-operative analgesia after shoulder surgery.

BACKGROUND: In contrast to interscalene block, there was little information regarding the analgesic efficacy of supraclavicular block for shoulder surgery. This study aimed to compare the analgesic efficacy and side effects of interscalene and supraclavicular blocks for shoulder surgery. METHODS: Patients scheduled for shoulder surgery were assigned to receive either ultrasound-guided interscalene (n = 25) or supraclavicular block (n = 24) with 20 ml of 0.375% ropivacaine. We assessed the duration of post-operative analgesia as a primary outcome and pain scores, supplemental analgesia, diaphragmatic excursion, motor block, fingertip numbness, side effects, and patient satisfaction as secondary outcomes. RESULTS: The duration of post-operative analgesia was not statistically different between groups: 868 (800-1440) min for supraclavicular block vs. 800 (731-922) min for interscalene block (median difference -85 min, 95% CI, -283 to 3 min, P = 0.095). The incidence of diaphragmatic paresis was significantly lower in the supraclavicular block group compared with that in the interscalene block group, both at 30 min after the block (66.7% vs. 92%, P = 0.021) and in the post-anaesthesia care unit (62.5% vs. 92%, P = 0.024). Motor block was higher in the supraclavicular block group in the post-anaesthesia care unit, however, not at 24 h. Other secondary outcomes were similar for both groups. CONCLUSIONS: This study showed no statistically significant difference in the duration of post-operative analgesia between the supraclavicular and interscalene blocks. However, the supraclavicular block was associated with a lower incidence of diaphragmatic paresis compared with that of the interscalene block after shoulder surgery.

Abscess of Native Kidney Caused by Carbapenem-Resistant Acinetobacter baumannii (CRAB) in Renal Transplantation: A Case Report.

BACKGROUND: Abscess of native kidney is a rare postoperative event after renal transplantation. This report describes a case of back pain, fever and pyuria caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in a patient who underwent renal-transplantation. CASE REPORT: A 40-year-old man, presenting with hypertension and renal failure, underwent renal transplantation 1 month previously. He developed sudden intense back pain and fever (39°C). There was normal blood flow in graft kidney but there were the swelling and cyst of right native kidney. We aspirated the pus in native kidney and performed the native nephrectomy. The carbapenem-resistant Acinetobacter baumannii (CRAB) was isolated as in pus and native kidney. We performed the tigecyline monotherapy during 3 weeks. He recovered without complication after treatment. CONCLUSIONS: To our knowledge, no report in the literature to date describes abscess in native kidney secondary to CRAB in a renal transplant. Infections caused by CRAB have become critical for immunosuppressed patients. The presence of complication greater risk, by an organism whose pathogenicity and virulence are not yet elucidated should determine an aggressive empirical antimicrobial therapy.

Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression.

Alterations in long non-coding RNAs (lncRNAs) are associated with human carcinogenesis. One group of lncRNAs, which are antisense in orientation to coding mRNAs (ASs), have been recently described in cancers but are poorly understood. We sought to identify ASs involved in human gastric cancer (GC) and to elucidate their mechanisms of action in carcinogenesis. We performed massively parallel RNA sequencing in GCs and matched normal tissues, as well as in GC-derived and normal gastric epithelial cell lines. One AS, designated Homo sapiens keratin 7 (KRT7-AS), was selected due to its marked upregulation and concordant expression with its cognate sense counterpart, KRT7, in GC tissues and cell lines. KRT7-AS formed an RNA-RNA hybrid with KRT7 and controlled KRT7 expression at both the mRNA and the post-transcriptional levels. Moreover, forced overexpression of the KRT7-overlapping region (OL) of KRT7-AS (but not its non-KRT7-OL portions) increased keratin 7 protein levels in cells. Finally, forced overexpression of full-length KRT7-AS or OL KRT7-AS (but not its non-KRT7-OL regions) promoted GC cell proliferation and migration. We conclude that lncRNA KRT7-AS promotes GC, at least in part, by increasing KRT7 expression.

Efficacy of type a botulinum toxin injections and infrared polarized light on treating chronic migraine.

OBJECTIVE: To investigate the clinical value of the combination of ultrasound-and-hyponome-guided type A botulinum toxin injection and infrared polarized light on treating chronic migraine. PATIENTS AND METHODS: Ninety-one patients with chronic migraine were randomly divided into four groups: in the control group (group A, 22 cases in total), nimodipine was used in the treatment of chronic migraine for two months; in the infrared polarized light therapy group (group B, 22 cases in total), infrared polarized light was adopted in the treatment of chronic migraine for 50-60d; in the botulinum toxin treatment group (group C, 24 cases in total), ultrasound-and-hyponome-guided type A botulinum toxin was injected into frontal, temporal, and occipital muscles in treating chronic migraine; in the joint treatment group (group D, 23 cases in total), ultrasound-and-hyponome-guided type A botulinum toxin injection in group C and infrared polarized light in group B were both used here in the treatment of chronic migraine. Infrared polarized light therapy lasted 50-60d and the time of study lasted six months. The survey would include the conditions of patients with chronic migraine three months before treatment and at one, three and six months after treatment. Patients were asked to fill the MIDAS (migraine disability assessment questionnaire) and were graded on the evaluation scale of life quality, so that the researchers would be able to compare attack frequency, duration of attack, attack severity, the use of painkillers and their recovery from chronic migraine, and then observe their adverse reactions. RESULTS: Eleven cases dropped out during the treatment, three cases in A group, two cases in group B, four cases in group C and two cases in group D. One, three and six months after treatment, the MIDAS scores in group A, B, C and D were significantly lower than before the treatment. Hence, the differences were statistically significant (p < 0.01). The scores in quality of life rating scale were significantly higher than pre-treatment scores, so the difference was statistically significant (p < 0.01). The MIDAS scores and quality of life rating scale scores in group D were compared with those in group A, B, and C respectively, and the differences were statistically significant (p < 0.05). Two patients were recorded with dizziness, and the dizziness disappeared after two weeks with no treatments at all. Forehead lines and crow's feet of 21 patients shallowed or disappeared in varying degrees after the injection. CONCLUSIONS: The combination of ultrasound-and-hyponome-guided type A botulinum toxin injection and infrared polarized light on treating chronic migraine demonstrated a significant clinical effect.

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

Talin1 phosphorylation activates ß1 integrins: a novel mechanism to promote prostate cancer bone metastasis.

Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We previously showed that ß1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph nodes and bone. However, how ß1 integrins are activated in PCa cells is unknown. In this study, we identified a novel mechanism of ß1 integrin activation. Using knockdown experiments, we first demonstrated that talin1, but not talin2, is important in ß1 integrin activation. We next showed that talin1 S425 phosphorylation, but not total talin1 expression, correlates with metastatic potential of PCa cells. Expressing a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 and C4-2B4 PCa cells, decreased activation of ß1 integrins, integrin-mediated adhesion, motility and increased the sensitivity of the cells to anoikis. In contrast, reexpression of the phosphorylation-mimicking mutant talin1(S425D) led to increased ß1 integrin activation and generated biologic effects opposite to talin1(S425A) expression. In the highly metastatic PC3-MM2 cells, expression of a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 cells, abolished their ability to colonize in the bone following intracardiac injection, while reexpression of phosphorylation-mimicking mutant talin1(S425D) restored their ability to metastasize to bone. Immunohistochemical staining demonstrated that talin S425 phosphorylation is significantly increased in human bone metastases when compared with normal tissues, primary tumors or lymph node metastases. We further showed that p35 expression, an activator of Cdk5, and Cdk5 activity were increased in metastatic tumor cells, and that Cdk5 kinase activity is responsible for talin1 phosphorylation and subsequent ß1 integrin activation. Together, our study reveals Cdk5-mediated phosphorylation of talin1 leading to ß1 integrin activation is a novel mechanism that increases metastatic potential of PCa cells.