Effect of emodin combined with cisplatin on the invasion and migration of HepG2 hepatoma cells.

Cisplatin is the leading chemotherapy agent for advanced liver cancer. However, the resistance to cisplatin in liver cancer reduces its efficacy. A potential strategy to increase its effectiveness and reduce toxicity is to combine cisplatin with 1,3,8-trihydroxy-6-methylanthraquinone (emodin). In this study, we examined the effects of emodin combined with cisplatin on the invasion and migration of HepG2 cells and analyzed the role of emodin. The effects of cisplatin, emodin and their combination were assessed in HepG2 cells. Proliferation, invasion and migration of HepG2 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), scar and Transwell assays. The gelatinase spectrum and an ELISA detected the expression of matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). The expression of E-cadherin and vimentin was detected by immunofluorescence and Western blots. Emodin inhibited cell invasion and migration in HepG2 hepatoma cells, increased E-cadherin expression, decreased vimentin, MMP-2, and MMP-9 expression. The combination of emodin and cisplatin-induced a more significant effect in a dose-dependent manner. In this study, we found that emodin inhibited hepatocellular carcinoma (HCC) metastasis. Compared with either cisplatin or emodin alone, the combination of both showed a more significant synergistic effect. Emodin can enhance the sensitivity of HepG2 HCC cells to cisplatin by inhibiting epithelial-mesenchymal transition, and thus, play a role in preventing recurrence and metastasis in HCC.

Use of telemedicine in the postoperative assessment of proctological patients: a case-control study.

BACKGROUND: Telemedicine is emerging as an easy way to communicate between patients and surgeons. Use of telemedicine increased during the coronavirus disease 2019 (COVID-19) pandemic. WhatsApp is one of the most common smartphone applications for user-friendly telemedicine. The aim of this study was to evaluate patient perception of health quality and positive outcomes using a diary sent by the patient to the surgeon via WhatsApp during the first post-discharge week after proctologic surgery. METHODS: Ninety-eight patients discharged after proctologic surgery at the Israelite Hospital of Rome and the AOU Policlinico Umberto I of Rome in 1 January-31 December 2019 were divided into two groups: the WhatsApp group (group A), (n = 36) and the no WhatsApp group (group B) (n = 62). Group A patients received a protocol to follow for the day-by-day diary during the first post-discharge week and sending it by WhatsApp to the surgeon. Group B patients only received recommendations at discharge. The tool's usefulness was assessed by a questionnaire one month after the intervention. RESULTS: The two groups were homogeneous for age, sex, schooling, employment, and proctologic pathology. Group A patients had less difficulty keeping a diary (p < 0.0001). Group A patients had the perception of better follow-up post-discharge (p = 0.002). The use of the diary sent by WhatsApp significantly improved the perception of positive post-intervention outcomes (p = 0.007). WhatsApp was the only independent predictor of perception of post-surgical positive outcomes (odds ratio = 4.06; 95% CI 1.35-12.24; p = 0.01). CONCLUSIONS: The use of WhatsApp in the post-discharge period improves the lifestyle quality of the patients and their perception of the safety and quality of care received.

How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27-24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Transarterial chemoembolization of hepatocellular carcinoma before liver transplantation and risk of post-transplant vascular complications: a multicentre observational cohort and propensity score-matched analysis.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular cancer (HCC) on the waiting list for liver transplantation may be associated with an increased risk for hepatic artery complications. The present study aims to assess the risk for, primarily, intraoperative technical hepatic artery problems and, secondarily, postoperative hepatic artery complications encountered in patients who received TACE before liver transplantation. METHODS: Available data from HCC liver transplantation recipients across six European centres from January 2007 to December 2018 were analysed in a 1 : 1 propensity score-matched cohort (TACE versus no TACE). Incidences of intraoperative hepatic artery interventions and postoperative hepatic artery complications were compared. RESULTS: Data on postoperative hepatic artery complications were available in all 876 patients (425 patients with TACE and 451 patients without TACE). Fifty-eight (6.6 per cent) patients experienced postoperative hepatic artery complications. In total 253 patients who had undergone TACE could be matched to controls. In the matched cohort TACE was not associated with a composite of hepatic artery complications (OR 1.73, 95 per cent c.i. 0.82 to 3.63, P = 0.149). Data on intraoperative hepatic artery interventions were available in 825 patients (422 patients with TACE and 403 without TACE). Intraoperative hepatic artery interventions were necessary in 69 (8.4 per cent) patients. In the matched cohort TACE was not associated with an increased incidence of intraoperative hepatic artery interventions (OR 0.94, 95 per cent c.i. 0.49 to 1.83, P = 0.870). CONCLUSION: In otherwise matched patients with HCC intended for liver transplantation, TACE treatment before transplantation was not associated with higher risk of technical vascular issues or hepatic artery complications.

Lay Summary Patients with liver cancer may be treated with transarterial chemoembolization (TACE) during the period on the transplant waiting list. With TACE, chemotherapeutic coils are injected directly into the small arteries supplying the tumour, after which these vessels are closed. The aim of this therapy is to decrease the tumour size and slow down tumour growth. However, concerns are raised that manipulation of the main hepatic artery by TACE may cause damage to the artery itself. If this would result in problems during or after liver transplantation when the artery is connected to the artery supplying the donor liver, this may endanger the donor liver graft survival. The present study shows no increased risk in problems to connect the artery during liver transplantation after TACE treatment. Also, arterial complications after liver transplantation did not occur more frequently if patients had received TACE treatment. The authors therefore conclude that TACE treatment before liver transplantation could be considered a safe approach.

Simvastatin relieves myocardial ischemia/reperfusion injury in rats through hedgehog signaling pathway.

OBJECTIVE: The aim of this study was to explore the effect of simvastatin (Sim) on myocardial ischemia/reperfusion (I/R) injury in rats and to elucidate the possible underlying mechanism. Our findings might help to provide a certain reference for the clinical prevention and treatment of myocardial I/R injury. MATERIALS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were randomized into three groups using a random number table, including: Sham group (n=20), I/R group (n=20) and I/R + Sim group (n=20). The I/R injury model was successfully established in rats via ligation of the left anterior descending coronary artery (LAD), followed by reperfusion. Before operation, the rats in I/R + Sim group were administered with Sim at 10 mg/kg/d through oral gavage for 7 d. Cardiac ejection fraction (EF) (%) and fractional shortening (FS) (%) of rats in each group were detected using echocardiography. 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to measure the myocardial infarction (MI) area in each group. Collagen deposition in myocardial tissues of rats in each group was detected by Masson's trichrome staining. The apoptosis level of myocardial cells and fibroblasts in myocardial tissues of rats in each group were evaluated via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The level of reactive oxygen species (ROS) in myocardial tissues of rats in each group was determined using fluorescent probes. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted to measure the expression levels of pro-inflammatory cytokines interleukin (IL)-1ß and monocyte chemoattractant protein-1 (MCP-1) in myocardial tissues of rats in each group. Furthermore, the effects of Sim on the hedgehog signaling pathway-associated proteins were detected using Western blotting. RESULTS: Sim significantly alleviated I/R-induced cardiac dysfunction in rats and increased EF (%) and FS (%) (p<0.05). Meanwhile, it also evidently mitigated the MI caused by I/R and reduced the infarction area (p<0.05). According to the Masson's trichrome staining results, I/R + Sim group exhibited remarkably declined myocardial interstitial collagen deposition compared with I/R group (p<0.05). ROS-sensitive fluorescent staining showed that Sim notably reversed the increase of ROS expression and the decrease of myocardial oxidative stress induced by I/R (p<0.05). Finally, Western blotting results revealed that Sim dramatically restrained the protein expressions of sonic hedgehog (SHH), patched 1 (PTC1) and glioma-associated oncogene homolog 1 (GLI1) (p<0.05). CONCLUSIONS: Sim can significantly relieve myocardial I/R injury in rats. The possible underlying mechanism may be related to its inhibition on the hedgehog signaling pathway.

Posterior pelvic tilt is a risk factor for rectal prolapse: a propensity score matching analysis.

BACKGROUND: There is little evidence about possible effects of pelvic anatomical characteristics on proctological complications. The aim of our study was to investigate the potential correlation between sagittal pelvic position and rectal prolapse. METHODS: A study was conducted on a proctology patients and patients without any specific history of proctological disorders who were divided into two groups according to the presence or the absence of rectal prolapse. In all cases, the pelvic angle was measured with a pelvic goniometer and categorized as posterior (< 10°), neutral (10°-15°), and anterior (> 15°). To minimize effects of potential confounders in the analysis, 3:1 nearest neighbor propensity score matching (PSM) method was implemented using age, sex, and diagnose of rectal disorders as confounding variables. RESULTS: Among the 143 screened patients, posterior tilt was more frequent in the 19 patients with rectal prolapse than in those without prolapse (42 vs. 18%; p = 0.027). This result was also confirmed in the post-PSM analysis (42 vs. 14%; p = 0.036) using 35 propensity score (PS)-matched controls compared with the rectal prolapse group. Posterior tilt was associated with an increased risk of prolapse in both the unmatched population (odds ratio = 3.37; p = 0.020) and PS-matched subset (odds ratio = 4.36; p = 0.028). CONCLUSIONS: A posterior pelvic angle was more frequently associated with the diagnosis of rectal prolapse. In both the entire population and in the PS-matched subset, posterior tilt was a significant risk factor for rectal prolapse. The easy-to-do investigation of the pelvic angle can provide several benefits in terms of rectal prolapse prevention and more precise management of post-surgical prolapse recurrence.

[Advances in the research of early deepening mechanism and prevention measures of burn wounds].

Deepening of wounds not only prolongs the wound repair time, increases the chance of scar formation after healing, but also is one of the important causes of death in severe burn patients. How to prevent wound deepening is a clinical problem in the treatment of burns. The mechanism of deepening burn wounds has not been fully elucidated, and the prevention and treatment measures in clinic need to be further explored. Based on the research results of the early deepening mechanism and prevention measures of burn wounds at home and abroad, this paper intends to summarize the three aspects including deepening mechanism, prevention measures, and research prospects of burn wounds.

FTO rs9939609 Gene Polymorphism and Obesity: Lack of Association in Kidney Transplantation.

The fat mass and obesity-associated (FTO) gene is one of the most important obesity susceptibility genes. Some FTO gene polymorphisms have been associated with obesity, diabetes, and hypertension, all conditions for which, after transplant, there is increased susceptibility, due to effects of immunosuppressive regimens. To evaluate whether FTO could be a candidate for targeted preventive intervention in the transplant setting, we investigated whether the common genetic variation, FTO rs9939609T>A, could affect weight gain and risk of cardiovascular complications in kidney transplantation. METHODS: In 198 kidney transplant recipients, FTO rs9939609 was investigated in association with body mass index (BMI)/obesity and with other clinical markers of posttransplant risk, then monitored up to 5 years after transplantation. Genotyping was performed using an allelic discrimination method on a real-time polymerase chain (PCR) system. Associations were analyzed using the chi-square test; differences between genotypes were examined with analysis of variance or Kruskal-Wallis test; tests for repeated measures and a general linear model analysis controlling for age and gender were also utilized. RESULTS: Allele and genotype frequencies of FTO rs9939609 in recipients (T/T, 29.8%; T/A, 49.0%; A/A, 21.2%; A, 45.7%; T, 54.3%) reflect those present in healthy Caucasian populations. In the face of pre-/posttransplant differences in total cholesterol, triglycerides, or fasting glucose, results did not show significant changes in these factors among genotypes either before or after transplantation. CONCLUSION: This study highlights a lack of association of FTO rs9939609T>A genotypes and posttransplant weight gain, plasma lipids, and fasting blood glucose in kidney transplantation.

Correlations between the level of antibody against peptide of glutamate receptor NR3B subunit in the CSF and cognitive comorbidities of patients with epilepsy.

OBJECTIVE: Autoimmune epilepsy is an under-recognized condition, and the mechanisms of antibody-mediated epileptogenesis are unknown. The N-methyl-D-aspartate (NMDA) receptor subunit 3 peptide B (NR3B) modulates Mg2+ sensitivity and Ca2+ mobilization of glutamate responses in the central nervous system (CNS). The levels of antibodies against NR3B (NR3B Ab's) in the cerebrospinal fluid (CSF) and the correlations between NR3B Ab's and cognitive comorbidities of epilepsy patients remain unclear. PATIENTS AND METHODS: CSF samples were collected from 36 patients with consecutive epilepsy and 17 healthy controls. The levels of NR3B Ab's in the CSF were measured by ELISA. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). RESULTS: The results showed that the levels of NR3B Ab's were significantly higher in patients with epilepsy than those in the controls (p<0.01). Thirteen of 36 patients had higher levels of NR3B Ab's exceeding mean+ 2SD of all patients, and the scores of MMSE and MoCA of these 13 patients were significantly lower than the other 23 patients and controls (p<0.01; p<0.001). However, there were no significant differences in the scores of MMSE and MoCA between the 23 patients and the controls. Correlation analysis indicated a significant negative correlation between the levels of NR3B Ab's and the scores of MMSE (correlation coefficient: r=-0.543; p<0.01) or the scores of MoCA (correlation coefficient: r=-0.548; p<0.01). CONCLUSIONS: We suggest that some patients with epilepsy may have immune process after onset and the presence of NR3B Ab's may be associated with cognitive comorbidities in patients with epilepsy.

Surgical Technique Notes of Arterial Vascular Reconstruction During Kidney Transplantation: Personal Experience and Literature Review.

BACKGROUND: Arterial vascular anomalies in patients undergoing kidney transplantation (KT) are correlated with a higher incidence of early surgical complications, potentially causing graft loss. Arterial reconstruction allows patients to overcome these surgical challenges, thus minimizing the risk of poor outcomes. The aim of the present study is to retrospectively investigate the safety and effectiveness of the multiple arterial reconstruction technique with a Teflon patch in case of an unavailable aortic patch: to do so, surgical complications, graft function, and patient survival were evaluated. METHODS: During the period January 2009 to August 2016, 202 adult deceased-donor KTs were performed at our center. Group A (n = 27; reconstruction of multiple arteries) and Group B (n = 175; control group) were compared. RESULTS: No differences were observed between the 2 groups in terms of early postoperative course, with no vascular complication observed in Group A. No vascular patch infections were reported, nor longer cold ischemia time rates. Similarly, long-term survival rates were similar between the 2 groups. CONCLUSIONS: The Teflon-patch arterial reconstruction technique appears to be safe and effective, with an acceptable balance of benefits and potential risks of using a prosthetic material. Studies based on larger series are needed to further validate this approach.

Automated Intelligent Microscopy for the Recognition of Decoy Cells in Urine Samples of Kidney Transplant Patients.

BACKGROUND: BK virus (BKV)-associated nephropathy is definitely involved in allograft failure after kidney transplant. Thus, the need for an early control of viral reactivation in immunocompromised patients is well established. Determination of urinary release of decoy cells (DC) and BK viral load in plasma and urine by polymerase chain reaction (PCR) usually precedes renal biopsy. The aim of the study is to assess viral reactivation by BKV-DNA PCR and DC detection in urinary sediment using automated intelligent microscopy. METHODS: Seventy-eight kidney transplant patients were analyzed for the presence of plasma BKV-DNA by quantitative TaqMan real-time PCR. Additionally, automated intelligent microscopy was used for urine sediment analysis, allowing to count cells with decoy feature, confirmed by phase contrast microscopic review. RESULTS: Plasma BKV-DNA PCR was detected in 14 (17.9%) patients. DC were identified in 19 (24.3%) urine sediments by automated analyzers and confirmed by microscopic observation. Two patients were BKV-DNA-positive/DC-negative; conversely, 7 subjects were DC-positive/BKV-DNA-negative. CONCLUSIONS: Plasma quantification of BK viral load is currently the best noninvasive method for the detection of viral reactivation. Nevertheless, automated methods to screen for the presence of DC in urine could facilitate early BK virus replication diagnosis and patient follow-up by quantitative and visual results.

[Plasma relative abundance of epidermal growth factor receptor mutations predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma].

Objective: To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods: In this prospective study, adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumor tissues were detected by ADx-amplification refractory mutation system (ADx-ARMS). EGFR mutations of plasma free tumor DNA were detected by ADx-ARMS and ADx-super amplification refractory mutation system (ADx-SuperARMS) at the same time. Patients with EGFR-mutant in tumor tissues and receiving EGFR-TKIs were finally enrolled. Plasma mutation-positive patients with both methods were high abundance group.Patients with positive mutations by ADx-SuperARMS but negative by ADx-ARMS were medium abundance group. Mutation-negative patients with both methods were recognized as low abundance group. The correlation between EGFR mutation abundance and clinical response to EGFR-TKIs were analyzed. Results: Among 71 patients enrolled, 42 harbored EGFR mutations in plasma were detected by ADx-ARMS, while 53 were found by ADx-SuperARMS.There were 42 patients in high abundance group, 11 in medium group while the other 18 in low group. The objective response rates (ORRs) were 69.0%, 7/11 and 10/18 in high, medium and low groups, respectively. The difference was significant between high and low abundances groups (P=0.006). Median progression-free survival (PFS) in high, medium and low groups were 11.0, 8.5 and 9.0 monthes, respectively (P<0.001). In patients with tumor 19-Del, the ORRs were 70.4%, 5/7 and 6/11 in high, medium and low abundance groups, respectively. The median PFS of high abundance group was significantly longer than the other two groups (12.0 monthes vs 9.0, 9.0 monthes). As to subjects with L858R mutation, the ORRs were 10/15, 2/4 and 3/6, respectively, with median PFS 9.6, 5.5 and 9.5 monthes. Conclusions: The relative abundance of EGFR mutations in plasma predicts clinical response to EGFR-TKIs in patients with advanced lung adenocarcinoma. The higher the mutation abundance is, the better the efficacy of EGFR-TKIs is.

Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS: We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. RESULTS: CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). CONCLUSION: Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

[Recurrent bleeding following the renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage: causes and countermeasure].

Objective: To explore the causes and countermeasure in recurrent bleeding following the selective renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage. Methods: A total of 334 patients of severe renal hemorrhage associated with percutaneous nephrolithotomy (PCNL) from March 2011 to April 2015 were analyzed retrospectively.All the patients underwent super selective angiography and renal artery embolization.The causes of recurrent hemorrhage were analyzed and principles for diagnosis and embolization were studied. Results: The initial embolization was performed in 329 cases hospitalized in the First Affiliated Hospital of Guangzhou Medical University and 318 cases were successfully stopped bleeding with a hemostatic rate of 96.7 %(318/329). Of total 334 consecutive cases, there were 16 cases of recurrent renal hemorrhage, 11 cases were initially embolized in this hospital, and otherwise the other 5 cases were in other hospitals. Causes of recurrent hemorrhage were missed embolization of tiny pseudoaneurysm (n=12), and two cases of 12, the tiny pseudoaneurysm were feeding by accessory renal arteries, undetected arteriovenous fistula(n=2), recanalization of the embolized arteries (n=2). Conclusion: The causes of recurrent bleeding fallowing the initial selective renal artery embolization treating post-percutaneous nephrolithotomy hemorrhage are varied, and missed embolization of tiny pseudoaneurysm is the major cause of unsuccessful initial renal artery embolization. To strengthen the understanding of tiny pseudoaneurysm is helpful to improve the success rate of hemostasis.

[The diagnostic performance of galactomannan detection for invasive pulmonary aspergillosis in non-neutropenic hosts].

Objective: To evaluate the diagnostic performance of galactomannan(GM)detection in serum and BALF for invasive pulmonary aspergillosis (IPA) in non-neutropenic hosts. Methods: A pospective study was performed for 1 356 non-neutropenic hosts admitted to the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from September 2014 to October 2015. Serum GM test was performed for all, and BALF GM test for a proportion of the patients. The patients were divided into an IPA group and a non-IPA group. SPSS 20.0 was adopted for statistical analysis. Results: A total of 1 361 cases were enrolled, aging 18-96 years, with an average age of (64±15) years. There were 879 male and 477 female patients. Thirty-nine cases were diagnosed as IPA, accounting for 2.9%. For serum GM test, the sensitivity, specificity, PPV and NPV were 43.6%(17/39), 94.1%(1 239/1 317), 17.9%(17/95)and 98.3%(1 239/1 261)respectively. Ninety-six cases received serum and BALF GM tests at the same time. If the cut-off value of BALF GM test was 0.8, the sensitivity, specificity, PPV and NPV were 86.7%(13/15), 60.5%(49/81), 28.9%(13/45), 96.1%(49/51)respectively, but if the value was 1.0, the sensitivity, specificity, PPV and NPV were 86.7%(13/15), 74.1%(60/81), 38.2%(13/34), 96.8%(60/62)respectively. The ROC curve area of BALF GM, serum GM and the combined serum and BALF GM was 0.87, 0.75 and 0.90, respectively. Conclusions: The sensitivity of serum GM test in non-neutropenic hosts was low, but it had a high negative predictive value.The best BALF GM cut-off value was 1.0. The combined serum and BALF GM tests improved the diagnostic performance.

Interleukin-8 -251A/T polymorphism and periodontitis susceptibility: a meta-analysis.

The -251A/T polymorphism in the anti-inflammatory cytokine interleukin-8 (IL-8) gene has been implicated in susceptibility to periodontitis; however, this correlation has not been elucidated. In this meta-analysis, we investigated the association between the IL-8 -251A/T polymorphism and the risk of periodontitis. All eligible case-control studies published until August 2014 were identified and extracted from PubMed, Web of Science, EMBASE, China National Knowledge Internet, and WanFang databases. The strength of this association was accessed by pooled odds ratios (ORs) with 95% confidence intervals (CIs), using either a fixed- or random-effect model. Nine case-control studies, including 1811 cases and 2043 controls, were identified. Overall, no significant associations were found between the IL-8 -251A/T polymorphism and the risk of periodontitis. The results of the analysis of periodontitis subgroup revealed similarities between chronic periodontitis and aggressive periodontitis. An additional analysis based on ethnicity revealed an association between the IL-8 -251A/T polymorphism and periodontitis among Asians (dominant model, OR = 1.784, 95%CI = 1.130-2.817) and a mixed population (AA vs TT, OR = 0.667, 95%CI = 0.471-0.974). The results of this meta-analysis suggest that the IL-8 -251A/T polymorphism may increase the risk of periodontitis in Asian and mixed populations. However, larger and well-designed studies are warranted to validate our findings.

Kidney Transplantation, Polymorphisms of IL-18, and Other Pro-Inflammatory Genes and Late Post-Transplant Outcome.

BACKGROUND: Functional polymorphisms of molecules involved in immune-mediated mechanisms of allograft rejection could be predictive of increased risk for early and late post-transplant complications. In the past years, the challenge for long-term graft survival in kidney recipients is the implementation of personalized approaches. In this study, effects of interleukin (IL)-18-137G/C (rs187238), -607C/A (rs1946518), and other pro-inflammatory cytokine gene polymorphisms (tumor necrosis factor [TNF]-α-308G/A, rs1800629, IL-6-174G/C, rs1800795, and interferon [IFN]-γ+874A/T, rs2430561) on the main post-transplant risk parameters and diseases (metabolic, cardiovascular, infective, and chronic allograft rejection) were assessed in kidney-transplanted patients. METHODS: One hundred seventy-nine transplanted patients were retrospectively analyzed for clinical and biochemical parameters and onset of post-transplant complications. Taqman allelic discrimination and PCR-SSP (polymerase chain reaction-sequence specific primers) techniques were used for genotyping. RESULTS: No predictive effects of allele and genotypes of IL-18-607C/A, TNF-α-308G/A, IL-6-174G/C, and IFN-γ+874A/T gene polymorphisms and onset of risk factors and late complications were evidenced. However, Kaplan-Meier analysis evidenced a weak effect of IL-18-137G/C genotypes on graft survival. CONCLUSIONS: Analyzing associations between some pro-inflammatory cytokine gene polymorphisms and onset of the most relevant risk factors and late complications of kidney transplant, results suggested a possible impact of IL-18-137G/C genotypes on graft survival, which deserves further studies.

Delayed Introduction of Everolimus in De Novo Renal Transplanted Patients: A Single-Center Experience.

INTRODUCTION: Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction. MATERIAL AND METHODS: This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen. Primary aims were 1-year patient and graft survivals and acute rejection rates. Secondary aims were related to wound, metabolic, and hematologic complications. RESULTS: Patient and graft survivals were similar in both groups. One year after KT, median serum creatinine was inferior in group A (1.4 vs 1.8 mg/dL; P = .004). Late acute rejection (8.3 vs 12.0%; P = 1.0) and wound complication (4.2 vs 4.0%; P = 1.0) rates were similar. Higher cholesterol and triglycerides and lower platelets and hemoglobin levels were observed in group A. CONCLUSIONS: In our experience, delayed introduction of EVR shows similar results with respect to its early introduction, contemporaneously presenting fewer wound complications and lymphoceles. A higher rate of metabolic and hematologic complications are, however, observed in patients under EVR therapy. Further multicenter studies should be performed to confirm these preliminary results.

Multiple Organ Failure Associated With Coxsackie Virus in a Kidney Transplant Patient: Case Report.

INTRODUCTION: Viral myocarditis can emerge with various symptoms, including fatal arrhythmia and cardiogenic shock, potentially evolving in chronic myocarditis or dilatative cardiomyopathy. We report a case of a kidney transplant patient affected by coxsackie viral myocarditis. METHODS: A 49-year-old man was admitted to our hospital with dyspnea and fever in August 2014. He underwent living donor kidney transplantation in 1986 and polar graft resection for papillary carcinoma in 2012. RESULTS: The initial investigation showed pulmonary congestion, pancreatitis, increased serum troponin I, and increased liver enzyme levels. Echocardiogram revealed an ejection fraction (EF) of 20% and PAPS 45 mm Hg. He underwent coronary stent implantation, started hemodialysis, and continued on low-dose steroid immunosuppressive therapy. The clinical course improved rapidly, but endomyocardial biopsy showed acute myocarditis. Further investigation revealed a high antibody titer against coxsackievirus B4 and B5. Pancreatic enzyme levels normalized 2 months after patient admission; his cardiac condition improved after 6 months. The patient has been followed for 1 year, and his left ventricular EF is stable (45%). CONCLUSIONS: Viral myocarditis represents a serious clinical condition requiring a fast therapeutic intervention. This patient's clinical course suggests that changes in his immunosuppressive therapy were associated with progressive amelioration of his viral myocarditis.