Mesh fixation techniques for inguinal hernia repair: an overview of systematic reviews of randomised controlled trials.

PURPOSE: Inguinal hernia repair using surgical mesh is a very common surgical operation. Currently, there is no consensus on the best technique for mesh fixation. We conducted an overview of existing systematic reviews (SRs) of randomised controlled trials to compare the risk of chronic pain and recurrence following open and laparoscopic inguinal hernia repairs using various mesh fixation techniques. METHODS: We searched major electronic databases in April 2020 and assessed the methodological quality of identified reviews using the AMSTAR-2 tool. RESULTS: We identified 20 SRs of variable quality assessing suture, self-gripping, glue, and mechanical fixation. Across reviews, the risk of chronic pain after open mesh repair was lower with glue fixation than with suture and comparable between self-gripping and suture. Incidence of chronic pain was lower with glue fixation than with mechanical fixation in laparoscopic repairs. There were no significant differences in recurrence rates between fixation techniques in open and laparoscopic mesh repairs, although fewer recurrences were reported with suture. Many reviews reported wide confidence intervals around summary estimates. Despite no clear evidence of differences among techniques, two network meta-analyses (one assessing open repairs and one laparoscopic repairs) ranked glue fixation as the best treatment for reducing pain and suture for reducing the risk of recurrence. CONCLUSION: Glue fixation may be effective in reducing the incidence of chronic pain without increasing the risk of recurrence. Future research should consider both the effectiveness and cost-effectiveness of fixation techniques alongside the type of mesh and the size and location of the hernia defect.

Occurrence of adverse events caused by valganciclovir as pre-emptive therapy for cytomegalovirus infection after allogeneic stem cell transplantation is reduced by low-dose administration.

BACKGROUND: Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. METHODS: We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. RESULTS: Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). CONCLUSIONS: Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV.

Post-operative infection of endoscopic submucosal dissection of early colorectal neoplasms: a case-controlled study using a Japanese database.

WHAT IS KNOWN AND OBJECTIVE: Endoscopic submucosal dissection of early colorectal neoplasms (ESD-ECN) is known to be an operation with risk of contamination, possibly requiring pre-operative antimicrobial prophylaxis for the prevention of post-operative infection. However, an evaluation of the need for pre-operative antimicrobial prophylaxis for ESD-ECN has yet to be reported. The objective of this study was to determine whether pre-operative antimicrobial prophylaxis is associated with a reduced incidence of post-operative infection following ESD-ECN. METHODS: The present retrospective case-controlled study utilized a database built from the medical records of 14 university hospitals throughout Japan. Patients who were admitted and discharged from the hospital from April 2012 to October 2013 and who had undergone ESD-ECN were included in the study. Patients who had been undergone any other operation during their course of hospitalization, and patients who were prescribed antimicrobial agents for reasons other than post-operative infection or for prophylaxis were excluded. Characteristics of the study population, pre-operative antimicrobial prophylaxis and antimicrobial therapy for post-operative infection were investigated. In addition, we compared the characteristics of patients with post-operative infection (PI) and those with no post-operative infection (NPI). Univariate analyses were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS AND DISCUSSION: We obtained the records of 522 patients who had undergone ESD-ECN from the database. After application of exclusion criteria, 421 patients were enrolled. The post-operative infection rate was 1·2%. Peritonitis was found most to be the most common post-operative infection (44%). Pre-operative antimicrobial prophylaxis was used for 314 patients (75%), with a median duration of 3·0 (range 1-11) days. Cefotiam was most frequently prescribed for pre-operative antimicrobial prophylaxis (56%). Antimicrobial therapies were started 1-10 days after ESD-ECN for a duration of 1-14 days. Pre-operative antimicrobial prophylaxis was not associated with post-operative infection rate, with an OR (95% CI) of 0·73 (0·08-6·61). However, digestive tract perforation was shown to be associated with post-operative infection and had an OR (95% CI) of 17·1 (1·66-176·45). WHAT IS NEW AND CONCLUSION: Post-operative infection is an exceedingly rare event following ESD-ECN. Pre-operative antimicrobial prophylaxis had no significant effect on post-operative infection following ESD-ECN and thus may be unnecessary. Instead, prevention of digestive tract perforation may be more critical for the decrease in post-operative infections.

Diffuse Liver Metastasis of Small-Cell Lung Cancer Presenting as Acute Liver Failure and Diagnosed by Transjugular Liver Biopsy: A Rare Case in Whom Nodular Lesions Were Detected by Enhanced CT Examination.

Small-cell lung cancer (SCLC) is a subgroup of lung cancer with a high frequency of liver metastasis, which is a predictor of poor prognosis. Diffuse liver metastases of SCLC with no visible nodular lesions in the liver when examined using computed tomography (CT) are relatively rare; however, a few cases with rapid progression to acute liver failure that were diagnosed after death have been reported. In this paper, we report a 63-year-old man with diffuse liver metastases of SCLC that were histologically diagnosed using a transjugular liver biopsy while the patient was alive, even though no lesions were visible during a contrast-enhanced CT examination.

Two patients treated with simeprevir plus pegylated-interferon and ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation: case report.

We previously reported our data on telaprevir (TVR) used in combination with pegylated-interferon and ribavirin (PEG-IFN/RBV) for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). TVR substantially increases the blood levels of immunosuppressive agents such as cyclosporine and tacrolimus for drug-drug interactions. On the other hand, the effect of simeprevir (SMV) on the blood levels of these immunosuppressive agents is unclear. We report 2 patients who achieved viral responses with little effect on the blood levels of cyclosporine and tacrolimus using SMV plus PEG-IFN/RBV treatment. The first was a 71-year-old woman with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. She was treated with 40 mg/d of cyclosporine, and received SMV plus PEG-IFN/RBV treatment. The second was a 65-year-old man with HCV-related liver cirrhosis who failed to respond to PEG-IFN/RBV after living donor LT. He was treated with 3 mg/d of tacrolimus, and received SMV plus PEG-IFN/RBV treatment. Serum HCV RNA became undetectable using TaqMan polymerase chain reaction (PCR) test after 4 weeks of treatment in both patients, and no remarkable fluctuation in blood concentration was observed either in cyclosporine or tacrolimus during the 12 weeks of SMV treatment. Completion of 12-week SMV triple therapy was followed by PEG-IFNα2b plus RBV, and both patients achieved sustained virological response 12 weeks after the end of treatment. SMV plus PEG-IFNRBV treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.

Hepatitis B virus (HBV) reverse seroconversion (RS) can be prevented even in non-responders to hepatitis B vaccine after allogeneic stem cell transplantation: long-term analysis of intervention in RS with vaccine for patients with previous HBV infection.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection, reverse seroconversion (RS), is a serious complication after allogeneic stem cell transplantation (alloHSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV-RS. This report is an update of the hepatitis B vaccine study. METHODS: In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. RESULTS: None of the 21 patients in the vaccine group developed HBV-RS and 12 controls developed HBV-RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody (HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. CONCLUSION: These results demonstrated the long-term effects of HBV vaccine for preventing HBV-RS after alloHSCT. Of note, no HBV-RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination.

Human microRNA hsa-miR-1231 suppresses hepatitis B virus replication by targeting core mRNA.

Pathogen-specific miRNA profiles might reveal potential new avenues for therapy. To identify miRNAs directly associated with hepatitis B virus (HBV) in hepatocytes, we performed a miRNA array analysis using urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice where the livers were highly repopulated with human hepatocytes and human immune cells are absent. Mice were inoculated with HBV-infected patient serum samples. Eight weeks after HBV infection, human hepatocytes were collected from liver tissues, and miRNAs were analysed using the Toray 3D array system. The effect of miRNAs on HBV replication was analysed using HBV-transfected HepG2 cells. Four miRNAs, hsa-miR-486-3p, hsa-miR-1908, hsa-miR-675 and hsa-miR-1231 were upregulated in mouse and human livers with HBV infection. These miRNAs were associated with immune response pathways such as inflammation mediated by chemokine and cytokine signalling. Of these miRNAs, hsa-miR-1231, which showed high homology with HBV core and HBx sequences, was most highly upregulated. In HBV-transfected HepG2 cells, overexpression of hsa-miR-1231 resulted in suppression of HBV replication with HBV core reduction. In conclusion, a novel interaction between hsa-miR-1231 and HBV replication was identified. This interaction might be useful in developing new therapeutic strategies against HBV.

PBSC collection from family donors in Japan: a prospective survey.

Severe adverse events (SAE) and late hematological malignancies have been reported after PBSC donation. No prospective data on incidence and risk factors have been available for family donors so far. The Japan Society for Hematopoietic Cell Transplantation (JSHCT) introduced therefore in 2000 a mandatory registration system. It defined standards for donor eligibility and asked harvest centers to report any SAE immediately. All donors were examined at day 30 and were to be contacted once each year for a period of 5 years. Acute SAEs within day 30 were reported from 47/3264 donations (1.44%) with 14 events considered as unexpected and severe (0.58%). No donor died within 30 days. Late SAEs were reported from 39/1708 donors (2.3%). The incidence of acute SAEs was significantly higher among donors not matching the JSHCT standards (P=0.0023). Late hematological malignancies in PBSC donors were not different compared with a retrospective cohort of BM donors (N:1/1708 vs N:2/5921; P=0.53). In conclusion, acute and late SAEs do occur in PBSC donors at relatively low frequency but risk factors can be defined.

Retrospective analysis of an efficient peripheral blood stem cell collection and the relation between infused cell dose and clinical outcome in patients with malignant lymphoma and multiple myeloma.

INTRODUCTION: Etoposide (VP16) is a drug used not only for the treatment of lymphoma but also for the collection of peripheral blood stem cells (PBSCs). We analysed the efficacy and adverse effects of collecting PBSCs and the relation between the infused cell dose and the clinical outcome in lymphoid malignancies. METHOD: Investigating 30 patients with non-Hodgkin's lymphoma, one patient with Hodgkin's lymphoma, and five patients with multiple myeloma, we compared the effects of several doses of etoposide with those of CHOP or CHOP-like treatments or salvage treatments. We also analysed the relation between the amount of CD34(+) cells collected (above or below 5.0 × 10(6) /kg/day) and prognosis of these patients. RESULTS: We found the collected cell count to be highest in patients treated with 500 mg/m(2) of VP16 and lowest in those not treated with VP16 (P = 0.0073). A CD34(+) cell count above 100/µL on the collection day indicates that the target amount of CD34(+) cells (4.0 × 10(6) /kg) can be readily obtained and was reached most rapidly by the patients who had received 500 mg/m(2) of VP16 (P = 0.01). The longer duration of neutropenia in those patients (P = 0.000006) resulted in longer antibiotic treatment (P = 0.0052). Both progression-free survival (PFS) and overall survival (OS) were better for the patients who yielded more than 5.0 × 10(6) CD34(+) cells/kg/day (P = 0.087 for PFS and P < 0.033 for OS). CONCLUSION: We show here that 3 days of VP16 at 500 mg/m(2) was useful for the collection of PBSCs and that patients who yielded more than 5.0 × 10(6) CD34(+) cells/kg/day survived longer than those who yielded less.

Efficacy of folinic acid in preventing oral mucositis in allogeneic hematopoietic stem cell transplant patients receiving MTX as prophylaxis for GVHD.

As the safety of folinic acid administration and its efficacy for reducing the toxicity of MTX remain controversial, we assessed the effect of folinic acid administration after MTX treatment for GVHD prophylaxis on the incidence of oral mucositis and acute GVHD. We retrospectively analyzed data for 118 patients who had undergone allogeneic hematopoietic SCT and had received MTX for GVHD prophylaxis. Multivariate analysis showed that systemic folinic acid administration significantly reduced the incidence of severe oral mucositis (odds ratio (OR)=0.13, 95% confidence interval (CI) 0.04-0.73, P=0.014). There was also a tendency for a lower incidence of severe oral mucositis in patients who received folinic acid mouthwash (OR=0.39, 95%CI 0.15-1.00, P=0.051). No significant difference was observed in the incidence of acute GVHD between patients who received systemic folinic acid administration and those who did not (P=0.88). Systemic folinic acid administration and mouthwash appear to be useful for reducing the incidence of severe oral mucositis in patients who have received allogeneic hematopoietic SCT using MTX as GVHD prophylaxis.

IL28B polymorphism may guide pegylated interferon plus ribavirin therapy even after curative treatment for hepatitis C virus-related hepatocellular carcinoma.

The present study was designed to determine the predictive factors for the viral response to pegylated interferon-alpha plus ribavirin combination therapy (PEGIFN/RBV) administered after curative treatment for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). The study group was 78 patients treated between January 2005 and January 2009. The sustained viral response (SVR) rate was 25.8% (15/58) in patients infected with HCV-genotype 1 and 55.0% (11/20) in those with genotype 2. Among the 78 patients, 32 (41.0%) could not complete the treatment protocol, and this was because of HCC recurrence in 17 (53%) of them. Multivariate analysis identified partial early viral response (pEVR) as the only independent determinant of SVR [odds ratio (OR) 14.73, P = 0.013] for patients with genotype 1. Multivariate analysis identified male gender (OR 8.72, P = 0.001) and interleukin-28B (IL-28B) genotype (rs8099917) TT (OR 7.93, P = 0.007) as independent predictors of pEVR. Multivariate analysis also identified IL-28B genotype GG+TG (OR 14.1, P = 0.021) and α-fetoprotein >30 (OR 5.4, P = 0.031) as independent predictors of null response. Patients with SVR showed a better survival rate than those without SVR (P = 0.034). The second HCC recurrence rate tended to be lower in patients with SVR than in those without SVR (P = 0.054). With regard to the prognosis of patients with SVR, it is desirable to achieve SVR with interferon therapy even when administered after HCC treatment. IL-28B genotype is a potentially useful marker for the response to PEGIFN/RBV therapy administered after curative treatment of HCV-related HCC.

Increased risk of bacterial infection after engraftment in patients treated with allogeneic bone marrow transplantation following reduced-intensity conditioning regimen.

Although bacterial infection is a major cause of death even after reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (SCT), little is known about the epidemiology and risk factors. The incidence of bacterial infection in 43 patients who received allogeneic bone marrow transplantation (BMT) using a RIC regimen was compared with that in 68 patients who received BMT using a myeloablative conditioning regimen, and risk factors for bacterial infection were identified. Before engraftment, incidences of febrile neutropenia (FN) and documented infections (DI) were significantly decreased in RIC patients (FN: 59.5% vs. 89.6%, P<0.01, DI: 4.8% vs. 17.9%, P<0.01). However, incidence of bacterial infection was significantly increased in RIC patients in the post-engraftment phase (53.8% vs. 11.1%, log-rank, P<0.01). Blood stream was the most frequent focus of infection in both groups. In multivariate analysis, RIC and acute graft-versus-host disease were revealed to be significant risk factors for bacterial infection in this phase. In summary, risk of bacterial infection after engraftment was significantly higher in RIC patients, although infection was decreased before engraftment, and we need to develop a RIC-specific strategy against bacterial infection after RIC SCT.

Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation.

Macrophage migration inhibitory factor (MIF) may play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), as MIF plays an important role to regulate the production of tumor necrosis factor-alpha (TNF-alpha), one of the inflammatory cytokines which induces and exacerbates aGVHD. We examined the association between serum MIF levels and aGVHD vs. chronic GVHD (cGVHD) in allo-SCT patients in this study. We found a significant increase in the peak serum MIF (14.46 ng +/- 1.47 ng/ml) at onset in patients that developed aGVHD (n = 23, P = 0.009). We also found that mean serum MIF levels in patients who developed extensive type cGVHD within 6 months (12.58 +/- 2.18 ng/ml, n = 13) were significantly higher than MIF levels before allo-HSCT (7.86 +/- 1.17 ng/ml, n = 19, P = 0.04). Therefore, we speculated that serum MIF levels increase during the active phase of both aGVHD and cGVHD.

Nickel-63 production in copper samples exposed to the Hiroshima atomic bomb: estimation based on an excitation function obtained by neutron irradiation experiments.

The upper and lower limits of the excitation function of the (63)Cu(n,p)(63)Ni reaction were experimentally determined, and the number of (63)Ni nuclei produced in copper samples exposed to atomic bomb neutrons in Hiroshima was estimated by using the experimental excitation functions and the neutron fluences given in the DS02 dosimetry system. The estimated number of (63)Ni nuclei was compared with that measured and with that calculated using the DS02 dosimetry system and the corresponding ENDF/B-VI cross section. In comparison with DS02, there is about a 60% maximum difference in (63)Ni production at the hypocenter when the experimental upper cross section values are used. The difference becomes smaller at greater distances from the hypocenter and decreases, for example, to less than 30 and 5% when using the upper and lower experimental cross sections at 1,000 m, respectively.

Chimerism and T-cell receptor repertoire analysis after unrelated cord blood transplantation with a reduced-intensity conditioning regimen following autologous stem cell transplantation for multiple myeloma.

A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (>0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.