Effect of unidirectional airflow ventilation on surgical site infection in cardiac surgery: environmental impact as a factor in the choice for turbulent mixed air flow.

BACKGROUND: Surgical site infection (SSI) in the form of postoperative deep sternal wound infection (DSWI) after cardiac surgery is a rare, but potentially fatal, complication. In addressing this, the focus is on preventive measures, as most risk factors for SSI are not controllable. Therefore, operating rooms are equipped with heating, ventilation and air conditioning (HVAC) systems to prevent airborne contamination of the wound, either through turbulent mixed air flow (TMA) or unidirectional air flow (UDAF). AIM: To investigate if the risk for SSI after cardiac surgery was decreased after changing from TMA to UDAF. METHODS: This observational retrospective single-centre cohort study collected data from 1288 patients who underwent open heart surgery over 2 years. During the two study periods, institutional SSI preventive measures remained the same, with the exception of the type of HVAC system that was used. FINDINGS: Using multi-variable logistic regression analysis that considered confounding factors (diabetes, obesity, duration of surgery, and re-operation), the hypothesis that TMA is an independent risk factor for SSI was rejected (odds ratio 0.9, 95% confidence interval 0.4-1.8; P>0.05). It was not possible to demonstrate the preventive effect of UDAF on the incidence of SSI in patients undergoing open heart surgery when compared with TMA. CONCLUSION: Based on these results, the use of UDAF in open heart surgery should be weighed against its low cost-effectiveness and negative environmental impact due to high electricity consumption. Reducing energy overuse by utilizing TMA for cardiac surgery can diminish the carbon footprint of operating rooms, and their contribution to climate-related health hazards.

Hepatitis E infection with a benign course during vedolizumab treatment for Crohn's disease: A case report.

We present a 49 year old female patient with Crohn's disease (CD) in remission on vedolizumab therapy who experienced a symptomatic, though benign, course of acute hepatitis E. Routine blood tests showed substantial elevation of liver enzymes and polymerase chain reaction (PCR) testing confirmed hepatitis E virus (HEV) infection. Vedolizumab therapy was paused, liver enzymes improved three weeks after infection and normalized after six months. The patient recovered completely from mild symptoms. This case shows that hepatitis E is a potential cause of acute hepatitis during vedolizumab therapy, and in this case the infection has run a benign course.

The diagnosis and management of CMV colitis in IBD patients shows high practice variation: a national survey among gastroenterologists.

BACKGROUND: Clinical guidelines on cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) are hampered by the low quality of evidence. In this study, we aim to explore the attitude and management of CMV colitis in IBD among gastroenterologists. METHODS: A web-based survey was distributed to adult and pediatric gastroenterologists and trainees in academic and general hospitals in the Netherlands. The survey comprised data collection on respondents' demographics, attitudes towards the importance of CMV infection in IBD on a visual analogue scale (from 0 to 100), and diagnostic and therapeutic strategies. RESULTS: A total of 73/131 invited respondents from 32 hospitals completed the survey (response rate of 56%). The importance of CMV infection was scored at a median 74/100. Respondents indicated CMV testing as appropriate in the clinical setting of steroid-refractory colitis (69% of respondents), hospitalized patients with active colitis (64%), immunomodulator or biological refractory colitis (55%) and active colitis irrespective of medication use (14%). CMV diagnostics include histology of colonic biopsies (88% of respondents), tissue CMV PCR (43%), serum CMV PCR (60%), CMV serology (25%) and fecal CMV PCR (4%). 82% of respondents start antiviral therapy after a positive CMV test on colonic biopsies (histology or PCR). CONCLUSIONS: Most Dutch gastroenterologists acknowledge the importance of CMV colitis in IBD. Strategies vary greatly with regard to the indication for testing and diagnostic method, as well as indication for the start of antiviral therapy. These findings underline the need for pragmatic clinical studies on different management strategies, in order to reduce practice variation and improve the quality of care. Summary of the established knowledge on this subject:The clinical significance of CMV-associated colitis in IBD remains a matter of debateRecommendations regarding CMV colitis in current international guidelines are based on low to moderate evidence levels and different diagnostic strategies are proposed What are the significant and/or new findings of this study?We show that there is a high practice variation of diagnosis and management of CMV colitis in IBD amongst adult and pediatric gastroenterologistsThis study underlined the need for pragmatic studies and guidelines on different management strategies including cut-off values to start therapy.

The Usefulness of Aqueous Fluid Analysis for Epstein-Barr Virus in Patients with Uveitis.

Purpose: To determine characteristics of patients with laboratory findings indicative of intraocular Epstein-Barr-virus (EBV) infection and to establish the usefulness of the laboratory analysis in patients with uveitis.Methods: Retrospective study of patients who underwent diagnostic aqueous fluid analysis. Diverse demographic data of patients were registered.Results: EBV-PCR tested positive in 3/201 (1%) and EBV-GWC in 22/245 (9%). The prevalence of immunosuppression was similar in EBV positive (by PCR/GWC) and EBV negative patients (7/25; 28% vs. 50/272;18%, P = 0.29). Out of all 22 EBV-GWC positive patients, GWC was between 3 and 10 in 91%. In total, 14 patients had laboratory results indicating only EBV infection. Patients without an alternative explanation for uveitis (6/14; 43%) had a chronic recurrent course and good visual prognosis.Conclusion: Low EBV-GWC values combined with multiple positive GWC and/or PCR for other infectious agents. Intraocular assessment for EBV in the initial examination of uveitis patients has limited value.

Fulminant Liver Failure due to Hepatitis B Reactivation During Treatment With Tocilizumab.

Tocilizumab is a humanized monoclonal antibody targeting the interleukin-6 receptor that is frequently used for the treatment of refractory rheumatoid arthritis. Since patients with hepatitis B virus (HBV) infection were excluded from pivotal trials, the risk of HBV reactivation with this novel drug class remains uncertain. We present the first case of tocilizumab-associated HBV reactivation resulting in fulminant hepatic failure and a need for liver transplant. Our findings underscore the need for prophylactic antiviral therapy in patients being treated with novel immunosuppressive agents.

[Zika virus and sexual transmission; when and for how long does one need to use a condom?] / Zikavirus en seksuele transmissie.

- More evidence has become available concerning the sexual transmission of Zika virus and viral shedding in semen, which has led to the expansion of international guidelines for prevention of sexual transmission; Dutch guidelines have not been altered.- Internationally, the use of condoms during sex or sexual abstinence is advised for the duration of the pregnancy. Furthermore, when actively trying to conceive one should use a condom for six months.- In the Dutch guidelines, men who have visited a Zika virus epidemic area are advised to use a condom for 2 months upon return, irrespective of their partner possibly being pregnant or their wish to conceive.- Based on reports to the World Health Organisation and patient reports, the serial interval between disease onsets of both sexual partners is 4-44 days (median: 15).- Zika virus RNA is often no longer detectable in semen 2-3 months after disease onset.- International guidelines are based on the maximum detection period of Zika virus RNA and on virus isolation. Dutch prevention guidelines, on the other hand, are based on the longest serial interval known for sexual transmission (44 days).- Detection of Zika virus RNA in semen does not give a definitive answer on contagiousness. Currently, following the Dutch prevention advice is the best option in order to prevent sexual transmission.

Chronic norovirus infection among solid organ recipients in a tertiary care hospital, the Netherlands, 2006-2014.

OBJECTIVES: Immunocompromised patients can suffer prolonged norovirus symptoms and virus shedding for many years. Little is known about the prevalence of chronic norovirus infection among solid organ transplant (SOT) recipients. In this study, 2182 SOT recipients were retrospectively tested for chronic norovirus infection. METHODS: The first and last norovirus positive faecal samples of SOT recipients were sequenced to distinguish between persisting infection and re-infection. Patient charts were reviewed to obtain data on health status and treatments. RESULTS: In all, 101 of 2182 (4.6%) recipients were norovirus infected and 23 (22.8%) of these developed chronic norovirus infection. Chronic norovirus infection was found among allogeneic heart, kidney and lung transplant recipients. The median shedding period at the end of the study period was 218 days (range 32-1164 days). CONCLUSIONS: This study shows that chronic norovirus infection is not a rare phenomenon among SOT recipients in a tertiary-care hospital. Further research is needed to study the risk of norovirus transmission to other immunocompromised patients in the hospital and to the general population.

[Guillain-Barré syndrome following infection with the Zika virus]. / Guillain-Barré-syndroom na zikavirus-infectie.

BACKGROUND: Guillain-Barré syndrome (GBS) has been identified as a possible complication of infections with the Zika virus (ZIKV) in the current epidemic in Central and South America. Here we describe the first case of GBS in the Netherlands following a ZIKV infection. CASE DESCRIPTION: A 60-year-old woman presented with diarrhoea, fever and an unsteady gait after returning from Surinam. As creatine kinase levels were raised the initial diagnosis was rhabdomyolysis associated with myositis or medication use. However, creatine kinase levels normalized rapidly and the patient developed muscle weakness, sensory disturbances, hyporeflexia in her limbs and facial diplegia. The diagnosis GBS was considered, which was supported by spinal fluid investigation and electromyography. ZIKV was detected in serum and urine. The patient was treated with intravenous immunoglobulins, and recovered. CONCLUSION: This patient developed GBS following a recent ZIKV infection acquired in Suriname. A causal relation between ZIKV infection and GBS, however, has not yet been demonstrated.

Zika virus and the current outbreak: an overview.

Zika virus (ZIKV), a mosquito-borne flavivirus closely related to yellow fever virus and dengue virus, is currently causing a large outbreak in the Americas. Historically, ZIKV infection was considered a sporadic, relatively mild disease characterised by fever, maculopapular rash, conjunctivitis and often arthralgia. However, current observational studies suggest that ZIKV may cause more severe neurological sequelae such as Guillain-Barre syndrome, and birth defects, mainly microcephaly, in babies of whom the mother was infected with ZIKV during pregnancy. This article provides a clinically focussed overview of ZIKV, with emphasis on the current outbreak, clinical manifestations, diagnostic tools and caveats.

Human bocavirus infection as a cause of severe acute respiratory tract infection in children.

In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections.

CMV Primary Infection Is Associated With Donor-Specific T Cell Hyporesponsiveness and Fewer Late Acute Rejections After Liver Transplantation.

Viral infections, including cytomegalovirus (CMV), abrogate transplantation tolerance in animal models. Whether this also occurs in humans remains elusive. We investigated how CMV affects T cells and rejection episodes after liver transplantation (LT). Phenotype and alloreactivity of peripheral and allograft-infiltrating T cells from LT patients with different CMV status were analyzed by flow cytometry. The association of CMV status with early and late acute rejection was retrospectively analyzed in a cohort of 639 LT patients. CMV-positivity was associated with expansion of peripheral effector memory T cell subsets after LT. Patients with CMV primary infection showed donor-specific CD8(+) T cell hyporesponsiveness. While terminally differentiated effector memory cells comprised the majority of peripheral donor-specific CD8(+) T cells in CMV primary infection patients, they were rarely present in liver allografts. Retrospective analysis showed that R(-) D(+) serostatus was an independent protective factor for late acute rejection by multivariate Cox regression analysis (hazard ratio [HR] = 0.18, 95% CI = 0.04-0.86, p = 0.015). Additionally, CMV primary infection patients showed the highest Vδ1/Vδ2 γδ T cell ratio, which has been shown to be associated with operational tolerance after LT. In conclusion, our data suggest that CMV primary infection may promote tolerance to liver allografts, and CMV status should be considered when tapering or withdrawing immunosuppression.

Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B.

BACKGROUND: Before stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6-12 months of consolidation therapy is recommended. AIM: To investigate the effect of consolidation therapy on off-treatment outcomes in CHB patients. METHODS: We included 94 patients who stopped NA after at least 1 year of therapy. Patients could be HBeAg-positive or HBeAg-negative at start-of-treatment, but were HBeAg-negative and had undetectable HBV DNA at time of discontinuation. Consolidation therapy was defined as treatment after the first undetectable HBV DNA (and HBeAg loss for HBeAg-positive patients) until NA cessation. RESULTS: At 3 years, 74% of the start-of-treatment HBeAg-positive and 75% of the start-of-treatment HBeAg-negative patients developed HBV DNA >2000 IU/mL at a single time point, whereas a persistent virological relapse (≥2 tests of HBV DNA >2000 IU/mL 6 months apart within 1 year) developed in 49% of the start-of-treatment HBeAg-positive and 53% of the start-of-treatment HBeAg-negative patients. For both HBeAg-positive and HBeAg-negative patients, consolidation therapy of ≥3 years was associated with lower persistent virological relapse rates compared to <1 year (1-year relapse rate: 25% vs. 54%; P = 0.063 and 24% vs. 57%; P = 0.036, respectively). At 3 years, 9% of the HBeAg-positive and 14% of the HBeAg-negative patients became HBsAg-negative. Prolonged consolidation therapy increased the likelihood of HBsAg loss. Two cirrhotic patients developed hepatic decompensation but both recovered. CONCLUSIONS: After nucleos(t)ide analogue discontinuation, relapse was common in patients with chronic hepatitis B. Prolongation of consolidation therapy beyond 3 years decreased the risk of persistent virological relapse and increased the likelihood of HBsAg loss.

Hepatitis E prevalence among HIV infected patients with elevated liver enzymes in the Netherlands.

BACKGROUND: In recent years chronic hepatitis E virus (HEV) infections have been reported in immunosuppressed patients, including HIV-positive patients with low CD4 cell counts. Because of delayed anti-HEV seroconversion in patients with CD4 cell count<200 cells/ml it is difficult to draw firm conclusions on HEV-seroprevalence in a population of HIV positive patients. OBJECTIVES: To determine the HEV seroprevalence in a population of HIV infected patients. STUDY DESIGN: We retrospectively analysed the HEV prevalence in a population of 256 HIV infected patients with liver enzyme elevations (LEEs), using HEV specific antibody testing and HEV-RNA detection. RESULTS: Within this cohort we observed a HEV-seroprevalence of 11.7%, without any anti-HEV IgM positive or HEV-RNA positive cases. HEV seropositivity was equally prevalent among different CD4(+) cell count groups. CONCLUSION: Although HIV infected patients in the Netherlands are at risk of acquiring HEV, the number of acute infections is low and no chronic cases were found.

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands, May 2014.

Two patients, returning to the Netherlands from pilgrimage in Medina and Mecca, Kingdom of Saudi Arabia, were diagnosed with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in May 2014. The source and mode of transmission have not yet been determined. Hospital-acquired infection and community-acquired infection are both possible.

In vitro measurement of flow rate variability in neonatal IV therapy with and without the use of check valves.

BACKGROUND: In multi-infusion IV therapy, the actual volume delivered to the neonate can vary over time. To reduce flow rate variability, check valves can be used. A check valve allows flow through the valve in only one direction. OBJECTIVE: To evaluate flow rate variability in a low flow dual-infusion setup with and without check valves. METHODS: The effect of changing the height of and adding syringes to the IV-administration set was tested with and without check valves in an in vitro dual-infusion setup with in-line flow meters. The pre-programmed flow rates were 2.5 and 0.1 ml/h. RESULTS: Twenty-four tests of 90 minutes were performed. Time to reach 75% of the pre-programmed 0.1 ml/h flow rate was >20 minutes. The highest total delivered volume during a test was (mean ± SD) 56 ± 8% of the expected delivery for tests without check valves, and diminished to 12 ± 24% of the expected delivery for check valves with a higher opening pressure. CONCLUSIONS: The actual flows and the total delivered volume in low flow dual-infusion setups are less than expected on the pre-programmed flow-rate. These findings emphasize the need for the development of more accurate delivery systems for drugs and fluids in neonatology. Caregivers should be aware of these findings, and optimise the delivery of IV substances by making use of check valves with low opening pressures and by minimising compliance and volume of the IV-administration set. Furthermore, changes in the relative height between pumps and catheter tip should be minimized.

Evaluation of the antiviral response to zanamivir administered intravenously for treatment of critically ill patients with pandemic influenza A (H1N1) infection.

A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4-11 days) compared with 14 days (range, 6-21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated.

Quantitative HBV DNA and AST are strong predictors for survival after HCC detection in chronic HBV patients.

Hepatitis B virus infection (HBV) is an important co-factor in the development of hepatocellular carcinoma (HCC). We studied whether quantitative HBV DNA at time of HCC detection influences survival of HCC patients. All diagnosed HCC cases between 2000 and 2008 at our university-based reference centre were analysed to determine the influence of hepatitis B viral load on overall survival. Clinical and virological findings were evaluated in univariate and multivariate analyses, survival rates were assessed for HCC patients with a high viral load (HBV DNA ≥10(5) copies/ml) and low viral load (HBV DNA <10(5) copies/ml). HCC was diagnosed in 597 patients, including 98 patients with HBV. The group of 37 patients (38%) who had a high viral load contained more HBeAg-positive patients, had lower serum albumin levels and higher serum aspartate aminotransferase (AST ) and alanine aminotransferase (ALT ) levels. The one- and five-year survival rates of HCC patients with a high viral load were 58% and 11% and for HCC patients with a low viral load 70% and 35%, respectively. In multivariate analysis a higher AST level and higher viral load were significantly associated with shorter overall survival (HR=2.30; p=0.018, HR=1.22; p=0.015, respectively). HBeAg positivity, low albumin level or high AST or ALT levels in HCC patients are associated with a higher HBV DNA . HBV DNA level at detection is associated with overall survival of HCC patients. These findings support the concept that after HCC detection adequate suppression of HBV DNA by nucleoside analogue therapy may improve survival.

Prolonged antiviral therapy for hepatitis B virus-infected health care workers: a feasible option to prevent work restriction without jeopardizing patient safety.

To prevent transmission of hepatitis B virus (HBV) from health care workers (HCWs) to patients, highly viraemic HCWs are often advised to restrict performing exposure prone procedures (EPPs). To prevent loss of highly qualified medical personnel and simultaneously minimize transmission risk to patients, we offered highly viraemic HCWs antiviral therapy and evaluated the effects of this strategy. Eighteen chronic HBV-infected HCWs have been monitored every 3-6 months for a median period of 5.6 years (range 1.1-12.5 years). Antiviral therapy was offered if HBV DNA was above 10(5) copies/mL and EPPs were performed or active liver disease was present. Median HBV DNA levels, the percentage of days with HBV DNA above 10(3), 10(4) and 10(5) copies/mL, and reduction of HBV DNA during antiviral treatment have been analysed for hepatitis B e antigen (HBeAg)-positive and HBeAg-negative HCWs separately. Prolonged viral suppression was achieved in both HBeAg-positive, as well as HBeAg-negative HCWs. In HBeAg-negative HCWs treatment with interferon or lamivudine maintained HBV DNA levels below 10(5) copies/mL. For HBeAg-positive HCWs continuous treatment with tenofovir or entecavir was essential for reaching low viraemia persistently. In 2004, median HBV DNA levels in both HBeAg-negative and HBeAg-positive HCWs were below 10(3) copies/mL and all HCWs executed their professional work full-range. For both HBeAg-positive and HBeAg-negative HCWs, antiviral treatment is effective in persistent suppression of virus levels below 10(5) copies/mL. This observation supports antiviral therapy as a viable management option instead of work restriction, with the provision of regular expert monitoring including quantification of HBV DNA.