Late-onset Infection Research Articles

CMV-specific Cell-mediated Immunity at 3-month Prophylaxis Withdrawal Discriminates D+/R+ Kidney Transplants at Risk of Late-onset CMV Infection Regardless the Type of Induction Therapy.

Whether cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) at prophylaxis cessation predicts D+/R+ kidney transplants at risk of late-onset CMV infection after receiving distinct induction therapies is still not well characterized. We prospectively assessed CMV-specific CMI predicting late-onset CMV infection at prophylaxis withdrawal and at earlier time-points, in 96 consecutive D+/R+ patients receiving either anti-interleukin 2-receptor antibody (anti-IL2RA; n = 50) or rabbit antithymoglobulin (n = 46). CMV-specific CMI was evaluated against CMV antigens (IE-1, pp65) using an IFN-γ ELISpot assay. Fourteen (14.6%) of 96 patients developed late-onset CMV infection and 2 (2.1%) of 96 displayed disease. At 3 months, CMV-specific CMI frequencies were significantly lower in patients developing late-onset CMV infection (P < 0.001 for IE-1, P = 0.030 for pp65), regardless the type of induction therapy. Receiver operating characteristic curve analyses showed accurate CMV-specific CMI cutoffs (25 and 130 IFN-γ spots for IE-1 and pp65, respectively) classifying patients into high risk, intermediate risk, or low risk (log-rank = 0.006; hazard ratio, 4.084; 95% confidence interval, 1.431-11.651; P = 0.009), being IE-1 CMI the strongest predictor (odds ratio, 5.554; 95% confidence interval, 1.486-20.766; P = 0.011). Although the profound posttransplant CMV-specific CMI inhibition among rabbit antithymocyte globulin-treated patients precludes its use for risk stratification both before and early after kidney transplant, a similar proportion of at-risk patients could be identified before month 3 within anti-interleukin 2-receptor antibody-treated patients. Monitoring CMV-specific CMI at 3-month prophylaxis cessation discriminates kidney transplant recipient at risk of late-onset CMV infection, regardless the type of induction therapy.

Molecular epidemiology of invasive and non-invasive group B Streptococcus circulating in Serbia

Streptococcus agalactiae (group B Streptococcus, GBS) remains the leading cause of invasive diseases in neonates and an important cause of infections in the elderly. The aim of this study was to access the prevalence of GBS genito-rectal colonisation of pregnant women and to evaluate the genetic characteristics of invasive and non-invasive GBS isolates recovered throughout Serbia.A total of 432 GBS isolates were tested for antimicrobial susceptibility, capsular polysaccharide (CPS) types and the presence of the hvgA gene. One hundred one randomly selected isolates were further characterized by clustered regularly interspaced short palindromic repeats (CRISPRs) analysis and/or multilocus sequence typing (MLST).The prevalence of GBS colonization in pregnant women was 15%. Overall, six capsular types (Ia, Ib, II to V) were identified, the most common being III (32.2%) and V (25.2%). The hiper-virulent clone type III/ST17 was present in 43.1% and 6.3% (p < 0.05) of paediatric and adults isolates, respectively. Comparative sequence analysis of the CRISPR1 spacers content indicated that a few clones comprised the vast majority of the tested GBS isolates. Thus, it was estimated that dominant clones recovered from infants were CPS III/ST17 in late-onset infections (19/23; 82.6%), and Ia/ST23 in early-onset disease (44.4%). Conversely, genotype CPS V/ST1 was the most prevalent in adults (4/9; 25.4%). All isolates were susceptible to penicillin. Macrolide resistance (23.1%) was strongly associated with the ermB gene and constitutive resistance to clindamycin (63.9%). The majority of strains was resistant to tetracycline (86.6%), mostly mediated by the tetM gene (87.7%). GBS isolates of CPS V/ST1 and CPS III/ST23 were significantly associated with macrolide and tetracycline resistance, respectively.In conclusion, hyper-virulent CPS III/ST17 and V/ST1 were recognized as dominant GBS clones in this study.

Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia.

The disease known as late-onset Alzheimer’s disease is a neurodegenerative condition recognized as the single most commonform of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary tangles, neuropil threads, neuritic senile plaques and often deposits of amyloid around the cerebrovasculature. Although many studies have provided a relatively detailed knowledge of these putatively pathogenic entities, understanding of the events that initiate and support the biological processes generating them and the subsequent observable neuropathology and neurodegeneration remain limited. This is especially true in the case of late-onset disease. Although early-onset Alzheimer’s disease has been shown conclusively to have genetic roots, the detailed etiologic initiation of late-onset disease without such genetic origins has remained elusive. Over the last 15 years, current and ongoing work has implicated infection in the etiology and pathogenesis of late-onset dementia. Infectious agents reported to be associated with disease initiation are various, including several viruses and pathogenic bacterial species. We have reported extensively regarding an association between late-onset disease and infection with the intracellular bacterial pathogen Chlamydia pneumoniae. In this article, we review previously published data and recent results that support involvement of this unusual respiratory pathogen in disease induction and development. We further suggest several areas for future research that should elucidate details relating to those processes, and we argue for a change in the designation of the disease based on increased understanding of its clinical attributes.

Therapeutic outcome of spinal implant infections caused by Staphylococcus aureus: A retrospective observational study.

Spinal implant infection is a rare but significant complication of spinal fusion surgery, and the most common pathogen is Staphylococcus aureus. It is difficult to treat due to this pathogen's biofilm-forming ability and antibiotic resistance. We evaluated the therapeutic outcome of treatments for S aureus spinal implant infections. We retrospectively reviewed all patients with S aureus spinal implant infections at 11 tertiary-care hospitals over a 9-year period. Parameters predictive of treatment failure and recurrence were analyzed by Cox regression. Of the 102 patients with infections, 76 (75%) were caused by methicillin-resistant S aureus (MRSA) and 51 (50%) were late-onset infections. In all, 83 (81%) patients were managed by debridement, antibiotics, and implant retention (DAIR) and 19 (19%) had their implants removed. The median duration of all antibiotic therapies was 52 days. During a median follow-up period of 32 months, treatment failure occurred in 37 (36%) cases. The median time to treatment failure was 113 days, being <1 year in 30 (81%) patients. DAIR (adjusted hazard ratio [aHR], 6.27; P = .01) and MRSA infection (aHR, 4.07; P = .009) were independently associated with treatment failure. Rifampin-based combination treatments exhibited independent protective effects on recurrence (aHR, 0.23; P = .02). In conclusion, among patients with S aureus spinal implant infections, MRSA and DAIR were independent risk factors for treatment failure, and these risk factors were present in the majority of patients. In this difficult-to-treat population, the overall treatment failure rate was 36%; rifampin may improve the outcomes of patients with S aureus spinal implant infections.

Early-Onset vs Late-Onset Inguinal Hernia Mesh Infections: A Retrospective Cohort Study

Early-Onset vs Late-Onset Inguinal Hernia Mesh Infections: A Retrospective Cohort Study

Study protocol: optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: observational study of routinely collected data using propensity matching

IntroductionTherapeutic hypothermia is standard of care for infants born ≥36 weeks gestation with hypoxic ischaemic encephalopathy (HIE); consensus on optimum nutrition during therapeutic hypothermia is lacking. This results in variation...

Prevalence of oropharyngeal group B Streptococcus colonization in mothers, family, and health care providers.

ObjectiveTo determine the prevalence and serotype of oropharyngeal Group B Streptococcal (GBS) colonization of mothers, their family & friends, and health care providers of recently delivered patients as a potential reservoir of neonatal exposure to GBS.MethodsThis is a prospective, single-center observational study of: (1) patients, (2) their family and friends, and (3) health care providers all of whom may come in close contact with neonates. Oropharyngeal GBS colonization and serotype was determined.ResultsThree hundred and seventy three samples were collected. The prevalence of oropharyngeal GBS colonization among all study participants was 23.1% (N = 86). The most commonly found serotypes were 1b (12.8%, N = 11), III (27.9%, N = 24), and V (17.4%, N = 15). The prevalence of oropharyngeal GBS colonization among mothers was 26% (N = 31/121), 22% (N = 39/178) in family and friends, and 21.6% (N = 16/74) in health care providers.ConclusionGroup B Streptococcus colonizes the oropharynx in 1 in 5 mothers, family and friends, and health care providers who come in direct contact with neonates. Further research is needed to determine if this potential reservoir for neonatal exposure could lead to early or late onset neonatal GBS colonization or infection.

Listerioza – rzadka choroba o poważnym rokowaniu

ABSTRAKTListerioza jest chorobą zakaźną wywołaną przez Gram-dodatnią bakterię występującą przede wszystkim w produktach spożywczych pochodzenia zwierzęcego spożywanych na zimno. Do zakażenia dochodzi najczęściej drogą pokarmową. Choroba dotyka głównie osób z obniżoną odpornością, kobiet ciężarnych i noworodków, u których może występować w postaci wczesnej lub późnej, w zależności od czasu, w jakim doszło do zakażenia. Przebieg choroby jest bardzo ciężki, śmiertelność bardzo wysoka, a powikłania neurologiczne występują u 10–15% dzieci. W pracy przedstawiono przypadek noworodka z wrodzonym zakażeniem Listeria monocytogenes.

Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants.

Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that stimulate the immune system and enhance intestinal growth. These benefits could potentially reduce the risk of infection and necrotising enterocolitis (NEC) and improve survival and long-term outcome. To determine if early (within the first 48 hours of life) oropharyngeal administration of mother's own fresh or frozen/thawed colostrum can reduce rates of NEC, late-onset invasive infection, and/or mortality in preterm infants compared with controls. To assess trials for evidence of safety and harm (e.g. aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC) versus no OPC, placebo, late OPC, and nasogastric colostrum. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August 2017). We also searched clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We performed the last search in August 2017. We contacted trial investigators regarding unpublished studies and data. We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast milk, or versus no intervention. We also searched for studies comparing early OPC versus early nasogastric or nasojejunal administration of colostrum. We considered only trials that included preterm infants at < 37 weeks' gestation. We did not limit the review to any particular region or language. Two review authors independently screened retrieved articles for inclusion and independently conducted data extraction, data analysis, and assessments of 'Risk of bias' and quality of evidence. We graded evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information or clarification when necessary. We included six studies that compared early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus no intervention, enrolling 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers found no significant differences between OPC and control for primary outcomes - incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50 to 4.02; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence), incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six studies, 335 infants; P = 0.50; I² = 0%; very low-quality evidence), and death before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence). Similarly, meta-analysis showed no difference in length of hospital stay between OPC and control groups (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P = 0.65; I² = 49%). Days to full enteral feeds were reduced in the OPC group with MD of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I² = 28%; very low-quality evidence).The effect of OPC was uncertain because of small sample sizes and imprecision in study results (very low-quality evidence).No adverse effects were associated with OPC; however, data on adverse effects were insufficient, and no numerical data were available from the included studies.Overall the quality of included studies was low to very low across all outcomes. We downgraded GRADE outcomes because of concerns about allocation concealment and blinding, reporting bias, small sample sizes with few events, and wide confidence intervals. Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.

Estimation of Extra Length of Stay Attributable to Hospital-Acquired Infections in Adult ICUs Using a Time-Dependent Multistate Model.

The objective of the study was to estimate the length of stay of patients with hospital-acquired infections hospitalized in ICUs using a multistate model. Active prospective surveillance of hospital-acquired infection from January 1, 1995, to December 31, 2012. Twelve ICUs at the University of Lyon hospital (France). Adult patients age greater than or equal to 18 years old and hospitalized greater than or equal to 2 days were included in the surveillance. All hospital-acquired infections (pneumonia, bacteremia, and urinary tract infection) occurring during ICU stay were collected. None. The competitive risks of in-hospital death, transfer, or discharge were considered in estimating the change in length of stay due to infection(s), using a multistate model, time of infection onset. Thirty-three thousand four-hundred forty-nine patients were involved, with an overall hospital-acquired infection attack rate of 15.5% (n = 5,176). Mean length of stay was 27.4 (± 18.3) days in patients with hospital-acquired infection and 7.3 (± 7.6) days in patients without hospital-acquired infection. A multistate model-estimated mean found an increase in length of stay by 5.0 days (95% CI, 4.6-5.4 d). The extra length of stay increased with the number of infected site and was higher for patients discharged alive from ICU. No increased length of stay was found for patients presenting late-onset hospital-acquired infection, more than the 25th day after admission. An increase length of stay of 5 days attributable to hospital-acquired infection in the ICU was estimated using a multistate model in a prospective surveillance study in France. The dose-response relationship between the number of hospitalacquired infection and length of stay and the impact of early-stage hospital-acquired infection may strengthen attention for clinicians to focus interventions on early preventions of hospital-acquired infection in ICU.

Summary Protocol for a Multi-Centre Randomised Controlled Trial of Enteral Lactoferrin Supplementation in Newborn Very Preterm Infants (ELFIN)

In a multi-centre randomised controlled trial (RCT), we are assessing whether giving very preterm (i.e., born at < 32 weeks’ gestation) infants prophylactic enteral bovine lactoferrin supplementation (150 mg/kg/day) from shortly after birth until 34 weeks’ post-menstrual age reduces the incidence of late-onset invasive infection (primary outcome), all-cause mortality, bronchopulmonary dysplasia, necrotising enterocolitis, retinopathy of prematurity, and the duration of antibiotic exposure, intensive care, and hospital admission. The trial is recruiting 2,200 participants from 37 neonatal care centres in the UK over 4 years. We will undertake an economic evaluation within the RCT to evaluate cost-effectiveness and provide an estimate of incremental costs for differences in the pre-specified outcomes in primary and subgroup analyses. If a statistically significant and clinically important effect on the primary outcome is detected, we will seek further funding and approval to assess the impact of enteral lactoferrin supplementation on rates of adverse neuro-developmental outcomes in the participating infants when they are 5 years old.

Late-onset Pneumocystis jirovecii pneumonia (PJP) in patients with ANCA-associated vasculitis.

Immunosuppression in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by increasing risk of infections including opportunistic infections like Pneumocystis jirovecii pneumonia (PJP). Available evidence on risk factors and indications for prophylaxis in AAV is derived from PJP occurring early in the course of AAV. In this retrospective study, we characterized the profile of PJP in patients with AAV. PJP cases were identified retrospectively based on positive polymerase chain reaction test from electronic record followed by confirmation from medical records over a 10-year period. AAV patients without PJP over the same period were used as control group. Sixteen PJP+AAV+ were identified; in 14 of them, we were able to confirm they received PJP prophylaxis during induction therapy, while in two cases, data were missing. The onset of the infection was after 6months from AAV diagnosis in 80% of cases. Escalations in immunosuppression prior to PJP were observed in six cases within 3months prior to PJP onset. Overall mortality was 12.5%. By univariate analysis, renal involvement at AAV diagnosis was associated with PJP. These results indicate that PJP is not limited to the first 6months following AAV diagnosis. Late-onset infection can occur in context of augmented immunotherapy, particularly with concurrent lymphopenia. Other risk factors that can independently predict late-onset PJP remain to be identified.

Mannose-binding lectin and mannose-binding protein-associated serine protease 2 levels and infection in very-low-birth-weight infants.

The aim of this study was to explore the role of the lectin pathway in neonatal sepsis through the study of MBL and MASP2 levels and their relationship with infection in a cohort of very-low-birth-weight infants (VLBWI). MBL and MASP2 were measured in plasma samples of n = 89 VLBWI using ELISA and correlated with clinical parameters. MBL plasma levels were aligned with genotyping data of mbl2 exon 1 polymorphisms, rs1800450, rs1800451, and rs5030737. MBL levels were clearly determined by MBL genotype, i.e., AA individuals had tenfold higher MBL levels than AO individuals. MBL and MASP2 levels did not correlate with gestational age, apart from MASP2 levels on day 7. During the first 21 days of life, we noted a gradual increase in both MBL and MASP2 levels. On day 7 of life, MASP2 levels in infants developing late-onset sepsis measured before the onset of symptoms were found to be lower, as compared to non-LOS infants. In our cohort of VLBWI, MBL levels were genetically determined, but not associated with gestational age or sepsis in the first 21 days of life. Lower MASP2 levels on day 7 may indicate increased risk for late-onset infection.

Advagraf® with or without an induction therapy for de novo kidney-transplant recipients

ABSTRACTIntroduction: Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company).Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed.Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p > 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients’ adherence to treatment.

Early abdominal aortic graft infection due to Propionibacterium acnes: a case report and review of the literature

Propionibacterium acnes is a member of the human microbiota that has been recently associated with late-onset infections of indwelling devices, especially shoulder prosthesis. Aortic graft infection are rare events with significant morbidity and mortality. Here, we describe the case of an abdominal aortic graft infection due to P. acnes with an unusual early onset. A review of the recent English language literature has been added.

Characteristics and Risk Factors of Late-onset Bloodstream Infection Beyond 6 Months After Liver Transplantation in Children.

Bloodstream infection (BSI) is a major cause of morbidity and mortality after pediatric liver transplantation (LT). However, most studies have focused on BSI occurring within a few months after LT. In this study, we evaluated the characteristics of BSI occurring beyond 6 months after pediatric LT. We conducted a retrospective cohort study at a pediatric LT center in Japan from November 2005 to March 2016. We evaluated the causative organisms and site of late-onset BSI in children ≤ 18 years of age. The risk factors for developing late-onset BSI and the associations of late-onset BSI with long-term outcomes were also evaluated. Three hundred forty cases of LT were evaluated. Thirty-eight BSI developed in 29 (9%) LT recipients. There were 42 organisms (nine Gram-positive cocci, 33 Gram-negative rods) isolated from the blood cultures of recipients with late-onset BSI. The most frequent sites of late-onset BSI was intraabdominal infection (18/38; 47%). There were also 14 (39%) episodes with no apparent focus. In multivariate analysis, a prolonged operative time > 12 hours (odds ratio [OR] = 3.55; P = 0.04) and biliary stenosis (OR = 4.60; P = 0.006) were independent risk factors for developing late-onset BSI. Late-onset BSI was associated with increased retransplantation rate (P = 0.04) and mortality (P < 0.001). Late-onset BSI developed in 9% of recipients after pediatric LT. Gram-negative rods accounted for the majority of late-onset BSI as a consequence of abdominal infection, but the focus was often unclear. Prolonged operative time at LT and biliary stenosis were independent risk factors for developing late-onset BSI.

Protective effect of Group B Streptococcus type-III polysaccharide conjugates against maternal colonization, ascending infection and neonatal transmission in rodent models

Group B Streptococcus (GBS) is a normal inhabitant of recto-vaginal mucosae in up to 30% of healthy women. Colonization is a major risk factor for perinatal infection which can lead to severe complications such as stillbirth and neonatal invasive disease. Intra-partum antibiotic prophylaxis in colonized women is a safe and cost-effective preventive measure against early-onset disease in the first days of life, but has no effect on late-onset manifestations or on early maternal infection. Maternal immunization with capsular polysaccharide-based vaccines shows promise for the prevention of both early-onset and late-onset neonatal infections, although ability to prevent maternal colonization and ascending infection has been less studied. Here we investigated the effect of a GBS glycoconjugate vaccine since the very early stage of maternal GBS acquisition to neonatal outcome by rodent models of vaginal colonization and ascending infection. Immunization of female mice and rats with a type III glycoconjugate reduced vaginal colonization, infection of chorioamniotic/ placental membranes and bacterial transmission to fetuses and pups. Type III specific antibodies were detected in the blood and vagina of vaccinated mothers and their offspring. The obtained data support a potential preventive effect of GBS glycoconjugate vaccines during the different stages of pregnancy.

Enteral Lactoferrin Supplementation for Very Preterm Infants: A Randomised Controlled Trial

Background: Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein usually processed from cow's milk, prevents infections and associated complications. Methods: In this randomised, placebo-controlled trial, very preterm infants (born before 32 weeks' gestation) were recruited within 72 hours of birth from 37 UK hospitals. Infants were allocated randomly (1:1) to receive enteral bovine lactoferrin (150 mg/kg/day; maximum 300 mg/day) versus sucrose (same dose) once daily until 34 weeks' postmenstrual age. Web-based randomisation used an algorithm minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers and outcomes assessors were unaware of group assignment. The primary outcome was microbiologically-confirmed or clinically-suspected late-onset infection until hospital discharge. The trial was registered with the International Standard Randomised Controlled Trial Number 88261002. Findings: We recruited 2203 participants between May 2014 and September 2017. Four infants had consent withdrawn or unconfirmed leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants were available for inclusion in the intention-to-treat analyses. In the intervention group, 316/1093 (28.9%) infants acquired a late-onset infection versus 334/1089 (30.7%) in the control group: risk ratio (RR) adjusted for minimisation factors 0.95 (95% confidence interval [CI] 0.81, 1.10). Pre-specified subgroup analyses did not show statistically significant interactions for gestation at birth (completed weeks') or type of enteral milk received (human, formula, or both). Interpretation: Enteral supplementation with bovine lactoferrin does not reduce the incidence of late-onset infection in very preterm infants. Trial Registration Number: The trial was registered with the International Standard Randomised Controlled Trial Number 88261002. Funding: The ELFIN trial was funded by the UK National Institute for Health Research Health Technology Assessment programme (10/57/49). Declaration of Interest: EJ is a member of the NIHR HTA General Board; WM is a member of the NIHR HTA Commissioning Board and the HTA Journals Library Editorial Board. JD is a member of the NIHR HTA Clinical Evaluation and Trials Board. PTH, WM, EJ, LL report receipt of funding from NIHR, outside the submitted work. NDE reports grants from Prolacta Biosciences US, grants from Danone Early Life Nutrition, personal fees from Nestle Nutrition Institute, and personal fees from Baxter, outside the submitted work. Ethical Approval: The trial protocol was approved by the National Research Ethics Service (NRES) Committee East Midlands - Nottingham 2 (Ref: 13/EM/0118). Local approval and site-specific assessments were obtained from the NHS Trusts for trial sites.

Prevention of Late-Onset Cytomegalovirus Infection and Disease in Donor-Positive/Recipient-Negative Kidney Transplant Recipients Using Low-Dose Valganciclovir

BackgroundThe main challenge with cytomegalovirus (CMV) prophylaxis in IgG donor-positive/recipient-negative (D+/R–) kidney transplant recipients is late-onset CMV disease. We evaluated a novel protocol for the prevention of late-onset CMV infection and disease in D+/R− organ recipients. MethodsOur prospective, observational, cohort study included 100 adult kidney transplant recipients. Prophylaxis with low-dose valganciclovir (450 mg/d, 3 times a week for 6 months) was administered to D+/R− recipients. Risk factors for CMV infection and disease were identified. Renal function and the outcomes of CMV infection and disease were compared between D+/R− (n = 15) and recipient-positive (R+; n = 81) organ recipients. ResultsD+/R− recipients showed significant independent risk factors with high hazard ratios for CMV infection (2.04) and disease (10.3). The proportion of CMV infection in D+/R− and R+ recipients was 80% and 46% (P = .023), and that of CMV disease was 33% and 6.2% (P = .008), repectively. D+/R− recipients developed CMV infection and disease within 6 months after transplantation. However, both CMV infection- and disease-free survival rates beyond 1 year post-transplantation defined as late-onset were stable in D+/R− recipients. Moreover, serum creatinine levels at 1 year post-transplantation were comparable between D+/R− and R+ recipients (1.45 ± 0.71 vs 1.16 ± 0.35 mg/dL, P = .26). ConclusionOur novel protocol prevented late-onset CMV infection and disease beyond 1 year post-transplantation in D+/R− recipients.

Retrospective research on initiative content reduction technique for obesity patients with huge abdominal incisional hernia

OBJECTIVE: The objective of this study is to assess the prophylactic and therapeutic effects of initiative content reduction on intra-abdominal hypertension in obesity patients with huge abdominal incisional hernia. MATERIALS AND METHODS: In this study, the retrospective cohort/descriptive research methods were applied. We collected the clinical data of a total of 62 obesity patients with single-onset huge abdominal incisional hernia who were admitted to Beijing Chaoyang Hospital of Capital Medical University for treatment between January 2011 and December 2015. In the operation, the initiative content reduction was performed. Following observation indexes were recorded as follows: (1) Surgical condition: surgical duration, length of resected intestinal tract, and length of stay (LOS) in hospital; (2) postoperative recovery: cardiac, pulmonary, hepatic and renal functions, and and intravesical pressure; (3) incidence of postoperative complications: infection of incision and intestinal fistula; and (4) patients' condition in follow-up. Return visits in outpatient service were required respectively at 1 week, 1 month, 3 months and 6 months after surgery, and 1 year after follow-up, the follow-up was carried out through telephone. Recurrences of hernia and late-onset infection were the question to be asked in follow-up, and June 2016 was set as the deadline of follow-up. RESULTS: (1) Surgical condition: The surgeries were successfully carried out for 62 patients, in which surgical duration was (115 ± 22) min, the length of resected intestinal tract was (207 ± 64) cm, and LOS was (14.5 ± 1.9) d. (2) Postoperative recovery: the intravesical pressure of patients was decreased in comparison with the level before operation, and after surgery, no hepatic, renal and respiratory dysfunctions were observed. (3) Incidence of postoperative complications: There were four patients with infection of incision; however, no intestinal fistula was found in any patients. (4) Follow-up: follow-up was performed for 62 patients, and the average length of follow-up was 35 months, during which three patients suffered recurrence of incisional hernia. CONCLUSION: For obesity patients with huge abdominal hernia, the application of initiative content reduction can effectively prevent the postoperative intra-abdominal hypertension, which is considered as an effective and feasible therapeutic procedure.