Early-onset sepsis in very preterm neonates in Australia and New Zealand, 2007-2018.

OBJECTIVE: To evaluate the epidemiology and population trends of early-onset sepsis in very preterm neonates admitted to neonatal intensive care units (NICU) in Australia and New Zealand. DESIGN: Retrospective observational cohort study using a dual-nation registry database. SETTING: 29 NICUs that have contributed to the Australian and New Zealand Neonatal Network. PARTICIPANTS: Neonates born at <32 weeks' gestation born between 2007 and 2018 and then admitted to a NICU. MAIN OUTCOME MEASURES: Microorganism profiles, incidence, mortality and morbidity. RESULTS: Over the 12-year period, 614 early-onset sepsis cases from 43 178 very preterm admissions (14.2/1000 admissions) were identified. The trends of early-onset sepsis incidence remained stable, varying between 9.8 and 19.4/1000 admissions (linear trend, p=0.56). The leading causative organisms were Escherichia coli (E. coli) (33.7%) followed by group B Streptococcus (GBS) (16.1%). The incidence of E. coli increased between 2007 (3.2/1000 admissions) and 2018 (8.3/1000 admissions; p=0.02). Neonates with E. coli had higher odds of mortality compared with those with GBS (OR=2.8, 95% CI 1.2 to 6.1). Mortality due to GBS decreased over the same period (2007: 0.6/1000 admissions, 2018: 0.0/1000 admissions; p=0.01). Early-onset sepsis tripled the odds of mortality (OR=3.0, 95% CI 2.4 to 3.7) and halved the odds of survival without morbidity (OR=0.5, 95% CI 0.4 to 0.6). CONCLUSION: Early-onset sepsis remains an important condition among very preterm populations. Furthermore, E. coli is a dominant microorganism of very preterm early-onset sepsis in Australia and New Zealand. Rates of E. coli have been increasing in recent years, while GBS-associated mortality has decreased.

When should intensive care be provided for the extremely preterm infants born at the margin of viability? A survey of Australasian parents and clinicians.

AIM: This study aimed to explore clinician and parent opinions of risk limits on resuscitation and intensive care (IC) for extremely premature infants born at the margin of viability. METHODS: Two anonymous on-line surveys were conducted from August 2016 to January 2017. Survey participants were: (i) clinicians affiliated with neonatal intensive care units in Australia; and (ii) parents or individuals who expressed interest in premature babies through the Facebook page of Miracle Babies Foundation. RESULTS: A total of 961 responses were received. Among 204 clinicians, 52% were neonatologists, 22% obstetricians, 20% neonatal intensive care unit nurses and 4% were midwives. Among 757 parents, 98% had a premature baby. Only 75% of clinicians responded to the risk limits questions. Median mortality risk above which they would not recommend resuscitation/IC was 70% (interquartile range (IQR) 50-80%); major disability risk in survivors 60% (IQR 50-75%); and composite risk of mortality and major disability 70% (IQR 50-80%). All parents answered the risk limit questions. The median mortality risk for not planning resuscitation was 90% (IQR 60-90%); major disability risk in survivors 50% (IQR 30-90%); and composite risk 90% (IQR 50-90%). Most clinicians (82%) stated that decisions should be guided by parent opinions if there are uncertainties. Parents had varying perception of previous counselling, and 57% stated that both their viewpoint and doctor's predicted risk influenced their decision-making. CONCLUSIONS: Clinicians and parents had different views on mortality and major disability risks when deciding on resuscitation/neonatal IC treatment. When there was uncertainty, both agreed on working together.

Probiotics for Prevention of Severe Necrotizing Enterocolitis: Experience of New Zealand Neonatal Intensive Care Units.

Introduction: Necrotizing enterocolitis (NEC) affects mainly preterm infants, has a multifactorial etiology and is associated with intestinal dysbiosis and disordered immunity. Use of probiotics for prophylaxis is beneficial with studies indicating reduction in NEC ≥ stage 2, late onset sepsis (LOS) and mortality. However, not all studies have shown a reduction, there are questions regarding which probiotic to use, whether infants <1,000 g benefit and the risk of probiotic sepsis. All neonatal intensive care units in New Zealand (NZ) use probiotics and contribute to an international database (Australian and New Zealand Neonatal Network or ANZNN). Objective: To use ANZNN data to investigate the experience of NZ neonatal units with probiotics for NEC prevention in a setting where the baseline incidence of severe NEC was low, to compare results of 2 commonly used probiotic regimes and report on the extremely low birth weight subgroup. Method: Outcomes before (Pre group 2007-2010) and after (Probiotic group 2013-2015) starting routine probiotics for preterm infants <1,500 g or <32 weeks were compared. Clinicians reviewed cases to ensure they met database criteria. Five units used Infloran (Bifidobacterium bifidum and Lactobacillus acidophilus) and 1 unit used Lactobacillus GG (LGG) and bovine lactoferrin (bLF). Results: Four thousand five hundred and twenty nine infants were included and Pre and Probiotic groups were well-balanced with regard to gestation, birth weight and gender. The incidence of NEC in the Probiotic group was 1.6 and 2.7% in the pre group (corrected OR 0.62 CI 0.41-0.94). There was one case of probiotic sepsis. There was no significant difference between the Infloran and LGG/bLF combinations in regard to observed NEC rates. Late onset sepsis rates were significantly lower in the Probiotic group (p < 0.01). Conclusions: Introduction of probiotics for preterm infants in NZ has been associated with significant reductions in NEC and late onset sepsis.

Astigmatism Correction Using SMILE.

Small incision lenticule extraction (SMILE) was introduced in the recent decade for the treatment of myopia and myopic astigmatism. This flap-free technique has a high efficacy and safety profile and also carries potential advantages over laser in situ keratomileusis such as a better corneal biomechanical stability, reduction in dry eyes rate, and the avoidance of flap complications. However, there have been concerns regarding the precision of astigmatism correction that undercorrection has been reported to be apparent. Various factors that affect astigmatism correction have been identified in the literature. The purpose of this review is to discuss the factors that affect astigmatism correction in SMILE and several techniques to improve the refractive outcomes.

Outcomes of presbyopia-correcting intraocular lenses after laser in situ keratomileusis.

BACKGROUND: Laser in situ keratomileusis (LASIK) is the most common refractive surgery in young patients, which aims at providing a clear distance vision without the use of spectacles. With time, these patients develop symptomatic cataract, which affects activities of daily living, and to improve visual acuity, intraocular lens (IOL) implantation can be considered. In post-myopic LASIK patients, to allow continuation of spectacle independence, the implantation of presbyopia-correcting IOLs is a suitable option. The purpose of this retrospective case series is to report the visual outcome and quality in post-myopic LASIK eyes after the implantation of AT LISA tri839MP IOL. METHOD: Twenty eyes of 13 patients with history of myopic LASIK within 20 years underwent phacoemulsification by one single surgeon. All eyes were implanted with AT LISA tri839PMP IOL, and their outcomes were evaluated at 6 months postoperation. RESULTS: The mean postoperative uncorrected distance visual acuity (VA) is 0.28 ± 0.29, while the corrected distance VA is 0.06 ± 0.14. The mean postoperative uncorrected near VA is 0.02 ± 0.05, while the corrected near VA is 0.01 ± 0.02. The mean postoperative manifest refraction spherical equivalent (SE) is - 0.92 ± 0.76D. There is a statistically significant difference between the preoperative and postoperative refraction (p = 0.02), which shows a postoperative myopic shift. There is also a statistically significant difference between the mean targeted SE and postoperative manifest refraction SE (p = 0.00). Only one out of 20 eyes (5%) reported halo and glare symptoms. Ten out of 20 eyes (50%) are able to achieve spectacles independence. CONCLUSION: In conclusion, in post-myopic LASIK eyes, AT LISA tri839MP provides a good visual outcome at both near and distance, but is more predictable at near than at distance. There is a myopic shift in the postoperative SE. Visual quality is satisfactory and has not been exacerbated. Most patients can remain to be spectacles free at all distances.

Early epithelial complications of accelerated trans-epithelial corneal crosslinking in treatment of keratoconus: a case series.

BACKGROUND: To report a case series of early postoperative complications following combined accelerated corneal crosslinking (CXL) and trans-epithelial technique in keratoconus. CASE PRESENTATIONS: Eleven eyes underwent accelerated trans-epithelial CXL (18 mW/cm2 for 5 min). Seven eyes (64%) developed complications in the first week postoperatively. Five eyes had large epithelial defects, and two eyes were complicated with diffuse punctate epithelial erosions. Early transient stromal haze was seen in eyes with epithelial complications. Anterior segment optical coherence tomography showed a faint demarcation line in six eyes (55%) with epithelial complications. CONCLUSION: A significant number of eyes developed epithelial complications shortly after combined accelerated trans-epithelial CXL, which defeated the benefits of leaving the epithelium intact.

A cross-sectional comparative study on chronic ocular manifestations of Stevens-Johnson syndrome and toxic epidermal necrolysis in Chinese eyes: a 15-year case series.

PURPOSE: To compare the chronic ocular manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis patients from a 15-year cohort. METHODS: All SJS and TEN patients admitted to our burn intensive care unit between 1999 and 2014 were invited for assessment. Slit-lamp examination was performed, and ocular condition was graded according to the Sotozono scoring System, which depended on the extent of cornea, conjunctiva and lid involvement. Tear osmolarity was also measured. RESULTS: A total of 18 SJS and 4 TEN cases with an average of 92 and 135 months from disease onset were included. The average age of onset was 46.4 ± 16.6 in SJS and 43.5 ± 19.3 in TEN patients. The LogMAR visual acuity was 0.209 ± 0.591 in SJS and 0.489 ± 0.688 in TEN patients (p = 0.048). The average total Sotozono score was 3.75 ± 7.32 in SJS and 6.88 ± 9.49 in TEN (p = 0.358). Neither the age of onset (p = 0.787), length of follow-up (p = 0.256) nor disease type (SJS vs TEN, p = 0.188) predicted the Sotozono score. There was a statistically significant correlation between Sotozono score and LogMAR VA (r s = 0.437, p = 0.003). CONCLUSION: The average total Sotozono score was higher in the TEN group than in the SJS group, but the difference was not statistically significant. Nevertheless, the score correlated with the visual acuity which was statistically worse in the TEN group.

Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants.

BACKGROUND: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. METHOD: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. RESULTS: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and ≥32 weeks, AUC 0.50-0.65; ≥1500 g and <32 weeks, AUC 0.60-0.62). CONCLUSION: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking.

Avoiding the Hughes flap in lower eyelid reconstruction.

PURPOSE OF REVIEW: To review current surgical practices of lower eyelid reconstruction with a focus on recent studies. RECENT FINDINGS: Combination techniques and new flap techniques offer efficacy comparable with existing reconstructive approaches, with the advantage of less local trauma. Inappropriate handling of posterior lamellar grafts, such as kerfing, may predispose to graft failures. Modified Hughes procedure is a favorable choice for large lower eyelid reconstruction; however, it requires temporary eye closure. Other surgical options have been developed to achieve a 1-stage procedure without the need of eye closure. These include the Smith-modified Kuhnt-Szymanowski procedure and the use of flaps. For posterior lamellar grafts, both nasal septal and ear cartilage donor tissue produce esthetically and functionally satisfactory outcomes and comparable efficacy. However, the ear cartilage carries a lower risk of donor site complications. SUMMARY: Lower eyelid reconstruction remains a challenge, especially for large or near total defects. Recent studies have explored modifications and alternatives to the conventional Hughes flap. New surgical procedures give surgeons more options. Taking into account the growing spectrum of reconstructive techniques, an individualized approach may facilitate better functional and esthetic outcomes.

Cytomegalovirus infection during pregnancy with maternofetal transmission induces a proinflammatory cytokine bias in placenta and amniotic fluid.

Congenital infection with cytomegalovirus (CMV) can induce immune responses and placental damage. By use of immunoassay panels, 27 cytokines were assessed in midtrimester amniotic fluid from 8 patients with congenital CMV, in midtrimester sera from 12 pregnant women with primary CMV infection, and in amniotic fluid and serum from uninfected maternal controls. Levels of the cytokines tumor necrosis factor α, interleukin 1ß, interleukin 12, and interleukin 17; the chemokines CCL2, CCL4, and CXCL10; and the growth factors granulocyte-macrophage colony-stimulating factor and platelet-derived growth factor bb were significantly elevated in amniotic fluid from congenital CMV patients (P < .01). Only CXCL10 was significantly higher in sera from CMV-infected pregnant women. CMV infection during pregnancy is associated with a shift in cytokine expression toward a proinflammatory state.

Amniotic fluid inflammatory score is associated with pregnancy outcome in patients with mid trimester short cervix.

OBJECTIVE: We propose a novel amniotic fluid inflammatory score from a comprehensive cytokine analysis of patients with mid-trimester short cervix. STUDY DESIGN: Amniotic fluid from singleton gestations (n = 44) with a cervical length of ≤25 mm between 16-24 weeks was assayed for 25 inflammatory mediators. Patient data were stratified according to gestational age at delivery (<34 vs ≥34 weeks). Mediators that reached statistical significance were included in the amniotic fluid inflammatory score. Patients were assigned 1 point for each significant mediator if their level was in the upper quartile. The amniotic fluid inflammatory score was determined, and its relationship to other clinical characteristics was examined. RESULTS: Fourteen mediators met the criteria. A score of ≥8 was predictive of delivery at <34 weeks' gestation (sensitivity, 87.0%; specificity, 100%; positive predictive value, 100%; negative predictive value, 87.5%). Twenty patients had a high inflammatory score (≥8); 24 patients had a low score. All patients with a high inflammatory score delivered at <30 weeks' gestation. CONCLUSION: The amniotic fluid inflammatory score is related to delivery outcome and clinical characteristics.

Differences in amniotic fluid and maternal serum cytokine levels in early midtrimester women without evidence of infection.

The amniotic fluid cytokine profile has been shown to be indicative of various disease states, and changes may be associated with preterm labor or infection. Anti-inflammatory cytokine profiles may be essential for successful normal pregnancy. However, there are currently few normative data on the concentration of cytokines in amniotic fluids during pregnancy. The aim of this study was to provide new amniotic fluid cytokine data for future comparative studies in disease states, notably in utero viral infections, and to compare these with maternal serum levels. Amniotic fluid was obtained from 100 pregnant women undergoing elective amniocentesis at the Royal Hospital for Women, Randwick. Concentrations of 27 cytokines were simultaneously measured in amniotic fluid and a subset of matching maternal sera (n=33) using a multiplex bead-based immunoassay system (Bio-Plex, Bio-Rad). To exclude infection, nested multiplex PCR targeting 17 known congenital infectious agents were performed on all amniotic fluid and maternal serum samples, and serological testing was also performed against some of these agents. Maternal serum concentration was positively correlated with amniotic fluid levels for MIP-1beta (r=0.39, P=0.027). IL-1ra was positively correlated to maternal age (r=0.210, P=0.036), and mean IL-5 levels were significantly higher in amniotic fluids from pregnancies with male fetuses than those with female fetuses (P=0.036). Normal amniotic fluid concentrations for five cytokines (IL-6, IL-8, IP-10, MCP-1, IL-1ra) were found to be significantly elevated over maternal serum concentrations in matched pairs (P<0.05). Concentrations of 12 cytokines (eotaxin, IFN-gamma, IL-9, IL-12, IL-15, IL-17, MIP-1alpha, MIP-1beta, RANTES, TNF-alpha, VEGF, PDGF bb) were significantly elevated in maternal serum compared to paired amniotic fluid at midtrimester (P<0.05). Amniotic fluid may be more representative of the fetal cytokine profile than cytokine analysis on antenatal sera as it represents predominantly fetal urinary and respiratory secretions. This study provides new normative data for multiple cytokine levels in amniotic fluid and maternal sera at 14-16 weeks gestation, and is a valuable tool for future diagnostic and comparative studies.