Increased risk of retinopathy of prematurity since increased O2 saturation targets: A multi-centre study.

BACKGROUND/AIMS: Retinopathy of prematurity (ROP) is a leading cause of visual impairment in premature neonates. The BOOST II, SUPPORT and COT trials recommended increasing O2 saturation targets for pre-term neonates to reduce mortality; however, this is a risk factor for ROP. We aimed to determine whether these targets increased prevalence of ROP among pre-term neonates and higher risk groups. METHODS: Retrospective cohort study conducted using data from the Australian and New Zealand Neonatal Network. 17 298 neonate cohort born 2012-2018 at <32 weeks' GA and/or <1500 g BW was analysed. Adjusted odds ratios (aORs) were calculated for post-2015 risk of: any ROP; ROP ≥ Stage 2; and treated ROP. Sub-analysis stratified at <28 GA, < 26 weeks' GA, <1500 g BW and <1000 g BW was performed. RESULTS: Risk of any ROP increased in the post-2015 group (aOR = 1.23, 95% confidence interval (CI) = 1.14-1.32), <28 weeks' GA (aOR = 1.31, 95% CI = 1.17-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.24, 95% CI = 1.14-1.34) and <1000 g (aOR = 1.34, 95% CI = 1.20-1.50). ROP ≥ Stage 2 increased at <28 weeks (aOR = 1.30, 95% CI = 1.16-1.46), <26 weeks (aOR = 1.57, 95% CI = 1.28-1.91), <1500 g (aOR = 1.18, 95% CI = 1.08-1.30), and <1000 g (aOR = 1.26, 95% CI = 1.13-1.42). CONCLUSION: O2 therapy guidelines since 2015 have resulted in decreased mortality but increased risk of ROP. Individualised NICU adjustments of ROP screening/follow-up methods are necessary to address the clinical burden.

Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants.

BACKGROUND: Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. METHODS: In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. RESULTS: Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. CONCLUSIONS: When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12613000303741 .).

Optimal detection of clinically relevant mutations in colorectal carcinoma: sample pooling overcomes intra-tumoral heterogeneity.

Intra-tumoral genomic heterogeneity is a well-established biologic property of human malignancies with emerging roles in cancer progression and therapy resistance. However, its impact on the clinical utility of genomic testing in patient management remains unclear. Furthermore, best practices to account for heterogeneity in the provision of highly accurate, clinically valid molecular testing have yet to be firmly established. Genomic biomarkers for the management of colorectal carcinoma are both well-established (ie, KRAS, NRAS) and emerging (BRAF, PIK3CA, and others) in respect to therapy selection and clinical trial eligibility. Critically, standard colorectal carcinoma management requires the exclusion of KRAS and NRAS mutations; thus optimal procedures to control for potential intra-tumoral heterogeneity are clinically important. Here, we assessed heterogeneity among three intra-tumoral sites within 99 colorectal carcinomas cases on a CLIA-validated oncology next generation sequencing assay and examined whether a pooling strategy overcame any discordant results. Overall, 11% of cases demonstrated discordant mutation results between sites; 2% of cases were discrepant for mutations within RAS genes while the remainder was discrepant in PIK3CA. Half of the discrepant cases were associated with borderline tumor cellularity assessment. Further, a sample pooling strategy across all three sites successfully detected the relevant mutation in all but one case. Our results indicate that intra-tumoral genomic heterogeneity of clinically relevant genes within colorectal carcinoma is a relatively infrequent occurrence and that a simple strategy to pool DNA from several tumor sites with adequate cellularity minimizes the risk of false negative results even further to ensure optimal patient management.

High-flow nasal cannulae in very preterm infants after extubation.

BACKGROUND: The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation. However, data on the efficacy or safety of such cannulae in this population are lacking. METHODS: In this multicenter, randomized, noninferiority trial, we assigned 303 very preterm infants to receive treatment with either high-flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment failure within 7 days. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the margin of noninferiority was 20 percentage points. Infants in whom treatment with high-flow nasal cannulae failed could be treated with nasal CPAP; infants in whom nasal CPAP failed were reintubated. RESULTS: The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). Almost half the infants in whom treatment with high-flow nasal cannulae failed were successfully treated with CPAP without reintubation. The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01), but there were no significant differences in rates of serious adverse events or other complications. CONCLUSIONS: Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.).

Subgaleal haemorrhage in the newborn: A call for early diagnosis and aggressive management.

Subgaleal haemorrhage (SGH) is an important cause of preventable morbidity and mortality in the neonate. Its increased prevalence in recent years has coincided with the rise in the number of births assisted by vacuum extraction. Three deaths in Australia within the last 7 years have been the subject of two coronial inquests. Subsequent coronial reports have highlighted that neonatal death from SGH can be prevented if appropriate attention is paid to identification of risk factors, early diagnosis, close observation and aggressive treatment. To prevent unnecessary deaths, all involved in the care of the baby after birth need to be aware of the importance of prompt diagnosis, monitoring and early treatment of SGH.

Determination of umbilical venous catheter tip position with radiograph.

OBJECTIVES: To compare the cardiac silhouette method with the vertebral body method in predicting the umbilical venous catheter tip position on ultrasound; to measure the length of the target zone for the umbilical venous catheter tip; and to determine the time taken for a neonatologist to ascertain position of the umbilical venous catheter tip with ultrasound. DESIGN: Prospective cohort study. SETTING: Neonatal ICU. PATIENTS: Newborn infants with an umbilical venous catheter. INTERVENTIONS: Ultrasound scans to determine the umbilical venous catheter tip position were performed within an hour of corresponding anteroposterior chest-abdominal radiograph. MEASUREMENTS AND MAIN RESULTS: Two hundred paired radiograph and ultrasound scans in 82 newborn infants were analyzed. Each radiograph was reviewed independently by an experienced neonatologist who recorded the position of the umbilical venous catheter tip by vertebral level and by the cardiac silhouette method. For each method, the sensitivity, specificity, and positive and negative predictive values were calculated for the prediction of the true position of the catheter tip on ultrasound. The umbilical venous catheter tip was well positioned in just 28 of 200 scans. The cardiac silhouette method was superior to the vertebral level method for all test variables, with a sensitivity and specificity of 86% and 94% compared with 61% and 74%. The length of the target zone approximates to a single T8 vertebral body height on radiograph. CONCLUSIONS: For radiograph and ultrasound scans performed within an hour of each other, the cardiac silhouette method more accurately predicts umbilical venous catheter tip than vertebral body level and methods described in previous studies. Catheters are frequently malpositioned. The length of the target zone for optimal umbilical venous catheter tip position is short. Ultrasound assessment of umbilical venous catheter tip position is quick.

Prevalence and outcomes of laser treatment of aggressive posterior retinopathy of prematurity.

BACKGROUND: To describe outcomes in a cohort of extremely premature infants treated for aggressive posterior retinopathy of prematurity by diode laser panretinal photocoagulation. DESIGN: Retrospective study. PARTICIPANTS: Fifteen eyes in eight infants. METHODS: A review was carried out on infants between 23 and 25.6 weeks gestational age admitted to The Royal Brisbane and Women's Hospital neonatal intensive care unit between 1992 and 2009. MAIN OUTCOME MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: Five hundred fifty-four infants were admitted to neonatal intensive care unit, 373 survived till screening, and 304 had retinopathy of prematurity. Sixty-six infants required treatment, and eight of these had aggressive posterior retinopathy of prematurity (2.5% of all infants with retinopathy of prematurity). Mean gestational age was 24.2 weeks, mean birthweight was 634 g, and treatment occurred at mean 34.1 weeks post-menstrual age. The mean total number of burns per eye was 2967. Five of 15 treated eyes required retreatment. Two patients subsequently died of unrelated causes. Regression occurred in 9 of 11 remaining eyes; one eye progressed to stage 4b and another to stage 5 retinopathy of prematurity. Vitrectomy was performed in two eyes. Five eyes had 6/12 vision, one had 3/60, and three had no perception of light. Of the remaining two eyes, one had good fixation and the other had poor fixation. CONCLUSIONS: Despite good structural outcomes, visual outcomes for conventional laser treatment of aggressive posterior retinopathy of prematurity are poor.

Pediatric acute liver failure: etiology, outcomes, and the role of serial pediatric end-stage liver disease scores.

To describe etiology, short-term outcomes and prognostic accuracy of serial PELD scores in PALF. Retrospective analysis of children aged ≤16 yr, admitted with PALF under the QLTS, Brisbane, Australia, between 1991 and 2011. PELD-MELD scores were ascertained at three time points (i) admission (ii), meeting PALF criteria, and (iii) peak value. Fifty-four children met criteria for PALF, median age 17 months (1 day-15.6 yr) and median weight 10.2 kg (1.9-57 kg). Etiology was known in 69%: 26% metabolic, 15% infective, 13% drug-induced, 6% autoimmune, and 9% hemophagocytic lymphohistiocytosis. Age <3 months and weight <4.7 kg predicted poor survival in non-transplanted children. Significant independent predictors of poor outcome (death or LT) were peak bilirubin > 220 µm/L and peak INR > 4. Serial PELD-MELD scores were higher in the 17 (32%) transplant recipients (mean: [i] 26.8, [ii] 31.8, [iii] 42.6); highest in the 12 (22%) non-transplanted non-survivors (mean: [i] 31.6, [ii] 37.2, [iii] 45.7) compared with the 25 (46%) transplant-free survivors (mean: [i] 25.3, [ii] 26.0, [iii] 30.3). PELD-MELD thresholds of ≥27 and ≥42 at (ii) meeting PALF criteria and (iii) peak predicted poor outcome (p < 0.001). High peak bilirubin and peak INR predict poor outcome and serial PELD-MELD is superior to single admission PELD-MELD score for predicting poor outcome.

Risk determinants in early intervention use during the first postnatal year in children born very preterm.

BACKGROUND: Early interventions (EI) are recognised for their potential risk-reduction capacity. Although developmental delay is common in children born very preterm reports continue to suggest poor uptake of EI services. This study examined the risk determinants of EI in Australian children born less than 32 weeks gestation during the first year of life. METHODS: As part of a multi-centre-randomised-trial, 195 children were prospectively studied during their first year of life and EI use, type of follow-up, perinatal, social and parental psychosocial risk factors were collected using questionnaires. Child neurodevelopmental disability-status was assessed at 12-months (cerebral palsy, blind, deaf, developmental quotient 1 standard deviation (SD) below mean). The associations between EI and variables were examined using Pearson's chi-squared test (χ2) and regression techniques. RESULTS: A total of 55% of children received EI, 51% attended post discharge neonatal intensive care unit (NICU) and the remainder attended exclusive primary health care. Risk factors included, 50% perinatal, 19% social and 34% psychosocial and at 12-months 23% were categorised as disabled. Low social risk and NICU follow-up attendance were significantly associated with EI use but only perinatal risk (OR 3.1, 95% CI 1.7, 5.6, p = <0.01) and disability (OR 2.2, 95% CI 1.1, 4.7, p = 0.04) independently predicted EI use. CONCLUSIONS: It is reassuring that children with perinatal risk receive EI, opportunity remains to improve EI uptake in families with social and parental psychosocial risk during the first year of life.

Treatment of retinopathy of prematurity in extremely premature infants over an 18-year period.

BACKGROUND: To report the efficacy of laser diode therapy in the treatment of retinopathy of prematurity (ROP) in extremely premature (EP) infants over an 18-year period. DESIGN: Retrospective study. PARTICIPANTS: One hundred twenty-eight eyes in 66 infants treated between 23 and 25.6 weeks. METHODS: Five hundred fifty-four infants between 23 and 25.6 weeks gestational age (GA) were admitted to The Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit (NICU) between 1992 and 2009. Three hundred seventy-three patients survived to undergo screening, 304 were diagnosed with ROP, and 66 infants required diode laser therapy. MAIN OUTCOME MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: One hundred twenty-eight eyes from 66 infants (18.8% of those screened) underwent laser treatment with a mean GA of 24.3 weeks and mean birth weight of 711.4g. Fifty-six eyes were treated at pre-threshold disease, and 72 eyes at threshold disease. Over the study period, the number of laser spots and regression rate of ROP increased, while the frequency of re-treatment decreased. At 40 weeks, 119 eyes had regressed ROP (93%), two advanced to stage 4a, three to stage 4b and four to stage 5. Aggressive posterior ROP (AP-ROP) occurred in 15 eyes (11.7% of those treated). Forty-three patients (65%) were followed up for a mean of 56.5 months. The number of laser spots correlated well with subsequent refractive error but poorly with corrected visual acuity. CONCLUSIONS: In EP infants, laser diode therapy is an effective technique to halt the progression of ROP in most cases. AP-ROP is uncommon, even in this subgroup of extremely premature infants.

Sex-specific effects of CD248 on metabolism and the adipose tissue lipidome.

Cd248 has recently been associated with adipose tissue physiology, demonstrated by reduced weight gain in high fat diet-fed mice with genetic deletion of Cd248 relative to controls. Here we set out to determine the metabolic consequences of loss of Cd248. Strikingly, we find these to be sex specific; By subjecting Cd248-/- and Cd248+/+ mice to a high fat diet and indirect calorimetry study, we identified that only male Cd248-/- mice show reduced weight gain compared to littermate control wildtype mice. In addition, male (but not female) mice showed a lower respiratory exchange ratio on both chow and high fat diets, indicating a predisposition to metabolise lipid. Lipidomic studies on specific fat depots found reduced triglyceride and diglyceride deposition in male Cd248-/- mice, and this was supported by reduced expression of lipogenic and adipogenic genes. Finally, metabolomic analysis of isolated, differentiated preadipocytes found alterations in metabolic pathways associated with lipid deposition in cells isolated from male, but not female, Cd248-/- mice. Overall, our results highlight the importance of sex controls in animal studies and point to a role for Cd248 in sex- and depot-specific regulation of lipid metabolism.

NAD depletion mediates cytotoxicity in human neurons with autophagy deficiency.

Autophagy is a homeostatic process critical for cellular survival, and its malfunction is implicated in human diseases including neurodegeneration. Loss of autophagy contributes to cytotoxicity and tissue degeneration, but the mechanistic understanding of this phenomenon remains elusive. Here, we generated autophagy-deficient (ATG5-/-) human embryonic stem cells (hESCs), from which we established a human neuronal platform to investigate how loss of autophagy affects neuronal survival. ATG5-/- neurons exhibit basal cytotoxicity accompanied by metabolic defects. Depletion of nicotinamide adenine dinucleotide (NAD) due to hyperactivation of NAD-consuming enzymes is found to trigger cell death via mitochondrial depolarization in ATG5-/- neurons. Boosting intracellular NAD levels improves cell viability by restoring mitochondrial bioenergetics and proteostasis in ATG5-/- neurons. Our findings elucidate a mechanistic link between autophagy deficiency and neuronal cell death that can be targeted for therapeutic interventions in neurodegenerative and lysosomal storage diseases associated with autophagic defect.

Incidence of retinopathy of prematurity in extremely premature infants over an 18-year period.

BACKGROUND: To report the incidence of retinopathy of prematurity (ROP) in a subgroup of extremely premature infants admitted to an Australian tertiary centre over an 18-year period. DESIGN: Retrospective study. Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit. PARTICIPANTS: Five hundred and fifty-four infants admitted between 23 and 25.6 weeks gestational age (GA). METHODS: The 18-year study was divided into three 6-year periods for analysis: period 1 (1992-1997), period 2 (1998-2003) and period 3 (2004-2009). Infants were compared based on their week of GA and by the study period in which they were born. MAIN OUTCOME MEASURES: GA, birthweight, incidence and severity of ROP. RESULTS: Three hundred seventy-three (67.3%) infants survived until ROP screening, and 351 (63.4%) survived until discharge. ROP incidence increased from 78.2% in period 1 to 86.1% in period 3. Over the entire study, 90.5% of 23-week GA infants had ROP compared with 89.7% of 24-week GA infants and 76.1% of 25-week GA infants. Mean birthweight was significantly lower in infants with any ROP (725.1 g) and ROP of at least stage 3 (720.8 g) compared with infants without ROP (806.5 g) (P < 0.0001). Twenty-three-week GA infants had more severe ROP (28.6%) than 24 weeks (18.3%) and 25 weeks GA (11.9%). CONCLUSIONS: There has been increased survival and incidence of ROP in extremely premature infants over the past 20 years. Lower birthweight and GA are both associated with higher incidence and more severe ROP.

Five new species and new records of caddisflies (Insecta: Trichoptera) from Australias Top End.

Five new species of caddisflies are described from the Top End of the Northern Territory, three in the family EcnomidaeEcnomina radonica sp. nov., Neboissomina topendica sp. nov., Wellsomina tamoides sp. nov.and two in PolycentropodidaePolyplectropus bamboosa sp. nov. and P. berryensis sp. nov. Four of these new species are endemic to the Top End, P. berryensis sp. nov. is also recorded from northern Western Australia. In addition, first reports are given for the Top End for two previously described species, one each in genera Ecnomus McLachlan and Wellsomina Cartwright, and new records are given for eighteen species of Ecnomus McLachlan, one further species of Ecnomina Kimmins and Neboissomina Cartwright, and six species of Wellsomina Cartwright (all Ecnomidae), four species of Nyctiophylax Brauer (Polycentropodidae), and Tinodes radona Neboiss (Psychomyiidae). Finally, one male (and three females) of Hyalopsyche disjuncta Neboiss (Dipseudopsidae) are recorded from the Northern Territory, the first adult specimens of this species found outside northeastern Queensland.

Association of Amount of Weight Lost After Bariatric Surgery With Intracranial Pressure in Women With Idiopathic Intracranial Hypertension.

BACKGROUND AND OBJECTIVES: The idiopathic intracranial hypertension randomized controlled weight trial (IIH:WT) established that weight loss through bariatric surgery significantly reduced intracranial pressure when compared with a community weight management intervention. This substudy aimed to evaluate the amount of weight loss required to reduce intracranial pressure and to explore the effect of different bariatric surgical approaches. METHODS: IIH:WT was a multicenter randomized controlled trial. Adult women with active idiopathic intracranial hypertension and a body mass index ≥35 kg/m2 were randomized to bariatric surgery or a community weight management intervention (1:1). This per-protocol analysis evaluated the relationship between intracranial pressure, weight loss, and the weight loss methods. A linear hierarchical regression model was used to fit the trial outcomes, adjusted for time, treatment arm, and weight. RESULTS: Sixty-six women were included, of whom 23 had received bariatric surgery by 12 months; the mean age was 31 (SD 8.7) years in the bariatric surgery group and 33.2 (SD 7.4) years in the dietary group. Baseline weight and intracranial pressure were similar in both groups with a mean weight of 119.5 (SD 24.1) and 117.9 (SD 19.5) kg and mean lumbar puncture opening pressure of 34.4 (SD 6.3) and 34.9 (SD 5.3) cmCSF in the bariatric surgery and dietary groups, respectively. Weight loss was significantly associated with reduction in intracranial pressure (R2 = 0.4734, p ≤ 0.0001). Twenty-four percentage of weight loss (weight loss of 13.3 kg [SD 1.76]) was associated with disease remission (intracranial pressure [ICP] ≤ 25 cmCSF). Roux-en-Y gastric bypass achieved greater, more rapid, and sustained ICP reduction compared with other methods. DISCUSSION: The greater the weight loss, the greater the reduction in ICP was documented. Twenty four percentage of weight loss was associated with disease remission. Such magnitude of weight loss was unlikely to be achieved without bariatric surgery, and hence, consideration of referral to a bariatric surgery program early for those with active idiopathic intracranial hypertension may be appropriate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02124486; ISRCTN registry number ISRCTN40152829; doi.org/10.1186/ISRCTN40152829. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that weight loss after bariatric surgery results in reduction in intracranial pressure in adult women with idiopathic intracranial hypertension. This study is Class II because of the use of a per-protocol analysis.

First records of Trichoptera from Timor-Leste, including seven newly described species.

Several collections of adults of the caddisfly order Trichoptera were studied from Timor-Leste, the nation-state comprising the eastern region of the island of Timor. The specimens represent ten families: Hydrobiosidae (2 species), Glossosomatidae (1 species), Hydroptilidae (3 species), Philopotamidae (5 species), Hydropsychidae (3 species), Polycentropodidae (1 species), Psychomyiidae (3 species), Xiphocentronidae (1 species), Lepidostomatidae (1 species), Leptoceridae (3 species). Among the 24 species listed, 16 were identified as established Southeast Asian species. Among these are two very widespread species, one extending further east to New Guinea, northern Australia, and New Caledonia and another that was described from Fiji. An additional seven species are newly described here: Ulmerochorema hatubuilico sp. nov., Hydroptila bellisi sp. nov. and H. aileuensis sp. nov., Chimarra lawaliu sp. nov., C. multidentata sp. nov., C. sameana sp. nov. and C. timorensis sp. nov. Hitherto, the genus Ulmerochorema Mosely was believed to be an Australian endemic. A xiphocentronid specimen could be identified to genus Drepanocentron only.

Gentamicin Dosing in Neonates with Normal Renal Function: Trough and Peak Levels.

BACKGROUND AND OBJECTIVE: Gentamicin is commonly used in neonates, and it requires drug concentration monitoring. The objective of this study was to determine the extent of high trough (≥ 2 mg/l) and therapeutic peak serum gentamicin concentrations (5-12 mg/l) using our current gentamicin regimen and to adjust the dosing regimen accordingly and reassess. METHODS: This was a prospective cohort study of neonates, with normal renal function, who were prescribed gentamicin. Group 1: March 2014-July 2017-gentamicin intravenous (IV) 2.5 mg/kg given every 36 h if < 30 weeks gestational age (GA) and every 24 h if ≥ 30 weeks GA; Group 2: August 2019-February 2020-gentamicin IV 3.5 mg/kg given every 36 h if < 30 weeks GA and every 24 h if ≥ 30 weeks GA. We assessed the number of neonates with aberrant trough and peak serum gentamicin concentrations. RESULTS: Forty-eight neonates < 30 weeks GA and 34 ≥ 30 weeks GA were given 2.5 mg/kg gentamicin. Eleven (23%) neonates < 30 weeks GA and four (13%) ≥ 30 weeks GA had subtherapeutic peak concentrations (< 5 mg/l); none had supratherapeutic (> 12 mg/l) or toxic trough concentrations (≥ 2 mg/l). Forty-four neonates < 30 weeks GA and 54 ≥ 30 weeks GA were given 3.5 mg/kg gentamicin. Eighty-four (86%) had non-toxic trough concentrations (< 2 mg/l). One (1%) < 30 weeks GA neonate had subtherapeutic (< 5 mg/l) and one (1%) neonate ≥ 30 weeks GA had supratherapeutic (> 12 mg/l) peak concentrations. CONCLUSIONS: Gentamicin regimen of 2.5 mg/kg given every 36 h for neonates < 30 weeks GA and every 24 h for neonates ≥ 30 weeks GA was suboptimal at achieving therapeutic gentamicin peak. Increasing the dosage to 3.5 mg/kg achieved therapeutic peak concentrations in 98% and non-toxic trough concentrations in 86% of all neonates (prior to dose interval adjustment).

Nicotinamide riboside has minimal impact on energy metabolism in mouse models of mild obesity.

Supplementation with precursors of NAD has been shown to prevent and reverse insulin resistance, mitochondrial dysfunction, and liver damage in mouse models of diet-induced obesity. We asked whether the beneficial effects of supplementation with the NAD precursor nicotinamide riboside (NR) are dependent on mouse strain. We compared the effects of NR supplementation on whole-body energy metabolism and mitochondrial function in mildly obese C57BL/6N and C57BL/6J mice, two commonly used strains to investigate metabolism. Male C57BL/6N and C57BL/6J mice were fed a high-fat diet (HFD) or standard chow with or without NR supplementation for 8 weeks. Body and organ weights, glucose tolerance, and metabolic parameters as well as mitochondrial O2 flux in liver and muscle fibers were assessed. We found that NR supplementation had no influence on body or organ weight, glucose metabolism or hepatic lipid accumulation, energy expenditure, or metabolic flexibility but increased mitochondrial respiration in soleus muscle in both mouse strains. Strain-dependent differences were detected for body and fat depot weight, fasting blood glucose, hepatic lipid accumulation, and energy expenditure. We conclude that, in mild obesity, NR supplementation does not alter metabolic phenotype in two commonly used laboratory mouse strains.

Effectiveness of Bariatric Surgery vs Community Weight Management Intervention for the Treatment of Idiopathic Intracranial Hypertension: A Randomized Clinical Trial.

Importance: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse. Objective: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the treatment of patients with active IIH. Design, Setting, and Participants: This 5-year randomized clinical trial (Idiopathic Intracranial Hypertension Weight Trial) enrolled women with active IIH and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or higher at 5 National Health Service hospitals in the UK between March 1, 2014, and May 25, 2017. Of 74 women assessed for eligibility, 6 did not meet study criteria and 2 declined to participate; 66 women were randomized. Data were analyzed from November 1, 2018, to May 14, 2020. Interventions: Bariatric surgery (n = 33) or CWM intervention (Weight Watchers) (n = 33). Main Outcomes and Measures: The primary outcome was change in intracranial pressure measured by lumbar puncture opening pressure at 12 months, as assessed in an intention-to-treat analysis. Secondary outcomes included lumbar puncture opening pressure at 24 months as well as visual acuity, contrast sensitivity, perimetric mean deviation, and quality of life (measured by the 36-item Short Form Health Survey) at 12 and 24 months. Because the difference in continuous outcomes between groups is presented, the null effect was at 0. Results: Of the 66 female participants (mean [SD] age, 32.0 [7.8] years), 64 (97.0%) remained in the clinical trial at 12 months and 54 women (81.8%) were included in the primary outcome analysis. Intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -6.0 [1.8] cm cerebrospinal fluid [CSF]; 95% CI, -9.5 to -2.4 cm CSF; P = .001) and at 24 months (adjusted mean [SE] difference, -8.2 [2.0] cm CSF; 95% CI, -12.2 to -4.2 cm CSF; P < .001) compared with the CWM arm. In the per protocol analysis, intracranial pressure was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -7.2 [1.8] cm CSF; 95% CI, -10.6 to -3.7 cm CSF; P < .001) and at 24 months (adjusted mean [SE] difference, -8.7 [2.0] cm CSF; 95% CI, -12.7 to -4.8 cm CSF; P < .001). Weight was significantly lower in the bariatric surgery arm at 12 months (adjusted mean [SE] difference, -21.4 [5.4] kg; 95% CI, -32.1 to -10.7 kg; P < .001) and at 24 months (adjusted mean [SE] difference, -26.6 [5.6] kg; 95% CI, -37.5 to -15.7 kg; P < .001). Quality of life was significantly improved at 12 months (adjusted mean [SE] difference, 7.3 [3.6]; 95% CI, 0.2-14.4; P = .04) and 24 months (adjusted mean [SE] difference, 10.4 [3.8]; 95% CI, 3.0-17.9; P = .006) in the bariatric surgery arm. Conclusions and Relevance: In this randomized clinical trial, bariatric surgery was superior to a CWM intervention in lowering intracranial pressure. The continued improvement over the course of 2 years shows the impact of this intervention with regard to sustained disease remission. Trial Registration: ClinicalTrials.gov Identifier: NCT02124486.