Survival following lung volume reduction procedures: results from the UK Lung Volume Reduction (UKLVR) registry.

INTRODUCTION: Lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement can produce substantial benefits in appropriately selected people with emphysema. The UK Lung Volume Reduction (UKLVR) registry is a national multicentre observational study set up to support quality standards and assess outcomes from LVR procedures at specialist centres across the UK. METHODS: Data were analysed for all patients undergoing an LVR procedure (LVRS/EBV) who were recruited into the study at participating centres between January 2017 and June 2022, including; disease severity and risk assessment, compliance with guidelines for selection, procedural complications and survival to February 2023. RESULTS: Data on 541 patients from 14 participating centres were analysed. Baseline disease severity was similar in patients who had surgery n=244 (44.9%), or EBV placement n=219 (40.9%), for example, forced expiratory volume in 1 s (FEV1) 32.1 (12.1)% vs 31.2 (11.6)%. 89% of cases had discussion at a multidisciplinary meeting recorded. Median (IQR) length of stay postprocedure for LVRS and EBVs was 12 (13) vs 4 (4) days(p=0.01). Increasing age, male gender and lower FEV1%predicted were associated with mortality risk, but survival did not differ between the two procedures, with 50 (10.8%) deaths during follow-up in the LVRS group vs 45 (9.7%) following EBVs (adjusted HR 1.10 (95% CI 0.72 to 1.67) p=0.661) CONCLUSION: Based on data entered in the UKLVR registry, LVRS and EBV procedures for emphysema are being performed in people with similar disease severity and long-term survival is similar in both groups.

Pooling sputum samples for Xpert® MTB/RIF and Xpert® Ultra testing for TB diagnosis.

BACKGROUND: The use of molecular amplification as-says for TB diagnosis is limited by their costs and cartridge stocks. Pooling multiple samples to test them together is reported to have similar accuracy to individual testing and to save costs. METHODS: Two surveys of individuals with presumptive TB were conducted to assess the performance of pooled testing using Xpert® MTB/RIF (MTB/RIF) and Xpert® Ultra (Ultra). RESULTS: A total of 500 individuals were tested using MTB/RIF, with 72 (14.4%) being MTB-positive. The samples were tested in 125 pools, with 50 pools having ⩾1 MTB-positive and 75 only MTB-negative samples: 46/50 (92%, 95% CI 80.8-97.8) MTB-positive pools tested MTB-positive and 71/75 (94.7%, 95% CI 86.9-98.5) MTB-negative pools tested MTB-negative in the pooled test (agreement: 93.6%, κ = 0.867). Five hundred additional samples were tested using Ultra, with 60 (12%) being MTB-positive. Samples were tested in 125 pools, with 42 having ⩾1 MTB-positive and 83 only MTB-negative samples: 35/42 (83.6%, 95% CI 68.6-93.0) MTB-positive pools tested MTB-positive and 82/83 (98.8%, 95% CI 93.5-100.0) MTB-negative pools tested MTB-negative in the pooled test (agreement: 93.6%, κ = 0.851; P > 0.1 between individual and pooled testing). Pooled testing saved 35% (MTB/RIF) and 46% (Ultra) of cartridges. CONCLUSIONS: Pooled and individual testing has a high level of agreement and improves testing efficiency.

CONTEXTE: Le coût et les stocks de cartouches des tests d'amplification moléculaire limitent leur utilisation pour le diagnostic de la TB. Regrouper plusieurs échantillons afin de les tester en même temps aurait une précision similaire à celle des tests individuels et permettrait de réaliser des économies. MÉTHODES: Deux enquêtes ont été menées auprès de personnes avec une TB présumée afin d'évaluer la performance des tests groupés en utilisant le test Xpert® MTB/RIF (MTB/RIF) et le test Xpert® Ultra (Ultra). RÉSULTATS: Au total, 500 personnes ont été testées par test MTB/RIF, dont 72 (14,4%) étaient MTB-positives. Les échantillons ont été testés dans 125 groupes, dont 50 groupes avaient ⩾1 échantillons MTB-positifs et 75 uniquement des échantillons MTB-négatifs : 46/50 (92% ; IC 95% 80,8­97,8) groupes MTB-positifs ont été testés MTB-positifs et 71/75 (94,7% ; IC 95% 86,9­98,5) groupes MTB-négatifs ont été testés MTB-négatifs dans le test groupé (concordance : 93,6% ; κ = 0,867). Cinq cents échantillons supplémentaires ont été testés par test Ultra, dont 60 (12%) étaient MTB-positifs. Les échantillons ont été testés dans 125 groupes, dont 42 avaient ⩾1 échantillons MTB-positifs et 83 uniquement des échantillons MTB-négatifs : 35/42 (83,6% ; IC 95% 68,6­93,0) groupes MTB-positifs ont été testés MTB-positifs et 82/83 (98,8% ; IC 95% 93,5­100,0) groupes MTB-négatifs ont été testés MTB-négatifs dans le test groupé (concordance : 93,6% ; κ = 0,851 ; P > 0,1 entre les tests individuels et groupés). Les tests groupés ont permis d'économiser 35% (MTB/RIF) et 46% (Ultra) des cartouches. CONCLUSIONS: Les tests groupés et individuels présentent un niveau élevé de concordance et améliorent l'efficacité des tests.

Understanding the impact of barriers to onward migration; a novel approach using translocated fish.

River catchments worldwide are heavily fragmented by anthropogenic barriers, reducing their longitudinal connectivity and contributing to the decline of migratory fish populations. Direct impacts of individual barriers on migratory fish are well-established, but barrier impacts on onward migration are poorly understood, despite their relevance to evidence-based, catchment-scale, management of threatened species. This study investigated the upstream spawning migration of 352 acoustic tagged river lamprey (Lampetra fluviatilis), translocated upstream of two key barriers (R2: n = 60 & 59; R3: n = 59 & 52) compared to a control group (R1: n = 61 & 59), across two contrasting (dry and wet, n = 180 and 172) years in the River Yorkshire Ouse, England, to reveal the impact of barriers on the onward migration of upstream migrating fish. Release further upstream increased the degree of catchment penetration, with median distance upstream of R1 56.1% and 68.6% greater for lamprey released at R2 and R3 respectively. Median delays at the two downstream-most main river barriers by the control group were 23.8 and 5.4 days (2018/19) and 9.3 and 11.4 days (2019/20). However, impacts of delay were only observed on the time to reach spawning habitat, time to reach final assumed spawning location and speed of movement in one upper catchment tributary during 2019/20 whilst they were only observed on time to reach spawning habitat during 2018/19 and on assumed spawning location distance during 2019/20 in the other. Ultimately, limited impacts of delay at barriers on onward fish migration post-passage were observed but median catchment penetration was increased with consecutive release upstream. This study demonstrated the importance of a true understanding of barrier impacts to inform catchment-wide planning, evidence vital for management worldwide. Although the findings of this study do support the use of trap and transport as a measure to remediate barrier impacts on migration, fish passage engineering improvements or barrier removal, at structures shown to be the most inhibiting to fish migration should be considered the best and most sustainable option to improve barrier passage.

Effects of pile driving sound playbacks and cadmium co-exposure on the early life stage development of the Norway lobster, Nephrops norvegicus.

There is an urgent need to understand how organisms respond to multiple, potentially interacting drivers in today's world. The effects of the pollutants anthropogenic sound (pile driving sound playbacks) and waterborne cadmium were investigated across multiple levels of biology in larval and juvenile Norway lobster, Nephrops norvegicus under controlled laboratory conditions. The combination of pile driving playbacks (170 dBpk-pk re 1 µPa) and cadmium combined synergistically at concentrations >9.62 µg[Cd] L-1 resulting in increased larval mortality, with sound playbacks otherwise being antagonistic to cadmium toxicity. Exposure to 63.52 µg[Cd] L-1 caused significant delays in larval development, dropping to 6.48 µg[Cd] L-1 in the presence of piling playbacks. Pre-exposure to the combination of piling playbacks and 6.48 µg[Cd] L-1 led to significant differences in the swimming behaviour of the first juvenile stage. Biomarker analysis suggested oxidative stress as the mechanism resultant deleterious effects, with cellular metallothionein (MT) being the predominant protective mechanism.

A large West Antarctic Ice Sheet explains early Neogene sea-level amplitude.

Early to Middle Miocene sea-level oscillations of approximately 40-60 m estimated from far-field records1-3 are interpreted to reflect the loss of virtually all East Antarctic ice during peak warmth2. This contrasts with ice-sheet model experiments suggesting most terrestrial ice in East Antarctica was retained even during the warmest intervals of the Middle Miocene4,5. Data and model outputs can be reconciled if a large West Antarctic Ice Sheet (WAIS) existed and expanded across most of the outer continental shelf during the Early Miocene, accounting for maximum ice-sheet volumes. Here we provide the earliest geological evidence proving large WAIS expansions occurred during the Early Miocene (~17.72-17.40 Ma). Geochemical and petrographic data show glacimarine sediments recovered at International Ocean Discovery Program (IODP) Site U1521 in the central Ross Sea derive from West Antarctica, requiring the presence of a WAIS covering most of the Ross Sea continental shelf. Seismic, lithological and palynological data reveal the intermittent proximity of grounded ice to Site U1521. The erosion rate calculated from this sediment package greatly exceeds the long-term mean, implying rapid erosion of West Antarctica. This interval therefore captures a key step in the genesis of a marine-based WAIS and a tipping point in Antarctic ice-sheet evolution.

Computational polarized Raman microscopy on sub-surface nanostructures with sub-diffraction-limit resolution.

Raman microscopy with resolution below the diffraction limit is demonstrated on sub-surface nanostructures. Unlike most other modalities for nanoscale measurements, our approach is able to image nanostructures buried several microns below the sample surface while still extracting details about the chemistry, strain, and temperature of the nanostructures. In this work, we demonstrate that combining polarized Raman microscopy adjusted to optimize edge enhancement effects and nanostructure contrast with fast computational deconvolution methods can improve the spatial resolution while preserving the flexibility of Raman microscopy. The cosine transform method demonstrated here enables significant computational speed-up from O(N3) to O(Nlog N) - resulting in computation times that are significantly below the image acquisition time. CMOS poly-Si nanostructures buried below 0.3 - 6 µm of complex dielectrics are used to quantify the performance of the instrument and the algorithm. The relative errors of the feature sizes, the relative chemical concentrations and the fill factors of the deconvoluted images are all approximately 10% compared with the ground truth. For the smallest poly-Si feature of 230 nm, the absolute error is approximately 25 nm.

Photonic Readout of Superconducting Nanowire Single Photon Counting Detectors.

Scalable, low power, high speed data transfer between cryogenic (0.1-4 K) and room temperature environments is essential for the realization of practical, large-scale systems based on superconducting technologies. A promising approach to overcome the limitations of conventional wire-based readout is the use of optical fiber communication. Optical fiber presents a 100-1,000x lower heat load than conventional electrical wiring, relaxing the requirements for thermal anchoring, and is also immune to electromagnetic interference, which allows routing of sensitive signals with improved robustness to noise and crosstalk. Most importantly, optical fibers allow for very high bandwidth densities (in the Tbps/mm2 range) by carrying multiple signals through the same physical fiber (Wavelength Division Multiplexing, WDM). Here, we demonstrate for the first time optical readout of a superconducting nanowire single-photon detector (SNSPD) directly coupled to a CMOS photonic modulator, without the need for an interfacing device. By operating the modulator in the forward bias regime at a temperature of 3.6 K, we achieve very high modulation efficiency (1,000-10,000 pm/V) and a low input impedance of 500 Ω with a low power dissipation of 40 µW. This allows us to obtain optical modulation with the low, millivolt-level signal generated by the SNSPD.

Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292.

Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma.

BACKGROUND: Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma. METHODS: Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs). RESULTS: Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis. CONCLUSION: Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment.

The characterisation of overweight and obese women who are under reporting energy intake during pregnancy.

BACKGROUND: Misreporting of energy intake is common and can contribute to biased estimates of the relationship between diet and disease. Energy intake misreporting is poorly understood in pregnancy and there is limited research assessing characteristics of women who misreport energy intake or changes in misreporting of energy intake across pregnancy. METHODS: An observational study in n = 945 overweight or obese pregnant women receiving standard antenatal care who participated in the LIMIT randomised trial. Diet, physical activity, psychological factors, body image satisfaction and dieting behaviour were assessed at trial entry (10-20 weeks gestation) and 36 weeks gestation. Energy misreporting status was assessed through the ratio of daily energy intake over basal metabolic rate. Logistic regression analyses were conducted with the dependent variable of under reporting of energy intake at study entry or 36 weeks in separate analysis. RESULTS: At study entry and 36 weeks, women were classified as under reporters (38 vs 49.4%), adequate reporters (59.7 vs 49.8%) or over reporters of energy intake (2.3 vs 0.8%) respectively. The prevalence of under reporting energy intake at 36 weeks was higher than at study entry (early pregnancy). Body mass index (BMI) at study entry and 36 weeks and socioeconomic status, dieting behaviour and risk of depression at 36 weeks were independent predictors of under reporting of energy intake. CONCLUSIONS: Under reporting of energy intake was present in over a third of overweight and obese pregnant women and was higher in late compared to early pregnancy. Characteristics such as BMI, socioeconomic status, past dieting behaviour and risk of depression may aid in identifying women who either require support in accurate recording of food intake or attention for improving diet quality. Results were unable to distinguish whether under reporting reflects misreporting or a true restriction of dietary intake. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12607000161426 , registered 9/3/2007.

The mediating effects of gestational diabetes on fetal growth and adiposity in women who are overweight and obese: secondary analysis of the LIMIT randomised trial.

OBJECTIVE: To describe the mediating effect of maternal gestational diabetes on fetal biometry and adiposity measures among overweight or obese pregnant women. DESIGN: Secondary analysis of the LIMIT randomised trial. SETTING: Public hospitals, metropolitan Adelaide, South Australia. POPULATION: Pregnant women with body mass index (BMI) ≥25 kg/m2 and singleton gestation. METHODS: Fetal ultrasound measures at 36 weeks of gestation and baseline BMI from women randomised to the LIMIT trial Standard Care group (n = 912 women) were used to conduct causal mediation analyses using regression-based methods. MAIN OUTCOMES MEASURES: Ultrasound measures of fetal biometry and adiposity at 36 weeks of gestation. RESULTS: Increased maternal BMI was associated with increased measures of fetal head circumference [direct (unmediated) effect 0.18 (95% CI: 0.05-0.31), P = 0.005; total effect 0.17 (95% CI: 0.02-0.31), P = 0.018], abdominal circumference [direct effect 0.26 (95% CI: 0.11-0.41), P = 0.001; total effect 0.26 (95% CI: 0.11-0.42), P = 0.001] and estimated fetal weight [direct effect 0.22 (95% CI: 0.08-0.35), P = 0.002; total effect 0.22 (95% CI: 0.08-0.35), P = 0.002], with no evidence of mediation by treated gestational diabetes. There was no apparent association between maternal BMI and fetal adiposity measures, or mediation by treated gestational diabetes. CONCLUSIONS: We show an important association between increased maternal BMI and fetal growth, not mediated by treated gestational diabetes. There was no association between increased maternal BMI and fetal adiposity measures, or mediation by treated gestational diabetes. Whether these findings represent 'saturation' in the effect of maternal BMI on fetal growth or the effect of treatment of GDM is unclear. FUNDING: This project was funded by a 4-year project grant from the National Health and Medical Research Council (NHMRC), Australia (ID 519240); The Channel 7 Children's Research Foundation, South Australia; and the US National Institutes of Health (R01 HL094235-01). TWEETABLE ABSTRACT: Increased fetal growth associated with maternal obesity is not mediated by gestational diabetes.

The influence of aquaculture unit proximity on the pattern of Lepeophtheirus salmonis infection of anadromous Salmo trutta populations on the isle of Skye, Scotland.

A total of 230 anadromous Salmo trutta (brown trout) were sampled in five sheltered coastal fjords (or sea lochs) on the Isle of Skye, Scotland, U.K., in 2016 at varying distances from active Atlantic salmon Salmo salar farms. Statistical models were developed to investigate potential correlations between salmon lice Lepeophtheirus salmonis burdens on S. trutta hosts and their proximity to S. salar farm cages. Significant correlations were found between lice burdens and fish fork length and proximity to the nearest S. salar farm. The probability of the presence of L. salmonis on fish hosts increased with fish host size and with distance from the nearest S. salar farm, but total lice burdens were highest in fish sampled near S. salar farms and decreased with distance. The proportion of different life-cycle stages of L. salmonis were also dependent on S. salar farm proximity, with higher juvenile lice numbers recorded at sites near S. salar farm cages. These results highlight the complexity of the relationship between S. trutta and L. salmonis infections on wild fish and emphasize the requirement of further research to quantify these effects to better inform conservation and management strategies, particularly in areas of active S. salar farm facilities.

Fetal middle cerebral artery Doppler to time intrauterine transfusion in red-cell alloimmunization: a randomized trial.

OBJECTIVES: To evaluate whether Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) for timing subsequent intrauterine transfusions (IUTs) in fetuses that had undergone one IUT for anemia secondary to red-cell alloimmunization is non-inferior to timing based on expected decrease in fetal hematocrit (Hct) or fetal hemoglobin level, without compromising infant hemoglobin at birth. METHODS: This was an international, pragmatic multicenter randomized controlled trial. Women with a pregnancy complicated by fetal anemia secondary to red-cell alloimmunization (due to any antibody alone or in combination), as indicated by the need to undergo a single IUT, were eligible for inclusion. Women were randomized to the determination of timing of further transfusion(s) by Doppler measurement of MCA-PSV (MCA-PSV Group), with a serial upward trend of values >1.5 multiples of the median considered indicative of the need for another IUT, or timing of transfusion by a decrease in fetal Hct (fetal Hct Group), with subsequent IUTs timed according to an estimated fall in fetal Hct of 1% per day or fetal hemoglobin of 0.3 g/dL per day, to maintain fetal hemoglobin level between 7 and 10 g/dL. The primary outcome was infant hemoglobin level measured at birth. RESULTS: A total of 71 women were randomized, 36 to the MCA-PSV Group and 35 to the fetal Hct Group. Median gestational age at randomization was 30.3 weeks, the majority of women were Caucasian and non-smokers, 9.9% of women had Kell alloimmunization, and 14% of fetuses were hydropic at their first IUT. No statistically significant differences between the two treatment groups were observed with regard to mean hemoglobin levels at birth (MCA-PSV Group, 10.36 ± 3.82 g/dL vs fetal Hct Group, 12.03 ± 3.14 g/dL; adjusted mean difference -1.56 g/dL (95% CI, -3.24 to 0.13 g/dL); P = 0.070), or the number of IUTs performed after randomization (MCA-PSV Group, 1.75 ± 1.79 vs fetal Hct Group 1.80 ± 1.32; adjusted relative risk 0.88 (95% CI, 0.61-1.26); P = 0.474). There was no statistically significant difference between the two groups with respect to the risk of adverse infant outcomes related to alloimmunization or procedure-related complications. CONCLUSION: Both Doppler measurement of MCA-PSV and estimation of the decrease in fetal Hct or hemoglobin can be used to determine the timing of second and subsequent IUTs in fetuses with red-cell alloimmunization. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Effectiveness of progesterone, cerclage and pessary for preventing preterm birth in singleton pregnancies: a systematic review and network meta-analysis.

BACKGROUND: Preterm birth (PTB) is the leading cause of infant death, but it is unclear which intervention is best to prevent it. OBJECTIVES: To compare progesterone, cerclage and pessary, determine their relative effects and rank them. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL and Web of Science (to April 2016), without restrictions, and screened references of previous reviews. SELECTION CRITERIA: We included randomised trials of progesterone, cerclage or pessary for preventing PTB in women with singleton pregnancies at risk as defined by each study. DATA COLLECTION AND ANALYSIS: We extracted data by duplicate using a piloted form and performed Bayesian random-effects network meta-analyses and pairwise meta-analyses. We rated evidence quality using GRADE, ranked interventions using SUCRA and calculated numbers needed to treat (NNT). MAIN RESULTS: We included 36 trials (9425 women; 25 low risk of bias trials). Progesterone ranked first or second for most outcomes, reducing PTB < 34 weeks [odds ratio (OR) 0.44; 95% credible interval (CrI) 0.22-0.79; NNT 9; low quality], <37 weeks (OR 0.58; 95% CrI 0.41-0.79; NNT 9; moderate quality), and neonatal death (OR 0.50; 95% CrI 0.28-0.85; NNT 35; high quality), compared with control, in women overall at risk. We found similar results in the subgroup with previous PTB, but only a reduction of PTB < 34 weeks in women with a short cervix. Pessary showed inconsistent benefit and cerclage did not reduce PTB < 37 or <34 weeks. CONCLUSIONS: Progesterone was the best intervention for preventing PTB in singleton pregnancies at risk, reducing PTB < 34 weeks, <37 weeks, neonatal demise and other sequelae. TWEETABLE ABSTRACT: Progesterone was better than cerclage and pessary to prevent preterm birth, neonatal death and more in network meta-analysis.

Immunohistochemical hENT1 expression as a prognostic biomarker in patients with resected pancreatic ductal adenocarcinoma undergoing adjuvant gemcitabine-based chemotherapy.

BACKGROUND: Human equilibrative nucleoside transporters (hENTs) are transmembranous proteins that facilitate the uptake of nucleosides and nucleoside analogues, such as gemcitabine, into the cell. The abundance of hENT1 transporters in resected pancreatic ductal adenocarcinoma (PDAC) might make hENT1 a potential biomarker of response to adjuvant chemotherapy. The aim of this study was to see whether hENT1 expression, as determined by immunohistochemistry, was a suitable predictive marker for subsequent treatment with gemcitabine-based adjuvant chemotherapy. METHODS: A systematic review was performed, searching databases from January 1997 to January 2016. Articles pertaining to hENT1 immunohistochemical analysis in resected PDAC specimens from patients who subsequently underwent adjuvant gemcitabine-based chemotherapy were identified. Eligible studies were required to contain survival data, reporting specifically overall survival (OS) and disease-free survival (DFS) with associated hazard ratios (HRs) stratified by hENT1 status. RESULTS: Of 42 articles reviewed, eight were suitable for review, with seven selected for quantitative meta-analysis. The total number of patients included in the meta-analysis was 770 (405 hENT1-negative, 365 hENT1-positive). Immunohistochemically detected hENT1 expression was significantly associated with both prolonged DFS (HR 0·58, 95 per cent c.i. 0·42 to 0·79) and OS (HR 0·52, 0·38 to 0·72) in patients receiving adjuvant gemcitabine but not those having fluoropyrimidine-based adjuvant therapy. CONCLUSION: Expression of hENT1 is a suitable prognostic biomarker in patients undergoing adjuvant gemcitabine-based chemotherapy.

Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis.

BACKGROUND: About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. OBJECTIVES: To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. SEARCH STRATEGY: We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. SELECTION CRITERIA: Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. MAIN RESULTS: We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64-1.05, seven studies, I2  36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52-0.98, four studies, I2  46%) and mechanical ventilation (RR 0.61, 95% CI 0.45-0.82, four studies, I2  22%). CONCLUSION: In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. TWEETABLE ABSTRACT: Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.