Preterm neonatal survival: what is the role of prognostic models?Elizabeth M McClure, PhD1Robert L Goldenberg, MD21Social, Statistical and Environmental Sciences, RTI International, Durham, NC2Columbia University, New York, NYEven before the 1960’s and the introduction of the specialty of neonatology, and continuing to the present, numerous efforts have been made to understand the relationship between newborn birthweight and the risk of mortality. (1) With the development of neonatal intensive care units (NICUs), attention to survival rates and neurologic outcomes among those at the lowest birthweights and gestational ages (GA) has grown. (2) Defining the lower limits of GA or birthweight associated with the neonatal outcomes is important for clinicians, families, and others to inform appropriate decision-making and clinical care.To predict newborn survival, numerous models have been developed to estimate risk at specific birthweights and/or GAs. To date, more than 35 have been published, almost exclusively from high-income countries with advanced NICU care. In a study published recently, van Beek et al sought to validate one of these predictive models from the United Kingdom (UK), deemed to be among the highest quality, with the objective of assessing its value for clinical use. (3)Van Beek et al used an independent Dutch population to validate survival among very preterm infants using the UK model’s parameters. Because they found relatively good performance, the authors’ concluded that the model could inform daily clinical practice. However, the generalizability of their results, especially to other populations differing by ethnicity or socioeconomic status, is questionable. The parameters for the model quality focused on birthweight, GA, and gender, but many other metrics (including the racial diversity, quality of care, etc.) were limited. In particular, the interventions available and utilized for obstetric and neonatal care were not specified, which would be important for their goal of clinical use of the model. Importantly, the quality of obstetric care is not considered. (4) Both the availability and quality of specific obstetric and neonatal interventions in any given setting may be among the most important factors impacting survival.Especially important for clinical considerations, long-term outcomes, including severe disabilities, were not addressed. Concerns about neurodevelopmental outcomes in infants at the lower limits of birthweight and GA are as or more important to parents and caregivers than survival. (5) It is thus unclear how this – or virtually any other model - can be useful for “daily clinical practice”.A better strategy to inform clinical care is for individual health-care facilities to maintain neonatal survival and neurological outcome statistics. These types of data within a specific context may be more helpful to physicians, including obstetricians and neonatologists, who often, together with parents and caregivers, make decisions related to interventions prior to delivery or during NICU care. Newborn outcomes, especially at the extreme lower limits of birthweight and GA, remains an area of intense interest. While models may provide some supportive information, it is difficult to imagine that these will ever replace clinical decisions informed by actual outcome data from the specific facility.Conflicts of interest: The authors declare no conflicts of interest.References:1. Goldenberg RL, Nelson KG, Dyer RL, Wayne JB. The variability of viability: the effect of physicians’ perceptions of viability on the survival of very low birth weight infants. Am J Obstet Gynecol 1982; 143:678-84.2. Bottoms SF, Paul RH, Mercer BM, MacPherson CA, Caritis SN, Moawad AW. Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants. Am J Obstet Gynecol. 1999 80(3 Pt 1):665-9.3. Van Beek P.E, Groenendaal F, Onland W, Koole S, Dijk PH, Dijkmanet KP et al. Prognostic model for predicting survival in very preterm infants: an external validation study. BJOG (in press)4. Goepfert AR, Goldenberg RL, Hauth JC, Bottoms SF, Iams JD, Mercer BM Obstetrical determinants of neonatal neurological morbidity in < or = 1000-gram infants. Am J Perinatol. 1999;16(1):33-42.5. Iams JD, Mercer BM. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. What we have learned about antenatal prediction of neonatal morbidity and mortality. Semin Perinatol 2003:247-52.

Mini commentary on BJOG-21-0823: Pregnancy outcomes in women with Budd-Chiari syndrome or portal vein thrombosis - A multicentre retrospective cohort study.Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) are rare thrombotic disorders which can affect females of reproductive age. Physiological changes in pregnancy may result in or exacerbate pre-existing known portal hypertension related issues associated with these conditions. These conditions may also present de-novo in pregnancy with acute onset ascites or variceal haemorrhage. Both in pregnancy and in the non-pregnant state, in those with established disease, in general, the overall balance of risk, favours continued anticoagulation.The study by Wiegers et al. has shown favourable maternal and foetal outcomes once greater than 20 weeks gestation is reached in patients with BCS and/or PVT. However, the risk of preterm birth and early pregnancy loss remains. These results are in keeping with the recent study by Andrade et al. (Journal of Hepatology 2018; 69: 1242-1249) looking at pregnancy outcomes from 24 pregnancies in 16 women with idiopathic non-cirrhotic portal hypertension (INCPH). Rautou et al. (Journal of Hepatology 2009; 51: 47-54) reviewed 24 pregnancies in 16 women with BCS and also reported similar findings. Taken as a whole, these results support the concept that patients with vascular liver disease can achieve favourable pregnancy outcomes but warrant careful consideration in pregnancy.Preconception counselling is a crucial opportunity to optimise patients with vascular liver disease who are considering pregnancy. This can be achieved in a multidisciplinary forum with input from obstetricians, haematologists and hepatologists. It is useful to identify those women with significant portal hypertension and varices before pregnancy so that appropriate surveillance and eradication with endoscopic band ligation and/or prophylaxis with beta blockers is undertaken. If pregnancy is achieved before surveillance, then a second trimester endoscopy for those with significant portal hypertension should be performed. In patients with portal and mesenteric vein thrombosis, magnetic resonance imaging of the pelvis may be needed to assess for the presence of abdominal wall/pelvic varices. This stratifies the risk of a variceal bleed and allows planning of the mode of delivery (caesarean, vaginal or assisted vaginal delivery). Wiegers et al. reported 2 variceal bleeds in pregnancy but did not find a significant association with adverse maternal outcomes, though this may be related to the low number of patients. Andrade et al. also reported 2 variceal bleeds including 1 patient with PVT without adequate endoscopic prophylaxis who required a portosystemic shunt. This outlines the need for appropriate screening and portal hypertension management according to findings.The majority of patients with BCS and PVT have an underlying pro-thrombotic tendency and the intra-partum and the post-partum periods are associated with thrombotic events. Vitamin K antagonists are historically the commonest anticoagulation used in BCS and PVT which should be switched to low molecular heparin ideally before conception. The use of anticoagulation is more common in patients with BCS and PVT than in INCPH (38/45 women in BCS and/or PVT compared to 4/16 in INCPH). 4 out of 6 women with BCS and/or PVT who experienced post-partum haemorrhage (PPH) were on anticoagulation. 2 patients with INCPH had PPH whilst on anticoagulation which may be confounded by the thrombocytopenia and type-2 error. In the study by Rautou et al., 17/24 pregnancies received anticoagulation and the 4 women who experienced post-partum bleeding (vaginal or intrauterine/parietal haematoma) were on anticoagulation which includes one woman with an ectopic pregnancy. No maternal deaths were reported in the three studies and the continued use of anticoagulation when indicated is safe and appropriate.The mode of delivery did not affect the risk of PPH in the three studies. The mode of delivery should be decided based on the individual risk profile taking into account the severity of portal hypertension, distribution of venous thrombosis, presence of coagulopathy and thrombocytopenia, obstetric indications and the presence of oesophageal or abdominal wall/pelvic varices.The live birth rates may be lower in patients with BCS compared to PVT (75% versus 82% after excluding first trimester pregnancy loss) but due to the low number of patients it remains difficult to interpret the results in this study. In the study by Andrade et al., all 18 pregnancies reaching 20 weeks gestation were delivered with 2 infant deaths (both preterm births). Rautou et al. reported 16/17 live births in pregnancies reaching 20 weeks gestation.To conclude, patients with BCS and PVT after 20 weeks gestation and appropriate planning can have a reasonable expectation for delivery and successful outcomes. Preconception counselling and antenatal care with multidisciplinary input is key to achieving this goal.

Resection or exclusion of scars following a myocardial infarction on the LAD territory started even before the beginning of the modern era of cardiac surgery. Many techniques were developed, but there is still confusion on who did what. The original techniques underwent modifications that brought to a variety of apparently new procedures that, however, were only a “revisitation” of what described before. In some case old techniques were reproposed and renamed, without giving credit to the surgeon that was the original designer. Herein we try to describe which are the seminal procedures and some of the most important modifications, respecting however the merit of who first communicated the procedure to the scientific world.

The use of whole-genome sequencing (WGS) has accelerated the pace of gene discovery and highlighted the need for open and collaborative data sharing in the search for novel disease genes and variants. GeneMatcher (GM) is designed to facilitate connections between researchers, clinicians, health-care providers and others to help in the identification of additional patients with variants in the same candidate disease genes. The Illumina Clinical Services Laboratory offers a WGS test for patients with suspected rare and undiagnosed genetic disease and regularly submits potential candidate genes to GM to strengthen gene-disease relationships. We describe our experience with GM, including criteria for evaluation of candidate genes, and our workflow for the submission and review process. We have made 69 submissions, 36 of which are currently active. Ten per cent of submissions have resulted in publications, with an additional 14 submissions part of ongoing collaborations and expected to result in a publication.

Bacterial infections, especially infections caused by multi-drug resistant bacteria, pose a serious threat to human health and bring huge challenges to clinical treatment. The excessive use of antibiotics can easily lead to the emergence of bacterial resistance, which severely limits clinical treatment options. There is an urgent need to develop high-efficiency antibacterial materials and treatment strategies to inhibit infections caused by multidrug-resistant bacteria. In this work, a nanocomposite named Ofloxacin@HMPB@HA(OHH NPs) combined with the laser irradiation was used to reduce the development of drug resistance and accelerate wound healing in a model infected by Klebsiella pneumoniae(K.Pneumoniae). In vitro results showed that compared with OHH NPs or NIR laser irradiation alone, this combination strategy can exert a synergistic effect on anti-K.Pneumoniae by destroying cell integrity with generating ROS and reducing ATP, and also inhibit the development of bacterial resistance. Moreover, in vivo experiments have shown that the system effectively promotes wound healing through killing K.Pneumoniae and promoting the formation of new tissues. In summary, these results indicate that OHH NPs show great potential in the clinical application of bacterial infections.

Closed form expressions in real Clifford geometric algebras Cl(0,3), Cl(3,0), Cl(1,2), and Cl(2,1) are presented in a coordinate-free form for exponential function when the exponent is a general multivector. The main difficulty in solving the problem is connected with an entanglement (or mixing) of vector and bivector components ai and ajk in a form (ai-ajk)2, i≠ j≠ k . After disentanglement, the obtained formulas simplify to the well-known Moivre-type trigonometric/hyperbolic function for vector or bivector exponentials. The presented formulas may find wide application in solving GA differential equations, in signal processing, automatic control and robotics.

The IDUA gene (MIM 252800) provides instructions for producing alpha-L-iduronidase, which is essential for the breakdown of glycosaminoglycans (GAGs). Mutations in the IDUA gene have been found to cause mucopolysaccharidosis type I (MIM 607014). This leads to the accumulation of GAGs within lysosomes causing different organs to be dysfunctional.

Post-operative polyuria due to Diabetes Insipidus is a commonly reported complication of pituitary surgery. However, central DI post abdominal surgery is rare and may be related to pre-existing DI or prolonged surgery with intraoperative blood loss. A thorough workup needs to be done to exclude central DI in such patients.

Acute exposure to warming temperatures increases minimum energetic requirements in ectotherms. However, over and within multiple generations, increased temperatures may cause plastic and evolved changes that modify the temperature sensitivity of energy demand and alter individual behaviours. Here, we aimed to test whether populations recently exposed to geothermally elevated temperatures express an altered temperature sensitivity of metabolism and behaviour. We expected that long-term exposure to warming would moderate metabolic rate, reducing the temperature sensitivity of metabolism, with concomitant reductions in boldness and activity. We compared the temperature sensitivity of metabolic rate (acclimation at 20 versus 30°C) and allometric slopes of routine, standard, and maximum metabolic rates, in addition to boldness and activity behaviours, across eight recently divergent populations of a widespread fish species (Gambusia affinis). Our data reveal that warm-source populations express a reduced temperature sensitivity of metabolism, with relatively high metabolic rates at cool acclimation temperatures and relatively low metabolic rates at warm acclimation temperatures. Allometric scaling of metabolism did not differ with thermal history. Across individuals from all populations combined, higher metabolic rates were associated with higher boldness and activity. However, warm-source populations displayed relatively more bold behaviour at both acclimation temperatures, despite their relatively low metabolic rates at warm acclimation temperatures. Overall, our data suggest that in response to warming, multigenerational processes may not direct trait change along a simple “pace-of-life syndrome” axis, instead causing relative decreases in metabolism and increases in boldness. Ultimately, our data suggest that multigenerational warming may produce a novel combination of physiological and behavioural traits, with consequences for animal performance in a warming world.

In this paper, we are concerned with the asymptotic behavior of solutions to the Cauchy problem (or initial-boundary value problem) of one-dimensional Keller-Segel model. For the Cauchy problem, we prove that the solutions time-asymptotically converge to the nonlinear diffusion wave whose profile is self-similar solution to the corresponding parabolic equation, which is derived by Darcy’s law, as in [11, 28]. For the initial-boundary value problem, we consider two cases: Dirichlet boundary condition and null-Neumann boundary condition on (u, ρ). In the case of Dirichlet boundary condition, similar to the Cauchy problem, the asymptotic profile is still the self similar solution of the corresponding parabolic equation, which is derived by Darcy’s law, thus we only need to deal with boundary effect. In the case of null-Neumann boundary condition, the global existence and asymptotic behavior of solutions near constant steady states are established. The proof is based on the elementary energy method and some delicate analysis of the corresponding asymptotic profiles.

COVID 19 has created one of the world’s worst pandemics and is associated with various life-threatening complications, such as Cytomegalovirus (CMV) co-infection. We present a life-threatening CMV viremia co-infection in a none-immunocompromised COVID 19 patient to highlight our management approach and a comprehensive literature review.

This paper is devoted to the study of Tur\’{an} type inequalities for some well-known special functions such as supersine and supercosine which are derived by using a new form of the Cauchy-Bunyakovsky-Schwarz inequality.

A recently published approach for modeling the cross flow in an extruder channel using a new solution to the biharmonic equation is utilized in a study of chaotic mixing in a free helix single screw extruder. This novel extruder was designed and constructed with the screw flight, also referred to as the helix, detached from the screw core. Each of the screw elements could be rotated independently to obtain chaotic motion in the screw channel. Using the new extruder, experimental evidence for the increased mixing of a dye, for both a Dirac and droplet input, with a chaotic flow field relative to the traditional residence time distribution is presented. These experimental results are compared using the new biharmonic equation-based model. Because of the ability to periodically rotate only the flight/helix, the chaotic mixing results are minimally confounded by the existence of Moffat eddies.

A document by Shawn Mondoux. Click on the document to view its contents.

Oxford Nanopore Technologies (ONT) is a third-generation sequencing technology that is gaining popularity in ecological research for its portable and low-cost sequencing possibilities. Although the technology is primarily developed for long-read sequencing, it can also be applied to sequence amplicons. The downside of ONT is the low quality of the raw reads. Hence, generating a high-quality consensus sequence is still a challenge. We present Amplicon_sorter, a tool for reference-free sorting of ONT sequenced amplicons based on their similarity in sequence and length and for building solid consensus sequences.

A 75-year-old male presented with an immediately threatened grade IIb acute ischemia of the left leg due to thrombosis of a femoro-infrapopliteal prosthetic bypass graft. After an urgent Computed Tomography Angiography, an urgent graft thrombectomy was performed using a 5 Fr Fogarty catheter, which had a troublesome distal passage.

Background: Cryoballoon (CB) based pulmonary vein isolation (PVI) has proven to be as effective as radiofrequency (RF) based ablation. Different ablation protocols took the individual time-to-isolation (TTI) into account aiming at shorter but equally or even more effective freeze-cycles. The current study sought to assess the impact of the TTI on PVI durability in patients undergoing a repeat procedure for recurrence of atrial tachyarrhythmia (ATA). Methods and Results: In 205 patients with ATA recurrence after previous CB-based PVI a total of 806 PVs were identified. One hundred-twenty-six out of 806 PVs (16%) were previously treated with a TTI guided ablation (protocol #1; TTI+120 sec.), in 92/806 (11%) PVs TTI was only monitored (m) but fixed freeze-cycles were applied (protocol #2; mTTI) and in 588/806 (73%) a fixed freeze-cycle was applied without TTI-monitoring. There was no difference in the PV-reconduction rate between the groups (P=0.23). The right inferior pulmonary vein (RIPV) showed overall significantly higher reconduction rates compared to the other PVs (RIPV – left inferior PV (LIPV) p<0.003, -left superior PV (LSPV) p<0.001, - right superior PV RSPV p<0.013). In 21 patients (10%) only for the RIPV reconduction was assessed. Conclusions: TTI based CB ablation did not show significant differences regarding PV-reconduction rates compared to the other protocols.

Unlike many viral infections such as influenza, and the two previous incarnations of the coronavirus, SARS and MERS, Covid-19 originally appeared to be of similar severity, after adjusting for age, BMI and other co-morbidities, in the pregnant as in the non-pregnant population. Worryingly the paper from the Italian Obstetric Surveillance System COVID-19 Working Group (p …), suggests that, in pregnancy, the virus may be getting more virulent with the advent of newer variants. Specifically the need for ventilation or ICU admission was significantly increased during the second wave (alpha variant predominant) compared to the first (wild-type predominant), albeit with no maternal deaths during the first wave and only one during the second. If real, this is both unexpected and concerning. Unexpected, because viruses tend to mutate in the direction of reduced severity; it is not in the interests of the virus that the host dies. Concerning, because it suggest that the newer variants are behaving more like other viral diseases; causing more severe disease in pregnancy.The evidence from Italy is supported by at least three other sources. In August a preprint from the UK Obstetric Surveillance Service (Vousden et al. MedRxiv 2021.07.22.21261000; doi: https://doi.org/10.1101/2021.07.22.21261000 accessed 30 September) reported disease severity in pregnancy when wild type predominated, when alpha predominated and when delta predominated. In each succeeding phase disease severity in increased. On 24 September the UK Intensive Care National Audit & Research Centre reported (ICNARC 17 September 2021 https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports accessed 30 September) that the absolute numbers of pregnant women admitted to critical care with Covid were significantly higher in the second (alpha) wave than the first (wild type), and looked set to be significantly higher again in the third (delta) wave. Finally a large series from Nair Hospital, the largest hospital caring for Covid in Mumbai (Mahajan et al. Obstet Gynecol: July 7, 2021 doi: 10.1097/AOG.0000000000004529), reported significantly higher maternal mortality during the second (alpha predominant) wave than the first (wild type).The lesson for women is simple, get vaccinated. Vaccines are safe and if the disease is really getting more severe, the balance of risks and benefits will be moving overwhelmingly in favour of vaccination. The lesson for obstetricians is more complicated. Encourage women to get vaccinated and take the disease seriously. Keep women with Covid out of hospital if possible, but monitor them with saturation monitors reliably, so those who deteriorate can be picked up quickly. When they need admission follow evidence-based treatment guidelines, and keep using personal protective equipment. We’re not yet done with Covid.Jim Thornton MD FRCOGEmeritus Professor of Obstetrics & Gynaecology, University of Nottingham.