Clinical pregnancy in Turner syndrome following re-implantation of cryopreserved ovarian cortex.

Turner syndrome (TS) leads to a characteristic phenotype, including premature ovarian insufficiency and infertility. Ovarian tissue cryopreservation (OTC) is becoming an established fertility preservation strategy for both pre- and post-pubertal females and may offer the chance of having a biological family to selected patients with TS. To date, women with TS have had ovarian tissue cryopreserved but there are few reports of autologous re-implantation and none of pregnancy. We herein report, to our knowledge, the first clinical pregnancy in a patient with TS, conceived naturally following re-implantation of cryopreserved ovarian tissue which had been removed soon after spontaneous puberty. This provides proof of concept for OTC as a means of fertility preservation in TS.

Clinical management of deviations in maternal temperature during labour and childbirth: an evidence-based intrapartum care algorithm.

AIM: The development of an evidence-based algorithm for the clinical management of deviations in maternal temperature during labour and childbirth. POPULATION: Pregnant women at any stage of labour, with singleton, term (37-42 weeks) pregnancies at low risk of developing complications. SETTING: Health facilities in low- and middle-income countries. SEARCH STRATEGY: We searched for international guidelines and prioritised WHO guidelines. In addition, we searched for other sources of evidence in the Cochrane Database of Systematic Reviews, EMBASE, MEDLINE and CINAHL until June 2020. Studies were prioritised according to the hierarchy of evidence. CASE SCENARIOS: Two case scenarios were identified: maternal hyperthermia and hypothermia. We developed a single algorithm including both, due to commonalities in diagnosis, monitoring and management of underlying causes. The underlying conditions covered in the pathway include maternal sepsis and infection, chorioamnionitis, pyelonephritis, lower urinary tract and respiratory infections. Key decision points in the algorithm are suspicion of condition, definition, differential diagnosis, monitoring and management. CONCLUSIONS: We present an evidence-based algorithm to assist healthcare professionals in making decisions about appropriate clinical management of deviations in maternal temperature. Research is needed to assess the views of healthcare professionals and women accessing healthcare on the feasibility of implementing the algorithm. TWEETABLE ABSTRACT: An evidence-based intrapartum care algorithm to support management of deviations in maternal temperature in labour and childbirth. #sepsis #maternitycare.

The FAST-M complex intervention for the detection and management of maternal sepsis in low-resource settings: a multi-site evaluation.

OBJECTIVE: To evaluate whether the implementation of the FAST-M complex intervention was feasible and improved the recognition and management of maternal sepsis in a low-resource setting. DESIGN: A before-and-after design. SETTING: Fifteen government healthcare facilities in Malawi. POPULATION: Women suspected of having maternal sepsis. METHODS: The FAST-M complex intervention consisted of the following components: the FAST-M maternal sepsis treatment bundle and the FAST-M implementation programme. Performance of selected process outcomes was compared between a 2-month baseline phase and 6-month intervention phase with compliance used as a proxy measure of feasibility. MAIN OUTCOME RESULT: Compliance with vital sign recording and use of the FAST-M maternal sepsis bundle. RESULTS: Following implementation of the FAST-M intervention, women were more likely to have a complete set of vital signs taken on admission to the wards (0/163 [0%] versus 169/252 [67.1%], P < 0.001). Recognition of suspected maternal sepsis improved with more cases identified following the intervention (12/106 [11.3%] versus 107/166 [64.5%], P < 0.001). Sepsis management improved, with women more likely to receive all components of the FAST-M treatment bundle within 1 hour of recognition (0/12 [0%] versus 21/107 [19.6%], P = 0.091). In particular, women were more likely to receive antibiotics (3/12 [25.0%] versus 72/107 [67.3%], P = 0.004) within 1 hour of recognition of suspected sepsis. CONCLUSION: Implementation of the FAST-M complex intervention was feasible and led to the improved recognition and management of suspected maternal sepsis in a low-resource setting such as Malawi. TWEETABLE ABSTRACT: Implementation of a sepsis care bundle for low-resources improved recognition & management of maternal sepsis.

Development of the FAST-M maternal sepsis bundle for use in low-resource settings: a modified Delphi process.

OBJECTIVE: To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. DESIGN: Modified Delphi process. SETTING: Participants from 34 countries. POPULATION: Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. METHODS: We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. MAIN OUTCOME MEASURE: Consensus on bundle items. RESULTS: Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher-level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym 'FAST-M'. CONCLUSION: A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. TWEETABLE ABSTRACT: A maternal sepsis bundle for low resource settings has been developed by international consensus.

Weaning practices in phenylketonuria vary between health professionals in Europe.

BACKGROUND: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. METHODS: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. RESULTS: Weaning started at 17-26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and < 17 weeks in 3% (n = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% (n = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% (n = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. CONCLUSIONS: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Early feeding practices in infants with phenylketonuria across Europe.

BACKGROUND: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. METHODS: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. RESULTS: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%. DISCUSSION: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Re-implantation of cryopreserved ovarian cortex resulting in restoration of ovarian function, natural conception and successful pregnancy after haematopoietic stem cell transplantation for Wilms tumour.

With the improvement of long-term cancer survival rates, growing numbers of female survivors are suffering from treatment-related premature ovarian insufficiency (POI). Although pre-treatment embryo and oocyte storage are effective fertility preservation strategies, they are not possible for pre-pubertal girls or women who cannot delay treatment. In these cases, the only available treatment option is ovarian cortex cryopreservation and subsequent re-implantation. A 32-year-old woman had ovarian cortex cryopreserved 10 years previously before commencing high-dose chemotherapy and undergoing a haematopoietic stem cell transplant for recurrent adult Wilms tumour, which resulted in POI. She underwent laparoscopic orthotopic transplantation of cryopreserved ovarian cortex to the original site of biopsy on the left ovary. She ovulated at 15 and 29 weeks post-re-implantation with AMH detectable, then rising, from 21 weeks, and conceived naturally following the second ovulation. The pregnancy was uncomplicated and a healthy male infant was born by elective Caesarean section at 36+4 weeks gestation. This is the first report of ovarian cortex re-implantation in the UK. Despite the patient receiving low-risk chemotherapy prior to cryopreservation and the prolonged tissue storage duration, the re-implantation resulted in rapid restoration of ovarian function and natural conception with successful pregnancy.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

Effect of contraception provided at termination of pregnancy and incidence of subsequent termination of pregnancy.

OBJECTIVE: To determine the incidence of subsequent termination of pregnancy (TOP) within a 2-year period in relation to the method of contraception provided to women following the index TOP. DESIGN: Case note review. SETTING: NHS hospital TOP service, Edinburgh, UK. POPULATION: Nine hundred and eighty-six women requesting a TOP in 2008. METHODS: Case notes were reviewed to determine the contraception provided at index TOP and whether women had subsequent TOP at the same hospital within 2 years. MAIN OUTCOME MEASURES: Incidence of subsequent TOP within 2 years amongst women receiving different contraceptive methods. RESULTS: One hundred and twenty-one women (12.3%) of the 986 who attended the clinic requesting a TOP returned requesting another TOP in the subsequent 2 years. Both intrauterine contraception and the progestogen-only implant were associated with the lowest incidence of subsequent TOP. Using the combined oral contraceptive pill as the reference method, the odds ratios (ORs) and 95% confidence intervals (CIs) of a further TOP within 2 years with intrauterine contraception and the implant were OR = 0.05 (95% CI, 0.01-0.41; P < 0.001) and OR =0.06 (95% CI, 0.01-0.23; P < 0.001), respectively. Women choosing the implant were significantly younger than those choosing the intrauterine method (P < 0.001). CONCLUSION: Women undergoing a TOP who wish to avoid another unintended pregnancy should consider immediate initiation of either intrauterine contraception or the progestogen-only implant. Service providers should be trained and supported to provide these methods to women at the time of TOP.

Dietary management of urea cycle disorders: UK practice.

BACKGROUND: There is no published data describing UK dietary management of urea cycle disorders (UCD). The present study describes dietary practices in UK inherited metabolic disorder (IMD) centres. METHODS: Cross-sectional data from 16 IMD centres were collected by a questionnaire describing the management of UCD patients on prescribed protein-restricted diets. RESULTS: One hundred and seventy-five patients [N-acetylglutamate synthase deficiency, n = 3; carbamoyl phosphate synthase deficiency (CPS), n = 8; ornithine transcarbamoylase deficiency (OTC), n = 75; citrullinaemia, n = 41; argininosuccinic aciduria (ASA), n = 36; arginase deficiency, n = 12] were reported; 70% (n = 123) aged 0-16 years; 30% (n = 52) >16 years. Prescribed median protein intake decreased with age (0-6 months: 2 g kg(-1) day(-1); 7-12 months: 1.6 g kg(-1) day(-1); 1-10 years: 1.3 g kg(-1) day(-1); 11-16 years: 0.9 g kg(-1) day(-1) and >16 years: 0.8 g kg(-1) day(-1)) with little variation between disorders. Adult protein prescription ranged 0.4-1.2 g kg(-1) day(-1) (40-60 g day(-1)). In the previous 2 years, 30% (n = 53) were given essential amino acid supplements (EAAs) (CPS, n = 2; OTC, n = 20; citrullinaemia, n = 15; ASA, n = 7; arginase deficiency, n = 9). EAAs were prescribed for low plasma quantitative essential amino acids (n = 13 centres); inadequate natural protein intake (n = 11) and poor metabolic control (n = 9). From diagnosis, one centre prescribed EAAs for all patients and one centre for severe defects only. Only 3% (n = 6) were given branch chain amino acid supplements. Enteral feeding tubes were used by 25% (n = 44) for feeds and 3% (n = 6) for medications. Oral energy supplements were prescribed in 17% (n = 30) of cases. CONCLUSIONS: In the UK, protein restriction based on World Health Organization 'safe intakes of protein', is the principle dietary treatment for UCD. EAA supplements are prescribed mainly on clinical need. Multicentre collaborative research is required to define optimal dietary treatments.

Multiconjugate adaptive optics: laboratory experience.

We present the results from a laboratory multiconjugate adaptive optics experiment. The experiment is differentiated from other published work in that it has a programmable deterministic turbulence generator and an output science camera. The turbulence was generated using a dual layer turbulence emulator, and then corrected using an AO system with 2 wavefront correctors and a Shack-Hartman wavefront sensor, which processed information from five artificial guide stars. We report our results and also describe some of the problems.

Bilateral anterior shoulder dislocation--a case report and review of the literature.

Bilateral dislocations of the shoulders are uncommon. Of the cases which do present, the majority are posterior and occur secondary to seizures associated with epilepsy, electrocution and hypoglycaemia. Bilateral anterior dislocations are thought to be very rare. This report describes such a case which occurred following minor trauma in an elderly lady. The literature review which follows would seem to suggest that this may not be as rare as previously thought.

Changes in anesthetic sensitivity and glutamate receptors in the aging canine brain.

This study investigated whether the aging process in dogs is associated with an increased sensitivity to inhalation anesthesia and whether age-related changes in glutamate receptors are related to the increased sensitivity. The mean minimum alveolar concentration (MAC) of isoflurane was 1.82 +/- .08% for 2-3 year olds and 1.45 +/- .06% for 11 years olds, indicating that there was an increased potency of isoflurane in the older dogs as compared to the young. These older animals also showed a significant decrease in binding of [3H]glutamate and [3H]dizocilpine ([3H]MK801) to N-methyl-D-aspartate (NMDA) receptors in multiple cortical and hippocampal regions. The density of binding to NMDA receptors in the cortex, using a single concentration of ligand, correlated significantly with individual MAC values. These results demonstrate that dogs experience an increase in anesthetic potency with increased age, similar to humans, and that age-related changes in the NMDA receptor may represent one mechanism underlying this increased sensitivity to anesthesia.

Dual-conjugate wavefront generation for adaptive optics.

We present results of the isoplanatic performance of an astronomical adaptive optics system in the laboratory, by using a dual layer turbulence simulator. We describe how the performance of adaptive correction degrades with off--axis angle. These experiments demonstrate that it is now possible to produce quantifiable multi-layer turbulence in the laboratory as a precursor to constructing multi-conjugate adaptive optics.

Cardiopulmonary measurements in dogs undergoing gastropexy without gastrectomy for correction of gastric dilatation-volvulus.

OBJECTIVE: To measure cardiopulmonary variables, including cardiac index, in dogs with naturally acquired gastric dilatation-volvulus (GDV). DESIGN: Prospective clinical study. ANIMALS: 6 dogs with GDV. PROCEDURE: In addition to typical medical and surgical management of GDV, the dorsal metatarsal and pulmonary arteries and right atrium of the dogs were catheterized to obtain cardiopulmonary measurements before and during anesthesia and surgery. RESULTS: All dogs underwent gastropexy but none required gastrectomy. Mean cardiac index and mean arterial blood pressure for this small population of dogs with GDV were not significantly different from those reported for clinically normal awake or anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with naturally acquired GDV without gastric necrosis may not have the classic characteristics, including decreased cardiac index and hypotension, of hypovolemic circulatory shock.

Characterization of a soluble mouse liver enzyme capable of hydrolyzing diisopropyl phosphorofluoridate.

A novel mouse liver soluble fraction DFPase which has organophosphatase activities with sarin, soman and tabun, was purified and characterized. However, it lacks paraoxonase and arylesterase activities with paraoxon and phenyl acetate, respectively. This DFPase closely resembles and may be identical with the one purified by Little et al. in 1989 from the soluble fraction of rat liver, based on its substrate specificity, size (approximately 39 kDa) and its stimulation by several metal ions, namely magnesium, manganese and cobalt. Sequencing of our purified mouse liver DFPase showed it to be identical in its amino acid sequence with the recently identified senescence marker protein-30 (SMP-30) by Fujita et al. in 1996. Other senescence marker proteins possessing high structural homology with the mouse SMP-30 have also been found and sequenced from human and rat livers. There is no structural homology between the senescence marker protein family and the group of mammalian paraoxonases. Thus, it is clear that there are at least two distinct, unrelated families of mammalian liver enzymes that share DFPase activity.

Arteriography in chronic renal failure: a case for carbon dioxide.

PURPOSE: The aim of this study was to assess the utilisation of carbon dioxide arteriography, performed with a simple injection system, as the imaging technique of choice in patients with chronic renal failure. METHODS: Patients with chronic renal impairment who required arterial imaging or intervention were recruited for carbon dioxide angiography. Demographic data were prospectively recorded and pre- and post-arteriogram renal function was quantified. Radiographic images were graded by an independent radiologist. RESULTS: Twenty-eight patients underwent renal or aorto-femoral studies with only one failure. There were no cases of contrast-induced nephropathy. Twenty-two of the films (79%) were graded as excellent or good, four as acceptable and two were considered to be poor (non-diagnostic). CONCLUSIONS: This study has demonstrated that carbon dioxide angiography is a safe and clinically effective procedure in patients with chronic renal failure.

A prospective randomized trial evaluating the haemodynamic role of incompetent calf perforating veins.

AIM: This study was undertaken to determine the haemodynamic effect of incompetent calf perforating veins in patients with uncomplicated varicose veins and long saphenous incompetence. METHODS: Thirty-eight limbs from 35 patients were studied. All patients had uncomplicated varicose veins with both long saphenous and calf perforator incompetence on duplex ultrasonography. Patients were randomized to have incompetent calf perforators ligated or left intact, in addition to saphenofemoral junction ligation, strip of long saphenous vein to knee and stab avulsion of any visible varicosities in the leg. Patients were assessed with air plethysmography pre-operatively and 3 months postoperatively. RESULTS: Superficial venous surgery improved venous volume, venous filling index and ejection fraction in the patient cohort. No significant haemodynamic difference was demonstrated between the two groups of patients who were randomized. CONCLUSIONS: At present, the results of this study do not support the use of routine perforator ligation during superficial surgery for uncomplicated varicose veins.

Complications and mortality associated with anesthesia in dogs and cats.

The complications and mortality associated with anesthesia of dogs and cats in a university teaching hospital were determined. During one year, 2,556 dogs and 683 cats were anesthetized by the anesthesia service. Hypotension occurred in 179 (7%) dogs and 58 (8.5%) cats. Cardiac dysrhythmias occurred in 64 (2.5%) dogs and 12 (1.8%) cats. Transfusions were required in 31 (1.2%) dogs. Hypercapnea occurred in 33 (1.3%) dogs and one (less than 1%) cat. Hypoxemia occurred in 14 (0.5%) dogs. Anesthetic complications, as defined, occurred in 12.0% of dogs and 10.5% of cats, while deaths associated with the perianesthetic period occurred in 0.43% of dogs and 0.43% of cats.