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Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT). NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m2 daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level. Three hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P =.35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P =.88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P <.05). Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival. [ABSTRACT FROM AUTHOR]

Background/Aim: Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygenenhanced MRI (OE-MRI) in xenografts derived from muscleinvasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery. Materials and Methods: The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm³) or large (700 mm3) tumours were imaged, breathing air then 100% O2, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N2, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays. Results: Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour. Conclusion: OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies. [ABSTRACT FROM AUTHOR]

Summary: Thrombolysis with prolonged cardiopulmonary resuscitation may be required for the successful resuscitation of patients presenting with massive pulmonary embolism leading to cardiac arrest. A rare, recognised complication of cardiopulmonary resuscitation is traumatic hepatic and splenic laceration. The incidence of complications is believed to be increased in those who receive automated mechanical cardiopulmonary resuscitation, compared to those who receive standard chest compressions. We present a case of a patient with massive pulmonary embolism leading to cardiac arrest which was successfully treated with thrombolysis and mechanical automated cardiopulmonary resuscitation. The patient suffered hepatic and splenic lacerations resulting in major haemorrhage. This required emergency resuscitation with blood products and splenic embolisation. This case highlights the importance of continual re‐assessment of patients, the early recognition of complications and an awareness of the potential complications of treatments we deliver. [ABSTRACT FROM AUTHOR]

Oxygen therapy is widely used in the community for patients with chronic hypoxaemia. Although only a small proportion of those are children, more and more paediatric patients are prescribed home oxygen for a variety of indications, most commonly for chronic lung disease related to premature birth. Chronic hypoxaemia in children is diagnosed using pulse oximetry, a method that has limitations, but alternative tests are rarely required. Whilst there are clear advantages in therapy with oxygen outside the hospital setting, clinicians need to be aware of potential impact on family life, housing, school attendance and travel. The process of prescribing is standardised in the UK, and it is crucial for clinicians to understand risks and equipment used to deliver oxygen in the community. Regular follow up is important and input from community-based professionals is hugely beneficial. Some children on long-term oxygen therapy may be able to wean and eventually stop therapy. This process can be supported by a structured protocol. New technologies such as remote monitoring may further improve the care of children with chronic conditions that require long term oxygen therapy. [ABSTRACT FROM AUTHOR]

Introduction : Simulation training offers an authentic team-based learning opportunity without risk to real patients. The Educational Corner at the annual congress of the European Branch of Extracorporeal Life Support Organisation (EuroELSO) provided an opportunity for multiple simulation training sessions facilitated by experts from all over the world. Aim : We aimed to review the educational impact of EuroELSO Educational Corner and whether it provides a quality ECLS training to a wide spectrum of multidisciplinary international attendees utilising high and low fidelity simulation, workshops and hands on sessions. Methods : During the congress, 43 sessions were conducted dedicated to ECLS education with identified educational objectives. The sessions focused on management of adults and children on V-V or V-A ECMO. Adult sessions covered emergencies on mechanical circulatory support with management of LVAD and Impella, managing refractory hypoxemia on V-V ECMO, emergencies on ECMO, renal replacement therapy on ECMO, V-V ECMO, ECPR cannulation and performing perfect simulation. Paediatric sessions covered ECPR neck and central cannulation, renal replacement on ECMO, troubleshooting, cannulation workshop, V-V recirculation, ECMO for single ventricle, PIMS-TS and CDH, ECMO transport and neurological injury. Results : The Educational Corner was attended by more than 400 participants over the two congress days. Majority of responders (88%) reported that training sessions met the set educational goals and objectives and that this would change their current practice. Almost all (94%) reported that they received useful information and 95% would recommend the session to their colleagues. Conclusion : The Educational Corner, as an integral component of the annual EuroELSO congress, achieved the set educational goals and provided quality education based on the recipient survey. Structured multidisciplinary ECLS education with standardised curriculum and feedback is an important key step in delivering quality training to an international audience. Standardisation of European ECLS education remains an important focus of the EuroELSO. [ABSTRACT FROM AUTHOR]

The article discusses research on early prediction of high-flow nasal cannula (HFNC) outcome in subjects with severe hypoxemic COVID-19 using the ROX index. The study recorded the duration and number of HFNC sessions and calculated the difference between ROX at 12 hour and baseline. It evaluated the association of oxygenation variables with HFNC failure defined as the need for intubation for respiratory acidosis, severe hypoxemia, severe hemodynamic instability, or deteriorating consciousness.

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Objective: This study aims to evaluate the safety, utilization, ability to reduce length of hospitalization and overall outcomes of a COVID-19 virtual ward providing ongoing treatment at home. Method: A retrospective single-center study of patients discharged to the COVID-19 virtual "step down" ward between January 27th 2021 and March 2nd 2021. The referral process, length of hospitalization, length of stay on the virtual ward, readmissions, and ongoing treatment requirements including supplemental oxygen, antibiotics, and/or steroids were all noted. Results: A total of 50 patients were referred to the virtual ward. 43 referrals were accepted, 39 of which were from the respiratory ward. Four patients were readmitted, all due to hypoxia. All readmissions occurred within 5 days of discharge. 72% (n = 31) were discharged home with an ongoing oxygen requirement. 14.3% of patients were discharged with antibiotics only, 9.5% with steroids only and 23.8% with both antibiotics and steroids. The mean length of hospital stay for patients discharged to the virtual ward was 10.3 ± 9.7 days and 11.9 ± 11.6 days for all covid positive patients during this time. On average, patients spent 13.7 ± 7.3 days on the virtual ward. The average number of days spent on oxygen on the virtual ward was 11.6 ± 6.0 days. Conclusion: The virtual ward model exemplifies the potential benefits of collaborative working between primary and secondary care services, relieving pressure on hospitals whilst providing ongoing treatments at home such as supplemental oxygen. It also facilitates an early supported discharge of clinically stable patients with an improving clinical trajectory by managing them in the community. [ABSTRACT FROM AUTHOR]

The fetal origins of adult disease (FOAD) hypothesis, which was proposed by David Barker in the United Kingdom in the late 1980s, posited that adult chronic diseases originated from various adverse stimuli in early fetal development. FOAD is associated with a wide range of adult chronic diseases, including cardiovascular disease, cancer, type 2 diabetes and neurological disorders such as schizophrenia, depression, anxiety, and autism. Intrauterine hypoxia/prenatal hypoxia is one of the most common complications of obstetrics and could lead to alterations in brain structure and function; therefore, it is strongly associated with neurological disorders such as cognitive impairment and anxiety. However, how fetal hypoxia results in neurological disorders remains unclear. According to the existing literature, we have summarized the causes of prenatal hypoxia, the effects of prenatal hypoxia on brain development and behavioral phenotypes, and the possible molecular mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to evaluate whether markers of intrapartum hypoxia differ according to sex, and if this could explain the increased risk of adverse perinatal outcomes in males.Study Design: This is a retrospective observational cohort study of non-anomalous, singleton deliveries >36 completed weeks' gestation at a UK teaching hospital over a 4.5 year period. Absent or incomplete cord gas results were excluded and the remaining data were validated according to an established method. The relations between sex and both arterial pH and a composite variable, 'fetal distress' (cases in which operative delivery or caesarean section were undertaken for presumed fetal compromise), were examined using independent samples t-test and Chi-square test. Odds ratios with 95 % confidence intervals were calculated to describe the relation between fetal sex and intermediate-term adverse outcomes. Binary logistic regression was performed to generate odds ratios (with 95 % confidence intervals) adjusted for arterial pH and fetal distress. This was repeated to adjust for labor and induction of labor.Results: There were eligible 8758 cases, of which 4655 were male and 4103 female, from a total of 39,148 deliveries during the study period. Neonatal unit admission (OR 1.54, 95 % CI; 1.31-1.80), renal impairment (OR 1.63, 95 % CI; 1.15-2.32), neurological impairment (OR 1.73, 95 % CI; 1.06-2.84) and a composite adverse outcome (OR 1.73, 95 % CI; 1.29-2.33) were all more likely in males, even after adjusting for labor and induction of labor, both of which were more likely males. The mean cord arterial pH of males was lower (7.23 vs 7.24, P = 0.019) although they were not more likely to be acidemic with a pH <7.0 (males 43 (0.92 %) vs females 41 (1.00 %), P = 0.717), and males were also more likely to have fetal distress (834 (17.9 %) vs 588 (14.3 %), P = <0.001). Being male remained associated with adverse outcomes despite adjustment for arterial pH and fetal distress.Conclusion: Despite a lower mean cord arterial pH and greater incidence of fetal distress in males, intrapartum hypoxia does not account for their worse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Smoking is a well-established risk factor for delayed wound healing and postoperative complications. Due to the overwhelming evidence of the detrimental health effects of smoking electronic cigarettes have become increasingly popular. The technology behind the devices has improved since their arrival in the UK and their use has been supported and encouraged by Public Health England; who stated they were 95% safer than smoking tobacco. But recent reports show a worrying link with serious respiratory illness and research has found that the nicotine, flavourings and diluents used in the e-cigarette fluids can have similar effects as tobacco on wound healing by increasing the risk of skin flap necrosis and hypoxia, with detrimental changes to the immune cells which aid healing. The recommendation is that patients should not be advised to use e-cigarettes as an alternative to conventional cigarettes prior to elective surgery. [ABSTRACT FROM AUTHOR]

The Early Toarcian, organic-rich, black shales of the Cleveland Basin, Yorkshire UK, are the type sediments for the supposed early Toarcian oceanic anoxic event. The sediments have values of Cd/Mo that are <0.1 and values of Co (mg/kg) × Mn (%) that are >0.4. These values are typical of sediment deposited in modern basins that are hydrographically restricted and show that the Cleveland Basin was hydrographically restricted when depositing organic-rich sediments. These palaeo-proxies confirm earlier interpretations, based on Mo/TOC values, that argued for hydrographic restriction. The term Toarcian oceanic anoxic event can now be discarded. [ABSTRACT FROM AUTHOR]

Oxygen restricted conditions were widespread in European shelf seas after the end-Triassic mass extinction event and they are reported to have hindered the recovery of marine benthos. Here we reconstruct the redox history of the Early Jurassic Blue Lias Formation of southwest Britain using pyrite framboid size analysis and compare this with the recovery of bivalves based on field and museum collections. Results suggest widespread dysoxia punctuated by periods of anoxia in the region, with the latter developing frequently in deeper water settings. Despite these harsh conditions, initial benthic recovery occurred rapidly in the British Jurassic, especially in shallowest settings, and shows no relationship with the intensity of dysoxia. A stable diversity was reached by the first recognised ammonite zone after the end-Triassic mass extinction. This contrasts with the deeper-water, more oxygen-poor sections where the diversity increase was still continuing in the earliest Sinemurian Stage, considerably longer than previously reported. Similar recovery rates are seen amongst other groups (brachiopods and ammonites). Oxygen-poor conditions have been suggested to delay recovery after the Permo-Triassic mass extinction, but this is not the case after the end-Triassic crisis. We suggest that this was because the European dysoxia was only a regional phenomenon and there were plenty of well-ventilated regions available to allow an untrammelled bounce back. • Dysoxia punctuated by periods of anoxia characterise the British Lower Jurassic. • Initial benthic recovery occurred 0.7 Myr after the end-Triassic mass extinction. • Oxygen-restriction did not delay recovery from end-Triassic mass extinction. [ABSTRACT FROM AUTHOR]

This study sought to establish perceptions of elite endurance athletes on the role and worth of altitude training. Elite British endurance runners were surveyed to identify the altitude and hypoxic training methods utilised, along with reasons for use, and any situational, cultural and behaviour factors influencing these. Prior to the 2012 Olympics Games, 39 athletes and 20 support staff (coaches/practitioners) completed an internet-based survey to establish differences between current practices and the accepted "best-practice". Almost all of the athletes (98%) and support staff (95%) surveyed had utilised altitude and hypoxic training, or had advised it to athletes. 75% of athletes believed altitude and hypoxia to be a "very important" factor in their training regime, with 50% of support staff believing the same. Athletes and support staff were in agreement of the methods of altitude training utilised (i.e. 'hypoxic dose' and strategy), with camps lasting 3-4 weeks at 1,500-2,500 m being the most popular. Athletes and support staff are utilising altitude and hypoxic training methods in a manner agreeing with research-based suggestions. The survey identified a number of specific challenges and priorities, which could provide scope to optimise future altitude training methods for endurance performance in these elite groups. [ABSTRACT FROM AUTHOR]

Objective: To determine if ingestion of lycosome-formulated dark chocolate (DC) containing astaxanthin (ASTX) improves bioavailability of ASTX and affects markers of hypoxia and oxidative stress in aging individuals.Design: Randomized, blinded, four-arm, prospective study.Settings: Lycotec Ltd, Cambridge, United Kingdom and Institute of Cardiology, Saratov, Russian Federation.Participants: 32 healthy individuals aged 60-70 years with confirmed signs of oxidative stress (increased serum levels of oxidized LDL and malonic dialdehyde) randomized into four study groups (8 volunteers each).Intervention: Volunteers of first group were given orally 10 gr of dark chocolate (DC). Individuals from the second group received 7 mg of astaxanthin (ASTX). Third group of volunteers was supplemented with 10 gr of DC and 7 mg of ASTX ingested simultaneously as two separate formulations. Last group of the individuals was given 10 gr of a lycosomal formulation of DC containing 7 mg of co-crystalized ASTX (L-DC-ASTX), a newly developed highly bioavailable nutraceutical composition of DC containing 2 groups of antioxidants (cocoa flavanols and ASTX). All formulations were given orally, once daily for a month.Measurements: Serum ASTX was measured by high-performance liquid chromatography. Nitric oxide, malonic dialdehyde and oxidized LDL were quantified spectrophotometrically. Oxygenation parameters were evaluated by near-infrared spectroscopy.Results: One month ingestion of singular formulation of ASTX lead to a 20 fold buildup in serum ASTX level whereas the 4 week ingestion of L-DC-ASTX formulation was accompanied by more prominent accumulation of ASTX in serum (a 40 fold increase over the basal values) at the same daily dose of ASTX. Both antioxidants taken separately decreased serum levels of oxidized LDL and malonic dialdehyde. However effect of L-DC-ASTX formulation was more prominent. ASTX ingested alone caused a borderline increase (p=0.054) in serum nitric oxide (NO) levels, whereas DC ingestion lead to small but statistically significant increase in serum NO concentration. Higher values of NO level were seen after co-ingestion of DC and ASTX, especially in case of L-DC-ASTX formulation suggesting additive/synergistic effects of DC and ASTX on nitric oxide production. These changes were in agreement with the increase in plasma oxygen transport and tissue oxygen saturation seen in the volunteers supplemented with L-DC-ASTX formulation.Conclusion: The nutraceutical formulation of DC and ASTX with an enhanced bioavailability of ASTX can be efficiently used for the correction of oxidative status in aging individuals. [ABSTRACT FROM AUTHOR]

Objective: To describe outcomes for women with a Fontan circulation attending preconception counselling (PCC). Exploring (1) impact of counselling on decision to become pregnant; (2) pregnancy rates in those opting for pregnancy and (3) short-term and long-term outcome of those who succeeded in becoming pregnant.Methods: Retrospective review of women aged 16-45 years with a Fontan circulation from 1994 to 2014.Results: 58 women were offered PCC, 3 declined and 55 received PCC. Following PCC, 15 opted against conception, 16 decided to delay pregnancy, 19 attempted pregnancy and 5 were lost to follow-up. Of the 19 women, 14 succeeded, becoming pregnant a total of 43 times (median 1, range 1-9). Of these, 6 miscarried all pregnancies. 8 carried 14 pregnancies to viability. Baseline hypoxaemia and cardiac disease in pregnancy (CARPREG) score was similar in those opting for and against pregnancy, but CARPREG score was better in those delaying conception. Women exclusively miscarrying or unable to conceive were more likely to have baseline hypoxaemia and greater CARPREG score. Cardiac complications included arrhythmia requiring treatment (n = 4) and one thromboembolism. Obstetric complications were greater in women with a Fontan circulation, 10 preterm births (< 37 weeks) and 8 small for gestational age babies (< 10th centile). There was one neonatal death. At follow-up, there was no deterioration in clinical status as determined by echo.Conclusions: Most women accept PCC and decided to pursue pregnancy; in some cases, this was despite being advised of a poor prognosis. Pregnancy outcome was related to baseline hypoxia and CARPREG scores. [ABSTRACT FROM AUTHOR]

Despite the fall in numbers of unexpected infant deaths that followed the 'Back to Sleep' campaigns in the early 1990 s in the UK and many other countries, such deaths remain one of the largest single groups of deaths in the postneonatal period in many Western countries. Changes in the ways in which unexpected infant deaths are categorised by pathologists and coroners, and increasing reluctance to use the term 'sudden infant death syndrome', make assessment of nationally and internationally collected data on incidence potentially inaccurate and confusing. In this paper, we review current understanding of the epidemiology and aetiology of unexpected deaths in infancy, and current hypotheses on the pathophysiology of the processes that may lead to death. We also review interventions that have been adopted, with variable degrees of effectiveness in efforts to reduce the numbers of deaths, and new approaches that offer the possibility of prevention in the future. [ABSTRACT FROM AUTHOR]

Background and Objective: 'Natural selection' has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations. Criteria for considering studies for this review: All studies of the association of genetic factors with human hypoxic exercise performance, whether at sea level using 'nitrogen dilution of oxygen' (normobaric hypoxia), or at altitude or in low-pressure chambers (field or chamber hypobaric hypoxia, respectively) were sought for review. Search strategy for identification of studies: Two electronic databases were searched (Ovid MEDLINE, Embase) up to 31 January 2014. We also searched the reference lists of relevant articles for eligible studies. All studies published in English were included, as were studies in any language for which the abstract was available in English. Data collection and analysis: Studies were selected and data extracted independently by two reviewers. Differences regarding study inclusion were resolved through discussion. The quality of each study was assessed using a scoring system based on published guidelines for conducting and reporting genetic association studies. Results: A total of 11 studies met all inclusion criteria and were included in the review. Subject numbers ranged from 20 to 1,931 and consisted of healthy individuals in all cases. The maximum altitude of exposure ranged from 2,690 to 8,848 m. The exercise performance phenotypes assessed were mountaineering performance ( n = 5), running performance ( n = 2), and maximum oxygen consumption ( $$ \dot{V} $$ Omax) ( n = 4). In total, 13 genetic polymorphisms were studied, four of which were associated with hypoxic exercise performance. The adenosine monophosphate deaminase (AMPD1) C34T (rs17602729), beta2-adrenergic receptor (ADRB2) Gly16Arg single nucleotide polymorphism (SNP) (rs1042713), and androgen receptor CAG repeat polymorphisms were associated with altitude performance in one study, and the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) (rs4646994) polymorphism was associated with performance in three studies. The median score achieved in the study quality analysis was 6 out of 10 for case-control studies, 8 out of 10 for cohort studies with a discrete outcome, 6 out of 9 for cohort studies with a continuous outcome, and 4.5 out of 8 for genetic admixture studies. Conclusion: The small number of articles identified in the current review and the limited number of polymorphisms studied in total highlights that the influence of genetic factors on exercise performance in hypoxia has not been studied in depth, which precludes firm conclusions being drawn. Support for the association between the ACE-I allele and improved high-altitude performance was the strongest, with three studies identifying a relationship. Analysis of study quality highlights the need for future studies in this field to improve the conduct and reporting of genetic association studies. [ABSTRACT FROM AUTHOR]

Key content ST analysis ( STAN) involves a combination of fetal heart rate interpretation and analysis of the fetal electrocardiogram., STAN has been available for over 5 years in the UK and is used in some, but not all, maternity units., STAN aims to reduce the incidence of fetal acidaemia and hypoxia by identifying these earlier and with greater sensitivity than cardiotocography ( CTG) alone., Learning objectives To be familiar with the background theory and evidence for the use of STAN., To learn the principles for interpretation of the STAN trace., To review practical tips for STAN application and use of STAN monitors., Ethical issues STAN interpretation is currently not part of the RCOG curriculum for obstetrics and gynaecology trainees., Trainees may rotate to a unit that uses STAN routinely and be expected to participate in its use with minimal training. [ABSTRACT FROM AUTHOR]

Objective. To investigate the role of hypoxia in the pathology of osteoarthritic (OA) bone by exploring its effect on the phenotype of isolated primary osteoblasts from patients with knee OA. Methods. OA bone samples were collected at the time of elective joint replacement surgery for knee or hip OA. Normal bone samples were collected postmortem from cadaver donors. Primary osteoblasts were isolated from knee OA bone chips and cultured under normoxic or hypoxic (2% O2) conditions. Alkaline phosphatase activity was quantified using an enzymatic assay, and osteopontin and prostaglandin E2 (PGE2) production was assayed by enzyme-linked immunosorbent assay. Total RNA was extracted from bone and osteoblasts, and gene expression was profiled by quantitative reverse transcription-polymerase chain reaction. Results. Human OA bone tissue sections stained positively for carbonic anhydrase IX, a biomarker of hypoxia, and exhibited differential expression of genes that mediate the vasculature and blood coagulation as compared to those found in normal bone. Culture of primary osteoblasts isolated from knee OA bone under hypoxic conditions profoundly affected the osteoblast phenotype, including the expression of genes that mediate bone matrix, bone remodeling, and bone vasculature. Hypoxia also increased the expression of cyclooxygenase 2 and the production of PGE2 by OA osteoblasts. Osteoblast expression of type II collagen α1 chain, angiopoietin-like 4, and insulin-like growth factor binding protein 1 was shown to be mediated by hypoxiainducible factor 1α. Chronic hypoxia reduced osteoblastmineralized bone nodule formation. Conclusion. These findings demonstrate that hypoxia can induce pathologic changes in osteoblast functionality consistent with an OA phenotype, providing evidence that hypoxia is a key driver of OA pathology. [ABSTRACT FROM AUTHOR]

The National Institute for Health and Clinical Excellence ( NICE) in the United Kingdom developed guidelines for the diagnosis, prevention, and management of delirium in July 2010 that included 10 recommendations for delirium prevention. The Hospital Elder Life Program ( HELP) is a targeted multicomponent strategy that has proven effective and cost-effective at preventing functional and cognitive decline in hospitalized older persons. HELP provided much of the basis for seven of the NICE recommendations. Given interest by new HELP sites to meet NICE guidelines, three new protocols addressing hypoxia, infection, and pain that were not previously included in the HELP program were developed. In addition, the NICE dehydration guideline included constipation, which was not specifically addressed in the HELP protocols. This project describes the systematic development of three new protocols (hypoxia, infection, pain) and the expansion of an existing HELP protocol (constipation and dehydration) to achieve alignment between the HELP protocols and NICE guidelines. Following the Institute of Medicine recommendations for developing trustworthy guidelines, an interdisciplinary group of experts conducted a systematic review of current literature, rated the quality of the evidence, developed intervention protocols based on the highest-quality evidence, and submitted the protocols first to internal review and then to external review by an interdisciplinary panel of experts. The protocols were revised based on the review process and incorporated into the HELP materials. Inclusion of these protocols enhances the scope of the HELP program and allows fulfillment of NICE guideline recommendations for delirium prevention. The rigorous process applied may provide a useful example for updating existing guidelines or protocols that may be applicable to a broad range of clinical applications. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen therapy (HBO) may be a useful adjunct for chronic nonhealing wounds when the aetiology includes a hypoxic component. Occasionally, HBO is administered in unusual cases that have no obvious hypoxic involvement. The aim of this case series was to assess whether HBO would be beneficial in the management of chronic wounds with no obvious hypoxic component. Three chronic wounds with no apparent hypoxic complications were treated with HBO and the outcomes reviewed. All three cases demonstrated improved wound healing during the course of HBO, suggesting it may be a beneficial adjunct in the management of chronic wounds with no obvious hypoxic component. [ABSTRACT FROM AUTHOR]

The case of Ryan St George v Home Office [2008] EWCA Civ 1068 raised unusual issues on breach of duty, causation and contributory negligence. The 29 year old claimant had a history of alcohol and drug abuse, withdrawal seizures, and previous custodial sentences. Five days after his admission to Prison he sustained a substance withdrawal seizure injury, falling from the top bunk and striking his head on a concrete floor. He developed status epilepticus and subsequent irreversible brain damage. The medical case on causation was whether the head injury resulting from the fall triggered status epilepticus or whether the status epilepticus was a consequence of the withdrawal seizure alone. Mackay J held that the head injury triggered the status epilepticus and that the Home Office had acted in breach of duty following the claimant's admission to prison when he was allocated a top bunk in a dormitory wing. A novel issue on contributory negligence arose because Mackay J reduced the claimant's damages by 15% because his injuries were caused partly by his substance abuse, therefore his "fault" within the meaning of section 1(1) of the Law Reform (Contributory Negligence) Act 1945 ("the 1945 Act"). There had been no previous direct authority on this point. The judge's findings were the subject of an appeal to the Court of Appeal where in the leading judgment Dyson LJ dismissed the appeal against the findings on breach of duty and causation and allowed the crossappeal against the finding of contributory negligence. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood operators have taken measures to reduce transfusion-related acute lung injury (TRALI). We classified suspected TRALI cases reported to Canadian Blood Services from 2001 to 2009 and assessed the impact of TRALI reduction measures. STUDY DESIGN AND METHODS: Using Canadian Consensus Conference definitions, cases were reviewed by two experts or, from 2006 to 2009, a TRALI Medical Review Group (TMRG). Detection of HLA antibodies was performed using the Luminex system starting in 2008. Measures implemented from 2007 to 2009 included use of predominantly male plasma, suspension of buffy coat platelets in male plasma, and deferral of females with a pregnancy history from plateletpheresis. The buffy coat production method was implemented from 2005 to 2008. RESULTS: Reporting of all suspected TRALI cases, as well as cases classified as definite or possible, increased from 2001 to 2004, was stable from 2004 to 2007, and declined in 2008 to 2009. The decline was most marked for plasma-associated cases, but occurred for all components. TMRG consensus on classification was achieved in 56% of cases. Cases identified as definitive or possible TRALI were significantly more likely to have donor antibody against a corresponding recipient antigen, compared to other cases. CONCLUSION: Hemovigilance data demonstrated an initial increase in TRALI cases, likely due to increased adverse event reporting and awareness of TRALI, followed by a decrease in cases related to all components. TRALI prevention measures and possibly the switch to the buffy coat production method may have contributed to the decline. Classification of cases remains challenging. [ABSTRACT FROM AUTHOR]

The article presents analysis on Mr. Faulkner, a Great Britain's Defence Ministry research scientist's experiences of three different causes of respiratory failure such as the pulmonary embolism (PE), altitude hypoxia, and myasthenia gravis. It leads to further understanding the physiology of breathing and the pathophysiology of respiratory failure. It concludes that Mr. Faulkner's near fatal misdiagnosis emphasizes the need for neurologist's knowledge on respiratory failure.

Background: Recent evidence suggests that the duodenum can regulate iron absorption independently of hepcidin via the transcription factor Hif-2α acting directly on the transcription of the proteins involved in the iron transport. The current study investigates the temporal relationship between Dcytb and Hif-2α during early hypoxic stimulus in the enterocyte in vivo. Methods: Duodenal Dcytb and Hif-2α protein expression was analysed by Western blot technique while gene regulation was determined by quantitative PCR. Results: Both Dcytb and Hif-2α protein expression were increased during the first hours of hypoxic duration. A change in hepcidin expression however, was significant only at 72 h hypoxia. Increased iron absorption reported in early hypoxia could be accounted for in part by the enhancement of Dcytb expression by Hif-2α in the duodenum. Conclusion: Modulation of Hif-2α predominates over hepcidin in the regulation of intestinal iron absorption during short hypoxic duration. The intestine exerts regulatory mechanisms in the dietary absorption of iron into systemic circulation. [ABSTRACT FROM AUTHOR]

There is considerable controversy concerning the benefits and risks of oxygen treatment in many situations and healthcare professionals receive conflicting advice about safe oxygen use. The British Thoracic Society (BTS) has published up-to-date, evidence-based guidelines for emergency oxygen use in the UK in order to encourage the safe use of oxygen in emergency situations and improve consistency of clinical practice. 1 The purpose of this concise guideline is to summarise the key recommendations, particularly concerning emergency oxygen use in the hospital setting. [ABSTRACT FROM AUTHOR]

The occurrence of subdural hemorrhage (SDH) on the convexities of the cerebral hemispheres is not an unusual finding in the setting of intrauterine, perinatal, or neonatal deaths, the hemorrhage usually presenting either as a thin film over the occipital poles or as a small infratentorial bleed. Working in 2 referral centers with over 30 000 deliveries per year, we routinely examine the dura macroscopically and histologically in nonmacerated fetuses over 24 weeks in gestation and in neonates. This paper describes our experience of intradural hemorrhage (IDH) and SDH associated with hypoxia. Our series comprises 25 fetuses and 30 neonates with obvious macroscopic intradural hemorrhage and hypoxia of varying degrees of severity diagnosed by systematic examination of the brain. Fetal gestational age ranged from 26-41/40 weeks (all no more than 24 hours from intrauterine death), while the 30 neonates lived for between 1 hour and 19 days. Simultaneously with IDH, frank SDH was seen in 2 of 3 of all cases (16 fetuses and 20 neonates). Intradural hemorrhage was more prominent in the posterior falx and tentorium, most likely because of the existence of 2 venous plexus at these sites. Our findings demonstrate that SDH and cerebral hypoxia are common associations of IDH and that SDH (often seen as a thin film of hemorrhage) almost always occurs in association with diffuse falcine IDH. Diffuse IDH with SDH are more frequently associated with severe or moderate hypoxic ischemic encephalopathy (HIE), while mild or early HIE is more common with focal IDH without SDH. [ABSTRACT FROM AUTHOR]

Abstract: Placental apoptosis is exaggerated in pre-eclampsia and cytotrophoblast proliferation is enhanced. This imbalance may be a primary pathogenic event, whereby excessive syncytiotrophoblast apoptosis counters cytotrophoblast fusion, promoting the liberation of syncytial material which perturbs the maternal vascular endothelium. We have previously shown that primary trophoblasts and explant cultured villous fragments from pre-eclamptic pregnancies elicit greater levels of terminal differentiation and apoptosis. This review considers current opinions in trophoblast cell turnover in normal pregnancy and pre-eclampsia. In the context of other findings, this review highlights: (i) the disparity in expression of pro-apoptotic transcription factor p53 in the syncytiotrophoblast in pre-eclampsia, (ii) the importance of reactive oxygen species and hypoxia in initiating villous trophoblast apoptosis and (iii) the concept that aberrant intervillous haemodynamics, as opposed to oxygen per se, initiates excessive syncytiotrophoblast shedding. Finally, therapeutic ways of restoring the syncytiotrophoblast in pre-eclampsia and preventing excessive placental apoptosis are considered, including a role for mitotic manipulators and growth factor replacement strategies. [Copyright &y& Elsevier]

George F Winter weighs in on pulse oximetry screening as an effective method of testing for critical congenital heart defects in newborns [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is an intensively studied molecule that has significant potential, both in stimulating angiogenesis and as a target for antiangiogenic approaches. We utilised MCF-7 breast cancer cells transfected with either of two of the major VEGF isoforms, VEGF(121) or VEGF(165), or fibroblast growth factor-1 (FGF-1) to distinguish the effects of these factors on tumour growth, vascular function, and oxygen delivery. While each transfectant demonstrated substantially increased tumorigenicity and growth rate compared to vector controls, only VEGF(121) produced a combination of significantly reduced total and perfused vessel spacing, as well as a corresponding reduction in overall tumour hypoxia. Such pathophysiological effects are of potential importance, since antiangiogenic agents designed to block VEGF isoforms could in turn result in the development of therapeutically unfavourable environments. If antiangiogenic agents are also combined with conventional therapies such as irradiation or chemotherapy, microregional deficiencies in oxygenation could play a key role in ultimate therapeutic success. [ABSTRACT FROM AUTHOR]

The article presents abstracts of studies on rheumatology which include the expression of autoimmune risk gene UBE2L3 during B cell proliferation, the impact of hypoxia on neutrophil extracellular trap formation and the influence of idiopathic inflammatory myopathies (IIM) on muscles.

Five patients are reported with sickle cell syndromes (HbSS, HbSC and HbSthal) in whom rapid exchange transfusion led to resolution of life threatening infarctive crises. The technique appears to be of value in the management of severe complications of sickle cell syndromes. [ABSTRACT FROM AUTHOR]

A high proportion of litigation claims against the NHS arise from decisions taken in obstetrics. Fetal blood sampling (FBS) is undertaken to establish fetal pH levels in cases where delivery by caesarean is contemplated because of an abnormal fetal heart-rate pattern and other indications of distress. Rapid falls in pH can be indicative of distress accompanied by a high risk of hypoxia. Accuracy in both sampling and analytical procedures is crucial, since the diagnostic outcome of FBS can provide the basis for decisions taken during the course of labour and may subsequently provide the necessary legal evidence that those decisions were correct. [ABSTRACT FROM AUTHOR]

Asthma is now the most common chronic childhood illness in Great Britain and the prevalence is increasing. Currently 1.5 million children (aged 2-15 years) in Great Britain are estimated to have asthma, giving the country one of the highest prevalences in the world. Asthma also has a significant social impact, including school absence and poorer psychological health. Effective management of asthma depends primarily on early recognition of asthma symptoms. Children with acute asthma, who have a poor perception of breathlessness, may present late, leading to a greater degree of hypoxia.

Any disease that affects one million people in the United Kingdom and causes 30 000 deaths a year must be so familiar to all practising doctors that articles on treatment and management might be considered superfluous, particularly when the effects of treatment are unlikely to be dramatic. No intervention short of a lung transplant is going to affect the irreversible changes ot chronic bronchitis and emphysema, but appropriate treatment can help the patient considerably and should reduce the number of hospital admissions. Unfortunately most patients present at a late stage of the disease when symptoms are becoming a problem and considerable airways obstruction is present.[4] I propose therefore to discuss treatment for these symptoms and the two main complications of arterial hypoxaemia-polycythaemia and pulmonary hypertension. [ABSTRACT FROM AUTHOR]

The article presents a study on the use of mains-powered hypoxic gas generator in evaluating patients at risk from hypoxia during air travel in Great Britain. The findings reveal that this generator offers results comparable with those obtained using oxygen desaturation and hypobaric chambers in patients with chronic obstructive pulmonary disease (COPD). This method is also safe and cost-effective alternative to using gas mixtures for centres offering a pre-flight assessment service.

The article presents a study on the effect of acute hypoxia on the QT interval corrected for heart rate (QTc) in patients with chronic respiratory disease who are undergoing fitness to fly tests in Great Britain. It notes that the findings of the study reveal that patients who have experienced acute hypoxia do not have significant changes in their cardiac QTc. It was also found out that sudden death in COPD patients is not associated with prolonged QTc.

The article presents questions and answers related to chronic heart failure (CHF) including one on the benefits of long-term home oxygen therapy in CHF, one on the prevalence of hypoxaemia in patients with CHF, and one on the use of oxygen to reduce breathlessness.

The article provides information on an analysis of normal Spo2 levels in children up to five years old that are living in regions as high as ∼400 m, by Subhi and colleagues of Great Britain. It mentions that predictive equation of the researchers for mean Spo2 relative to altitude is also an indication of functional adaptation over-and-above acute homeostasis. They suggest that the lower limit of the meta-regression offers a "hypoxaemia threshold." This threshold can be used as the threshold for escalating Fio2 in acute respiratory illnesses.

Presents several issues related to the field of aviation medicine in Great Britain. Discussion on aviation hypoxia acquired from balloon flights; Safety of hang gliding; Need for pilots of microlight aircraft to have a license and medical certificate.

Presents case studies of patients diagnosed with bilateral diaphragmatic paralysis in Great Britain. Symptoms of the disease; Reduction of the total lung capacity; Association of the disease with mild nocturnal hypoxemia.

Presents a study evaluating the outcome of laparoscopic adjustable Swedish gastric banding among obese patients in Great Britain. Result of massive fatty liver or severe intraoperative hypoxia and hypotension; Absence of perioperative deaths; Occurrence of several complications.

Focuses on the case of a triathlete who presented with fever, headache, myalgia, and nausea after competing in triathlons which involved swimming in the river Liffey in Ireland and the Severn in England. How he became breathless and hypoxemic following antimicrobial treatment, signalling a Jarisch-Herxheimer reaction; Diagnosis of acute leptospirosis.