A Genetic Basis of Susceptibility to Acute Pyelonephritis

For unknown reasons, urinary tract infections (UTIs) are clustered in certain individuals. Here we propose a novel, genetically determined cause of susceptibility to acute pyelonephritis, which is the most severe form of UTI. The IL-8 receptor, CXCR1, was identified as a candidate gene when mIL-8Rh mutant mice developed acute pyelonephritis (APN) with severe tissue damage.We have obtained CXCR1 sequences from two, highly selected APN prone patient groups, and detected three unique mutations and two known polymorphisms with a genotype frequency of 23% and 25% compared to 7% in controls (p<0.001 and p<0.0001, respectively). When reflux was excluded, 54% of the patients had CXCR1 sequence variants. The UTI prone children expressed less CXCR1 protein than the pediatric controls (p<0.0001) and two sequence variants were shown to impair transcription.The results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring

Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test_2-sided). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p

Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China:lessons learnt and international expert recommendations

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 &lt;90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 &lt;90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure &lt;90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients

Extubación del paciente perioperatorio con una vía aérea difícil

ResumenExiste un volumen importante de literatura dedicada al tema del manejo de la vía aérea difícil, y se han desarrollado una serie de algoritmos y recomendaciones para el manejo seguro de pacientes en riesgo de una intubación difícil. Sin embargo, solo recientemente se ha despertado una mayor conciencia acerca de la extubación de la vía aérea difícil, pues aun cuando sea un procedimiento programado, suele estar plagado de complicaciones. La importancia de desarrollar estrategias pre-programadas para la extubación de la vía aérea difícil a fin de aumentar la seguridad del paciente y sus desenlaces se hace evidente a partir de los datos del ASA Closed Claims Analysis y del reciente Cuarto Proyecto Nacional de Auditoría del Reino Unido sobre complicaciones mayores en el manejo de la vía aérea. La clave para un manejo exitoso de los pacientes en riesgo de extubación difícil es efectuar una evaluación precisa de riesgo, aplicar estrategias apropiadas y la preparación tanto del médico como de la institución.AbstractA considerable amount of literature has been dedicated to the topic of difficult airway management and a number of algorithms and recommendations have been established to safely manage patients at risk for difficult intubation. Only recently, however, has extubation of the difficult airway gained more awareness since this procedure, although elective, is often fraught with complications. The importance of developing pre-planned strategies for extubation of the difficult airway to improve patient safety and outcomes is apparent from data from both the ASA Closed Claims Analysis and the UK's recent Fourth National Audit Project of major complications of airway management. The key to successful management of patients at risk for difficult extubation is accurate risk assessment, application of appropriate strategies, and preparedness by both the individual practitioner and the institution

Identification of the Epidural Space Using Pressure Measurement With the Compuflo Injection Pump – A Pilot Study

While epidural anesthesia (EA) is frequently used, success rate varies and complications associated with incorrect needle placement can occur. Different methods of objective identification of the epidural space (ES) have been suggested, without receiving widespread popularity. This prospective pilot study evaluated continuous pressure measurement during low speed injection with a computerized injection pump to objectively identify the ES. While EA was performed using a conventional loss of resistance technique in 20 consecutive patients, the injection pump technology was used to obtain pressure readings from the supraspinous ligament, the ligamentum flavum, and the ES. In the next 20 patients, the epidural space was solely identified with the computerized injection pump. Pressure reading obtained during the first part of the study revealed significant differences between the ES vs. the supraspinous ligament, and the ES vs. the ligamentum flavum (8 mm Hg, 95% confidence interval [CI] 6-11 vs 79 mm Hg, 95% CI 74-83 and 92 mm Hg, 95% CI 83-102, respectively) ( P < .001). In the second part of the study, the injection pump allowed for successful identification of the ES and performance of EA in all 20 patients. This investigation demonstrates that a computerized injection pump can be used to identify the epidural space and can serve as a base for further comparative research to determine whether this technology can increase the success rate of EA or lower the incidence of side effects