Ultrasound-guided caudal blockade and sedation for paediatric surgery: a retrospective cohort study.

Data on safety and success rates of ultrasound-guided caudal blockade, performed on sedated children with an uninstrumented airway, are scarce. We performed a retrospective observational study of validated data from April 2014 to December 2020 in a paediatric cohort where the initial plan for anaesthetic management was sedation and caudal epidural without general anaesthesia or airway instrumentation. We examined success rates of this approach and rates of block failure and block-related complications. In total, 2547 patients ≤ 15 years of chronological age met inclusion criteria. Among the 2547 cases, including 453 (17.8%) former preterm patients, caudal-plus-sedation success rate was 95.1%. The primary anaesthesia plan was abandoned for general anaesthesia in 124 cases. Pain-related block failure in 83 (3.2%) was the most common cause for conversion. Complications included 39 respiratory events and 9 accidental spinal anaesthetics. Higher odds of pain-related block failure were associated with higher body weight (adjusted OR 1.063, 95%CI 1.035-1.092, p < 0.001) as well as with mid-abdominal surgery (e.g. umbilical hernia repair) (adjusted OR 15.11, 95%CI 7.69-29.7, p < 0.001), whereas extreme (< 28 weeks) former prematurity, regardless of chronological age, was associated with higher odds (adjusted OR 3.62, 95%CI 1.38-9.5, p = 0.009) for respiratory problems. Ultrasound-guided caudal epidural, performed under sedation with an uninstrumented airway, is an effective technique in the daily clinical routine. Higher body weight and mid-abdominal surgical procedures are risk factors for pain-related block failure. Patients who, regardless of chronological age, had been born as extreme preterm babies are at the highest risk for respiratory events.

Biallelic CSGALNACT1-mutations cause a mild skeletal dysplasia.

Genetic causes of skeletal disorders are manifold and affect, among others, enzymes of bone and connective tissue synthesis pathways. We present a twelve-year-old boy with a mild skeletal dysplasia, hypermobility of joints and axial malalignment of lower limbs and feet. Exome sequencing revealed a biallelic loss of function mutation in CSGALNACT1, which encodes chondroitin sulfate N-acetylgalactosaminyltransferase 1 and plays a major role in the chondroitin sulfate chain biosynthesis and therefore in the synthesis of glycosaminoglycans. Recently, the first case of a pediatric patient with a mild skeletal dysplasia due to a compound heterozygous large intragenic deletion and a damaging missense variant in CSGALNACT1 was reported. We here identify a second case and the first juvenile patient with a homozygous frameshift variant in CSGALNACT1 which corroborates its role in mild and non-progressive skeletal dysplasia with joint laxity.

Incidence of hyperoxia and related in-hospital mortality in critically ill patients: a retrospective data analysis.

BACKGROUND: Mechanical ventilation with oxygen is life-saving, however, may result in hyperoxia. The aim was to analyse the incidence and duration of hyperoxia burden and related in-hospital mortality in critically ill patients. METHODS: Patients of all ages admitted to intensive care units (ICUs) and with mechanical ventilation for at least seven consecutive days were included in this single centre retrospective medical record audit. The main outcome measure was time-weighted arterial partial pressure of oxygen (PaO2 ) over 7 days. Logistic regression for association with in-hospital mortality and propensity score matching was performed. RESULTS: In total, 20,889 arterial blood gases of 419 patients were analysed. Time-weighted mean PaO2 was 14.0 ± 2.4 kPa. Time-weighted mean FiO2 was 49.2 ± 12.1%. Seventy-six (18.1%) patients showed continuous hyperoxia exposure, defined as time-weighted mean PaO2 > 16 kPa. Duration of hyperoxia, hypoxia (PaO2 < 8 kPa) and normoxia (PaO2 8-16 kPa) were 37.9 ± 31.0 h (23.7%), 4.9 ± 9.5 h (3.1%), and 116.8 ± 29.6 h (73.2%). Hyperoxia occurred especially at low to moderate FiO2 in patients of first and second age quartiles (1-57 years) with smaller SAPS2 score. In-hospital mortality of patients with hyperoxia (32.9%) or normoxia did not differ (35.9%; P = 0.691). Conditional logistic regression showed no association between hyperoxia and in-hospital mortality (OR 1.46; 95%CI 0.72-2.96; P = 0.29). CONCLUSION: Substantial hyperoxia burden was observed in ICU patients. Young patients with less comorbidities showed hyperoxic episodes more often, especially with lower FiO2 . Hyperoxia during 7 days of mechanical ventilation did not correlate to increased in-hospital mortality.

Hydroxyethyl starch 130/0.4 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation.

BACKGROUND: During systemic inflammation, leucocytes are activated and extravasate into damaged tissue. Activation and recruitment are influenced by different mechanisms, including the interaction of leucocytes with platelets and neutrophil extracellular traps (NET) formation. Here, we investigated the molecular mechanism by which hydroxyethyl starch (HES 130/0.4) dampens systemic inflammation in vivo. METHODS: Systemic inflammation was induced in C57Bl/6 wild-type mice by caecal ligation and puncture and cytokine concentrations in the blood, neutrophil recruitment, platelet-neutrophil aggregates, and NET formation were investigated in vivo. Intravascular adherent and transmigrated neutrophils were analysed by intravital microscopy (IVM) of the cremaster muscle and the kidneys. Flow chamber assays were used to investigate the different steps of the leucocyte recruitment cascade. RESULTS: By using flow cytometry, we demonstrated that HES 130/0.4 reduces neutrophil recruitment into the lung, liver, and kidneys during systemic inflammation (n=8 mice per group). IVM revealed a reduced number of adherent and transmigrated neutrophils in the cremaster and kidney after HES 130/0.4 administration (n=8 mice per group). Flow chamber experiments showed that HES 130/0.4 significantly reduced chemokine-induced neutrophil arrest (n=4 mice per group). Furthermore, HES 130/0.4 significantly reduced the formation of platelet-neutrophil aggregates, and NET formation during systemic inflammation (n=8 mice per group). CONCLUSIONS: Our findings suggest that HES 130/0.4 significantly reduces neutrophil-platelet aggregates, NET formation, chemokine-induced arrest, and transmigration of neutrophils under inflammatory conditions.

Identifying the health conscious consumer.

Individuals who lead a "wellness-oriented" lifestyle are concerned with nutrition, fitness, stress, and their environment. They accept responsibility for their health and are excellent customers for health-related products and services. Those who lack a wellness orientation are identified as higher health risks and become candidates for health promotion program intervention. The authors report a new scale by which to measure the wellness-oriented lifestyle. Scale development procedures are detailed, followed by information from five studies that support its validity. The authors suggest ways health care marketers may use the Wellness Scale to segment and target potential customers and position their products and services.

Estrogen metabolism in rat liver microsomal and isolated hepatocyte preparations--I. Metabolite formation and irreversible binding to cellular macromolecules.

The metabolism of endogenous estrogens, estradiol and estrone, and the irreversible binding of estrogens to cellular macromolecules have been examined and compared in subcellular microsomal and in intact hepatocyte preparations. In studies with rat liver microsomal preparations containing estradiol, an NADPH-generating system, and denatured DNA, the irreversible binding of radiolabeled steroid metabolite(s) to the microsomal proteins was 3.26 nmoles/mg protein in 1 hr (S.D. 0.39; 7.9% of total steroid) while binding to DNA was found to be 0.288 nmole/mg DNA/mg protein (S.D. 0.025; 0.39% of total steroid). No significant difference was observed between microsomal preparations from untreated, phenobarbital-treated or 3-methylcholanthrene-treated rats. Irreversible binding to proteins was also demonstrated in the intact hepatocyte cell incubations. After 2-hr incubations of estradiol with hepatocytes, 5.9% (S.D. 1.4%) of the steroid(s) was irreversibly associated with cellular proteins (approximately 1.43 pmoles/mg/min). Analysis of the organic-soluble metabolites demonstrated the presence of the catechol estrogens and their metabolites, 2-hydroxyestradiol, 2-hydroxyestrone, 2-methoxyestradiol, and 2-methoxyestrone. Estrone and estriol were also identified. The aqueous-soluble materials isolated from hepatocyte incubations contained glucuronide, sulfate, and apparent thioether conjugates, as determined by liberation from estrogen metabolites by treatment with beta-glucuronidase, sulfatase, and Raney nickel. Thus, extensive primary and secondary metabolism of estrogens occurs in intact hepatocyte incubations. Furthermore, irreversible binding of estrogens to cellular proteins occurs in these intact cells having demonstrated conjugative pathways of metabolism.

Estrogen metabolism in rat liver microsomal and isolated hepatocyte preparations--II. Inhibition studies.

The abilities of various inhibitors and metabolism modifiers to alter the metabolism of estradiol and the irreversible binding of estradiol to proteins were examined in subcellular microsomal incubations and in intact hepatocyte preparations. In studies with rat liver microsomal preparations containing estradiol and an NADPH-generating system, the irreversible binding of radiolabeled steroid metabolite(s) to the microsomal proteins was 77.59 pmol/mg/min (SD 6.1; 7.6% of total steroid). 2-Bromoestradiol and 4-bromoestradiol, inhibitors of estrogen 2-hydroxylase, effectively decreased this irreversible binding of radiolabeled estradiol metabolite(s) to microsomal proteins to 17 pmol mg-1 min-1 (2.1% of total estradiol). These haloestrogens were also effective inhibitors in the intact hepatocyte cells, decreasing the amounts of organic metabolites, aqueous-soluble conjugates, and protein-bound materials. The HPLC radiochromatograms of the organic-extracted fractions from the 2 h hepatocyte incubations demonstrate that the catechol estrogen products, i.e. 2-hydroxyestrogens and 2-methoxyestrogens, were present in lower amounts in the incubations containing the bromoestrogens than in control incubations containing no inhibitor. Ascorbic acid and cysteine, general modifiers of oxidative pathways of metabolism, also affected estradiol metabolism in microsomal and hepatocyte preparations. Both these agents were able to decrease the irreversible binding of estradiol to proteins in the microsomal assays. Ascorbic acid decreased the general metabolism of estradiol in the hepatocyte incubations but did not decrease irreversible binding to proteins. The addition of cysteine to the hepatocyte incubation resulted in an increased metabolism of estradiol and the production of more aqueous-soluble radiolabeled metabolites than the control incubations; however, cysteine did not decrease the amounts of estradiol metabolite(s) irreversibly bound to proteins. Investigations of steroid metabolism in the isolated hepatocytes thus provide an effective in vitro technique for examining the overall oxidative, reductive, and conjugative pathways that are functional in the liver and enables one to investigate the abilities of inhibitors, regulators, and modifiers to affect the metabolic processes. Also, these hepatocyte studies demonstrate that the inhibitors of estrogen 2-hydroxylase, 2-bromoestradiol and 4-bromoestradiol, can enter and act in the intact cells. Consequently, these agents may be useful pharmacological probes for examining the functions of catechol estrogens in other tissues.

[Antigenicity and resorptive behavior of the usual gelatin preparations and of dry fibrin foam]. / Uber Antigenität und Resorptionsverhalten gebräuchlicher Gelatinepräparate und von Trockenfibrinschaum.

Immunofluorescence studies of Gelastypt, Gelfoam, and Fibrospum showed species-specific, protein-dependent antigen characteristics. Additional experimental studies using guinea pigs revealed that, after subcutaneous implantation, these materials do not lose their antigen characteristics during the resorptive process. Remnants of subcutaneously implanted material could be demonstrated intracellularly (macrophages) in the spleens of the experimental animals four weeks later.