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A comprehensive pharmacy service for patients with asthma and chronic obstructive pulmonary disease is no more effective than giving patients a peak flow meter and teaching them how to use it. This was the conclusion of a study of 1,113 patients. In fact, the comprehensive pharmacy service actually caused an increase in the number of hospitalizations and visits to an emergency department.

To investigate peak expiratory flow rate (PEFR) and quality of life scores for their ability to predict exacerbations of asthma. We identified adults who received oral or inhaled asthma medications from 36 community drugstores. We administered the McMaster Asthma Quality of Life Questionnaire (AQLQ) and measured PEFR, defining “red zone” (highest risk) as a PEFR < 50% of each patient's expected value based on gender, age, and height. We identified asthma exacerbations (breathing-related emergency department visits and hospitalizations) within 4 and 12 months after enrollment and used proportional hazards regression to assess the ability of PEFR and AQLQ scores to predict exacerbations, controlling for clinical and demographic factors. A red zone PEFR was a significant univariable predictor of exacerbations within 12 months (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1 to 3.0; P = .027). However, neither a red zone PEFR, the raw PEFR, or percent of predicted maximal PEFR were significantly predictive when controlling for AQLQ scores, clinical characteristics, or demographic data ( P > .2). However, the 4 subscales of the AQLQ were each significant univariable and multivariable predictors of asthma exacerbations. For example, the overall AQLQ scale had a multivariable HR of 0.63 (95% CI, 0.46 to 0.87; P = .005) for exacerbations occurring within 4 months and 0.66 (95% CI, 0.54 to 0.82; P < .001) within 12 months. PEFR added no predictive information to that contained in AQLQ scores and clinical and demographic data. These results support the National Institutes of Health asthma guidelines’ recommendation for routinely assessing symptoms but not PEFR. J GEN INTERN MED 2004;19:237–242. [ABSTRACT FROM AUTHOR]

Background: Oxygen radicals have been implicated as important mediators in the early pathogenesis of acute pancreatitis, but the mechanism by which they produce pancreatic tissue injury remains unclear. We have, therefore, investigated the effects of oxygen radicals on isolated rat pancreatic acinar cells as to the ultrastructure, cytosolic Ca[sup 2+] concentration and energy metabolism. Methods: Acinar cells were exposed to an oxygen radical-generating system consisting of xanthine oxidase, hypoxanthine and chelated iron ions. Cell injury was assessed by LDH release and electron microscopy. Cytosolic Ca[sup 2+] levels and mitochondrial membrane potential were determined by flow cytometry; adenine nucleotide concentrations by HPLC. Mitochondrial dehydrogenase activity was measured by spectrophotometric assay. Results: Oxygen radicals damaged the plasma membrane as shown by a 6-fold LDH increase in the incubation medium within 180 min. At the ultrastructural level, mitochondria were the most susceptible to oxidative stress. In correlation to the pronounced mitochondrial damage, the mitochondrial dehydrogenase activity declined by 70%, whereas the mitochondrial membrane potential was enhanced by 27% after 120 min. Together this may cause the 85% decrease in the ATP concentration and the corresponding increase in ADP/AMP observed in parallel. In addition, an immediate 26% increase in cytosolic Ca[sup 2+] was found, a change which could be inhibited by BAPTA, reducing cellular damage. Conclusion: Cytosolic Ca[sup 2+] synergizes with oxygen radicals causing alterations of the ultrastructure and energy metabolism of acinar cells which might contribute to the cellular changes found in early stages of acute pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains.Methods: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90.Results: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.Conclusions: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.). [ABSTRACT FROM AUTHOR]

The western honeybee, Apis mellifera, is a managed pollinator of many crops and potentially exposed to a wide range of foreign compounds, including pesticides throughout its life cycle. Honeybees as well as other insects recruit molecular defense mechanisms to facilitate the detoxification of xenobiotic compounds. The inventory of detoxification genes (DETOXome) is comprised of five protein superfamilies: cytochrome P450 monooxygenases (P450), carboxylesterases, glutathione S-transferases (GST), UDP-glycosyl transferases (UGT) and ATP-binding cassette (ABC) transporters. Here we characterized the gene expression profile of the entire honeybee DETOXome by analyzing 47 transcriptomes across the honeybee life cycle, including different larval instars, pupae, and adults. All life stages were well separated by principal component analysis, and K-means clustering revealed distinct temporal patterns of gene expression. Indeed, >50% of the honeybee detoxification gene inventory is found in one cluster and follows strikingly similar expression profiles, i.e., increased expression during larval development, followed by a sharp decline after pupation and a steep increase again in adults. This cluster includes 29 P450 genes dominated by CYP3 and CYP4 clan members, 15 ABC transporter genes mostly belonging to the ABCC subfamily and 13 carboxylesterase genes including almost all members involved in dietary/detox and hormone/semiochemical processing. RT-qPCR analysis of selected detoxification genes from all families revealed high expression levels in various tissues, especially Malpighian tubules, fatbody and midgut, supporting the view that these tissues are essential for metabolic clearance of environmental toxins and pollutants in honeybees. Our study is meant to spark further research on the molecular basis of detoxification in this critical pollinator to better understand and evaluate negative impacts from potentially toxic substances. Additionally, the entire gene set of 47 transcriptomes collected and analyzed provides a valuable resource for future honeybee research across different disciplines., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: With large numbers of COVID-19 patients requiring mechanical ventilation and ventilators possibly being in short supply, in extremis two patients may have to share one ventilator. Careful matching of patient ventilation requirements is necessary. However, good matching is difficult to achieve as lung characteristics can have a wide range and may vary over time. Adding flow restriction to the flow path between ventilator and patient gives the opportunity to control the airway pressure and hence flow and volume individually for each patient. This study aimed to create and validate a simple model for calculating required flow restriction., Methods and Findings: We created a simple linear resistance-compliance model, termed the BathRC model, of the ventilator tubing system and lung allowing direct calculation of the relationships between pressures, volumes, and required flow restriction. Experimental measurements were made for parameter determination and validation using a clinical ventilator connected to two test lungs. For validation, differing amounts of restriction were introduced into the ventilator circuit. The BathRC model was able to predict tidal lung volumes with a mean error of 4% (min:1.2%, max:9.3%)., Conclusion: We present a simple model validated model that can be used to estimate required flow restriction for dual patient ventilation. The BathRC model is freely available; this tool is provided to demonstrate that flow restriction can be readily estimated. Models and data are available at DOI 10.15125/BATH-00816., Competing Interests: No conflict of interest. The support from BMI Bath Clinic does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Endoscopic resection of sinonasal cancer has become an alternative to open craniofacial surgery and leads to safe and satisfying results in emerging numbers. Randomized study data comparing outcomes between approaches are missing. Hence, it remains unclear which subgroups of patients might profit most from each technique. We aimed to identify such patient and tumor characteristics and gather information for future prospective study design., Study Design: Case series with chart review., Setting: Tertiary academic center., Subjects and Methods: This study is based on a retrospective chart review of 225 patients undergoing open craniofacial or endoscopic resection for sinonasal malignancy between 1993 and 2015 at Munich University Hospital. Statistical analyses include t test, chi-square, Kaplan-Meier charts, and univariate and multivariate analyses., Results: The sample size was similar between the endoscopic and open surgery groups. Tumors were significantly larger in patients who underwent open craniofacial resection. The risk of notable bleeding ( P = .041) was lower and hospital stay shorter ( P = .001) for endoscopic interventions of all tumor stages. Rates of overall ( P = .024) and disease-specific ( P = .036) survival were significantly improved for endoscopic cases; improved recurrence-free survival rates did not achieve statistical significance ( P = .357). For cases matched for tumor size, this improvement was confirmed for T3 tumors ( P = .038). Regional and distant metastatic tumor spread generally worsened survival in both surgical subgroups. Multivariate Cox regression analysis revealed independent prognosticators for overall survival., Conclusion: Endoscopic tumor resection remains a suitable option for distinct indications and showed improved outcome in intermediate-stage tumors in our collective. Further randomized studies acknowledging the here-identified factors are needed to improve future therapy guidelines and patient care.

Background: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery., Methods: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery., Results: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10 - 8 ) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10 - 5 from the GWAS., Conclusions: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery., Trial Registration: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.

Background: Surgical treatment of late diagnosed development dysplasia of the hip (DDH) remains challenging with several methods being described. We therefore retrospectively evaluated the outcome of Salter innominate osteotomy (SIO) in patients with fully-grown bone, to evaluate whether this surgical procedure allows sufficient acetabular correction., Material and Methods: Between 2004-2012 SIO had been performed in 45 patients (49 hips) with late diagnosed DDH. The evaluation included pre- and postoperative radiographs (n=49), the complication rate (n=49) and the clinical outcome (WOMAC, HHS, UCLA) (n=34)., Results: Mean age at surgery was 27.6 (16-51) with a follow-up of 6.7±2.7 (0.9-11.0) years. Radiologically, a good acetabular correction with a significant improvement of the Center Edge angle (15.4° to 34.9°), sharps angle (45.7° to 32.0°) and migration percentage (33.2% to 14.4%) (p<0.001) was found. Clinical results revealed a WOMAC of 13.9±13.3, UCLA of 7.8±2.1 and HHS of 85.0±11.8. Complications were noted for 10 patients (20%) with 7 (14%) requiring revision., Conclusion: The results demonstrated that SIO achieved a satisfying acetabular correction and good clinical results in late diagnosed DDH. It therefore might be an option in some cases, although periacetabular osteotomy techniques are currently preferable used as they allow a wider range of acetabular correction., Level of Evidence: IV, retrospective observational study., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC., Methods and Results: In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively., Conclusions: Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Introduction: Current treatment strategies for osteoporotic vertebral compression fractures (VCFs) focus on cement-associated solutions. Complications associated with cement application are leakage, embolism, adjacent fractures, and compromise in bony healing. This study comprises a validated VCF model in osteoporotic sheep in order to (1) evaluate a new cementless fracture fixation technique using titanium mesh implants (TMIs) and (2) demonstrate the healing capabilities in osteoporotic VCFs., Methods: Twelve 5-year-old Merino sheep received ovariectomy, corticosteroid injections, and a calcium/phosphorus/vitamin D-deficient diet for osteoporosis induction. Standardized VCFs (type AO A3.1) were created, reduced, and fixed using intravertebral TMIs. Randomly additional autologous spongiosa grafting (G1) or no augmentation was performed (G2, n = 6 each). Two months postoperatively, macroscopic, micro-CT and biomechanical evaluation assessed bony consolidation., Results: Fracture reduction succeeded in all cases without intraoperative complications. Bony consolidation was proven for all cases with increased amounts of callus development for G2 (58.3%). Micro-CT revealed cage integration. Neither group showed improved results with biomechanical testing., Conclusions: Fracture reduction/fixation using TMIs without cement in osteoporotic sheep lumbar VCF resulted in bony fracture healing. Intravertebral application of autologous spongiosa showed no beneficial effects. The technique is now available for clinical use; thus, it offers an opportunity to abandon cement-associated complications.

Introduction: Vertebral compression fractures (VCFs) are one of the most common injuries in the aging population presenting with an annual incidence of 1.4 million new cases in Europe. Current treatment strategies focus on cement-associated solutions (kyphoplasty/vertebroplasty techniques). Specific cement-associated problems as leakage, embolism and the adjacent fracture disease are reported adding to open questions like general fracture healing properties of the osteoporotic spine. In order to analyze those queries animal models are of great interest; however, both technical difficulties in the induction of experimental osteoporosis in animal as well as the lack of a standardized fracture model impede current and future in vivo studies. This study introduces a standardized animal model of an osteoporotic VCF type A3.1 that may enable further in-depth analysis of the afore mentioned topics., Material and Methods: Twenty-four 5-year-old female Merino sheep (mean body weight: 67 kg; range 57-79) were ovariectomized (OP1) and underwent 5.5 months of weekly corticosteroid injections (dexamethasone and dexamethasone-sodium-phosphate), adding to a calcium/phosphorus/vitamin D-deficient diet. Osteoporosis induction was documented by pQCT and micro-CT BMD (bone mineral density) as well as 3D histomorphometric analysis postoperatively of the sheep distal radius and spine. Non osteoporotic sheep served as controls. Induction of a VCF of the second lumbar vertebra was performed via a mini-lumbotomy surgical approach with a standardized manual compression mode (OP2)., Results: PQCT analysis revealed osteoporosis of the distal radius with significantly reduced BMD values (0.19 g/cm(3), range 0.13-0.22 vs. 0.27 g/cm(3), range 0.23-0.32). Micro-CT documented significant lowering of BMD values for the second lumbar vertebrae (0.11 g/cm(3), range 0.10-0.12) in comparison to the control group (0.14 g/cm(3), range 0.12-0.17). An incomplete burst fracture type A3.1 was achieved in all cases and resulted in a significant decrease in body angle and vertebral height (KA 4.9°, range: 2-12; SI 4.5%, range: 2-12). With OP1, one minor complication (lesion of small bowel) occurred, while no complications occurred with OP2., Conclusions: A suitable spinal fracture model for creation of VCFs in osteoporotic sheep was developed. The technique may promote the development of improved surgical solutions for VCF treatment in the experimental and clinical setting., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This study analyses the effect of eptotermin α application into fractured vertebrae. It is hypothesized that eptotermin α is capable to enhance bony healing of the osteoporotic spine. In 10 Merino sheep osteoporosis induction was performed by ovariectomy, corticosteroid therapy and calcium/phosphorus/vitamin D-deficient diet; followed by standardized creation of lumbar vertebral compression fractures (VCFs) type A3.1 and consecutive fracture reduction/fixation using expandable mesh cages. Randomly, intravertebral eptotermin α (G1) or no augmentation was added (G2). Macroscopic, micro-CT, and biomechanical evaluation assessed bony consolidation two months postoperatively: Micro-CT data revealed bony consolidation for all cases with significant increased callus development for G2 (60%) and BV/TV (bone volume/total volume 73.45%, osteoporotic vertebrae 35.76%). Neither group showed improved biomechanical stability. Eptotermin α enhanced mineralisation in VCFs in an experimental setup with use of cementless augmentation via an expandable cage. However, higher bone mineral density did not lead to superior biomechanical properties.

Aims: Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study"., Methods: We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge., Conclusion: The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.

Background: Over the last 15 years, there has been growing interest in the noble gas xenon as a new inhalational anesthetic. This is due to its favorable pharmacological properties such as short onset and offset, as well as its hemodynamic stability. However, most volatile anesthetics appear to play an important role in the multi-factorial etiology of perioperative liver injury by decreasing liver blood flow with a subsequent reduction of hepatic oxygen supply. However, the effects of the anesthetic gas xenon on hepatic perfusion and oxygenation have not been completely investigated., Methods: Following ethical approval, 18 anesthetized and acutely monitored pigs were randomly assigned to the two following groups: 9 animals received xenon anesthesia in increasing inspiratory concentrations of 0%, 20%, 50%, and 65% in addition to their basic intravenous anesthesia; 9 animals served as a control group. Measurement points for systemic and regional hemodynamic and oxygenation parameters were performed 30 min after changing the xenon concentration., Results: Xenon elicited dose-dependent systemic hemodynamic changes such that the mean arterial pressure did not change, while the heart rate and cardiac output decreased by about 30%, thereby indicating an increase in the systemic vascular resistance. Portal venous blood flow decreased, while hepatic arterial blood flow was unchanged. The oxygen supply of the liver was reduced, but not the rate of indocyanine plasma disappearance from the liver. Furthermore, the increase of liver surface pO2 to systemic hyperoxia was absent, and hepatic lactate uptake was reduced., Conclusion: Xenon, in addition to basic intravenous anesthesia, elicited a decrease in heart rate and cardiac output and an increase in mean arterial pressure. Similar to volatile anesthetics, xenon does reduce portal venous flow and influences hepatic tissue oxygenation. In contrast, hepatic arterial blood flow remains stable in the presence of xenon, and no changes in the hepatic arterial buffer responses were evident. Xenon does affect hepatic perfusion and oxygenation.

Background: Increased sympathetic nervous activity which induces vasoconstriction and decreases perfusion may be an underlying mechanism behind the development of perioperative liver damage. This animal study was designed to assess how clonidine-induced systemic sympathicolysis affects liver oxygenation with respect to induced hypotension and vasodilatation under physiological conditions., Methods: Following ethical approval 17 anesthetized and acutely instrumented pigs were randomly assigned to 2 groups. Group 1 consisted of 8 animals receiving intravenous clonidine (2 microg x kg(-1) bolus and 2 microg x kg(-1) x h(-1) for induction of sympathicolysis and group 2 consisted of 9 animals serving as controls. After obtaining baseline values, measurements were repeated 90 and 250 min after starting to reduce systemic sympathetic nervous activity., Results: Clonidine-induced systemic sympathicolysis was associated with decreased mean arterial blood pressure, cardiac output and heart rate. Portal venous and hepatic arterial blood flow, oxygen delivery to the liver, oxygen uptake and liver tissue oxygen partial pressure remained unchanged. The plasma indocyanine green disappearance rate increased., Conclusion: We concluded that despite decreased mean arterial pressure and cardiac output, clonidine-induced systemic sympathicolysis did not affect liver oxygenation or perfusion.

Background: Xenon is a narcotic gas that might be able to replace volatile anaesthetics or nitrous oxide due to its favourable pharmacological properties, such as providing haemodynamic stability. Intestinal oxygenation is affected by most volatile anaesthetics as a result of cardiodepressive effects. Reducing oxygenation of the gut might be a factor leading to perioperative organ dysfunction. This animal study was designed to assess the effects of xenon on intestinal oxygenation., Methods: After ethical approval, 24 anaesthetized, acutely instrumented pigs were randomly assigned to three groups: nine animals received xenon anaesthesia with inspiratory concentrations of 0, 20, 50 and 65% in addition to their basic i.v. anaesthesia, nine animals served as a study control group, and five animals were used to assess model stability. Measurement of systemic and regional haemodynamic and oxygenation parameters was made 30 min after changing the xenon concentration., Results: Xenon elicited dose-dependent systemic haemodynamic changes: heart rate and cardiac output decreased by 30%, while mean arterial pressure was stable. Superior mesenteric artery blood flow was lower in the xenon group. Vascular resistance of the superior mesenteric artery increased. The small intestinal oxygen supply decreased with increasing xenon concentration; the mucosal tissue oxygen partial pressure decreased but did not reach hypoxic (<5 mm Hg) values. Serosal tissue oxygen partial pressure was maintained., Conclusions: Xenon, in addition to basic i.v. anaesthesia, elicited a decrease in cardiac output and maintained mean arterial pressure. Intestinal oxygenation was maintained, although regional macrohaemodynamic perfusion decreased. Xenon does not impair intestinal oxygenation under physiological conditions.