Lower leukotriene C4 levels in bronchoalveolar lavage fluid of asthmatic subjects after 2.5 years of inhaled corticosteroid therapy

Long-term treatment with inhaled corticosteroids has been shown to result in improvement of symptoms and lung function in subjects with asthma. Arachidonic acid (AA) metabolites are thought to play a role in the pathophysiology of asthma. It was assessed whether differences could be found in bronchoalveolar lavage (BAL) AA metabolite levels between subjects with asthma who were treated for 2.5 years with inhaled bronchodilators alone or in combination with inhaled corticosteroids. Prostaglandin (PG)D2, PGF2α, 6-keto-PGF1α, thromboxane B2, leukotriene (LT)C4 and LTB4 levels and cell numbers were assessed in BAL fluid from 22 non-smoking asthmatic subjects. They were participating in a randomized, double-blind multicentre drug trial over a period of 2.5 years. Results of the group treated with inhaled corticosteroids (CS+: beclomethasone 200 μg four times daily) were compared with the other group (CS−) which was treated with either ipratropium bromide (40 μg four times daily) or placebo. BAL LTC4 levels of asthmatic subjects were significantly lower after 2.5 years inhaled corticosteroid therapy (CS+, 9(1–17) pg/ml vs. CS−, 16(6-53) pg/ml; p = 0.01). The same trend was observed for the PGD2 levels. The results suggest that inhaled corticosteroids may exert their beneficial effect on lung function via a mechanism in which inhibition of LTC4 synthesis in the airways is involved

Another Faint UV Object Associated with a Globular Cluster X-Ray Source: The Case of M92

The core of the metal poor Galactic Globular Cluster M92 (NGC 6341) has been observed with WFPC2 on the Hubble Space Telescope through visual, blue and mid-UV filters in a program devoted to study the evolved stellar population in a selected sample of Galactic Globular Clusters. In the UV $(m_{255}, m_{255}-U)$ color magnitude diagram we have discovered a faint `UV-dominant' object. This star lies within the error box of a Low Luminosity Globular Cluster X-ray source (LLGCX) recently found in the core of M92. The properties of the UV star discovered in M92 are very similar to those of other UV stars found in the core of some clusters (M13, 47 Tuc, M80, etc)---all of them are brighter in the UV than in the visible and are located in the vicinity of a LLGCX. We suggest that these stars are a new sub-class of cataclysmic variables.Comment: 21 pages, 4 figures. Astrophysical journal in pres

Does the SORG Orthopaedic Research Group Hip Fracture Delirium Algorithm Perform Well on an Independent Intercontinental Cohort of Patients With Hip Fractures Who Are 60 Years or Older?

Background Postoperative delirium in patients aged 60 years or older with hip fractures adversely affects clinical and functional outcomes. The economic cost of delirium is estimated to be as high as USD 25,000 per patient, with a total budgetary impact between USD 6.6 to USD 82.4 billion annually in the United States alone. Forty percent of delirium episodes are preventable, and accurate risk stratification can decrease the incidence and improve clinical outcomes in patients. A previously developed clinical prediction model (the SORG Orthopaedic Research Group hip fracture delirium machine-learning algorithm) is highly accurate on internal validation (in 28,207 patients with hip fractures aged 60 years or older in a US cohort) in identifying at-risk patients, and it can facilitate the best use of preventive interventions; however, it has not been tested in an independent population. For an algorithm to be useful in real life, it must be valid externally, meaning that it must perform well in a patient cohort different from the cohort used to "train" it. With many promising machine-learning prediction models and many promising delirium models, only few have also been externally validated, and even fewer are international validation studies. Question/purpose Does the SORG hip fracture delirium algorithm, initially trained on a database from the United States, perform well on external validation in patients aged 60 years or older in Australia and New Zealand? Methods We previously developed a model in 2021 for assessing risk of delirium in hip fracture patients using records of 28,207 patients obtained from the American College of Surgeons National Surgical Quality Improvement Program. Variables included in the original model included age, American Society of Anesthesiologists (ASA) class, functional status (independent or partially or totally dependent for any activities of daily living), preoperative dementia, preoperative delirium, and preoperative need for a mobility aid. To assess whether this model could be applied elsewhere, we used records from an international hip fracture registry. Between June 2017 and December 2018, 6672 patients older than 60 years of age in Australia and New Zealand were treated surgically for a femoral neck, intertrochanteric hip, or subtrochanteric hip fracture and entered into the Australian & New Zealand Hip Fracture Registry. Patients were excluded if they had a pathological hip fracture or septic shock. Of all patients, 6% (402 of 6672) did not meet the inclusion criteria, leaving 94% (6270 of 6672) of patients available for inclusion in this retrospective analysis. Seventy-one percent (4249 of 5986) of patients were aged 80 years or older, after accounting for 5% (284 of 6270) of missing values; 68% (4292 of 6266) were female, after accounting for 0.06% (4 of 6270) of missing values, and 83% (4690 of 5661) of patients were classified as ASA III/IV, after accounting for 10% (609 of 6270) of missing values. Missing data were imputed using the missForest methodology. In total, 39% (2467 of 6270) of patients developed postoperative delirium. The performance of the SORG hip fracture delirium algorithm on the validation cohort was assessed by discrimination, calibration, Brier score, and a decision curve analysis. Discrimination, known as the area under the receiver operating characteristic curves (c-statistic), measures the model's ability to distinguish patients who achieved the outcomes from those who did not and ranges from 0.5 to 1.0, with 1.0 indicating the highest discrimination score and 0.50 the lowest. Calibration plots the predicted versus the observed probabilities, a perfect plot has an intercept of 0 and a slope of 1. The Brier score calculates a composite of discrimination and calibration, with 0 indicating perfect prediction and 1 the poorest. Results The SORG hip fracture algorithm, when applied to an external patient cohort, distinguished between patients at low risk and patients at moderate to high risk of developing postoperative delirium. The SORG hip fracture algorithm performed with a c-statistic of 0.74 (95% confidence interval 0.73 to 0.76). The calibration plot showed high accuracy in the lower predicted probabilities (intercept -0.28, slope 0.52) and a Brier score of 0.22 (the null model Brier score was 0.24). The decision curve analysis showed that the model can be beneficial compared with no model or compared with characterizing all patients as at risk for developing delirium. Conclusion Algorithms developed with machine learning are a potential tool for refining treatment of at-risk patients. If high-risk patients can be reliably identified, resources can be appropriately directed toward their care. Although the current iteration of SORG should not be relied on for patient care, it suggests potential utility in assessing risk. Further assessment in different populations, made easier by international collaborations and standardization of registries, would be useful in the development of universally valid prediction models. The model can be freely accessed at: https://sorg-apps.shinyapps.io/hipfxdelirium/

The Globular Cluster Omega Centauri and the Oosterhoff Dichotomy

CCD observations obtained by the OGLE team for 128 RR Lyrae variables in Omega Cen have been analysed. The P-L and P-A plots indicate that, in addition to fundamental (RRab) and first overtone (RRc) pulsators, the Omega Cen RR Lyrae population seems to include second overtone (RRe) and possibly third overtone pulsators. The mean periods derived for the RRab and RRc stars are typical values for an Oosterhoff type II (OoII) cluster. Nevertheless, the P-A plot plot also shows that some of the RR Lyrae variables have `Oosterhoff type I' (OoI) characteristics. Relative luminosities derived for the RRc variables from Fourier coefficients correlate with the observed apparent magnitudes. Masses for the RRc stars have been calculated from Fourier coefficients. A comparison of the derived masses for RRc stars in the four OoII clusters Omega Cen, M15, M55 and M68 indicates that the masses of the RRc stars in M15 and M68 are almost 0.2 solar masses greater than those in the other two. Since M15 and M68 have a high frequency of RRd stars among their first overtone pulsators, while none have been identified in Omega Cen or M55, this suggests that the double-mode pulsation phenomenon may be associated with mass. Among the RRc variables in Omega Cen, the OoII variables have lower derived masses and higher luminosities than the OoI variables. An application of the period-density law to pairs of OoI and OoII RRab stars selected according to their position in the P-A plot also indicates that the OoII variables in general have lower masses and higher luminosities. These findings support the hypothesis that RR Lyrae variables in OoII systems are evolved HB stars that spend their ZAHB phase on the blue side of the instability strip.Comment: 52 pages, 10 figures, to appear in the AJ (November 2000

Boron Abundances in Main Sequence B-type Stars: A Test of Rotational Depletion during Main Sequence Evolution

Boron abundances have been derived for seven main sequence B-type stars from HST STIS spectra around the B III 2066 A line. In two stars, boron appears to be undepleted with respect to the presumed initial abundance. In one star, boron is detectable but it is clearly depleted. In the other four stars, boron is undetectable implying depletions of 1 to 2 dex. Three of these four stars are nitrogen enriched, but the fourth shows no enrichment of nitrogen. Only rotationally induced mixing predicts that boron depletions are unaccompanied by nitrogen enrichments. The inferred rate of boron depletion from our observations is in good agreement with these predictions. Other boron-depleted nitrogen-normal stars are identified from the literature. Also, several boron-depleted nitrogen-rich stars are identified, and while all fall on the boron-nitrogen trend predicted by rotationally-induced mixing, a majority have nitrogen enrichments that are not uniquely explained by rotation. The spectra have also been used to determine iron-group (Cr, Mn, Fe, and Ni) abundances. The seven B-type stars have near solar iron-group abundances, as expected for young stars in the solar neighborhood. We have also analysed the halo B-type star, PG0832+676. We find [Fe/H] = -0.88 +/- 0.10, and the absence of the B III line gives the upper limit [B/H]<2.5. These and other published abundances are used to infer the star's evolutionary status as a post-AGB star.Comment: 31 pages, 14 figures. accepted to Ap

Do symptoms of anxiety and/or depression and pain intensity before primary Total knee arthroplasty influence reason for revision? Results of an observational study from the Dutch arthroplasty register in 56,233 patients

Objective: Anxiety, depression and greater pain intensity before total knee arthroplasty (TKA) may increase the probability of revision surgery for remaining symptoms even without clear pathology or technical issues. We aimed to assess whether preoperative anxiety/depression and pain intensity are associated with revision TKA for less clear indications. Methods: Less clear indications for revision were defined after a Delphi process in which consensus was reached among 59 orthopaedic knee experts. We performed a cox regression analyses on primary TKA patients registered in the Dutch Arthroplasty Registry (LROI) who completed the EuroQol 5D 3 L (EQ5D-3 L) anxiety/depression score to examine associations between preoperative anxiety/depression and pain (Numeric Rating Scale (NRS)) with TKA revision for less clear reasons. These analyses were adjusted for age, BMI, sex, smoking, ASA score, EQ5D-3 L thermometer and OKS score. Results: In total, 25.9% patients of the 56,233 included patients reported moderate or severe symptoms of anxiety/depression on the EQ5D-3 L anxiety/depression score. Of those, 615 revisions (45.5%) were performed for less clear reasons for revision (patellar pain, malalignment, instability, progression of osteoarthritis or arthrofibrosis). Not EQ5D-3 L anxiety/depression score, but higher NRS pain at rest and EQ5D-3 L pain score were associated with revision for less clear reason (HR: 1.058, 95% CI 1.019-1.099 & HR: 1.241, 95% CI 1.044-1.476, respectively). Conclusion: Our findings suggest that pain intensity is a risk factor for TKA revision for a less clear reason. The finding that preoperative pain intensity was associated with reason for revision confirms a likely influence of subjective, personal factors on offer and acceptance of TKA revision. The association between anxiety/depression and reason for revision after TKA may also be found when including more specific outcome measures to assess anxiety/depression and we therefore hope to encourage further research on this topic with our study, ideally in a prospective setting. Study design: Longitudinal Cohort Study Level III, Delphi Consensu

Stellar Rotation in Young Clusters. I. Evolution of Projected Rotational Velocity Distributions

Open clusters offer us the means to study stellar properties in samples with well-defined ages and initial chemical composition. Here we present a survey of projected rotational velocities for a large sample of mainly B-type stars in young clusters to study the time evolution of the rotational properties of massive stars. The survey is based upon moderate resolution spectra made with the WIYN 3.5 m and CTIO 4 m telescopes and Hydra multi-object spectrographs, and the target stars are members of 19 young open clusters with an age range of approximately 6 to 73 Myr. We made fits of the observed lines He I 4026, 4387, 4471 and Mg II 4481 using model theoretical profiles to find projected rotational velocities for a total of 496 OB stars. We find that there are fewer slow rotators among the cluster B-type stars relative to nearby B stars in the field. We present evidence consistent with the idea that the more massive B stars (M > 9 solar masses) spin down during their main sequence phase. However, we also find that the rotational velocity distribution appears to show an increase in the numbers of rapid rotators among clusters with ages of 10 Myr and higher. These rapid rotators appear to be distributed between the zero age and terminal age main sequence locations in the Hertzsprung-Russell diagram, and thus only a minority of them can be explained as the result of a spin up at the terminal age main sequence due to core contraction. We suggest instead that some of these rapid rotators may have been spun up through mass transfer in close binary systems.Comment: 33 pages, 11 figures, accepted by Ap

Hot Horizontal-Branch Stars: The Ubiquitous Nature of the "Jump" in Stromgren u, Low Gravities, and the Role of Radiative Levitation of Metals

A "jump" in the BHB distribution in the V, u-y CMD was recently detected in the GC M13. It is morphologically best characterized as a discontinuity in u, u-y, with stars in the range 11,500<Teff(K)<20,000 deviating systematically from (in the sense of appearing brighter and/or hotter than) canonical ZAHBs. We present u, y photometry of 14 GCs obtained with 3 different telescopes (Danish, NOT, HST) and demonstrate that the u-jump is present in every GC whose HB extends beyond 11,500K, irrespective of [Fe/H], mixing history on the RGB, and other GC parameters. We suggest that the u-jump is a ubiquitous feature, intrinsic to all HB stars hotter than 11,500K. We draw a parallel between the ubiquitous nature of the u-jump and the problem of low measured gravities among BHB stars. We note that the "logg-jump" occurs over the same temperature range as the u-jump, and that it occurs in every metal-poor GC for which gravities have been determined--irrespective of [Fe/H], mixing history on the RGB, or any other GC parameters. Furthermore, the u-jump and the logg-jump are connected on a star-by-star basis. The two are likely different manifestations of the same physical phenomenon. We present a framework which may simultaneously account for the u-jump and the logg-jump. Reviewing spectroscopic data for several field BHB stars, as well as two BHB stars in the GC NGC 6752, we find evidence that radiative levitation of heavy elements takes place at Teff>11,500 K, dramatically enhancing their abundances in the atmospheres of BHB stars in the "critical" temperature region. Model atmospheres taking diffusion effects into account are badly needed, and will likely lead to better overall agreement between canonical evolutionary theory and observations for BHB stars.Comment: ApJ, Main Journal, accepted. Contains several changes and update

Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement

BACKGROUND CONTEXT: Patients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions. PURPOSE: In this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included. OUTCOME MEASURES: The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations. METHODS: Data were collected through manual chart review. Hosmer and Lemeshow's purposeful regression method was used to identify risk factors for complications and reoperations. RESULTS: The median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04-1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79-9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30-36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19-5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37-0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript. CONCLUSION: The goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial