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Objective: To describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation. Methods: Clinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry. Results: The skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra. Conclusion: This is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra). [ABSTRACT FROM AUTHOR]

Objective: Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Our objective was to test physician global assessment (PhGA), a measure of disease activity commonly used in rheumatic diseases, in a cohort of patients with RP, which has not been done before.Methods: Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by 3 physicians from the evaluating institution on a scale of 0-10 for each visit. A random subset of 20 visits was scored by 3 independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased, or unchanged.Results: In total, 78 patients were evaluated over 164 visits. The intraclass correlation coefficient (ICC2,1 ) for the 3 raters from the evaluating institution was excellent (0.79 [95% confidence interval (95% CI) 0.73, 0.84]) but was poor in the subset of cases scored by the additional raters (ICC2,1 0.27 [95% CI -0.01, 0.53]). Median PhGA was 3 (range 0-7). PhGA weakly correlated with C-reactive protein level (rs = 0.30, P < 0.01). In response to increased treatment, median PhGA decreased from 3 (interquartile range [IQR] 2, 4) to 2 (IQR 2, 3) (P < 0.01) but rarely went to 0.Conclusion: Within a single center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP. [ABSTRACT FROM AUTHOR]

Objectives Relapsing polychondritis (RP) is a rare, heterogeneous, systemic inflammatory disease that targets cartilage. Patient-reported outcome measures may differ from physician assessment. This study compared patient global assessment (PtGA) and physician global assessment (PhGA) scores in a prospective cohort of patients with RP. Methods Adult patients with RP underwent a standardized comprehensive evaluation at ∼6 month intervals. At each visit, three physicians scored PhGA by consensus. The patient independently completed four patient-reported outcomes: PtGA, 36-item Short Form Health Survey (SF-36), Brief Illness Perception Questionnaire (BIPQ) and Multidimensional Fatigue Inventory (MFI). Patient–physician discordance was defined as a difference between PtGA and PhGA of ≥3 on a 0–10 scale. Results A total of 76 patients were evaluated over 154 visits. The median PhGA was 3 [interquartile range (IQR) 2–3] and the median PtGA was 5 (IQR 4–7). PtGA and PhGA were concordant in 66 visits (42.9%) and patients scored disease severity ≥3 points higher than physicians scored disease activity (positive discordance) in 84 visits (54.5%). Compared with visits with concordance, visits with positive discordance were associated with significantly worse scores on the MFI, BIPQ, SF-36 physical component score and SF-36 mental component score. Conclusion Patients with RP typically self-report high PtGA that does not align with PhGA. Discordance is likely driven by the high physical and psychological burden of illness experienced by patients. Multifaceted treatment approaches that address the burden of disease in RP from the patient perspective are needed. [ABSTRACT FROM AUTHOR]

Background: Sleep is an important component of neurorehabilitation. This study evaluates sleep quality in the acute inpatient rehabilitation setting and is the first to compare sleep quality in acute rehabilitation versus the acute care hospital and home settings. Objective: To assess patient sleep quality in the acute inpatient rehabilitation setting. Design Cross‐sectional survey study. Setting: Acute inpatient rehabilitation unit. Patients Seventy‐three patients admitted to the acute rehabilitation unit participated in the study. Interventions: A validated sleep questionnaire was provided on admission regarding sleep at home and in the acute care hospital. The questionnaire was repeated on discharge from the acute rehabilitation unit regarding sleep during their rehabilitation admission. Main Outcome Measures: Visual analog scale of sleep depth, falling asleep, number of awakenings, percentage of time awake, and quality of sleep were obtained through use of the Richards‐Campbell Sleep Questionnaire. These values were averaged to obtain "overall sleep perception." An additional question on environmental noise was added. Scores ranged from 0 for "worst sleep possible" to 100 for "best sleep possible." Results: Patients reported significantly better sleep in all domains and overall in the acute rehabilitation unit compared to the acute care hospital, with the exception of percentage of time awake. Patients also reported significantly better sleep depth but worse noise in the acute rehabilitation unit when compared to home. Similarly, patients reported significantly better sleep in all domains and overall at home in comparison to the acute care hospital with the exception of percentage of time awake. Conclusions: Patient in the acute rehabilitation unit experience sleep quality that matches their experience at home and exceeds that in the hospital. [ABSTRACT FROM AUTHOR]

Purpose: The apparent lag between macro-economic behavior and financial implications in the construction industry is yet to be examined. The purpose of this paper is to understand the nature of the lag and the relationship between economic changes from year-to-year and the impact on the financial status of construction companies. Design/methodology/approach: Correlation was made between US economic growth and construction industry financial indicators over a 28-year period. Cumulative per cent growth in US GDP was considered an independent variable, while nine financial ratios were calculated and considered dependent variables in this study. Findings: The results of this study found that correlation improved when considering lag of two, three or sometimes four years after the economic event. Some financial ratios proved more sensitive than others, supporting the hypothesis of this study. Research limitations/implications: The practical application of this study for construction companies is to understand how the construction industry lag impacts financial behavior. It therefore informs managerial decisions related to solvency, liquidity, equity structure and managerial practices; all of which are measured by financial ratios. Practical implications: This study was intended to advance the research in this area and also to serve to strengthen industry members in their financial management of construction companies. Economic dynamics have long-lasting implications, which can be addressed through an increased focus on managing financial health. Originality/value: Though the lag is intuitively known and has been studied from market perspectives, there is a lack of empirical study evaluating the impact of lag on financial key performance indicators. [ABSTRACT FROM AUTHOR]

Objective: Relapsing polychondritis (RP) is a systemic disease. Failure to recognize RP can lead to diagnostic delay and further complications, including death. This study was undertaken to identify clinical patterns in a prospective cohort of patients with RP. Methods: Patient subgroups were identified using latent class analysis based on 8 clinical variables: saddle‐nose deformity, subglottic stenosis, tracheomalacia, bronchomalacia, ear chondritis, tenosynovitis/synovitis, inflammatory eye disease, and audiovestibular disease. Model selection was based on Akaike's information criterion. Results: Seventy‐three patients were included in this study. Patients were classified into 1 of 3 subgroups: type 1 RP (14%), type 2 RP (29%), and type 3 RP (58%). Type 1 RP was characterized by ear chondritis (100%), tracheomalacia (100%), saddle‐nose deformity (90%), and subglottic stenosis (80%). These patients had the shortest median time to diagnosis (1 year), highest disease activity, and greatest frequency of admission to the intensive care unit and tracheostomy. Type 2 RP was characterized by tracheomalacia (100%) and bronchomalacia (52%), but no saddle‐nose deformity or subglottic stenosis. These patients had the longest median time to diagnosis (10 years) and highest percentage of work disability. Type 3 RP was characterized by tenosynovitis/synovitis (60%) and ear chondritis (55%). There were no significant differences in sex, race, or treatment strategies between the 3 subgroups. Conclusion: Our findings indicate that there are 3 subgroups of patients with RP, with differences in time to diagnosis, clinical and radiologic characteristics, and disease‐related complications. Recognizing a broader spectrum of clinical patterns in RP, beyond cartilaginous involvement of the ear and upper airway, may facilitate more timely diagnosis. [ABSTRACT FROM AUTHOR]

PURPOSE: In response to growing concern about the effect of blue light on ocular tissue, companies have created mobile device screen protectors to block blue light. This project evaluates one of these screen protectors' ability to reduce blue light intensity. METHODS: The intensity of light at 450 nm from an iPhone 8, iPhone X, and iPad was measured in a dark room. The averages of three measurements were taken with and without the screen protector at different distances, settings of brightness, and Apple's night shift (NS) mode. Results were analyzed using paired t-tests. RESULTS: At 33 cm, 100% brightness, and 0% NS, the screen protector decreased intensity by 43.9%, 32.3%, and 34.9% for the iPhone 8, iPhone X, and iPad, respectively. At 33 cm and 100% brightness, increasing NS mode from 0% to 100% decreased intensity by 81.2%, 84.2%, and 86.5%. At 33 cm without NS, decreasing the brightness from 100% to 0% decreased intensity by 99.5%, 99.8%, and 97.8%. CONCLUSIONS: The screen protector decreased the intensity at 450 nm for every setting other than those at 0% brightness. Decreasing brightness and applying NS mode were more effective in reducing blue light. More research is needed to determine the benefits of decreasing blue light exposure from electronic devices. [ABSTRACT FROM AUTHOR]

The article offers information on multicenter audit of COVID-19 intubations in New South Wales metropolitan hospitals. It mentions Safe airway management of patients with suspected or confirmed severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) is a priority during the current pandemic.

Many Gram-negative bacterial pathogens express contact-dependent growth inhibition (CDI) systems that promote cell-cell interaction. CDI+ bacteria express surface CdiA effector proteins, which transfer their C-terminal toxin domains into susceptible target cells upon binding to specific receptors. CDI+ cells also produce immunity proteins that neutralize the toxin domains delivered from neighboring siblings. Here, we show that CdiAEC536 from uropathogenic Escherichia coli 536 (EC536) uses OmpC and OmpF as receptors to recognize target bacteria. E. coli mutants lacking either ompF or ompC are resistant to CDIEC536-mediated growth inhibition, and both porins are required for target-cell adhesion to inhibitors that express CdiAEC536. Experiments with single-chain OmpF fusions indicate that the CdiAEC536 receptor is heterotrimeric OmpC-OmpF. Because the OmpC and OmpF porins are under selective pressure from bacteriophages and host immune systems, their surface-exposed loops vary between E. coli isolates. OmpC polymorphism has a significant impact on CDIEC536 mediated competition, with many E. coli isolates expressing alleles that are not recognized by CdiAEC536. Analyses of recombinant OmpC chimeras suggest that extracellular loops L4 and L5 are important recognition epitopes for CdiAEC536. Loops L4 and L5 also account for much of the sequence variability between E. coli OmpC proteins, raising the possibility that CDI contributes to the selective pressure driving OmpC diversification. We find that the most efficient CdiAEC536 receptors are encoded by isolates that carry the same cdi gene cluster as E. coli 536. Thus, it appears that CdiA effectors often bind preferentially to "self" receptors, thereby promoting interactions between sibling cells. As a consequence, these effector proteins cannot recognize nor suppress the growth of many potential competitors. These findings suggest that self-recognition and kin selection are important functions of CDI. [ABSTRACT FROM AUTHOR]

Contact-dependent growth inhibition ( CDI) is a widespread form of inter-bacterial competition that requires direct cell-to-cell contact. CDI+ inhibitor cells express CdiA effector proteins on their surface. CdiA binds to specific receptors on susceptible target bacteria and delivers a toxin derived from its C-terminal region ( CdiA- CT). Here, we show that purified CdiA- CT536 toxin from uropathogenic E scherichia coli 536 translocates into bacteria, thereby by-passing the requirement for cell-to-cell contact during toxin delivery. Genetic analyses demonstrate that the N-terminal domain of CdiA- CT536 is necessary and sufficient for toxin import. The CdiA receptor plays no role in this import pathway; nor do the Tol and Ton systems, which are exploited to internalize colicin toxins. Instead, CdiA- CT536 import requires conjugative F pili. We provide evidence that the N-terminal domain of CdiA- CT536 interacts with F pilin, and that pilus retraction is critical for toxin import. This pathway is reminiscent of the strategy used by small RNA leviviruses to infect F+ cells. We propose that CdiA- CT536 mimics the pilin-binding maturation proteins of leviviruses, allowing the toxin to bind F pili and become internalized during pilus retraction. [ABSTRACT FROM AUTHOR]

The article focuses on a research conducted to study local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma. The study was conducted on 77 patients with unresectable adenocarcinoma of the pancreas. It was found in the study that SBRT for pancreatic adenocarcinoma was effective for local control with associated risk of toxicity and should be used with rigorous attention to quality assurance.

Background: Children with spina bifida, high anorectal anomalies, or neuronal intestinal dysplasia who are treated with a laparoscopic antegrade continence enema to achieve a socially acceptable level of fecal continence sometimes have problems with the stoma and its catheterization. The goal of this study was to determine the nature and incidence of these problems, and their relationship to the underlying condition. Materials and Methods: A retrospective review of the hospital case notes of 74 consecutive patients who had a laparoscopic antegrade continence enema was undertaken. Results: The laparoscopic antegrade continence enema procedure is well tolerated but is associated with a variety of usually minor complications including stomal stenosis, leakage, peristomal infection, granulation tissue overgrowth, mucosal prolapse, abdominal discomfort during irrigation, appendiceal false passage, and ineffective irrigation. Surgical revision of the stoma was required in 19% of the cases in this study, usually because of stenosis and skin overgrowth. Ongoing problems achieving colonic emptying were most likely to occur in patients with an anorectal malformation. Conclusion: Overall, the laparoscopic antegrade continence enema provides an effective method of facilitating emptying of the bowel. However, it has a high incidence of minor troublesome problems, with stenosis and skin overgrowth of the stoma being the most common. Younger children tend to have more complications and difficulty performing effective irrigation. Children with anorectal malformations were more likely to require surgical revision of the stoma, and often needed ongoing manual evacuation and bowel washouts despite the laparoscopic antegrade continence enema. [ABSTRACT FROM AUTHOR]