Search

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

Abstract Most hospitalized patients with inflammatory bowel disease (IBD) experience pain. Despite the known risks associated with opioids in IBD including risk for misuse, overdose, infection, readmission, and even death, opioid use is more prevalent in IBD than any other chronic gastrointestinal condition. Most hospitalized IBD patients receive opioids; however, opioids have not been shown to improve pain during hospitalization. We conducted a randomized controlled trial in hospitalized patients with IBD to evaluate the impact of a proactive opioid-sparing analgesic protocol. Wearable devices measured activity and sleep throughout their hospitalization. Chronic opioid users, post-operative, and pregnant patients were excluded. The primary endpoint was a change in pain scores from admission to discharge. Secondary endpoints included opioid use, functional activity, sleep duration and quality, and length of stay. Of 329 adults with IBD evaluated for eligibility, 33 were enrolled and randomized to the intervention or usual care. Both the intervention and control group demonstrated significant decreases in pain scores from admission to discharge (− 2.6 ± 2.6 vs. − 3.0 ± 3.2). Those randomized to the intervention tended to have lower pain scores than the control group regardless of hospital day (3.02 ± 0.90 vs. 4.29 ± 0.81, p = 0.059), used significantly fewer opioids (daily MME 11.8 ± 15.3 vs. 30.9 ± 42.2, p = 0.027), and had a significantly higher step count by Day 4 (2330 ± 1709 vs. 1050 ± 1214; p = 0.014). There were no differences in sleep duration, sleep quality, readmission, or length-of-stay between the two groups. A proactive analgesic protocol does not result in worsening pain but does significantly reduce opioid-use in hospitalized IBD patients. Clinical trial registration number: NCT03798405 (Registered 10/01/2019).

BackgroundPatient portals allow communication with clinicians, access to test results, appointments, etc, and generally requires another set of log-ins and passwords, which can become cumbersome, as patients often have records at multiple institutions. Social credentials (eg, Google and Facebook) are increasingly used as a federated identity to allow access and reduce the password burden. Single Federated Identity Log-in for Electronic health records (Single-FILE) is a real-world test of the feasibility and acceptability of federated social credentials for patients to access their electronic health records (EHRs) at multiple organizations with a single sign-on (SSO).ObjectiveThis study aims to deploy a federated identity system for health care in a real-world environment so patients can safely use a social identity to access their EHR data at multiple organizations. This will help identify barriers and inform guidance for the deployment of such systems.MethodsSingle-FILE allowed patients to pick a social identity (such as Google or Facebook) as a federated identity for multisite EHR patient portal access with an SSO. Binding the identity to the patient's EHR records was performed by confirming that the patient had a valid portal log-in and sending a one-time passcode to a telephone (SMS text message or voice) number retrieved from the EHR. This reduced the risk of stolen EHR portal credentials. For a real-world test, we recruited 8 patients and (or) their caregivers who had EHR data at 2 independent health care facilities, enrolled them into Single-FILE, and allowed them to use their social identity credentials to access their patient records. We used a short qualitative interview to assess their interest and use of a federated identity for SSO. Single-FILE was implemented as a web-based patient portal, although the concept can be readily implemented on a variety of mobile platforms.ResultsWe interviewed the patients and their caregivers to assess their comfort levels with using a social identity for access. Patients noted that they appreciated only having to remember 1 log-in as part of Single-FILE and being able to sign up through Facebook.ConclusionsOur results indicate that from a technical perspective, a social identity can be used as a federated identity that is bound to a patient's EHR data. The one-time passcode sent to the patient's EHR phone number provided assurance that the binding is valid. The patients indicated that they were comfortable with using their social credentials instead of having to remember the log-in credentials for their EHR portal. Our experience will help inform the implementation of federated identity systems in health care in the United States.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

Purpose This meta-analysis of all relevant clinical trials investigated surgical plethysmographic index (SPI)-guided analgesia's efficacy under general anesthesia for perioperative opioid requirement and emergence time after anesthesia. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched up to January 2022 to identify clinical trials comparing SPI-guided and conventional clinical practice for patients who underwent general anesthesia. With the random-effects model, we compared intraoperative opioid consumption, emergence time, postoperative pain, analgesia requirement, and incidence of postoperative nausea and vomiting (PONV). Results Thirteen randomized controlled trials (RCTs) (n = 1314) met our selection criteria. The overall pooled effect sizes of all RCTs indicated that SPI-guided analgesia could not significantly reduce opioid consumption during general anesthesia. SPI-guided analgesia accompanied with hypnosis monitoring could decrease intraoperative opioid consumption (standardized mean difference [SMD] - 0.31, 95% confidence interval [CI] - 0.63 to 0.00) more effectively than SPI without hypnosis monitoring (SMD 1.03, 95% CI 0.53-1.53), showing a significant difference (p < 0.001). SPI-guided analgesia could significantly shorten the emergence time, whether assessed by extubation time (SMD - 0.36, 95% CI - 0.70 to - 0.03, p < 0.05, I.sup.2 = 67%) or eye-opening time (SMD - 0.40, 95% CI - 0.63 to - 0.18, p < 0.001, I.sup.2 = 54%). SPI-guided analgesia did not affect the incidence of PONV, postoperative pain, and analgesia management. Conclusion SPI-guided analgesia under general anesthesia could enhance recovery after surgery without increasing the postoperative complication risk. However, it did not affect intraoperative opioid requirement. Notably, SPI-guided analgesia with hypnosis monitoring could effectively reduce intraoperative opioid requirement., Author(s): Shao-Chi Hung [sup.1], Wei-Ti Hsu [sup.1] [sup.2], Chi-Lin Fu [sup.3], Yu-Wen Lai [sup.3] [sup.4], Mei-Ling Shen [sup.5], Kuen-Bao Chen [sup.1] [sup.6] Author Affiliations: (1) grid.411508.9, 0000 0004 0572 9415, [...]

This paper develops an optimal replacement policy V* for a multi-state manufacturing system. The manufacturing system would be repaired imperfectly once its performance cannot meet the production demand, and would be replaced when the production demand is not met for the V*-th time. Due to imprecise state assignments and unpredictable external working conditions, the performance and transition intensity of the multi-state machine cannot be accurately identified and then inevitably lead to epistemic uncertainty. In addition, the economic dependence and resource dependence that prevailed in the manufacturing system should be considered. In this paper, economic dependence is described as the time and cost saved by simultaneously repairing multiple identical machines, and resource dependence is caused by finite capacity buffers. To take these into account, the fuzzy Markov model and fuzzy stochastic flow manufacturing network (FSFMN) are tailored to evaluate the fuzzy reliability of machines and manufacturing systems, respectively. To obtain the optimal replacement policy V*, we derive the expression of the long run fuzzy profit rate under epistemic uncertainty. The replacement policy is demonstrated on the ferrite phase shifting unit manufacturing system, and the results of the subsequent comparative study and sensitivity analysis show that this policy is more effective. [ABSTRACT FROM AUTHOR]

A molecular link between the milk fat globule–epidermal growth factor 8 (MFG-E8), activation of vascular calcification driver TGF-β1 and osteogenic differentiation of vascular smooth muscle cells suggests that MFG-E8 could be a therapeutic target for vascular calcification.

Summary: Polyfluoroaryl sulfide is one of the prevalent motifs ubiquitous in materials and pharmaceutical chemistry. We herein describe a simple yet efficient procedure for their synthesis from readily available thiols and polyfluoroarenes via an SNAr step. We detail specific steps for a gram-scale preparation of 2-((perfluoropyridin-4-yl)thio)benzo[d]thiazole 3 from mercaptobenzothiazole 1 and pentafluoropyridine 2.For complete details on the use and execution of this protocol, please refer to Liao et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Membranous CD14 is crucial in the phagocytic activity of neutrophils. However, the role of CD14(+) microparticles (MPs) derived from apoptotic neutrophils (apo-MP) during the phagocytic process is not clear. All trans-retinoic acid (ATRA) induces acute promyelocytic leukemic NB4 cells along granulocytic differentiation. In this study, we investigated the role of CD14(+)apo-MP in the cell–cell interaction during the phagocytic process of apoptotic cells by viable ATRA-NB4 cells. We firstly demonstrate that CD14 expression and phagocytic activity of NB4 cells were upregulated simultaneously after ATRA treatment in a time-dependent manner, and both were significantly enhanced via concurrent lipopolysaccharide treatment. The phagocytic activity of ATRA-NB4 cells and lipopolysaccharide-treated ATRA-NB4 cells were both significantly attenuated by pre-treating cells with an antibody specific to either CD14 or TLR4. Further flow cytometric analysis demonstrates that apoptotic ATRA-NB4 cells release CD14(+)apo-MP in an idarubicin dosage-dependent manner. Both CD14 expression and the phagocytic activity of viable ATRA-NB4 cells were significantly enhanced after incubation with apo-MP harvested from apoptotic ATRA-NB4 cells, and the apo-MP-enhanced phagocytic activity was significantly attenuated by pre-treating apo-MP with an anti-CD14 antibody before incubation with viable cells. We conclude that CD14(+)apo-MP derived from apoptotic ATRA-NB4 cells promotes the phagocytic activity of viable ATRA-NB4 cells in engulfing apoptotic cells.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications. [ABSTRACT FROM AUTHOR]

Obesity and metabolic syndrome are strong risk factors for incident chronic kidney disease (CKD). However, the predictive accuracy of metabolic body composition status (MBCS), which combines the status of obesity and metabolic syndrome, for rapid kidney function decline (RKFD) is unclear. The aim of this study was to investigate the relationship between MBCS and RKFD in a healthy population in a prospective community-based cohort study. In the current study, we followed changes in renal function in 731 people residing in northern Taiwan for 5 years. The participants were divided into four groups according to their MBCS, including metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight (MUOW). We evaluated traditional risk factors for CKD and metabolic profiles. The primary outcome was RKFD, which was defined as a 15% decline in estimated glomerular filtration rate (eGFR) within the first 4 years, and a reduction in eGFR which did not improve in the 5th year. During the study period, a total of 731 participants were enrolled. The incidence of RKFD was 17.1% (125/731). Multiple Cox logistic regression hazard analysis revealed that age, cerebrovascular accident, eGFR, urine albumin-to-creatinine ratio, use of painkillers, depressive mood, MUNW and MUOW were independent predictors of RKFD. After adjusting for age, sex, eGFR and total cholesterol, the participants with MUNW and MUOW had higher hazard ratios (HRs) for RKFD [HR: 2.19, 95% confidence interval (CI): 1.22–3.95 for MUNW; HR: 1.86, 95% CI: 1.21–2.87 for MUOW] than those with MHNW. Similar results were also observed in subgroup analysis of those aged above 65 years. On the basis of the results of this study, we conclude that MBCS was independently associated with RKFD, especially in the older adults. On the basis of our results, we suggest that MUNW and MUOW should be considered as risk factors for RKFD.

BackgroundPatient portals allow communication with clinicians, access to test results, appointments, etc, and generally requires another set of log-ins and passwords, which can become cumbersome, as patients often have records at multiple institutions. Social credentials (eg, Google and Facebook) are increasingly used as a federated identity to allow access and reduce the password burden. Single Federated Identity Log-in for Electronic health records (Single-FILE) is a real-world test of the feasibility and acceptability of federated social credentials for patients to access their electronic health records (EHRs) at multiple organizations with a single sign-on (SSO). ObjectiveThis study aims to deploy a federated identity system for health care in a real-world environment so patients can safely use a social identity to access their EHR data at multiple organizations. This will help identify barriers and inform guidance for the deployment of such systems. MethodsSingle-FILE allowed patients to pick a social identity (such as Google or Facebook) as a federated identity for multisite EHR patient portal access with an SSO. Binding the identity to the patient’s EHR records was performed by confirming that the patient had a valid portal log-in and sending a one-time passcode to a telephone (SMS text message or voice) number retrieved from the EHR. This reduced the risk of stolen EHR portal credentials. For a real-world test, we recruited 8 patients and (or) their caregivers who had EHR data at 2 independent health care facilities, enrolled them into Single-FILE, and allowed them to use their social identity credentials to access their patient records. We used a short qualitative interview to assess their interest and use of a federated identity for SSO. Single-FILE was implemented as a web-based patient portal, although the concept can be readily implemented on a variety of mobile platforms. ResultsWe interviewed the patients and their caregivers to assess their comfort levels with using a social identity for access. Patients noted that they appreciated only having to remember 1 log-in as part of Single-FILE and being able to sign up through Facebook. ConclusionsOur results indicate that from a technical perspective, a social identity can be used as a federated identity that is bound to a patient’s EHR data. The one-time passcode sent to the patient’s EHR phone number provided assurance that the binding is valid. The patients indicated that they were comfortable with using their social credentials instead of having to remember the log-in credentials for their EHR portal. Our experience will help inform the implementation of federated identity systems in health care in the United States.

Background: Fibroblast growth factor-23 (FGF-23) associates with decreased kidney function in patients with chronic kidney disease (CKD). However, the correlation between circulating FGF-23 levels and the rate of renal function decline in healthy individuals is largely unknown. We aimed to evaluate the predictive performance of FGF-23 for rapid kidney function decline (RKFD) in a community-based study. Methods: A total of 2963 people residing in northern Taiwan were enrolled from August 2013 to May 2018 for an annual assessment of kidney function for five years. The baseline estimated glomerular filtration rates (eGFR) were calculated using the 2009 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which aggregates the values of serum creatinine and cystatin C (eGFRcr-cys). The outcome was RKFD—a 15% decrease in estimated glomerular filtration rate (eGFR) within the first four years, and a reduction in eGFR without improvement in the 5th year. A generalized additive model (GAM) was used to determine the cut-off value of FGF-23 to predict RKFD. Results: The incidence of RKFD was 18.0% (114/634). After matching for age and sex at a 1:1 ratio, a total of 220 subjects were analyzed. eGFRcr-cys was negatively correlated with total vitamin D level but seemed irrelevant to FGF-23. Multivariable logistic regression analysis showed that FGF-23, eGFRcr-cys, and urine albumin-to-creatinine ratio (UACR) were independent predictors of the possibility of RKFD. FGF-23 showed the best predictive performance for RKFD (AUROC: 0.803), followed by baseline eGFRcr-cys (AUROC: 0.639) and UACR (AUROC: 0.591). From the GAM, 32 pg/mL was the most appropriate cut-off value of FGF-23 with which to predict RKFD. The subgroup and sensitivity analyses showed consistent results that high-FGF-23 subjects had higher risks of RKFD. Conclusions: Circulating FGF-23 level could be a helpful predictor for RKFD in this community-based population.

Background: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. Methods: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. Results: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. Conclusions: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects.