bluuebunny/crossref_metadata_2025_split huggingface dataset:
Joint tenderness at 3 months follow-up better predicts long-term pain than baseline characteristics in early rheumatoid arthritis patients
Authors: Eberhard Anna , Bergman Stefan , Mandl Thomas , Olofsson Tor , Sharma Ankita , Turesson Carl 
Published: June 2023

Abstract

Objective
To investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA.

Methods
A cohort of 275 patients with early RA, recruited in 2012–2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0–100 mm). Unacceptable pain was defined as VAS pain &gt;40, and low inflammation as CRP &lt;10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis.

Results
After 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures.

Conclusion
A substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA.
Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries
Authors: Linde Louise , Ørnbjerg Lykke M , Georgiadis Stylianos , H. Rasmussen Simon , Lindström Ulf , Askling Johan , Michelsen Brigitte , Di Giuseppe Daniela , Wallman Johan K , Gudbjornsson Bjorn , Love Thorvardur Jon , Nordström Dan C , Yli-Kerttula Timo , Nekvindová Lucie , Vencovský Jiří , Iannone Florenzo , Cauli Alberto , Loft Anne Gitte , Glintborg Bente , Laas Karin , Rotar Ziga , Tomšič Matija , Macfarlane Gary J , Möller Burkhard , van de Sande Marleen , Codreanu Catalin , Nissen Michael J , Birlik Merih , Erten Sukran , Santos Maria J , Vieira-Sousa Elsa , Hetland Merete L , Østergaard Mikkel 
Published: June 2023

Abstract

Objectives
In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries.

Methods
Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors.

Results
In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n = 6954, n = 5275 and n = 13 369, respectively). Five common baseline predictors of remission, moderate response and 12-month drug retention were identified across all three outcomes. The odds ratios (95% CIs) for DAPSA28 remission were: age, per year: 0.97 (0.96–0.98); disease duration, years (&lt;2 years as reference): 2–3 years: 1.20 (0.89–1.60), 4–9 years: 1.42 (1.09–1.84), ≥10 years: 1.66 (1.26–2.20); men vs women: 1.85 (1.54–2.23); CRP of &gt;10 vs ≤10 mg/l: 1.52 (1.22–1.89) and 1 mm increase in patient fatigue score: 0.99 (0.98–0.99).

Conclusion
Baseline predictors of remission, response and adherence to TNFi therapy were identified, of which five were common for all three outcomes, indicating that the predictors emerging from our pooled cohort may be considered generalizable from country level to disease level.
Legislating Through Policy Statements: The Authority of National Visions in the Arabian Gulf
Authors: Bantekas Ilias 
Published: June 2023

Abstract
National Visions are policy instruments characterized by an outlook that is constitutional in nature, while also appealing to a country’s external relations, as well as its citizens. They are unique to the law and policy of Gulf States and set out decade-long policy aims that are subsequently translated into legislation or/and foreign policy objectives. This article examines the sports-related dimension of the Qatari National Vision, which was the basis for the country’s bid for the 2022 FIFA World Cup. It is demonstrated that the constitutional nature of the sports dimension of the Vision helped to shape social attitudes in Qatar, as well as facilitate a rapid legislative reform in the field of labor relations, such that would have been unthinkable in the absence of strong sports-oriented policy underpinning the entire nation. National Visions should therefore be viewed as accelerators of social change and drivers of rapid legislative reform, even if they themselves do not outward display normative qualities.
Management of anesthetic complications outside the operating room
Authors: Hardman Bailor , Karamchandani Kunal 
Published: June 2023

Purpose of reviewNonoperating room anesthesia (NORA) procedures have seen a significant growth over the years along with an increase in the complexity and severity of cases. Providing anesthesia care in these often-unfamiliar locations is risky, and complications are common. This review aims to report the most recent updates regarding managing anesthesia-related complications in patients undergoing procedures in non-operating room locations.Recent findingsSurgical innovations, advent of new technology, and the economics of a healthcare environment that strives to improve value by decreasing costs, has expanded the indications for and complexity of NORA cases. In addition, an aging population with increasing comorbidity burden, requirements for deeper levels of sedation have all increased the risk of complications in NORA environments. In such a situation, improvement in monitoring and oxygen delivery techniques, better ergonomics of NORA sites and development of multidisciplinary contingency plans are likely to improve our management of anesthesia-related complications.SummaryDelivery of anesthesia care in out-of-operating room locations is associated with significant challenges. Meticulous planning, close communication with the procedural team, establishing protocols and pathways for help, along with interdisciplinary teamwork can facilitate safe, efficient, and cost-effective procedural care in the NORA suite.
Pharmacokinetic and pharmacodynamic drug display and simulation systems in anesthesia practice
Authors: Kennedy R Ross 
Published: June 2023

Purpose of review
This review explores the use of tools and displays based on pharmacokinetic and pharmacodynamic (PK/PD) modelling of drugs used in anesthesia. The primary focus is on those tools designed to illustrate the interactions between two or more drugs, or classes of drugs, and in particular, their use in a real-time clinical support role. Off-line, educational tools are also explored.

Recent findings
Despite initial promise and encouraging supporting data, the use of real-time display of PK/PD is not common except in target-controlled infusion (TCI) pumps.

Summary
PK/PD simulation is a useful tool for exposition of the relationship between drug dosing and effect. The initial promise of real-time tools has yet to be realized in routine clinical practice.
DHCR7 Expression Predicts Poor Outcomes and Mortality From Sepsis
Authors: Guirgis Faheem W. , Jacob Vinitha , Wu Dongyuan , Henson Morgan , Daly-Crews Kimberly , Hopson Charlotte , Black Lauren Page , DeVos Elizabeth L. , Sulaiman Dawoud , Labilloy Guillaume , Brusko Todd M. , Shavit Jordan A. , Bertrand Andrew , Feldhammer Matthew , Baskovich Brett , Graim Kiley , Datta Susmita , Reddy Srinivasa T. 
Published: June 2023

IMPORTANCE:
This is a study of lipid metabolic gene expression patterns to discover precision medicine for sepsis.

OBJECTIVES:
Sepsis patients experience poor outcomes including chronic critical illness (CCI) or early death (within 14 d). We investigated lipid metabolic gene expression differences by outcome to discover therapeutic targets.

DESIGN, SETTING, AND PARTICITPANTS:
Secondary analysis of samples from prospectively enrolled sepsis patients (first 24 hr) and a zebrafish endotoxemia model for drug discovery. Patients were enrolled from the emergency department or ICU at an urban teaching hospital. Enrollment samples from sepsis patients were analyzed. Clinical data and cholesterol levels were recorded. Leukocytes were processed for RNA sequencing and reverse transcriptase polymerase chain reaction. A lipopolysaccharide zebrafish endotoxemia model was used for confirmation of human transcriptomic findings and drug discovery.

MAIN OUTCOMES AND MEASURES:
The derivation cohort included 96 patients and controls (12 early death, 13 CCI, 51 rapid recovery, and 20 controls) and the validation cohort had 52 patients (6 early death, 8 CCI, and 38 rapid recovery).

RESULTS:
The cholesterol metabolism gene 7-dehydrocholesterol reductase (DHCR7) was significantly up-regulated in both derivation and validation cohorts in poor outcome sepsis compared with rapid recovery patients and in 90-day nonsurvivors (validation only) and validated using RT-qPCR analysis. Our zebrafish sepsis model showed up-regulation of dhcr7 and several of the same lipid genes up-regulated in poor outcome human sepsis (dhcr24, sqlea, cyp51, msmo1, and ldlra) compared with controls. We then tested six lipid-based drugs in the zebrafish endotoxemia model. Of these, only the Dhcr7 inhibitor AY9944 completely rescued zebrafish from lipopolysaccharide death in a model with 100% lethality.

CONCLUSIONS:

DHCR7, an important cholesterol metabolism gene, was up-regulated in poor outcome sepsis patients warranting external validation. This pathway may serve as a potential therapeutic target to improve sepsis outcomes.
E3 Ubiquitin Ligases in Endothelial Dysfunction and Vascular Diseases: Roles and Potential Therapies
Authors: Wang Yihan , Zhan Yixiong , Wang Linsiqi , Huang Xuan , Xin Hong-Bo , Fu Mingui , Qian Yisong 
Published: June 2023

Abstract:
Ubiquitin E3 ligases are a structurally conserved family of enzymes that exert a variety of regulatory functions in immunity, cell death, and tumorigenesis through the ubiquitination of target proteins. Emerging evidence has shown that E3 ubiquitin ligases play crucial roles in the pathogenesis of endothelial dysfunction and related vascular diseases. Here, we reviewed the new findings of E3 ubiquitin ligases in regulating endothelial dysfunction, including endothelial junctions and vascular integrity, endothelial activation, and endothelial apoptosis. The critical role and potential mechanism of E3 ubiquitin ligases in vascular diseases, such as atherosclerosis, diabetes, hypertension, pulmonary hypertension, and acute lung injury, were summarized. Finally, the clinical significance and potential therapeutic strategies associated with the regulation of E3 ubiquitin ligases were also proposed.
Using Prior Knowledge on Systems Through PBPK to Gain Further Insight into Routine Clinical Data on Trough Concentrations: The Case of Tacrolimus in Chronic Kidney Disease
Authors: El-Khateeb Eman , Chinnadurai Rajkumar , Al Qassabi Jokha , Scotcher Daniel , Darwich Adam S. , Kalra Philip A. , Rostami-Hodjegan Amin 
Published: June 2023

Background:
Routine therapeutic drug monitoring (TDM) relies heavily on measuring trough drug concentrations. Trough concentrations are affected not only by drug bioavailability and clearance, but also by various patient and disease factors and the volume of distribution. This often makes interpreting differences in drug exposure from trough data challenging. This study aimed to combine the advantages of top-down analysis of therapeutic drug monitoring data with bottom-up physiologically-based pharmacokinetic (PBPK) modeling to investigate the effect of declining renal function in chronic kidney disease (CKD) on the nonrenal intrinsic metabolic clearance (CL

int
) of tacrolimus as a case example.

Methods:
Data on biochemistry, demographics, and kidney function, along with 1167 tacrolimus trough concentrations for 40 renal transplant patients, were collected from the Salford Royal Hospital's database. A reduced PBPK model was developed to estimate CL

int
for each patient. Personalized unbound fractions, blood-to-plasma ratios, and drug affinities for various tissues were used as priors to estimate the apparent volume of distribution. Kidney function based on the estimated glomerular filtration rate (eGFR) was assessed as a covariate for CL

int
using the stochastic approximation of expectation and maximization method.

Results:
At baseline, the median (interquartile range) eGFR was 45 (34.5–55.5) mL/min/1.73 m2. A significant but weak correlation was observed between tacrolimus CL

int
and eGFR (r = 0.2, P < 0.001). The CL

int
declined gradually (up to 36%) with CKD progression. Tacrolimus CL

int
did not differ significantly between stable and failing transplant patients.

Conclusions:
Kidney function deterioration in CKD can affect nonrenal CL

int
for drugs that undergo extensive hepatic metabolism, such as tacrolimus, with critical implications in clinical practice. This study demonstrates the advantages of combining prior system information (via PBPK) to investigate covariate effects in sparse real-world datasets.
Effect of Tacrolimus Time in Therapeutic Range on Postoperative Recurrence in Patients Undergoing Liver Transplantation for Liver Cancer
Authors: Lao Qianying , Wu Xuanyu , Zheng Xinxin , Hu Jinwei , Huang Siqi , Li Danying , Du Yao , Yang Na , Zhu Huaijun 
Published: June 2023

Background and Objective:
Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines.

Methods:
A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus.

Result:
Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation.

Conclusions:
TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.
The Value of Case Reports in Plastic Surgery: An Analysis of 68,444 Articles across Six Major Plastic Surgery Journals
Authors: Ormseth Benjamin H. , Sarac Benjamin A. , Westvik Tormod S. , Janis Jeffrey E. 
Published: June 2023

Background:
Case reports provide a salient contribution to the field of plastic surgery through the timely dissemination of knowledge on previously underreported topics. Once a time-honored hallmark of the surgical literature, the perceived value of case reports has decreased with the ongoing prioritization of higher levels of evidence. In this study, we aimed to assess long-term trends in case report publication rates and discuss the continued merits of case reports in the modern-day landscape.

Methods:
A PubMed search was used to identify articles published in six prominent plastic surgery journals since 1980. Articles were separated as case reports versus all other publication types. The total number of articles published by group was tracked, and citation rates were compared across groups. Additionally, the most cited articles from each journal were identified for both groups.

Results:
A total of 68,444 articles were included for analysis. In 1980, there were 181 case reports published compared with 413 other articles across all six journals. In 2022, there were 188 case reports published compared with 3343 other articles. When comparing citations per year of case reports versus other article types across all journals since 1980, case reports were found to be cited significantly less frequently (P < 0.001).

Conclusions:
Case reports have been published and cited less frequently than other types of literature over the last 42 years. However, despite these trends, they have demonstrated significant historical contributions and provide continued value as an impactful forum for highlighting novel clinical entities.
Low-dose supplementation with retinol improves retinal function in eyes with age-related macular degeneration but without reticular pseudodrusen
Authors: Pfau Kristina , Jeffrey Brett G. , Cukras Catherine A. 
Published: June 2023

ABSTRACT

Aims:
To determine the functional impact of oral Vitamin A supplementation in patients with intermediate age-related macular degeneration (iAMD) with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation (DA).

Methods:
Five patients with iAMD and without RPD (AMD group; mean ± SD age 78.0 ± 4.7 years) and seven with RPD (RPD group; age 74.1 ± 11.2 years) were supplemented with 16,000 IU of Vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8 and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities and the low-luminance quality of life questionnaire.

Results:
In the linear mixed model, RIT improved significantly in the AMD group (mean[95% CI] change -1.1 min [-1.8; -0.5] after 4 weeks (p<0.001) and -2.2 min[-2.9; 1.6] after 8 weeks of Vitamin A supplementation (p<0.001). The DA cone plateau also significantly improved (i.e. more sensitive cone threshold) at 4 and 8 weeks (p=0.026 and p=0.001). No other parameters improved in the AMD group and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum Vitamin A levels measurable in both groups after supplementation (p=0.024 and p=0.013).

Conclusions:
Supplementation with 16,000IU Vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients, and/or may reflect the higher variability observed in the functional parameters for this group.
Pure Red Cell Aplasia Caused by Parvovirus B19 in Patients with Human Immunodeficiency Virus Infection: A Series of Four Cases
Authors: Xu Feilong , Wang Yulong , Fan Linjin , He Yaozu , Chen Xiejie , Ye Pengfei , Liu Linna , Qian Jun , Li Linghua 
Published: June 2023

Abstract
Parvovirus B19 (B19V) infection can cause pure red cell aplasia (PRCA) in patients with human immunodeficiency virus (HIV) infection. Intravenous immunoglobulin (IVIG) is a preferred treatment option. From July 2019 to March 2022, four patients with HIV infection were admitted to Guangzhou Eighth People’s Hospital with dizziness and fatigue and were diagnosed with PRCA. Blood investigations revealed severe anemia and the B19V genome. Therefore, the four patients were diagnosed with B19V-induced PRCA. All four patients received red blood cell transfusion in the setting of antiretroviral therapy, and two of the four patients received intravenous immunoglobulin (IVIG). After 3–7 months of treatment, all four patients recovered, although two did not receive IVIG. This suggests that IVIG is not always necessary for the treatment of PRCA in patients with HIV infection and that effective antiretroviral therapy and immunological reconstitution play an important role in the eradication of parvovirus.
Influence of Refractive Error on Circumpapillary Structure–Function Versus Vessel Density–Function Relationships in Open Angle Glaucoma
Authors: Emoto Yoshinobu , Hollό Gábor , Kita Yoshiyuki , Saito Tsunehiro , Kita Ritsuko 
Published: June 2023

Précis:
In Japanese open angle glaucoma (OAG) eyes correlation of 30-degree visual field mean deviation (MD) and visual field index (VFI) with circumpapillary vessel density is systematically stronger than that with circumpapillary retinal nerve fiber layer thickness (RNFLT), and is preserved in myopia and high myopia.

Purpose:
The purpose of this study was to investigate the influence of refractive error on the relationship between circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and circumpapillary vessel density (cpVD), respectively, and global visual field parameters in Japanese open angle glaucoma (OAG) eyes.

Material and Methods:
One eye of 81 Japanese OAG patients (spherical equivalent refractive error: +3.0 to −9.0 D) underwent 360-degree cpRNFLT and cpVD measurements with Cirrus HD 5000-AngioPlex optical coherence tomography and 30-2 Humphrey visual field testing for mean deviation (MD) and visual field index (VFI) within 1 month. Correlations were determined for the whole population and each refractive error subgroups, separately: emmetropia/hyperopia (n=24), mild (n=18), moderate (n=20), and high myopia (n=19).

Results:
For the total population, significant strong to very strong correlations were found between MD, VFI, and both cpRNFLT and cpVD, respectively, with consistently higher r-values for cpVD (highest r-values: 0.532 for cpRNFLT, P<0.001; 0.722 for cpVD, P<0.001). Of the refractive subgroups, statistically significant correlations between cpRNFLT and the visual field parameters were maintained only in the hyperopia/emmetropia and moderate myopia groups. In contrast, statistically significant, strong to very strong correlations between cpVD and both MD and VFI, always exceeding the corresponding r-values found for cpRNFLT were found in all refractive subgroups, with r-values ranging between 0.548 (P=0.005) and 0.841 (P<0.001).

Conclusions:
Our results suggest that in Japanese OAG eyes the relationship of MD and VFI with cpVD is strong. It is systematically stronger than that with cpRNFLT and preserved in each conventional refractive error category including high myopia.