bluuebunny/crossref_metadata_2025_split huggingface dataset:
GSK‐3β/β‐catenin pathway plays crucial roles in the regulation of NK cell cytotoxicity against myeloma cells
Authors: Ren Jing , Feng Xiumei , Guo Yanan , Kong Dexiao , Wang Yongjing , Xiao Juan , Jiang Wen , Feng Xiaoli , Liu Xiaoli , Li Ai , Sun Congcong , He Mingming , Li Bingen , Wang Juandong , Jiang Yang , Zheng Chengyun 
Published: February 2023

AbstractThe plasma cell malignancy, multiple myeloma (MM), has significantly improved by the application of new drugs and autologous hematopoietic stem cell transplantation. However, MM remains incurable. A number of studies have revealed an anti‐MM effect of natural killer (NK) cells; however, their clinical efficacy is limited. Furthermore, glycogen synthase kinase (GSK)‐3β inhibitors show an antitumor function. In this study, we aimed to evaluate the potential roles of a GSK‐3β inhibitor (TWS119) in the regulation of NK cell cytotoxicity against MM. Our results showed that, in the presence of TWS119, the NK cell line, NK‐92, and in vitro‐expanded primary NK cells exhibited a significantly higher degranulation activity, expression of activating receptors, cellular cytotoxicity, and cytokine secretion when they were exposed to MM cells. Mechanistic studies indicated that TWS119 treatment markedly upregulated RAB27A expression, a key molecule for NK cell degranulation, and induced the colocalization of β‐catenin with NF‐κB in the nucleus of NK cells. More importantly, GSK‐3β inhibition combined with the adoptive transfer of TWS119‐treated NK‐92 cells significantly reduced tumor volume and prolonged the survival time of myeloma‐bearing mice. In summary, our novel findings suggest that targeting GSK‐3β through the activation of β‐catenin/NF‐κB pathway may be an important approach to improve therapeutic efficacy of NK cell transfusion for MM.
Fibromyalgia and centralized pain in the rheumatoid arthritis patient
Authors: Minhas Deeba , Murphy Anne , Clauw Daniel J. 
Published: February 2023

Purpose of review
Individuals with rheumatoid arthritis (RA) have traditionally been characterized as having nociceptive pain, leading to the assumption that effective immunosuppression should be enough to provide effective pain management. However, despite therapeutic advancements providing excellent control of inflammation, patients continue to have significant pain and fatigue. The presence of concurrent fibromyalgia, driven by augmented central nervous system processing and largely unresponsive to peripheral therapies, may contribute to this pain persistence. This review provides updates on fibromyalgia and RA as relevant for the clinician.

Recent findings
Patients with RA have high levels of concomitant fibromyalgia and nociplastic pain. The presence of fibromyalgia can lead to higher scores on disease measures, erroneously indicating that worse disease is presently leading to the increased use of immunosuppressives and opioids. Disease scores that provide a comparison between patient-reported and provider-reported and clinical factors may be helpful to indicate centralized pain. IL-6 and Janus kinase inhibitors, in addition to targeting peripheral inflammation, may provide pain relief by acting on peripheral and central pain pathways.

Summary
Central pain mechanisms that may be contributing to pain in RA are common and should be distinguished from pain directly arising from peripheral inflammation.
Real-World Outcomes of Proprotein Convertase Subtilisin Kexin-9 Inhibitor Use
Authors: Kim Olivia M. , Givens Tatyana K. , Tang Emily G. , Schimmer Jennifer J. , Ramsey Tanya , Boyd Kayla , Delate Thomas 
Published: February 2023

Abstract:
Although the proprotein convertase subtilisin kexin-9 inhibitors (PCSK9i) were shown to significantly lower low-density lipoprotein and reduce atherosclerotic cardiovascular disease events in clinical trials, there is a dearth of use data on these agents in real-world settings. This study compares PCSK9i use in a population of real-world patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia. This was a matched cohort study of adult patients who were dispensed a PCSK9i along with adult patients who did not receive a PCSK9i. PCSK9i patients were matched on a propensity to have received a PCSK9i score up to 1:10 to non-PCSK9i patients. The primary outcomes were changes in cholesterol levels. Secondary outcomes included a composite outcome of all-cause mortality, major cardiovascular events, and ischemic strokes along with health care utilization during follow-up. Adjusted conditional, multivariate Cox proportional hazards, and negative binomial modeling were performed. Ninety-one PCSK9i patients were matched to 840 non-PCSK9i patients. Seventy-one percent of PCSK9i patients either discontinued or switched PCSK9i therapy. PCSK9i patients had greater median reductions in low-density lipoprotein (−73.0 mg/dL vs. −30.0 mg/dL) and total (−77.0 vs. −31.0) cholesterol (both P < 0.001). No adjusted between-group differences in the composite outcome or individual components of the composite outcome were identified (all P > 0.05). PCSK9i patients had a lower rate of medical office visits during follow-up (adjusted incidence rate ratio = 0.61, P = 0.019). These findings support the effectiveness of PCSK9i therapy in real-world settings but suggest that use may be limited by PCSK9i adverse reactions and patient cost barriers.
Perceptions of information continuity key to understanding quality of post-acute care transitions
Authors: Cross Dori A. , Hogan Tory H. , Adler-Milstein Julia 
Published: February 2023

Background
Skilled nursing facilities’ (SNFs) ability to provide optimal post-acute care depends on effective receipt of information from hospitals (“information continuity”). Little is known about how SNFs perceive information continuity and how it may relate to upstream information sharing processes, organizational context, and downstream outcomes.

Purpose
First, this study aims to identify how SNF perceptions of information continuity may be shaped by hospital information sharing practices, including measures of completeness, timeliness, and usability, as well as characteristics of the transitional care environment (i.e., integrated care relationships and/or consistency of information sharing practices across different hospital partners). Second, we analyze which of these characteristics are associated with quality of transitional care (measured by 30-day readmissions).

Approach
A cross-sectional analysis of nationally representative SNF survey (N = 212) linked to Medicare claims was performed.

Results
SNF perceptions of information continuity are strongly and positively associated with hospital information sharing practices. Adjusting for actual information sharing practices, SNFs that experienced discordance across hospitals reported lower perceptions of continuity (β = −0.73, p = .022); evidence of stronger relationships with a given hospital partner appears to help facilitate resources and communication that helps to close this gap. Perceptions of information continuity, more so than the upstream information sharing processes reported, exhibited a more reliable and significant association with rates of readmissions as an indicator of transitional care quality.

Conclusion
SNF perceptions of information continuity are strongly associated with patient outcomes and are reflective of both hospital information sharing practices as well as characteristics of the transitional care environment that can mitigate or amplify the cognitive and administration challenge of their work.

Practice Implications
Improving transitional care quality requires that hospitals improve information sharing behaviors but also invest in capacity for learning and process improvement in the SNF environment.
0.18 MG FLUOCINOLONE ACETONIDE INSERT FOR THE TREATMENT OF CHRONIC POSTOPERATIVE PSEUDOPHAKIC CYSTOID MACULAR EDEMA
Authors: Deaner Jordan D. , Mammo Danny , Gross Andrew , Lee Terry , Sharma Sumit , Srivastava Sunil K. , Jaffe Glenn J. , Grewal Dilraj S. 
Published: February 2023

Purpose:
To report the outcomes of the 0.18 mg fluocinolone acetonide insert (FAi) in the treatment of chronic (>6 months) postoperative cystoid macular edema after cataract surgery.

Methods:
This was a retrospective consecutive case series of eyes with chronic postoperative cystoid macular edema treated with the FAi. Visual acuity, intraocular pressure, optical coherence tomography metrics, and supplemental therapies were extracted from the charts before and at 3, 6, 12, 18, and 21 months after FAi placement, when available.

Results:
Nineteen eyes of 13 patients with chronic postoperative cystoid macular edema after cataract surgery underwent FAi placement with an average follow-up of 15.4 months. Ten eyes (52.6%) had a ≥2-line gain in visual acuity. Sixteen eyes (84.2%) had a ≥20% reduction in optical coherence tomography central subfield thickness. Eight eyes (42.1%) had complete resolution of CME. Improvements in central subfield thickness and visual acuity were sustained throughout individual follow-up. Compared with 18 eyes (94.7%) requiring local corticosteroid supplementation before FAi, only six eyes (31.6%) required supplementation after FAi. Similarly, of the 12 eyes (63.2%) that were on corticosteroid drops before FAi, only 3 (15.8%) required drops after FAi.

Conclusion:
Eyes with chronic postoperative cystoid macular edema after cataract surgery treated with the FAi had improved and sustained visual acuity and optical coherence tomography metrics, along with a reduction in supplemental treatment burden.
Clinical and Histopathologic Characteristics and Template of the TGFBI p.(His626Arg) Missense Variant Lattice Corneal Dystrophy
Authors: Jaakkola Aino M. , Kivelä Tero T. 
Published: February 2023

Purpose:
The aim of this study was to define, following the IC3D template format, the clinical and histopathologic phenotype of the p.(His626Arg) missense variant lattice corneal dystrophy (LCDV-H626R), the most common variant lattice dystrophy, and to record long-term outcome of corneal transplantation in this dystrophy.

Methods:
A database search and a meta-analysis of published data on LCDV-H626R were conducted. A patient diagnosed with LCDV-H626R who underwent bilateral lamellar keratoplasty followed by rekeratoplasty of 1 eye is described, including histopathologic examination of the 3 keratoplasty specimens.

Results:
One hundred forty-five patients from at least 61 families and 11 countries diagnosed with LCDV-H626R were found. This dystrophy is characterized by recurrent erosions, asymmetric progression, and thick lattice lines that extend to corneal periphery. The median age is 37 (range, 25–59) years at the onset of symptoms, 45 (range, 26–62) years at the time of diagnosis, and 50 (range, 41–78) years at the time of the first keratoplasty, suggesting a median interval from the first symptoms to diagnosis and to keratoplasty of 7 and 12 years, respectively. Clinically unaffected carriers have been of age 6 to 45 years. Central anterior stromal haze and centrally thick, peripherally thinner branching lattice lines in the anterior to midstroma of the cornea were noted preoperatively. Histopathology of the host anterior corneal lamella showed a subepithelial fibrous pannus, a destroyed Bowman layer, and amyloid deposits extending to the deep stroma. In the rekeratoplasty specimen, amyloid localized to scarring along the Bowman membrane and to the margins of the graft.

Conclusions:
The IC3D-type template for LCDV-H626R should help diagnose and manage variant carriers. The histopathologic spectrum of findings is broader and more nuanced than what has been reported.
One Year Results of the Preserflo MicroShunt Implantation for Refractory Glaucoma
Authors: Seuthe Anna-Maria , Erokhina Mariya , Szurman Peter , Haus Arno 
Published: February 2023

Précis:
The Preserflo MicroShunt is an effective method to achieve a satisfying intraocular pressure (IOP) reduction in patients with complicated forms of glaucoma.

Purpose:
To evaluate the efficacy and safety of the Preserflo MicroShunt with mitomycin C in patients with complicated glaucoma.

Methods:
This prospective interventional study included all patients that underwent Preserflo MicroShunt Implantation between April 2019 and January 2021 to treat severe and therapy refractory glaucoma. The patients either suffered from primary open angle glaucoma with already failed incisional glaucoma surgery or presented severe forms of secondary glaucoma (eg, after penetrating keratoplasty or globe penetrating injury). Primary endpoint was the IOP-lowering effect and the success rate after 12 months. Secondary endpoint was the occurrence of intraoperative or postoperative complications. Complete success was defined as reaching the target IOP (>6 mm Hg and <14 mm Hg) without additional IOP-lowering medication whereas qualified success was attained with the same IOP target regardless of the medication.

Results:
A total of 40 eyes of 38 patients were enrolled. After 12 months 85.7% of the eyes achieved complete success with an average IOP of 10.5 ± 2.0 mm Hg, without the use of glaucoma eye drops. The average IOP reduction was 58.4% from baseline. In 5 cases (12.5%) failure occurred as revisional surgery was required.

Conclusion:
The Preserflo MicroShunt for refractory glaucoma cases achieved a high complete success rate without additional medication at 1 year. Revisional surgery was needed in some cases and long-term studies are needed
Gonioscopy-Assisted Transluminal Trabeculotomy and Goniotomy, With or Without Concomitant Cataract Extraction, in Steroid-Induced and Uveitic Glaucoma: 24-Month Outcomes
Authors: Chen Rebecca I. , Purgert Robert , Eisengart Jonathan 
Published: February 2023

Précis:
Gonioscopy-assisted transluminal trabeculotomy (GATT) and goniotomy with Kahook Dual Blade both achieved sustained reductions in intraocular pressure (IOP) and medication burden in eyes with steroid-induced or uveitic glaucoma at 24 months. Both procedures had favorable safety profiles.

Purpose:
To characterize the 24-month surgical outcomes of GATT and excisional goniotomy in eyes with steroid-induced or uveitic glaucoma.

Patients and Methods:
A retrospective chart review was performed of eyes with steroid-induced or uveitic glaucoma that underwent GATT or excisional goniotomy, either standalone or combined with phacoemulsification cataract surgery, by a single surgeon at the Cole Eye Institute. IOP, number of glaucoma medications, and steroid exposure were recorded preoperatively and at multiple postoperative timepoints up to 24 months. Surgical success was defined as at least 20% IOP reduction or IOP <12, 15, or 18 mm Hg (Criterion A, B, or C). Surgical failure was defined as need for additional glaucoma surgery or loss of light perception vision. Intraoperative and postoperative complications were reported.

Results:
Forty eyes of 33 patients underwent GATT, and 24 eyes of 22 patients underwent goniotomy, of which 88% and 75%, respectively, had 24-months’ follow-up. Concomitant phacoemulsification cataract surgery was performed in 38% (15/40) GATT eyes and 17% (4/24) goniotomy eyes. IOP and number of glaucoma medications were reduced at all postoperative timepoints in both groups. At 24 months, GATT eyes had mean IOP 12.9±3.5 mm Hg on 0.9±1.2 medications, and goniotomy eyes had mean IOP 14.3±4.1 mm Hg on 1.8±1.3 medications. Surgical failure was 8% for GATT and 14% for goniotomy at 24 months. Transient hyphema and transient IOP elevation were the most common complications, and 10% GATT eyes required surgical evacuation of hyphema.

Conclusions:
Both GATT and goniotomy demonstrate favorable efficacy and safety in steroid-induced and uveitic glaucoma eyes. Both procedures achieved sustained reductions in IOP and glaucoma medication burden at 24 months.
Reported History of Measles and Long-term Impact on Tetanus Antibody Detected in Children 9–59 Months of Age and Receiving 3 Doses of Tetanus Vaccine in the Democratic Republic of the Congo
Authors: Ashbaugh Hayley R. , Cherry James D. , Hoff Nicole A. , Doshi Reena H. , Mukadi Patrick , Higgins Stephen G. , Budd Roger , Randall Christina , Okitolonda-Wemakoy Emile , Muyembe-Tamfum Jean Jacques , Gerber Sue K. , Wells Christine , Rimoin Anne W. 
Published: February 2023

Background:
Recent studies suggest measles-induced immune amnesia could have long-term immunosuppressive effects via preferential depletion of memory CD150+ lymphocytes, and associations with a 2–3 year period of increased mortality and morbidity from infectious diseases other than measles has been shown in children from wealthy and low-income countries. To further examine the associations previous measles virus infection may have on immunologic memory among children in the Democratic Republic of the Congo (DRC), we assessed tetanus antibody levels among fully vaccinated children, with and without a history of measles.

Methods:
We assessed 711 children 9–59 months of age whose mothers were selected for interview in the 2013–2014 DRC Demographic and Health Survey. History of measles was obtained by maternal report and classification of children who had measles in the past was completed using maternal recall and measles IgG serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. Tetanus IgG antibody serostatus was similarly obtained. A logistic regression model was used to identify association of measles and other predictors with subprotective tetanus IgG antibody.

Results:
Subprotective geometric mean concentration tetanus IgG antibody values were seen among fully vaccinated children 9–59 months of age, who had a history of measles. Controlling for potential confounding variables, children classified as measles cases were less likely to have seroprotective tetanus toxoid antibody (odds ratio: 0.21; 95% confidence interval: 0.08–0.55) compared with children who had not had measles.

Conclusions:
History of measles was associated with subprotective tetanus antibody among this sample of children in the DRC who were 9–59 months of age and fully vaccinated against tetanus.
Has COVID-19 Changed Pediatric Acute Rhinosinusitis Epidemiology During the First 2 Pandemic Years?
Authors: Hazan Itai , Ziv Oren , Marom Tal , Zloczower Elchanan , Pitaro Jacob , Warman Meir 
Published: February 2023

Objective:
To study national pediatric acute rhinosinusitis (ARS) burden fluctuations before and during the first 2 coronavirus-19 (COVID) years, characterized by alternating lockdown and relaxation periods, the introduction of COVID vaccines, and the emergence of nonalpha COVID variants.

Methods:
This was a cross-sectional, population-based study covering the 3 pre-COVID years and the first 2 COVID years from a big database of the largest Israeli Health Maintenance Organization. For comparison purposes, we explored ARS burden trends with those of urinary tract infection (UTI), which is unrelated to viral diseases. We identified children <15 years presenting with ARS and UTI episodes and categorized them according to their age and presentation date. The average ARS and UTI episodes of the 3 pre-COVID years were used to calculate the incidence rate ratios (IRRs) of the 2 COVID years, analyzed separately. Seasonal variations were explored.

Results:
We identified 44,483 ARS and 121,263 UTI episodes. There was a substantial reduction in ARS episodes during the COVID years (IRR 0.36, 95% CI: 0.24–0.56, P < 0.001). Although UTI episode rates also decreased during COVID (IRR 0.79, 95% CI: 0.72–0.86, P < 0.001), the reduction in ARS burden was 3-fold higher. The dominant pediatric ARS age group was between 5 and 15 years. The largest decrease in ARS burden was during the first COVID year. ARS episode distribution showed a seasonal fluctuation, with a peak during the summer months during the COVID years.

Conclusions:
Pediatric ARS burden decreased during the first 2 COVID years. Episode distribution was noted to be year-round.
The Evolving Pediatric HIV Epidemic in Rural Southern Zambia: The Beneficial Impact of Advances in Prevention and Treatment at a District Hospital From 2007 to 2019
Authors: Sutcliffe Catherine G. , Moyo Nkumbula , Hamahuwa Mutinta , Mutanga Jane N. , van Dijk Janneke H. , Hamangaba Francis , Schue Jessica L. , Thuma Philip E. , Moss William J. 
Published: February 2023

Background:
Remarkable progress has been made in expanding access to services addressing the pediatric HIV epidemic, including programs to prevent mother-to-child transmission, early diagnosis and treatment for children living with HIV. Few long-term data are available from rural sub-Saharan Africa to assess implementation and impact of national guidelines.

Methods:
Results from 3 cross-sectional studies and 1 cohort study conducted at Macha Hospital in Southern Province, Zambia from 2007 to 2019 were summarized. For infant diagnosis, maternal antiretroviral treatment, infant test results and turnaround times for results were evaluated by year. For pediatric HIV care, the number and age of children initiating care and treatment, and treatment outcomes within 12 months were evaluated by year.

Results:
Receipt of maternal combination antiretroviral treatment increased from 51.6% in 2010–2012 to 93.4% in 2019, and the proportion of infants testing positive decreased from 12.4% to 4.0%. Turnaround times for results returning to clinic varied but were shorter when labs consistently used a text messaging system. The proportion of mothers receiving results was higher when a text message intervention was piloted. The number of children living with HIV enrolled into care and the proportion initiating treatment with severe immunosuppression and dying within 12 months decreased over time.

Conclusions:
These studies demonstrate the long-term beneficial impact of implementing a strong HIV prevention and treatment program. While expansion and decentralization brought challenges, the program succeeded in decreasing the rate of mother-to-child transmission and ensuring that children living with HIV benefit from access to life-saving treatment.
Predictive Factors to Guide Empiric Antimicrobial Therapy of Acute Hematogenous Osteomyelitis in Children
Authors: Hoyer Elisabeth A. , Joseph Marritta , Kaplan Sheldon L. , Vallejo Jesus G. , McNeil Jonathon Chase 
Published: February 2023

Background:
Acute hematogenous osteomyelitis (AHO) is a serious infection in children. Pediatric Infectious Diseases Society guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA) therapy in regions where MRSA accounts for more than 10–20% of all staphylococcal osteomyelitis. We sought to examine factors present at the time of admission which may predict etiology and guide empiric treatment for pediatric AHO in a region with endemic MRSA.

Methods:
We reviewed admissions with International Classification of Diseases 9/10 codes for AHO from 2011 to 2020 in otherwise healthy children. Medical records were reviewed for clinical and laboratory parameters present on the day of admission. Logistic regression was used to determine clinical variables independently associated with (1) MRSA infection and (2) non-Staphylococcus aureus infection.

Results:
A total of 545 cases were included. An organism was identified in 77.1% of cases and S. aureus was the most common (66.2%); 18.9% of all AHO cases were MRSA. Organisms besides S. aureus were identified in 10.8% of cases. CRP >7 mg/dL, subperiosteal abscess, history of any prior skin or soft tissue infection (SSTI) and need for intensive care unit admission were independently associated with MRSA infection. Vancomycin was used as an empiric treatment in 57.6% of cases. If the above criteria were relied upon to predict MRSA AHO, empiric vancomycin use could have been reduced by 25%.

Conclusions:
Critical illness, CRP >7 mg/dL at the time of presentation, subperiosteal abscess and history of SSTI are suggestive of MRSA AHO, and could be considered when planning empiric therapy. Further work is needed to validate these findings before wider implementation.