bluuebunny/crossref_metadata_2025 huggingface dataset:
Paediatric Surgery
Authors: Davenport Mark , De Coppi Paolo
Published: February 2023

This book offers a contemporary overview of the subject in general, as well as detailed information about core subjects. Structured to assist problem-solving and diagnosis, the handbook contains detailed clinical features on all aspects of neonatal and general paediatric surgical conditions and is a patient guide for GPs, paediatricians, and general and specialist paediatric surgeons. The contents have been designed to align with the MRCS and FRCS (Paediatrics) postgraduate exams, and the European Union of Medical Specialists (UEMS) European exam in paediatric surgery. With a focus on knowledge needed in clinical practice, the book also provides supporting background, and science is included to strengthen understanding.
First Report of Peripheral Nerves in Post-Cranial Elements ofCacopsWilliston, 1910, (Temnospondyli: Dissorophidae) from the Lower Permian Richards Spur, Oklahoma
Authors: Armitage Mark H
Published: February 2023

Permian bone beds that extend across several states in the US have been known for over 200 years. Those beds have yielded the richest assemblage of the world’s oldest amphibian tetrapod bones in the world. Cacops sp., a well-known amphibian tetrapod from these deposits, has been widely studied, however, no bone histology or bone decalcification has been conducted on these important animals. We report here on the results of decalcification of post-cranial limb elements of Cacops sp., donated by the Sam Nobel Oklahoma Museum of Natural History. Our results include the presence of nerve fibers that display the diagnostic crosshatch pattern known to enclose nerve fascicles and axons, and lipid droplets that exude under cover slip pressure.
A Beginner’s Guide to Dye Selection and Labeling Strategies for Single-Molecule Localization Microscopy
Authors: Gagnon Lauren
Published: February 2023

Single-molecule localization microscopy (SMLM) is an optical super-resolution technique that circumvents the diffraction limit of light by localizing the center point of each fluorophore’s recorded point spread function. SMLM requires the use of labeling strategies and specialized fluorophores and/or buffer conditions that enable most of the fluorophores in the sample to be “turned off” during the experiment so that a sparse subset of the fluorophores in the sample can be isolated from their nearest “on” neighbors and localized to build up an image of interest. Due to the nature of super-resolution single-molecule imaging, careful sample preparation, imaging buffer preparation, and optimized imaging conditions are fundamental requirements for obtaining quality data. This article discusses key factors to consider when preparing samples and acquiring data for SMLM to serve as a starting point for sample preparation and acquisition optimization.
Use of Fish Skin Graft in Management of Combat Injuries Following Military Drone Assaults in Field-Like Hospital Conditions
Authors: Reda Fouad , Kjartansson Hilmar , Jeffery Steven L A
Published: February 2023

Introduction

The 2020 Nagorno-Karabakh war was an armed conflict between Azerbaijan and Armenia over an ethnically and historically significant region. This manuscript is a report on the forward deployment of acellular fish skin graft (FSG) from Kerecis™, a biologic, acellular matrix derived from the skin of wild-caught Atlantic cod that contains intact epidermis and dermis layers. The usual intention of treatment under adverse circumstances is to temporize wounds until better treatment can be attained, although ideally, rapid coverage and treatment are necessary to prevent long-term complications and loss of life and limb. An austere environment, such as the one experienced during the conflict described here, presents considerable logistical barriers for the treatment of wounded soldiers.

Materials and Methods

Dr H. Kjartansson from Iceland and Dr S. Jeffery from the United Kingdom traveled to Yerevan, near the heart of the conflict, to deliver and train on using FSG in wound management. The primary goal was to use FSG in patients where stabilization and improvement in the wound bed were needed before skin grafting. Other goals were to improve healing time, achieve earlier skin grafting, and have better cosmetic outcomes upon healing.

Results

Over the course of two trips, several patients were managed with fish skin. Injuries included large-area full-thickness burn and blast injuries. Management with FSG induced wound granulation several days sooner in all cases, and even weeks in some instances, allowing a stepdown in the reconstruction ladder with earlier skin grafting procedures and a reduction in requirement of flap surgery.

Conclusions

This manuscript describes a successful first instance of forward deployment of FSGs to an austere environment. FSG, in this military context, has shown great portability, with easy transfer of knowledge. More importantly, management with fish skin has shown faster granulation rates in burn wounds for skin grafting, resulting in improved patient outcomes with no documented infections.
AGN candidates in the VVV near-IR galaxy catalogue
Authors: Baravalle Laura D , Schmidt Eduardo O , Alonso M Victoria , Pichel Ana , Minniti Dante , Rodríguez-Kamenetzky Adriana R , Masetti Nicola , Villalon Carolina , Smith Leigh C , Lucas Philip W
Published: February 2023

The goal of this work is to search for Active Galactic Nuclei (AGN) in the Galactic disc at very low latitudes with |b| < 2°. For this, we studied the five sources from the VVV near-infrared (IR) galaxy catalogue that have also WISE counterparts and present variability in the VIrac VAriable Classification Ensemble (VIVACE) catalogue. In the near-IR colour–colour diagrams, these objects have in general redder colours compared to the rest of the sources in the field. In the mid-IR ones, they are located in the AGN region, however, there is a source that presents the highest interstellar extinction and different mid-IR colours to be a young stellar object (YSO). We also studied the source variability using two different statistical methods. The fractional variability amplitude σrms ranges from 12.6 to 33.8, being in concordance with previous results found for type-1 AGNs. The slopes of the light curves are in the range (2.6 − 4.7) × 10−4 mag d–1, also in agreement with results reported on quasars variability. The combination of all these results suggest that four galaxies are type-1 AGN candidates, whereas the fifth source likely a YSO candidate.
p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-κB signaling pathway
Authors: Zhu Xinxing , Huang Beijia , Zhao Fengting , Lian Jie , He Lixiang , Zhang Yangxia , Ji Longkai , Zhang Jinghang , Yan Xin , Zeng Taoling , Ma Chunya , Liang Yinming , Zhang Chen , Lin Juntang
Published: February 2023

NF-κB activates the primary inflammatory response pathway responsible for methicillin-resistant Staphylococcus aureus (MRSA)-induced lung inflammation and injury. Here, we report that the Forkhead box transcription factor FOXN3 ameliorates MRSA-induced pulmonary inflammatory injury by inactivating NF-κB signaling. FOXN3 competes with IκBα for binding to heterogeneous ribonucleoprotein-U (hnRNPU), thereby blocking β-TrCP-mediated IκBα degradation and leading to NF-κB inactivation. FOXN3 is directly phosphorylated by p38 at S83 and S85 residues, which induces its dissociation from hnRNPU, thus promoting NF-κB activation. After dissociation, the phosphorylated FOXN3 becomes unstable and undergoes proteasomal degradation. Additionally, hnRNPU is essential for p38-mediated FOXN3 phosphorylation and subsequent phosphorylation-dependent degradation. Functionally, genetic ablation of FOXN3 phosphorylation results in strong resistance to MRSA-induced pulmonary inflammatory injury. Importantly, FOXN3 phosphorylation is clinically positively correlated with pulmonary inflammatory disorders. This study uncovers a previously unknown regulatory mechanism underpinning the indispensable role of FOXN3 phosphorylation in the inflammatory response to pulmonary infection.
Cellular responses to long-term phosphate starvation of fission yeast: Maf1 determines fate choice between quiescence and death associated with aberrant tRNA biogenesis
Authors: Garg Angad , Sanchez Ana M , Miele Matthew , Schwer Beate , Shuman Stewart
Published: February 2023

Inorganic phosphate is an essential nutrient acquired by cells from their environment. Here, we characterize the adaptative responses of fission yeast to chronic phosphate starvation, during which cells enter a state of quiescence, initially fully reversible upon replenishing phosphate after 2 days but resulting in gradual loss of viability during 4 weeks of starvation. Time-resolved analyses of changes in mRNA levels revealed a coherent transcriptional program in which phosphate dynamics and autophagy were upregulated, while the machineries for rRNA synthesis and ribosome assembly, and for tRNA synthesis and maturation, were downregulated in tandem with global repression of genes encoding ribosomal proteins and translation factors. Consistent with the transcriptome changes, proteome analysis highlighted global depletion of 102 ribosomal proteins. Concomitant with this ribosomal protein deficit, 28S and 18S rRNAs became vulnerable to site-specific cleavages that generated temporally stable rRNA fragments. The finding that Maf1, a repressor of RNA polymerase III transcription, was upregulated during phosphate starvation prompted a hypothesis that its activity might prolong lifespan of the quiescent cells by limiting production of tRNAs. Indeed, we found that deletion of maf1 results in precocious death of phosphate-starved cells via a distinctive starvation-induced pathway associated with tRNA overproduction and dysfunctional tRNA biogenesis.
HDGFRP3 interaction with 53BP1 promotes DNA double-strand break repair
Authors: Zhang Zhen , Samsa William E , De Yanyan , Zhang Fan , Reizes Ofer , Almasan Alexandru , Gong Zihua
Published: February 2023

The 53BP1-dependent end-joining pathway plays a critical role in double-strand break (DSB) repair. However, the regulators of 53BP1 in chromatin remain incompletely characterized. In this study, we identified HDGFRP3 (hepatoma-derived growth factor related protein 3) as a 53BP1-interacting protein. The HDGFRP3–53BP1 interaction is mediated by the PWWP domain of HDGFRP3 and the Tudor domain of 53BP1. Importantly, we observed that the HDGFRP3–53BP1 complex co-localizes with 53BP1 or γH2AX at sites of DSB and participates in the response to DNA damage repair. Loss of HDGFRP3 impairs classical non-homologous end-joining repair (NHEJ), curtails the accumulation of 53BP1 at DSB sites, and enhances DNA end-resection. Moreover, the HDGFRP3–53BP1 interaction is required for cNHEJ repair, 53BP1 recruitment at DSB sites, and inhibition of DNA end resection. In addition, loss of HDGFRP3 renders BRCA1-deficient cells resistant to PARP inhibitors by facilitating end-resection in BRCA1 deficient cells. We also found that the interaction of HDGFRP3 with methylated H4K20 was dramatically decreased; in contrast, the 53BP1-methylated H4K20 interaction was increased after ionizing radiation, which is likely regulated by protein phosphorylation and dephosphorylation. Taken together, our data reveal a dynamic 53BP1-methylated H4K20–HDGFRP3 complex that regulates 53BP1 recruitment at DSB sites, providing new insights into our understanding of the regulation of 53BP1-mediated DNA repair pathway.
Structure of theCaenorhabditis elegansm6A methyltransferase METT10 that regulates SAM homeostasis
Authors: Ju Jue , Aoyama Tomohiko , Yashiro Yuka , Yamashita Seisuke , Kuroyanagi Hidehito , Tomita Kozo
Published: February 2023

In Caenorhabditis elegans, the N6-methyladenosine (m6A) modification by METT10, at the 3'-splice sites in S-adenosyl-l-methionine (SAM) synthetase (sams) precursor mRNA (pre-mRNA), inhibits sams pre-mRNA splicing, promotes alternative splicing coupled with nonsense-mediated decay of the pre-mRNAs, and thereby maintains the cellular SAM level. Here, we present structural and functional analyses of C. elegans METT10. The structure of the N-terminal methyltransferase domain of METT10 is homologous to that of human METTL16, which installs the m6A modification in the 3'-UTR hairpins of methionine adenosyltransferase (MAT2A) pre-mRNA and regulates the MAT2A pre-mRNA splicing/stability and SAM homeostasis. Our biochemical analysis suggested that C. elegans METT10 recognizes the specific structural features of RNA surrounding the 3'-splice sites of sams pre-mRNAs, and shares a similar substrate RNA recognition mechanism with human METTL16. C. elegans METT10 also possesses a previously unrecognized functional C-terminal RNA-binding domain, kinase associated 1 (KA-1), which corresponds to the vertebrate-conserved region (VCR) of human METTL16. As in human METTL16, the KA-1 domain of C. elegans METT10 facilitates the m6A modification of the 3'-splice sites of sams pre-mRNAs. These results suggest the well-conserved mechanisms for the m6A modification of substrate RNAs between Homo sapiens and C. elegans, despite their different regulation mechanisms for SAM homeostasis.
Acceptability, Feasibility, and Validity of Detecting Respiratory Pathogens During Acute Respiratory Illness in Participant-Collected Swabs in a Low-Income, Community Sample
Authors: Thind Priyam , Vargas Celibell Y , Reed Carrie , Wang Liqun , Alba Luis R , Larson Elaine L , Saiman Lisa , Stockwell Melissa S
Published: February 2023

Background

Community surveillance for acute respiratory illness (ARI) can include unsupervised participant-collected nasal swabs. Little is known about use of self-swabs in low-income populations or among households including extended family members and the validity of self-collected swabs. We assessed the acceptability, feasibility, and validity of unsupervised participant-collected nasal swabs in a low-income, community sample.

Methods

This was a substudy of a larger prospective community-based ARI surveillance study in 405 households in New York City. Participating household members self-collected swabs on the day of a research home visit for an index case, and for 3–6 subsequent days. Demographics associated with agreement to participate and swab collection were assessed, and index case self-collected versus research staff–collected swab results were compared.

Results

Most households (n = 292 [89.6%]) agreed to participate, including 1310 members. Being <18 years old, female, and the household reporter or member of the nuclear family (parents and children) were associated with both agreement to participate and self-swab collection. Being born in the United States or immigrating ≥10 years ago was associated with participation, and being Spanish-speaking and having less than a high school education were associated with swab collection. In all, 84.4% collected at least 1 self-swabbed specimen; self-swabbing rates were highest during the first 4 collection days. Concordance between research staff–collected swabs and self-swabs was 88.4% for negative swabs, 75.0% for influenza, and 69.4% for noninfluenza pathogens.

Conclusions

Self-swabbing was acceptable, feasible, and valid in this low-income, minoritized population. Some differences in participation and swab collection were identified that could be noted by future researchers and modelers.
Higher-level phylogeny and evolutionary history of nonditrysians (Lepidoptera) inferred from mitochondrial genome sequences
Authors: Liao Cheng-Qing , Yagi Sadahisa , Chen Lu , Chen Qi , Hirowatari Toshiya , Wang Xing , Wang Min , Huang Guo-Hua
Published: February 2023

As one of the largest single-radiation sources of phytophagous insects, the higher level phylogeny of lepidopteran lineages has been debated for decades, especially the early divergences of nonditrysia. Here, we use 74 mitochondrial genomes representing seven nonditrysian superfamilies, including the newly sequenced mitochondrial genomes of eight families and 30 species. Four datasets were constructed and used for a phylogenetic analysis based on maximum likelihood (ML) and Bayesian inference (BI) methods. The results reveal that (1) nonditrysian lineages presented typically nested relationships with the family Micropterigidae as the sister-group to the remaining Lepidoptera, (2) monophyly of major clades in Lepidoptera, including Glossata, Heteroneura, Eulepidoptera and Ditrysia, was strongly supported, and (3) Neopseustoidea formed the sister of the remaining Glossata. Divergence-time analysis estimated that Lepidoptera originated c. 222 Mya during the Middle Triassic and that most superfamilies/families of nonditrysia originated from the Early Cretaceous to the Early Palaeogene, which largely coincided with the radiation of angiosperms. Additionally, three novel gene rearrangements in the gene cluster ‘MIQ’ and ‘TP’ were found in nonditrysian groups. Further mitochondrial genome data will help us to better understand the evolution of early nonditrysian lineages.
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

The 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.

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

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.
Disseminated Neonatal Monkeypox Virus Infection: Case Report in Brazil
Authors: Antonello Vicente Sperb , Cornelio Paula Elexina , Dallé Jessica
Published: February 2023

We present here a case of a newborn presenting with a vesicular rash on the scalp and thorax on day 9 of life. Vesicular fluid polymerase chain reaction testing confirmed the presence of Mpox virus DNA. Similar reports in newborns are rare, and we suggest that Mpox infection should be considered in the differential diagnosis of a neonatal vesicular rash, particularly if there is a history of similar rashes in the family.
An Introduction to the Japanese Immunization Program: Past, Present, and Future Perspectives
Authors: Kamiya Hajime , Kamidani Satoshi , Saitoh Akihiko
Published: February 2023

In Japan, immunization is regulated by the Immunization Law, enacted shortly after World War II ended. It has been subsequently revised in response to social changes; however, after public health conditions improved, adverse events following immunization have received more public attention than the effectiveness of vaccination. This kind of public opinion had a major impact on the immunization program, leading to a so-called “vaccine gap” around a decade ago, that is, the less availability of vaccines for routine vaccination as compared with other countries. However, in recent years, several vaccines have been approved and are being routinely administered with the same schedule as in other countries. National immunization programs are influenced by various factors, such as cultures, customs, habits and ideas. This paper summarizes the status of immunization schedule and practices in Japan, process of policymaking, and possible future issues.
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.
Plasma Cell Vulvitis: A Case Series and Follow-Up Study
Authors: Nguyen Jennifer , Veysey Emma
Published: February 2023

Objectives

Plasma cell vulvitis (PCV) is a rare inflammatory vulvar condition. The aim of this study was to describe the natural history, treatment, impact on quality of life, and factors associated with poorer outcomes for PCV.

Methods

A mixed-methods approach was used combining a retrospective case note review with a cross-sectional telephone questionnaire. All women diagnosed with PCV attending the vulvar disorders clinic at the Royal Women's Hospital between January 2011 and December 2020 were included.

Results

During the 10-year study period, 7,500 women were seen at the vulval disorders clinic, of whom 21 were diagnosed with PCV (0.28%). Of these women, 12 who were followed up for more than 12 months agreed to participate in the study. At a median of 5 years follow-up, there was variability in symptom severity, with more than half of the women still symptomatic with pain, precipitated by friction and dyspareunia, resulting in a moderate to large impact on quality of life. There were 5 women who were asymptomatic. Only 1 woman had a preexisting history of lichen planus and lichen sclerosus. Potent topical corticosteroids were identified as the preferred treatment.

Conclusions

Women with PCV can remain symptomatic for many years with significant impacts on quality of life, which may consequently require long-term support and follow-up.
Vulvar High-Grade Squamous Intraepithelial Lesion and the Risk of Recurrence and Progression to Cancer
Authors: Xavier Joana , Figueiredo Rita , Vieira-Baptista Pedro
Published: February 2023

Objective

This study aimed to analyze which clinical characteristics are associated with recurrence and progression of vulvar high-grade squamous intraepithelial lesion (vHSIL).

Materials and Methods

This was a retrospective cohort study, including all women with vHSIL followed in 1 center between 2009 and 2021. Women with a concomitant diagnosis of invasive vulvar cancer were excluded. Medical records were reviewed for demographic factors, clinical data, treatment type, histopathologic results, and follow-up information.

Results

A total of 30 women were diagnosed with vHSIL. The median follow-up time was 4 years (range = 1–12 years). More than half of the women (56.7% [17/30]) underwent excisional treatment, whereas 26.7% (8/30) underwent combined (excisional plus medical) treatment, and 16.7% (5/30) only had medical treatment (imiquimod). Six women had recurrence of vHSIL (20% [6/30]), with a mean time to recurrence of 4.7 ± 2.88 years. The progression rate to invasive vulvar cancer was 13.3% (4/30), with a mean time to progression of 1.8 ± 0.96 years. Multifocal disease was associated with progression to vulvar cancer (p = .035). We did not identify other variables associated with progression; no differences were found between women with and without recurrences.

Conclusions

Multifocality of the lesions was the only variable associated with progression to vulvar cancer. This reinforces the idea that these lesions are a challenge in both treatment and surveillance, involving a more difficult therapeutic decision with greater associated morbidity.
The epigenetic legacy of ICU feeding and its consequences
Authors: Vanhorebeek Ilse , Van den Berghe Greet
Published: February 2023

Purpose of review

Many critically ill patients face physical, mental or neurocognitive impairments up to years later, the etiology remaining largely unexplained. Aberrant epigenetic changes have been linked to abnormal development and diseases resulting from adverse environmental exposures like major stress or inadequate nutrition. Theoretically, severe stress and artificial nutritional management of critical illness thus could induce epigenetic changes explaining long-term problems. We review supporting evidence.

Recent findings

Epigenetic abnormalities are found in various critical illness types, affecting DNA-methylation, histone-modification and noncoding RNAs. They at least partly arise de novo after ICU-admission. Many affect genes with functions relevant for and several associate with long-term impairments. As such, de novo DNA-methylation changes in critically ill children statistically explained part of their disturbed long-term physical/neurocognitive development. These methylation changes were in part evoked by early-parenteral-nutrition (early-PN) and statistically explained harm by early-PN on long-term neurocognitive development. Finally, long-term epigenetic abnormalities beyond hospital-discharge have been identified, affecting pathways highly relevant for long-term outcomes.

Epigenetic abnormalities induced by critical illness or its nutritional management provide a plausible molecular basis for their adverse effects on long-term outcomes. Identifying treatments to further attenuate these abnormalities opens perspectives to reduce the debilitating legacy of critical illness.