bluuebunny/crossref_metadata_2025 huggingface dataset:
CHD4 acts as a critical regulator in the survival of spermatogonial stem cells in mice
Authors: Li Pengyu , Tang Jielin , Yu Zhixin , Jin Cheng , Wang Zhipeng , Li Mengzhen , Zou Dingfeng , Mang Xinyu , Liu Jun , Lu Yan , Miao Shiying , Wang Linfang , Li Kai , Song Wei
Published: August 2022

Spermatogenesis is sustained by homeostatic balance between the self-renewal and differentiation of spermatogonial stem cells, which is dependent on the strict regulation of transcription factor and chromatin modulator gene expression. Chromodomain helicase DNA-binding protein 4 is highly expressed in spermatogonial stem cells but roles in mouse spermatogenesis are not fully understood. Here, we report that the germ-cell-specific deletion of chromodomain helicase DNA-binding protein 4 resulted in complete infertility in male mice, with rapid loss of spermatogonial stem cells and excessive germ cell apoptosis. Chromodomain helicase DNA-binding protein 4-knockdown in cultured spermatogonial stem cells also promoted the expression of apoptosis-related genes and thereby activated the tumor necrosis factor signaling pathway. Mechanistically, chromodomain helicase DNA-binding protein 4 occupies the genomic regulatory region of key apoptosis-related genes, including Jun and Nfkb1. Together, our findings reveal the determinant role of chromodomain helicase DNA-binding protein 4 in spermatogonial stem cells survival in vivo, which will offer insight into the pathogenesis of male sterility and potential novel therapeutic targets.
Effectiveness of melatonin adjuvant treatment in cisplatin to prevent depletion of ovarian follicles in mice: systematic review
Authors: Rodrigues Tairini Damiani , Lima Kellen R , Uggioni Maria Laura R , Ferraz Sarah Dagostin , Cardoso Hemmylly Silveira , Colonetti Tamy , da Rosa Maria Inês
Published: August 2022

Introduction: Cisplatin-based chemotherapy is the standard cancer therapy; however, this treatment causes depletion of ovarian follicles in women of reproductive age. Adjuvant treatment with melatonin can protect the ovaries from oxidative stress, reducing the side effects of chemotherapy. The objective was to evaluate the effects of the use of melatonin on the ovarian follicles of mice treated with cisplatin. Methodology: A systematic review was performed. The search strategy used the terms: “cisplatin”, “melatonin,” and “ovarian”. MEDLINE EMBASE, Cochrane Library, and gray literature (Google Scholar) were used as databases. The search was limited to experimental studies, performed on animals, with no language restrictions. Results: The search identified 30 studies and 5 primary studies, published between 2016 and 2021, and met the inclusion criteria, with a total of 115 mice. For the p-FOX3a/FOXO3a pathway, the meta-analysis showed a standard mean difference (SMD) of −4.79 (95% CI −6.16 to −3.42; P < 0.00001, two studies, 38 mice; I2 = 0%). For the p-PTEN pathway, the meta-analysis showed an SMD of −1.65 (95% CI −2.71 to −0.59; P = 0.002, two studies, 38 mice; I2 = 47%). Conclusion: Melatonin variation in efficacy varies according to the dose used in mice previously exposed to cisplatin. However, melatonin was able to alter the p-PTEN and p-FOX3a/FOXO3a pathways.
The long Filamin-A isoform is required for intestinal development and motility: implications for chronic intestinal pseudo-obstruction
Authors: Zada Almira , Zhao Yuying , Halim Danny , Windster Jonathan , van der Linde Herma C , Glodener Jackleen , Overkleeft Sander , de Graaf Bianca M , Verdijk Robert M , Brooks Alice S , Shepherd Iain , Gao Ya , Burns Alan J , Hofstra Robert M W , Alves Maria M
Published: August 2022

Filamin A (FLNA) is a cytoplasmic actin binding protein, recently shown to be expressed as a long and short isoform. Mutations in FLNA are associated with a wide spectrum of disorders, including an X-linked form of chronic intestinal pseudo-obstruction (CIPO). However, the role of FLNA in intestinal development and function is largely unknown. In this study, we show that FLNA is expressed in the muscle layer of the small intestine from early human fetal stages. Expression of FLNA variants associated with CIPO, blocked expression of the long flna isoform and led to an overall reduction of RNA and protein levels. As a consequence, contractility of human intestinal smooth muscle cells was affected. Lastly, our transgenic zebrafish line showed that the flna long isoform is required for intestinal elongation and peristalsis. Histological analysis revealed structural and architectural changes in the intestinal smooth muscle of homozygous fish, likely triggered by the abnormal expression of intestinal smooth muscle markers. No defect in the localization or numbers of enteric neurons was observed. Taken together, our study demonstrates that the long FLNA isoform contributes to intestinal development and function. Since loss of the long FLNA isoform does not seem to affect the enteric nervous system, it likely results in a myopathic form of CIPO, bringing new insights to disease pathogenesis.
Expansion and mechanistic insights into de novo DEAF1 variants in DEAF1-associated neurodevelopmental disorders
Authors: McGee Stacey R , Rajamanickam Shivakumar , Adhikari Sandeep , Falayi Oluwatosin C , Wilson Theresa A , Shayota Brian J , Cooley Coleman Jessica A , Skinner Cindy , Caylor Raymond C , Stevenson Roger E , Quaio Caio Robledo D' Angioli Costa , Wilke Berenice Cunha , Bain Jennifer M , Anyane-Yeboa Kwame , Brown Kaitlyn , Greally John M , Bijlsma Emilia K , Ruivenkamp Claudia A L , Politi Keren , Arbogast Lydia A , Collard Michael W , Huggenvik Jodi I , Elsea Sarah H , Jensik Philip J
Published: August 2022

De novo deleterious and heritable biallelic mutations in the DNA binding domain (DBD) of the transcription factor deformed epidermal autoregulatory factor 1 (DEAF1) result in a phenotypic spectrum of disorders termed DEAF1-associated neurodevelopmental disorders (DAND). RNA-sequencing using hippocampal RNA from mice with conditional deletion of Deaf1 in the central nervous system indicate that loss of Deaf1 activity results in the altered expression of genes involved in neuronal function, dendritic spine maintenance, development, and activity, with reduced dendritic spines in hippocampal regions. Since DEAF1 is not a dosage-sensitive gene, we assessed the dominant negative activity of previously identified de novo variants and a heritable recessive DEAF1 variant on selected DEAF1-regulated genes in 2 different cell models. While no altered gene expression was observed in cells over-expressing the recessive heritable variant, the gene expression profiles of cells over-expressing de novo variants resulted in similar gene expression changes as observed in CRISPR-Cas9-mediated DEAF1-deleted cells. Altered expression of DEAF1-regulated genes was rescued by exogenous expression of WT-DEAF1 but not by de novo variants in cells lacking endogenous DEAF1. De novo heterozygous variants within the DBD of DEAF1 were identified in 10 individuals with a phenotypic spectrum including autism spectrum disorder, developmental delays, sleep disturbance, high pain tolerance, and mild dysmorphic features. Functional assays demonstrate these variants alter DEAF1 transcriptional activity. Taken together, this study expands the clinical phenotypic spectrum of individuals with DAND, furthers our understanding of potential roles of DEAF1 on neuronal function, and demonstrates dominant negative activity of identified de novo variants.
What establishment expresses
Authors: Ahmed Farrah
Published: August 2022

Religious establishment is said to be wrong partly because of what it expresses. But the typical arguments about what establishment expresses are obscure and ambiguous. This article aims to provide a framework, illustrated by two hypothetical states, to better isolate and understand expressive reasons why establishment might be wrong. The article argues for the disambiguation of expressive claims about establishment, distinguishes between four types of expression, and suggests tests for expression of each type. It illustrates how expressive claims might be contextually assessed using the suggested tests. The article aims to allow lawyers, judges, policymakers, scholars, and members of the public to better understand, assess, and appreciate the moral significance of expressive claims about establishment and, potentially, expressive claims about law and government action more generally.
Using allele scores to identify confounding by reverse causation: studies of alcohol consumption as an exemplar
Authors: Sallis Hannah M , Palmer Tom , Tilling Kate , Davey Smith George , Munafò Marcus R
Published: August 2022

Background

Mendelian randomization (MR) is a form of instrumental variable analysis used to investigate causality using observational data. Another important, although less frequently applied, use of this technique is to investigate confounding due to reverse causality.

Methods

We used a form of reverse MR and data from UK Biobank in a proof-of-principle study to investigate confounding due to reverse causation. Here we focus on the association between alcohol consumption (exposure) and outcomes including educational attainment, and physical and mental health. First, we examined the observational relationship between alcohol consumption and these outcomes. Allele scores were then derived for educational attainment, and physical and mental health, and the association with alcohol consumption (as the outcome) was explored. Sample sizes ranged from 114 941–336 473 in observational analyses and 142 093–336 818 in genetic analyses.

Results

Conventional observational analyses indicated associations between alcohol consumption and a number of outcomes (e.g. neuroticism, body mass index, educational attainment). Analyses using allele scores suggested evidence of reverse causation for several of these relationships (in particular physical health and educational attainment).

Conclusion

Allele scores allow us to investigate reverse causation in observational studies. Our findings suggest that observed associations implying beneficial effects of alcohol consumption may be due to confounding by reverse causation in many cases.
A new genus and species of shrew-like mouse (Rodentia: Muridae) from a new center of endemism in eastern Mindanao, Philippines
Authors: Rowsey Dakota M , Duya Mariano Roy M , Ibañez Jayson C , Jansa Sharon A , Rickart Eric A , Heaney Lawrence R
Published: August 2022

The Philippine archipelago hosts an exceptional diversity of murid rodents that have diversified following several independent colonization events. Here, we report the discovery of a new species of rodent from Mt. Kampalili on eastern Mindanao Island. Molecular and craniodental analyses reveal this species as a member of a Philippine “New Endemic” clade consisting of Tarsomys, Limnomys, and Rattus everetti (tribe Rattini). This new species of “shrew-mouse” is easily distinguished from its relatives in both craniodental and external characteristics including a long, narrow snout; small eyes and ears; short, dark, dense fur dorsally and ventrally; stout body with a tapering, visibly haired tail shorter than head and body length; stout forepaws; bulbous and nearly smooth braincase; narrow, tapering rostrum; short incisive foramina; slender mandible; and narrow, slightly opisthodont incisors. This new genus and species of murid rodent illustrates that murids of the tribe Rattini have exhibited greater species and morphological diversification within the Philippines than previously known and provides evidence that Mt. Kampalili represents a previously unrecognized center of mammalian endemism on Mindanao Island that is deserving of conservation action.
Heterozygous BRCA1 and BRCA2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents With Cancer
Authors: Kratz Christian P , Smirnov Dmitrii , Autry Robert , Jäger Natalie , Waszak Sebastian M , Großhennig Anika , Berutti Riccardo , Wendorff Mareike , Hainaut Pierre , Pfister Stefan M , Prokisch Holger , Ripperger Tim , Malkin David
Published: August 2022

Background

Genetic predisposition is has been identified as a cause of cancer, yet little is known about the role of adult cancer predisposition syndromes in childhood cancer. We examined the extent to which heterozygous pathogenic germline variants in BRCA1, BRCA2, PALB2, ATM, CHEK2, MSH2, MSH6, MLH1, and PMS2 contribute to cancer risk in children and adolescents.

Methods

We conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer. ClinVar pathogenic or likely pathogenic variants (PVs) in genes of interest were compared with 2 control groups. Results were validated in a cohort of mainly European patients and controls. We employed the Proxy External Controls Association Test to account for different pipelines.

Results

Among 3975 children and adolescents with cancer, statistically significant associations with cancer risk were observed for PVs in BRCA1 and 2 (26 PVs vs 63 PVs among 27 501 controls, odds ratio = 2.78, 95% confidence interval = 1.69 to 4.45; P < .001) and mismatch repair genes (19 PVs vs 14 PVs among 27 501 controls, odds ratio = 7.33, 95% confidence interval = 3.64 to 14.82; P <.001). Associations were seen in brain and other solid tumors but not in hematologic neoplasms. We confirmed similar findings in 1664 pediatric cancer patients primarily of European descent.

Conclusion

These data suggest that heterozygous PVs in BRCA1 and 2 and mismatch repair genes contribute with reduced penetrance to cancer risk in children and adolescents. No changes to predictive genetic testing and surveillance recommendations are required.
The Changing Face of Cancer Surgery During Multiple Waves of COVID-19
Authors: Fu Rui , Kamalraj Pabiththa , Li Qing , Hallet Julie , Gomez David , Sutradhar Rinku , Eskander Antoine
Published: August 2022

COVID-19 has had a detrimental effect on the provision of cancer surgery, but its impact beyond the first 6 months of the pandemic remains unclear. We used data on 799 220 cancer surgeries performed in Ontario, Canada, during 2018-2021 and segmented regression to address this knowledge gap. With the arrival of the first COVID-19 wave (March 2020), mean cancer surgical volume decreased by 57%. Surgical volume then rose by 2.5% weekly and reached prepandemic levels in 8 months. The surgical backlog after the first wave was 47 639 cases. At the beginning of the second COVID-19 wave (January 2021), mean cancer surgical volume dropped by 22%. Afterward, surgical volume did not actively recover (2-sided P = .25), resulting in a cumulative backlog of 66 376 cases as of August 2021. These data urge the strengthening of the surgical system to quickly clear the backlog in anticipation of a tsunami of newly diagnosed cancer patients in need of surgery.
Semi-analytic forecasts for JWST – VI. Simulated light-cones and galaxy clustering predictions
Authors: Yung L Y Aaron , Somerville Rachel S , Ferguson Henry C , Finkelstein Steven L , Gardner Jonathan P , Davé Romeel , Bagley Micaela B , Popping Gergö , Behroozi Peter
Published: August 2022

In anticipation of the new era of high-redshift exploration marked by the commissioning of the James Webb Space Telescope (JWST), we present two sets of galaxy catalogues that are designed to aid the planning and interpretation of observing programs. We provide a set of 40 wide-field light-cones with footprints spanning approximately ∼1000 arcmin2 containing galaxies up to z = 10, and a new set of eight ultradeep light-cones with 132 arcmin2 footprints, containing galaxies up to z ∼ 12 down to the magnitudes expected to be reached in the deepest JWST surveys. These mock light-cones are extracted from dissipationless N-body simulations and populated with galaxies using the well-established, computationally efficient Santa Cruz semi-analytic model for galaxy formation. We provide a wide range of predicted physical properties, and simulated photometry from Near-Infrared Camera (NIRCam) and many other instruments. We explore the predicted counts and luminosity functions and angular two-point correlation functions for galaxies in these simulated light-cones. We also explore the predicted field-to-field variance using multiple light-cone realizations. We find that these light-cones reproduce the available measurements of observed clustering from 0.2 ≲ z ≲ 7.5 very well. We provide predictions for galaxy clustering at high redshift that may be obtained from future JWST observations. All of the light-cones presented here are made available through a web-based interactive data release portal.
Markov state models elucidate the stability of DNA influenced by the chiral 5S-Tg base
Authors: Wang Shu-dong , Zhang Ru-bo , Eriksson Leif A
Published: August 2022

The static and dynamic structures of DNA duplexes affected by 5S-Tg (Tg, Thymine glycol) epimers were studied using MD simulations and Markov State Models (MSMs) analysis. The results show that the 5S,6S-Tg base caused little perturbation to the helix, and the base-flipping barrier was determined to be 4.4 kcal mol−1 through the use of enhanced sampling meta-eABF calculations, comparable to 5.4 kcal mol−1 of the corresponding thymine flipping. Two conformations with the different hydrogen bond structures between 5S,6R-Tg and A19 were identified in several independent MD trajectories. The 5S,6R-Tg:O6HO6•••N1:A19 hydrogen bond is present in the high-energy conformation displaying a clear helical distortion, and near barrier-free Tg base flipping. The low-energy conformation always maintains Watson–Crick base pairing between 5S,6R-Tg and A19, and 5S-Tg base flipping is accompanied by a small barrier of ca. 2.0 KBT (T = 298 K). The same conformations are observed in the MSMs analysis. Moreover, the transition path and metastable structures of the damaged base flipping are for the first time verified through MSMs analysis. The data clearly show that the epimers have completely different influence on the stability of the DNA duplex, thus implying different enzymatic mechanisms for DNA repair.
Evaluating data integrity in ribosome footprinting datasets through modelled polysome profiles
Authors: Hedayioglu Fabio , Mead Emma J , O'Connor Patrick B F , Skiotys Matas , Sansom Owen J , Mallucci Giovanna R , Willis Anne E , Baranov Pavel V , Smales C Mark , von der Haar Tobias
Published: August 2022

The assessment of transcriptome-wide ribosome binding to mRNAs is useful for studying the dynamic regulation of protein synthesis. Two methods frequently applied in eukaryotic cells that operate at different levels of resolution are polysome profiling, which reveals the distribution of ribosome loads across the transcriptome, and ribosome footprinting (also termed ribosome profiling or Ribo-Seq), which when combined with appropriate data on mRNA expression can reveal ribosome densities on individual transcripts. In this study we develop methods for relating the information content of these two methods to one another, by reconstructing theoretical polysome profiles from ribosome footprinting data. Our results validate both approaches as experimental tools. Although we show that both methods can yield highly consistent data, some published ribosome footprinting datasets give rise to reconstructed polysome profiles with non-physiological features. We trace these aberrant features to inconsistencies in RNA and Ribo-Seq data when compared to datasets yielding physiological polysome profiles, thereby demonstrating that modelled polysomes are useful for assessing global dataset properties such as its quality in a simple, visual approach. Aside from using polysome profile reconstructions on published datasets, we propose that this also provides a useful tool for validating new ribosome footprinting datasets in early stages of analyses.
Perceptions and experiences of the subjective well-being of people with glioblastoma: a longitudinal phenomenological study
Authors: Sutton Katie , Moore Jaqualyn , Armes Jo , Briggs Emma
Published: August 2022

Background

Glioblastoma (GBM) is a devastating form of brain cancer, with a short life expectancy. In addition to this poor prognosis, people with GBM often experience symptoms that may have a profound impact on their subjective well-being (SWB). The aim of this study was to investigate the lived experiences and perceptions of people with GBM regarding their SWB.

Methods

The study adopted a longitudinal, hermeneutical phenomenological approach. Twenty-seven interviews were conducted with 15 patients over a period of two years. Most participants were interviewed twice on a face-to-face basis (during combined chemotherapy and radiotherapy, and again during adjuvant chemotherapy). The hermeneutic circle was used to guide data analysis.

Results

Data analysis identified four key themes that depicted the lived experiences and perceptions of SWB of people with GBM. “Experience of the disease” focuses on the impact of diagnosis, symptoms and side effects. “Daily life” relates to daily activities, family roles, work and social lives. “Coping” includes the importance of normality and goal-setting. “Experiences of care” focuses on the impact of the treatment schedule, experiences of care and impressions of the monitoring of QoL.

Conclusion

SWB is affected by a variety of factors throughout the GBM disease and treatment journey. The findings of this study suggest that healthcare professionals can enhance the SWB of people with GBM by providing personalized care that supports people to set themselves goals for the future and retain a degree of normality wherever possible.
Patient-individual tapering of DMARDs in rheumatoid arthritis patients in a real-world setting
Authors: Birkner Benjamin , Rech Jürgen , Edelmann Edmund , Verheyen Frank , Schett Georg , Stargardt Tom
Published: August 2022

Objective

We aim to provide real-world evidence on the effectiveness of patient-individual tapering of DMARDs for patients with RA in daily clinical practice using medical records and claims data.

Methods

We utilize data obtained through a controlled prospective cohort study in Germany conducted from July 2018 to March 2021. Participants consist of RA patients in sustained remission (>6 months) who were eligible for tapering at enrolment. Patients treated with individual tapering based on shared decision making (n = 200) are compared with patients without any dose reduction (n = 237). The risk of loss of remission and the risk of flare is assessed with risk-adjusted Kaplan–Meier estimators and Cox regressions. We evaluate differences in costs 1 year before and after baseline based on claims data for the subgroup of patients insured at one major sickness fund in Germany (n = 76).

Results

The risk of flare (hazard ratio 0.88, 95% CI 0.59, 1.30) or loss of remission (hazard ratio 1.04, 95% CI 0.73, 1.49) was not statistically different between the individual tapering group and the continuation group. Minor increases of disease activity and decreases of quality of life were observed 12 months after baseline, again with no statistically significant difference. Drug costs decreased by 1017€ in the individual tapering group while they increased by 1151€ in the continuation group (P < 0.01).

Conclusion

Individual tapering of DMARDs does not increase the average risk of experiencing flares or loss of remission. Encouraging rheumatologists and patients to apply tapering in shared decision making may be a feasible approach to allow individualization of treatment in RA.
Predicting Long Pendant Edges in Model Phylogenies, with Applications to Biodiversity and Tree Inference
Authors: Bocharov Sergey , Harris Simon , Kominek Emma , Mooers Arne Ø , Steel Mike
Published: August 2022

In the simplest phylogenetic diversification model (the pure-birth Yule process), lineages split independently at a constant rate $\lambda$ for time $t$. The length of a randomly chosen edge (either interior or pendant) in the resulting tree has an expected value that rapidly converges to $\frac{1}{2\lambda}$ as $t$ grows and thus is essentially independent of $t$. However, the behavior of the length $L$ of the longest pendant edge reveals remarkably different behavior: $L$ converges to $t/2$ as the expected number of leaves grows. Extending this model to allow an extinction rate $\mu$ (where $\mu<\lambda$), we also establish a similar result for birth–death trees, except that $t/2$ is replaced by $t/2 \cdot (1-\mu/\lambda)$. This “complete” tree may contain subtrees that have died out before time $t$; for the “reduced tree” that just involves the leaves present at time $t$ and their direct ancestors, the longest pendant edge length $L$ again converges to $t/2$. Thus, there is likely to be at least one extant species whose associated pendant branch attaches to the tree approximately half-way back in time to the origin of the entire clade. We also briefly consider the length of the shortest edges. Our results are relevant to phylogenetic diversity indices in biodiversity conservation, and to quantifying the length of aligned sequences required to correctly infer a tree. We compare our theoretical results with simulations and with the branch lengths from a recent phylogenetic tree of all mammals. [Birth–death process; phylogenetic diversification models; phylogenetic diversity.]
Flexible intramedullary nails or Spica casting? A meta-analysis on the treatment of femur fractures in preschool children aged 2–5 years
Authors: Duan Lian , Canavese Federico , Li Lianyong
Published: August 2022

The objective of this study is to conduct a meta-analysis (1) to evaluate outcomes of flexible intramedullary nails (FIN) versus Spica casting for treating femur shaft fractures in children aged 2–5 years and (2) to investigate the associated complications. The PubMed, Cochrane Library, Embase and Web of Science databases were searched to identify available studies comparing the outcomes of FIN and Spica casting for the treatment of femoral shaft fracture in preschool children. Meta-analysis was conducted with adherence to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Eight observational studies involving 4995 patients were included. Two were judged to be of moderate quality, with the remainder being high quality. There were 1573 patients treated by FIN and 3422 by Spica casting. Compared to Spica casting, FIN allowed a quicker return to normal activities (40.49 ± 13.43 vs. 46.97 ± 14.32 days; P < 0.001), had a lower incidence of malunion (0.88 vs. 4.19%; P = 0.01) and unplanned interventions (2.87 vs. 7.53%; P < 0.001), but had slightly longer hospital stay (2.01 ± 1.01 vs. 1.10 ± 0.93 days; P = 0.01) and required a second surgery to remove the nails. Compared with Spica casting, FIN has the advantages of faster returning to normal activities and lower incidence of residual deformities and unplanned reoperation, but a slightly longer time of hospitalization and needs a second surgery to remove the hardware. Existing studies on duration of care and financial burden are insufficient, so further studies are warranted on multicenter and high-level evidence studies. Level of evidence: III.
Forearm Compartment Pressure Change in Children Operated for Supracondylar Humerus Fracture
Authors: Toğaç Soner , Eken Gökay , Ermutlu Cenk , Sarisözen Bartu
Published: August 2022

Background:

The aim of this study is to examine the preoperative and postoperative forearm compartment pressures in patients treated operatively for Gartland type III extension type supracondyler humerus fractures and understand the course of these values over postoperative period.

Methods:

Deep volar compartment pressure of 31 patients were measured in the proximal one third of the forearm preoperatively, and measurements were continued every 4 hours for the first 24 hours after the operation with a catheter. Type of the reduction technique (open reduction vs. closed reduction), duration of surgery, the time from the injury to surgery were all evaluated.

Results:

In the measurements made immediately after the operation (0 h), a sudden increase in the compartment pressure was detected in all patients (15.0±5.9 to 27.9±7.5 mm Hg) independent of the reduction technique and gradually decreased over time. The mean compartment pressure at the 12th hour postoperatively was higher in the open reduction group than in the CR group (24.5±3.4, 20.7±6.7 mm Hg, respectively) (P=0.044). The mean preoperative compartment pressure was 17.7±5.8 mm Hg in patients with a time from injury to surgery longer than 12 hours, and 12.4±4.8 mm Hg in patients with 12 hours or less (P=0.006). The postoperative 0-, 12-, and 20-hour pressure values were higher in the >1 hour operation time group than in the ≤1 hour group and the differences were statistically significant (P=0.046, 0.016, and 0.032, respectively).

Conclusions:

In pediatric supracondylar humeral fractures, those who underwent open reduction had higher preoperative and postoperative compartment pressures. The reduction attempt was found to be a factor that increased the compartment pressure and after the operation, the compartment pressure values decrease gradually. Prolonged operative time (>1 h) and increased time from injury to operative fixation (>12 h) were associated with higher compartment pressures.

Level of Evidence:

Level II—prospective study.
Prognostic Potential of Metabolic Activity on 18F-FDG Accumulation in Advanced NSCLC Receiving Combining Chemotherapy Plus PD-1 Blockade
Authors: Hashimoto Kosuke , Kaira Kyoichi , Imai Hisao , Mouri Atsuto , Shiono Ayako , Miura Yu , Yamaguchi Ou , Kobayashi Kunihiko , Kagamu Hiroshi , Kuji Ichiei
Published: August 2022

Combined chemotherapy plus programmed death-1 (PD-1) blockade is an established treatment against patients with advanced non–small cell lung cancer (NSCLC). However, a promising predictor besides programmed death ligand-1 expression remains uncertain. We examined the prognostic significance of baseline 18F-FDG-positron emission tomography for predicting first-line combined chemotherapy plus PD-1 blockade in NSCLC patients. Forty-five patients with advanced NSCLC who received 18F-FDG-positron emission tomography immediately before combined platinum-based chemotherapy with PD-1 blockade as first-line setting were eligible for this study, and assessment of maximum of standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on 18F-FDG uptake was performed. The objective response rate, median progression-free survival, and overall survival were 51.2%, 206 days, and 681 days, respectively. High SUVmax, TLG, and MTV significantly correlated with age and performance status (PS), C-reactive protein (CRP), and PS, CRP, albumin, and baseline tumor size, respectively. Univariate analysis identified albumin, TLG and MTV as significant predictors of progression-free survival, and CRP, albumin, TLG and MTV as significant factors for predicting overall survival. High TLG was confirmed as an independent factor associated with poor prognosis in multivariate analysis. In particular, TLG is identified as the most powerful predictor in patients with good PS, adenocarcinoma, programmed death ligand-1≥1%, and low baseline tumor size. The tumor metabolic volume by MTV and TLG at pretreatment was clarified as a significant predictor for combined chemotherapy with PD-1 blockade, but not maximal glycolytic level by SUVmax.
Correlation of MRI signal characteristics of intracranial melanoma metastases with BRAF mutation status
Authors: Lasocki Arian , McArthur Grant A.
Published: August 2022

BRAF V600 mutations (BRAFmut) are associated with more pigmentation in primary melanomas, but data on melanin content of metastases are limited. This study compares signal characteristics of BRAFmut and BRAF-wildtype (BRAFwt) intracranial melanoma metastases (IMM). MRI brain examinations at first diagnosis of IMM were identified, all performed at 3-Tesla including 1 mm volumetric pre- and postcontrast T1-weighted imaging and susceptibility-weighted imaging (SWI). Individual metastases were assessed by a neuroradiologist, stratified by size (≥10 mm, ‘larger’, vs. 2–9 mm, ‘small’; up to 10 per group); presence of intrinsic T1-hyperintensity (T1H) and, if present, whether confidently attributable to melanin as opposed to haemorrhage; evidence of haemorrhage; presence of central necrosis. A total of 267 IMM in 73 patients were assessed (87 larger IMM, 180 small). The proportion of larger IMM was similar in both groups (31% BRAFmut and 36% BRAFwt). In small IMM, MRI evidence of melanin was more common in BRAFmut patients (42% vs. 26%; P = 0.038). Haemorrhage was more common in larger IMM (51%, vs. 20% of small IMM; P < 0.0001), but did not differ based on BRAF status. Central necrosis was more common in larger IMM (44% vs. 7%; P < 0.0001) and in BRAFmut IMM (23% vs. 11%; P = 0.011). In the BRAFmut cohort, central necrosis was more common in patients without previous anti-BRAF therapy (33% vs. 7%; P = 0.0001). T1H attributable to melanin is only slightly more common in BRAFmut IMM than BRAFwt. Higher rates of central necrosis in BRAFmut patients without previous anti-BRAF therapy suggest that anti-BRAF therapy may affect the patterns of IMM growth.
The Challenges of Managing Pain in the Intensive Care Unit
Authors: Leininger Susan
Published: August 2022

Pain management in the intensive care unit can be challenging. It is important to assess and reassess the patient for pain using the appropriate pain assessment tool for the patient's condition. It is critical to use these tools for compliance to best practice recommendations by The Joint Commission, the Society of Critical Care Management, and the American Association of Critical Care Nurses. Critical care nurses need to know the types of pain and how everyday nursing care and procedures affect the patient's pain level. This article reviews the types and characteristics of pain, the best practice guidelines, and shares a pathway for the best management of a patient's pain.
The Evolution of Palliative Medicine in Intensive Care
Authors: Stamper Tara Orgon , Kerr Renee , Sporter Daniela
Published: August 2022

Supportive, or palliative, care has moved into medicine's mainstream with well-known and studied benefits but continues to be inadequately utilized in many health care environments particularly intensive care units (ICUs). With diverse patient populations in the various ICU settings, the supportive care team must adapt and mold their goals-of-care discussions and relationship building based on the ICU culture and individuals involved. Despite the differences in disease processes, early supportive care involvement in the ICU provides much needed emotional support and symptom management to patients and families in addition to identifying the patient's goals of care early in the hospital stay. The purpose of this article is to provide a general overview of the history of supportive care and clarify current misperceptions, particularly related to hospice, surrounding the specialty. The types of supportive care consults will be explained and their uses in the various ICU settings, and illustrate the advantage of early involvement to not only patients and families but the medical team as well.
Real-world Medicare Healthcare Costs of Patients with Dupuytren’s Contracture Treated with Collagenase or Fasciectomy
Authors: Zah Vladimir , Stanicic Filip , Ruby Jane , Vukicevic Djurdja , Hurley David
Published: August 2022

Background:

Our study aimed to compare real-world healthcare resource utilization (HRU) and healthcare cost (HC) of Medicare-insured patients (≥65 years old) with Dupuytren’s contracture (DC) treated with Clostridium histolyticum (collagenase) or fasciectomy.

Methods:

DC patients treated with collagenase or fasciectomy between July 2011 and June 2017 were identified using the IBM MarketScan Medicare Supplemental Database. The index date was the date of the first procedure. Demographic characteristics were captured on the index date, and comorbidities were assessed during the 24-month preindex period. HRU and HC were analyzed throughout the 12-month postindex period. Patients were matched using propensity score weights. Gamma log-linked generalized linear models were used to evaluate HC drivers.

Results:

Out of 37,374 DC patients, 2911 received collagenase, while 6258 underwent fasciectomy. Postmatching, the total average annual HC was similar between collagenase and fasciectomy ($7271 versus $6220, P = 0.357). When HCs were stratified by the service provider, outpatient facility and physician office costs were lower in the collagenase cohort ($850 versus $1284, P = 0.047 and $546 versus $1001, P < 0.001). The costs of professional services were significantly higher than in the fasciectomy cohort due to the cost of collagenase injection ($1682 versus $629, P < 0.001). The HRU was similar between cohorts, except for more frequent outpatient facility visits in fasciectomy patients (12.3 versus 22.9, P < 0.001). Generalized linear model revealed Charlson comorbidity index, plan type, patients’ residence region, sleep disorder, and hyperlipidemia as significant predictors of total HC.

Conclusion:

This study found comparable total annual HC and HRU between collagenase- and fasciectomy-treated Medicare patients.
An Analysis of Racial Diversity in the Breast Reconstruction and Aesthetic Surgery Literature
Authors: Chawla Sahil , Shihadeh Hanaa , Patel Ashit
Published: August 2022

Background:

Racial disparities in the visual representation of patients in the plastic surgery literature can contribute to health inequities. This study evaluates racial diversity in photographs published in the aesthetic and breast reconstruction literature.

Methods:

A photogrammetric analysis of plastic surgery journals from the USA, Canada, and Europe was performed. Color photographs depicting human skin, pertaining to breast reconstruction and aesthetic surgery in 2000, 2010, and 2020, were categorized as White (1–3) or non-White (4–6) based on the Fitzpatrick scale.

Results:

All journals demonstrated significantly more White skin images than non-White for all procedures (P < 0.05) except blepharoplasty and rhinoplasty. Blepharoplasty was the only procedure with more non-White images (P = 0.02). When examining USA journals, significant differences were not found in blepharoplasty, rhinoplasty, and male chest surgery. European journals published a greater proportion of non-White images than USA journals (P < 0.0001). There was a decreasing rate of change in diversity with 15.5% of images being non-White in 2000, 32.7% in 2010, and 40.7% in 2020 (P < 0.01). Percentage of non-White images varied by geographical region and ranged from 3.6% in Oceania to 93.5% in Asia (P < 0.01).

Conclusions:

Diversity of patient populations depicted in plastic surgery literature has increased over the past two decades. Despite this improvement, the racial diversity seen in photographs published in the literature does not adequately reflect this demographic for aesthetic and breast procedures. Equitable visual representation may promote cultural competency and improve care for the populations we serve.
Post-cataract surgery optic neuropathy: a chronological narrative review of the literature and speculation on pathogenesis
Authors: Bhatti M. Tariq , Miller Neil R.
Published: August 2022

Purpose of review

To appraise the literature on the incidence of an acute anterior optic neuropathy resembling spontaneous nonarteritic anterior ischemic optic neuropathy (NAION) following uncomplicated cataract surgery and to explore the proposed pathogenesis of both immediate and delayed onset post-cataract surgery optic neuropathy (PCSON).

Recent findings

A number of case reports, case series, and retrospective case-controlled, big data, and population-based studies have identified an apparent association between cataract surgery and the occurrence of an acute anterior optic neuropathy that can either be immediate or delayed in onset. However, a recent study found no link between modern day cataract surgery and an increased risk of an acute anterior optic neuropathy.

Immediate PCSON appears to be related to negative perfusion pressure at the level of the optic disc due to increased intraocular pressure. The pathogenesis of delayed PCSON is unknown but probably multifactorial. Patients who have experienced spontaneous NAION or PCSON in one eye may be at risk of PCSON in the fellow eye.
Primary Open Angle Glaucoma Prevalence in Europe: A Systematic Review and Meta-Analysis
Authors: Gallo Afflitto Gabriele , Aiello Francesco , Cesareo Massimo , Nucci Carlo
Published: August 2022

Purpose:

This study aimed to evaluate the prevalence of POAG in Europe.

Methods:

Two authors independently conducted a systematic literature search on PubMed/MedLine, Web of Science, and Google Scholar to identify papers analyzing the prevalence of POAG in European countries. After removal of duplicates, title and abstract screening, and full-text analysis, data from selected articles were entered in an Excel spreadsheet. We performed risk of bias assessment using the Joanna Briggs Institute Prevalence Critical Appraisal Tool and conducted a meta-analysis using the R software (version 1.4.1106).

Results:

We retrieved 9348 eligible papers from the initial electronic search and included 10 of them in the qualitative and quantitative analyses. A total of 26,993 patients were included in this meta-analysis (11,927 male and 14,556 female). We identified 755 POAG cases (397 male and 348 female), with a pooled prevalence estimate in Europe of 2.60% (95% confidence interval: 1.90%–3.56%). Increasing odds for POAG were related to increasing age and some geographic differences in the disease distribution in the continent were identified. Statistically significant sex-related differences in the prevalence rate of POAG were not observed in this cohort.

Conclusion:

POAG is a neurodegenerative disease that affects a large proportion of the older European population. In the future, the prevalence of POAG is expected to grow in Europe because of the progressive aging populations of Western countries. Future high-quality epidemiological studies for the evaluation of POAG prevalence rates are warranted.
Novel Bleb Classification Following Ab Interno Implantation of Gel-Stent Using Anterior Segment Optical Coherence Tomography
Authors: Hasan Somar M. , Theilig Theresa , Tarhan Melih , Papadimitriou Menelaos , Unterlauft Jan Darius , Meller Daniel
Published: August 2022

Précis:

A novel qualitative tomographical classification for bleb after implantation of XEN-Gel-Stent using ab interno approach is presented. Association of anatomic patterns to intraocular pressure (IOP) and success rates (SR) illustrates that anterior segment optical coherence tomography can be useful tool in clinical guidance.

Purpose:

To present a novel classification of bleb resulting from ab interno implantation of XEN-Gel-Stent and report association of tomographical patterns with IOP and SR.

Materials and Methods:

A cross-sectional 1-armed study of patients receiving XEN-Gel-Stent. Tomographical changes in the bleb area were studied using swept-source optical coherence tomography in an early (d 29–90 postsurgery) and late (starting from d 91 postsurgery) phase. Frequency of patterns and their association with IOP and SR (defined as IOP<18 mmHg without medications) were studied.

Results:

One hundred eleven examinations of 49 blebs (49 patients) were included. Three tomographical patterns at conjunctival, 4 at tenons capsule, and 2 at episcleral level were characterized. Most frequent conjunctival pattern was subconjunctival spaces (56.3% and 53.2% in the early and late phase, respectively) and associated with lower IOP (13.0±6.0 mmHg) and higher SR (89%) but only in the early phase compared with other conjunctival patterns (P<0.05). At tenons capsule level, the hyporeflective pattern was most frequent (50% and 51.9% in early and late phase) followed by the cavernous pattern. Both patterns associated with lower IOP and higher SR compared with hyper-reflective or loss of tenon changes (P<0.005). Most blebs showed no episcleral lake (87.5% and 89.9% in early and late phase). No difference of IOP and SR was noted compared with those showing an episcleral lake.

Conclusion:

A practical and clinically relevant novel classification system is proposed to tomographically describe and classify blebs after implantation of XEN-Gel-Stent. Certain patterns were associated with lower IOP and higher SR.
The Effect of Latanoprost on Choroidal Vascularity Index in Glaucoma and Ocular Hypertension
Authors: Cakir Ihsan , Pehlivanoglu Seren , Yalcinkaya Gulay , Altan Cigdem
Published: August 2022

Précis:

The choroidal vascularity index (CVI) is a new marker for the choroid. The decrease in CVI following latanoprost use can provide a better understanding of the pathogenesis of the posterior segment side effects of latanoprost such as cystoid macular edema and central serous choroidopathy.

Purpose:

The purpose of this paper is to evaluate the changes in the CVI, total choroidal area (TCA), stromal area (SA), luminal area (LA), and choroidal thickness (CT) following latanoprost therapy in patients with primary open angle glaucoma and ocular hypertension.

Materials and Methods:

Patients with newly diagnosed primary open angle glaucoma or ocular hypertension who had never received antiglaucoma therapy were included. Each patient received latanoprost 0.005% once daily. Enhanced depth imaging mode of spectral-domain optical coherence tomography scans was taken before the start of latanoprost therapy and in the first and third months. Subfoveal CT, CVI, TCA, LA, and SA for the submacular area, and 4 quadrants of the peripapillary area were calculated from the scans.

Results:

A total of 36 eyes of 18 patients were analyzed. Subfoveal CT increased significantly (P=0.007). Mean TCA (P=0.008) and SA (P<0.001) in the first and third months were higher than baseline in the submacular regions. Mean CVI was lower in the first and third months (P<0.001). There was an increase in the mean TCA and SA in the peripapillary temporal (P=0.001 and 0.028) and inferior (P=0.002 and <0.001) quadrants and a decrease in mean CVI in the temporal (P=0.027) and inferior (P=0.003) peripapillary quadrants. A negative correlation was found between the rate of decrease in intraocular pressure and the macular region CVI.

Conclusions:

Following latanoprost use for several months, the CVI was significantly decreased in newly treated patients with glaucoma or ocular hypertension, among other changes to the choroid. These findings may contribute to a better understanding of the effects of prostaglandins on the posterior segment of the eye.