bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review
Authors: Lai Tony , Yeo Chin-Yen , Rockliff Bradley , Stokes Michael , Kim Hannah Yejin , Marais Ben J , McLachlan Andrew J , Alffenaar Jan-Willem C
Published: January 2024

Introduction

Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children.

Objectives

To evaluate the concentration–efficacy relationship, concentration–toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children.

Methods

We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0–18 years. Review articles, case series of <five patients, editorials and animal studies were excluded. Quality assessment was performed using the Critical Appraisal of Clinical Pharmacokinetics tool. The concentration–efficacy and concentration–toxicity relationships and PK/PD variability were analysed.

Results

In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (Cmax/MIC) of 25–50 for optimal efficacy and an AUC24 of >600 mg·h/L for nephrotoxicity. L-amb doses of 2.5–10 mg/kg/day were reported to achieve Cmax/MIC > 25 using an MIC of 1 mg/L.

Conclusions

While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.
Depth sectioning using environmental and atomic-resolution STEM
Authors: Takeguchi Masaki , Hashimoto Ayako , Mitsuishi Kazutaka
Published: January 2024

(Scanning) transmission electron microscopy (TEM) images of samples in gas and liquid media are acquired with an environmental cell (EC) via silicon nitride membranes. The ratio of sample signal against the background is a significant factor for resolution. Depth-sectioning scanning TEM (STEM) is a promising technique that enhances the signal for a sample embedded in a matrix. It can increase the resolution to the atomic level, thereby enabling EC-STEM applications in important areas. This review introduces depth-sectioning STEM and its applications to high-resolution EC-STEM imaging of samples in gases and in liquids.
Microscopy of Woven and Nonwoven Face Covering Materials: Implications for Particle Filtration
Authors: Vicenzi Edward P , Whittaker Scott , Weaver Jamie L , Staymates Matthew E , Radney James G , Zangmeister Christopher D
Published: January 2024

A suite of natural, synthetic, and mixed synthetic-natural woven fabrics, along with nonwoven filtration layers from a surgical mask and an N95 respirator, was examined using visible light microscopy, scanning electron microscopy, and micro-X-ray computed tomography (µXCT) to determine the fiber diameter distribution, fabric thickness, and the volume of solid space of the fabrics. Nonwoven materials exhibit a positively skewed distribution of fiber diameters with a mean value of ≈3 μm, whereas woven fabrics exhibit a normal distribution of diameters with mean values roughly five times larger (>15 μm). The mean thickness of the N95 filtration material is 1093 μm and is greater than that of the woven fabrics that span from 420 to 650 μm. A new procedure for measuring the thickness of flannel fabrics is proposed that accounts for raised fibers. µXCT allowed for a quantitative nondestructive approach to measure fabric porosity as well as the surface area/volume. Cotton flannel showed the largest mean isotropy of any fabric, though fiber order within the weave is poorly represented in the surface electron images. Surface fabric isotropy and surface area/volume ratios are proposed as useful microstructural quantities to consider for future particle filtration modeling efforts of woven materials.
Reduction in Long COVID Symptoms and Symptom Severity in Vaccinated Compared to Unvaccinated Adults
Authors: Maier Hannah E , Kowalski-Dobson Theresa , Eckard Ashley , Gherasim Carmen , Manthei David , Meyers Alyssa , Davis Dawson , Bakker Kevin , Lindsey Kathleen , Chu Zijin , Warsinske Lauren , Arnold Matthew , Buswinka Anna , Stoneman Emily , Valdez Riccardo , Gordon Aubree
Published: January 2024

Background

The impact of vaccination prior to infection on postacute sequelae of coronavirus disease 2019 (COVID-19, PASC), also known as long COVID, remains unclear. Here we assess the protective effect of vaccination on long COVID in a community-based setting.

Methods

The Immunity Associated with SARS-CoV-2 (IASO) study is an ongoing prospective cohort of working adults that began in October 2020. Participants are actively followed for severe acute respiratory syndrome coronavirus 2 infection. We compared the prevalence of symptoms and symptom severity in vaccinated compared to unvaccinated cases. Our primary definition of long COVID was the presence of symptoms at 90 days postinfection; 30 days postinfection was also examined.

Results

Overall, by 90 days postinfection, 13% of cases had long COVID, with 27% of unvaccinated cases and 8% of vaccinated cases reporting long COVID (relative risk [RR], 0.31 [95% confidence interval {CI}, .22–.42]). Vaccination was also associated with significantly lower average severity scores at all timepoints (eg, relative severity at 90 days postinfection: −2.70 [95% CI, −1.68 to −3.73]). In the pre-Omicron era, 28% of unvaccinated cases and 18% of vaccinated cases reported long COVID (P = .07), and vaccinated cases reported less severe symptoms including less difficulty breathing (P = .01; 90-day RR, 0.07).

Conclusions

Vaccinated cases had lower prevalence of long COVID and reduced symptom severity.
Characterization of Unique Eukaryotic Sphingolipids with Temperature-Dependent Δ8-Unsaturation from the Picoalga Ostreococcus tauri
Authors: Ishikawa Toshiki , Domergue Frédéric , Amato Alberto , Corellou Florence
Published: January 2024

Sphingolipids (SLs) are ubiquitous components of eukaryotic cell membranes and are found in some prokaryotic organisms and viruses. They are composed of a sphingoid backbone that may be acylated and glycosylated. Assembly of various sphingoid base, fatty acyl and glycosyl moieties results in highly diverse structures. The functional significance of variations in SL chemical diversity and abundance is still in the early stages of investigation. Among SL modifications, Δ8-desaturation of the sphingoid base occurs only in plants and fungi. In plants, SL Δ8-unsaturation is involved in cold hardiness. Our knowledge of the structure and functions of SLs in microalgae lags far behind that of animals, plants and fungi. Original SL structures have been reported from microalgae. However, functional studies are still missing. Ostreococcus tauri is a minimal microalga at the base of the green lineage and is therefore a key organism for understanding lipid evolution. In the present work, we achieved the detailed characterization of O. tauri SLs and unveiled unique glycosylceramides as sole complex SLs. The head groups are reminiscent of bacterial SLs, as they contain hexuronic acid residues and can be polyglycosylated. Ceramide backbones show a limited variety, and SL modification is restricted to Δ8-unsaturation. The Δ8-SL desaturase from O. tauri only produced E isomers. Expression of both Δ8-SL desaturase and Δ8-unsaturation of sphingolipids varied with temperature, with lower levels at 24°C than at 14°C. Overexpression of the Δ8-SL desaturase dramatically increases the level of Δ8 unsaturation at 24°C and is paralleled by a failure to increase cell size. Our work provides the first characterization of O. tauri SLs and functional evidence for the involvement of SL Δ8-unsaturation for temperature acclimation in microalgae, suggesting that this function is an ancestral feature in the green lineage.
Hypoxia-Inducible Factor-1α (HIF-1α) as a Factor to Predict the Prognosis of Spinal Chordoma
Authors: He Guanping , Liu Xiaoguang
Published: January 2024

Study Design.

Retrospective study.

Objective.

In this study, the authors explore the potential relationship between hypoxia inducible factor-1α (HIF-1α) and the prognosis of patients with spinal chordoma.

Summary of Background Data.

Currently, prognostic factors related to the clinical course in the setting of spinal chordoma are poorly understood. Although the close relationship between HIF-1α and tumor angiogenesis, metastasis, and recurrence have been widely reported, it has not been investigated in the context of spinal chordoma.

Materials and Methods.

In this study, 32 samples of chordoma patients were compared with 14 nucleus pulposus tissues as controls. The specific expression of HIF-1α was detected by immunohistochemistry. Continuous disease-free survival (CDFS) was defined as the interval from tumor resection to confirmation of the first local recurrence or distant metastasis. Overall survival (OS) was defined as the interval from the date of surgery to death related to any cause. The relationship between HIF-1α expression and the clinicopathologic characteristics of patients with chordoma was analyzed using the Pearson χ2test. Multivariate Cox analysis was used to evaluate whether HIF-1α expression was associated with the prognosis of patients after controlling for confounders.

Results.

HIF-1α was mainly expressed in the cytoplasm or nucleus in all of the chordoma samples, which showed significantly higher than that in the normal nucleus pulposus tissue (P=0.004). Multivariate Cox regression analyses showed that high HIF-1α expression and location of HIF-1α expression were significantly associated with poor CDFS (hazard ratio (HR)=3.374;P=0.021) and OS (HR=4.511;P=0.012). In addition, we further found that high HIF-1α expression both in the cytoplasm and nucleus indicated a stronger prognostic factor for poor CDFS (HR=3.885;P=0.011) and OS (HR=4.014;P=0.011) in spinal chordoma patients.

Conclusion:

High HIF-1α expression may become a potential new biological indicator to predict a poor prognosis in patients with spinal chordoma. HIF-1α may also represent a novel therapeutic target for the treatment of spinal chordoma.
Diagnostic and prognostic risk factors analysis for distant metastasis in melanoma: a population-based study
Authors: Sun Junwei , Wang Mingyu , Kan Zhisheng
Published: January 2024

Background

We aimed to develop tools that could predict the occurrence of distant metastases in melanoma and its prognosis based on clinical and pathological characteristics.

Materials and methods

We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database of melanoma patients diagnosed between 2010 and 2019. Logistic analyses were performed to identify independent risk factors associated with distant metastasis. Additionally, multivariate Cox analyses were conducted to determine independent prognostic factors for patients with distant metastasis. Two nomograms were established and evaluated with the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Furthermore, we performed a retrospective analysis of melanoma with distant metastasis from our institute between March 2018 and June 2022.

Results

Of the total 19 396 melanoma patients, 352 (1.8%) had distant metastases at the time of diagnosis. The following clinical and pathological characteristics were identified as independent risk factors for distant metastasis in melanoma: N stage, tumor size, ulceration, mitosis, primary tumor site, and pathological subtype. Furthermore, tumor size, pathological subtype, and radiotherapy were identified as independent prognostic factors. The results of the training and validation cohorts’ ROC curves, calibration, DCA, and Kaplan–Meier survival curves demonstrate the effectiveness of the two nomograms. The retrospective study results from our center supported the results from the SEER database.

Conclusion

The clinical and pathological characteristics of melanoma can predict a patient’s risk of metastasis and prognosis, and the two nomograms are expected to be effective tools to guide therapy decisions.
Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer
Authors: Zhu Lingling , Yu Xianzhe , Tang Xiaojun , Hu Chenggong , Wu Lei , Liu Yanyang , Zhou Qinghua
Published: January 2024

Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.
Feasibility, Tolerability, and Effectiveness of Transbronchial Interventions in Elderly Patients With Malignant Central Airway Obstruction
Authors: Kashiwabara Kosuke , Fujii Shinji , Tsumura Shinsuke , Tokunaga Ryuki
Published: January 2024

Background:

In elderly patients with malignant central airway obstruction (MCAO), the treating physicians often hesitate to undertake transbronchial interventions (TBIs) as a palliative procedure in view of the advanced age of the patients.

Methods:

We conducted this retrospective study to evaluate the differences in the feasibility, tolerability, and effectiveness of TBIs between elderly (aged 75 years old or above; elderly group; n=27) and nonelderly (aged below 75 years old; nonelderly group; n=50) patients with MCAO. The primary endpoint was the incidence of complications during (within 24 hours) and after (>24 hours) TBIs.

Results:

The mean age of the patients was 81 years in the elderly group and 61 years in the nonelderly group. The complications encountered during/after TBI included endobronchial bleeding or hypoxemia requiring intubation occurring during the TBIs, and bacterial pneumonia, airway reocclusion, and stent migration occurring after the TBIs, although there was no difference in the frequency of complications during/after the TBIs between the elderly group and nonelderly group (26% vs. 30%, P=0.706). There was no difference in the percentage of patients in whom successful airway recanalization was achieved by TBI (93% vs. 80%, P=0.197), the percentage of patients who showed symptomatic improvement after the TBIs (67% vs. 76%, P=0.380) and the OS after the TBIs (6.1 vs. 7.3 months, P=0.704) between the 2 groups.

Conclusions:

TBIs can be undertaken without hesitation as a palliative procedure in elderly patients with MCAO.
Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition
Authors: Bao Haili , Wang Haibin
Published: January 2024

This review aimed to summarize the major progress in maternal-fetal medicine achieved by Chinese scientists in recent years. PubMed was systematically searched from January 2020 to November 2023. Publications that reported the progress in embryo implantation, placentation, and parturition made by Chinese scientists in the last 3 years were selected. The milestone events during gestation, embryo implantation, endometrial decidualization, placentation, and parturition are pivotal to a successful pregnancy. Embryo implantation requires intricate interactions between implantation-competent blastocysts and receptive endometrium. To adapt to pregnancy, endometrial stromal cells transform into specialized decidual cells, which occur spontaneously under the influence of ovarian hormones in humans but require the presence of embryos in mice. With embryonic development, the placenta forms to support fetal growth until parturition. The maternal-fetal interface is composed of diverse cell types, including endometrial decidual cells, placental trophoblast cells, endothelial cells, and various immune cells, a sophisticated interplay among which contributes to the maintenance of pregnancy. Near term, the uterus transitions from quiescence to contractility, in preparation for delivery. Disruptions to these events lead to pregnancy-related disorders such as repeated implantation failure, recurrent pregnancy loss, preeclampsia, fetal growth restriction, preterm birth, and infertility. In recent years, Chinese scientists have made prominent achievements in basic research on the aforementioned pregnancy events. Chinese scientists have made remarkable contributions to reproductive biology and maternal-fetal medicine research in recent years, highlighting future research directions in this field.
Wide Awake Local Anesthetic No Tourniquet in Hand and Wrist Surgery: Current Concepts, Indications, and Considerations
Authors: Sawhney Akshat , Thacoor Amitabh , Nagra Raveenjot , Geoghegan Luke , Akhavani Mo
Published: January 2024

Background:

Traditionally, the use of a pneumatic arterial tourniquet was requisite for safe and effective surgery of the hand. The use of arterial tourniquets necessitates the use of regional or general anaesthesia. Wide-awake local anaesthetic no tourniquet (WALANT) has emerged as a novel technique to overcome the limitations of tourniquet use in conjunction with regional/general anaesthesia. This review aimed to examine the safety and effectiveness of WALANT and provide guidance for surgeons with limited WALANT experience.

Methods:

A literature review of MEDLINE was performed up to March 2021 to identify all articles related to the use of WALANT in hand surgery. Any article reporting original data related to the use of WALANT was eligible for inclusion.

Results:

A total of 101 articles were identified through database searching. Of these, 79 met full inclusion criteria and described the use of WALANT in 19 elective and trauma procedures. Current data suggest that WALANT is safe and effective for use in a range of procedures.

Conclusions:

WALANT surgery is increasing in popularity as evidenced by the variety of surgical indications reported in the literature. There is limited comparative data on the cost-effectiveness of WALANT compared to conventional methods. Current data suggest that WALANT is safe, better tolerated by patients and associated with direct and indirect cost savings.
Lumbosacral Plexogram: An Aid to Reconstructive Nerve Possibilities in the Lower Extremity
Authors: Ramadan Sami , Leng Catherine , Duraku Liron S. , Chaudhry Tahseen , Power Dominic M. , George Samuel
Published: January 2024

The lumbosacral plexus is the network of nerves responsible for the motor and sensory function of the pelvis and lower limb. Our observation is that the anatomy of this plexus is less familiar to surgeons than that of the brachial plexus. Damage to the lumbosacral plexus and its terminal branches may have a significant impact on locomotion, posture, and stability. We have designed a visual representation of the lumbosacral plexus to aid clinicians treating peripheral nerve disorders. The utility is illustrated with a case report in which a patient underwent nerve transfers in the lower limb to restore function. A visual representation of the lumbosacral plexus is a valuable adjunct to a clinical examination and helps make sense of clinical signs. The color-coding of each root level and the arrangement of muscles from proximal to distal helps with visual recall. A clear assessment of complex lumbosacral plexus patients is essential for diagnosis and planning. As with the case described, a sound knowledge of the “plexogram” can identify solutions for complex patients and result in significant functional improvements. We hope it helps advance the field of nerve surgery and, particularly, nerve transfers.
Complications Associated with Facial Autologous Fat Grafting for Aesthetic Purposes: A Systematic Review of the Literature
Authors: Brucato Davide , Ülgür Ismail I. , Alberti Andrea , Weinzierl Andrea , Harder Yves
Published: January 2024

Background:

With the increasing demand for aesthetic procedures, autologous fat grafting (AFG) seems to be an attractive option for facial volumization and rejuvenation. The aim of this study was to assess the type and severity of associated complications after facial AFG for aesthetic purposes.

Methods:

The entire PubMed/Medline and Cochrane databases were screened to identify studies describing complications that occurred after the injection of autologous fat into the face. These complications have been reviewed and analyzed according to their occurrence and severity in the different anatomical regions of the face.

Results:

Twenty-two articles including 38 patients reported on a total of 58 complications. Thirty-two complications have been classified as severe or permanent, including hemiplegia (n = 11), loss of vision (n = 7), or skin necrosis (n = 3). The other 26 complications were classified as mild or transient, such as lipogranuloma (n = 12) or mycobacterial abscess (n = 2). The majority of complications were reported after injection to the forehead (n = 26) and the temporal region (n = 21). Interestingly, this location seems to be the area at risk because 53% of all severe complications occurred in this anatomical region.

Conclusions:

AFG to the face is associated with a low incidence of complications, but if they occur, they can be dramatic, particularly in the forehead and temporal region. Nevertheless, AFG can be used to correct age-related changes of the face and volume loss and may represent an alternative to synthetic fillers. Therefore, AFG to the face should be performed by qualified doctors under careful consideration of risks and facial anatomy.
How Hermann J. Muller Viewed the Ernest Sternglass Contributions to Hereditary and Cancer Risk Assessment
Authors: Calabrese Edward J. , Giordano James
Published: January 2024

As one of the most influential radiation geneticists of the 20th century, Hermann J. Muller had a major role in the development and widespread acceptance of the linear no-threshold (LNT) dose response for hereditary and cancer risk assessments worldwide. However, a spate of historical reassessments have challenged the fundamental scientific foundations of the LNT model, drawing considerable attention to issues of ethical probity and the scientific leadership of Muller. This review paper raises further questions about the objectivity of Muller with respect to the LNT model. It is shown that Muller supported Ernest Sternglass’s findings and interpretations concerning radiation-induced childhood leukemia, which have been widely and consistently discredited. These findings provide further evidence that Muller’s actions with respect to radiation cancer risk assessment were far more ideologically than scientifically based.
Recurrence and Survival Prediction Models for Receiving Preoperative Chemotherapy Pancreatic Ductal Adenocarcinoma Cancer: A Single-center Retrospective Research
Authors: Zhang Yixin , Han Xin , Sun Zhongquan , You Wanlu , Cao Haoze , Wu Xiaochang , Wang Weilin , Ding Yuan
Published: January 2024

Purpose:

Regard preoperative chemotherapy as a holistic sequential treatment modality to identify predictive factors associated with recurrence and survival in pancreatic ductal adenocarcinoma (PDAC) and construct models to provide decision support and treatment selection for the candidate patients.

Methods:

Retrospect PDAC patients who received preoperative chemotherapy from January 2016 to June 2023 at the Second Affiliated Hospital of Zhejiang University School of Medicine. Run a univariate and multivariate analysis of factors associated with recurrence-free survival (RFS) and overall survival (OS). Scoring systems were developed based on the hazard ratios (HR) of all significant predictors. Kaplan–Meier analyses and log-rank tests were used to calculate RFS and OS.

Results:

A total of 72 PDAC patients with preoperative chemotherapy were analyzed. After preoperative chemotherapy, 21(29.17%) patients achieved any radiologic downstaging with 68(94.44%) patients achieving negative resection margin status (R0 margins). For carbohydrate antigen 19-9(CA19-9) non-secreting patients, shrinkage rate of length diameter of tumor≥20%(P=0.027), resection margin status(P=0.011) were independent predictors of OS. And for CA19-9 secreting patients, CA19-9 serum level at the end of chemotherapy≥1000(P=0.027) and resection margin status (P=0.012) were independent predictors of OS. Points according HR were allocated to these factors in the proposed scoring system, respectively. Recurrence curves and survival curves with statistically significant differences were also presented for patients grouped according to the scoring systems. For CA19-9 non-secreting patients, the OS of patients with a score from 2 to 2.97 was significantly shorter than that of patients with a score from 4.94 to 5.91 (P=0.009). And for CA19-9 secreting patients, the OS of patients with a score of 2 was significantly shorter than that of patients with a score from 3.75 to 4.99 (P<0.001).

Conclusion:

Simple scoring models for RFS and OS incorporating CA19-9 serum levels or the tumor shrinkage rate and postoperative pathology may assist clinicians in evaluating prognosis of PDAC patients with preoperative chemotherapy.
Diagnostic value of clot formation parameters determined by rotational thromboelastometry in 63 patients with congenital dysfibrinogenemia
Authors: Simurda Tomas , Marchi Rita , Casini Alessandro , Neerman-Arbez Marguerite , Drotarova Miroslava , Skornova Ingrid , Zolkova Jana , Kolkova Zuzana , Loderer Dusan , Brunclikova Monika , Belakova Kristina Maria , Stasko Jan
Published: January 2024

Rotational thromboelastometry (ROTEM) is a global hemostasis assay. The diagnosis added value of ROTEM in congenital dysfibrinogenemia remains to be established.

The aim of this study was to analyze clot formation by ROTEM in a cohort of dysfibrinogenemic patients and to establish correlations with genotype, clinical features, and coagulation parameters.

The study included genetically confirmed congenital dysfibrinogenemia cases (n = 63) and healthy controls (n = 50). EXTEM, INTEM, FIBTEM tests were used to measure ROTEM parameters, that is, clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and amplitude 10 min after CT (A10). The ISTH bleeding assessment tool was used to determine bleeding episodes.

CT (INTEM) was statistically significantly shorter in congenital dysfibrinogenemia patients compared to controls while CFT (EXTEM) was prolonged. Patients's MCF in EXTEM, INTEM, and FIBTEM were similar to controls while A10 (FIBTEM) was statistically significantly lower. Fibrinogen activity was positively correlated with fibrinogen antigen, A10 and MCF in all three assays. Bleeding phenotypes were observed in 23 (36.5%) patients. Only CFT in EXTEM and CT in INTEM were statistically different in patients with bleeding phenotype versus controls. Carriers of the FGA mutation p.Arg35His had a CT (EXTEM) slightly prolonged and a reduced A10 (FIBTEM) compared to controls.

Some ROTEM parameters were able to distinguish congenital dysfibrinogenemia patients from controls, and patients with a bleeding phenotype. Prolonged CFT in EXTEM were associated with congenital dysfibrinogenemia and bleeding phenotype. Bleeding episodes in most patients were generally mild and prevalence of thrombosis was very low.
Reflections on Studying Huang Di Nei Jing in the West
Authors: Neal Edward
Published: January 2024

Huang Di Nei Jing (《黄帝内经》The Yellow Emperor’s Inner Classic) has been the source text of Chinese medicine knowledge and innovation for over two thousand years. Despite this key relevance, many of its ideas and practices have proven difficult to understand and implement fully into clinical practice. Cultural and language differences can be compounded with these challenges but may also present new opportunities for advancement and insight when studied by researchers outside of the originating culture. This article introduces the method of Classical-Text Archaeology and delves into the author’s two-decade journey of researching this text, with a discussion on cultural differences and issues of medical scholarship.
Anomalous right coronary artery originating from the left anterior descending artery with stenosis: a highlighted imaging observation
Authors: Xu Zhanwen , Li Yaqin , Liu Yi
Published: January 2024

This imaging observation underscores a rare single coronary artery anomaly, wherein the right coronary artery originates from the left anterior descending artery (LAD). The stenosis in the proximal LAD adds complexity, emphasizing the need for multidisciplinary evaluation and decision-making.
The impact of the site of myocardial infarction on in-hospital outcomes for patients with STEMI
Authors: Kwok Chun Shing , Qureshi Adnan I. , Lip Gregory Y.H.
Published: January 2024

Background

The territory and vessel involved in ST-elevation myocardial infarction (STEMI) is an important and there are limited contemporary studies from the national perspective.

Methods

A retrospective cohort study was undertaken of national representative hospital admission in the National Inpatient Sample with a diagnosis of anterior or non-anterior STEMI between 2017 and 2020. Multiple logistic regression and multiple linear regressions were used to determine if there are any differences in in-hospital mortality, length of stay (LOS) and cost for anterior and non-anterior STEMI.

Results

A total of 655 915 admissions with STEMI were included in the analysis (267 920 anterior STEMI, and 387 995 non-anterior STEMI). Non-anterior STEMI was associated with a significant reduction in mortality (OR 0.91 95% CI 0.89–0.99,P = 0.011) and LOS (coefficient −0.15 95% CI −0.22 to −0.08,P < 0.001) compared to anterior STEMI but there was no significant difference in healthcare costs (−297 95% CI −688 to 74). Analyses considering the infarct-related artery showed that the worse outcomes were associated with left main lesions and left-sided lesions had worse outcomes than right coronary artery lesions.

Conclusion

Non-anterior STEMI is associated with reduced mortality and LOS compared to anterior STEMI. Left-sided coronary lesions had worse outcomes, compared to right coronary lesions. STEMI should be considered in terms of the vessel or territory affected, in relation to outcomes and healthcare costs.
Endoscopy in pediatric polyposis syndromes: why, when and how
Authors: Cohen Shlomi , Hyer Warren , Attard Thomas
Published: January 2024

Single or multiple polyps are frequently encountered during colonoscopy among children and adolescents and may be indicative of hereditary polyposis syndrome (HPS). The management of children with single or multiple polyps is guided by the number of polyps, their distribution and the histological findings. Children with HPS carry a high risk of complications, including intestinal and extra-intestinal malignancies. The goals of surveillance in pediatric HPS are to treat symptoms, monitor the burden of polyps and prevent short- and long-term complications. Therefore, the management of children with HPS is based on therapeutic endoscopy. The strategy of therapeutic endoscopy is a careful assessment and characterization of the polyps and performing polypectomies using advanced endoscopic techniques. A multidisciplinary approach, comprising clinical, interventional endoscopy, cancer surveillance and support of familial and emotional aspects is essential in the management of children with HPS.
Assessing nuclear medicine practices: a critical evaluation of QUANUM through a quality improvement perspective and its wider relevance
Authors: Vinjamuri Sobhan , Pant Vineet , Bomanji Jamshed B. , Marengo Mario , Zanial Ahmadzaid , Dondi Maurizio , Paez Diana
Published: January 2024

Quality Management Audits in Nuclear Medicine (QUANUM) is an initiative conceived by the International Atomic Energy Agency to enhance global standards in Nuclear Medicine practices. Acknowledging the intricate regulatory frameworks and the necessity for multidisciplinary collaboration, QUANUM has gained global acceptance, demonstrating widespread implementation and positive impacts on patient care. This manuscript critically evaluates the QUANUM program through the lens of quality improvement (QI), by employing established and validated QI tools. Our analysis identifies areas of conformance, underscores key strengths inherent to QUANUM, and pinpoints further learning opportunities for continuous enhancement. Additionally, we assert that the insights derived from scrutinizing this global project within Nuclear Medicine, have valuable implications for departments aspiring for establishing good quality management systems, thereby contributing to the improvement of patient care.
Challenges in applying minimal clinically important difference: a critical review
Authors: Podurgiel Joseph , Piscitelli Daniele , Denegar Craig
Published: January 2024

Healthcare clinicians strive to make meaningful changes in patient function and participation. A minimal clinically important difference (MCID) is an estimate of the magnitude of change needed to be meaningful to a patient. Clinicians and investigators may assume that a cited MCID is a valid and generalizable estimate of effect. There are, however, at least two concerns about this assumption. First, multiple methods exist for calculating an MCID that can yield divergent values and raise doubt as to which one to apply. Second, MCID values may be erroneously generalized to patients with dissimilar health conditions. With this in mind, we reviewed the methods used to calculate MCID and citations of reported MCID values for outcome measures commonly used in neurologic, orthopedic, and geriatric populations. Our goal was to assess whether the calculation methods were acknowledged in the cited work and whether the enrolled patients were similar to the sample from which the MCID estimate was derived. We found a concerning variation in the methods employed to estimate MCID. We also found a lack of transparency in identifying calculation methods and applicable health conditions in the cited work. Thus, clinicians and researchers must pay close attention and exercise caution in assuming changes in patient status that exceed a specific MCID reflect meaningful improvements in health status. A common standard for the calculation and reporting of an MCID is needed to address threats to the validity of conclusions drawn from the interpretation of an MCID.
Cerebral Tumefactive Inflammatory Lesion Occurrence During Ixekizumab Treatment in a Patient With Active Psoriatic Arthritis
Authors: Marangi Antonio , Benvenuti Francesco , Mazzai Linda , Riva Giulio , Polo Diana , Franceschetti Ilaria , De Sandre Pierino , Zanusso Mariano Agostino , Scanelli Giovanni , Perini Francesco
Published: January 2024

Introduction:

Ixekizumab is an anti–interleukin-17A (IL-17A) humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and ankylosing spondylitis. Central nervous system inflammatory manifestations are atypical during therapy with IL-17A inhibitors, with only one case of myelitis described to date.

Case Report:

A 72-year-old man with a medical history of active psoriatic arthritis was admitted to our department owing to the acute onset of left face numbness 1 month after the first ixekizumab administration. Magnetic resonance imaging of the brain displayed a large T2-hyperintense infratentorial lesion involving the root of the fifth and seventh left cranial nerves. A thorough laboratoristic and instrumental work-up did not show elements suggestive of extracerebral neoplasms or infections. Therefore, neuronavigation-assisted brain biopsy was performed, and histologic analysis of the lesion revealed the presence of wide aggregates of foamy histiocytes diffusely infiltrating the brain parenchyma, in the absence of malignant tissue or histologic elements suggestive of central nervous system infections or primary histiocytoses. Steroid treatment (dexamethasone 8 mg/daily) was then administered with subsequent clinical amelioration. One month after hospital discharge, a brain magnetic resonance imaging showed a nearly complete resolution of the lesion.

Conclusion:

This is the first case of a cerebral inflammatory lesion occurring during treatment with ixekizumab. Although very rare, neurological complications may occur during anti–IL-17A therapies, thus leading to the need for careful monitoring of patients exposed to these drugs.
Anticonvulsant Agents for Treatment of Restless Legs Syndrome
Authors: Al-Kassmy Jawad , Alsalmi Mohammed , Kang Woojin , Huot Philippe
Published: January 2024

Introduction:

Restless Legs Syndrome (RLS) is a neurological disorder primarily treated with pregabalin and gabapentin, followed by dopamine agonists later in the process due to the risk of augmenting RLS symptoms. In addition, clinical reports have disclosed varying degrees of success employing other agents in patients unresponsive to traditional agents. Here, we present a patient who had success in the reduction of RLS symptoms with lamotrigine, a broad-spectrum anticonvulsant. Previously, lamotrigine had been used in 2 trials with successful treatment of RLS.

Case Report:

We present a 58-year-old right-handed lady with long-standing history of smoking, hypertension, dyslipidaemia, prediabetes, gastro-esophageal reflux disease, asthma, strabismus, uterine cancer, severe and debilitating course of RLS accompanied by unexplained deterioration. The patient initially demonstrated abnormal sensation in all her limbs, which worsened with radiotherapy treatment, and was eventually diagnosed with RLS based on the diagnostic criteria. Subsequent examinations were unremarkable and revealed no further explanation for the deterioration of the RLS symptoms. While the complexity of the patient’s medical history had exposed her to a variety of medications, she reported that only lamotrigine, in addition to her original regimen of methadone and pramipexole, offered significant symptomatic relief. It must be noted that no adverse side effects, including impulse-control disorder, were reported by the patient.

Conclusions:

We present a case of a woman whose deteriorating symptoms of RLS were successfully alleviated by the administration of lamotrigine. This is only the third case in the literature to have successfully utilized lamotrigine as a treatment option for RLS.
Age-friendly healthcare: integrating the 4Ms to enable age-friendly cancer care
Authors: Hodge Oliver , Rasekaba Tshepo , Blackberry Irene , Steer Christopher B.
Published: January 2024

Purpose of review

There is a growing movement towards person-centred, age-friendly healthcare in the care of older adults, including those with cancer. The Age-Friendly Health Systems (AFHS) initiative uses the 4Ms framework to enable this change. This review documents the utility and implications of 4Ms implementation across different settings, with a particular focus on cancer care.

Recent findings

The AFHS initiative 4Ms framework uses a set of core, evidence-based guidelines (focussing on What Matters, Medication, Mentation and Mobility) to improve person-centred care. The successful implementation of the 4Ms has been documented in many different healthcare settings including orthopaedics primary care, and cancer care. Implementation of the 4Ms framework into existing workflows complements the use of geriatric assessment to improve care of older adults with cancer. Models for implementation of the 4Ms within a cancer centre are described. Active engagement and education of healthcare providers is integral to success. Solutions to implementing the What Matters component are addressed.

Cancer centres can successfully implement the 4Ms framework into existing workflows through a complex change management process and development of infrastructure that engages healthcare providers, facilitating cultural change whilst employing quality improvement methodology to gradually adapt the status quo to age-friendly processes.
The Relationship Between Choroidal Abnormalities and Visual Outcomes in Pediatric Patients With NF1-Associated Optic Pathway Gliomas
Authors: Estrela Tais , Truong Saprina , Garcia Arielle , He Jocelyn , Ying Gui-Shuang , Devakandan Keshini , Reginald Y. Arun , Fisher Michael J. , Liu Grant T. , Ullrich Nicole J. , Avery Robert A. , Heidary Gena
Published: January 2024

Background:

Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs).

Methods:

Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell–inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations.

Results:

Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05).

Conclusions:

CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function.
Absence of eye position effects in the early auditory cortex of monkeys
Authors: Huang Ying , Brosch Michael
Published: January 2024

This study aims to investigate whether the position of the eyes affects the neuronal activity in auditory cortex in a condition in which not the active control of eye position but the execution of hand movements was required relative to stimuli. Two monkeys were trained to perform audio-visual tasks in which they had to use their hand to respond to both the visual and the auditory stimuli to earn a reward. We recorded the spiking activity and the local field potentials from the core fields of auditory cortex, along with the eye position of the monkeys while they performed the tasks. We found that both the spiking activity and the local field potentials did not significantly vary with the eye position. This was the case both during the presentation of sounds and during other periods of the tasks. Our results indicate that eye position did not affect the neuronal activity in auditory cortex during the audio-visual tasks. Our results, together with the previous finding that eye position affects the neuronal activity in auditory cortex during eye fixation tasks, suggest that the presence of eye position effects in auditory cortex depends on the specific behavior a subject has to exhibit to obtain a reward.
Clinical impact and public health challenges of a PVL- MRSA bacteraemia outbreak amongst people who inject drugs in South Yorkshire.
Authors: Beaumont Matthew , Subramanian Bala , Agwuh Ken , Ryan Yan , Pichon Bruno
Published: January 2024

Background: Panton-Valentine leukocidin (PVL) Staphylococcus aureus (SA) is an emergent public health concern. PVL toxin has been mostly associated with methicillin-sensitive Staphylococcus aureus (MSSA) related skin and soft tissue infections occurring in high-risk groups such as people who inject drugs (PWID). The emergence of PVL- methicillin resistant Staphylococcus aureus (MRSA) infection is causing severe and life-threatening disease in PWID.
Clinical cases: we present an outbreak of eight PVL-MRSA bacteraemia cases at a UK teaching hospital between 2018 and 2022. An additional four patients developed bacteraemia cases with PVL-negative MRSA of the same multi-locus sequence type (MLST). All patients were PWID and aged between 33- 51 years old. Four patients developed MRSA bacterial endocarditis. Three patients died. These cases represent the initial cases detected at Doncaster and Bassetlaw Teaching Hospitals of what is an ongoing and developing outbreak.
Management: an outbreak investigation has been undertaken in association with the UK Health Security Agency.  Epidemiological factors have been explored, including via direct contact at a local sheltered accommodation and the possibility of a contaminated drug supply. Whole-genome sequencing confirmed that all isolates were closely related and of the same MLST (sequence type 5). A community substance misuse group disseminated health education on the prevention of PVL-MRSA. Preventing infection in PWID presents a major challenge due to the impact of addiction on engagement with services and the significant barriers faced by our patients to observing infection prevention measures.
Conclusion: PVL-MRSA is of major public health concern and outbreak investigation and mapping out local epidemiological patterns plays a vital role in preventing further spread throughout the community. Additionally, this work enables targeted and early treatment in patients in high-risk categories for disease. These cases of PVL-MRSA infection in PWID highlights the transmissibility, pathogenic potential and severe clinical disease spectrum within this population. Further work is required to tackle transmission and infection from this pathogenic strain.