bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Three-Day Atorvastatin Administration on Coagulation Factors in Patients With Prior Venous Thromboembolism and Healthy Subjects: A Preliminary Study
Authors: Stępień Konrad , Żółciński Marek , Ząbczyk Michał , Zalewski Jarosław , Undas Anetta 
Published: December 2023

Abstract:
Statins exert antithrombotic effects, which might contribute to reduced risk of venous thromboembolism (VTE). Rosuvastatin 20 mg/d administered for 4 weeks has been reported to decrease coagulation factors (F) VII, FVIII, and FXI in VTE patients. Moreover, in accordance with recent registry data in non-VTE subjects, statins usage was associated with lower FXI. We investigated whether 3 doses of a statin decrease coagulation factors activity and if such changes can alter fibrin clot properties in VTE patients and healthy subjects. We enrolled 28 consecutive first-ever prior VTE patients after 6 months of anticoagulation and 25 healthy controls well-matched for demographics and lipid profiles (aged 44 [interquartile range 34–51] years) in an interventional nonrandomized study. Before and after 3 doses of atorvastatin 40 mg/d, activity of FVII, FVIII, FIX, and FXI was measured, along with fibrin clot properties, including permeability (Ks) and clot lysis using 3 various assays. After a 3-day statin administration, we observed the decrease of FVII (by 6.2%, P = 0.046) and FXI (by 8.6%, P = 0.044), irrespective of low-density lipoprotein cholesterol reduction (by 24%, P < 0.001), whereas other coagulation factors remained unaltered. Reduction of FVII and FXI activity was inversely correlated with Ks alterations (R = −0.292, P = 0.034 and R = −0.335, P = 0.014, respectively). After adjustment for age, studied group, and fibrinogen level, the reduction of FXI was independently associated with an increase of fibrin clot permeability (B = −0.084, P = 0.027). In conclusion, a 3-day 40 mg atorvastatin administration is sufficient to reduce FVII and FXI activity in our pilot study, which is associated with favorable fibrin clot properties modification.
Intravenous Drug Abuser Treated for Chronic Infected Open Forearm Fracture with Shortening and Primary Wound Closure
Authors: Annasamudram Abhijith , Elhessy Ahmed H. , Eralp Ipek G. , Conway Janet D. 
Published: December 2023

Summary:
Neglected and open forearm fracture wounds accompanied by shortening are complex injuries that are seldom reported in the known literature. We describe a patient with a history of chronic intravenous drug abuse (IVDA) and a neglected forearm wound with radius and ulna fractures with chronic osteomyelitis managed by limb salvage. The patient had a history of IVDA and a neglected forearm wound with fractures in both the radius and ulna, along with chronic osteomyelitis. The approach taken to manage this complex injury involved limb salvage. The case emphasizes the treatment challenges associated with patients who had IVDA and neglected their wounds. Thorough evaluation combining clinical and radiological assessments, followed by appropriate surgical planning and intervention, played a crucial role in restoring the functional status of the limb. Neglected open fracture wounds in the forearm are uncommon and have limited documentation in the existing literature. The described patient’s chronic history of IVDA and the disregarded open forearm osteomyelitis exemplify the severe consequences that can arise from injectable drug abuse in the upper extremity. In such cases, limb preservation and optimization of functional outcomes become paramount. To the best of our knowledge, this is one among the few reported cases of this nature, highlighting the significance of sharing such experiences to enhance medical understanding and inform future treatment approaches.
Heart transplant donation after circulatory death: current status and implications
Authors: Fedson Savitri 
Published: December 2023

Purpose of review
The use of cardiac transplantation following circulatory death (DCD) has been limited worldwide. Concerns about cardiac function after warm ischemia and the potential for decreased graft function have been important considerations in this hesitancy. In addition, ethical and legal questions about the two widely used organ procurement methods have led to discussions and public education in many countries.

Recent findings
Publication of a US randomized trial of cardiac transplantation following DCD has shown that it is both feasible and has similar short-term outcomes compared with cardiac transplantation following brain death (DBD). These data support those from both Australia and the UK who have largest experience to date.

Summary
The adoption of cardiac transplantation following circulatory death has increased overall cardiac transplantation in those transplant centers who have incorporated these donors. Short term outcomes for DCD organ procurement methods are similar to those outcomes using DBD hearts. Continued study and standardization of warm ischemic times will allow for better comparisons of organ procurement techniques and organ optimization. The ethical concerns about procurement methods, in addition to a discussion of procurement costs and feasibility will need to be addressed further in the efforts to expand the organ pool and increase overall cardiac transplantation numbers.
Leber hereditary optic neuropathy gene therapy
Authors: Lam Byron L. 
Published: December 2023

Purpose of review
To discuss relevant clinical outcomes, challenges, and future opportunities of gene therapy in Leber hereditary optic neuropathy (LHON).

Recent findings
Results of G11778A LHON Phase 3 randomized clinical trials with unilateral intravitreal rAAV2/2-ND4 allotopic gene therapy show good safety and unexpected bilateral partial improvements of BCVA (best-corrected visual acuity) with mean logMAR BCVA improvements of up to near ∼0.3 logMAR (3 lines) in the treated eyes and ∼0.25 logMAR (2.5 lines) in the sham-treated or placebo-treated fellow eyes. Final mean BCVA levels after gene therapy were in the range of ∼1.3 logMAR (20/400) bilaterally.

Summary
Bilateral partial improvement with unilateral LHON gene therapy was unanticipated and may be due to treatment efficacy, natural history, learning effect, and other mediators. The overall efficacy is limited given the final BCVA levels. The sequential progressive visual loss and varied occurrence of spontaneous partial improvement in LHON confound trial results. Future clinical trials with randomization of patients to a group not receiving gene therapy in either eye would help to assess treatment effect. Promising future LHON gene therapy strategies include mitochondrially-targeted-sequence adeno-associated virus (‘MTS-AAV’) for direct delivery of the wild-type mitochondrial DNA into the mitochondria and CRISPR-free, RNA-free mitochondrial base editing systems. Signs of anatomical optic nerve damage and objective retinal ganglion cell dysfunction are evident in the asymptomatic eyes of LHON patients experiencing unilateral visual loss, indicating the therapeutic window is narrowing before onset of visual symptoms. Future treatment strategies utilizing mitochondrial base editing in LHON carriers without optic neuropathy holds the promise of a more advantageous approach to achieve optimal visual outcome by reducing disease penetrance and mitigating retinal ganglion cell loss when optic neuropathy develops.
Dequalinium Chloride for the Treatment of Vulvovaginal Infections: A Systematic Review and Meta-Analysis
Authors: Eckel Fanny , Farr Alex , Deinsberger Julia , Kernmayer-Farr Karin , Foessleitner Philipp 
Published: December 2023

Objective/Purpose
Women at reproductive age frequently experience vulvovaginal infections and vaginitis. The most common etiologies are vulvovaginal candidiasis (VVC), bacterial vaginosis (BV), desquamative inflammatory vaginitis/aerobic vaginitis, and trichomoniasis. Various treatment options are available for these infections, such as specific antimicrobial or antiseptic agents. Dequalinium chloride (DQC) is a local antiseptic agent with a broad antimicrobial and antifungal spectrum. Multiple studies suggest that DQC is an efficient treatment for vaginal infections; however, it is not widely recommended as a first-line treatment. This systematic review and meta-analysis aims to evaluate the efficacy of DQC compared with that of standard treatment.

Methods
Our systematic review was conducted according to the PRISMA guidelines. PubMed/MEDLINE, EMBASE, CENTRAL, and clinicaltrials.org were searched to retrieve relevant reports up to October 2022.

Results
Four randomized controlled studies and 1 observational study were included in this review. Overall, DQC showed noninferiority to the reference treatments for BV and VVC, and to the evaluated treatment options for desquamative inflammatory vaginitis/aerobic vaginitis. For BV and VVC, this could also be confirmed in a meta-analysis including 3 randomized controlled studies. No serious adverse events were reported in any of these studies.

Conclusions
Dequalinium chloride offers a safe, well-tolerated, and efficient treatment option for vulvovaginal infections of different etiologies. However, further studies are needed to confirm our findings and allow inclusion of DQC as a first-line treatment into guidelines.
Genetic variation in apolipoprotein A-V in hypertriglyceridemia
Authors: Perera Shehan D. , Hegele Robert A. 
Published: December 2023

Purpose of review
While biallelic rare APOA5 pathogenic loss-of-function (LOF) variants cause familial chylomicronemia syndrome, heterozygosity for such variants is associated with highly variable triglyceride phenotypes ranging from normal to severe hypertriglyceridemia, often in the same individual at different time points. Here we provide an updated overview of rare APOA5 variants in hypertriglyceridemia.

Recent findings
Currently, most variants in APOA5 that are considered to be pathogenic according to guidelines of the American College of Medical Genetics and Genomics are those resulting in premature termination codons. There are minimal high quality functional data on the impact of most rare APOA5 missense variants; many are considered as variants of unknown or uncertain significance. Furthermore, particular common polymorphisms of APOA5, such as p.Ser19Trp and p.Gly185Cys in Caucasian and Asian populations, respectively, are statistically overrepresented in hypertriglyceridemia cohorts and are sometimes misattributed as being causal for chylomicronemia, when they are merely risk alleles for hypertriglyceridemia.

Summary
Both biallelic and monoallelic LOF variants in APOA5 are associated with severe hypertriglyceridemia, although the biochemical phenotype in the monoallelic state is highly variable and is often exacerbated by secondary factors. Currently, with few exceptions, the principal definitive mechanism for APOA5 pathogenicity is through premature truncation. The pathogenic mechanisms of most missense variants in APOA5 remain unclear and require additional functional experiments or family studies.
Oncology for the rhinologist
Authors: Tam Kenric , Dunn Lara A. , Cohen Marc A. 
Published: December 2023

Purpose of review
The purpose of this review is to summarize current evidence regarding the use of induction chemotherapy for a variety of histopathologies of sinonasal malignancy (SNMs) and to review the potential adverse effects of cytotoxic agents.

Recent findings
Historically, patients with locally advanced SNMs have had relatively poor prognoses and high morbidity from treatment. The available retrospective data suggests that induction chemotherapy may improve outcomes for patients with sinonasal undifferentiated carcinoma (SNUC), neuroendocrine carcinoma, squamous cell carcinoma (SSCC), and esthesioneuroblastoma. For SNUC and SSCC, response or nonresponse to induction chemotherapy may prognosticate outcomes and for SNUC specifically, drive selection of definitive therapy. In chemosensitive pathologies, induction chemotherapy appears to improve organ preservation.

Summary
Induction chemotherapy may improve functional and oncologic outcomes for patients with SNMs. Because of the rarity of these pathologies, the available data is primarily retrospective. Future randomized, prospective studies should be performed to further optimize and elucidate the role of induction chemotherapy for SNMs.
Extranodal extension in head and neck squamous cell carcinoma: need for accurate pretherapeutic staging to select optimum treatment and minimize toxicity
Authors: Bradley Patrick J. 
Published: December 2023

Purpose of reviewIn 2017, the American Joint Committee on Cancer (AJCC) introduced the inclusion of extracapsular nodal extension (ENE) into the N staging of nonviral head and neck squamous cell carcinoma (HNSCC), while retaining the traditional N classification based on the number and sizes of metastatic nodes. The extent of ENE was further defined as microscopic ENE (ENEmi) and major ENE (ENEma) based on extent of disease beyond the nodal capsule (≤ or > 2 mm). This article reviews the evidence and progress made since these changes were introduced.Recent findingsThe ‘gold standard’ for evaluation ENE is histopathologic examination, the current preferred primary treatment of patients with HNSCC is by radiation-based therapy ± chemotherapy or biotherapy. The current pretreatment staging is by imaging, which needs improved reliability of radiologic rENE assessment with reporting needs to consider both sensitivity and specificity (currently computed tomography images have high-specificity but low-sensitivity). Adjuvant chemotherapy is indicated for patients with ENEma to enhance disease control, whereas for patients with ENEmi, there is a need to assess the benefit of adjuvant chemotherapy. Evidence that the presence of pENE in HPV-positive oropharyngeal carcinoma is an independent prognostic factor and should be considered for inclusion in future AJCC editions has recently emerged.SummaryThere remains a paucity of data on the reliability of imaging in the staging of rENE, more so the for the accurate assessment of ENEmi. Optimistic early results from use of artificial intelligence/deep learning demonstrate progress and may pave the way for better capabilities in tumor staging, treatment outcome prediction, resulting in improved survival outcomes.
Resilience and Ethics in Nursing Education and Practice
Authors: Wright Erin , D'Aoust Rita , Swoboda Sandra M. , Hughes Victoria , Hudson Krysia , Reller Nancy , Rushton Cynda 
Published: December 2023

Background:Nursing faculty and clinicians are leaving the profession due to increased workload and burnout. Evidence-based interventions to build skills in resilience and well-being are encouraged; however, strategies to implement them in nursing curricula and nurse residency programs (NRPs) are not well known.Purpose:To understand the current state of resilience, well-being, and ethics content in the curriculum in schools of nursing and NRPs in the state of Maryland as part of a statewide initiative for Renewal, Resilience and Retention of Maryland Nurses (R3).Methods:A descriptive survey was distributed to leaders of all Maryland nursing schools and NRP directors.Results:Respondents (n = 67) reported minimal resilience, well-being, and ethics content. Teaching modalities included lecture, journaling, mindfulness, and the code of ethics. Barriers included lack of faculty knowledge, low priority, time constraints, and limited resources.Conclusion:Resilience, well-being, and ethics content is limited in nursing curricula. Developing educator skills and best practices to foster resilience and ethical practice are needed.
Unveiling the Link Between Antiphospholipid Antibodies and Cognitive Dysfunction in the Almenara Lupus Cohort
Authors: Velarde-Mejía Yelitza , Gamboa-Cárdenas Rocío , Zevallos Francisco , Medina Mariela , Rodriguez-Bellido Zoila , Pastor-Asurza Cesar , Alarcón Graciela S. , Ugarte-Gil Manuel F. 
Published: December 2023

Objective
Cognitive dysfunction is a prevalent manifestation of systemic lupus erythematosus (SLE). There is evidence for the role of antiphospholipid (aPL) antibodies on its etiopathogenesis. Our objective was to identify the association between aPL antibodies and cognitive dysfunction in SLE patients.

Methods
This cross-sectional study included 135 patients evaluated from March 2015 to October 2017 at one center. Cognitive deficit was measured using the NEUROPSI test. Disease activity and damage were ascertained using the SLEDAI-2K (SLE Disease Activity Index 2000) and the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), respectively; aPL antibodies were measured by enzyme-linked immunosorbent assay. The association between cognitive dysfunction and aPL antibodies was evaluated using univariable and multivariable linear regression models adjusted for age, sex, education, socioeconomic status, disease duration, SLEDAI-2K, SDI, mean current dose of prednisone, time of exposure to glucocorticoids, and drug use (immunosuppressants, hydroxychloroquine, aspirin, and warfarin).

Results
One hundred thirty-one patients (97.1%) were women; their mean (SD) age was 46.6 (12.5) years; 59 patients (43.7%) had positivity for at least 1 aPL antibody. IgM anticardiolipin (aCL) was positive in 24.5%, IgG in 13.5%, IgM aβ2GP1 in 16.8%, IgG anti-β2 glycoprotein in 24.6%, and the lupus anticoagulant in 5.3%. Ninety patients (66.7%) had some cognitive dysfunction. In the univariable analysis, a significant correlation between the NEUROPSI score and IgM aCL antibodies was found (B = −20.87 [SE, 3.2]; p < 0.001), which remained significant in the multivariable model (B = −13.89 [SE, 3.14]; p < 0.001).

Conclusions
IgM aCL antibodies are associated with cognitive dysfunction in patients with SLE. Larger and longitudinal studies are needed to assess the impact of these findings.
Multiparametric Cardiovascular MRI Assessment of Post-COVID Syndrome in Children in Comparison to Matched Healthy Individuals
Authors: Eckstein Jan , Skeries Valentina , Pöhler Gesa , Babazade Nigar , Kaireit Till , Gutberlet Marcel , Kornemann Norman , Hellms Susanne , Pfeil Alexander , Bucher Andreas Michael , Hansmann Georg , Beerbaum Philipp , Hansen Gesine , Wacker Frank , Vogel-Claussen Jens , Wetzke Martin , Renz Diane Miriam 
Published: December 2023

Background
Post-COVID syndrome (PCS) can adversely affect the quality of life of patients and their families. In particular, the degree of cardiac impairment in children with PCS is unknown.

Objective
The aim of this study was to identify potential cardiac inflammatory sequelae in children with PCS compared with healthy controls.

Methods
This single-center, prospective, intraindividual, observational study assesses cardiac function, global and segment-based strains, and tissue characterization in 29 age- and sex-matched children with PCS and healthy children using a 3 T magnetic resonance imaging (MRI).

Results
Cardiac MRI was carried out over 36.4 ± 24.9 weeks post-COVID infection. The study cohort has an average age of 14.0 ± 2.8 years, for which the majority of individuals experience from fatigue, concentration disorders, dyspnea, dizziness, and muscle ache. Children with PSC in contrast to the control group exhibited elevated heart rate (83.7 ± 18.1 beats per minute vs 75.2 ± 11.2 beats per minute, P = 0.019), increased indexed right ventricular end-diastolic volume (95.2 ± 19.2 mlm−2 vs 82.0 ± 21.5 mlm−2, P = 0.018) and end-systolic volume (40.3 ± 7.9 mlm−2 vs 34.8 ± 6.2 mlm−2, P = 0.005), and elevated basal and midventricular T1 and T2 relaxation times (P < 0.001 to P = 0.013). Based on the updated Lake Louise Criteria, myocardial inflammation is present in 20 (69%) children with PCS. No statistically significant difference was observed for global strains.

Conclusions
Cardiac MRI revealed altered right ventricular volumetrics and elevated T1 and T2 mapping values in children with PCS, suggestive for a diffuse myocardial inflammation, which may be useful for the diagnostic workup of PCS in children.
Evaluation of the Efficacy and Safety of FFX Facet Cages Compared to Pedicle Screw Fixation in Patients with Lumbar Spinal Stenosis: A Long-Term Study
Authors: Houari Omar , Douanla Arnaud , Ammar Mehdi Ben , Benmekhbi Mustapha , Mortada Jihad , Lungu Gabriel , Magheru Cristian , Voirin Jimmy , Lebedinsky Pablo Ariel , Musacchio Mariano , Bolognini Federico , Srour Robin 
Published: December 2023

AbstractObjectiveThe study evaluated the long-term safety and efficacy of the FFX facet cage versus pedicle screw (PS) fixation in patients with lumbar spinal stenosis (LSS).MethodsA hybrid retrospective/prospective study design was used. Following a medical records review, subjects meeting the inclusion/exclusion criteria were consented and enrolled in the prospective arm of the study. CT-scans and dynamic X-rays were performed to assess fusion rates, range of motion and translation. Adverse events during the 2-year post-index procedure were also analyzed. Pre-operative and 2+ year Visual Analogue Scale (VAS) back and leg scores and Oswestry Disability Index (ODI) were also obtained.ResultsA total of 112 subjects were enrolled with 56 patients included in the PS and FFX groups. Mean age was 63.1±11.2 and 67.1±10.9 years and the mean number of levels operated was 1.8±0.8 and 2.3±1.0 respectively for the PS and FFX groups. There was no difference between the two groups for the primary composite fusion endpoint assessed (respectively 60.0% vs. 70.9%, p=0.120). There was also no difference in postoperative complications or adverse events during the 2-year follow-up period. A higher percentage of patients in the PS group (10.7%) required reoperation compared to the FFX group (3.6%). While both groups experienced significant improvements in VAS and ODI scores versus pre-operative assessment, there was no difference between the two groups.ConclusionThe present study documents the long-term safety and efficacy of the FFX device in patients with LSS with a reduction in reoperation rate when compared to PS fixation.
Spatial and Compositional Biomarkers in Tumor Microenvironment Predicts Clinical Outcomes in Triple-Negative Breast Cancer
Authors: Mi Haoyang , Varadhan Ravi , Cimino-Mathews Ashley M. , Emens Leisha A. , Santa-Maria Cesar A. , Popel Aleksander S. 
Published: December 2023

AbstractTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, which warrants identification of novel therapeutic targets. Deciphering nuances in the tumor microenvironment (TME) may unveil insightful links between anti-tumor immunity and clinical outcomes, yet such connections remain underexplored. Here we employed a dataset derived from imaging mass cytometry of 58 TNBC patient specimens at single-cell resolution and performed in-depth quantifications with a suite of multi-scale computational algorithms. We detected distinct cell distribution patterns among clinical subgroups, potentially stemming from different infiltration related to tumor vasculature and fibroblast heterogeneity. Spatial analysis also identified ten recurrent cellular neighborhoods (CNs) - a collection of local TME characteristics with unique cell components. Coupling of the prevalence of pan-immune and perivasculature immune hotspot CNs, enrichment of inter-CN interactions was associated with improved survival. Using a deep learning model trained on engineered spatial data, we can with high accuracy (mean AUC of 5-fold cross-validation = 0.71) how a separate cohort of patients in the NeoTRIP clinical trial will respond to treatment based on baseline TME features. These data reinforce that the TME architecture is structured in cellular compositions, spatial organizations, vasculature biology, and molecular profiles, and suggest novel imaging-based biomarkers for treatment development in the context of TNBC.