Computational Analysis of the Influence of Menopause and Ageing on Bone Mineral Density, Exploring the Impact of Bone Turnover and Focal Bone Balance-A Study on Overload and Underload Scenarios.

This study aims to investigate the impact of hormonal imbalances during menopause, compounded by the natural ageing process, on bone health. Specifically, it examines the effects of increased bone turnover and focal bone balance on bone mass. A three-dimensional computational bone remodeling model was employed to simulate the response of the femur to habitual loads over a 19-year period, spanning premenopause, menopause, and postmenopause. The model was calibrated using experimental bone mineral density data from the literature to ensure accurate simulations. The study reveals that individual alterations in bone turnover or focal bone balance do not fully account for the observed experimental outcomes. Instead, simultaneous changes in both factors provide a more comprehensive explanation, leading to increased porosity while maintaining the material-to-apparent density ratio. Additionally, different load scenarios were tested, demonstrating that reaching the clinical osteoporosis threshold is independent of the timing of load changes. However, underload scenarios resulted in the threshold being reached approximately 6 years earlier than overload scenarios. These findings hold significant implications for strategies aimed at delaying the onset of osteoporosis and minimizing fracture risks through targeted mechanical stimulation during the early stages of menopause.

Combined rapid sequence MRI protocol and skull radiography as an alternative to head CT in the evaluation of abusive head trauma in children: a pilot study.

The aim of our pilot study was to compare the performance of the RS-MRI protocol combined with skull radiography versus CT for the detection of skull fractures, scalp hematomas, and intracranial hemorrhage in patients with abusive head trauma (AHT). Additionally, our study aimed to determine whether the presence of scalp hematoma predicts concurrent skull fracture. We conducted a pilot study through retrospective chart review of 24 patients between ages 0 and 15 months who experienced AHT and who received CT, MRI, and skull radiography between May 2020 and August 2021. Two blinded board certified neuroradiologists reviewed the skull radiographs alongside the rapid trauma MRI. Their impressions were documented and compared with findings derived from CT. Combination imaging detected ten out of the 12 skull fractures noted on CT (sensitivity 83.3%, specificity 100%, p=0.48). RS-MRI detected 15 out of the 16 intracranial hemorrhages detected by CT (sensitivity 93.75%, p >0.9). When scalp hematoma was detected on RS-MRI, nine out of the 12 had associated skull fractures when reviewed by radiologist 1 (sensitivity 75%, specificity 100%, p=0.22), and seven out of the 12 had associated skull fractures when reviewed by radiologist 2 (sensitivity 58%, specificity 92%, p=0.25). In pediatric patients with suspected AHT, we found that RS-MRI combined with skull radiographs was not significantly different than CT for the detection of skull fractures, scalp hematomas, and intracranial hemorrhage. This combination has the potential to replace the use of CT as a screening tool for abusive head trauma, while avoiding the risks of sedation often required for routine MRI.

Imaging of Skull Base Tumors.

The skull base provides a platform for supporting the brain while serving as a conduit for major neurovascular structures. In addition to malignant lesions originating in the skull base, there are many benign entities and developmental variants that may simulate disease. Therefore, a basic understanding of the relevant embryology is essential. Lesions centered in the skull base can extend to the adjacent intracranial and extracranial compartments; conversely, the skull base can be secondarily involved by primary extracranial and intracranial disease. CT and MRI are the mainstay imaging methods and are complementary in the evaluation of skull base lesions. Advances in cross-sectional imaging have been crucial in the management of patients with skull base pathology, as this represents a complex anatomical area that is hidden from direct clinical exam. Furthermore, the clinician must rely on imaging studies for therapy planning and to monitor treatment response. It is crucial to have a thorough understanding of skull base anatomy and its various pathologies, as well as to recognize the appearance of treatment-related changes. In this review, we aim to describe skull base tumors and tumor-like lesions in an anatomical compartmental approach and present imaging methods that aid in diagnosis, management, and follow-up.

Dysregulated neutrophil extracellular traps formation in sepsis.

The migration and antimicrobial functions of neutrophils seem to be impaired during sepsis and contribute to the dysregulation of immune responses and disease pathogenesis. However, the role of neutrophil extracellular traps (NETs) remains to be clarified. The study aimed to analyse sequential phenotypic and functional changes of neutrophils during the time following the diagnosis of sepsis. We prospectively enrolled 49 septic and 18 non-septic patients from the intensive care unit (ICU) and emergency room (ER) and 20 healthy volunteers (HV). Baseline blood samples from septic and non-septic patients were collected within 12 h of admission to the hospital. Additional septic samples were drawn at 24, 48 and 72 h after baseline. Neutrophil phenotype and degranulation capacity were assessed by flow cytometry and NET formation was quantified by fluorescence. Neutrophils from septic patients exhibited increased CD66b, CD11b and CD177 expression but displayed reduced NET formation at baseline compared with non-septic patients and HV controls. Neutrophils expressing CD177 interacted less with platelets, were related to reduced NETosis and tended to indicate a worse sepsis outcome. In vitro experiments revealed that neutrophil function is compromised by the origin of sepsis, including the pathogen type and the affected organ. Assessing a decision tree model, our study showed that CD11b expression and NETosis values are useful variables to discriminate septic from non-septic patients. We conclude that sepsis induces changes in neutrophil phenotype and function that may compromise the effective capacity of the host to eliminate pathogens.

Bibliometric Analysis: Six Decades of Scientific Production from a Nationwide Institution: Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) from Mexico.

BACKGROUND: This study employed bibliometric analysis to ascertain the research focus areas among a group of Mexican physicians affiliated with the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE). ISSSTE, a healthcare institution catering to a diverse range of diseases, offers a distinctive perspective on the investigated specialties within the realm of health. The primary objective was to identify knowledge gaps in medical care disciplines through a comprehensive examination of scholarly publications. METHODS: We retrieved Scopus papers affiliated with "ISSSTE" and saved them as .CSV files. Subsequently, we employed VOSviewer, biblioshiny, and bibliometrix for bibliometric analysis. This enabled us to identify prominent institutions, prolific authors, highly cited researchers, and their respective affiliations. RESULTS: Our analysis identified 2063 publications; the specialty internal medicine accounted for the greatest proportion with 831 publications. Original papers accounted for 82% of the total, with 52% of them being written in Spanish. The majority of scientific output, 92%, originated from Mexico City. The annual production has steadily increased since 2010, peaking in 2021 with over 200 publications. However, papers on prevalent conditions, such as metabolic syndrome, received limited citations, and the L0 index (percentage of uncited items) for all papers is close to 60%. Scopus mislabeled one affiliation, and some cases show a low paper-to-author ratio of 0.5 Discussion: Additional concerns, such as honorary authorship due to excessive authors per paper, and the underlying causes of low citation rates in Mexican publications, warrant further examination. Moreover, our research emphasizes the urgency of bolstering research and development funding, which was consistently below 0.5% of GDP for the past four decades, falling short of legal mandates and international benchmarks. We endorse the establishment of robust research collectives in Latin America to address these challenges, foster regional scientific output, and transition from knowledge consumers to knowledge producers, thereby reducing dependence on foreign technology.

Troublemaking Lesions: Spinal Tumor Mimics.

There are various mass-like lesions that can mimic true neoplasms in the spine, including inflammatory, infectious, vascular, congenital, and degenerative etiologies. While some lesions have distinctive imaging features that suggest a correct diagnosis, others have overlapping characteristics that do not allow their differentiation based solely on their imaging findings. For entities with nonspecific imaging features, knowledge of the clinical and laboratory information is critical to provide an accurate diagnosis.

Bloqueo de plexo braquial con ultrasonido: estudio descriptivo de práctica clínica habitual en 283 niños / Brachial plexus block with ultrasound: a descriptive study of routine clinical practice in 283 children

Resumen: Introducción: en años recientes con el renacimiento de la anestesia regional a causa de los avances técnicos en equipamiento como el ultrasonido, estos han permitido llevar a cabo bloqueos de plexo braquial con varias técnicas de abordaje, alta eficacia de éxito y disminución de complicaciones. Objetivo: conocer la eficacia y seguridad del bloqueo de plexo braquial con ultrasonido, en anestesiólogos con especialidad en anestesia regional. Material y métodos: se realizó el estudio observacional, descriptivo y retrospectivo de la práctica clínica habitual en 283 pacientes de 0 a 15 años, programados para cirugía electiva de ortopedia y traumatología, de extremidad superior (húmero tercio distal, codo, antebrazo y mano), con manejo anestésico: sedación más bloqueo de plexo braquial con ultrasonido abordaje supraclavicular o infraclavicular. Durante dos años, de enero de 2018 a diciembre de 2019. Resultados: los bloqueos fueron realizados por 11 anestesiólogos con especialidad en anestesia regional. Se evaluó la eficacia con 99.65% de éxito. En cuanto a la seguridad no se registraron complicaciones. Conclusiones: el uso de ultrasonido en bloqueo de plexo braquial con abordaje supraclavicular e infraclavicular es una técnica con éxito alto y sin complicaciones; sin embargo, es necesario tener capacitación y experiencia.

Abstract: Introduction: in recent years with the revival of regional anesthesia due to technical advances in equipment such as ultrasound, have allowed to carry out brachial plexus blocks with several approach techniques with high efficiency of success and reduction of complications. Objective: to know the efficacy and safety of brachial plexus block with ultrasound, in anesthesiologists with a specialty in regional anesthesia. Material and methods: the observational, descriptive, retrospective study of the usual clinical practice was carried out in 283 patients from 0 to 15 years old, scheduled for elective orthopedic surgery and traumatology, of the upper extremity (distal third humerus, elbow, forearm and hand), with anesthetic management: sedation plus brachial plexus block with ultrasound supraclavicular or infraclavicular approach. For two years from January 2018 to December 2019. Results: the blocks were performed by 11 anesthesiologists specializing in regional anesthesia. Efficacy was evaluated with 99.65% success. In terms of safety, there were no complications. Conclusions: the use of ultrasound in brachial plexus block with supraclavicular and infraclavicular approach is a technique with high success and without complications however it is necessary to have training and experience.

Editorial Comment: Estimation of venous sinus pressure drop in patients with idiopathic intracranial hypertension using 4D-flow MRI.

KEY POINTS: • Work-energy equation using 4D-flow MRI is a promising technique for non-invasive estimation of trans-stenotic pressure drop in patients with idiopathic intracranial hypertension.• Additional research with larger and multicentric prospective cohorts is needed to validate the results, along with improvement of the segmentation process with automated techniques and shortening of scanning times to allow for practical clinical use.

Oncologic Emergencies in the Head and Neck.

Patients with head and neck cancers are susceptible to emergencies related to tumor infiltration, systemic disorders, or treatment. Computed tomography plays a major role in imaging assessment and MRI provides further characterization. Hematologic disorders may lead to hemorrhage, thrombosis, or ischemia. Patients are susceptible to metabolic derangements that are often not recognized. Complications in the neck are threatening due to compromise of vascular structures and airway.

Altered CD39 and CD73 Expression in Rheumatoid Arthritis: Implications for Disease Activity and Treatment Response.

In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8+CD39-CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39-CD73- cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA.

Day one postoperative MRI findings following electrode placement for deep brain stimulation: analysis of a large case series.

Objective: This study sought to characterize postoperative day one MRI findings in deep brain stimulation (DBS) patients. Methods: DBS patients were identified by CPT and had their reviewed by a trained neuroradiologist and neurosurgeon blinded to MR sequence and patient information. The radiographic abnormalities of interest were track microhemorrhage, pneumocephalus, hematomas, and edema, and the occurrence of these findings in compare the detection of these complications between T1/T2 gradient-echo (GRE) and T1/T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) sequences was compared. The presence, size, and association of susceptibility artifact with other radiographic abnormalities was also described. Lastly, the association of multiple microelectrode cannula passes with each radiographic finding was evaluated. Ad-hoc investigation evaluated hemisphere-specific associations. Multiple logistic regression with Bonferroni correction (corrected p = 0.006) was used for all analysis. Results: Out of 198 DBS patients reviewed, 115 (58%) patients showed entry microhemorrhage; 77 (39%) track microhemorrhage; 44 (22%) edema; 69 (35%) pneumocephalus; and 12 (6%) intracranial hematoma. T2 GRE was better for detecting microhemorrhage (OR = 14.82, p < 0.0001 for entry site and OR = 4.03, p < 0.0001 for track) and pneumocephalus (OR = 11.86, p < 0.0001), while T2 FLAIR was better at detecting edema (OR = 123.6, p < 0.0001). The relatively common findings of microhemorrhage and edema were best visualized by T2 GRE and T2 FLAIR sequences, respectively. More passes intraoperatively was associated with detection of ipsilateral track microhemorrhage (OR = 7.151, p < 0.0001 left; OR = 8.953, p < 0.0001 right). Susceptibility artifact surrounding electrodes possibly interfered with further detection of ipsilateral edema (OR = 4.323, p = 0.0025 left hemisphere only). Discussion: Day one postoperative magnetic resonance imaging (MRI) for DBS patients can be used to detect numerous radiographic abnormalities not identifiable on a computed tomographic (CT) scan. For this cohort, multiple stimulating cannula passes intraoperatively was associated with increased microhemorrhage along the electrode track. Further studies should be performed to evaluate the clinical relevance of these observations.

Response to Selpercatinib in a Patient With Recurrent Glioblastoma and RET Amplification.

Glioblastoma (GBM) is a malignant central nervous system neoplasm that remains largely incurable. Limited treatment options currently exist after disease progression on standard-of-care first-line therapy. However, repurposing the use of approved therapies in patients with potentially targetable genomic alterations continues to be an emerging area of interest. This report presents the first description of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response while receiving therapy with the RET inhibitor selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in the management of RET-amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. Given the rare incidence of RET alterations in GBM, findings from this report can help guide and support optimal treatment strategies for patients with RET-altered GBM.

Corrigendum: Patients with myeloproliferative neoplasms harbor high frequencies of CD8 T cell-platelet aggregates associated with T cell suppression.

[This corrects the article DOI: 10.3389/fimmu.2022.866610.].

Headache Attributed to Non-vascular Intracranial Disorder: Neoplasms, Infections, and Substance Abuse.

Evaluation of headaches warrants a careful history and neurologic assessment to determine the need for further workup and imaging. Identifying patients who are at risk for underlying pathology is important and this includes individuals with known or suspected malignancy and those who are immunocompromised and at increased risk for intracranial infection. While CT is helpful in the acute setting and to screen for intracranial hypertension, MRI is the modality of choice for the evaluation of underlying pathologies. Imaging in substance abuse may show injury related to direct toxicity or secondary to vascular complications.

Role of MRI and CT in the Evaluation of Headache in Pregnancy and the Postpartum Period.

Approximately 35% of acute headaches in pregnant women are secondary to an underlying condition. Headaches are also common in the postpartum period where they occur in 30% to 40% of patients. The majority of secondary headaches are due to hypertensive disorders: preeclampsia-eclampsia, posterior reversible encephalopathy syndrome, and acute arterial hypertension. Other causes include reversible cerebral vasoconstriction syndrome and pituitary apoplexy, as well as life-threatening conditions such as cerebral venous thrombosis. In this article, we review general recommendations for imaging the pregnant patients and discuss the imaging findings of common causes of headaches in pregnancy and the postpartum period.

Relationship between Anterior Pituitary Volume and IGF-1 Serum Levels in Soldiers with Mild Traumatic Brain Injury History.

PURPOSE: A high mild traumatic brain injury (mTBI) incidence rate exists in military and sport. Hypopituitarism is an mTBI sequela; however, few studies have examined this phenomenon in those with an mTBI history. This cross-sectional study of Special Operations Forces combat soldiers aimed 1) to relate anterior pituitary gland volumes (actual and normalized) to insulin-like growth factor 1 (IGF-1) concentrations, 2) to examine the effect of mTBI history on anterior pituitary gland volumes (actual and normalized) and IGF-1 concentrations, and 3) to measure the odds of demonstrating lower anterior pituitary gland volumes (actual and normalized) or IGF-1 concentrations if self-reporting mTBI history. METHODS: Anterior pituitary gland volumes were manually segmented from T1-weighted 3D brain MRI sequences; IGF-1 serum concentrations were quantified using commercial enzyme-linked immunosorbent assays. Correlations and linear regression were used to determine the association between IGF-1 serum concentration and anterior pituitary gland volume (n = 74). Independent samples t-tests were used to compare outcomes between mTBI groups and logistic regression models were fit to test the odds of demonstrating IGF-1 concentration or anterior pituitary volume less than sample median based on mTBI group (n = 54). RESULTS: A significant linear relationship between the subjects' anterior pituitary gland volumes and IGF-1 concentrations (r72 = 0.35, P = 0.002) was observed. Soldiers with mTBI history had lower IGF-1 concentrations (P < 0.001) and lower anterior pituitary gland volumes (P = 0.037) and were at greater odds for IGF-1 serum concentrations less than the sample median (odds ratio = 5.73; 95% confidence interval = 1.77-18.55). CONCLUSIONS: Anterior pituitary gland volume was associated with IGF-1 serum concentrations. Mild TBI history may be adversely associated with anterior pituitary gland volumes and IGF-1 concentrations. Longitudinal IGF-1 and anterior pituitary gland monitoring may be indicated in those who report one or more mTBI.

Influence of Malignant Pleural Fluid from Lung Adenocarcinoma Patients on Neutrophil Response.

Malignant pleural effusion (MPE) is a common severe complication of advanced lung adenocarcinoma (LAC). Neutrophils, an essential component of tumor infiltrates, contribute to tumor progression and their counts in MPE have been associated with worse outcome in LAC. This study aimed to evaluate phenotypical and functional changes of neutrophils induced by MPE to determine the influence of MPE immunomodulatory factors in neutrophil response and to find a possible association between neutrophil functions and clinical outcomes. Pleural fluid samples were collected from 47 LAC and 25 heart failure (HF) patients. We measured neutrophil degranulation products by ELISA, oxidative burst capacity and apoptosis by flow cytometry, and NETosis by fluorescence. The concentration of degranulation products was higher in MPE-LAC than in PE-HF. Functionally, neutrophils cultured with MPE-LAC had enhanced survival and neutrophil extracellular trap (NET) formation but had reduced oxidative burst capacity. In MPE, NETosis was positively associated with MMP-9, P-selectin, and sPD-L1 and clinically related to a worse outcome. This is the first study associating NETs with a worse outcome in MPE. Neutrophils likely contribute to tumor progression through the release of NETs, suggesting that they are a potential therapeutic target in LAC.

Increase of Circulating Monocyte-Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage.

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte−PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte−PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.

Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression.

Myeloproliferative neoplasms (MPN) are chronic cancers of the hematopoietic stem cells in the bone marrow, and patients often harbor elevated numbers of circulating platelets (PLT). We investigated the frequencies of circulating PLT-lymphocyte aggregates in MPN patients and the effect of PLT-binding on CD8 T cell function. The phenotype of these aggregates was evaluated in 50 MPN patients and 24 controls, using flow cytometry. In vitro studies compared the proliferation, cytokine release, and cytoxicity of PLT-bound and PLT-free CD8 T cells. Frequencies of PLT-CD8 T cell aggregates, were significantly elevated in MPN patients. Advanced disease stage and CALR mutation associated with the highest aggregate frequencies with a predominance of PLT-binding to antigen-experienced CD8 T cells. PLT-bound CD8 T cells showed reduction in proliferation and cytotoxic capacity. Our data suggest that CD8 T cell responses are jeopardized in MPN patients. JAK2 and CALR exon 9 mutations - the two predominant driver mutations in MPN - are targets for natural T cell responses in MPN patients. Moreover, MPN patients have more infections compared to background. Thus, PLT binding to antigen experienced CD8 T cells could play a role in the inadequacy of the immune system to control MPN disease progression and prevent recurrent infections.