[Translated article] Total hip arthroplasty with second generation dual mobility system as a treatment for primary coxarthrosis, medium-term results.

INTRODUCTION: Osteoarthritis is a disabling pathology characterised by joint pain and stiffness. A prevalence of coxarthrosis of 7.4% is reported in our country. Total hip joint replacement is indicated in advanced stages, a procedure that is not free of complications, the most frequent being prosthetic dislocation, which can be prevented with dual mobility systems. The following study aims to determine the rate of complications and clinical outcomes in dual mobility systems in primary coxarthrosis. MATERIALS AND METHODS: A retrospective study included 120 cases in 114 patients diagnosed with grade III coxarthrosis, mean age was 62.43 years, with a mean follow-up of 4.5 years. Joint replacement was performed by Hardinge approach. All cases were assessed clinically using the Harris Hip Score (HHS) and radiologically to demonstrate mid-term results. RESULTS: The preoperative value on the HHS scale had a mean of 56.45, postoperative at one month 74.23; 6 months 85.40; 1 year 94.01 and at 5 years 94.84 points, representing a functional improvement of 17.78 postoperative month; 28.95 at 6 months postoperative; 37.56 at one year postoperative and 38.39 points at 5 years postoperative. A complication rate of 3.44%; 0.86% of complications were associated with the prosthetic components. CONCLUSION: The dual mobility system should be considered as a therapeutic option in primary hip joint replacement due to excellent functional results and low complication rates. EVIDENCE LEVEL: IV. Retrospective observational case series study.

Alterations in Neural Activation During Facial Emotion Processing in Adolescent Male Participants With Klinefelter Syndrome.

OBJECTIVE: Klinefelter syndrome (KS) is the most common sex-chromosome aneuploidy (47,XXY), affecting 1 in 500 male participants. The phenotype of male participants with KS includes both physical features, such as tall stature and testicular insufficiency, and behavioral alterations, including difficulties in social functioning, anxiety, and depression. Studies examining underlying neural alterations associated with the behavioral phenotype, however, are sparse. We aimed to address this gap in knowledge using functional magnetic resonance imaging in conjunction with an emotion processing paradigm. METHOD: Functional magnetic resonance imaging was conducted on 38 children and adolescents with KS (Mage = 12.85, SD = 2.45) and 47 typical developing (control) boys (Mage = 12.04, SD = 1.82) as they completed a facial emotion processing task. Group differences in activation occurring during the processing of angry versus neutral faces were examined while controlling for age. RESULTS: The results indicated that relative to typically developing boys, boys with KS exhibited anomalous increases in activation of frontal, temporal, and occipital cortices. Within the KS group, secondary analyses indicated that greater activation in these regions was associated with more internalizing symptoms (e.g., anxiety, depression, withdrawn behaviors) and greater social impairments (e.g., social cognition, social communication, social motivation, social communication and interaction, functional communication). CONCLUSION: The findings from this study indicate a possible neural correlation for difficulties in social and emotional function in KS and add to a growing body of research aimed at increasing our understanding of neural biomarkers in this condition. Future studies that examine the influence of testosterone-replacement therapy on these differences are warranted.

A novel protocol for three-dimensional mapping of sand tiger shark (Carcharias taurus) enclosure use in aquaria: Implications for management.

This study investigated sand tiger shark (STS; Carcharias taurus) spatial use and exclusion in public aquarium enclosures using a novel protocol for three-dimensional mapping. Fifty-one STS were observed in 14 enclosures, and swimming pattern, depth, and location were recorded in ZooMonitor. Data were converted into quantitative, three-dimensional representations using ArcGIS® Pro v. 2.9. All observed STS except one swam in circular patterns, and 80% (n = 41) showed a directional swimming bias. Most STS (80%; n = 41) predominantly utilized the top two-thirds of the enclosures, though 83% (n = 34) of those had swimming obstructions in the bottom of the enclosure. Avoidance of obstructed areas, sections <7 m wide, as well as behavioral spatial separation, resulted in utilization of between 27% and 66% of available enclosure space. STS underutilized corners, pinch-points, and obstructed areas requiring abrupt directional changes and instead exhibited continual, unimpeded swimming patterns. In addition, this study found no relationship between directional swimming bias or use of smaller enclosure volumes and spinal deformity, a health issue affecting 26% of STS 10 years ago but now with an incidence of 6%. Using novel protocols for three-dimensional mapping and volume estimation, this study demonstrated that enclosures facilitating unimpeded, continuous swimming are most usable for STS and provides important information that will be useful for future enclosure design.

Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome. METHODS: We recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed. RESULTS: We found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition. CONCLUSION: Our results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.

Hypothalamic AgRP neurons regulate the hyperphagia of lactation.

OBJECTIVE: The lactational period is associated with profound hyperphagia to accommodate the energy demands of nursing. These changes are important for the long-term metabolic health of the mother and children as altered feeding during lactation increases the risk of mothers and offspring developing metabolic disorders later in life. However, the specific behavioral mechanisms and neural circuitry mediating the hyperphagia of lactation are incompletely understood. METHODS: Here, we utilized home cage feeding devices to characterize the dynamics of feeding behavior in lactating mice. A combination of pharmacological and behavioral assays were utilized to determine how lactation alters meal structure, circadian aspects of feeding, hedonic feeding, and sensitivity to hunger and satiety signals in lactating mice. Finally, we utilized chemogenetic, immunohistochemical, and in vivo imaging approaches to characterize the role of hypothalamic agouti-related peptide (AgRP) neurons in lactational-hyperphagia. RESULTS: The lactational period is associated with increased meal size, altered circadian patterns of feeding, reduced sensitivity to gut-brain satiety signals, and enhanced sensitivity to negative energy balance. Hypothalamic AgRP neurons display increased sensitivity to negative energy balance and altered in vivo activity during the lactational state. Further, using in vivo imaging approaches we demonstrate that AgRP neurons are directly activated by lactation. Chemogenetic inhibition of AgRP neurons acutely reduces feeding in lactating mice, demonstrating an important role for these neurons in lactational-hyperphagia. CONCLUSIONS: Together, these results show that lactation collectively alters multiple components of feeding behavior and position AgRP neurons as an important cellular substrate mediating the hyperphagia of lactation.

Transorbital Ultrasound in the Diagnosis of Giant Cell Arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß=-1.91; p=0.029; EDV: ß=-0.57; p=0.032) and significantly elevated OND (ß = 0.79; p=0.003) compared with controls. RI did not significantly differ from controls (ß=-0.06, p=0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (p=0.048) and EDV (p=0.040). No association was found with RI (p=0.249), while a positive significant association was noted with OND (p<0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Workforce strategies during the first wave of the COVID-19 pandemic: a retrospective online survey at intensive care units in Germany.

BACKGROUND: As the COVID-19 pandemic swept across the globe at the beginning of 2020, healthcare systems were forced to rapidly adapt and expand to meet the sudden surge in demand for intensive care services. This study is the first systematic analysis of the strategies employed by German hospitals to recruit personnel and expand bed capacities during the first wave of the pandemic, and to evaluate the effectiveness of those recruitment measures. METHODS: 152 German hospitals with intensive care capacities were selected and invited to participate in an online-based retrospective survey. Factors like the geographic distribution, individual COVID burden and level of care were considered for inclusion in the sample. The data were analyzed descriptively. RESULTS: A total of 41 hospitals participated in the survey. The additional demand for intensive care beds was met primarily by activating intensive care beds that were previously considered as non-operational in existing intensive care units (81% of respondents) and by upgrading recovery rooms (73%). The physician staffing requirements were met at approximately 75%, while the nursing staffing requirements were only met by about 45%. Staffing needs were met through reallocations/transfers (85%), staff recruitment from parental leave or retirement (49%), increased hours worked by internal staff (49%), new staff hiring (44%) and increased use of temporary staff (32%). Staff reallocations/transfers to critical care within a hospital were rated as the most effective measure. In this context, specialized personnel mostly from anesthesiology departments were appointed to intensive care medicine. CONCLUSIONS: Despite multiple recruitment efforts, the pandemic has exacerbated the nursing staff shortage. The reallocation of existing staff within hospitals was a key element in covering the staffing needs. However, additional measures and efforts are required in order to ensure that critically ill patients can be cared for without compromise. The results of this study may have important implications for healthcare providers and policymakers, offering an evidence-based foundation for responding to future public health emergencies with agility, efficiency, and success.

Pediatric Pulmonary Milestones 2.0: Development, Lessons Learned, and Future Directions.

Pediatric pulmonology fellowship training programs are required by the Accreditation Council for Graduate Medical Education to report Pediatric Subspecialty Milestones biannually to track fellow progress. However, several issues, such as lack of subspecialty-specific context and ambiguous language, have raised concerns about their validity and applicability to use for fellow assessment and curriculum development. In this Perspective, we briefly share the process of the Pediatric Pulmonology Milestones 2.0 Work Group in creating new specialty-specific Milestones and tailoring information on the Harmonized Milestones to pediatric pulmonologists, with the goal of improving the Milestones' utility for stakeholders, including pulmonology fellows, faculty, program directors, and accrediting bodies. In addition, we created a supplemental guide to better link the Milestones to pulmonary-specific scenarios to create a shared mental model between stakeholders and remove a potential detriment to validity. Through the process, a number of guiding principles were clarified, including: 1) every Milestone should be able to be assessed independently, without overlap with other Milestones; 2) there should be clear developmental progression from one Milestone to the next; 3) Milestones should be based on the unique skills expected of pediatric pulmonologists; and 4) health equity should be a core component to highlight as a top priority to all stakeholders. In this Perspective, we describe these principles that guided formulation of the Pediatric Pulmonary Milestones to help familiarize the pediatric pulmonary community with the new Milestones. In addition, we share lessons learned and challenges in our process to inform other specialties that may soon participate in this process.

Outcome and microbiological findings of patients with cardiac implantable electronic device infection.

INTRODUCTION: Infections associated with cardiac implantable electronic devices (CIEDs) are a multifactorial disease that leads to increased morbidity and mortality. OBJECTIVE: The aim was to analyze patient-, disease- and treatment-related characteristics including microbiological and bacterial spectrum according to survival status and to identify risk factors for 1- and 3-year mortality in patients with local and systemic CIED infection. METHODS: In a retrospective cohort study, we analyzed data from patients with CIED-related local or systemic infection undergoing successful transvenous lead extraction (TLE). Survival status as well as incidence and cause of rehospitalization were recorded. Microbiology and antibiotics used as first-line therapy were compared according to mortality. Independent risk factors for 1- and 3-year mortality were determined. RESULTS: Data from 243 Patients were analyzed. In-hospital mortality was 2.5%. Mortality rates at 30 days, 1- and 3 years were 4.1%, 18.1% and 30%, respectively. Seventy-four (30.5%) patients had systemic bacterial infection. Independent risk factors for 1-year mortality included age (OR 1.05 [1.01-1.10], p = 0.014), NT-proBNP at admission (OR 4.18 [1.81-9.65], p = 0.001), new onset or worsened tricuspid regurgitation after TLE (OR 6.04 [1.58-23.02], p = 0.009), and systemic infection (OR 2.76 [1.08-7.03], p = 0.034), whereas systemic infection was no longer an independent risk factor for 3-year mortality. Staphylococcus aureus was found in 18.1% of patients who survived and in 25% of those who died, p = 0.092. There was a high proportion of methicillin-resistant strains among coagulase-negative staphylococci (16.5%) compared to Staphylococcus aureus (1.2%). CONCLUSIONS: Staphylococci are the most common causative germs of CIED-infection with coagulase-negative staphylococci showing higher resistance rates to antibiotics. The independent risk factors for increased long-term mortality could contribute to individual risk stratification and well-founded treatment decisions in clinical routine. Especially the role of tricuspid regurgitation as a complication after TLE should be investigated in future studies.

Telocytes: current methods of research, challenges and future perspectives.

Telocytes (TCs) are CD34-positive interstitial cells that have long cytoplasmic projections, called telopodes; they have been identified in several organs and in various species. These cells establish a complex communication network between different stromal and epithelial cell types, and there is growing evidence that they play a key role in physiology and pathology. In many tissues, TC network impairment has been implicated in the onset and progression of pathological conditions, which makes the study of TCs of great interest for the development of novel therapies. In this review, we summarise the main methods involved in the characterisation of these cells as well as their inherent difficulties and then discuss the functional assays that are used to uncover the role of TCs in normal and pathological conditions, from the most traditional to the most recent. Furthermore, we provide future perspectives in the study of TCs, especially regarding the establishment of more precise markers, commercial lineages and means for drug delivery and genetic editing that directly target TCs.

Follow-up ultrasound examination in patients with newly diagnosed giant cell arteritis.

OBJECTIVES: Ultrasound is a standard tool to diagnose giant cell arteritis (GCA). Until now, only few studies investigated the role of ultrasound in the follow-up of GCA. The aim of this study was to assess the changes in the intima media thickness (IMT), total number of affected arteries and provisional OMERACT GCA ultrasonography score (OGUS) in a 12-months follow-up period. METHODS: Patients with newly diagnosed GCA were prospectively enrolled. Ultrasound examinations of facial, temporal, carotid, vertebral and axillary arteries were performed at baseline, after three, six, nine and 12 months. Changes of IMT, total number of affected arteries, and OGUS values were evaluated. In a subgroup of patients, exams were conducted weekly in the first 100 days. RESULTS: Fifty patients were enrolled, 36 completed the follow-up. Significant reductions in IMT, total number of affected arteries and OGUS were observed. Eighteen patients presented to weekly exams. The mean IMT of the axillary artery normalized after seven days, while IMT of the common temporal artery normalized after 50 days. The mean OGUS values were below one after six months. There were no differences in IMT changes between GCA patients with or without PMR or between those with and without additional tocilizumab treatment. A relapse occurred in 4 patients. At relapse, mean IMT and OGUS were higher as compared with the preceding assessment. No predictive values indicating a relapse were identified. CONCLUSION: Vascular ultrasound is sensitive to change in GCA. The presence of PMR or treatment with tocilizumab did not affect IMT decrease.

Molecular characteristics and improved survival prediction in a cohort of 2023 ependymomas.

The diagnosis of ependymoma has moved from a purely histopathological review with limited prognostic value to an integrated diagnosis, relying heavily on molecular information. However, as the integrated approach is still novel and some molecular ependymoma subtypes are quite rare, few studies have correlated integrated pathology and clinical outcome, often focusing on small series of single molecular types. We collected data from 2023 ependymomas as classified by DNA methylation profiling, consisting of 1736 previously published and 287 unpublished methylation profiles. Methylation data and clinical information were correlated, and an integrated model was developed to predict progression-free survival. Patients with EPN-PFA, EPN-ZFTA, and EPN-MYCN tumors showed the worst outcome with 10-year overall survival rates of 56%, 62%, and 32%, respectively. EPN-PFA harbored chromosome 1q gains and/or 6q losses as markers for worse survival. In supratentorial EPN-ZFTA, a combined loss of CDKN2A and B indicated worse survival, whereas a single loss did not. Twelve out of 200 EPN-ZFTA (6%) were located in the posterior fossa, and these tumors relapsed or progressed even earlier than supratentorial tumors with a combined loss of CDKN2A/B. Patients with MPE and PF-SE, generally regarded as non-aggressive tumors, only had a 10-year progression-free survival of 59% and 65%, respectively. For the prediction of the 5-year progression-free survival, Kaplan-Meier estimators based on the molecular subtype, a Support Vector Machine based on methylation, and an integrated model based on clinical factors, CNV data, and predicted methylation scores achieved balanced accuracies of 66%, 68%, and 73%, respectively. Excluding samples with low prediction scores resulted in balanced accuracies of over 80%. In sum, our large-scale analysis of ependymomas provides robust information about molecular features and their clinical meaning. Our data are particularly relevant for rare and hardly explored tumor subtypes and seemingly benign variants that display higher recurrence rates than previously believed.

Monoclonal Antibody Infusions for Outpatient Management of Mild-Moderate COVID-19.

BACKGROUND: The COVID-19 pandemic has led to a rapid, exponential increase in hospitalizations and morbidity/mortality. In November 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) permitting administration of the first monoclonal antibodies (mAb) for outpatient treatment of COVID-19. Early data showed a reduction in COVID-19-related hospitalizations with few adverse events. However, since these treatments are only authorized under an EUA, real-world data are minimal. OBJECTIVE: To assess efficacy and safety of mAbs in a veteran population. METHODS: This retrospective study analyzed veterans at the Ralph H. Johnson Veterans Affairs Health Care System with mild-moderate COVID-19 and screened for mAb eligibility between December 1, 2020, and October 31, 2021. The primary outcome was hospitalizations and/or emergency department (ED) visits within 30 days. Secondary outcomes included 30-day mortality and post-COVID-19 conditions. Adverse events were also evaluated. Outcomes were compared between mAb-treated patients and eligible veterans who were not treated. RESULTS: There were 296 and 275 veterans in the mAb and control groups, respectively. No statistically significant difference was found for the primary outcome overall (25.7% vs 25.1%; P = 0.87), nor for COVID-19-related return visits or hospitalizations (13.9% v. 16%; P = 0.4). However, the mAb group had more return ED visits (P = 0.35), and the control group had significantly more hospitalizations (P = 0.02). Vaccinated veterans who received an mAb had fewer return visits and hospitalizations (P = 0.01). More mAb-treated veterans experienced post-COVID-19 conditions. No difference in mortality was found. Four nonsevere adverse events occurred after the mAb therapy. CONCLUSION AND RELEVANCE: Overall, the mAbs appeared safe and effective. Sicker, higher-risk mAb-treated veterans faired similarly to less-sick, high-risk veterans not treated. Those who were vaccinated seemed to benefit the most from mAb therapy. Future prospective studies with more matched groups are needed to assess full benefits and risks of mAbs shown to neutralize the predominant variants.