Effect of Aging on Long-Term Functional Outcomes After Open Partial Laryngectomy.

OBJECTIVE: Open partial horizontal laryngectomies (OPHLs) represent a comparable alternative to total laryngectomy and nonsurgical protocols in selected cases. While short-term functional outcomes of OPHLs have been widely investigated, few have focused on the effect of aging on residual laryngeal structures. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic center. METHODS: Patients who underwent OPHLs after at least 1 year follow-up and optimal functional rehabilitation were included in the study. Swallowing function was assessed according to PAS (Penetration aspiration scale) and Pooling scores. Spectrogram analysis of voice was conducted according to Yanagihara classification and acoustic parameters were also recorded. Subjective questionnaire data about phonation and swallowing were also recorded. Data obtained were compared among patients according to age at time of surgery, evaluation and duration of follow-up. RESULTS: Ninety-seven patients were enrolled with a mean age at surgery and evaluation of 63 and 70 years old, respectively. Median follow-up length was 5 years. OPHL type II was mostly performed. No significant correlation was observed between most of the analyzed variables and patient's age at the time of surgery and at the time of evaluation. Some acoustic parameters were negatively correlated with follow-up length, while Jitter, NHR (Noise-Harmonic Ratio), and Global grade and Roughness were significantly higher in patients >65 years old. CONCLUSION: Patients who complete rehabilitation reach equally good results as their younger peers with stability over time. Finally, the effects of aging on residual larynx are of minor entity compared to the nonoperated patients. LEVEL OF EVIDENCE: Level IV-retrospective cohort study.

Loneliness and global cognitive functioning in racially and ethnically diverse US midlife and older adults.

Introduction: Few studies have examined the association of loneliness and cognitive functioning in the US. We used two common measures of loneliness and examined their association in a large sample of US Black, Latino, and White adults (ages ≥ 50). Methods: We analyzed Wave 3 of the National Social Life, Health, and Aging Project (N = 2,757). We examined loneliness using one item from the CES-D and the Felt Loneliness Measure (NFLM); cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA) tool, where higher scores indicated better functioning. We used weighted ordinary least squares regressions to examine the effects of loneliness (CES-D loneliness and NFLM in separate models) on MoCA scores. In exploratory analyses, we examined if these relationships varied by race and ethnicity. We adjusted all models for sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone). Results: Mean age was 63.49 years, 52% were female, and 9% were Black and 6% Latino persons. Approximately 54% endorsed feeling lonely on at least one measure; 31% (CES-D) and 46% (NFLM). The relationship between loneliness measures was positive and significant, X 2 (1, N = 2,757) = 435.493 p < 0.001. However, only 40% of lonely individuals were identified as lonely on both assessments. CES-D loneliness was inversely (߈ = -0.274, p = 0.032) associated with MoCA scores and this association did not vary by race and ethnicity. Greater NFLM loneliness was positively associated (߈ = 0.445, p < 0.001) with higher MoCA scores for Latino participants only. Discussion: Loneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning varied when using the CES-D loneliness item or the NFLM. Future work is needed to understand how loneliness and its clinically relevant dimensions (social, emotional, existential, chronicity) relate to global and individual cognitive domains. Research is needed with racially and ethnically diverse midlife and older adults, particularly to understand our counterintuitive finding for Latino participants. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.

[Recommendations for the management of latex allergy in pediatrics]. / Recomendaciones para el manejo de la alergia al látex en pediatría.

Latex allergy, or natural rubber latex allergy (NRLA), is a global health concern, even among the pediatric population, with symptoms varying in severity from mild to potentially life-threatening. Latex is derived from the Hevea Brasiliensis tree, producing twelve million tons annually for use in various everyday and medical products. Despite efforts to mitigate NRLA, its prevalence remains high, especially in at- risk groups such as children with spina bifida. Clinical manifestations include immediate and delayed symptoms, even anaphylactic reactions. Diagnosis involves a detailed medical history and specific tests. Prevention focuses on avoiding exposure, especially in medical and educational settings. Treatment, including immunotherapy, exhibits variable efficacy. NRLA has a strong negative impact on children's quality of life. The objective of this publication is to provide updated information and practical tools for the pediatrician's and allergist's practice.

La alergia al látex del caucho natural (ALCN) es un problema de salud global, incluso en población pediátrica, con síntomas de gravedad variable, desde leves hasta potencialmente mortales. El látex se obtiene del árbol Hevea brasiliensis; se producen doce millones de toneladas anuales que se utilizan en diversos productos cotidianos y médicos. A pesar de los esfuerzos para mitigar la ALCN, su prevalencia sigue siendo alta, especialmente en grupos de riesgo, como niños con espina bífida. Las manifestaciones clínicas incluyen síntomas inmediatos y retardados, hasta reacciones anafilácticas. El diagnóstico requiere una historia clínica detallada y pruebas específicas. La prevención se centra en evitar la exposición, especialmente en entornos médicos y escolares. El tratamiento, incluida la inmunoterapia, muestra eficacia variable. La ALCN tiene un fuerte impacto negativo en la calidad de vida. El objetivo de esta publicación es proveer información actualizada y herramientas prácticas para el consultorio del pediatra y el alergólogo.

Elements of Weight Management Among Pre-Kidney Transplant Candidates: The Patient Perspective.

Obesity and related comorbidities heighten risks for complications in kidney transplant settings. While pre-transplant patients often have access to nutrition counseling and health support, literature is limited on patients' perceptions of weight and motivation to lose weight prior to transplantation. We conducted a survey among ≥18-year-old patients on the kidney transplant waitlist at a single center. Questions addressed weight perception, motivation for weight loss, available resources, and engagement in physical activity. Medical records provided demographic and clinical data. Statistical tests analyzed quantitative data, while free-text responses were thematically grouped and described. Of 1055 patients, 291 responded and were matched with demographic data. Perceived weight changes correlated with actual changes in body mass index (BMI) (<24.9) were more receptive to weight center resources (<30 kg/m2) are most interested in weight loss resources and demonstrate motivation. Furthermore, pre-transplant nutrition counseling correlates with healthier behaviors. Integrating patients' perspectives enhances pre-transplant protocols by encouraging active involvement in health decisions.

HLA Genotype Imputation Results in Largely Accurate Epitope Mismatch Risk Categorization Across Racial Groups.

Background: Biomarkers that predict posttransplant alloimmunity could lead to improved long-term graft survival. Evaluation of the number of mismatched epitopes between donor and recipient HLA proteins, termed molecular mismatch analysis, has emerged as an approach to classify transplant recipients as having high, intermediate, or low risk of graft rejection. When high-resolution genotypes are unavailable, molecular mismatch analysis requires algorithmic assignment, or imputation, of a high-resolution genotyping. Although imputation introduces inaccuracies in molecular mismatch analyses, it is unclear whether these inaccuracies would impact the clinical risk assessment for graft rejection. Methods: Using renal transplant patients and donors from our center, we constructed cohorts of surrogate donor-recipient pairs with high-resolution and low-resolution HLA genotyping that were racially concordant or discordant. We systemically assessed the impact of imputation on molecular mismatch analysis for cohorts of 180-200 donor-recipient pairs for each of 4 major racial groups. We also evaluated the effect of imputation for a racially diverse validation cohort of 35 real-world renal transplant pairs. Results: In the surrogate donor-recipient cohorts, imputation preserved the molecular mismatch risk category for 90.5%-99.6% of racially concordant donor-recipient pairs and 92.5%-100% of racially discordant pairs. In the validation cohort, which comprised 72% racially discordant pairs, we found that imputation preserved the molecular mismatch risk category for 97.1% of pairs. Conclusions: Overall, these data demonstrate that imputation preserves the molecular mismatch risk assessment in the vast majority of cases and provides evidence supporting imputation in the performance of molecular mismatch analysis for clinical assessment.

Expression of tumor antigens within an oncolytic virus enhances the anti-tumor T cell response.

Although patients benefit from immune checkpoint inhibition (ICI) therapy in a broad variety of tumors, resistance may arise from immune suppressive tumor microenvironments (TME), which is particularly true of hepatocellular carcinoma (HCC). Since oncolytic viruses (OV) can generate a highly immune-infiltrated, inflammatory TME, OVs could potentially restore ICI responsiveness via recruitment, priming, and activation of anti-tumor T cells. Here we find that on the contrary, an oncolytic vesicular stomatitis virus, expressing interferon-ß (VSV-IFNß), antagonizes the effect of anti-PD-L1 therapy in a partially anti-PD-L1-responsive model of HCC. Cytometry by Time of Flight shows that VSV-IFNß expands dominant anti-viral effector CD8 T cells with concomitant relative disappearance of anti-tumor T cell populations, which are the target of anti-PD-L1. However, by expressing a range of HCC tumor antigens within VSV, combination OV and anti-PD-L1 therapeutic benefit could be restored. Our data provide a cautionary message for the use of highly immunogenic viruses as tumor-specific immune-therapeutics by showing that dominant anti-viral T cell responses can inhibit sub-dominant anti-tumor T cell responses. However, through encoding tumor antigens within the virus, oncolytic virotherapy can generate anti-tumor T cell populations upon which immune checkpoint blockade can effectively work.

Hypoxia Increases the Efficiencies of Cellular Reprogramming and Oncogenic Transformation in Human Blood Cell Subpopulations In Vitro and In Vivo.

Patients with chronic hypoxia show a higher tumor incidence; however, no primary common cause has been recognized. Given the similarities between cellular reprogramming and oncogenic transformation, we directly compared these processes in human cells subjected to hypoxia. Mouse embryonic fibroblasts were employed as controls to compare transfection and reprogramming efficiency; human adipose-derived mesenchymal stem cells were employed as controls in human cells. Easily obtainable human peripheral blood mononuclear cells (PBMCs) were chosen to establish a standard protocol to compare cell reprogramming (into induced pluripotent stem cells (iPSCs)) and oncogenic focus formation efficiency. Cell reprogramming was achieved for all three cell types, generating actual pluripotent cells capable for differentiating into the three germ layers. The efficiencies of the cell reprogramming and oncogenic transformation were similar. Hypoxia slightly increased the reprogramming efficiency in all the cell types but with no statistical significance for PBMCs. Various PBMC types can respond to hypoxia differently; lymphocytes and monocytes were, therefore, reprogrammed separately, finding a significant difference between normoxia and hypoxia in monocytes in vitro. These differences were then searched for in vivo. The iPSCs and oncogenic foci were generated from healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). Although higher iPSC generation efficiency in the patients with COPD was found for lymphocytes, this increase was not statistically significant for oncogenic foci. Remarkably, a higher statistically significant efficiency in COPD monocytes was demonstrated for both processes, suggesting that physiological hypoxia exerts an effect on cell reprogramming and oncogenic transformation in vivo in at least some cell types.

The dynamics of cyclic-periodic phenomena during non-rapid and rapid eye movement sleep.

Sleep is a complex physiological state characterized by distinct stages, each exhibiting unique electroencephalographic patterns and physiological phenomena. Sleep research has unveiled the presence of intricate cyclic-periodic phenomena during both non-rapid eye movement and rapid eye movement sleep stages. These phenomena encompass a spectrum of rhythmic oscillations and periodic events, including cyclic alternating pattern, periodic leg movements during sleep, respiratory-related events such as apneas, and heart rate variability. This narrative review synthesizes empirical findings and theoretical frameworks to elucidate the dynamics, interplay and implications of cyclic-periodic phenomena within the context of sleep physiology. Furthermore, it invokes the clinical relevance of these phenomena in the diagnosis and management of sleep disorders.

Association of Age at Menarche with Inflammation and Glucose Metabolism Biomarkers in U.S. Adult Women: NHANES 1999-2018.

CONTEXT: Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown. OBJECTIVE: We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among U.S. adult women who were free of diabetes. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19,228 women over 20 years old who were free of self-reported cancer and diabetes were included in this cross-sectional analysis. AAM was the self-reported age at first menstruation. CRP, fasting glucose, fasting insulin, and ferritin levels were measured as biomarkers of inflammation and glucose metabolism in adult blood samples using latex-enhanced nephelometry, enzymatic, and immunoassay methods. Multiple linear regression was used to relate AAM to the biomarkers. RESULTS: The median age at the time of blood sample collection was 44 years (IQR, 33-62). After age adjustment, there was an association between a lower AAM and higher CRP (P-trend=0.006); fasting glucose (P-trend<0.0001); fasting insulin (P-trend <0.0001); and ferritin (p-trend<0.0001). These remained significant after additional adjustment for demographic, reproductive, lifestyle, and adiposity variables, except for ferritin. Smoking modified the effect of AAM on CRP (p-interaction = 0.014), fasting insulin (p-interaction <0.001), and fasting glucose (p-interaction<0.001). In stratified analysis, the observed associations became more pronounced in non-smokers, while they were attenuated to non-significance in active smokers. CONCLUSION: Earlier age at menarche is associated with an unfavorable inflammatory and glucose metabolic biomarker profile in a nationally representative sample of adult women free of diabetes, especially among non-smokers.

New bioelectrode based on graphene quantum dots-polypyrrole film and Concanavalin A for pathogenic microorganism detection.

Infections caused by microorganisms are a public health problem worldwide. New biodetection systems are essential to diagnose with accuracy resulting in more effective treatment. In this work, we propose a ConA-conjugated graphene quantum dots and polypyrrole film-based biosensor for label-free detection of Candida albicans, Candida glabrata, Candida tropicalis, E. coli, B. subitilis, and S. aureus. We modified polypyrrole and graphene quantum dots (PPY-QDGs) with Concanavalin A (Con A) lectin. ConA is a glucose/mannose-specific lectin. The results showed that ConA lectin has the highest binding affinity for C. tropicalis and S. subtilis. PPY-GQDs-ConA binding profile revealed differential response for Candida spp (C. tropicalis > C. albicans > C. glabrata) and bacterial (B. subtilis > S. aureus > E. coli). The limits of detection (LOD) obtained were 1.42 CFU/mL for C. albicans, and 3.72 CFU/mL for C. glabrata. C. tropicalis yielded a LOD of 0.18 CFU/mL. The respective LODs for the evaluated bacteria were 0.39 CFU/mL for S. aureus, 0.72 CFU/mL for S. subtilis, and 2.63 CFU/mL for E. coli. The differential response obtained for the sensor can be attributed to the heterogeneous distribution of carbohydrates on the microorganism's surfaces. The proposed system based on a flexible substrate is effective for microbiological diagnosis.

Endometriosis, Severe Maternal Morbidity, and the effect of Infertility: Population-Based Cohort Study.

This population-based cohort evaluated the association between endometriosis and severe maternal morbidity (SMM), and the mediating effect of infertility and fertility treatment. Included were all singleton deliveries in Ontario between 2006 and 2014. Modified Poisson regression generated adjusted relative risks (aRRs). Mediation analysis estimated direct effect of endometriosis and indirect effect through infertility and mode of conception. 787 449 deliveries were included (19 099, 2.4% with endometriosis). SMM occurred in 29.0 per 1000 deliveries among women with endometriosis, in contrast to 18.2 per 1000 deliveries among those without endometriosis-corresponding to an adjusted RR of SMM of 1.43 (95% CI 1.31-1.56). Mediation analysis demonstrated that the effect of endometriosis on SMM was independent of infertility or fertility treatment. We conclude that SMM in women with endometriosis appears to be due to the disease itself and not to infertility or related treatments.

A targeted likelihood estimation comparing cefepime and piperacillin/tazobactam in critically ill patients with community-acquired pneumonia (CAP).

Cefepime and piperacillin/tazobactam are antimicrobials recommended by IDSA/ATS guidelines for the empirical management of patients admitted to the intensive care unit (ICU) with community-acquired pneumonia (CAP). Concerns have been raised about which should be used in clinical practice. This study aims to compare the effect of cefepime and piperacillin/tazobactam in critically ill CAP patients through a targeted maximum likelihood estimation (TMLE). A total of 2026 ICU-admitted patients with CAP were included. Among them, (47%) presented respiratory failure, and (27%) developed septic shock. A total of (68%) received cefepime and (32%) piperacillin/tazobactam-based treatment. After running the TMLE, we found that cefepime and piperacillin/tazobactam-based treatments have comparable 28-day, hospital, and ICU mortality. Additionally, age, PTT, serum potassium and temperature were associated with preferring cefepime over piperacillin/tazobactam (OR 1.14 95% CI [1.01-1.27], p = 0.03), (OR 1.14 95% CI [1.03-1.26], p = 0.009), (OR 1.1 95% CI [1.01-1.22], p = 0.039) and (OR 1.13 95% CI [1.03-1.24], p = 0.014)]. Our study found a similar mortality rate among ICU-admitted CAP patients treated with cefepime and piperacillin/tazobactam. Clinicians may consider factors such as availability and safety profiles when making treatment decisions.

Quantitative and qualitative evaluation of microorganism profile identified in bioburden analysis in a biopharmaceutical facility in Brazil: Criteria for classification and management of results.

Microbiological contamination may cause microbial proliferation and consequently additional problems for pharmaceutical companies through production stoppage, product contamination, investigations of process deviations, out-of-specification results and product disposal. This is one of the major concerns of the regulatory health agencies. Microbiological load (bioburden) may represent a potential risk for patients if the sterilization process is not effective and/or due to the production of toxins. Although bioburden can be eliminated by terminal sterilization or filtration processes, it is important to monitor the amount and determine the identity and characteristics of the microorganisms present prior to final processing. The application of microorganism identification systems is crucial for identifying the type of contamination, which can be extremely useful for investigating. The aim of this study was to evaluate the profiles of microorganisms identified in bioburden assays from solutions, culture medias, and products (SCP) from a pharmaceutical industry facility. From 2018-2020, a total of 1,078 samples from 857 different lots of SCP were analyzed and isolated microorganisms were identified. A prefiltering step was included after March 2020, in order to reduce the bioburden before sterilizing filtration. Criteria for the definition and management of microorganisms identified were evaluated after an integrative bibliographic review, and three groups were proposed (critical, objectionable, and nonobjectionable microorganisms). For the samples that did not include prefiltering (n=636), 227 (35.7%) presented microbial growth. For those that included prefiltering, before prefiltering (n=221), 60.6% presented microbial growth, and after prefiltering, this value was reduced to 4.1%, which can be attributed to a contamination during the sampling or a wrong filtering. From the samples that presented microbial growth, 678 microorganisms were identified as bacteria and 59 as molds and yeasts. A total of 120 microorganisms (56 and 27 Gram-positive and negative bacteria, respectively, 31 yeasts, and six filamentous molds) could not be identified, and the remaining microorganisms were classified as objectionable (n=507; 82.2%), nonobjectionable (n=103; 16.7%) and critical (n=7; 1.1%). Most of the bioburden species (>80.0%) were considered objectionable microorganisms. A process for classification and management of bioburden analysis results based on a literature review of pathogenic and physiological characteristics of the microorganisms was proposed.

Incidence of type 1 diabetes in Sardinian children aged 0-14 years has almost doubled in the last twenty years. On top of the world.

AIMS: The primary objectives were to investigate the incidence rate (IR) of type 1 diabetes (T1D) in Sardinian children aged 0-14 years in 2019-2022 and to examine the temporal trend from 1989-1999. METHODS: Data from new-onset T1D patients aged 0-14 years who were residents of Sardinia were collected from all pediatric diabetology clinics. The overall, sex- and age specific (groups 0-4, 5-9, and 10-14 years), and calendar year IRs were calculated. The standardized IR (SIR) was also calculated using the direct method. Poisson regression was used to estimate the temporal trend in the SIRs from 1989-1999 to 2019-2022. RESULTS: In 2019-2022, 512 patients aged 0-14 years were diagnosed with T1D in Sardinia. The overall IR was 73.9 per 100,000 person-years (95 % CI 67.6-80.0). Since 1989, the SIR has increased by 2.3 % per year (CI 1.7-2.8, p < 0.0001). The frequency of ketoacidosis at onset was 26.4 %, with no significant differences among the four years. CONCLUSIONS: The incidence of T1D in Sardinia, unlike in other countries such as Finland, has almost doubled in the last 20 years, and currently, it appears to be the highest in the world.

Calcifediol or Corticosteroids in the Treatment of COVID-19: An Observational Study.

Medical treatment of coronavirus 19 disease (COVID-19) is a therapeutic challenge. The available data strongly suggest that calcifediol treatment may reduce the severity of COVID-19, and corticosteroids are the treatment of choice worldwide for severe COVID-19. Both have a very similar action profile, and their combined use in patients may modify the contribution of each administered compound. OBJECTIVE: To evaluate how treatment with calcifediol and/or corticosteroids in medical practice modified the need for ICU admission, death, or poor prognosis of patients hospitalized with COVID-19 during the first outbreaks. DESIGN, PATIENTS AND SETTING: A retrospective observational cohort study of patients admitted for COVID-19 to the Pneumology Unit of the Hospital Universitario Reina Sofía (Córdoba, Spain). INTERVENTIONS: Patients were treated with calcifediol or/and corticosteroids with the best available therapy and standard care, according to clinical practice guidelines. MEASUREMENTS: Admission to the intensive care unit (ICU) or death during hospitalization and poor prognosis. RESULTS: Seven hundred and twenty-eight patients were included. According to the treatment received, they were included in four groups: calcifediol (n = 68), glucocorticoids (n = 112), both (n = 510), or neither (n = 38). Of the 578 patients treated with calcifediol, 88 were admitted to the ICU (15%), while of the 150 not treated with calcifediol, 39 required ICU admission (26%) (p < 0.01). Among the patients taking calcifediol without glucocorticoids, only 4 of 68 (5.8%) required ICU admission, compared to 84 of 510 (16.5%) treated with both (p = 0.022). Of the 595 patients who had a good prognosis, 568 (82.01%) had received treatment with calcifediol versus the 133 patients with a poor prognosis, of whom 90 (67.66%) had received calcifediol (p < 0.001). This difference was not found for corticosteroids. INTERPRETATION: The treatment of choice for hospitalized patients with moderate or mild COVID-19 could be calcifediol, not administering corticosteroids, until the natural history of the disease reaches a stage of hyperinflammation.

Detection of Tumor-Associated Autoantibodies in the Sera of Pancreatic Cancer Patients Using Engineered MUC1 Glycopeptide Nanoparticle Probes.

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure-guided approach to develop unnatural glycopeptides as model antigens for tumor-associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot-blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best-discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19-9 and carcinoembryonic antigen (CEA).

Romosozumab versus parathyroid hormone receptor agonists: which osteoanabolic to choose and when.

Osteoanabolic agents are used as a first line treatment in patients at high fracture risk. The PTH receptor 1 (PTH1R) agonists teriparatide (TPTD) and abaloparatide (ABL) increase bone formation, bone mineral density (BMD), and bone strength by activating PTH receptors on osteoblasts. Romosozumab (ROMO), a humanized monoclonal antibody against sclerostin, dramatically but transiently stimulates bone formation and persistently reduces bone resorption. Osteoanabolic agents increase BMD and bone strength while being more effective than antiresorptives in reducing fracture risk in postmenopausal women. However, direct comparisons of the antifracture benefits of osteoanabolic therapies are limited. In a direct comparison of TPTD and ABL, the latter resulted in greater BMD increases at the hip. While no differences in vertebral or non-vertebral fracture risk were observed between the two drugs, ABL led to a greater reduction of major osteoporotic fractures. Adverse event profiles were similar between the two agents except for hypercalcemia, which occurred more often with TPTD. No direct comparisons of fracture risk reduction between ROMO and the PTH1R agonists exist. Individual studies have shown greater increases in BMD and bone strength with ROMO compared to TPTD in treatment-naïve women and in women previously treated with bisphosphonates. Some safety aspects, such as a history of tumor precluding the use of PTH1R agonists, and a history of major cardiovascular events precluding the use of ROMO, should also be considered when choosing between these agents. Lastly, convenience of administration, reimbursement by national health systems and length of clinical experience may influence patient choice.

Serum biomarkers for liver fibrosis assessment.

Liver fibrosis is the result of chronic liver injury of different etiologies produced by an imbalance between the synthesis and degeneration of the extracellular matrix and dysregulation of physiological mechanisms. Liver has a high regenerative capacity in the early stage of chronic diseases so a prompt liver fibrosis detection is important. Consequently, an easy and economic tool that could identify patients with liver fibrosis at the initial stages is needed. To achieve this, many non-invasive serum direct, such as hyaluronic acid or metalloproteases, and indirect biomarkers have been proposed to evaluate liver fibrosis. Also, there have been developed formulas that combine these biomarkers, some of them also introduce clinical and/or demographic parameters, like FIB-4, non-alcoholic fatty liver disease fibrosis score (NFS), enhance liver fibrosis (ELF) or Hepamet fibrosis score (HFS). In this manuscript we critically reviewed different serum biomarkers and formulas for their utility in the diagnosis and progression of liver fibrosis.

Polysomnographically Defined Restless Sleep Disorder and Periodic Limb Movements during Sleep in Children Born Prematurely.

INTRODUCTION: Children born prematurely (<37 weeks' gestation) are at increased risk of perinatal complications, comorbidities, and iron deficiency. Iron deficiency is associated with restless legs syndrome and periodic limb movement disorder. In this study, we assessed the prevalence of restless sleep disorder (RSD) and elevated periodic limb movements during sleep (PLMS) in children born prematurely who underwent polysomnography. METHODS: A retrospective chart review of sleep studies was conducted in children aged 1-18 years (median age 4 years) with a history of premature birth. Children with genetic syndrome, airway surgery, or tracheostomy were excluded. Three groups were compared: children with PLMS index >5, children with RSD, and children with neither elevated PLMS index nor RSD. RESULTS: During the study, 2577 sleep studies were reviewed. Ninety-two studies fit our criteria and were included in the analysis. The median age at birth was 31 weeks, and the interquartile range (IQR) was 27-34 weeks. A total of 32 (34.8%) children were referred for restless sleep and 55 (59.8%) for snoring. After polysomnography, 18% were found to have a PLMS index >5/h, and 14% fit the criteria for restless sleep disorder (RSD). There were no statistically significant differences in PSG parameters among the children with RSD, PLMS, and the remaining group, except for lower obstructive apnea/hypopnea index (Kruskal-Wallis ANOVA 8.621, p = 0.0135) in the RSD group (median 0.7, IQR 0.3-0.9) than in the PLMS (median 1.7, IQR 0.7-3.5) or the non-RSD/non-PLMS (median 2.0, IQR 0.8-4.5) groups. CONCLUSIONS: There was an elevated frequency of RSD and elevated PLMS in our cohort of children born prematurely. Children born prematurely are at higher risk of iron deficiency which can be a contributor factor to sleep -related movement disorders. These results add new knowledge regarding the prevalence of RSD and PLMS in these children.