Haemoglobinopathies and other rare anemias in Spain: ten years of a nationwide registry (REHem-AR).

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments.

Precursors to oliguria during major burn resuscitation: An analysis of a prospective observational trial at 5 major US burn centers.

Currently, urine output is the leading variable used to tailor fluid resuscitation in patients with large TBSA burns. However, this metric often lags with respect to resuscitation. Our group sought to identify derangements in variables that precede development of oliguria (<30 cc/hr) that we hypothesize will aid in more efficient resuscitation. We performed a retrospective analysis of 146 adult patients admitted within 4 h of a large TBSA (>20%) burn. We then divided them into two cohorts: those who developed oliguria within 6 h of admission and those who did not. Patients who experienced early oliguria had a higher incidence of invasive SBP < 90 (p = 0.02) or DBP < 40 (p = 0.009), lower minimum bicarbonate level (p = 0.04), more full thickness burns (p = 0.004), and higher TBSA (p = 0.01). More female patients were found in the oliguric group (p = 0.003). Multivariate analysis was used to develop a model to predict development of oliguria. When evaluated together, minimum DBP, sex, TBSA (or percent full thickness burn), and maximum base deficit constituted the most parsimonious model that significantly predicted oliguria (AUC = 0.92). Interestingly, the model lost significance when DBP was omitted, highlighting the importance of diastolic pressure in the development of oliguria.

Toward Smart, Automated Junctional Tourniquets-AI Models to Interpret Vessel Occlusion at Physiological Pressure Points.

Hemorrhage is the leading cause of preventable death in both civilian and military medicine. Junctional hemorrhages are especially difficult to manage since traditional tourniquet placement is often not possible. Ultrasound can be used to visualize and guide the caretaker to apply pressure at physiological pressure points to stop hemorrhage. However, this process is technically challenging, requiring the vessel to be properly positioned over rigid boney surfaces and applying sufficient pressure to maintain proper occlusion. As a first step toward automating this life-saving intervention, we demonstrate an artificial intelligence algorithm that classifies a vessel as patent or occluded, which can guide a user to apply the appropriate pressure required to stop flow. Neural network models were trained using images captured from a custom tissue-mimicking phantom and an ex vivo swine model of the inguinal region, as pressure was applied using an ultrasound probe with and without color Doppler overlays. Using these images, we developed an image classification algorithm suitable for the determination of patency or occlusion in an ultrasound image containing color Doppler overlay. Separate AI models for both test platforms were able to accurately detect occlusion status in test-image sets to more than 93% accuracy. In conclusion, this methodology can be utilized for guiding and monitoring proper vessel occlusion, which, when combined with automated actuation and other AI models, can allow for automated junctional tourniquet application.

Next-generation tourniquet: Recommendations for future capabilities and design requirements.

BACKGROUND: Advances in tourniquet development must meet new military needs for future large-scale combat operations or civilian mass casualty scenarios. This includes the potential use of engineering and automation technologies to provide advanced tourniquet features. A comprehensive set of design capabilities and requirements for an intelligent or smart tourniquet needed to meet the challenges currently does not exist. The goal of this project was to identify key features and capabilities that should be considered for the development of next-generation tourniquets. METHODS: We used a modified Delphi consensus technique to survey a panel of 34 tourniquet subject matter experts to rate various statements and potential design characteristics relevant to tourniquets systems and their use scenarios. Three iterative rounds of surveys were held, followed by virtual working group meetings, to determine importance or agreement with any given statement. We used a tiered consensus system to determine final agreement over key features that were viewed as important or unimportant features or capabilities. This information was used to refine and clarify the necessary tourniquet design features and adjust questions for the following surveys. RESULTS: Key features and capabilities of various were agreed upon by the panelists when consensus was reached. Some tourniquet features that were agreed upon included but are not limited to: Capable of being used longer than 2 hours, applied and monitored by anyone, data displays, semiautomated capabilities with inherent overrides, automated monitoring with notifications and alerts, and provide recommended actions. CONCLUSION: We were able to identify key tourniquet features that will be important for future device development. These consensus results can guide future inventors, researchers, and manufacturers to develop a portfolio of next-generation tourniquets for enhancing the capabilities of a prehospital medical provider. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level V.

Verification and Validation of Lower Body Negative Pressure as a Non-Invasive Bioengineering Tool for Testing Technologies for Monitoring Human Hemorrhage.

Since hemorrhage is a leading cause of preventable death in both civilian and military settings, the development of advanced decision support monitoring capabilities is necessary to promote improved clinical outcomes. The emergence of lower body negative pressure (LBNP) has provided a bioengineering technology for inducing progressive reductions in central blood volume shown to be accurate as a model for the study of the early compensatory stages of hemorrhage. In this context, the specific aim of this study was to provide for the first time a systematic technical evaluation to meet a commonly accepted engineering standard based on the FDA-recognized Standard for Assessing Credibility of Modeling through Verification and Validation (V&V) for Medical Devices (ASME standard V&V 40) specifically highlighting LBNP as a valuable resource for the safe study of hemorrhage physiology in humans. As an experimental tool, evidence is presented that LBNP is credible, repeatable, and validated as an analog for the study of human hemorrhage physiology compared to actual blood loss. The LBNP tool can promote the testing and development of advanced monitoring algorithms and evaluating wearable sensors with the goal of improving clinical outcomes during use in emergency medical settings.

Clinical Decision Support systems: A step forward in establishing the clinical laboratory as a decision maker hubA CDS system protocol implementation in the clinical laboratory.

Background: New tools for health information technology have been developed in recent times, such as Clinical Decision Support (CDS) systems, which are any digital solutions designed to help healthcare professionals when making clinical decisions. The study aimed to show how we have adopted a CDS system in the San Juan de Alicante Clinical Laboratory and facilitate the implementation of our protocol in other clinical laboratories. We have user experience and the motivation to improve healthcare tools. The improvement, measurement, and monitoring of interventions and laboratory tests has been our motto for years. Materials and methods: A descriptive research was conducted. All stages in the design of the project are as follows: 1. Set up a multidisciplinary workgroup. 2. Review patients' data. 3. Identify relevant data from main sources. 4. Design the likely outcomes. 5. Define a complete integration scenario. 6. Monitor and track the impact. To set up this protocol, two new software systems were implemented in our laboratory: AlinIQ CDS v8.2 as Rule Engine, and AlinIQ AIP Integrated Platform v1.6 as Business Intelligence (BI) tool. Results: Our protocol shows the workflow and actions that can be done with a CDS system and also how it could be integrated with other monitoring systems, as well as some examples of KPIs and their outcomes. Conclusions: CDS could be a great strategic asset for clinical laboratories to improve the integration of care, optimize the use of laboratory tests, and add more clinical value to physicians in the interpretation of results.

Circulatory HMGB1 is an early predictive and prognostic biomarker of ARDS and mortality in a swine model of polytrauma.

Acute respiratory distress syndrome (ARDS) is a leading cause of morbidity and mortality in polytrauma patients. Pharmacological treatments of ARDS are lacking, and ARDS patients rely on supportive care. Accurate diagnosis of ARDS is vital for early intervention and improved outcomes but is presently delayed up to days. The use of biomarkers for early identification of ARDS development is a potential solution. Inflammatory mediators high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1), and C3a have been previously proposed as potential biomarkers. For this study, we analyzed these biomarkers in animals undergoing smoke inhalation and 40% total body surface area burns, followed by intensive care for 72 h post-injury (PI) to determine their association with ARDS and mortality. We found that the levels of inflammatory mediators in serum were affected, as well as the degree of HMGB1 and Toll-like receptor 4 (TLR4) signal activation in the lung. The results showed significantly increased HMGB1 expression levels in animals that developed ARDS compared with those that did not. Receiver operating characteristic (ROC) analysis showed that HMGB1 levels at 6 h PI were significantly associated with ARDS development (AUROC=0.77) and mortality (AUROC=0.82). Logistic regression analysis revealed that levels of HMGB1 ≥24.10 ng/ml are associated with a 13-fold higher incidence of ARDS [OR:13.57 (2.76-104.3)], whereas the levels of HMGB1 ≥31.39 ng/ml are associated with a 12-fold increase in mortality [OR: 12.00 (2.36-93.47)]. In addition, we found that mesenchymal stem cell (MSC) therapeutic treatment led to a significant decrease in systemic HMGB1 elevation but failed to block SDC-1 and C3a increases. Immunohistochemistry analyses showed that smoke inhalation and burn injury induced the expression of HMGB1 and TLR4 and stimulated co-localization of HMGB1 and TLR4 in the lung. Interestingly, MSC treatment reduced the presence of HMGB1, TLR4, and the HMGB1-TLR4 co-localization. These results show that serum HMGB1 is a prognostic biomarker for predicting the incidence of ARDS and mortality in swine with smoke inhalation and burn injury. Therapeutically blocking HMGB1 signal activation might be an effective approach for attenuating ARDS development in combat casualties or civilian patients.

Higher Initial Formula for Resuscitation After Severe Burn Injury Means Higher 24-Hour Volumes.

Initial fluid infusion rates for resuscitation of burn injuries typically use formulas based on patient weight and total body surface area (TBSA) burned. However, the impact of this rate on overall resuscitation volumes and outcomes have not been extensively studied. The purpose of this study was to determine the impact of initial fluid rates on 24-hour volumes and outcomes using the Burn Navigator (BN). The BN database is composed of 300 patients with ≥20% TBSA, >40 kg that were resuscitated utilizing the BN. Four study arms were analyzed based on the initial formula-2 ml/kg/TBSA, 3 ml/kg/TBSA, 4 ml/kg/TBSA or the Rule of Ten. Total fluids infused at 24 hours after admission were compared as well as resuscitation-related outcomes. A total of 296 patients were eligible for analysis. Higher starting rates (4 ml/kg/TBSA) resulted in significantly higher volumes at 24 hours (5.2 ± 2.2 ml/kg/TBSA) than lower rates (2 ml/kg/TBSA resulted in 3.9 ± 1.4 ml/kg/TBSA). No shock was observed in the high resuscitation cohort, whereas the lowest starting rate exhibited a 12% incidence, lower than both the Rule of Ten and 3 ml/kg/TBSA arms. There was no difference in 7-day mortality across groups. Higher initial fluid rates resulted in higher 24-hour fluid volumes. The choice of 2ml/kg/TBSA as initial rate did not result in increased mortality or more complications. An initial rate of 2ml/kg/TBSA is a safe strategy.

Impact of Alcohol and Methamphetamine Use on Burn Resuscitation.

Mortality associated with burn injuries is declining with improved critical care. However, patients admitted with concurrent substance use have increased risk of complications and poor outcomes. The impact of alcohol and methamphetamine use on acute burn resuscitation has been described in single-center studies; however, has not been studied since implementation of computerized decision support for resuscitation. Patients were evaluated based presence of alcohol, with a minimum blood alcohol level of 0.10, or positive methamphetamines on urine drug screen. Fluid volumes and urine output were examined over 48 hours. A total of 296 patients were analyzed. 37 (12.5%) were positive for methamphetamine use, 50 (16.9%) were positive for alcohol use, and 209 (70.1%) with negative for both. Patients positive for methamphetamine received a mean of 5.30 ± 2.63 cc/kg/TBSA, patients positive for alcohol received a mean of 5.41 ± 2.49 cc/kg/TBSA, and patients with neither received a mean of 4.33 ± 1.79 cc/kg/TBSA. Patients with methamphetamine or alcohol use had significantly higher fluid requirements. In the first 6 hours patients with alcohol use had significantly higher urinary output (UO) in comparison to patients with methamphetamine use which had similar output to patients negative for both substances. This study demonstrated that patients with alcohol and methamphetamine use had statistically significantly greater fluid resuscitation requirements compared to patients without. The effects of alcohol as a diuretic align with previous literature. However, patients with methamphetamine lack the increased UO as a cause for their increased fluid requirements.

Adaptive changes in redox response and decreased platelet aggregation in lead-exposed workers.

Chronic lead exposure can generate pro-oxidative and pro-inflammatory conditions in the blood, related to high platelet activation and aggregation, altering cell functions. We studied ADP-stimulated aggregation and the oxidant/antioxidant system of platelets from chronically lead-exposed workers and non-exposed workers. Platelet aggregation was low in lead-exposed workers (62 vs. 97%), who had normal platelet counts and showed no clinical manifestations of hemostatic failure. ADP-activated platelets from lead-exposed workers failed to increase superoxide release (3.3 vs. 6.6 µmol/g protein), had low NADPH concentration (60 vs. 92 nmol/mg protein), high concentration of hydrogen peroxide (224 vs. 129 nmol/mg protein) and high plasma PGE2 concentration (287 vs. 79 pg/mL). Altogether, those conditions, on the one hand, could account for the low platelet aggregation and, on the other, indicate an adaptive mechanism for the oxidative status of platelets and anti-aggregating molecules to prevent thrombotic problems in the pro-oxidant and pro-inflammatory environment of chronic lead exposure.

Haploidentical vs. HLA-matched donor hematopoietic stem-cell transplantation for pediatric patients with acute lymphoblastic leukemia in second remission: A collaborative retrospective study of the Spanish Group for Bone Marrow Transplantation in Children (GETMON/GETH) and the Spanish Childhood Relapsed ALL Board (ReALLNet).

Introduction: Studies addressing the role of haploidentical as alternative to HLA-matched donors for stem cell transplantation (SCT) often include patients with diverse hematological malignancies in different remission statuses. Methods: We compared outcomes of children with acute lymphoblastic leukemia (ALL) undergoing SCT in second complete remission (CR2) from haploidentical (n = 25) versus HLA-matched donor (n = 51). Results: Patients were equally distributed across both groups according to age, immunophenotype, time to and site of relapse, relapse risk-group allocation, and minimal residual disease (MRD) before SCT. Incidence of graft failure, acute graft versus host disease (GVHD), and other early complications did not differ between both groups. We found no differences in overall survival (58.7% versus 59.5%; p = .8), leukemia free survival (LFS) (48% versus 36.4%; p = .5), event free survival (40% versus 34.4%; p = .69), cumulative incidence (CI) of subsequent relapse (28% versus 40.9%; p = .69), treatment related mortality (24% versus 23.6%; p = .83), CI of cGVHD (4.5% versus 18.7%; p = .2), and chronic GVHD-free and leukemia-free survival (44% versus 26.3%; p = .3) after haploidentical donor SCT. Chronic GVHD (HR = 0.09; p=.02) had protective impact, and MRD ≥ 0.01% before SCT (HR = 2.59; p=.01) had unfavorable impact on LFS. Discussion: These results support the role of haploidentical donor SCT in children with ALL in CR2.

A Retrospective Analysis of Combat Injury Patterns and Prehospital Interventions Associated with the Development of Sepsis.

BACKGROUND: Combat injury related wound infections are common. Untreated, these wound infections may progress to sepsis and septic shock leading to increased morbidity and mortality rates. Understanding infectious complications, patterns, progression, and correlated prehospital interventions are vital to understand the development of sepsis. We aim to analyze demographics, injury patterns, and interventions associated with sepsis in battlefield settings. MATERIALS AND METHODS: This is a secondary analysis of previously published data from the Department of Defense Trauma Registry (DoDTR) from 2007 to 2020. We searched for casualties diagnosed with sepsis (excluding line-sepsis) throughout their initial hospitalization. Regression models were used to seek associations. RESULTS: Our initial request yielded 28,950 encounters, of which 25,654 (88.6%) were adults that met inclusion, including 243 patients (0.9%) diagnosed with sepsis. Patients included US military (34%), non-North Atlantic Treaty Organization (NATO) military (33%) and humanitarian (30%) groups. Patients diagnosed with sepsis had a significantly lower survival rate than non-septic patients (78.1% vs. 95.7%, p < 0.001). There was no significant difference in administration of prehospital antibiotics between septic and the general populations (10.6% vs. 12.3%, p = 0.395). Prehospital intraosseous access (OR 1.56, 95% CI 1.27-1.91, p = 0.207) and packed red cell administration (1.63, 1.24-2.15, 0.029) were the interventions most associated with sepsis. CONCLUSIONS: Sepsis occurred infrequently in the DoDTR when evacuation from battlefield is not delayed, but despite increased intervention frequency, developing sepsis demonstrates a significant drop in survival rates. Future research would benefit from the development of risk mitigation measures.

How common is nerve injury after reverse shoulder arthroplasty? A systematic review.

BACKGROUND: Nerve injury following reverse shoulder arthroplasty (RSA) is a known risk factor with wide ranging incidences reported. This systematic review evaluates the overall incidence of nerve injury following primary and revision RSA and summarizes the characteristics of the nerve injuries reported in the current literature. METHODS: A systematic review was performed using separate database searches (Pubmed, Embase, Web of Science, Cochrane) following the PRISMA guidelines. Search criteria included the title terms "reverse shoulder," "reverse total shoulder," "inverted shoulder," and "inverted total shoulder" with publication dates ranging from 01/01/2010 to 01/01/2022. Studies that reported neurological injuries and complications were included and evaluated for primary RSA, revision RSA, number of nerve injuries, and which nerves were affected. RESULTS: After exclusion, our systematic review consisted of 188 articles. A total of 40,146 patients were included, with 65% female. The weighted mean age was 70.3 years. The weighted mean follow-up was 35.4 months. The rate of nerve injury after RSA was 1.3% (510 of 40,146 RSAs). The rate of injury was greater in revision RSA compared to primary RSA (2.4% vs. 1.3%). Nerve injury was most common in RSAs done for a primary diagnosis of acute proximal humerus fracture (4.0%), followed by cuff tear arthropathy (3.0%), DJD (2.6%), and inflammatory arthritis (1.7%). Massive rotator cuff tears and post-traumatic arthritis cases had the lowest nerve injury rates (1.0% and 1.4%, respectively). The axillary nerve was the most commonly reported nerve that was injured in both primary and revision RSA (0.6%), followed by the ulnar nerve (0.26%) and median nerve (0.23%). Brachial plexus injury was reported in 0.19% of overall RSA cases. CONCLUSION: Based on current English literature, nerve injuries occur at a rate of 1.3% after primary RSA compared with 2.4% after revision RSA. The most common nerve injury was to the axillary nerve (0.64%), with the most common operative diagnosis associated with nerve injury after RSA being acute proximal humerus fracture (4.0%). Surgeons should carefully counsel patients prior to surgery regarding the risk of nerve injury.

Hypothermia in the Combat Trauma Population.

BACKGROUND: The MARCH (Massive hemorrhage, Airway, Respirations, Circulation, and Hypothermia/Head injuries) algorithm taught to military medics includes interventions to prevent hypothermia. As possible sequelae from major trauma, hypothermia is associated with coagulopathy and lower survival. This paper sought to define hypothermia within our combat trauma population using an outcomes-based method, and determine clinical variables associated with hypothermia. METHODS: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry focused on casualties who received prehospital care. A receiver operating curve was constructed and Youden's index was used to define hypothermia within the predetermined population based on mortality risk. A multivariable regression model was used to identify associations. RESULTS: There were 23,243 encounters that met the inclusion criteria for this study with patients having received prehospital care and documentation of at least one emergency department temperature. An optimal threshold of 36.2° C was found to predict mortality; 3,159 casualties had temperatures below this threshold (14%). Survival to discharge was lower among casualties with hypothermia (91% versus 98%). Hypothermic casualties were less likely to undergo blanket application (38% versus 40%). However, they had higher proportions with Hypothermia Prevention and Management Kit application (11% versus 7%) and radiant warming (2% versus 1%). On multivariable regression modeling, none of the hypothermia interventions were associated with a decreased likelihood of hypothermia. Non-hypothermia interventions associated with hypothermia included prehospital intubation (OR 1.57, 95% CI 1.45-1.69) and blood product administration. CONCLUSIONS: Hypothermia, including a single recorded low temperature in the patient care record, was associated with worse outcomes in this combat trauma population. Prehospital intubation was most strongly associated with developing hypothermia. Prehospital warming interventions were not associated with a reduction in hypothermia risk. Our dataset suggests that current methods for prehospital warming are inadequate.

The Battle of the Titans-Comparing Resuscitation Between Five Major Burn Centers Using the Burn Navigator.

The goal of burn resuscitation is to provide the optimal amount of fluid necessary to maintain end-organ perfusion and prevent burn shock. The objective of this analysis was to examine how the Burn Navigator (BN), a clinical decision support tool in burn resuscitation, was utilized across five major burn centers in the United States, using an observational trial of 300 adult patients. Subject demographics, burn characteristics, fluid volumes, urine output, and resuscitation-related complications were examined. Two hundred eighty-five patients were eligible for analysis. There was no difference among the centers on mean age (45.5 ± 16.8 years), body mass index (29.2 ± 6.9), median injury severity score (18 [interquartile range: 9-25]), or total body surface area (TBSA) (34 [25.8-47]). Primary crystalloid infusion volumes at 24 h differed significantly in ml/kg/TBSA (range: 3.1 ± 1.2 to 4.5 ± 1.7). Total fluids, including colloid, drip medications, and enteral fluids, differed among centers in both ml/kg (range: 132.5 ± 61.4 to 201.9 ± 109.9) and ml/kg/TBSA (3.5 ± 1.0 to 5.3 ± 2.0) at 24 h. Post-hoc adjustment using pairwise comparisons resulted in a loss of significance between most of the sites. There was a total of 156 resuscitation-related complications in 92 patients. Experienced burn centers using the BN successfully titrated resuscitation to adhere to 24 h goals. With fluid volumes near the Parkland formula prediction and a low prevalence of complications, the device can be utilized effectively in experienced centers. Further study should examine device utility in other facilities and on the battlefield.

La displasia del desarrollo de la cadera puede predisponer a osteoartritis: de la inflamación a la destrucción. Revisión de la literatura / Developmental dysplasia of the hip may predispose to osteoarthritis: From inflammation to destruction. A literature review

Introducción. La displasia del desarrollo de la cadera (DDC) abarca un conjunto de anormalidades relacionadas con el proceso de maduración del acetábulo y del tercio proximal del fémur Si no se trata de manera adecuada y oportuna, los pacientes con esta condición pueden desarrollar osteoartritis (OA) eventualmente.Objetivo. Recopilar y sintetizar evidencia científica publicada entre enero de 2000 y febrero de 2023 sobre la fisiopatología de la DDC y su relación con el desarrollo de OA de cadera en términos de los mecanismos fisiopatológicos genéticos, inflamatorios e inmunológicos. Materiales y métodos. Se realizó una revisión de la literatura en bases de datos de literatura biomédica (PubMed/Medline, Embase, SciELO) y herramientas bioinformáticas (e-Ensambl, STRING), mediante términos como "displasia de cadera", "osteoartritis", "etiología" y "genes". Se incluyeron estudios observacionales clínicos y genéticos realizados en humanos.Resultados. La búsqueda inicial arrojó 349 registros, de los cuales 23 cumplieron los criterios de elegibilidad. Los genes que interactúan con módulos genéticos parecen participar en el desarrollo articular y la etiología de las enfermedades relacionadas con el cartílago y el hueso; sin embargo, la inestabilidad mecánica producida por la DCC activa factores inflamatorios e inmunológicos, predisponiendo OA. A partir de la información encontrada, se puede considerar que existe una relación muy estrecha entre DDC y OA.Conclusiones. Conocer los mecanismos fisiopatológicos genéticos, inflamatorios e inmunológicos de DDC y OA favorece la realización de un diagnóstico oportuno y, en consecuencia, posibilita brindar un tratamiento adecuado para disminuir y controlar el daño a largo plazo y mejorar la calidad de vida del paciente

Introduction: Developmental dysplasia of the hip (DDH) encompasses a set of abnormalities related to the maturation process of the acetabulum and the proximal third of the femur. If not treated properly and promptly, patients with this condition may eventually develop osteoarthritis (OA).Objective: To compile and synthesize scientific evidence published between January 2000 and February 2023 on the pathophysiology of DDH and its relationship to the development of hip OA in terms of genetic, inflammatory and immunological pathophysiological mechanisms.Methodology: A literature review was performed in biomedical literature databases (PubMed/Medline, Embase, SciELO) and bioinformatic resources (e-Ensambl, STRING), using terms such as "hip dysplasia", "osteoarthritis", "etiology", and "genes". Clinical and genetic observational studies involving human subjects were included.Results: The initial search yielded 349 records, of which 23 met the eligibility criteria. Genes that interact with genetic modules may play a role in the development of joints and the etiology of diseases that affect the bones and cartilage; however, the mechanical instability caused by DDH activates inflammatory and immunological factors, predisposing to OA. Based on the information obtained, it is possible to consider that there is a very close relationship between DDH and OA.Conclusions: Knowing the genetic, inflammatory and immunological pathophysiological mechanisms of DDH and OA favors timely diagnosis and, consequently, allows providing proper treatment to reduce and control long-term damage and improve the patient's quality of life

The metabolic phenotype of the patient influences the reduction in carotid intima-media thickness achieved following metabolic surgery.

OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.

Non-linearity in event runoff generation in a small agricultural catchment.

Understanding the role of soil moisture and other controls in runoff generation is important for predicting runoff across scales. This paper aims to identify the degree of non-linearity of the relationship between event peak runoff and potential controls for different runoff generation mechanisms in a small agricultural catchment. The study is set in the 66 ha Hydrological Open Air Laboratory, Austria, where discharge was measured at the catchment outlet and for 11 sub-catchments or hillslopes with different runoff generation mechanisms. Peak runoff of 73 events was related to three potential controls: event precipitation, soil moisture and groundwater levels. The results suggest that the hillslopes dominated by ephemeral overland flow exhibit the most non-linear runoff generation behaviour for its controls; runoff is only generated above a threshold of 95% of the maximum soil moisture. Runoff generation through tile drains and in wetlands is more linear. The largest winter and spring events at the catchment outlet are caused by runoff from hillslopes with shallow flow paths (ephemeral overland flow and tile drainage mechanisms), while the largest summer events are caused by other hillslopes, those with deeper flow paths or with saturation areas throughout the year. Therefore, the response of the entire catchment is a mix of the various mechanisms, and the groundwater contribution makes the response more linear. The implications for hydrological modelling are discussed.

Closed-Loop Controlled Fluid Administration Systems: A Comprehensive Scoping Review.

Physiological Closed-Loop Controlled systems continue to take a growing part in clinical practice, offering possibilities of providing more accurate, goal-directed care while reducing clinicians' cognitive and task load. These systems also provide a standardized approach for the clinical management of the patient, leading to a reduction in care variability across multiple dimensions. For fluid management and administration, the advantages of closed-loop technology are clear, especially in conditions that require precise care to improve outcomes, such as peri-operative care, trauma, and acute burn care. Controller design varies from simplistic to complex designs, based on detailed physiological models and adaptive properties that account for inter-patient and intra-patient variability; their maturity level ranges from theoretical models tested in silico to commercially available, FDA-approved products. This comprehensive scoping review was conducted in order to assess the current technological landscape of this field, describe the systems currently available or under development, and suggest further advancements that may unfold in the coming years. Ten distinct systems were identified and discussed.

Role of Ape1 in Impaired DNA Repair Capacity in Battery Recycling Plant Workers Exposed to Lead.

Exposure to lead in environmental and occupational settings continues to be a serious public health problem. At environmentally relevant doses, two mechanisms may underlie lead exposition-induced genotoxicity, disruption of the redox balance and an interference with DNA repair systems. The aim of the study was to evaluate the ability of lead exposition to induce impaired function of Ape1 and its impact on DNA repair capacity of workers chronically exposed to lead in a battery recycling plant. Our study included 53 participants, 37 lead exposed workers and 16 non-lead exposed workers. Lead intoxication was characterized by high blood lead concentration, high lipid peroxidation and low activity of delta-aminolevulinic acid dehydratase (δ-ALAD). Relevantly, we found a loss of DNA repair capacity related with down-regulation of a set of specific DNA repair genes, showing specifically, for the first time, the role of Ape1 down regulation at transcriptional and protein levels in workers exposed to lead. Additionally, using a functional assay we found an impaired function of Ape1 that correlates with high blood lead concentration and lipid peroxidation. Taken together, these data suggest that occupational exposure to lead could decrease DNA repair capacity, inhibiting the function of Ape1, as well other repair genes through the regulation of the ZF-transcription factor, promoting the genomic instability.