Systematic review of machine-learning models in orthopaedic trauma.

Aims: Machine-learning (ML) prediction models in orthopaedic trauma hold great promise in assisting clinicians in various tasks, such as personalized risk stratification. However, an overview of current applications and critical appraisal to peer-reviewed guidelines is lacking. The objectives of this study are to 1) provide an overview of current ML prediction models in orthopaedic trauma; 2) evaluate the completeness of reporting following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement; and 3) assess the risk of bias following the Prediction model Risk Of Bias Assessment Tool (PROBAST) tool. Methods: A systematic search screening 3,252 studies identified 45 ML-based prediction models in orthopaedic trauma up to January 2023. The TRIPOD statement assessed transparent reporting and the PROBAST tool the risk of bias. Results: A total of 40 studies reported on training and internal validation; four studies performed both development and external validation, and one study performed only external validation. The most commonly reported outcomes were mortality (33%, 15/45) and length of hospital stay (9%, 4/45), and the majority of prediction models were developed in the hip fracture population (60%, 27/45). The overall median completeness for the TRIPOD statement was 62% (interquartile range 30 to 81%). The overall risk of bias in the PROBAST tool was low in 24% (11/45), high in 69% (31/45), and unclear in 7% (3/45) of the studies. High risk of bias was mainly due to analysis domain concerns including small datasets with low number of outcomes, complete-case analysis in case of missing data, and no reporting of performance measures. Conclusion: The results of this study showed that despite a myriad of potential clinically useful applications, a substantial part of ML studies in orthopaedic trauma lack transparent reporting, and are at high risk of bias. These problems must be resolved by following established guidelines to instil confidence in ML models among patients and clinicians. Otherwise, there will remain a sizeable gap between the development of ML prediction models and their clinical application in our day-to-day orthopaedic trauma practice.

Systematic review of motivational interventions to improve adherence to medication in patients with hypertension and meta-analysis / Revisión sistemática de intervenciones motivacionales para mejorar la adherencia a la medicación en pacientes con hipertensión y metanálisis

Introduction: Antihypertensive medication non-adherence is an important cause of poor control in hypertension. The role of motivational interventions to increase antihypertensive medication adherence remains unclear. Objective: To systematically review RCTs of motivational interventions for improving medication adherence in hypertension. Methods: EMBASE and Pubmed were searched from inception to February 2019 for RCTs of motivational interventions for improving medication adherence in hypertension vs. usual care. Inclusion criteria: RCTs with motivational intervention to improve medication adherence in adults with hypertension. A blinded review was conducted by 2 reviewers. Disagreements were resolved by consensus/a third reviewer. Data extraction and quality appraisal was performed using the risk of bias tool from cochrane collaboration. The meta-analyses of blood pressure control used random-effects models to report mean difference and 95% CIs. Primary outcome was medication adherence and second outcome was blood pressure control. Results: The search methodology yielded 10 studies comprising 1171 participants. Medication adherence improved significantly in 5 studies. We could not perform pool analysis for this outcome due to different measurements of medication adherence. Seven trials reported significant results regarding blood pressure control. On pooled analysis, motivational interventions were not significantly associated with a systolic blood pressure (mean difference, −0.06; 95% CI, −0.05 to 0.18; p=0.63; I2=0.0%) or diastolic blood pressure (mean difference, −0.11; 95% CI, −0.10 to 0.31; p=0.28; I2=23.8%) decrease or blood pressure control. (AU)

Introducción: La falta de adherencia a la terapia farmacológica es una de las principales razones del descontrol de la hipertensión arterial. Se desconoce el papel de las intervenciones motivacionales en el aumento de la adherencia. Objetivo: Realizar una revisión sistemática de ensayos clínicos aleatorizados (ECA) dirigidos a mejorar la adherencia a la medicación en hipertensión arterial. Métodos: Se buscaron ECA de intervenciones motivacionales vs. atención habitual en las bases de datos Embase y PubMed desde su inicio hasta febrero de 2019. Criterios de inclusión: ECA de intervenciones motivacionales para aumentar la adherencia a la terapia con medicamentos en adultos con hipertensión. Dos revisores realizaron una revisión ciega y sus desacuerdos se resolvieron por consenso/por un tercer revisor. La extracción de datos y la evaluación de la calidad se realizaron mediante la herramienta Cochrane de evaluación del riesgo de sesgo. El metaanálisis del control de la presión arterial utilizó modelos de efectos aleatorios para informar la diferencia en las medias y los intervalos de confianza de 95% (IC 95%). El outcome primario fue la adherencia a la medicación y el secundario fue el control de la presión arterial. Resultados: Se obtuvieron 10 estudios con 1.171 participantes. La adherencia mejoró significativamente en cinco estudios. No fue posible realizar un análisis agrupado de la adherencia debido al uso de diferentes medidas de cumplimiento. Siete estudios mostraron una diferencia significativa en el control de la presión arterial. En el análisis conjunto, las intervenciones motivacionales no se asociaron a una disminución significativa de la presión arterial sistólica (diferencia de medias, -0,06; IC 95%, -0,05-0,18; p=0,63; I2=0%) o de la presión arterial diastólica (diferencia de medias, -0,11; IC 95%, -0,10-0,31; p=0,28; I2=23,8%) o a mejora en control de la misma.(AU)

Heart transplantation in patients with anthracycline-induced cardiomyopathy / Trasplante cardiaco en pacientes con cardiotoxicidad inducida por antraciclinas

Abstract Objective: The objective of this study was to describe the clinical and imaging characteristics and the evolution of heart transplantation patients due to anthracycline-induced cardiomyopathy Methods: Patients with a diagnosis of ACM who received a heart transplantation in our institution in the period of November 2009-April 2021 were included. Clinical characteristics, pre-transplant studies, and clinical outcomes after transplantation were collected retrospectively from the electronic medical record. Results: A total of 11 patients were included in the study. The median age at the time of cancer diagnosis was 15 years (IQR 10-37 years), while the median age at the time of heart transplant was 56 years (IQR 39-62 years). Regarding post-transplant outcomes, three patients died in the post-operative period. One died 4 years after the intervention due to chronic rejection, while the other seven had a favorable evolution. No oncological relapse was observed with a median follow-up of 2.5 years (IQR 1.86-3.85 years). Conclusion: End-stage anthracycline-induced cardiomyopathy can occur many years after chemotherapy treatment, so close cardiovascular follow-up is extremely important. Heart transplantation is a treatment option after an exhaustive multidisciplinary evaluation, to minimize the risk of oncological relapse.

Resumen Objetivo: Describir las características clínicas, imagenológicas y la evolución de los pacientes trasplantados cardiacos por cardiotoxicidad inducida por antraciclinas. Métodos: Serie de casos descriptiva de pacientes consecutivos trasplantados cardiacos debido a cardiotoxicidad mediada por antraciclinas en el periodo de Noviembre de 2009 a Abril de 2021.Las características clínicas, los estudios complementarios pretrasplante y la información sobre la evolución posterior al trasplante fue recolectada de la historia clínica electrónica de forma retrospectiva. Resultados: Se incluyeron un total de 11 pacientes. La mediana de edad al diagnóstico de la patología oncológica fue de 15 años (RIC 10-37 años), mientras que la mediana de edad en la que recibieron el trasplante cardiaco fue de 56 años (RIC 39-62 años). Con respecto a la evolución posterior al trasplante, 3 pacientes murieron en el periodo del post operatorio inmediato. 1 paciente falleció a los 4 años del trasplante y los otros 7 pacientes tuvieron una evolución favorable. No se observó recaída oncológica en ningún paciente durante una mediana de seguimiento o de 2,5 años (RIC 1.86-3.85 años). Conclusión: La etapa final de la miocardiopatía inducida por antraciclinas puede ocurrir muchos años después del tratamiento con quimioterapia, por lo que es extremadamente importante un seguimiento cardiológico estricto. El trasplante cardiaco es una opción en este grupo de pacientes luego de una exhaustiva evaluación multidisciplinaria, con el fin de minimizar el riesgo de recaída oncológica.

Heart transplantation in patients with anthracycline-induced cardiomyopathy.

OBJECTIVE: The objective of this study was to describe the clinical and imaging characteristics and the evolution of heart transplantation patients due to anthracycline-induced cardiomyopathy. METHODS: Patients with a diagnosis of ACM who received a heart transplantation in our institution in the period of November 2009-April 2021 were included. Clinical characteristics, pre-transplant studies, and clinical outcomes after transplantation were collected retrospectively from the electronic medical record. RESULTS: A total of 11 patients were included in the study. The median age at the time of cancer diagnosis was 15 years (IQR 10-37 years), while the median age at the time of heart transplant was 56 years (IQR 39-62 years). Regarding post-transplant outcomes, three patients died in the post-operative period. One died 4 years after the intervention due to chronic rejection, while the other seven had a favorable evolution. No oncological relapse was observed with a median follow-up of 2.5 years (IQR 1.86-3.85 years). CONCLUSION: End-stage anthracycline-induced cardiomyopathy can occur many years after chemotherapy treatment, so close cardiovascular follow-up is extremely important. Heart transplantation is a treatment option after an exhaustive multidisciplinary evaluation, to minimize the risk of oncological relapse.

OBJETIVO: Describir las características clínicas, imagenológicas y la evolución de los pacientes trasplantados cardiacos por cardiotoxicidad inducida por antraciclinas. MÉTODOS: Serie de casos descriptiva de pacientes consecutivos trasplantados cardiacos debido a cardiotoxicidad mediada por antraciclinas en el periodo de Noviembre de 2009 a Abril de 2021.Las características clínicas, los estudios complementarios pretrasplante y la información sobre la evolución posterior al trasplante fue recolectada de la historia clínica electrónica de forma retrospectiva. RESULTADOS: Se incluyeron un total de 11 pacientes. La mediana de edad al diagnóstico de la patología oncológica fue de 15 años (RIC 10-37 años), mientras que la mediana de edad en la que recibieron el trasplante cardiaco fue de 56 años (RIC 39-62 años). Con respecto a la evolución posterior al trasplante, 3 pacientes murieron en el periodo del post operatorio inmediato. 1 paciente falleció a los 4 años del trasplante y los otros 7 pacientes tuvieron una evolución favorable. No se observó recaída oncológica en ningún paciente durante una mediana de seguimiento o de 2,5 años (RIC 1.86-3.85 años). CONCLUSIÓN: La etapa final de la miocardiopatía inducida por antraciclinas puede ocurrir muchos años después del tratamiento con quimioterapia, por lo que es extremadamente importante un seguimiento cardiológico estricto. El trasplante cardiaco es una opción en este grupo de pacientes luego de una exhaustiva evaluación multidisciplinaria, con el fin de minimizar el riesgo de recaída oncológica.

Sequencing paired tumor DNA and white blood cells improves circulating tumor DNA tracking and detects pathogenic germline variants in localized colon cancer.

BACKGROUND: In the setting of localized colon cancer (CC), circulating tumor DNA (ctDNA) monitoring in plasma has shown potential for detecting minimal residual disease (MRD) and predicting a higher risk of recurrence. With the tumor-only sequencing approach, however, germline variants may be misidentified as somatic variations, precluding the possibility of tracking in up to 11% of patients due to a lack of known somatic mutations. In this study, we assess the potential value of adding white blood cells (WBCs) to tumor tissue sequencing to enhance the accuracy of sequencing results. PATIENTS AND METHODS: A total of 148 patients diagnosed with localized CC were prospectively recruited at the Hospital Clínico Universitario in Valencia (Spain). Employing a custom 29-gene panel, sequencing was conducted on tumor tissue, plasma and corresponding WBCs. Droplet digital PCR and amplicon-based NGS were performed on plasma samples post-surgery to track MRD. Oncogenic somatic variants were identified by annotating with COSMIC, OncoKB and an internal repository of pathogenic mutations database. A variant prioritization analysis, mainly characterized by the match of oncogenic mutations with the evidence levels defined in OncoKB, was carried out to select specific targeted therapies. RESULTS: Utilizing paired tumor and WBCs sequencing, we identified somatic mutations in all patients (100%) within our cohort, compared to 89% using only tumor tissue. Consequently, the top 10 most frequently mutated genes for plasma monitoring were altered. The sequencing of WBCs identified 9% of patients with pathogenic mutations in the germline, with APC and TP53 being the most frequently mutated genes. Additionally, mutations in genes related to clonal hematopoiesis of indeterminate potential were detected in 27% of the cohort, with TP53, KRAS, and KMT2C being the most frequently altered genes. There were no observed differences in the sensitivity of monitoring MRD using ddPCR or amplicon-based NGS (p = 1). Ultimately, 41% of the patients harbored potentially targetable alterations at diagnosis. CONCLUSION: The germline testing method not only enhanced sequencing results and raised the proportion of patients eligible for plasma monitoring, but also uncovered the existence of pathogenic germline variations, thereby aiding in the identification of patients at a higher risk of hereditary cancer syndromes.

Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology.

Loss of function (LoF) of TAR-DNA binding protein 43 (TDP-43) and mis-localization, together with TDP-43-positive and hyperphosphorylated inclusions, are found in post-mortem tissue of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those carrying LoF variants in the progranulin gene (GRN). Modeling TDP-43 pathology has been challenging in vivo and in vitro. We present a three-dimensional induced pluripotent stem cell (iPSC)-derived paradigm-mature brain organoids (mbOrg)-composed of cortical-like-astrocytes (iA) and neurons. When devoid of GRN, mbOrgs spontaneously recapitulate TDP-43 mis-localization, hyperphosphorylation, and LoF phenotypes. Mixing and matching genotypes in mbOrgs showed that GRN-/- iA are drivers for TDP-43 pathology. Finally, we rescued TDP-43 LoF by adding exogenous progranulin, demonstrating a link between TDP-43 LoF and progranulin expression. In conclusion, we present an iPSC-derived platform that shows striking features of human TDP-43 proteinopathy and provides a tool for the mechanistic modeling of TDP-43 pathology and patient-tailored therapeutic screening for FTD and ALS.

Registro Nacional Argentino de Resonancia Cardíaca (RENAREC) / Argentine National Cardiac Magnetic Resonance Imaging Registry (RENAREC)

RESUMEN Introducción: La utilidad de la resonancia magnética cardíaca (RMC) ha crecido ampliamente en los últimos años, en los cuales se han publicado distintos registros internacionales sobre su uso e impacto clínico. Sin embargo, no contamos con este tipo de información en Argentina. Objetivo: Evaluar indicaciones, protocolos utilizados, seguridad y consecuencias terapéuticas de la RMC en la República Argentina. Material y métodos: Se diseñó un registro prospectivo a nivel nacional con recolección de datos demográficos, indicaciones de RMC, complicaciones asociadas, diagnósticos y consecuencias terapéuticas. Resultados: Participaron 34 centros de 10 provincias de Argentina (85% centros privados, 59% centros con internación). Se incluyeron 1131 pacientes (edad 54 ± 18 años, 61% varones). Las principales indicaciones para el estudio de RMC fueron la miocardiopatía hipertrófica (13,9%) y la arritmia ventricular (12,3%). El 99,7% de los estudios fueron reportados sin complicaciones. Los resultados más frecuentes de la RMC fueron: normal (31,2%), miocardiopatía no isquémica (14,7%), miocardiopatía isquémico-necrótica (11,6%) y miocardiopatía hipertrófica (8,9%). La sospecha clínica fue confirmada en el 23,6% de los casos y la RMC generó un diagnóstico nuevo no sospechado en el 48,7% de los casos. Las consecuencias terapéuticas más frecuentes fueron el alta hospitalaria (31,6%) seguida por el cambio en la medicación (28,1%). Conclusiones: La RMC es un estudio ampliamente utilizado en Argentina, principalmente en centros privados, con un número muy bajo de complicaciones. Las principales indicaciones son las miocardiopatías (hipertrófica y dilatada) y la arritmia ventricular, y provee un diagnóstico nuevo no sospechado en casi la mitad de los casos. Se requieren de otros estudios en el futuro para evaluar las implicancias clínicas y terapéuticas.

ABSTRACT Background: The usefulness of cardiac magnetic resonance imaging (MRI) has greatly increased in the last years. Different international registries have been published on its use; however, there is no data available from Argentina. Objective: The aim of this study was to evaluate different indications, protocols, safety and therapeutic consequences of cardiac MRI in Argentina. Methods: A prospective national registry was designed with collection of demographic data, indications for cardiac MRI, associated complications, diagnoses and therapeutic consequences. Results: A total of 34 centers from 10 provinces of Argentina (85% private and 59% with inpatient capacity) participated in the study, including 1131 patients (mean age 54±18 years and 61% males). The main indications for cardiac MRI were hypertrophic cardiomyopathy (13.9%), and ventricular arrhythmia (12.3%). In 99.7% of cases, no study complications were reported. The most frequent results of cardiac MRI were: normal (31.2%), non-ischemic cardiomyopathy (14.7%), ischemic-necrotic cardiomyopathy (11.6%) and hypertrophic cardiomyopathy (8.9%). Clinical suspicion was confirmed in 23.6% of cases and cardiac MRI generated an unsuspected new diagnosis in 48.7% of cases. The main therapeutic consequences were hospital discharge (31.6%) followed by change in medication (28.1%). Conclusions: Cardiac MRI is widely used in Argentina, mainly in private centers with a very low incidence of complications. Cardiomyopathies (hypertrophic and dilated) and ventricular arrhythmia are its main indication, and it provides a new unsuspected diagnosis in almost half of the cases. Further studies are required to assess its clinical and therapeutic impact.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study.

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 µg/mL Mat and 9.71 µg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Examining the Relationship Between Mild Traumatic Brain Injuries and Development of Mental Illness Disorders in a Mid-Term Follow-up Period.

OBJECTIVE: The sequalae of mild concussions continue to emerge with increased awareness in sports-related injuries. This study aimed to quantify the number of patients who are affected by a mental illness within 3 yrs of a concussion and identify whether demographic differences exist that may influence a mental illness diagnosis. DESIGN: Using a nationwide database, data were queried for a diagnosis of concussion, capturing patients aged 18-45 yrs with no previous mental illness, and then identified if these patients were diagnosed with a mental illness within 3 yrs of their concussion. The mental illnesses specifically chosen for this study included depression, anxiety, panic disorder, posttraumatic stress disorder, bipolar, and schizophrenia. RESULTS: Within 3 yrs after a concussion, 48% of patients were later diagnosed with a mental illness. All of the mental illnesses this study chose to evaluate were present in a higher proportion of patients after a concussion than the general population. CONCLUSIONS: The mechanism between concussions and mental illness remains unclear. A large proportion of patients who experience a concussion are later diagnosed with a mental illness within 3 yrs. Patients with a history of a previous concussion may benefit from screening for the development of a mental illness.

Comparison of automated and traditional ECAP recording approaches in clinical practice.

OBJECTIVE: The traditional method of recording electrically evoked compound action potentials (ECAPs), as implemented in the MAESTRO clinical software (standard ART), requires manual adjustments during threshold determination through a specialist. The "FineGrain" research tool (FineGrain RT) uses a continuous stimulation paradigm combined with automatic ECAP threshold determination. The aim of this study was to compare the FineGrain RT with standard ART. DESIGN: ECAPs were recorded with standard ART and the FineGrain RT in paediatric cochlear implant recipients. Different stimulation rates were used for FineGrain ECAP recordings (40, 60, and 76 Hz). STUDY SAMPLE: Thirteen children (6 - 19 years) participated in this study - nine were bilaterally and four unilaterally implanted, resulting in a total of twenty-two implanted ears. RESULTS: ECAP threshold determination success rates were similar between the two approaches (92% and 89%) and ECAP thresholds correlated well (r: 0.94, p < 2.2e-16) with average ART thresholds being lower than FineGrain RT thresholds. FineGrain stimulation with different stimulation rates did not have a significant effect on ECAP thresholds but ECAP thresholds at medial and apical contacts were lower compared to basal contacts. CONCLUSIONS: TheFineGrain research approach is a reliable replacement for standard ART in clinical practice.

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

Glioblastoma is the most prevalent and malignant brain tumor identified in adults. Surgical resection followed by radiotherapy and chemotherapy, mainly with temozolomide (TMZ), is the chosen treatment for this type of tumor. However, the average survival of patients is around 15 months. Novel approaches to glioblastoma treatment are greatly needed. Here, we aimed to investigate the anti-glioblastoma effect of the combination of matteucinol (Mat) (dihydroxyflavanone derived from Miconia chamissois Naudin) with the chemotherapeutic TMZ in vitro using tumor (U-251MG) and normal astrocyte (NHA) cell lines and in vivo using the chick embryo chorioallantoic membrane (CAM) assay. The combination was cytotoxic and selective for tumor cells (28 μg/mL Mat and 9.71 μg/mL TMZ). Additionally, the combination did not alter cell adhesion but caused morphological changes characteristic of apoptosis in vitro. Notably, the combination was also able to reduce tumor growth in the chick embryo model (CAM assay). The docking results showed that Mat was the best ligand to the cell death membrane receptor TNFR1 and to TNFR1/TMZ complex, suggesting that these two molecules may be working together increasing their potential. In conclusion, Mat-TMZ can be a good candidate for pharmacokinetic studies in view of clinical use for the treatment of glioblastoma.

Diagnosis of multiple sclerosis using multifocal ERG data feature fusion.

The purpose of this paper is to implement a computer-aided diagnosis (CAD) system for multiple sclerosis (MS) based on analysing the outer retina as assessed by multifocal electroretinograms (mfERGs). MfERG recordings taken with the RETI-port/scan 21 (Roland Consult) device from 15 eyes of patients diagnosed with incipient relapsing-remitting MS and without prior optic neuritis, and from 6 eyes of control subjects, are selected. The mfERG recordings are grouped (whole macular visual field, five rings, and four quadrants). For each group, the correlation with a normative database of adaptively filtered signals, based on empirical model decomposition (EMD) and three features from the continuous wavelet transform (CWT) domain, are obtained. Of the initial 40 features, the 4 most relevant are selected in two stages: a) using a filter method and b) using a wrapper-feature selection method. The Support Vector Machine (SVM) is used as a classifier. With the optimal CAD configuration, a Matthews correlation coefficient value of 0.89 (accuracy = 0.95, specificity = 1.0 and sensitivity = 0.93) is obtained. This study identified an outer retina dysfunction in patients with recent MS by analysing the outer retina responses in the mfERG and employing an SVM as a classifier. In conclusion, a promising new electrophysiological-biomarker method based on feature fusion for MS diagnosis was identified.

Midterm results and complications rates in vancouver type B2 and B3 periprosthetic femoral fractures treated with modular fluted tapered stems.

Evaluate the mid-term success rate of these stems in periprosthetic femur fractures and to analyze the complications observed with the use of these stems. METHODS: Thirty five patients that underwent hip revision surgery secondary to Vancouver type B2 and B3 periprosthetic femur fracture were evaluated. In all cases, modular fluted tapered stems were used. RESULTS: Average follow-up was 42 months. Average Postoperative Harris Hip Score (HHS) was 78.11. Fracture healing was obtained in a 100% of the patients. Average implant survival was 50 months. CONCLUSION: Modular fluted tapered stems demonstrated a high rate implant stability, proximal femoral bone reconstitution, and fracture healing.

GraXRS-Dependent Resistance of Staphylococcus aureus to Human Osteoarthritic Synovial Fluid.

Osteoarthritis is the most prevalent joint disease in the United States, with many patients requiring surgical replacement of the affected joint. The number of joint arthroplasty procedures performed each year is increasing, and infection is a leading cause of implant failure. Staphylococcus aureus is the most frequently isolated organism associated with periprosthetic joint infections of the knee or hip, and due to the emergence of antibiotic-resistant strains, treatment options are limited. Here, we show that synovial fluid from osteoarthritic patients is iron restrictive toward S. aureus and, for strains representing the clonal lineages USA100, USA200, USA400, and USA600, bactericidal. Remarkably, community-associated methicillin-resistant S. aureus (CA-MRSA) strain USA300-LAC was highly resistant to synovial fluid killing but could be sensitized to killing by mutation of the GraXRS regulatory system and GraXRS-regulated mprF gene or by small-molecule inhibition of GraR. Thus, we propose the GraXRS-VraFG regulatory system and mprF as targets for future therapeutics for treatment of S. aureus bone and joint infections.IMPORTANCE Osteoarthritis, a degenerative disease that results in the breakdown of joint cartilage and underlying bone, is the most prevalent joint disease in the United States. Surgical intervention, including total joint replacement, is a clinically effective procedure that can help to restore the patient's quality of life. Unfortunately, joint replacement procedures come with a risk of infection that is estimated to occur in 1 to 2% of cases, and periprosthetic joint infection (PJI) is a leading cause of implant failure, requiring revision surgery. Staphylococcus aureus is well known for its ability to cause PJIs and was found to be the most frequently isolated organism from PJIs of the knee or hip. Antibiotic-resistant strains can often limit treatment options. In this study, we demonstrate that the MRSA strain LAC can resist killing and grow in human synovial fluid from osteoarthritic knees. Furthermore, we show that the GraXRS regulatory system is required for the displayed synovial fluid resistance. We further demonstrate that a small-molecule inhibitor of GraR sensitizes LAC to synovial fluid, validating the Gra system as a therapeutic target for the treatment of PJIs in humans.

Is sarcopenia a risk factor for rotator cuff tears?

BACKGROUND: Sarcopenia is the loss of muscle mass and consequent loss of muscle function with aging. Currently, it is considered an independent risk factor for falls and fractures, disability, postoperative complications, and mortality. Rotator cuff tears are known to be influenced by systemic diseases such as diabetes mellitus, hypercholesterolemia, thyroid disease, and osteoporosis. The aim of our study was to determine if there is a correlation between sarcopenia prevalence and rotator cuff tears. METHODS: This is a prospective case-control study. Between May 2017 and May 2018, 106 patients were evaluated and divided into 2 groups. Group 1 (cases) included 53 consecutive patients with chronic symptomatic full-thickness rotator cuff tears (mean age, 72 ± 5 years), and group 2 (controls) included 53 patients without rotator cuff tears (mean age, 71 ± 6 years). Sarcopenia was diagnosed with the presence of 2 of 3 criteria: low skeletal muscle mass, inadequate muscle strength, and inadequate physical performance. Rotator cuff integrity was evaluated with magnetic resonance imaging in all patients. RESULTS: No significant differences were found in baseline data and demographic factors between the groups, except for the smoking habit (P = .02). The prevalence of sarcopenia was not significantly different between the groups, nor were gait speed, grip strength, and skeletal muscle mass index (P = .15, .99, and .9, respectively). CONCLUSION: The prevalence of sarcopenia in patients with rotator cuff tears was similar to an age- and sex-matched control population. Thus, with these results, we are not able to consider sarcopenia as an independent risk factor for rotator cuff tears.

Influencia de la fusión espinal en la orientación del implante acetabular / Influence of spinal fusion on acetabular implant orientation

Introducción: Las enfermedades degenerativas de la cadera y la columna vertebral son causas comunes de discapacidad y dolor y los síntomas suelen superponerse. Cuando algún parámetro se altera, otro debe modificarse para evitar el choque femoroacetabular y una posible luxación. Se piensa que la fijación lumbar afectaría la adaptación de la unidad espino-pélvica en las diferentes posturas. El objetivo de este estudio fue analizar el comportamiento espino-pélvico en pacientes con artroplastia total de cadera y artrodesis lumbar. Materiales y Métodos: Se realizó un estudio no aleatorizado, retrospectivo, de casos y controles en pacientes con artroplastia total de cadera evaluados con radiografía lumbopélvica de frente y de perfil en posición erecta y en sedestación, divididos en dos grupos: con artrodesis lumbar o sin ella. Se midieron parámetros espino-pélvicos y femoroacetabulares. Resultados: La muestra tenía 50 pacientes: 25 en cada grupo. Quince tenían artroplastia total de cadera bilateral y el nivel de fijación lumbar más frecuente era L5-S1. No hubo diferencia estadísticamente significativa en la edad y el sexo entre ambos grupos. Los pacientes con artrodesis lumbar necesitaron más flexión de cadera para sentarse, sin un aumento significativo asociado en la tasa de luxación. Conclusiones: La composición ideal de los componentes aún es difícil de alcanzar. La reconsideración de las "zonas seguras" de los componentes ha comenzado a alejarse de los valores del plano coronal de Lewinnek. Se ha propuesto un nuevo enfoque en las zonas seguras del plano sagital más apropiadas y precisas en pacientes seleccionados con enfermedad espino-pélvica grave. Nivel de Evidencia: III

Introduction: Degenerative diseases of the hip and spine are common causes of disability and pain, and the symptoms usually overlap. When a parameter is altered, another one should be modified to avoid femoroacetabular impingement and a potential dislocation. It is believed that lumbar fixation would affect the adaptation of the spinopelvic unit in different postures. This article aims to analyze the spinopelvic behavior in patients with Total Hip Arthroplasty (THA) and lumbar arthrodesis. Materials and Methods: A non-randomized retrospective study of cases and controls was carried out in patients with THA, who were assessed using anterior and lateral X-ray views in functional sitting and standing postures, divided into two groups depending on the presence or absence of lumbar arthrodesis. Spinopelvic parameters as well as femoroacetabular parameters were measured. Results: A sample of 50 patients was selected, 25 in each group. In total, 15 patients had bilateral THA, and the most common level of lumbar fixation was L5-S1. There was no statistically significant difference in gender and age between both groups. Lumbar arthrodesis patients required more hip flexion to sit, without being associated with a significant increase in the rate of dislocation. Conclusion: The ideal composition of the components is still difficult to achieve. The review of the "safe zones" of the components has started to depart from the values of the body plane proposed by Lewinnek. A new approach has been proposed to the safe zones of the sagittal plane, which are more appropriate and accurate in selected patients with severe spinopelvic pathology. Level of Evidence: IIII

Vástagos estriados cónicos modulares en revisión de artroplastia total de cadera. Estudio multicéntrico. Resultados y complicaciones a mediano plazo / Modular fluted tapered stems in revision total hip arthroplasty. Multicenter study. Medium-term results and complication rate

Introducción: Debido al crecimiento exponencial del número de artroplastias de cadera, se espera una mayor cantidad de re-visiones en las próximas décadas. Los vástagos cónicos estriados modulares se han vuelto populares en la última década por sus resultados favorables. El objetivo de este estudio es evaluar los resultados, las complicaciones y la tasa de supervivencia de estos vástagos en las revisiones de cadera, con un seguimiento a mediano plazo. materiales y métodos: Estudio multicéntrico, retrospectivo. Se incluyeron 182 pacientes a quienes se les realizó una cirugía de revisión de cadera entre 2007 y 2017. Se colo-caron 185 vástagos cónicos estriados de fijación distal. El déficit de stock óseo femoral se clasificó según Paprosky y Burnett; y las facturas periprotésicas, según la clasificación de Vancouver. Se evaluó a los pacientes clínicamente con el Harris Hip Score (HHS) y con radiografías a los 3 meses y anualmente para evaluar la estabilidad del vástago, la subsidencia y el aflojamiento, así como la consolidación de la osteotomía. Resultados: Seguimiento medio 55.18 meses. El HHS posoperatorio tuvo una media de 80,28 (DE = 12,8, IC95% 78,5-82,97). No hubo complicaciones posoperatorias en el 75,4% de los pacientes. Las complicaciones más frecuentes fueron inestabilidad (7,6%) y subsidencia del implante (11,5%). Al final del seguimiento, el 95,05% de los pacientes tenía un implante estable. Conclusiones: Los vástagos cónicos estriados modulares de fijación distal proporcionan una solución confiable, reproducible y duradera para el manejo de revisiones de componentes femorales a medio plazo. Nivel de Evidencia: IV

Background: The number of arthroplasties performed every year is increasing; therefore, a greater number of revisions is expected in the coming decades. Modular fluted tapered stems have become the gold standard for their results in different series of patients. The objective of this article is to evaluate the results, complications and the survival rate of these stems in hip revisions with a medium-term follow-up. Materials and Methods: Retrospective, multicenter analysis. One hundred eighty-two patients who had undergone hip revision surgery between 2007 and 2017 were included. One hundred eighty-five modular fluted tapered stems were placed. Femoral bone stock defects were classified according to Paprosky and Burnett; and periprosthetic femur fractures according to Vancouver classification. Patients were evaluated clinically with Harris Hip Score (HHS) and radiographically 3 months after surgery and every year to assess stem stability, subsidence and loosening, as well as osteotomy healing. Results: Average follow-up was 55.18 months. Postoperative HHS had an average of 80.28 (SD = 12.8, 95% CI = [78.5, 82.97]). There were no postoperative complications in 75.4% of the patients. The most frequent complications were instability in 7.6% and implant subsidence in 11.5%. At the end of the follow-up, 95.05% of the patients had a stable implant. Conclusion: Modular fluted tapered stems provide a reliable, reproducible solution for the management of femoral component revisions at medium-term. Level of Evidence: IV