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1.
BMC Musculoskelet Disord ; 25(1): 413, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802816

RESUMEN

BACKGROUND: Femoral fractures significantly contribute to disability, predominantly in the elderly. Despite this, data on postoperative pneumonia following femoral fracture surgeries remains sparse. Our study sought to explore the incidence and impact of postoperative pneumonia on outcomes following such surgeries. METHODS: A retrospective study analyzed femoral fracture patients hospitalized from 2016 to 2022. We scrutinized postoperative outcomes, including pneumonia, hospital stay duration, intensive care unit (ICU) admissions, and in-hospital mortality. We established stringent diagnostic criteria for postoperative pneumonia, incorporating both clinical signs and radiological evidence, excluding patients with prior infections or those discharged within 24 h post-surgery. Statistical analyses involved Chi-square and t-tests, linear regression, and logestic regression using SPSS. RESULTS: Out of 636 patients, 10.8% were diagnosed with postoperative pneumonia. The average age was 79.55 ± 8.57 years, with a male prevalence of 47.8%. Common comorbidities were hypertension (78.3%), diabetes (60.9%), and cardiovascular diseases (40.6%). Surgical interventions were categorized as intramedullary nailing (40.6%), partial hip replacement (37.7%), and dynamic hip screw (21.7%). Postoperative pneumonia was associated with older age (AOR = 1.053, 95% CI 1.020 to 1.087, p = 0.002), ICU admission (AOR = 2.283, 95% CI 1.256 to 4.148, p = 0.007), and longer length of hospital stay (AOR = 1.079, 95% CI 1.030 to 1.130, p = 0.001). The presence of pneumonia was associated with a 2.621-day increase in hospitalization after adjusting for other variables (p < 0.001, 95% CI: 1.454 to 3.789). CONCLUSION: This study accentuates the clinical significance of postoperative pneumonia in femoral fracture patients, with a noted incidence of 10.8%. A notable association with older age, prolonged hospital stays, and ICU admissions was observed, underscoring the necessity of addressing this complication to improve patient outcomes and healthcare resource allocation.


Asunto(s)
Fracturas del Fémur , Tiempo de Internación , Neumonía , Complicaciones Posoperatorias , Humanos , Masculino , Estudios Retrospectivos , Femenino , Anciano , Fracturas del Fémur/cirugía , Fracturas del Fémur/epidemiología , Neumonía/epidemiología , Neumonía/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Anciano de 80 o más Años , Tiempo de Internación/estadística & datos numéricos , Incidencia , Mortalidad Hospitalaria , Factores de Riesgo , Persona de Mediana Edad , Fijación Intramedular de Fracturas/efectos adversos , Prevalencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Artroplastia de Reemplazo de Cadera/efectos adversos
2.
Int Orthop ; 48(1): 71-78, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38051384

RESUMEN

PURPOSE: Total Hip Arthroplasty (THA) is one of the most commonly performed orthopaedic surgeries, with hip arthritis being the main indication. This procedure is usually performed when other non-surgical methods fail to relieve patients' hip pain and improve their quality of life. However, limited information exists to identify and compare the demographics and clinical characteristics of patients undergoing this procedure in Jordan. This study aims to identify these demographic and clinical characteristics and compare the findings in terms of gender differences. METHODOLOGY: This is a retrospective study that analysed the hospital records of 650 patients undergoing THA in tertiary referral hospital in Jordan over a four-year period from January 2019 to December 2022. The collected data were classified into three categories: demographic characteristics, perioperative variables, and patients' related health profiles. IBM's Statistical Package for the Social Sciences (SPSS) version 23 software (IBM, USA) and descriptive analysis were used for data analysis. RESULTS: Two-thirds of the sample studied were female (63.4%). In terms of bleeding profiles, the mean intraoperative blood loss was 542 millilitres. The major indication for THA was degenerative hip arthritis (50.5%), followed by hip dysplasia (40.3%).. Comparing the findings of the two gender groups, females were more likely to have degenerative and dysplastic hip arthritis (221 and 157, p = 0.04 and p = 0.1, respectively) when compared to males. Although males were more likely to lose more blood during the surgery (557 ml vs. 533 ml, p = 0.33, females needed more blood transfusions both during (21 vs. 6 patients, p = 0.12) and after the surgery (57 vs. 16 patients, p = 0.006). Furthermore, females were more likely to have comorbidities such hypertension (293 vs. 179 patients, p = 0.20), and hypothyroidism (313 vs 187, p = 0.36), and diabetes (85 vs. 38 patients, p = 0.15), among many other health conditions. However, in the study sample, male smokers outnumbered female smokers (132 vs. 63). CONCLUSION: Gender highly impacted the immediate surgical outcomes of patients who underwent THA. Females were more likely to need blood transfusions both during and after the surgery and had lower post-operative haemoglobin readings. In addition, females had more comorbidities and degenerative hip osteoarthritis. We believe that raising awareness about comorbidity management, preoperative smoking cessation, and perioperative blood transfusion management can improve medical and surgical outcomes.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Osteoartritis de la Cadera , Adulto , Humanos , Masculino , Femenino , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Estudios Retrospectivos , Calidad de Vida , Jordania/epidemiología , Factores de Riesgo , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/etiología
3.
BMC Surg ; 23(1): 266, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37658363

RESUMEN

PURPOSE: Hip fracture surgery is associated with a risk of morbidity and mortality, with admission hemoglobin levels being a significant predictor of mortality risk. The aim of this study is to evaluate the relationship between the preoperative hemoglobin (Hb) levels and mortality in patients who underwent hip fracture surgeries, with the goal of enhancing prognosis prediction and reducing complications within this patient subset. In addition, to assess the characteristics of patients at a higher risk of postoperative mortality. METHODS: This retrospective study was conducted at Jordan University Hospital, a single tertiary care and educational center. It included patients with hip fractures who underwent surgical repair at the Department of Orthopedic Surgery and were recruited between December 2019 and February 2022. We examined the relationships between preoperative hemoglobin status and variables such as age at admission, gender, fracture type, surgery type, comorbidities, duration of hospital stay, intensive care unit (ICU) admission, and survival outcomes. RESULTS: We included 626 patients; the mean age was 76.27 ± 9.57 years. 3-month and 6-month mortality rates were 11.2% and 14.1%, respectively. The highest mortality was observed in patients aged over 80 years (n = 53/245, 21.6%), and in male patients (n = 53/300, 17.7%). The Hb level upon admission was lower in individuals who died within 6 months compared to those who survived (10.97 ± 2.02 vs. 11.99 ± 2.39, p < 0.001). In multivariate analysis, the independent factors that were statistically significant in the model included gender (OR = 1.867; 95% CI 1.122-3.107, p = 0.016), age (OR = 1.060; 95% CI 1.029-1.092; p < 0.001), hemoglobin level upon admission (OR = 0.827; 95% CI 0.721-0.949; p = 0.007), history of renal disease (OR = 1.958; 95% CI 1.014-3.784; p = 0.045), length of hospital stay (OR = 1.080; 95% CI 1.036-1.126; p < 0.001), and ICU admission (OR = 1.848; 95% CI 1.049-3.257; p = 0.034). CONCLUSION: Our study illustrates that low hemoglobin levels, history of renal disease, along with male gender, advanced age, extended hospital stays, and ICU admission were significantly associated with 6-month mortality. Future investigations should consider assessing varying degrees of anemia based on hemoglobin concentrations to provide a more comprehensive understanding of anemia's impact on mortality. This study investigated the relationship between preoperative hemoglobin levels, patient characteristics, and mortality in patients who underwent hip fracture surgeries. The results showed that lower hemoglobin levels, history of renal disease, male gender, advanced age, extended hospital stays, and ICU admission were significant predictors for mortality.


Asunto(s)
Fracturas de Cadera , Procedimientos Ortopédicos , Humanos , Masculino , Anciano de 80 o más Años , Anciano , Estudios Retrospectivos , Fracturas de Cadera/cirugía , Hospitalización , Tiempo de Internación
4.
Ren Fail ; 45(1): 2223313, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37340972

RESUMEN

INTRODUCTION: Hip fractures have several adverse effects on patients' morbidity and mortality. Postoperative Acute kidney injury (AKI) is one of the complications that have a significant impact on the patient's overall prognosis. We aimed to identify AKI risk after hip fracture surgery and the preoperative and intraoperative risk factors. METHODOLOGY: We conducted a retrospective cohort study in a tertiary care hospital on adult patients who underwent surgery for hip fractures between January 2015 and August 2021. All clinical data were reviewed. RESULT: A total of 611 patients were included (age = 76.44 ± 9.69 years). 126 (20.6%) of them developed AKI postoperatively. In multilinear logistic regression analysis, factors associated with postoperative AKI included eGFR [odds ratio (OR): 0.98; 95% confidence interval (CI): 0.97-0.99 with a p value .01], spinal anesthesia [OR: 1.78; 95% CI: 1.1-2.9 with a p value .01], and partial hip replacement (PHR) type of surgery [OR: 0.56; 95% CI: 0.32-0.96 with a p value .036]. The development of postoperative AKI was the strongest factor that increase mortality of the patients as the (HR = 2.42, CI 95% [1.57-3.74]; p value <.001). CONCLUSION: In this study, we highlight that lower eGFR, and spinal anesthesia were associated with a higher risk of AKI, and PHR surgery has lower odds to develop AKI. Postoperative AKI is associated with a higher mortality rate after hip fracture surgery.


Asunto(s)
Lesión Renal Aguda , Fracturas de Cadera , Adulto , Humanos , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Incidencia , Estudios de Cohortes , Factores de Riesgo , Fracturas de Cadera/cirugía , Fracturas de Cadera/complicaciones , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología
5.
BMC Med Educ ; 23(1): 593, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37605179

RESUMEN

BACKGROUND: Burnout is a serious issue that affects physicians more than the general population; however, those with higher levels of grit and resilience have been shown to experience lower levels of burnout. The primary aim was to determine the prevalence of burnout among Jordanian orthopedic surgeons, explore its risk factors, and investigate the relationship between burnout and grit and resilience. METHODS: We conducted a questionnaire-based cross-sectional study targeting a total of 180 orthopedic surgeons attending the yearly Jordanian National Orthopedic Conference (JNOC). Non-random sampling (i.e., convenience) was utilized to recruit participants. The abbreviated Maslach Burnout Inventory, short grit scale, and Connor-Davidson Resilience Scale were used. Scores were examined using the Mann-Whitney U, Kruskal-Wallis H, and Spearman's rho tests, of which results were corrected using the Bonferroni method. RESULTS: Among 135 respondents, 62.2% were specialists and 37.8% were residents. About 52.0% practiced in public hospitals. Approximately 69.0% worked for more than 50 h weekly. The prevalence of burnout among all participants was 45.2% with more frequency among residents (66.7%). Burnout and the participants' grit and resilience showed an inverse relationship (ρ = -0.441 and ρ = -0.312, respectively). Age (ρ = 0.337), number of children (ρ = 0.245), and years of experience (ρ = 0.331) were positively correlated with grit. The median score for grit was higher in physicians who had or are having their residency outside Jordan (p < 0.001). Age (ρ = 0.233) and years of experience (ρ = 0.269) were positively correlated with resilience. CONCLUSION: Jordanian orthopedic surgeons face significant rates of burnout. Institutional efforts should be taken to detect and prevent burnout in addition to enhancing the grit and resilience among orthopedic professionals.


Asunto(s)
Cirujanos Ortopédicos , Médicos , Niño , Humanos , Lactante , Estudios Transversales , Jordania/epidemiología , Agotamiento Psicológico
6.
Int Orthop ; 47(12): 2933-2940, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37341749

RESUMEN

PURPOSE: Developmental dysplasia of the hip is still a prevailing secondary cause of early hip osteoarthritis in Jordan. Dysplastic coxarthrosis can result in significant and disabling hip pain with impaired patient's functionality. Due to this significant morbidity, patients ultimately need total hip arthroplasty, which offers the best functional outcome. Significant anatomical aberrances do exist in such hips as a result of old dysplasia; such pathoanatomical changes can complicate an already difficult surgery and lead to significant intraoperative blood loss and haemoglobin drop postoperatively. So, the aim of this research was to investigate on the intraoperative blood loos, and postoperative haemoglobin drop in these patients. METHODS: A cross-sectional study design was adopted, and 162 patients with advanced hip osteoarthrosis secondary to developmental dysplasia of the hip (DDH) were studied. We studied predictors of hemoglobin drop and blood loss and linked some variables to this outcome variable using different statistical tests. RESULTS: Our results showed a positive correlation between blood loss and BMI (r = 0.27, p = 0.73), haemoglobin drop and duration of surgery (r = 0.14, p = 0.07), length of hospital stay and duration of surgery (r = 0.25, p = 0.001). No significant differences between outcome measures (blood loss, haemoglobin drop, and duration of surgery) between males and females (p = 0.38, 0.93, 0.77 respectively). However, there was a statistically significant differences in haemoglobin drop among patients underwent general versus spinal anaesthesia (p = 0.03). additionally, there was a statistically significant association in length of hospital stay among smokers (p = 0.03), and patients who didn't prescribed anxiolytic preoperatively (p = 0.008). CONCLUSION: Haemoglobin drop and blood loss in patients with dysplastic coxarthrosis were linked to increased preoperative BMI. Use of preoperative anxiolytics, and being non-smoker decreased the length of hospital stays. General anaesthesia was associated with more haemoglobin drop as well.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Osteoartritis de la Cadera , Masculino , Femenino , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Osteoartritis de la Cadera/complicaciones , Osteoartritis de la Cadera/epidemiología , Osteoartritis de la Cadera/cirugía , Luxación Congénita de la Cadera/cirugía , Pérdida de Sangre Quirúrgica , Jordania/epidemiología , Estudios Transversales , Displasia del Desarrollo de la Cadera/cirugía , Resultado del Tratamiento , Estudios Retrospectivos
7.
BMC Musculoskelet Disord ; 23(1): 1092, 2022 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-36514028

RESUMEN

INTRODUCTION: Neck-shaft angle (NSA) is of paramount importance to orthopedic surgeons due to its implications for various pathologies of the hip and femur. The primary aim of the study was to establish if NSA measurement may be affected by imaging position (standing and supine) and provide evidence regarding whether the contralateral NSA can be used as a template. The secondary aim was to determine a reference value and precisely understand the effects of sex on NSA measurement. MATERIALS AND METHODS: We measured bilateral NSA in a retrospective study of 200 standing and 200 supine anteroposterior pelvis radiographs that met the inclusion criteria, while paying special attention to bilateral hip symmetry. The overall inter-rater reliability was 0.688 (CI 0.128-0.851). Matching was performed according to sex (exact matching) and age. Paired t-test, Pearson correlation coefficient, and independent sample t-test were used (p < 0.01). RESULTS: A total of 400 pairs of femoral necks were reviewed, comprising of 200 males and 200 females. In the upright radiograph, the overall mean NSA was 131.21° ± 4.72°. There was no significant difference between right and left femur NSA among the patients (p = 0.95). On both sides, male NSA was higher than female NSA (p < 0.001). In supine radiograph, the overall mean NSA for the supine position was 133.06° ± 5.71°. There was a significant difference between NSA of the right and left femur among the patients in the supine position (p < 0.001). On supine radiographs there was no statistically significant difference between male and female NSA (p = 0.85). CONCLUSION: Our findings indicated no significant variability in upright radiographs between the right and left NSA. In contrast, significant asymmetry between the right and left NSA was found in the supine radiographs. However, this study does not provide definitive clinical evidence, and further clinical-oriented research is required. LEVEL OF EVIDENCE: Level III; retrospective comparative study.


Asunto(s)
Cuello Femoral , Fémur , Humanos , Masculino , Femenino , Cuello Femoral/diagnóstico por imagen , Estudios Retrospectivos , Reproducibilidad de los Resultados , Radiografía , Fémur/diagnóstico por imagen
8.
Int J Cancer ; 149(10): 1817-1827, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34289100

RESUMEN

Approximately one-third of estrogen receptor (ER) positive breast tumors fail to respond to or become resistant to hormonal therapy. Although the mechanisms responsible for hormone resistance are not completely understood, resistance is associated with alterations in ERα; overexpression of proteins that interact with the receptor; and hormone-independent activation of the receptor by growth factor signal transduction pathways. Our previous studies show that in estrogen dependent breast cancer cells, activation of the epidermal growth factor signaling pathway increases intracellular calcium which binds to and activates ERα through sites in the ligand-binding domain of the receptor and that treatment with extracellular calcium increases the concentration of intracellular calcium which activates ERα and induces hormone-independent cell growth. The present study asked whether overexpression of calcium channels contributes to the hormone-independent and -resistant phenotype of breast cancer cells and whether clinically used calcium channel blockers reverse hormone independence and resistance. The results show that hormone-independent and -resistant cells overexpress calcium channels, have high concentrations of intracellular calcium, overexpress estrogen responsive genes and, as expected, grow in the absence of estradiol and that treatment with calcium channel blockers decreased the concentration of intracellular calcium, the expression of estrogen responsive genes and cell growth. More importantly, in hormone-resistant cells, treatment that combined a calcium channel blocker with an antiestrogen reversed resistance to the antiestrogen.


Asunto(s)
Neoplasias de la Mama/genética , Calcio/metabolismo , Resistencia a Antineoplásicos/genética , Estradiol/farmacología , Regulación Neoplásica de la Expresión Génica/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/genética , Canales de Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Moduladores de los Receptores de Estrógeno/farmacología , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Estrógenos/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo
9.
J Orthop Sci ; 24(2): 290-293, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30316659

RESUMEN

BACKGROUND: Patellofemoral knee pain is a common cause of anterior knee pain. The Kujala anterior knee pain score is a scoring system for the clinical assessment of disease severity. The purpose of this cross-sectional study was to validate an Arabic translation of the original Kujala anterior knee pain score to assess Arabic-speaking patients with patellofemoral pain syndrome. METHODS: The Kujala anterior knee pain score was translated into Arabic by a group of native Arabic and native English speakers including orthopedic surgeons, residents, and a medical student. Questionnaires were filled by 127 patients visiting our outpatient department complaining of anterior knee pain diagnosed clinically and after exclusion of other pathologies. Questionnaires were re-filled at least 2 weeks later via phone contact from a member of our team. After exclusions, 97 questionnaires were analyzed for reliability using Cronbach's alpha for the scoring system's internal consistency and intraclass correlation coefficient for test-retest analysis. RESULTS: The mean score of the questionnaire before the follow-up was 62.38 (±17.78) and 64.02 (±18.47) after the follow-up. The scoring system's internal consistency measured via Cronbach's alpha was 0.824. Average ICC for the scoring system was 0.948 (CI: 0.923-0.965) and for single measures, 0.902 (CI: 0.856-0.933). Further, 94.8% of patients were contacted before initiating physiotherapy. Forty-six of the patients (47.4%) showed improvement in their scores when contacted, 44 patients (45.4%) showed a slight worsening of their scores and seven patients' (7.2%) scores were unchanged. CONCLUSIONS: The Arabic translation of the Kujala anterior knee pain score is a valid, reliable, useful, and easy-to-interpret scoring system to assess Arabic-speaking patients with patellofemoral pain syndrome.


Asunto(s)
Evaluación de la Discapacidad , Dimensión del Dolor , Síndrome de Dolor Patelofemoral/diagnóstico , Encuestas y Cuestionarios , Traducciones , Adulto , Factores de Edad , Anciano , Árabes , Intervalos de Confianza , Estudios Transversales , Femenino , Humanos , Jordania , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto Joven
10.
Am J Pathol ; 182(6): 2264-75, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23660011

RESUMEN

The molecular mechanisms underlying progression of prostate cancer (PCa) to castrate-resistant (CR) and metastatic disease are poorly understood. Our previous mechanistic work shows that inhibition of transcription factor Stat5 by multiple alternative methods induces extensive rapid apoptotic death of Stat5-positive PCa cells in vitro and inhibits PCa xenograft tumor growth in nude mice. Furthermore, STAT5A/B induces invasive behavior of PCa cells in vitro and in vivo, suggesting involvement of STAT5A/B in PCa progression. Nuclear STAT5A/B protein levels are increased in high-grade PCas, CR PCas, and distant metastases, and high nuclear STAT5A/B expression predicts early disease recurrence and PCa-specific death in clinical PCas. Based on these findings, STAT5A/B represents a therapeutic target protein for advanced PCa. The mechanisms underlying increased Stat5 protein levels in PCa are unclear. Herein, we demonstrate amplification at the STAT5A/B gene locus in a significant fraction of clinical PCa specimens. STAT5A/B gene amplification was more frequently found in PCas of high histologic grades and in CR distant metastases. Quantitative in situ analysis revealed that STAT5A/B gene amplification was associated with increased STAT5A/B protein expression in PCa. Functional studies showed that increased STAT5A/B copy numbers conferred growth advantage in PCa cells in vitro and as xenograft tumors in vivo. The work presented herein provides the first evidence of somatic STAT5A/B gene amplification in clinical PCas.


Asunto(s)
Amplificación de Genes , Neoplasias de la Próstata/genética , Factor de Transcripción STAT5/genética , Proteínas Supresoras de Tumor/genética , Animales , Variaciones en el Número de Copia de ADN , ADN de Neoplasias/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Hibridación Fluorescente in Situ , Masculino , Ratones , Ratones Desnudos , Clasificación del Tumor , Trasplante de Neoplasias , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Recurrencia , Factor de Transcripción STAT5/biosíntesis , Trasplante Heterólogo , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/biosíntesis
11.
Front Endocrinol (Lausanne) ; 15: 1380047, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184142

RESUMEN

The estrogen receptor alpha (ERα) plays a central role in the etiology, progression, and treatment of breast cancers. Constitutively activating somatic mutations Y537S and D538G, in the ligand binding domain (LBD) of ESR1, are associated with acquired resistance to endocrine therapies. We have previously shown that the metalloestrogen calcium activates ERα through an interaction with the LBD of the receptor. This study shows that cadmium activates ERα through a mechanism similar to calcium and contributes to, and further increases, the constitutive activity of the ERα mutants Y537S and D538G. Mutational analysis identified C381, N532A, H516A/N519A/E523A, and E542/D545A on the solvent accessible surface of the LBD as possible calcium/metal interaction sites. In contrast to estradiol, which did not increase the activity of the Y537S and D538G mutants, cadmium increased the activity of the constitutive mutants. Mutation of the calcium/metal interaction sites in Y537S and D538G mutants resulted in a significant decrease in constitutive activity and cadmium induced activity. Mutation of calcium/metal interaction sites in wtERα diminished binding of the receptor to the enhancer of estrogen responsive genes and the binding of nuclear receptor coactivator 1 and RNA polymerase II. In contrast to wtERα, mutation of the calcium/metal interaction sites in the Y537S and D538G mutants did not diminish binding to DNA but prevented a stable interaction with the coactivator and polymerase. Growth assays further revealed that calcium channel blockers and chelators significantly decreased the growth of MCF7 cells expressing these constitutively active mutants. Taken together, the results suggest that exposure to cadmium plays a role in the etiology, progression, and response to treatment of breast cancer due, in part, to its ability to activate ERα.


Asunto(s)
Cadmio , Receptor alfa de Estrógeno , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genética , Humanos , Mutación , Células MCF-7 , Femenino , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Calcio/metabolismo
12.
Cureus ; 16(1): e52631, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38374843

RESUMEN

Purpose Hip fractures are common and serious injuries as they lead to high mortality and morbidity and have a significant effect on patients' lives. Additionally, these injuries have substantial socioeconomic consequences for patients' quality of life, their families, and healthcare systems. The aim of this study is to assess the quality of life (QoL) in patients after hip fracture surgery. Methods This study involved a cross-sectional survey between February 2016 and December 2019, with a sample of 199 patients who suffered a hip fracture and were treated at a tertiary care teaching hospital. The participants completed the EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) questionnaire. Pearson's chi-squared test, independent sample t-test, and Pearson's correlation coefficient (r) were used in the analysis. Results We found that there is a statistically significant association between age and having problems with mobility (p=0.023), self-care (p<0.001), and usual activity (p=0.029). In addition, increased age was significantly associated with decreased EuroQol Visual Analog Scale (EQ-VAS) scores (r=-0.213, p=0.003). We also found a statistically significant association between gender and self-care, as males were more likely to report having problems with self-care when compared to females (OR: 3.63; CI 95%: 1.77-7.44; p<0.001). Conclusion Mobility, self-care, and usual activity were the most significantly affected quality of life measures and were more apparent in older age groups. Patients should be educated about the possibility of a decline in their QoL and the role of postoperative rehabilitation in improving patients' mobility. Periodic QoL screening should be done as early as possible to detect any further decrease. Future research should standardize postoperative interview intervals to improve QoL evaluation and include a control group.

13.
Am J Pathol ; 180(2): 599-607, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22189618

RESUMEN

We demonstrate that a Rho kinase inhibitor (Y-27632), in combination with fibroblast feeder cells, induces normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro, without transduction of exogenous viral or cellular genes. Primary prostate and mammary cells, for example, are reprogrammed toward a basaloid, stem-like phenotype and form well-organized prostaspheres and mammospheres in Matrigel. However, in contrast to the selection of rare stem-like cells, the described growth conditions can generate 2 × 10(6) cells in 5 to 6 days from needle biopsies, and can generate cultures from cryopreserved tissue and from fewer than four viable cells. Continued cell proliferation is dependent on both feeder cells and Y-27632, and the conditionally reprogrammed cells (CRCs) retain a normal karyotype and remain nontumorigenic. This technique also efficiently establishes cell cultures from human and rodent tumors. For example, CRCs established from human prostate adenocarcinoma displayed instability of chromosome 13, proliferated abnormally in Matrigel, and formed tumors in mice with severe combined immunodeficiency. The ability to rapidly generate many tumor cells from small biopsy specimens and frozen tissue provides significant opportunities for cell-based diagnostics and therapeutics (including chemosensitivity testing) and greatly expands the value of biobanking. In addition, the CRC method allows for the genetic manipulation of epithelial cells ex vivo and their subsequent evaluation in vivo in the same host.


Asunto(s)
Amidas/farmacología , Proliferación Celular/efectos de los fármacos , Reprogramación Celular/fisiología , Inhibidores Enzimáticos/farmacología , Células Epiteliales/efectos de los fármacos , Células Nutrientes/fisiología , Piridinas/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidores , Animales , Mama/citología , Técnicas de Cultivo de Célula , Reprogramación Celular/efectos de los fármacos , Colágeno , Combinación de Medicamentos , Células Epiteliales/citología , Células Nutrientes/citología , Femenino , Humanos , Laminina , Masculino , Ratones , Ratones SCID , Trasplante de Neoplasias , Próstata/citología , Neoplasias de la Próstata/patología , Proteoglicanos , Trasplante Heterólogo
14.
Orthop Res Rev ; 15: 191-198, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37791038

RESUMEN

Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical efficacy. Its use is significantly hindered due to label warnings resulting from pre-clinical rat studies demonstrating an increased risk of osteosarcoma. However, clinical trials and post-marketing surveillance studies did not demonstrate any increased risk of osteosarcoma, even after prolonged periods of surveillance reaching up to 15 years, with most of the identified cases of osteosarcomas being solitary and predominantly attributed to other factors. This systematic review provides a comprehensive overview of the currently available literature and provides the highest level of clinical evidence towards demonstrating the lack of any substantial evidence towards osteosarcoma development in patients utilizing TPTD.

15.
PLoS One ; 18(6): e0287337, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37352251

RESUMEN

AIM: To investigate the extent of complementary medicine (CM) use and the most common therapies utilized by Jordanian patients with musculoskeletal (MSK) diseases. METHODS: A semi-structured questionnaire was used to conduct a cross-sectional survey of outpatient orthopedic and rheumatology patients at an academic medical center in Amman, Jordan between January and September 2020. RESULTS: A convenience sample of 1001 patients was interviewed (82% females). Pearson's chi-square comparisons showed that nutritional CM was used by 43.4% of patients, while 29.8% used physical CM, and 16% used both. Almost all used the nutritional or physical CM in addition to their prescribed treatment. Nutritional form use was significantly higher among females, older age groups, married people, and those who worked (p < .05). Physical form use was statistically more prevalent in older age groups and those with a higher level of education (p < .05). Family income and urban residence were not significantly associated with the use of either form of CM therapy. Olive oil was the most frequently reported nutritional type (22.9%), and cupping was the most reported physical type (41.6%). Recommendations to use CM came primarily from family members or friends (64% of nutritional CM users and 59% of physical CM users). A physician or pharmacist was cited more frequently with physical CM (24% versus 8% for the nutritional form). In contrast, media sources were cited more for nutritional than physical form (28% versus 7%). Over half of the patients believed they received the desired effect from CM. Surprisingly, only 9.5% of the patients admitted to discussing their CM use with their physician. CONCLUSION: CM use is prevalent among Jordanian patients with MSK disorders. Most patients rely on family and friends for recommendations, and they rarely inform their physician of the CM use. Physicians should routinely inquire about CM to provide patients with information regarding their benefits and risks.


Asunto(s)
Terapias Complementarias , Enfermedades Musculoesqueléticas , Médicos , Femenino , Humanos , Anciano , Masculino , Estudios Transversales , Enfermedades Musculoesqueléticas/terapia , Pacientes Ambulatorios
16.
Int J Endocrinol ; 2023: 9907948, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38131032

RESUMEN

Background: Although prostate cancer patients initially respond to androgen deprivation therapy, most patients progress to a resistant phenotype. Castration resistance is due, in part, to intratumoral and/or adrenal synthesis of androgens, overexpression or mutation of the androgen receptor (AR), stabilization of AR by chaperones, and ligand-independent activation of AR. Increasing evidence also links disruption of calcium homeostasis to progression of prostate cancer. Our previous study shows that heavy metal cadmium activates the AR through a ligand-independent mechanism. Cadmium mimics calcium in biological systems due to their similar ionic charge and radius. This study determines whether calcium activates AR and whether first- and second-generation antiandrogens block the ability of calcium to activate the receptor. Methods: The expression of androgen-responsive genes and calcium channels was measured in prostate cells using a quantitative real-time polymerase chain reaction assay. Cell growth was measured. Results: To ask whether calcium activates AR, prostate cells were treated with calcium in the absence and presence of the first-generation antiandrogens hydroxyflutamide and bicalutamide and the second-generation antiandrogen enzalutamide, and the expression of androgen-responsive genes and cell growth was measured. In the normal PWR-1E cells and HEK293T cells transiently expressing AR, treatment with calcium increased the expression of androgen-responsive genes by approximately 3-fold. The increase was blocked by enzalutamide but was not consistently blocked by the first-generation antiandrogens. In LNCaP cells which contain a mutant AR, treatment with calcium also increased the expression of androgen-responsive genes by approximately 3-fold, and the increase was more effectively blocked by enzalutamide than by hydroxyflutamide or bicalutamide. Treatment with calcium also increased cell growth that was blocked by enzalutamide. To ask whether dysregulation of calcium channels is associated with castration resistance, calcium channels were measured in the normal PWR-1E prostate cells, the hormone-responsive LNCaP cells, and the castration-resistant VCaP and 22RV1 cells. Compared to normal prostate cells, the hormone-responsive and hormone-resistant cells overexpressed several calcium channels. Conclusions: The results of this study show that calcium activates AR and increases cell growth and that calcium channels are overexpressed in hormone-responsive and hormone-resistant prostate cancer cells. Taken together, the results suggest a novel role of calcium in the castration-resistant phenotype.

17.
J Immunother Cancer ; 11(2)2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36731891

RESUMEN

Women with BRCA1 germline mutations have approximately an 80% lifetime chance of developing breast cancer. While the tumor suppressor function of BRCA1 in breast epithelium has been studied extensively, it is not clear whether BRCA1 deficiency in non-breast somatic cells also contribute to tumorigenesis. Here, we report that mouse Brca1 knockout (KO) in mature T lymphocytes compromises host antitumor immune response to transplanted syngeneic mouse mammary tumors. T cell adoptive transfer further corroborates CD8+ T cell-intrinsic impact of Brca1 KO on antitumor adaptive immunity. T cell-specific Brca1 KO mice exhibit fewer total CD8+, more exhausted, reduced cytotoxic, and reduced memory tumor-infiltrating T cell populations. Consistent with the preclinical data, cancer-free BRCA1 mutation-carrying women display lower abundance of circulating CD8+ lymphocytes than the age-matched control group. Thus, our findings support the notion that BRCA1 deficiency in adaptive immunity could contribute to BRCA1-related tumorigenesis. We also suggest that prophylactic boosting of adaptive immunity may reduce cancer incidence among at-risk women.


Asunto(s)
Antineoplásicos , Neoplasias , Femenino , Ratones , Animales , Linfocitos T CD8-positivos , Inmunidad , Ratones Noqueados , Carcinogénesis
18.
Metabolites ; 12(5)2022 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-35629952

RESUMEN

Breast cancer (BC) is one of the leading causes of cancer mortality in women worldwide, and therefore, novel biomarkers for early disease detection are critically needed. We performed herein an untargeted plasma metabolomic profiling of 55 BC patients and 55 healthy controls (HC) using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS). Pre-processed data revealed 2494 ions in total. Data matrices' paired t-tests revealed 792 ions (both positive and negative) which presented statistically significant changes (FDR < 0.05) in intensity levels between cases versus controls. Metabolites identified with putative names via MetaboQuest using MS/MS and mass-based approaches included amino acid esters (i.e., N-stearoyl tryptophan, L-arginine ethyl ester), dipeptides (ile-ser, met-his), nitrogenous bases (i.e., uracil derivatives), lipid metabolism-derived molecules (caproleic acid), and exogenous compounds from plants, drugs, or dietary supplements. LASSO regression selected 16 metabolites after several variables (TNM Stage, Grade, smoking status, menopausal status, and race) were adjusted. A predictive conditional logistic regression model on the 16 LASSO selected ions provided a high diagnostic performance with an area-under-the-curve (AUC) value of 0.9729 (95% CI 0.96−0.98) on all 55 samples. This study proves that BC possesses a specific metabolic signature that could be exploited as a novel metabolomics-based approach for BC detection and characterization. Future studies of large-scale cohorts are needed to validate these findings.

19.
Int Med Case Rep J ; 15: 287-292, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35726264

RESUMEN

Introduction: Aneurysmal bone cysts (ABC) are expansile, lytic, and benign but locally aggressive lesions. Pelvic ABCs are rare and sometimes difficult to manage surgically. Case Report: A 17-year-old female presented with progressive pain and swelling in the right inguinal region. Pelvis radiograph showed a lytic expansile lesion of the superior pubic ramus. A multiloculated cystic lesion was evident on magnetic resonance imaging, and postoperative histopathological evaluation confirmed the diagnosis of ABC. The patient was treated successfully with an intralesional curettage and bone grafting. The postoperative course was uncomplicated with complete healing and no recurrence after 14 months of follow-up. Conclusion: ABC of the pubic ramus is a rare entity. Complete intralesional curettage and bone grafting is an effective treatment for pubic ABC. An individualized management approach considering the surgical team expertise, tumor size, and proximity to neighboring structures is recommended. .

20.
BMC Sports Sci Med Rehabil ; 14(1): 98, 2022 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-35655282

RESUMEN

BACKGROUND: Anterior cruciate ligament (ACL) injuries have been increasing significantly over time. The relationship between the ACL injury and the knee joint structures is poorly understood. The purpose of this study is to examine whether the measurements of different structures in the knee joint are linked with ACL injury in affected patients. METHODS: This retrospective case-control study included patients who suffered from ACL tears and underwent magnetic resonance imaging (MRI). A control group of patients with no knee pathologies on MRI was included. Fourteen knee variables, including lateral meniscus (LM) posterior horn height, length, depth, and volume; medial meniscus (MM) posterior horn height, length, depth, and volume; lateral and medial (MFC) femoral condyle sphere diameter; lateral and medial tibial plateau length; and patella tendon horizontal and vertical diameter, were collected. A multivariate logistic regression including LM posterior horn depth, MM posterior horn length, MM volume, MFC sphere diameter, and patella tendon horizontal diameter and receiver operating characteristic curve, was used to compare the two groups. RESULTS: A total of 85 patients were included in our study; 54 suffered from ACL injuries and 31 as a control group with normal knee MRI. Logistic regression revealed that increased LM posterior horn depth (OR = 1.27; 95% CI = 1.03-1.56; p = 0.028), decreased MM posterior horn length (OR = 0.71; 95% CI = 0.55-0.93; p = 0.013), and MFC sphere diameter (OR = 1.20; 95% CI = 1.01-1.43; p = 0.035) were independent risk factors for ACL rupture. The MFC sphere diameter yielded the highest area under the curve: 0.747 (95% CI, 0.632-0.862). No difference was found in the other measurements between the two groups. CONCLUSIONS: Concerning the difference in anatomical variations, the lateral meniscus posterior horn depth and medial femoral condyle sphere diameter were higher, while medial meniscus posterior horn length was lower in patients with an ACL injury. These structural knee measurements could have a possible increase in the likelihood of sustaining an ACL injury and can be used by clinicians to predict ACL injury.

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