Postoperative pneumonia after femoral fracture surgery: an in-depth retrospective analysis.

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.

Quality of Life After Hip Fracture Surgery in the Elderly: A Cross-Sectional Study.

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.

Total hip arthroplasty for adult patients with hip arthritis in Jordan: clinical profiles and patient characteristics.

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.

Calcium Activation of the Androgen Receptor in Prostate Cells.

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.

The Risk of Developing Osteosarcoma After Teriparatide Use: A Systematic Review.

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.

Preoperative hemoglobin levels and mortality outcomes after hip fracture patients.

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.

Burnout, grit and resilience among Jordanian orthopedic surgeons: a cross-sectional study.

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.

Preoperative and intraoperative risk factors for acute kidney injury after hip fracture surgery: a cohort retrospective study.

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.

Intraoperative blood loss and haemoglobin drop in patients with developmental dysplasia of the hip in Jordan undergoing total hip arthroplasty.

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.

Rates, patterns, and predictors of complementary medicine use among patients with musculoskeletal diseases.

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.

BRCA1 deficiency in mature CD8+ T lymphocytes impairs antitumor immunity.

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.

Femoral neck shaft angle measurement on plain radiography: is standing or supine radiograph a reliable template for the contralateral femur?

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.

Microbiological Profile and Drug Resistance Analysis of Postoperative Infections following Orthopedic Surgery: A 5-Year Retrospective Review.

Background: The distribution of postoperative orthopedic infection and their susceptibility pattern to antibiotics vary regionally and change over time. The incidence of methicillin-resistant Staphylococcus aureus infection is rising worldwide. Therefore, knowledge of the frequency of the causative microorganisms and their susceptibility to antibiotics are necessary for an improved therapeutic outcome. This study aims to study the frequency and distribution of postoperative orthopedic infection and their resistance pattern to antibiotics. Methods: The study utilized a retrospective design that took place over a period of 5 years from 2016 and 2020 at a tertiary care hospital. The bacterial culture testing was performed by a recommended method. Descriptive statistics were used to analyze the data. Results: A total of 158 patients (100 males and 58 females) with positive cultures of postoperative orthopedic infection were included. The most common infective organism was Staphylococcus aureus, 64 patients (38.1%); coagulase-negative staphylococci, 40 patients (23.8%); Klebsiella species, 14 patients (8.3%); and Enterococcus species, Escherichia coli, and Pseudomonas aeruginosa in 10 patients (6%). Data also showed that gram-positive bacteria were detected in 118 patients (70.8%), while gram-negative microorganisms were found in 50 patients (29.8%). Among Staphylococcus aureus, 79.7% were MRSA, and vancomycin was the most effective antibiotic in staphylococcus infections. The antibiotics with the greatest sensitivity to gram-positive bacteria were vancomycin, linezolid, tigecycline, moxifloxacin, and nitrofurantoin, while the antibiotics for gram-negative bacteria with greater sensitivity were tigecycline, amikacin, ertapenem, imipenem, and cefotaxime. Conclusion: Staphylococcus aureus is the most common postoperative orthopedic infection, which was predominantly MRSA with vancomycin being the most effective antibiotic. In addition, the results showed a high resistance pattern to the commonly used antibiotics, leaving few choices. Antibiotic agents should be carefully selected according to specific drug sensitivity through routine monitoring of drug resistance patterns and to help formulate hospital antibiotic policy.

Can MRI knee joint measurements predict the population at risk of ACL injury?

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.

Temozolomide-induced guanine mutations create exploitable vulnerabilities of guanine-rich DNA and RNA regions in drug-resistant gliomas.

Temozolomide (TMZ) is a chemotherapeutic agent that has been the first-line standard of care for the aggressive brain cancer glioblastoma (GBM) since 2005. Although initially beneficial, TMZ resistance is universal and second-line interventions are an unmet clinical need. Here, we took advantage of the known mechanism of action of TMZ to target guanines (G) and investigated G-rich G-quadruplex (G4) and splice site changes that occur upon TMZ resistance. We report that TMZ-resistant GBM has guanine mutations that disrupt the G-rich DNA G4s and splice sites that lead to deregulated alternative splicing. These alterations create vulnerabilities, which are selectively targeted by either the G4-stabilizing drug TMPyP4 or a novel splicing kinase inhibitor of cdc2-like kinase. Last, we show that the G4 and RNA binding protein EWSR1 aggregates in the cytoplasm in TMZ-resistant GBM cells and patient samples. Together, our findings provide insight into targetable vulnerabilities of TMZ-resistant GBM and present cytoplasmic EWSR1 as a putative biomarker.

Surgical Management of Aneurysmal Bone Cyst of the Pubis: A Case Report and Review of Literature.

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. .

Metabolomic Analysis of Plasma from Breast Cancer Patients Using Ultra-High-Performance Liquid Chromatography Coupled with Mass Spectrometry: An Untargeted Study.

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.

Incidence and Durability of SARS-CoV-2 Antibodies in Patients with Cancer and Health Care Workers following the First Wave of the Pandemic.

BACKGROUND: Patients with cancer and health care workers (HCW) are at higher risk for SARS-CoV-2 infection. There are limited data regarding the rate of symptomatic versus asymptomatic infection and subsequent seropositivity in both populations. METHODS: We performed a prospective study of patients and HCW across two institutions during the first wave of the pandemic to analyze the prevalence of SARS-CoV-2 antibodies, the extent of associated symptoms, and durability of serologic response. RESULTS: In 1,953 persons (733 patients and 1,220 HCW), overall seropositivity rates for 3.1% patients (95% CI 2.0-4.7) and 3.7% HCW (95% CI 2.7-4.9, p=0.520), were similar. Each institutions' seropositivity rates were numerically higher in HCW than patients. Non-Hispanic Whites and Asians had lower antibody rates (2.8%, 95% CI 2.0-3.8 and 3.3%, 95% CI 1.2-7.0) compared to Hispanics (6.9%, 95% CI 3.4-12.4) and non-Hispanic Blacks (5.9%, 95% CI 3.3-9.7), p < 0.001. Among persons with a positive SARS-CoV-2 antibody, 87% of patients and 56% of HCW did not recall having had a fever. Among HCW, administrative and technical personnel were most likely to be seropositive. The rate of persistent seropositivity at 3 months was similar between patients and HCW and was not influenced by the reporting of fever, cancer type, or therapy. CONCLUSION: These data suggest that patients are not at higher risk for febrile SARS-CoV-2 infections or more transient immunity than HCWs. Furthermore, racial differences and lack of association with the extent of HCW contact with COVID-19 patients suggest that community rather than hospital virus exposure was a source of many infections.

The Effect of a Single Intravenous Corticosteroid Administration on Pain after Knee Arthroscopy: A Prospective, Double-Blind, Non-Randomized Controlled Clinical Trial.

BACKGROUND: Knee arthroscopy is a standard surgical procedure that is nowadays widely performed as day-case surgery. The aim of the study was to observe the effect of a single dose of intravenous corticosteroid on pain after undergoing knee arthroscopy for non-bony procedures. METHODS: A prospective, double-blind study design was adopted. Patients undergoing knee arthroscopy for non-bony procedures were prospectively assigned into two equal groups: control (those who were not given steroids) and treatment (those who were given eight milligrams of dexamethasone intravenously 15 min prior to the inflation of the tourniquet). The pain was assessed pre-operatively on admission and on the first post-operative day during the morning round in five different movements using a visual analogue scale (VAS). RESULTS: A total of 60 patients were included in the study. There was no significant difference in the pre-and post-operatively scores between both groups. The treatment group experienced a significant reduction in post-operative morphine requirements, with 80% of patients who did not receive dexamethasone requiring post-operative morphine compared to only 53.3% of patients who did (p = 0.027). CONCLUSIONS: Pre-operative intravenous administration of a single dose of dexamethasone may decrease opioid requirements for adequate pain control after knee arthroscopy.

Lower Limb Reconstruction Using Tibial Strut Autograft after Resection of Primary Malignant Bone Tumors in Skeletally Immature Patients.

BACKGROUND: Reconstruction of large bone defects in skeletally immature patients remains a surgical challenge. We report the long-term clinical outcomes of a novel surgical technique for lower limb reconstruction using the tibia as a strut autograft following resection of primary malignant bone tumors in skeletally immature patients. METHODS: We retrospectively reviewed the medical records of six patients diagnosed with lower limb primary bone sarcoma. All patients underwent tumor resection and reconstruction using tibial strut autograft. The radiological and clinical outcomes including complications at the recipient and donor sites were assessed. RESULTS: The mean age at presentation was ten years (range 6-15 years). Two cases had osteosarcoma and four had Ewing sarcoma. The mean length of the resected tumor and tibial autografts were 20.83 and 19.33 cm respectively. Union at both ends was achieved in five grafts while one graft achieved union only at the distal end. The mean time for union of the proximal and distal junctions was 4 and 8.8 months respectively. The mean follow-up period was 8.4 years (range 14 months-20 years). One patient developed a foot drop, and three patients underwent subsequent joint arthrodesis (2 knees and 1 ankle). The mean musculoskeletal tumor society functional score was 80.8%. Two patients had clinically significant leg-length discrepancy that needs further lengthening procedure. Four patients survived with no evidence of disease and two patients died due to their primary oncologic disease. All donor sites regenerated, with the earliest signs of new bone formation at (2-4) weeks post-operatively. CONCLUSION: Reconstruction using non-vascularized tibia strut autograft after resection of primary malignant lower limb bone tumors can be a viable alternative method for reconstructing large bone defects in the immature skeleton.