30 research outputs found
Fracture of neck of femur with fracture of posterior column of acetabulum: a rare case of floating hip
Injuries around the hip joint are one of the most common orthopedic injuries and these types of injuries are grossly debilitating until treated properly. Simultaneous occurrence of fracture of proximal femur with fracture of ipsilateral acetabulum or pelvis is termed as floating hip injury. These injuries are very rare, only to be found 1 in 10,000 as well as there is lack of literature support regarding proper treatment protocol. Here we are going to present a case of fracture of neck of left femur along with fracture of left acetabulum in a 45 years old male undergone road traffic accident.
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Systemic and Tumor-directed Therapy for Oligorecurrent Metastatic Prostate Cancer (SATURN): Primary Endpoint Results from a Phase 2 Clinical Trial.
Nearly all men with metastatic hormone-sensitive prostate cancer treated with intermittent androgen deprivation therapy (ADT) experience recurrence within 6 mo of testosterone recovery. We conducted a single-arm phase 2 trial to evaluate whether addition of dual androgen receptor pathway inhibitors (ARPIs) and metastasis-directed stereotactic body radiotherapy (SBRT) to intermittent ADT improves recurrence rates for men with between one and five nonvisceral, extrapelvic metastases on prostate-specific membrane antigen positron emission tomography/computed tomography after prior radical prostatectomy. Patients received 6 mo of androgen annihilation therapy (AAT; leuprolide, abiraterone acetate plus prednisone, and apalutamide) and metastasis-directed SBRT. The primary endpoint was the percentage of patients with prostate-specific antigen (PSA) <0.05 ng/ml 6 mo after testosterone recovery (≥150 ng/dl), with the study powered to detect an improvement from 1% to 12%. We enrolled 28 men between March 2021 and June 2022. Median follow-up was 20 mo (interquartile range 16-22). Twenty-six patients (93%) completed SBRT with 6 mo of hormone therapy, of whom six discontinued at least one ARPI; two patients withdrew prematurely. At 6 mo after testosterone recovery, PSA was maintained at <0.05 ng/ml in 13/26 patients (50%, 95% confidence interval 32-67%). Rates of grade 2 and 3 AAT toxicity were 21% and 21%. The results confirm that addition of metastasis-directed SBRT to highly potent systemic therapy can maintain low PSA after testosterone recovery, although further studies are needed to clarify the optimal systemic therapy regimen. PATIENT SUMMARY: We tested a combination of intensified hormone therapy (called androgen annihilation therapy) and radiotherapy targeted at metastases in men with recurrence of metastatic prostate cancer. We found that half of patients were recurrence-free 6 months after their testosterone level recovered, and that less than a quarter of patients experienced a severe drug-related side effect. Overall, this appears to be an effective therapy with acceptable side effects. This trial is registered on ClinicalTrials.gov as NCT03902951
Quality-of-Life Outcomes and Toxicity Profile Among Patients With Localized Prostate Cancer After Radical Prostatectomy Treated With Stereotactic Body Radiation: The SCIMITAR Multicenter Phase 2 Trial.
PURPOSE: Postoperative radiation therapy (RT) is an underused standard-of-care intervention for patients with prostate cancer and recurrence/adverse pathologic features after radical prostatectomy. Although stereotactic body RT (SBRT) is a well-studied and convenient option for definitive treatment, data on the postprostatectomy setting are extremely limited. The purpose of this study was to evaluate short-term physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities and patient-reported outcomes after postprostatectomy SBRT. METHODS AND MATERIALS: The SCIMITAR trial was a phase 2, dual-center, open-label, single-arm trial that enrolled patients with postoperative prostate-specific antigen >0.03 ng/mL or adverse pathologic features. Coprimary endpoints were 4-year biochemical recurrence-free survival, physician-scored acute and late GU and GI toxicities by the Common Terminology Criteria for Adverse Events (version 4.03) scale, and patient-reported quality-of-life (QOL) outcomes, as represented by the Expanded Prostate Cancer Index-26 and the International Prostate Symptom Score. Patients received SBRT 30 to 34 Gy/5 fractions to the prostate bed ± bed boost ± pelvic nodes with computed tomography (CTgRT) or magnetic resonance imaging guidance (MRgRT) in a nonrandomized fashion. Physician-scored toxicities and patient-reported QOL outcomes were collected at baseline and at 1, 3, and 6 months of follow-up. Univariable and multivariable analyses were performed to evaluate predictors of toxicities and QOL outcomes. RESULTS: One hundred participants were enrolled (CTgRT, n = 69; MRgRT, n = 31). The median follow-up was 29.5 months (CTgRT: 33.3 months, MRgRT: 22.6 months). The median (range) prostate bed dose was 32 (30-34) Gy. Acute and late grade 2 GU toxicities were both 9% while acute and late grade 2 GI toxicities were 5% and 0%, respectively. Three patients had grade 3 toxicity (n = 1 GU, n = 2 GI). No patient receiving MRgRT had grade 3 GU or grade ≥2 GI toxicity. Compared with CTgRT, MRgRT was associated with a 30.5% (95% confidence interval, 11.6%-49.5%) reduction in any-grade acute GI toxicity (P = .006). MRgRT was independently associated with improved any-grade GI toxicity and improved bowel QOL. CONCLUSIONS: Postprostatectomy SBRT was well tolerated at short-term follow-up. MRgRT may decrease GI toxicity. Longer toxicity and/or efficacy follow-up and randomized studies are needed
Anticancer activity of RM-3-22: a TAZQ-based hydroxamic acid derivative targeting NSCLC in vitro and in vivo
IntroductionLung cancer remains the leading cause of cancer-related deaths, necessitating novel therapeutic strategies. In this study, we developed RM-3-22, a TAZQ-based hydroxamic acid derivative with histone deacetylase (HDAC) inhibitory properties. We evaluated its anticancer activity in non-small cell lung cancer (NSCLC), using A549 adenocarcinoma cells as the primary model.MethodsThe anticancer efficiency of RM-3-22 was assessed in 2D and 3D cell culture models. Cell survivalism was analysed by MTT assay. Different microscopical staining methods, including acridine orange and DAPI, were employed to evaluate autophagy, nuclear changes, and apoptosis. Cell cycle progression, mitochondrial membrane potential, and apoptosis-necrosis profiles were assessed using flow cytometry. Protein and gene expression related to the RM-3-22 induced pathway were evaluated via immunofluorescence (IF), Western blotting, and RT-PCR. Functional gene analysis was performed using siRNA-mediated knockdown. Different in silico studies were also conducted to check the clinical relevance and expression pattern of the RM-3-22-induced gene. Additionally, the in vivo efficiency of the molecule was evaluated using the NOD/SCID xenograft model.ResultsRM-3-22 potentially suppressed cell viability and decreased the tumor spheroid size of A549s in vitro. It induced autophagy via downregulation of PI3K/Akt/mTOR signalling pathway. Besides, flow cytometry confirmed increased apoptotic cell population and decreased mitochondrial membrane potential due to the exposure of RM-3-22. RM-3-22 also promoted G2/M arrest. Signalling cascade confirmed that autophagy regulates RM-3-22-mediated apoptosis and cell cycle arrest. Additionally, RM-3-22 upregulated FTH1, a tumor suppressor, reinforcing its anticancer potential. Notably, RM-3-22 exhibited lower toxicity to normal cells, underscoring its selectivity. In vivo, RM-3-22 markedly reduced tumor growth in the xenograft mouse model.ConclusionRM-3-22 demonstrates potent anticancer activity through different mechanisms, including inhibition of the PI3K/Akt/mTOR pathway and activation of autophagy, apoptosis, and cell cycle arrest. Further, in vivo validation also supports that RM-3-22 represents a promising therapeutic candidate against lung cancer
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
