Image-Guided Energy Ablation for Palliation of Painful Bony Metastases-A Systematic Review.

PURPOSE: To analyze the effectiveness of image-guided energy ablation techniques with and without concurrent therapies in providing palliative pain relief in patients with bone metastases. MATERIALS AND METHODS: Ovid Embase, Ovid Medline, and Pubmed were searched from inception to April 14, 2023, using search terms related to bone lesions and MeSH terms regarding ablation therapy. English peer-reviewed primary articles were included that reported pain scores following image-guided energy-based ablation of bone metastases. Exclusion criteria included nonpalliative treatment, pain scores associated with specific treatment modalities not reported, and nonmetastatic bone lesions. Mean percentage reduction in pain score was calculated. RESULTS: Of the 1,396 studies screened, 54 were included. All but 1 study demonstrated decreased pain scores at final follow-up. Mean reductions in pain scores at final follow-up were 49% for radiofrequency (RF) ablation, 58% for RF ablation and adjunct, 54% for cryoablation (CA), 72% for cryoablation and adjunct (CA-A), 48% for microwave ablation (MWA), 81% for microwave ablation and adjunct (MWA-A), and 64% for high-intensity focused ultrasound (US). Postprocedural adverse event rates were 4.9% for RF ablation, 34.8% for RF ablation and adjunct, 9.6% for CA, 12.0% for CA-A, 48.9% for MWA, 33.5% for MWA-A, and 17.0% for high-intensity focused US. CONCLUSIONS: Image-guided energy ablation demonstrated consistently strong reduction in pain across all modalities, with variable postprocedural adverse event rates. Owing to heterogeneity of included studies, quantitative analysis was not appropriate. Future primary research should focus on creating consistent prospective studies with established statistical power, explicit documentation, and comparison with other techniques.

Tendon cross-sectional area on magnetic resonance imaging and anthropometric characteristics can be used to predict insufficient four-strand hamstring autograft diameter in anterior cruciate ligament reconstruction: A systematic review.

PURPOSE: To evaluate the utility of semitendinosus tendon (ST) and gracilis tendon (GT) cross-sectional area (CSA) on magnetic resonance imaging (MRI) and anthropometric characteristics in preoperative estimation of graft diameter in patients undergoing anterior cruciate ligament reconstruction (ACLR) with four-strand hamstring autografts. METHODS: Three databases were searched on 29 August 2023. The authors adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and R-AMSTAR (Revised Assessment of Multiple Systematic Review) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Data on demographics, anthropometric characteristics, imaging techniques, tendon CSA, correlation coefficients, sensitivities, specificities, regression models and cutoffs for predicting intraoperative graft diameters above 8 mm were recorded. RESULTS: Forty-six studies comprising 4140 patients were included. Twelve of 19 (63.2%) studies reporting on ST + GT CSA found a moderate to very high correlation with intraoperative graft diameter. Five of 10 (50%) and one of seven (14.3%) studies reporting on ST CSA and GT CSA, respectively, found a moderate to high correlation with intraoperative graft diameter. Cutoffs of ST + GT CSA for predicting graft diameters above 8 mm ranged from 15.8 to 31.2 mm2. Nine of 35 (25.7%) studies that reported on height found a moderate to very high correlation with graft diameter. Seven of 33 (21.2%) studies reporting on weight found a moderate correlation with graft diameter. CONCLUSION: Of the MRI parameters assessed, ST + GT CSA was the most reliable predictor of graft diameter. However, cutoffs, sensitivities, and specificities for predicting diameters above 8 mm were highly variable. Anthropometric characteristics in general were less predictive of graft diameter than MRI parameters. This information can be used by clinicians to predict patients at risk for ACLR failure due to insufficient graft size. LEVEL OF EVIDENCE: Level IV.

Identifying positive and negative use of non-technical skills by anesthesiologists in the clinical operating room: An exploratory descriptive study.

Background: Teamwork is a critical competency in high-risk settings like the operating room (OR). While conventional approaches focus on describing and learning from negative performance, there may be value in learning from high-performing behaviour, particularly in specialties where serious safety events are relatively rare. This study aimed to explore both the positive and negative use of non-technical skills by anesthesia practitioners in the OR and situate them within the clinical OR context. Methods: This study employed a prospective observational design. Following research ethics approval, a sample of surgical cases in a tertiary hospital were recorded using the OR Black Box®. Data related to surgical phase timing, non-technical skills, team factors, and environmental factors were identified by analysts according to a modified Systems Engineering Initiative for Patient Safety model. We performed descriptive statistics and qualitative description of these observations. Results: We observed 25 surgical cases capturing 242 instances of positive non-technical skills among anesthesiologists in the operating room and 9 instances of negative demonstrations. Situational awareness was most frequently (n = 160) observed, followed by communication and teamwork skills (n = 82), and were most often demonstrated in the context of potential environmental distractions (e.g., doors opening, unnecessary interruptions). The least common category of positive non-technical skills observed was leadership (n = 3). Conclusions: Our findings show anesthesiologists are doing a lot "right" and there may be many opportunities for learning from positive practice in the clinical setting. These findings can inform future work to better understand and standardize best practices for non-technical performance in anesthesia.

Effectiveness of interprofessional teamwork interventions for improving occupational well-being among perioperative healthcare providers: a systematic review.

The occupational well-being of healthcare providers is crucial for safe and effective patient care, especially in the complex, high acuity operating room (OR) setting. There has been a recent proliferation of interventions to improve teamwork in the OR setting, but the impact of these interventions on clinician occupational well-being has yet to be systematically assessed. This systematic review aimed to summarize the impact of interprofessional teamwork interventions on occupational well-being among perioperative healthcare providers. We included all qualitative or quantitative peer-reviewed studies assessing a multidisciplinary teamwork intervention including members of at least two professions. We included seven studies which involved checklists (n = 2), simulation-based training (n = 2), and various teamwork development and training programs (n = 3). Five of the seven included studies reported no significant effect on job satisfaction, while one found a significant negative association between the intervention and job satisfaction (p < .0001), and another showed significant decrease in worker stress. Our findings highlight the gaps in our understanding of the impact of interprofessional teamwork interventions on healthcare worker well-being in the perioperative environment and the multi-level factors influencing OR teamwork, intervention implementation, and well-being across the different professions.

Mapping multicenter randomized controlled trials in anesthesiology: a scoping review.

BACKGROUND: Evidence suggests that there are substantial inconsistencies in the practice of anesthesia. There has not yet been a comprehensive summary of the anesthesia literature that can guide future knowledge translation interventions to move evidence into practice. As the first step toward identifying the most promising interventions for systematic implementation in anesthesia practice, this scoping review of multicentre RCTs aimed to explore and map the existing literature investigating perioperative anesthesia-related interventions and clinical patient outcomes. METHODS: Multicenter randomized controlled trials were eligible for inclusion if they involved a tested anesthesia-related intervention administered to adult surgical patients (≥ 16 years old), with a control group receiving either another anesthesia intervention or no intervention at all. The electronic databases Embase (via OVID), MEDLINE, and MEDLINE in Process (via OVID), and Cochrane Central Register of Control Trials (CENTRAL) were searched from inception to February 26, 2021. Studies were screened and data were extracted by pairs of independent reviewers in duplicate with disagreements resolved through consensus or a third reviewer. Data were summarized narratively. RESULTS: We included 638 multicentre randomized controlled trials (n patients = 615,907) that met the eligibility criteria. The most commonly identified anesthesia-related intervention theme across all studies was pharmacotherapy (n studies = 361 [56.6%]; n patients = 244,610 [39.7%]), followed by anesthetic technique (n studies = 80 [12.5%], n patients = 48,455 [7.9%]). Interventions were most often implemented intraoperatively (n studies = 233 [36.5%]; n patients = 175,974 [28.6%]). Studies typically involved multiple types of surgeries (n studies = 187 [29.2%]; n patients = 206 667 [33.5%]), followed by general surgery only (n studies = 115 [18.1%]; n patients = 201,028 [32.6%]) and orthopedic surgery only (n studies = 94 [14.7%]; n patients = 34,575 [5.6%]). Functional status was the most commonly investigated outcome (n studies = 272), followed by patient experience (n studies = 168), and mortality (n studies = 153). CONCLUSIONS: This scoping review provides a map of multicenter RCTs in anesthesia which can be used to optimize future research endeavors in the field. Specifically, we have identified key knowledge gaps in anesthesia that require further systematic assessment, as well as areas where additional research would likely not add value. These findings provide the foundation for streamlining knowledge translation in anesthesia in order to reduce practice variation and enhance patient outcomes.

Interpreting pragmatic markers following proverbs.

This research examined the interpretation of the pragmatic markers literally and figuratively when they followed familiar and unfamiliar proverbs (e.g., "Birds of a feather will flock together, literally"). Event-related brain potential methodology was used to measure costs associated with interpreting the markers during online comprehension, and an offline task provided additional insight into how sensible the markers were in the proverbial contexts. N400 potentials revealed that literally was less semantically congruent than figuratively with familiar and unfamiliar proverbial contexts, and differences in late positive potentials showed that resolving the interpretation of markers inconsistent with the salient meaning of the proverbs was more difficult following unfamiliar than familiar proverbs. Sensibility ratings showed that literally was less sensible than figuratively following both types of proverbs, and that both markers were more sensible following familiar proverbs. These results have implications for understanding how people interpret the pragmatic intent of these markers when they appear after the figurative statements they modify, and highlight the sensitivity of the markers to context. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impact of physician's sex/gender on processes of care, and clinical outcomes in cardiac operative care: a systematic review.

OBJECTIVES: This systematic review aimed to assess the role of physician's sex and gender in relation to processes of care and/or clinical outcomes within the context of cardiac operative care. DESIGN: A systematic review. DATA SOURCES: Searches were conducted in PsycINFO, Embase and Medline from inception to 6 September 2018. The reference lists of relevant systematic reviews and included studies were also searched. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Quantitative studies of any design were included if they were published in English or French, involved patients of any age undergoing a cardiac surgical procedure and specifically assessed differences in processes of care or clinical patient outcomes by physician's sex or gender. Studies were screened in duplicate by two pairs of independent reviewers. OUTCOME MEASURES: Processes of care, patient morbidity and patient mortality. RESULTS: The search yielded 2095 publications after duplicate removal, of which two were ultimately included. These studies involved various types of surgery, including cardiac. One study found that patients treated by female surgeons compared with male surgeons had a lower 30-day mortality. The other study, however, found no differences in patient outcomes by surgeon's sex. There were no studies that investigated anaesthesiologist's sex/gender. There were also no studies investing physician's sex or gender exclusively in the cardiac operating room. CONCLUSIONS: The limited data surrounding the impact of physician's sex/gender on the outcomes of cardiac surgery inhibits drawing a robust conclusion at this time. Results highlight the need for primary research to determine how these factors may influence cardiac operative practice, in order to optimise provider's performance and improve outcomes in this high-risk patient group.

Association of intraoperative anaesthesia handovers with patient morbidity and mortality: a systematic review and meta-analysis.

BACKGROUND: Handover of anaesthesia patient care during surgery is common; however, its association with patient outcome is unclear. This systematic review aimed to assess the impact of anaesthesia handover during surgery on patient outcome. METHODS: All prospective and retrospective clinical studies specifically investigating the association of intraoperative transfer of anaesthesia care between anaesthesia providers in the operating room with patient morbidity and mortality were included. Searches were conducted from inception to April 24, 2019 in Medline, Medline in Process, CINAHL, and Embase. Reference lists of included studies were searched. Studies were assessed for eligibility and data were extracted by independent reviewers in duplicate with disagreements resolved by consensus or a third reviewer. Risk of bias was assessed in duplicate using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Data were summarised narratively given substantial heterogeneity. An exploratory meta-analysis was conducted using a random-effects model for a subset of comparable studies. RESULTS: Eight studies met the inclusion criteria. Six studies focused on patients as the unit of analysis (npatients=605 678) and two focused on anaesthesia providers as the unit of analysis (nproviders=307). Seven studies identified a relationship between anaesthesia handovers and adverse patient outcomes, whereas one suggested that handover may be beneficial to error detection or rectification. Included studies were of fair or good quality. Meta-analysis of four studies found a 40% increased risk of patients experiencing an adverse event when an anaesthesia handover occurs during the procedure (pooled risk ratio=1.40; 95% confidence interval, 1.19 to 1.65; P<0.001; I2=98%). CONCLUSIONS: Intraoperative anaesthesia handovers generally increase morbidity and mortality for surgical patients but could have the potential to improve safety in certain contexts. Future research should determine the specific handover characteristics that impact safety.

Corrigendum: Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III.

This corrects the article DOI: 10.1038/srep42957.

Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy.

Harsh adverse effects as a result of nonspecific targeting of chemotherapeutics currently pose obstacles in cancer therapy; thus, it would be invaluable to devise novel approaches to specifically target cancer cells. The natural compound pancratistatin (PST) has been shown to preferentially induce apoptosis in a variety of cancer cell types. Recently, several analogs of PST were shown to be efficacious in inducing apoptosis in a variety of aggressive cancer cell types via cancer cell mitochondrial targeting; it caused dissipation of mitochondrial membrane potential and decreased oxygen consumption, and with isolated mitochondria, it induced the release of apoptogenic factors. The natural compound piperlongumine has been shown to target the stress response to reactive oxygen species in cancer cells. We explored the combinatorial potential of two small molecules (SVTH-6 and piperlongumine) that target these vulnerabilities in cancer cells. Interestingly, when combined with the PST analog, SVTH-6, an increase in mitochondrial dysfunction was observed, leading to an enhanced cytotoxic effect against several human cancer cell types. Additionally, this combination treatment was effective in reducing cancer cell growth in physiologically more relevant 3-dimensional spheroid cell cultures. This enhanced effect was found to be dependent on reactive oxygen species generation because an antioxidant could rescue cancer cells from this combination treatment. Importantly, noncancerous cells were markedly less sensitive to this combination treatment. Thus, targeting mitochondrial and oxidative stress vulnerabilities of cancer cells could be an effective strategy for cancer therapy.-Ma, D., Gilbert, T., Pignanelli, C., Tarade, D., Noel, M., Mansour, F., Gupta, M., Ma, S., Ropat, J., Curran, C., Vshyvenko, S., Hudlicky, T., Pandey. S. Exploiting mitochondrial and oxidative vulnerabilities with a synthetic analog of pancratistatin in combination with piperlongumine for cancer therapy.

Selective Targeting of Cancer Cells by Oxidative Vulnerabilities with Novel Curcumin Analogs.

Recently, research has focused on targeting the oxidative and metabolic vulnerabilities in cancer cells. Natural compounds like curcumin that target such susceptibilities have failed further clinical advancements due to the poor stability and bioavailability as well as the need of high effective doses. We have synthesized and evaluated the anti-cancer activity of several monocarbonyl analogs of curcumin. Interestingly, two novel analogs (Compound A and I) in comparison to curcumin, have increased chemical stability and have greater anti-cancer activity in a variety of human cancer cells, including triple-negative, inflammatory breast cancer cells. In particular, the generation of reactive oxygen species was selective to cancer cells and occurred upstream of mitochondrial collapse and execution of apoptosis. Furthermore, Compound A in combination with another cancer-selective/pro-oxidant, piperlongumine, caused an enhanced anti-cancer effect. Most importantly, Compound A was well tolerated by mice and was effective in inhibiting the growth of human triple-negative breast cancer and leukemia xenografts in vivo when administered intraperitoneally. Thus, exploiting oxidative vulnerabilities in cancer cells could be a selective and efficacious means to eradicate malignant cells as demonstrated by the curcumin analogs presented in this report with high therapeutic potential.

Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest.

The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level and extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment to the development of CA4 is an inherent conformational instability about the ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives of CA4, lacking an ethylene linker, which retain anti-proliferative and pro-apoptotic activity, albeit at higher doses. Our current study provides a more comprehensive evaluation regarding the anti-proliferative and pro-apoptotic properties of biphenyl CA4 derivatives in both 2D and 3D cancerous and non-cancerous cell models. Computational analysis has revealed that cytotoxicity of CA4 and biphenyl analogues correlates with predicted tubulin affinity. Additional mechanistic evaluation of the biphenyl derivatives found that their anti-cancer activity is dependent on prolonged mitotic arrest, in a similar manner to CA4. Lastly, we have shown that cancer cells deficient in the extrinsic pathway of apoptosis experience delayed cell death following treatment with CA4 or analogues. Biphenyl derivatives of CA4 represent structurally simplified analogues of CA4, which retain a similar mechanism of action. The biphenyl analogues warrant in vivo examination to evaluate their potential as vascular damaging agents.

Cancer Cell Mitochondria Targeting by Pancratistatin Analogs is Dependent on Functional Complex II and III.

Enhanced mitochondrial stability and decreased dependence on oxidative phosphorylation confer an acquired resistance to apoptosis in cancer cells, but may present opportunities for therapeutic intervention. The compound pancratistatin (PST) has been shown to selectively induce apoptosis in cancer cells. However, its low availability in nature has hindered its clinical advancement. We synthesized PST analogs and a medium-throughput screen was completed. Analogs SVTH-7, -6, and -5 demonstrated potent anti-cancer activity greater than PST and several standard chemotherapeutics. They disrupted mitochondrial function, activated the intrinsic apoptotic pathway, and reduced growth of tumor xenografts in vivo. Interestingly, the pro-apoptotic effects of SVTH-7 on cancer cells and mitochondria were abrogated with the inhibition of mitochondrial complex II and III, suggesting mitochondrial or metabolic vulnerabilities may be exploited by this analog. This work provides a scaffold for characterizing distinct mitochondrial and metabolic features of cancer cells and reveals several lead compounds with high therapeutic potential.

Cymbopogon citratus and Camellia sinensis extracts selectively induce apoptosis in cancer cells and reduce growth of lymphoma xenografts in vivo.

Cancer cells are reported to have elevated levels of reactive oxygen species (ROS) and are highly dependent on cellular defense mechanisms against oxidative stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide range of abilities to alter cellular redox states with potential implications in various diseases. Furthermore, therapeutic options for cancers are mostly nonselective treatments including genotoxic or tubulin-targeting compounds. Some of the natural extracts, containing multiple bioactive compounds, could target multiple pathways in cancer cells to selectively induce cell death. Cymbopogon citratus (lemongrass) and Camellia sinensis (white tea) extracts have been shown to have medicinal properties, however, their activity against lymphoma and leukemia, as well as mechanistic details, have not been fully characterized. Herein, we report potent anti-cancer properties in dose and time-dependent manners of ethanolic lemongrass and hot water white tea extracts in lymphoma and leukemia models. Both extracts were able to effectively induce apoptosis selectively in these human cancer cell types. Interestingly, ethanolic lemongrass extract induces apoptosis primarily by the extrinsic pathway and was found to be dependent on the generation of ROS. Conversely, apoptotic induction by hot water white tea extract was independent of ROS. Furthermore, both of these extracts caused mitochondrial depolarization and decreased rates of oxygen consumption in lymphoma and leukemia cells, leading to cell death. Most importantly, both these extracts were effective in reducing tumor growth in human lymphoma xenograft models when administered orally. Thus, these natural extracts could have potential for being nontoxic alternatives for the treatment of cancer.

Fusion-optimized intervals (FOI): a new method to achieve the narrowest QRS for optimization of the AV and VV intervals in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Optimization of atrioventricular (AV) and interventricular (VV) intervals may improve cardiac resynchronization therapy (CRT) response but is a complex task. Fusion with intrinsic conduction may increase the benefit of CRT. The aim was to describe fusion-optimized intervals (FOI), a new method of optimizing CRT based on QRS duration. METHODS AND RESULTS: Seventy-six consecutive patients with preserved AV conduction who received CRT were prospectively included. The AV interval was optimized by searching the narrowest QRS obtained within the fusion band during left ventricular (LV) pacing. The VV interval was then adjusted, comparing QRS duration in simultaneous biventricular, LV preexcitation (-30 milliseconds), right ventricular (RV) preexcitation (-30 milliseconds) and LV-only pacing. A substudy in 31 patients evaluated the invasive LV +dP/dtmax . The best fusion-optimized AV interval was 136 ± 30 milliseconds during atrial sensing and 192 ± 35 milliseconds during atrial pacing. The best QRS was obtained with simultaneous biventricular pacing in 28 patients (37%), LV preexcitation in 22 (29%), LV-only in 20 (26%), and RV preexcitation in 6 (8%). Baseline QRS was shortened more by FOI (59 ± 19 milliseconds) than by nominal settings (40 ± 21 milliseconds; P < 0.001). Sixty-five patients (86%) showed >10% shortening of the baseline QRS with FOI; none prolonged the QRS duration by FOI compared to nominal settings. All echocardiographic asynchrony parameters were corrected by FOI. Baseline +dP/dtmax improvement was greater in FOI (127 ± 95 mmHg/seconds) than in nominal settings (102 ± 71 mmHg/seconds; P = 0.05). CONCLUSION: The FOI method is feasible, further reduces QRS duration, and improves acute hemodynamic response compared to nominal programming of CRT.