A Multidisciplinary Protocolized Approach for Ruptured Abdominal Aortic Aneurysm Management: A Retrospective Before-After Study.

OBJECTIVES: To investigate whether implementation of a multidisciplinary protocol for ruptured abdominal aortic aneurysm (rAAA) management reduces rates of adverse complications. DESIGN: A retrospective before-after study. SETTING: A tertiary-care academic hospital. PARTICIPANTS: Adult patients who underwent open or endovascular rAAA repair; data were stratified into before-protocol implementation (group 1: 2015-2018) and after-protocol implementation (group 2: 2019-2022) groups. INTERVENTION: The protocol details the workflow for vascular surgery, anesthesia, emergency department, and operating room staff for a rAAA case; training was accomplished through yearly workshops. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause morbidity and other major complications. Differences in postoperative complication rates between groups were assessed using Pearson's χ2 test. Of the 77 patients included undergoing rAAA repair, 41 (53.2%) patients were in group 1, and 36 (46.8%) patients were in group 2. Patients in group 2 had a significantly shorter median time to incision (1.0 v 0.7 hours, p = 0.022) and total procedure time (180.0 v 160.5 minutes, p = 0.039) for both endovascular and open repair. After protocol implementation, patients undergoing endovascular repair exhibited significantly lower rates of mortality (46.2% v 20.0%, p = 0.048), all-cause morbidity (65.4% v 44.0%, p = 0.050), and renal complications (15.4% v 0.0%, p = 0.036); patients undergoing open repair for a rAAA exhibited significantly lower rates of mortality (53.3% v 27.3%, p = 0.018) and bowel ischemia (26.7% v 0.0%, p = 0.035). CONCLUSIONS: Implementation of a multidisciplinary protocol for the management of a rAAA may reduce rates of adverse complications and improve the quality of care.

Implementation of Routine In Situ Simulation in Residency Curriculum Targeting Competency in Technical and Decision-Making Skills.

OBJECTIVE: To describe the development and implementation of a comprehensive in situ simulation-based curriculum for anesthesia residents. DESIGN: This is a prospective study. SETTING: This study was conducted at a university hospital. PARTICIPANTS: This single-center prospective study included all 53 anesthesia residents enrolled in the anesthesia residency program. INTERVENTIONS: Introduction of a routine, high-fidelity, in situ simulation program that incorporates short sessions to train residents in the necessary skill sets and decision-making processes required in the operating room. MEASUREMENTS AND MAIN RESULTS: Our team conducted 182 individual 15-minute simulation sessions over 3 months during regular working hours. All 53 residents in our program actively participated in the simulations. Most residents engaged in at least 3 sessions, with an average participation rate of 3.4 per resident (range, 1-6 sessions). Residents completed an online anonymous survey, with a response rate of 71.7% (38 of 53 residents) over the 3-month period. The survey aimed to assess their overall impression and perceived contribution of this project to their training. CONCLUSIONS: Our proposed teaching method can bridge the gap in resident training and enhance their critical reasoning to manage diverse clinical situations they may not experience during their residency.

Novel Three-Dimensionally Printed Ultrasound Probe Simulator and Heart Model for Transthoracic Echocardiography Education.

Simulation-based training is an essential component in the education of transthoracic echocardiography (TTE). Nevertheless, current TTE teaching methods may be subject to certain limitations. Hence, the authors in this study aimed to invent a novel TTE training system employing three-dimensional (3D) printing technology to teach the basic principles and psychomotor skills of TTE imaging more intuitively and understandably. This training system comprises a 3D-printed ultrasound probe simulator and a sliceable heart model. The probe simulator incorporates a linear laser generator to enable the visualization of the projection of the ultrasound scan plane in a 3D space. By using the probe simulator in conjunction with the sliceable heart model or other commercially available anatomic models, trainees can attain a more comprehensive understanding of probe motion and related scan planes in TTE. Notably, the 3D-printed models are portable and low-cost, suggesting their potential utility in various clinical scenarios, particularly for just-in-time training.

Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/ß-Catenin Interplay with Embryonic Markers.

Osteosarcoma is a highly malignant bone tumor derived from mesenchymal cells that contains self-renewing cancer stem cells (CSCs), which are responsible for tumor progression and chemotherapy resistance. Understanding the signaling pathways that regulate CSC self-renewal and survival is crucial for developing effective therapies. The Notch, Hedgehog, and Wnt/ß-Catenin developmental pathways, which are essential for self-renewal and differentiation of normal stem cells, have been identified as important regulators of osteosarcoma CSCs and also in the resistance to anticancer therapies. Targeting these pathways and their interactions with embryonic markers and the tumor microenvironment may be a promising therapeutic strategy to overcome chemoresistance and improve the prognosis for osteosarcoma patients. This review focuses on the role of Notch, Hedgehog, and Wnt/ß-Catenin signaling in regulating CSC self-renewal, pluripotency, and chemoresistance, and their potential as targets for anti-cancer therapies. We also discuss the relevance of embryonic markers, including SOX-2, Oct-4, NANOG, and KLF4, in osteosarcoma CSCs and their association with the aforementioned signaling pathways in overcoming drug resistance.

3% polidocanol foam sclerotherapy versus hemorrhoidal artery ligation with recto anal repair in hemorrhoidal disease grades II-III: a randomized, pilot trial.

PURPOSE: Polidocanol foam sclerotherapy (SP) versus doppler-guided hemorrhoidal artery ligation with recto-anal repair (HAL-RAR) in the treatment of hemorrhoidal disease (HD) was analyzed. METHODS: A prospective, randomized study including patients with HD grades II and III was performed. Participants were randomly assigned (1:1) into SP or HAL-RAR, during a recruitment period between September 2019 and February 2020. Therapeutic success (Sodergren's and bleeding scores) was the primary outcome. Other outcomes evaluated included complications and implication in the professional life. Efficacy and safety outcomes were evaluated during the 8 weeks after surgery or the final SP session. RESULTS: Forty-six patients were allocated either to SP (n=22) or HAL-RAR (n=24). Most patients achieved therapeutic success (SP 100% vs. HAL-RAR 90.9%, p=0.131). Complete success was higher in the SP group (91.7% vs. 68.2%, p=0.045) and SP patients had less complications (25% vs. 68.2%, p=0.003). HAL-RAR had a greater negative impact on work activity of the patient. CONCLUSION: SP was more effective and safer than HAL-RAR. SP patients had less impact on their work activity. Clinical trials identifier NCT04675177.

National Delphi Survey on Anesthesiology Resident Training in Perioperative Ultrasound.

OBJECTIVE: To establish agreement among nationwide experts through a Delphi process on the key components of perioperative ultrasound and the recommended minimum number of examinations that should be performed by a resident upon graduation. DESIGN: A prospective cross-sectional study. SETTING: A survey on multiinstitutional academic medical centers. PARTICIPANTS: Anesthesiology residency program directors and/or experts in perioperative ultrasound. INTERVENTIONS: A list of components and examinations recommended for anesthesiology resident training in perioperative ultrasound was developed based on guidelines and 2 survey rounds among a steering committee of 10 experts. A questionnaire asking for a rating of each component on a 5-point Likert scale subsequently was sent to an expert panel of 120 anesthesiology residency program directors across the United States. An agreement of at least 70% of participants, rating a component as 4 or 5, was compulsory to list a component as essential for anesthesiology resident training in perioperative ultrasound. MEASUREMENTS AND MAIN RESULTS: The nationwide survey's response rate was 62.5%, and agreement was reached after 2 Delphi rounds. The final list included 44 essential components for basic ultrasound physics and knobology, cardiac ultrasound, lung ultrasound, and ultrasound-guided vascular access. Agreement was not reached for abdominal ultrasound, gastric ultrasound, and ultrasound-guided airway assessment. Agreement for the recommended minimum number of examinations that should be performed by a resident upon graduation included 50 each for transthoracic and transesophageal echocardiography, and 20 each for lung ultrasound, ultrasound-guided central line, and ultrasound-guided arterial line placements. CONCLUSIONS: The recommendations outlined in this survey can be used to establish standardized training for perioperative ultrasound by anesthesiology residency programs.

Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.

Osteosarcoma is amongst the most prevalent bone sarcomas and majorly afflicts children and adolescents. Therapeutic regimens based on the triad of doxorubicin, cisplatin and methotrexate have been used as the state-of-the-art approach to clinical treatment and management, with no significant improvements in the general outcomes since their inception in the early 1970s. This fact raises the following problematic questions: Why do some patients still relapse despite an initial good response to therapy? Why do nearly 30% of patients not respond to neoadjuvant therapies? Does residual persistent disease contribute to relapses and possible metastatic dissemination? Accumulating evidence suggests that chemoresistant cancer stem cells may be the major culprits contributing to those challenging clinical outcomes. Herein, we revisit the maneuvers that cancer stem cells devise for eluding cell killing by the classic cytotoxic therapies used in osteosarcoma, highlighting studies that demonstrate the complex crosstalk of signaling pathways that cancer stem cells can recruit to become chemoresistant.

A Tool to Predict Readmission to the Intensive Care Unit in Surgical Critical Care Patients-The RISC Score.

BACKGROUND: Readmission to the Intensive Care Unit (ICU) is associated with a high risk of in-hospital mortality and higher health care costs. Previously published tools to predict ICU readmission in surgical ICU patients have important limitations that restrict their clinical implementation. We sought to develop a clinically intuitive score that can be implemented to predict readmission to the ICU after surgery or trauma. We designed the score to emphasize modifiable predictors. METHODS: In this retrospective cohort study, we included surgical patients requiring critical care between June 2015 and January 2019 at Beth Israel Deaconess Medical Center, Harvard Medical School, MA, USA. We used logistic regression to fit a prognostic model for ICU readmission from a priori defined, widely available candidate predictors. The score performance was compared with existing prediction instruments. RESULTS: Of 7,126 patients, 168 (2.4%) were readmitted to the ICU during the same hospitalization. The final score included 8 variables addressing demographical factors, surgical factors, physiological parameters, ICU treatment and the acuity of illness. The maximum score achievable was 13 points. Potentially modifiable predictors included the inability to ambulate at ICU discharge, substantial positive fluid balance (>5 liters), severe anemia (hemoglobin <7 mg/dl), hyperglycemia (>180 mg/dl), and long ICU length of stay (>5 days). The score yielded an area under the receiver operating characteristic curve of 0.78 (95% CI 0.74-0.82) and significantly outperformed previously published scores. The performance of the underlying model was confirmed by leave-one-out cross-validation. CONCLUSION: The RISC-score is a clinically intuitive prediction instrument that helps identify surgical ICU patients at high risk for ICU readmission. The simplicity of the score facilitates its clinical implementation across surgical divisions.

Educating Anesthesiologists During the Coronavirus Disease 2019 Pandemic and Beyond.

The coronavirus disease 2019 (COVID-19) pandemic has altered approaches to anesthesiology education by shifting educational paradigms. This vision article discusses pre-COVID-19 educational methodologies and best evidence, adaptations required under COVID-19, and evidence for these modifications, and suggests future directions for anesthesiology education. Learning management systems provide structure to online learning. They have been increasingly utilized to improve access to didactic materials asynchronously. Despite some historic reservations, the pandemic has necessitated a rapid uptake across programs. Commercially available systems offer a wide range of peer-reviewed curricular options. The flipped classroom promotes learning foundational knowledge before teaching sessions with a focus on application during structured didactics. There is growing evidence that this approach is preferred by learners and may increase knowledge gain. The flipped classroom works well with learning management systems to disseminate focused preclass work. Care must be taken to keep virtual sessions interactive. Simulation, already used in anesthesiology, has been critical in preparation for the care of COVID-19 patients. Multidisciplinary, in situ simulations allow for rapid dissemination of new team workflows. Physical distancing and reduced availability of providers have required more sessions. Early pandemic decreases in operating volumes have allowed for this; future planning will have to incorporate smaller groups, sanitizing of equipment, and attention to use of personal protective equipment. Effective technical skills training requires instruction to mastery levels, use of deliberate practice, and high-quality feedback. Reduced sizes of skill-training workshops and approaches for feedback that are not in-person will be required. Mock oral and objective structured clinical examination (OSCE) allow for training and assessment of competencies often not addressed otherwise. They provide formative and summative data and objective measurements of Accreditation Council for Graduate Medical Education (ACGME) milestones. They also allow for preparation for the American Board of Anesthesiology (ABA) APPLIED examination. Adaptations to teleconferencing or videoconferencing can allow for continued use. Benefits of teaching in this new era include enhanced availability of asynchronous learning and opportunities to apply universal, expert-driven curricula. Burdens include decreased social interactions and potential need for an increased amount of smaller, live sessions. Acquiring learning management systems and holding more frequent simulation and skills sessions with fewer learners may increase cost. With the increasing dependency on multimedia and technology support for teaching and learning, one important focus of educational research is on the development and evaluation of strategies that reduce extraneous processing and manage essential and generative processing in virtual learning environments. Collaboration to identify and implement best practices has the potential to improve education for all learners.

Using Machine Learning to Evaluate Attending Feedback on Resident Performance.

BACKGROUND: High-quality and high-utility feedback allows for the development of improvement plans for trainees. The current manual assessment of the quality of this feedback is time consuming and subjective. We propose the use of machine learning to rapidly distinguish the quality of attending feedback on resident performance. METHODS: Using a preexisting databank of 1925 manually reviewed feedback comments from 4 anesthesiology residency programs, we trained machine learning models to predict whether comments contained 6 predefined feedback traits (actionable, behavior focused, detailed, negative feedback, professionalism/communication, and specific) and predict the utility score of the comment on a scale of 1-5. Comments with ≥4 feedback traits were classified as high-quality and comments with ≥4 utility scores were classified as high-utility; otherwise comments were considered low-quality or low-utility, respectively. We used RapidMiner Studio (RapidMiner, Inc, Boston, MA), a data science platform, to train, validate, and score performance of models. RESULTS: Models for predicting the presence of feedback traits had accuracies of 74.4%-82.2%. Predictions on utility category were 82.1% accurate, with 89.2% sensitivity, and 89.8% class precision for low-utility predictions. Predictions on quality category were 78.5% accurate, with 86.1% sensitivity, and 85.0% class precision for low-quality predictions. Fifteen to 20 hours were spent by a research assistant with no prior experience in machine learning to become familiar with software, create models, and review performance on predictions made. The program read data, applied models, and generated predictions within minutes. In contrast, a recent manual feedback scoring effort by an author took 15 hours to manually collate and score 200 comments during the course of 2 weeks. CONCLUSIONS: Harnessing the potential of machine learning allows for rapid assessment of attending feedback on resident performance. Using predictive models to rapidly screen for low-quality and low-utility feedback can aid programs in improving feedback provision, both globally and by individual faculty.

Case Study: Fatal Exertional Rhabdomyolysis Possibly Related to Drastic Weight Cutting.

Rapid weight loss or "weight cutting" is a dangerous practice that is ubiquitous in modern combat sports yet underrepresented in the medical literature. We present a case of exertional rhabdomyolysis in a mixed martial artist with sickle cell trait to illustrate the hazards of weight cutting and ensuing critical illness. Sickle cell trait is known to predispose patients to exertional rhabdomyolysis, and multiple fatal cases have been reported in the setting of strenuous exercise. Dehydration and consequent electrolyte abnormalities make combat sport athletes with sickle cell trait particularly vulnerable to this entity. This case suggests a potential role for sickle cell trait screening in this population and underscores the need for safer weight-control practices and monitoring among all combat sport athletes.

Therapy-induced enrichment of cancer stem-like cells in solid human tumors: Where do we stand?

The development of local recurrence and metastatic disease, most probably attributable to the intrinsic or acquired resistance of tumor cells to standard therapy, still constitute the major clinical problem preventing the cure of cancer patients. Despite progress in the research of new therapeutic targets and compounds, resistant cells displaying stem-like properties seem to play a leading role in therapeutic failures and to be the culprit cells responsible for associated tumor recurrence. A whole new plethora of research studies suggest that drug-tolerant cancer stem cells may be induced by conventional cancer chemotherapeutics such as doxorubicin, cisplatinum and ionizing radiation. This phenotypic plasticity and transition from a differentiated to stem-like cell state associates with the activation of diverse stem cell self-renewal (e.g. Notch, Hedgehog, Wnt), drug efflux (e.g. ABC transporters) and survival-related pathways (e.g. TGF-ß, ERK, AKT), which may confer resistance and treatment failures in solid tumors. Therefore, combined therapeutic strategies aiming to simultaneously target drug-sensitive tumor cells and their capacity of phenotypic switching may lead to survival benefits and meaningful disease remissions. This knowledge can be applicable to the clinic and contribute to better therapeutic outcomes and prevent tumor recurrence.

Osteosarcoma Stem Cells Have Active Wnt/ß-catenin and Overexpress SOX2 and KLF4.

Osteosarcoma is a bone tumor, displaying significant cellular and histological heterogeneity and a complex genetic phenotype. Although multiple studies strongly suggest the presence of cancer stem cells in osteosarcoma, a consensus on their characterization is still missing. We used a combination of functional assays (sphere-forming, Aldefluor, and side-population) for identification of cancer stem cell populations in osteosarcoma cell lines. Expression of stemness-related transcription factors, quiescent nature, in vivo tumorigenicity, and Wnt/ß-catenin activation were evaluated. We show that different cancer stem cell populations may co-exist in osteosarcoma cell lines exhibiting distinct functional properties. Osteosarcoma spheres are slowly-proliferating populations, overexpress SOX2, and KLF4 stemness-related genes and have enhanced tumorigenic potential. Additionally, spheres show specific activation of Wnt/ß-catenin signaling as evidenced by increased nuclear ß-catenin, TCF/LEF activity, and AXIN2 expression, in a subset of the cell lines. Aldefluor-positive populations were detected in all osteosarcoma cell lines and overexpress SOX2, but not KLF4. The side-population phenotype is correlated with ABCG2 drug-efflux transporter expression. Distinct functional methods seem to identify cancer stem cells with dissimilar characteristics. Intrinsic heterogeneity may exist within osteosarcoma cancer stem cells and can have implications on the design of targeted therapies aiming to eradicate these cells within tumors. J. Cell. Physiol. 231: 876-886, 2016. © 2015 Wiley Periodicals, Inc.

Antitumor Properties of the Essential Oil From the Leaves of Duguetia gardneriana.

Duguetia gardneriana, popularly known in the Brazilian northeast as "jaquinha", is a species belonging to the family Annonaceae. The aim of this work was to assess the chemical composition and antitumor properties of the essential oil from the leaves of D. gardneriana in experimental models. The chemical composition of the essential oil was analyzed via gas chromatography-flame ionization detector and gas chromatography-mass spectrometry. In vitro cytotoxic activity was determined in cultured tumor cells, and in vivo antitumor activity was assessed in B16-F10-bearing mice. The identified compounds were ß-bisabolene (80.99%), elemicin (8.04%), germacrene D (4.15%), and cyperene (2.82%). The essential oil exhibited a cytotoxic effect, with IC50 values of 16.89, 19.16, 13.08, and 19.33 µg/mL being obtained for B16-F10, HepG2, HL-60, and K562 cell lines, respectively. On the other hand, ß-bisabolene was inactive in all of the tested tumor cell lines (showing IC50 values greater than 25 µg/mL). The in vivo analysis revealed tumor growth inhibition rates of 5.37-37.52% at doses of 40 and 80 mg/kg/day, respectively. Herein, the essential oil from the leaves of D. gardneriana presented ß-bisabolene as the major constituent and showed cytotoxic and antitumor potential.

Pulmonary Mucormycosis: Beyond Classic COVID-19-Associated Fungal Infections.

Coronavirus disease 2019 (COVID-19) is often linked to a broad range of opportunistic bacterial and fungal infections. The second wave of the COVID-19 pandemic has witnessed an unprecedented surge in mucormycosis cases, predominantly in India, while the disease remained relatively rare in Europe. The authors describe the case of a 62-year-old female patient admitted to the hospital for consolidation therapy with chemotherapy as a part of the treatment protocol for acute myeloid leukemia. During hospitalization, she was diagnosed with nosocomial COVID-19, which later progressed to respiratory deterioration. COVID-19 with bacterial superinfection was presumed, leading to the initiation of empirical antibiotic therapy. A bronchoscopy was performed several days later due to a lack of improvement, revealing an infection by the Rhizopus microsporus complex. Despite antifungal treatment, the patient experienced an unfavorable clinical course and ultimately died. Given the high index of suspicion required to diagnose pulmonary mucormycosis, which can lead to delays in appropriate treatment and increase the burden of disease, the authors are aiming to enhance its awareness.

Ru(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling.

Cancer stem cells (CSCs) are defined as a rare population of cancer cells related to tumor initiation and maintenance. These cells are primarily responsible for tumor growth, invasion, metastasis, recurrence, and resistance to chemotherapy. In this paper, we demonstrated the ability of Ru(II)-based complexes containing 2-thiouracil derivatives with the chemical formulas trans-[Ru(2TU)(PPh3)2(bipy)]PF6 (1) and trans-[Ru(6m2TU)(PPh3)2(bipy)]PF6 (2) (where 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil) to suppress liver CSCs by targeting NF-κB and Akt/mTOR signaling. Complexes 1 and 2 displayed potent cytotoxic effects on cancer cell lines and suppressed liver CSCs from HepG2 cells. Increased phosphatidylserine exposure, loss of mitochondrial transmembrane potential, increased PARP (Asp214) cleavage, DNA fragmentation, chromatin condensation and cytoplasmic shrinkage were detected in HepG2 cells treated with these complexes. Mechanistically, complexes 1 and 2 target NF-κB and Akt/mTOR signaling in HepG2 cells. Cell motility inhibition was also detected in HepG2 cells treated with these complexes. Complexes 1 and 2 also inhibited tumor progression in mice with HepG2 cell xenografts and exhibited tolerable systemic toxicity. Taken together, these results indicate that these complexes are new anti-HCC drug candidates that can suppress liver CSCs.

Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death.

Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs.