Contemporary approach to cardiogenic shock care: a state-of-the-art review.

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes.

Small bowel perforation due to ingested frog bone: a case report.

Perforation of the gastrointestinal tract by ingested foreign body is an uncommon surgical emergency, most typically associated with the consumption of fish and chicken bones. We present an unusual case of a gentleman presenting emergently with an acute abdomen following ingestion of a meal containing frog meat. Emergent computed tomography (CT) revealed findings suggestive of jejunal perforation due to a foreign body. At laparotomy, a mid-jejunal site of perforation was noted due to a protruding piece of fractured frog bone. Washout and primary repair of the small bowel enterotomy were performed, and the patient made an excellent post-operative recovery.

An Improved Toolkit of Gateway- and Gibson Assembly-Compatible Vectors for Protoplast Transfection and Agrobacterium-Mediated Plant Transformation.

Objective: Understanding the regulation and function of plant genes is essential for addressing the challenges faced by modern agriculture. Plant transformation, in conjunction with fluorescence microscopy, offers a powerful approach to investigate the dynamic behavior of plant genes and the proteins they encode. We previously developed a set of Gateway-compatible tissue-specific plant transformation vectors. In this paper we aim to expand the toolkit of vectors available for Agrobacterium-mediated plant transformation and protoplast transfection. Results: Here, we introduce new Agrobacterium-mediated plant transformation vectors by introducing additional fluorophores to create the pJRA vector series. Additionally, we introduce the pLCS series of vectors, a new set of modular Gateway- and Gibson assembly-compatible vectors designed for protoplast transfection. All described vectors are available from Addgene to serve as a resource for the plant research community.

Hydrogel Delivery Device for the In Vitro and In Vivo Sustained Release of Active rhGALNS Enzyme.

Morquio A disease is a genetic disorder resulting in N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, and patients are currently treated with enzyme replacement therapy via weekly intravenous enzyme infusions. A means of sustained enzyme delivery could improve patient quality of life by reducing the administration time, frequency of hospital visits, and treatment cost. In this study, we investigated poly(ethylene-glycol) (PEG) hydrogels as a tunable, hydrolytically degradable drug delivery system for the encapsulation and sustained release of recombinant human GALNS (rhGALNS). We evaluated hydrogel formulations that optimized hydrogel gelation and degradation time while retaining rhGALNS activity and sustaining rhGALNS release. We observed the release of active rhGALNS for up to 28 days in vitro from the optimized formulation. rhGALNS activity was preserved in the hydrogel relative to buffer over the release window, and encapsulation was found to have no impact on the rhGALNS structure when measured by intrinsic fluorescence, circular dichroism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In vivo, we monitored the retention of fluorescently labeled rhGALNS in C57BL/6 albino mice when administered via subcutaneous injection and observed rhGALNS present for up to 20 days when delivered in a hydrogel versus 7 days in the buffer control. These results indicate that PEG hydrogels are suitable for the encapsulation, preservation, and sustained release of recombinant enzymes and may present an alternative method of delivering enzyme replacement therapies that improve patient quality of life.

Structural analysis of a fibre-reinforced composite blade for a 1 MW tidal turbine rotor under degradation of seawater.

This paper presents a structural performance study of a fibre-reinforced composite blade for a 1 MW tidal turbine rotor blade that was designed for a floating tidal turbine device. The 8-m long blade was manufactured by ÉireComposites Teo and its structural performance was experimentally evaluated under mechanical loading in the Large Structures Research Laboratory at the University of Galway. Composite coupons, applied with an accelerated ageing process, were tested to evaluate the influence of seawater ageing effects on the performance of the materials. The material strength of the composites was found to have a considerable degradation under the seawater ingress. As part of the design stage, a digital twin of the rotor blade was developed, which was a finite-element model based on layered shell elements. The finite-element model was verified to have good accuracy, with a difference of 4% found in the blade tip deflection between the physically measured test results in the laboratory and numerical prediction from the model. By updating the numerical results with the material properties under seawater ageing effects, the structural performance of the tidal turbine blade under the working environment was studied. A negative impact from seawater ingress was found on the blade stiffness, strength and fatigue life. However, the results show that the blade can withstand the maximum design load and guarantee the safe operation of the tidal turbine within its design life under the seawater ingress.

Competency in trauma surgery: a national survey of trainees and consultants.

BACKGROUND: The current sparsity of surgical trainees' exposure to training in operative trauma surgery is multifactorial. This concern has been addressed in the revised Intercollegiate Surgical Curriculum Programme (ISCP) for general and vascular surgery (2021). In the lead up to its implementation, we aimed to assess both trainee and consultant confidence levels as a surrogate reflection in the core competency operative skills in general emergency trauma surgery, identify individual experience in commonly performed trauma procedures and gauge interest in a career in trauma surgery. METHOD: An online survey was circulated to general surgery and vascular surgery trainees and consultants. Self-reported competencies were assessed using a 1-10 confidence rating scale. Most questions were based on competencies in emergency trauma surgery as set out by the ISCP. RESULTS: Out of 251 surgical trainees and consultants, 119 responded to our survey (47.4% response rate). Less than half (44.1%; n = 52) of respondents had experienced a trauma thoracotomy. Respondents scored 'somewhat' or 'not at all' competent in the majority of competencies assessed. CONCLUSION: Self-reported competencies in operative trauma skills across all subgroups were sub-standard with incremental levels of perceived competence proportional to years of surgical training. Our data supports the necessity of the new curriculum, in addition to modern training pathways with direct exposure to operative trauma surgery involving dedicated trauma centres and networks, and responsibility of training pathways in the provision of training trauma surgery.

How to design and implement a Group Poem activity.

Museum-based learning activities provide interactive and innovative ways to integrate the arts and humanities into medical education. Like other museum-based activities, the Group Poem supports the development of multiple clinically relevant skills and attributes, such as observation, communication, perspective-taking, empathy, and implicit bias awareness. In this paper, we present a step-by-step guide for educators seeking to design and implement a museum-based Group Poem activity for medical learners. The overall 'task' of the activity is for learners to collectively create a poem that they perform for others, a process that participants find to be engaging and meaningful to their formation as physicians. In this paper, we provide specific directions on pre-selecting the works of art, preparing the supplies, dividing into small groups, providing iterative instructions to learners, managing the timing of the session, and debriefing the activity. Although designed to be experienced in an art museum, we note that the Group Poem activity can also be conducted in the classroom or virtually using photographic or digital reproductions of artwork.

A Standardized and Regionalized Network of Care for Cardiogenic Shock.

BACKGROUND: The benefits of standardized care for cardiogenic shock (CS) across regional care networks are poorly understood. OBJECTIVES: The authors compared the management and outcomes of CS patients initially presenting to hub versus spoke hospitals within a regional care network. METHODS: The authors stratified consecutive patients enrolled in their CS registry (January 2017 to December 2019) by presentation to a spoke versus the hub hospital. The primary endpoint was 30-day mortality. Secondary endpoints included bleeding, stroke, or major adverse cardiovascular and cerebrovascular events. RESULTS: Of 520 CS patients, 286 (55%) initially presented to 34 spoke hospitals. No difference in mean age (62 years vs 61 years; P = 0.38), sex (25% vs 32% women; P = 0.10), and race (54% vs 52% white; P = 0.82) between spoke and hub patients was noted. Spoke patients more often presented with acute myocardial infarction (50% vs 32%; P < 0.01), received vasopressors (74% vs 66%; P = 0.04), and intra-aortic balloon pumps (88% vs 37%; P < 0.01). Hub patients were more often supported with percutaneous ventricular assist devices (44% vs 11%; P < 0.01) and veno-arterial extracorporeal membrane oxygenation (13% vs 0%; P < 0.01). Initial presentation to a spoke was not associated with increased risk-adjusted 30-day mortality (adjusted OR: 0.87 [95% CI: 0.49-1.55]; P = 0.64), bleeding (adjusted OR: 0.89 [95% CI: 0.49-1.62]; P = 0.70), stroke (adjusted OR: 0.74 [95% CI: 0.31-1.75]; P = 0.49), or major adverse cardiovascular and cerebrovascular events (adjusted OR 0.83 [95% CI: 0.50-1.35]; P = 0.44). CONCLUSIONS: Spoke and hub patients experienced similar short-term outcomes within a regionalized CS network. The optimal strategy to promote standardized care and improved outcomes across regional CS networks merits further investigation.

Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women.

Exercise tolerance appears to benefit most from dietary nitrate (NO3-) supplementation when muscle oxygen (O2) availability is low. Using a double-blind, randomized cross-over design, we tested the hypothesis that acute NO3- supplementation would improve blood flow restricted exercise duration in post-menopausal women, a population with reduced endogenous nitric oxide bioavailability. Thirteen women (57-76 yr) performed rhythmic isometric handgrip contractions (10% MVC, 30 per min) during progressive forearm blood flow restriction (upper arm cuff gradually inflated 20 mmHg each min) on three study visits, with 7-10 days between visits. Approximately one week following the first (familiarization) visit, participants consumed 140 ml of NO3- concentrated (9.7 mmol, 0.6 gm NO3-) or NO3-depleted beetroot juice (placebo) on separate days (≥7 days apart), with handgrip exercise beginning 100 min post-consumption. Handgrip force recordings were analyzed to determine if NO3- supplementation enhanced force development as blood flow restriction progressed. Nitrate supplementation increased plasma NO3- (16.2-fold) and NO2- (4.2-fold) and time to volitional fatigue (61.8 ± 56.5 s longer duration vs. placebo visit; p = 0.03). Nitrate supplementation increased the rate of force development as forearm muscle ischemia progressed (p = 0.023 between 50 and 75% of time to fatigue) with non-significant effects thereafter (p = 0.052). No effects of nitrate supplementation were observed for mean duration of contraction or relaxation rates (all p > 0.150). These results suggest that acute NO3- supplementation prolongs time-to-fatigue and speeds grip force development during progressive forearm muscle ischemia in postmenopausal women.

Evolving Trends in Surgical Management of Breast Cancer: An Analysis of 30 Years of Practice Changing Papers.

The management of breast cancer has evolved into a multidisciplinary evidence-based surgical speciality, with emphasis on conservative surgery. A number of landmark trials have established lumpectomy followed by radiation as the standard of care for many patients. The aim of this study is to construct a narrative review of recent developments in the surgical management of breast cancer and how such developments have impacted surgical practice. A comprehensive literature search of Pubmed was conducted. The latest search was performed on October 31st, 2020. Search terms "breast cancer" were used in combinations with specific key words and Boolean operators relating to surgical management. The reference lists of retrieved articles were comprehensively screened for additional eligible publications. Articles were selected and reviewed based on relevance. We selected publications in the past 10 years but did not exclude commonly referenced and highly regarded previous publications. Review articles and book chapters were also cited to provide reference on details not discussed in the academic literature. This article reviews the current evidence in surgical management of early-stage breast cancer, discusses recent trends in surgical practice for therapeutic and prophylactic procedures and provides commentary on implications and factors associated with these trends.

Umbilical mesenchymal stem cell-derived extracellular vesicles as enzyme delivery vehicle to treat Morquio A fibroblasts.

BACKGROUND: Mucopolysaccharidosis IVA (Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which results in the accumulation of the glycosaminoglycans (GAGs), keratan sulfate, and chondroitin-6-sulfate in the lysosomes of all tissues causing systemic dysfunction. Current treatments include enzyme replacement therapy (ERT) which can treat only certain aspects of the disease such as endurance-related biological endpoints. A key challenge in ERT is ineffective enzyme uptake in avascular tissues, which makes the treatment of the corneal, cartilage, and heart valvular tissue difficult. The aim of this study was to culture human umbilical mesenchymal stem cells (UMSC), demonstrate presence of GALNS enzyme activity within the extracellular vesicles (EVs) derived from these UMSC, and study how these secreted EVs are taken up by GALNS-deficient cells and used by the deficient cell's lysosomes. METHODS: We obtained and cultured UMSC from the umbilical cord tissue from anonymous donors from the Saint Louis Cord Blood Bank. We characterized UMSC cell surface markers to confirm phenotype by cell sorting analyses. In addition, we confirmed that UMSC secrete GALNS enzyme creating conditioned media for co-culture experiments with GALNS deficient cells. Lastly, we isolated EVs derived from UMSC by ultracentrifugation to confirm source of GALNS enzyme. RESULTS: Co-culture and confocal microscopy experiments indicated that the lysosomal content from UMSC migrated to deficient cells as evidenced by the peak signal intensity occurring at 15 min. EVs released by UMSC were characterized indicating that the EVs contained the active GALNS enzyme. Uptake of GALNS within EVs by deficient fibroblasts was not affected by mannose-6-phosphate (M6P) inhibition, suggesting that EV uptake by these fibroblasts is gradual and might be mediated by a different means than the M6P receptor. CONCLUSIONS: UMSC can deliver EVs containing functional GALNS enzyme to deficient cells. This enzyme delivery method, which was unaffected by M6P inhibition, can function as a novel technique for reducing GAG accumulation in cells in avascular tissues, thereby providing a potential treatment option for Morquio A syndrome.

Neoadjuvant Short-Course Radiotherapy for Upper Third Rectal Tumors: Systematic Review and Individual Patient Data Metaanalysis of Randomized Controlled Trials.

BACKGROUND: There is no consensus on the use of neoadjuvant radiotherapy for tumors of the upper third of the rectum. Due to conflicting findings in high-quality trials and significant long-term side effects associated with neoadjuvant radiotherapy, the benefit of neoadjuvant radiotherapy for upper third rectal tumors is less certain than for lower two third rectal tumors. This metaanalysis compares oncological outcomes with neoadjuvant radiotherapy and surgery versus surgery alone for upper third rectal tumors. PATIENTS AND METHODS: PubMed, Embase, and the Cochrane library databases were searched. Randomized controlled trials (RCT) comparing neoadjuvant radiotherapy and surgery versus surgery alone for resectable rectal cancer were included. Individual patient data were sought from the principal investigator of each eligible trial for comparative data on patients with upper third rectal tumors. The main outcomes measured were survival outcomes, oncological outcomes, postoperative morbidity, and late toxicity. RESULTS: Individual patient data from two RCTs examining outcomes in 758 patients were obtained. Published data from one further RCT containing comparable data on upper third rectal tumors were included in analysis of local recurrence. In patients with curative surgery, there was no significant reduction in local recurrence or significant improvement in overall survival or disease-free survival with neoadjuvant radiotherapy (LR RR: 0.38, 95% CI 0.14-1.04, p = 0.06) (OS RR: 1.10, 95% CI 0.98-1.24, p = 0.11) (DFS RR: 1.11, 95% CI 0.97-1.26, p = 0.13). CONCLUSIONS: The benefit of neoadjuvant radiotherapy for upper third rectal tumors is not certain, and surgery alone for patients with potentially curative disease at preoperative staging may be sufficient.