Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: systematic review.

BACKGROUND: Ileal pouch-anal anastomosis ('pouch surgery') provides a chance to avoid permanent ileostomy after proctocolectomy, but can be associated with poor outcomes. The relationship between hospital-level/surgeon factors (including volume) and outcomes after pouch surgery is of increasing interest given arguments for increasing centralization of these complex procedures. The aim of this systematic review was to appraise the literature describing the influence of hospital-level and surgeon factors on outcomes after pouch surgery for inflammatory bowel disease. METHODS: A systematic review was performed of studies reporting outcomes after pouch surgery for inflammatory bowel disease. The MEDLINE (Ovid), Embase (Ovid), and Cochrane CENTRAL databases were searched (1978-2022). Data on outcomes, including mortality, morbidity, readmission, operative approach, reconstruction, postoperative parameters, and pouch-specific outcomes (failure), were extracted. Associations between hospital-level/surgeon factors and these outcomes were summarized. This systematic review was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42022352851). RESULTS: A total of 29 studies, describing 41 344 patients who underwent a pouch procedure, were included; 3 studies demonstrated higher rates of pouch failure in lower-volume centres, 4 studies demonstrated higher reconstruction rates in higher-volume centres, 2 studies reported an inverse association between annual hospital pouch volume and readmission rates, and 4 studies reported a significant association between complication rates and surgeon experience. CONCLUSION: This review summarizes the growing body of evidence that supports centralization of pouch surgery to specialist high-volume inflammatory bowel disease units. Centralization of this technically demanding surgery that requires dedicated perioperative medical and nursing support should facilitate improved patient outcomes and help train the next generation of pouch surgeons.

Restoration of intestinal continuity following emergency sigmoid colectomy for sigmoid volvulus: An American College of Surgeons National Surgical Quality Improvement Program analysis using coarsened exact matching.

BACKGROUND: There is limited data to guide decision-making between performing a primary anastomosis and fashioning an end colostomy following emergency sigmoid colectomy for patients with sigmoid volvulus. The aim of this study was to compare the outcomes of these two approaches. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2006 to 2021 was retrospectively analyzed. Missing data were multiply imputed, and coarsened exact matching was performed to generate matched cohorts. Rates of major complications and other postoperative outcomes were evaluated among patients who had a primary anastomosis as compared with matched controls who had an end colostomy following emergency sigmoid colectomy. RESULTS: Overall, 4041 patients who had a primary anastomosis and 1240 who had an end colostomy met the inclusion criteria. After multiple imputation and coarsened exact matching, 895 patients who had a primary anastomosis had a matched control. The rate of major complications was lower in patients who had an end colostomy (33.2% vs. 36.7%), but this difference was not statistically significant (OR 0.86, 95% CI 0.70-1.05). Results were similar in subgroup analyses of higher-risk patients. There were no significant differences in overall complication rate, mortality, length of hospital stay, or readmission rate. Patients with a colostomy were more likely to be discharged to a care facility (OR 1.35, 95% CI 1.09-1.67). CONCLUSION: Differences in rates of major complications and many other outcomes after primary anastomosis as compared with end colostomy were not statistically significant following emergency sigmoid colectomy for sigmoid volvulus.

Cloud-Based Machine Learning Platform to Predict Clinical Outcomes at Home for Patients With Cardiovascular Conditions Discharged From Hospital: Clinical Trial.

BACKGROUND: Hospitalizations account for almost one-third of the US $4.1 trillion health care cost in the United States. A substantial portion of these hospitalizations are attributed to readmissions, which led to the establishment of the Hospital Readmissions Reduction Program (HRRP) in 2012. The HRRP reduces payments to hospitals with excess readmissions. In 2018, >US $700 million was withheld; this is expected to exceed US $1 billion by 2022. More importantly, there is nothing more physically and emotionally taxing for readmitted patients and demoralizing for hospital physicians, nurses, and administrators. Given this high uncertainty of proper home recovery, intelligent monitoring is needed to predict the outcome of discharged patients to reduce readmissions. Physical activity (PA) is one of the major determinants for overall clinical outcomes in diabetes, hypertension, hyperlipidemia, heart failure, cancer, and mental health issues. These are the exact comorbidities that increase readmission rates, underlining the importance of PA in assessing the recovery of patients by quantitative measurement beyond the questionnaire and survey methods. OBJECTIVE: This study aims to develop a remote, low-cost, and cloud-based machine learning (ML) platform to enable the precision health monitoring of PA, which may fundamentally alter the delivery of home health care. To validate this technology, we conducted a clinical trial to test the ability of our platform to predict clinical outcomes in discharged patients. METHODS: Our platform consists of a wearable device, which includes an accelerometer and a Bluetooth sensor, and an iPhone connected to our cloud-based ML interface to analyze PA remotely and predict clinical outcomes. This system was deployed at a skilled nursing facility where we collected >17,000 person-day data points over 2 years, generating a solid training database. We used these data to train our extreme gradient boosting (XGBoost)-based ML environment to conduct a clinical trial, Activity Assessment of Patients Discharged from Hospital-I, to test the hypothesis that a comprehensive profile of PA would predict clinical outcome. We developed an advanced data-driven analytic platform that predicts the clinical outcome based on accurate measurements of PA. Artificial intelligence or an ML algorithm was used to analyze the data to predict short-term health outcome. RESULTS: We enrolled 52 patients discharged from Stanford Hospital. Our data demonstrated a robust predictive system to forecast health outcome in the enrolled patients based on their PA data. We achieved precise prediction of the patients' clinical outcomes with a sensitivity of 87%, a specificity of 79%, and an accuracy of 85%. CONCLUSIONS: To date, there are no reliable clinical data, using a wearable device, regarding monitoring discharged patients to predict their recovery. We conducted a clinical trial to assess outcome data rigorously to be used reliably for remote home care by patients, health care professionals, and caretakers.

Optimizing theatre utilization for abscess drainage: going beyond priority categories.

BACKGROUND: Day-only emergency surgery for abscess drainage is poorly implemented in Australia. This study assessed the feasibility, outcomes, cost, and impact of an acute day-only surgery (ADOS) program. METHOD: A retrospective pre-post implementation study of patients requiring abscess drainage in theatre was performed. Following implementation of an ADOS program for abscess management, eligible patients were discharged from the emergency department and prioritized first on the following day's emergency list. Outcomes from the first 12 months of the ADOS era were compared with those of the preceding 6 months (pre-ADOS). Primary outcome was length of hospital stay (LOS). Secondary outcomes included 30-day complications, admission costs, and impact on overall emergency theatre workflow (measured by emergency appendicectomy metrics). RESULTS: Overall, 266 patients during the ADOS era (including 95 eligible for the ADOS pathway) were compared with 115 patients during the pre-ADOS era. Baseline characteristics were comparable. Median LOS was shorter during the ADOS era (21.9 h (IQR 11.8-43.3) vs. 30.1 h (IQR 24.7-48.8), P < 0.001). Median LOS was 10.2 h (IQR 8.9-13.1) for patients on the ADOS pathway. There were no significant differences in 30-day complications (9.3% vs. 9.5%), emergency department re-presentations (7.4% vs. 5.1%), or abscess recurrence (5.6% vs. 5.7%). Average cost per patient was lower during the ADOS era ($4155 vs. $4916, p = 0.005). ADOS did not appear to materially impact other emergency procedures. CONCLUSION: ADOS for abscess drainage is feasible, safe, and produces cost savings, while being implemented without significant additional resources.

Anti-breast cancer-induced cardiomyopathy: Mechanisms and future directions.

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects. Targeted drugs have always been considered a relatively safe option. However, in recent years, some random clinical trials have observed the occurrence of subclinical cardiotoxicity in targeted antitumor drug users, which may be related to the effects of targeted drugs on the angiotensin converting enzyme, angiotensin receptor and ß receptor. The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and beta-blockers may prevent clinical cardiotoxicity. This article reviews the toxicity and mechanisms of current clinical anti-breast cancer drugs and proposes strategies for preventing cardiovascular toxicity to provide recommendations for the clinical prevention and treatment of chemotherapy-related cardiomyopathy.

Impact of obesity on patients undergoing surgery for rectal cancer in Australia and New Zealand.

PURPOSE: Patients with obesity undergoing rectal cancer surgery may have an increased risk of developing complications, though evidence is inconclusive. The aim of this study was to determine the direct impact of obesity on postoperative outcomes using data from a large clinical registry. METHOD: The Binational Colorectal Cancer Audit registry was used to identify patients who underwent rectal cancer surgery in Australia and New Zealand from 2007-2021. Primary outcomes were inpatient surgical and medical complications. Logistic regression models were developed to describe the association between body-mass index (BMI) and outcomes. RESULTS: Among 3,708 patients (median age 66 years [IQR 56.75-75], 65.0% male), 2.0% had a BMI < 18.5 kg/m2, 35.4% had a BMI of 18.5-24.9 kg/m2, 37.6% had a BMI of 25.0-29.9 kg/m2, 16.7% had a BMI of 30.0-34.9 kg/m2, and 8.2% had a BMI ≥ 35.0 kg/m2. Surgical complications occurred in 27.7% of patients with a BMI of 18.5-24.9 kg/m2, 26.6% of patients with a BMI of 25.0-29.9 kg/m2 (OR 0.91, 95% CI 0.76-1.10), 28.5% with a BMI of 30.0-34.9 kg/m2 (OR 0.96, 95% CI 0.76-1.21), and 33.2% with a BMI ≥ 35.0 kg/m2 (OR 1.27, 95% CI 0.94-1.71). Modelling BMI as a continuous variable confirmed a J-shaped relationship. The association between BMI and medical complications was more linear. CONCLUSION: Risk of postoperative complications is increased in patients with obesity undergoing rectal cancer surgery.

Evaluating the impact of metabolic surgery on patients with prior opioid use.

BACKGROUND: Metabolic surgery is the most effective treatment for obesity and may improve obesity-related pain syndromes. However, the effect of surgery on the persistent use of opioids in patients with a history of prior opioid use remains unclear. OBJECTIVE: To determine the effect of metabolic surgery on opioid use behaviors in patients with prior opioid use. SETTING: A consortium of public and private hospitals in Michigan. METHODS: Using a statewide metabolic-specific data registry, we identified 16,820 patients who self-reported opioid use before undergoing metabolic surgery between 2006 and 2020 and analyzed the 8506 (50.6%) patients who responded to 1-year follow-up. We compared patient characteristics, risk-adjusted 30-day postoperative outcomes, and weight loss between patients who self-reported discontinuing opioid use 1 year after surgery and those who did not. RESULTS: Among patients who self-reported using opioids before metabolic surgery, 3864 (45.4%) discontinued use 1 year after surgery. Predictors of persistent opioid use included an annual income of <$10,000 (odds ratio [OR] = 1.24; 95% confidence interval [CI], 1.06-1.44; P = .006), Medicare insurance (OR = 1.48; 95% CI, 1.32-1.66; P < .0001), and preoperative tobacco use (OR = 1.36; 95% CI, 1.16-1.59; P = .0001). Patients with persistent use were more likely to have a surgical complication (9.6% versus 7.5%, P = .0328) and less percent excess weight loss (61.6% versus 64.4%, P < .0001) than patients who discontinued opioids after surgery. There were no differences in the morphine milligram equivalents prescribed within the first 30 days following surgery between groups (122.3 versus 126.5, P = .3181). CONCLUSIONS: Nearly half of patients who reported taking opioids before metabolic surgery discontinued use at 1 year. Targeted interventions aimed at high-risk patients may increase the number of patients who discontinue opioid use after metabolic surgery.

Microvascular obstruction identifies a subgroup of patients who benefit from stem cell therapy following ST-elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarction (STEMI). We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. METHODS AND RESULTS: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs or placebo / control as part of 4 randomized clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot, the multicenter French BONAMI trial and SWISS-AMI trials. A total of 327 patients had paired imaging data at 1 year. All patients received 100 to 150 million intracoronary autologous BMCs or placebo / control 3 to 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n = 210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n = 146) (P < .01). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7%; P < .05). Similarly, left-ventricular end-diastolic (LVEDVI) and end-systolic volume indices (LVESVI) demonstrated significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo. In contrast, no improvement in LVEF or LV volumes was observed in those patients without MVO who received BMCs compared to placebo. CONCLUSIONS: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who benefit from intracoronary stem cell therapy.

Angiogenic stem cell delivery platform to augment post-infarction neovasculature and reverse ventricular remodeling.

Many cell-based therapies are challenged by the poor localization of introduced cells and the use of biomaterial scaffolds with questionable biocompatibility or bio-functionality. Endothelial progenitor cells (EPCs), a popular cell type used in cell-based therapies due to their robust angiogenic potential, are limited in their therapeutic capacity to develop into mature vasculature. Here, we demonstrate a joint delivery of human-derived endothelial progenitor cells (EPC) and smooth muscle cells (SMC) as a scaffold-free, bi-level cell sheet platform to improve ventricular remodeling and function in an athymic rat model of myocardial infarction. The transplanted bi-level cell sheet on the ischemic heart provides a biomimetic microenvironment and improved cell-cell communication, enhancing cell engraftment and angiogenesis, thereby improving ventricular remodeling. Notably, the increased density of vessel-like structures and upregulation of biological adhesion and vasculature developmental genes, such as Cxcl12 and Notch3, particularly in the ischemic border zone myocardium, were observed following cell sheet transplantation. We provide compelling evidence that this SMC-EPC bi-level cell sheet construct can be a promising therapy to repair ischemic cardiomyopathy.

Patient characteristics and outcomes among bariatric surgery patients with high narcotic overdose scores.

BACKGROUND: Obesity-related chronic pain can increase the risk of narcotic abuse in bariatric surgery patients. However, assessment of overdose risk has not been evaluated to date. METHODS: A NARxCHECK® overdose score ("Narx score") was obtained preoperatively on all patients undergoing bariatric surgery (n = 306) between 2018 and 2020 at a single-center academic bariatric surgery program. The 3-digit score ranges from 000 to 999 and is based on patient risk factors found within the Prescription Drug Monitoring Program. A Narx score ≥ 200 indicates tenfold increased risk of narcotic overdose. Patient characteristics, comorbidities, and emergency room (ER) visits were compared between patients in the upper (≥ 200) and lower (000) terciles of Narx scores. Morphine milligram equivalent (MME) prescribed at discharge and refills was also evaluated. RESULTS: Patients in the upper tercile represented 32% (n = 99) of the study population, and compared to the lower tercile (n = 101, 33%), were more likely to have depression (63.6% vs 38.6%, p = 0.0004), anxiety (47.5% vs 30.7%, p = 0.0150), and bipolar disorder (6.1% vs 0.0%, p = 0.0120). Median MME prescribed at discharge was the same between both groups (75); however, high-risk patients were more likely to be prescribed more than 10 tablets of a secondary opioid (83.3% vs 0.0%, p = 0.0111), which was prescribed by another provider in 67% of cases. ER visits among patients who did not have a complication or require a readmission was also higher among high-risk patients (7.8% vs 0.0%, p = 0.0043). There were no deaths or incidents of mental health-related ER visits in either group. CONCLUSION: Patients with a Narx score ≥ 200 were more likely to have mental health disorders and have potentially avoidable ER visits in the setting of standardized opioid prescribing practices. Narx scores can help reduce ER visits by identifying at-risk patients who may benefit from additional clinic or telehealth follow-up.

Surgical quality assurance at expanding health networks: A qualitative study.

BACKGROUND: Even after decades of network expansion and increased care being delivered within health networks, health network expansion has not led to uniform improvements in patient outcomes and satisfaction. The reasons for the lack of universal surgical quality improvement are unclear. This study used qualitative methods to understand the nuances that affect the variation in network-level surgical quality assurance and provides strategies that surgical leaders use to improve surgical quality at expanding health networks. METHODS: This qualitative study obtained information through 30 semistructured interviews conducted from August to December 2019 with surgical leaders whose institutions were associated with health networks. The topic of surgical quality assurance was an emergent theme that was informed by thematic analysis. RESULTS: Interviews with leaders revealed 3 themes with regard to surgical quality assurance. First, participants wanted standardized tools for quality measurement. Leaders frequently referred to the National Surgical Quality Improvement Program registry and shared electronic health records, but some networks did not have these available at all sites. Second, participants wanted an organizational structure that provides clear oversight over quality. Some leaders appointed executives or created committees to help manage quality improvement initiatives. Third, participants wanted a culture shift toward quality improvement. Many leaders faced resistance to quality initiatives from frontline clinicians; some implemented events and retreats to help garner support and a culture of quality. CONCLUSION: These interviews offer critical insights into 3 domains that can be leveraged for sustained improvement and detail strategies that leaders used for surgical quality assurance at hospital networks.

Challenges and Opportunities for the Academic Mission Within Expanding Health Systems: A Qualitative Study.

OBJECTIVE: To explore challenges and opportunities for surgery departments' academic missions as they become increasingly affiliated with expanding health systems. SUMMARY BACKGROUND DATA: Academic medicine is in the midst of unprecedented change. In addition to facing intense competition, narrower margins, and decreased federal funding, medical schools are becoming increasingly involved with large, expanding health systems. The impact of these health system affiliations on surgical departments' academic missions is unknown. METHODS: Semistructured interviews with 30 surgical leaders at teaching hospitals affiliated with health systems from August - December 2019. Interviews were transcribed verbatim and coded in an iterative process using MaxQDA software. The topic of challenges and opportunities for the academic mission was an emergent theme, analyzed using thematic analysis. RESULTS: Academic health systems typically expanded to support their business goals, rather than their academic mission. Changes in governance sometimes disempowered departmental leadership, shifted traditional compensation models, redirected research programs, and led to cultural conflict. However, at many institutions, health system growth cross-subsidized surgical departments' research and training missions, expanded their clinical footprint, enabled them to improve standards of care, and enhanced opportunities for researchers and trainees. CONCLUSIONS: Although health system expansion generally intended to advance business goals, the accompanying academic and clinical opportunities were not always fully captured. Alignment between medical school and health system goals enabled some surgical department leaders to take advantage of their health systems' reach and resources to support their academic missions.

Comparing Diabetes Outcomes: Weight-independent Effects of Sleeve Gastrectomy Versus Matched Patients With Similar Weight Loss.

OBJECTIVE: To determine if sleeve gastrectomy has weight-independent benefits on diabetes outcomes. SUMMARY BACKGROUND DATA: Weight loss is recommended when treating conditions such as diabetes, hypertension, and hyperlipidemia. Bariatric surgery has been shown to improve or resolve metabolic conditions, but weight loss outcomes vary by procedure type. METHODS: Using data from a statewide bariatric surgery registry, a total of 988 patients with a preoperative diagnosis of diabetes who underwent either laparoscopic sleeve gastrectomy (LSG) or laparoscopic adjustable gastric banding (LAGB) were included in the study. The patients were matched based on age, race, sex, preoperative body mass index (BMi) and weight loss at 1 year after surgery. Chi-square comparisons were conducted for medication discontinuation for diabetes. Secondary outcome measures included discontinuation of medications for hypertension and hyperlipidemia. RESULTS: The mean age of patients was 53.9 years, 75.5% were female, 89.3% were White. Mean preoperative BMi was 44.8 kg/m2 and 75.7% had noninsulin dependent diabetes, whereas 24.3% had insulin dependent diabetes. Mean % BMi loss at 1 year is similar between the 2 groups (8.3% vs 8.1%, P = 0.3811). LSG patients had significantly higher rates of discontinuation of oral diabetes medication (70.4% vs 46.0%, P < 0.0001), insulin (51.7% vs 38.3%, P = 0.0341), anti-hypertensive (41.1% vs 26.0%, P < 0.0001), and cholesterol-lowering medications (40.1% vs 27.8%, P = 0.0016) when compared to LAGB patients. CONCLUSIONS: Despite similar preoperative characteristics and postoperative weight loss, LSG patients experienced significantly higher rates of medication discontinuation for diabetes, hypertension, and hyperlipidemia than LAGB. These results suggest that LSG may have weight-independent effects on metabolic disease and should be considered in the treatment of diabetes, regardless of perceived weight loss outcomes.

Robotic colorectal surgery and ergonomics.

Improved ergonomics for the operating surgeon may be an advantage of robotic colorectal surgery. Perceived robotic ergonomic advantages in visualisation include better exposure, three-dimensional vision, surgeon camera control, and line of sight screen location. Postural advantages include seated position and freedom from the constraints of the sterile operating field. Manipulation benefits include articulated instruments with seven degrees of freedom movement, elimination of fulcrum effect, tremor filtration, and scaling of movement. Potential ergonomic detriments of robotic surgery include lack of haptic feedback, visual, and mental strain from increased operating time and interruptions to workflow from crowding.

Cultural Variations of Areca Nut Utilization and Its Availability in San Antonio, Texas.

Unknown in the U.S., areca nut (AN) is the fourth most used psychoactive substance in the world and is associated with oral cancers. We investigated the availability of AN in San Antonio ethnic grocery stores and assessed AN practices in immigrant communities. Grocery stores were contacted to assess AN availability. A survey on AN knowledge and utilization were administered at four community sites with large immigrant populations. 13 of the 19 identified grocery stores carried AN. Most survey participants (n = 66) recognized AN. Most Southeast Asians and South Asians knew what AN is, knew someone who uses it, and knew where to buy it. Most South Asian participants knew its harmful effects. AN usage is associated with older age, male sex, and recent immigration. AN is widely available and utilized among immigrant populations in San Antonio. Further work is needed to raise AN awareness among healthcare workers.

Recommendations for nomenclature and definition of cell products intended for human cardiovascular use.

Exogenous cell-based therapy has emerged as a promising new strategy to facilitate repair of hearts damaged by acute or chronic injury. However, the field of cell-based therapy is handicapped by the lack of standardized definitions and terminology, making comparisons across studies challenging. Even the term 'stem cell therapy' is misleading because only a small percentage of cells derived from adult bone marrow, peripheral blood, or adipose tissue meets the accepted haematopoietic or developmental definition of stem cells. Furthermore, cells (stem or otherwise) are dynamic biological products, meaning that their surface-marker expression, phenotypic and functional characteristics, and the products they secrete in response to their microenvironment can change. It is also important to point out that most surface markers are seldom specific for a cell type. In this article, we discuss the lack of consistency in the descriptive terminology used in cell-based therapies and offer guidelines aimed at standardizing nomenclature and definitions to improve communication among investigators and the general public.

Mitochondria-Rich Extracellular Vesicles Rescue Patient-Specific Cardiomyocytes From Doxorubicin Injury: Insights Into the SENECA Trial.

BACKGROUND: Anthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute-sponsored study, but the mechanisms underpinning efficacy in human tissue need clarification. OBJECTIVES: The purpose of this study was to perform an in vitro clinical trial evaluating the efficacy and putative mechanisms of SENECA trial-specific MSCs in treating doxorubicin (DOX) injury, using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iCMs) generated from SENECA patients. METHODS: Patient-specific iCMs were injured with 1 µmol/L DOX for 24 hours, treated with extracellular vesicles (EVs) from MSCs by either coculture or direct incubation and then assessed for viability and markers of improved cellular physiology. MSC-derived EVs were separated into large extracellular vesicles (L-EVs) (>200 nm) and small EVs (<220nm) using a novel filtration system. RESULTS: iCMs cocultured with MSCs in a transwell system demonstrated improved iCM viability and attenuated apoptosis. L-EVs but not small EVs recapitulated this therapeutic effect. L-EVs were found to be enriched in mitochondria, which were shown to be taken up by iCMs. iCMs treated with L-EVs demonstrated improved contractility, reactive oxygen species production, ATP production, and mitochondrial biogenesis. Inhibiting L-EV mitochondrial function with 1-methyl-4-phenylpyridinium attenuated efficacy. CONCLUSIONS: L-EV-mediated mitochondrial transfer mitigates DOX injury in patient-specific iCMs. Although SENECA was not designed to test MSC efficacy, consistent tendencies toward a positive effect were observed across endpoints. Our results suggest a mechanism by which MSCs may improve cardiovascular performance in AIC independent of regeneration, which could inform future trial design evaluating the therapeutic potential of MSCs.

A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial.

AIMS: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. METHODS AND RESULTS: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. CONCLUSIONS: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.

Bowel Preparation and Oral Antibiotic Agents for Selective Decontamination in Colorectal Surgery: Current Practice, Perspectives, and Trends in Australia and New Zealand, 2019-2020.

Background: There has been much debate as to the importance of mechanical bowel preparation (MBP) and oral antibiotic agents (OAB) prior to elective colorectal surgery over the past two decades. There is no consensus between international guidelines. Methods: The Australia and New Zealand Mechanical Bowel Preparation and Oral Antibiotics (ANZ-MBP-OAB) questionnaire was distributed to colorectal surgeons after institutional board approval assessing specialist attitudes toward 18 enhanced recovery after surgery (ERAS) interventions. Data were analyzed using a rating scale and graded response model in item response theory (IRT) on Stata MP, version 15 (StataCorp LP, College Station, TX). Specialist attitudes toward the effectiveness of MBP and OAB strategies in providing better short-term outcomes was ranked alongside other ERAS interventions. This was followed by specific questions examining current practice, perspectives, and trends. Results: Ninety-five of 300 (31.7%) colorectal surgeons in Australia and New Zealand participated in the survey. Statistical modeling was achieved in 13 ERAS interventions. Compared with other ERAS interventions, the use of MBP with OAB and MBP alone ranked nine of 13 and 10 of 13, respectively, in order of effectiveness in providing better short-term outcomes after colorectal surgery. Oral antibiotic agents alone was not considered effective. Mechanical bowel preparation with OAB was considered to be the best strategy in both colon (37%) and rectal surgery (48%) but current practice varied substantially from perspective. Mechanical bowel preparation alone was strongly favored in rectal surgery (81%) with only 14% using MBP with OAB. In colon surgery, only 10% used MBP with OAB, with MBP alone (45%) and no preparation (45%) being equally the most commonly used strategies. Conclusions: Among Australian and New Zealand colorectal surgeons, MBP with OAB was considered the best bowel preparation strategy. However, despite an awareness of its benefits, MBP with OAB has yet to be widely adopted into clinical practice or guidelines in Australia and New Zealand.