Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction

Congestive heart failure developing after acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Clinical trials of cell-based therapy after AMI evidenced only a moderate benefit. We could show previously that suspensions of apoptotic peripheral blood mononuclear cells (PBMC) are able to reduce myocardial damage in a rat model of AMI. Here we experimentally examined the biochemical mechanisms involved in preventing ventricular remodelling and preserving cardiac function after AMI. Cell suspensions of apoptotic cells were injected intravenously or intramyocardially after experimental AMI induced by coronary artery ligation in rats. Administration of cell culture medium or viable PBMC served as controls. Immunohistological analysis was performed to analyse the cellular infiltrate in the ischaemic myocardium. Cardiac function was quantified by echocardiography. Planimetry of the infarcted hearts showed a significant reduction of infarction size and an improvement of post AMI remodelling in rats treated with suspensions of apoptotic PBMC (injected either intravenously or intramoycardially). Moreover, these hearts evidenced enhanced homing of macrophages and cells staining positive for c-kit, FLK-1, IGF-I and FGF-2 as compared to controls. A major finding in this study further was that the ratio of elastic and collagenous fibres within the scar tissue was altered in a favourable fashion in rats injected with apoptotic cells. Intravenous or intramyocardial injection of apoptotic cell suspensions results in attenuation of myocardial remodelling after experimental AMI, preserves left ventricular function, increases homing of regenerative cells and alters the composition of cardiac scar tissue. The higher expression of elastic fibres provides passive energy to the cardiac scar tissue and results in prevention of ventricular remodelling

The PrEDICT-DGE score as a simple preoperative screening tool identifies patients at increased risk for delayed gastric emptying after pancreaticoduodenectomy

BACKGROUND: Morbidity after Pancreaticoduodenectomy (PD) has remained unchanged over the past decade. Delayed Gastric Emptying (DGE) is a major contributor with significant impact on healthcare-costs, quality of life and, for malignancies, even survival. We sought to develop a scoring system to aid in easy preoperative identification of patients at risk for DGE. METHODS: The ACS-NSQIP dataset from 2014 to 2018 was queried for patients undergoing PD with Whipple or pylorus preserving reconstruction. 15,154 patients were analyzed using multivariable logistic regression to identify risk factors for DGE, which were incorporated into a prediction model. Subgroup analysis of patients without SSI or fistula (primary DGE) was performed. RESULTS: We identified 9 factors independently associated with DGE to compile the PrEDICT-DGE score: Procedures (Concurrent adhesiolysis, feeding jejunostomy, vascular reconstruction with vein graft), Elderly (Age\u3e70), Ductal stent (Lack of biliary stent), Invagination (Pancreatic reconstruction technique), COPD, Tobacco use, Disease, systemic (ASA\u3e2), Gender (Male) and Erythrocytes (preoperative RBC-transfusion). PrEDICT-DGE scoring strongly correlated with actual DGE rates (R = 0.95) and predicted patients at low, intermediate, and high risk. Subgroup analysis of patients with primary DGE, retained all predictive factors, except for age\u3e70 (p = 0.07) and ASA(p = 0.30). CONCLUSION: PrEDICT-DGE scoring accurately identifies patients at high risk for DGE and can help guide perioperative management

Presenting Symptomatology of Mediastinal Masses and Its Effect on Surgical Outcomes

OBJECTIVE: Mediastinal masses are commonly encountered by the thoracic surgeon. Few studies have reported on the frequency and characteristics of symptoms at presentation. The primary objective of this study is to determine how often patients present with symptoms from a mediastinal mass. The secondary objective is to determine if the presence of symptoms has an effect on outcomes after surgery. METHODS: A retrospective review of an institutional database was performed. All patients who underwent surgical resection of a mediastinal mass from 2013 to 2019 were included in the analysis. Medical records were reviewed for the presence or absence of symptoms preoperatively, and these cohorts were compared. Multivariable analysis was performed, adjusting for clinical variables to assess for differences between these cohorts. RESULTS: 70 patients underwent surgery for a mediastinal mass. The average age was 49.2 years, and 46 patients (65.7%) presented with symptoms. There were no significant differences in demographics between the symptomatic and asymptomatic groups. The most common symptom was dyspnea in 18 patients (22%), followed by chest pain (15 patients, 19%) and dysphagia (8 patients, 10%). When comparing symptomatic and asymptomatic patients, symptomatic patients had a larger tumor size (5.8 cm vs 3.8 cm, = .04) and a longer length of stay (2.0 days vs 1.2 days, = .02). CONCLUSIONS: The majority of patients with mediastinal masses present with symptoms, with the most common symptom being dyspnea. Symptomatic patients are more likely to have a larger tumor and tend to have a longer length of hospital stay postoperatively compared to asymptomatic patients

Impact of preoperative biliary drainage on 30 Day outcomes of patients undergoing pancreaticoduodenectomy for malignancy

BACKGROUND: Preoperative biliary drainage (PBD) has been advocated to address the plethora of physiologic derangements associated with cholestasis. However, available literature reports mixed outcomes and is based on largely outdated and/or single-institution studies. METHODS: Patients undergoing PBD prior to pancreaticoduodenectomy (PD) for periampullary malignancy between 2014-2018 were identified in the ACS-NSQIP pancreatectomy dataset. Patients with PBD were propensity-score-matched to those without PBD and 30-day outcomes compared. RESULTS: 8,970 patients met our inclusion criteria. 4,473 with obstruction and PBD were matched to 829 with no preoperative drainage procedure. In the non-jaundiced cohort, 711 stented patients were matched to 2,957 without prior intervention. PBD did not influence 30-day mortality (2.2% versus 2.4%) or major morbidity (19.8% versus 20%) in patients with obstructive jaundice. Superficial surgical site infections (SSIs) were more common with PBD (6.8% versus 9.2%), however, no differences in deep or organ-space SSIs were found. Patients without obstruction prior to PBD exhibited a 3-fold increase in wound dehiscence (0.5% versus 1.5%) additionally to increased superficial SSIs. CONCLUSION: PBD was not associated with an increase in 30-day mortality or major morbidity but increased superficial SSIs. PBD should be limited to symptomatic, profoundly jaundiced patients or those with a delay prior to PD

Arterial, but Not Venous, Reconstruction Increases 30-Day Morbidity and Mortality in Pancreaticoduodenectomy

© 2019, The Society for Surgery of the Alimentary Tract. Background: Vascular reconstruction during pancreaticoduodenectomy is increasingly utilized to improve pancreatic cancer resectability. However, few multi-institutional studies have evaluated the morbidity and mortality of arterial and venous reconstruction during this procedure. Methods: A retrospective analysis was performed utilizing the targeted pancreas module of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) for pancreaticoduodenectomy from 2014 to 2015. Demographics, comorbidities, and 30-day outcomes for patients who underwent venous or arterial reconstruction and both were compared to no reconstruction. Results: A total of 3002 patients were included in our study: 384 with venous reconstruction, 52 with arterial, 81 with both, and 2566 without. Compared to patients without reconstruction, those who underwent venous reconstruction had more congestive heart failure (1.8% vs 0.2%, P \u3c 0.01), those with arterial reconstruction had higher rates of pulmonary disease (11.5% vs. 4.5%, P = 0.02), and neoadjuvant chemotherapy was more common in both venous (34% vs 12%, P \u3c 0.01) and arterial reconstruction (21% vs 12%, P = 0.04). In multivariable analysis, there was no increase in morbidity or mortality following venous reconstruction. However, arterial reconstruction was associated with increased 30-day mortality with an odds ratio (OR): 6.7, 95%; confidence interval (CI): 1.8–25. Morbidity was increased as represented with return to the operating room (OR: 4.5, 95%; CI: 1.5–15), pancreatic fistula (OR: 4.4, 95%; CI: 1.7–11), and reintubation (OR: 3.9, 95%; CI: 1.1–14). Conclusions: Venous reconstruction during pancreaticoduodenectomy does not increase perioperative morbidity or mortality and should be considered for patients previously considered to be unresectable or those where R0 resection would otherwise not be possible due to venous involvement. Careful consideration should be made prior to arterial reconstruction given the significant increase in perioperative complications and death within 30 days

Arterial, but Not Venous, Reconstruction Increases 30-Day Morbidity and Mortality in Pancreaticoduodenectomy.

© 2019, The Society for Surgery of the Alimentary Tract. Background: Vascular reconstruction during pancreaticoduodenectomy is increasingly utilized to improve pancreatic cancer resectability. However, few multi-institutional studies have evaluated the morbidity and mortality of arterial and venous reconstruction during this procedure. Methods: A retrospective analysis was performed utilizing the targeted pancreas module of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) for pancreaticoduodenectomy from 2014 to 2015. Demographics, comorbidities, and 30-day outcomes for patients who underwent venous or arterial reconstruction and both were compared to no reconstruction. Results: A total of 3002 patients were included in our study: 384 with venous reconstruction, 52 with arterial, 81 with both, and 2566 without. Compared to patients without reconstruction, those who underwent venous reconstruction had more congestive heart failure (1.8% vs 0.2%, P \u3c 0.01), those with arterial reconstruction had higher rates of pulmonary disease (11.5% vs. 4.5%, P = 0.02), and neoadjuvant chemotherapy was more common in both venous (34% vs 12%, P \u3c 0.01) and arterial reconstruction (21% vs 12%, P = 0.04). In multivariable analysis, there was no increase in morbidity or mortality following venous reconstruction. However, arterial reconstruction was associated with increased 30-day mortality with an odds ratio (OR): 6.7, 95%; confidence interval (CI): 1.8–25. Morbidity was increased as represented with return to the operating room (OR: 4.5, 95%; CI: 1.5–15), pancreatic fistula (OR: 4.4, 95%; CI: 1.7–11), and reintubation (OR: 3.9, 95%; CI: 1.1–14). Conclusions: Venous reconstruction during pancreaticoduodenectomy does not increase perioperative morbidity or mortality and should be considered for patients previously considered to be unresectable or those where R0 resection would otherwise not be possible due to venous involvement. Careful consideration should be made prior to arterial reconstruction given the significant increase in perioperative complications and death within 30 days

Robotic Foregut Surgery in the Veterans Health Administration: Increasing Prevalence, Decreasing Operative Time, and Improving Outcomes

BACKGROUND: Historically, robotic surgery incurs longer operative times, higher costs, and nonsuperior outcomes compared with laparoscopic surgery. However, in areas of limited visibility and decreased accessibility such as the gastroesophageal junction, robotic platforms may improve visualization and facilitate dissection. This study compares 30-day outcomes between robotic-assisted foregut surgery (RAF) and laparoscopic-assisted foregut surgery in the Veterans Health Administration. STUDY DESIGN: This is a retrospective review of the Veterans Affairs Quality Improvement Program database. Patients undergoing laparoscopic-assisted foregut surgery and RAF were identified using CPT codes 43280, 43281, 43282, and robotic modifier S2900. Multivariable logistic regression and multivariable generalized linear models were used to analyze the independent association between surgical approach and outcomes of interest. RESULTS: A total of 9,355 veterans underwent minimally invasive fundoplication from 2008 to 2019. RAF was used in 5,392 cases (57.6%): 1.63% of cases in 2008 to 83.41% of cases in 2019. After adjusting for confounding covariates, relative to laparoscopic-assisted foregut surgery, RAF was significantly associated with decreased adjusted odds of pulmonary complications (adjusted odds ratio [aOR] 0.44, p \u3c 0.001), acute renal failure (aOR 0.14, p = 0.046), venous thromboembolism (aOR 0.44, p = 0.009) and increased odds of infectious complications (aOR 1.60, p = 0.017). RAF was associated with an adjusted mean ± SD of 29 ± 2-minute shorter operative time (332 minutes vs 361 minutes; p \u3c 0.001). CONCLUSIONS: Veterans undergoing RAF ascertained shorter operative times and reduced complications vs laparoscopy. As surgeons use the robotic platform, clinical outcomes and operative times continue to improve, particularly in operations where extra articulation in confined spaces is required

Secretome of peripheral blood mononuclear cells enhances wound healing.

Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SEC(PBMC)). Six mm punch biopsy wounds were set on the backs of C57BL/6J-mice and SEC(PBMC) containing emulsion or controls were applied daily for three days. Morphology and neo-angiogenesis were analyzed by H&E-staining and CD31 immuno-staining, respectively. In vitro effects on diverse skin cells were investigated by migration assays, cell cycle analysis, and tube formation assay. Signaling pathways were analyzed by Western blot analysis. Application of SEC(PBMC) on 6 mm punch biopsy wounds significantly enhanced wound closure. H&E staining of the wounds after 6 days revealed that wound healing was more advanced after application of SEC(PBMC) containing emulsion. Furthermore, there was a massive increase in CD31 positive cells, indicating enhanced neo-angiogenesis. In primary human fibroblasts (FB) and keratinocytes (KC) migration but not proliferation was induced. In endothelial cells (EC) SEC(PBMC) induced proliferation and tube-formation in a matrigel-assay. In addition, SEC(PBMC) treatment of skin cells led to the induction of multiple signaling pathways involved in cell migration, proliferation and survival. In summary, we could show that emulsions containing the secretome of PBMC derived from healthy individuals accelerates wound healing in a mouse model and induce wound healing associated mechanisms in human primary skin cells. The formulation and use of such emulsions might therefore represent a possible novel option for the treatment of non-healing skin ulcers