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1.
BJS Open ; 6(4)2022 07 07.
Article in English | MEDLINE | ID: mdl-35876188

ABSTRACT

BACKGROUND: Emergency laparotomy is associated with high morbidity and mortality. The early identification of high-risk patients allows for timely perioperative care and appropriate resource allocation. The aim of this study was to develop a nationwide surgical trainee-led quality improvement (QI) programme to increase the use of perioperative risk scoring in emergency laparotomy. METHODS: The programme was structured using the active implementation framework in 15 state-funded Irish hospitals to guide the staged implementation of perioperative risk scoring. The primary outcome was a recorded preoperative risk score for patients undergoing an emergency laparotomy at each site. RESULTS: The rate of patients undergoing emergency laparotomy receiving a perioperative risk score increased from 0-11 per cent during the exploratory phase to 35-100 per cent during the full implementation phase. Crucial factors for implementing changes included an experienced central team providing implementation support, collaborator engagement, and effective communication and social relationships. CONCLUSIONS: A trainee-led QI programme increased the use of perioperative risk assessment in patients undergoing emergency laparotomy, with the potential to improve patient outcomes and care delivery.


Subject(s)
Laparotomy , Quality Improvement , Humans , Laparotomy/adverse effects , Perioperative Care , Risk Assessment , Risk Factors
2.
Cell Death Differ ; 29(4): 806-817, 2022 04.
Article in English | MEDLINE | ID: mdl-34754079

ABSTRACT

Cancer cells' ability to inhibit apoptosis is key to malignant transformation and limits response to therapy. Here, we performed multiplexed immunofluorescence analysis on tissue microarrays with 373 cores from 168 patients, segmentation of 2.4 million individual cells, and quantification of 18 cell lineage and apoptosis proteins. We identified an enrichment for BCL2 in immune, and BAK, SMAC, and XIAP in cancer cells. Ordinary differential equation-based modeling of apoptosis sensitivity at single-cell resolution was conducted and an atlas of inter- and intra-tumor heterogeneity in apoptosis susceptibility generated. Systems modeling at single-cell resolution identified an enhanced sensitivity of cancer cells to mitochondrial permeabilization and executioner caspase activation compared to immune and stromal cells, but showed significant inter- and intra-tumor heterogeneity.


Subject(s)
Colorectal Neoplasms , X-Linked Inhibitor of Apoptosis Protein , Apoptosis/physiology , Colorectal Neoplasms/metabolism , Humans , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , X-Linked Inhibitor of Apoptosis Protein/metabolism
3.
JAMA Netw Open ; 4(8): e2115274, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34459908

ABSTRACT

Importance: Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer. Objectives: To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes. Design, Setting, and Participants: This multicenter translational cohort study included patients with nonmetastatic colon cancer who did not have underlying chronic inflammatory disorders and were not receiving anti-inflammatory drugs referred to tertiary cancer centers from 2009 to 2015. Preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), vascular endothelial growth factor (VEGF), and cell surface receptor expression levels (CD11b and CD14) were measured. All patients underwent follow-up for at least 5 years. Data were analyzed in December 2020. Exposure: Nonmetastatic colon cancer. Main Outcomes and Measures: The associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test and Kaplan-Meier curves. Results: A total of 28 patients were included (median [interquartile range] age, 67 [58-72] years; 22 [78.6%] men). Low skeletal muscle area (SMA) and high visceral to total fat ratio were associated with poor clinical and oncological outcomes, including increased 5-year recurrence (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41-2.89]; P = .04; high visceral to total fat ratio: HR, 5.78 [95% CI, 3.66-7.95]; P = .02). High visceral to total fat ratio was associated with increased 5-year disease-specific mortality (HR, 5.92 [95% CI, 4.04-8.00]; P = .02). Patients with low SMA who developed a cancer recurrence, compared with those who did not, had higher C-reactive protein (mean [SD], 31.24 [6.95] mg/dL vs 8.11 [0.58] mg/dL; P = .003), IL-6 (mean [SD], 1.93 [1.16] ng/mL vs 0.88 [0.14] ng/mL; P = .004), VEGF (mean [SD], 310.03 [122.66] ng/mL vs 176.12 [22.94] ng/mL; P = .007), and CD14 (mean [SD], 521.23 [302.02] ng/mL vs 322.07 [98.35] ng/mL; P = .03) expression and lower albumin (mean [SD], 3.8 [0.6] g/dL vs 43.50 [3.69] g/dL; P = .01), IL-2 (mean [SD], 0.45 [0.25] ng/mL vs 0.94 [0.43] ng/mL; P < .001), IL-10 (mean [SD], 8.15 [1.09] ng/mL vs 16.32 [4.43] ng/mL; P = .004), and interferon γ (mean [SD], 2.61 [1.36] ng/mL vs 14.87 [3.43] ng/mL; P = .02) levels. Patients with high visceral to total fat ratio who developed recurrence had higher levels of IL-6 (mean [SD], 5.26 [7.05] ng/mL vs 2.76 [3.11] ng/mL; P = .03) and tumor necrosis factor α (mean [SD], 5.74 [4.53] ng/mL vs 4.50 [1.99] ng/mL; P = .03). Conclusions and Relevance: These findings suggest that low SMA and high visceral to total fat ratio were associated with worse colon cancer outcomes and with increased expression of proinflammatory cytokines and VEGF and inhibition of anti-inflammatory cytokines.


Subject(s)
Body Composition , Colonic Neoplasms/mortality , Colonic Neoplasms/physiopathology , Adipose Tissue/physiopathology , Aged , C-Reactive Protein/analysis , CD11b Antigen/blood , Colonic Neoplasms/surgery , Cytokines/blood , Female , Humans , Inflammation , Intra-Abdominal Fat/physiopathology , Kaplan-Meier Estimate , Leukocyte Count , Lipopolysaccharide Receptors/blood , Male , Middle Aged , Muscle, Skeletal/physiopathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/physiopathology , Preoperative Period , Proportional Hazards Models , Serum Albumin/analysis , Vascular Endothelial Growth Factor A/blood
4.
Dis Colon Rectum ; 62(6): 703-710, 2019 06.
Article in English | MEDLINE | ID: mdl-30762598

ABSTRACT

BACKGROUND: Unplanned readmission after surgery negatively impacts surgical recovery. Few studies have sought to define predictors of readmission in a rectal cancer cohort alone. Readmission following rectal cancer surgery may be reduced by the identification and modification of factors associated with readmission. OBJECTIVES: This study seeks to characterize the predictors of 30-day readmission following proctectomy for rectal cancer. DESIGN: This study is a retrospective analysis of prospectively gathered cohort data. Outcomes were compared between readmitted and nonreadmitted patients. Multivariate analysis of factors association with readmission was performed by using binary logistic regression. SETTINGS: This study was conducted at Beaumont Hospital, a nationally designated, publicly funded cancer center. PATIENTS: Two hundred forty-six consecutive patients who underwent proctectomy for rectal cancer between January 2012 and December 2015 were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were readmission within 30 days of discharge and the variables associated with readmission, categorized into patient factors, perioperative factors, and postoperative factors. RESULTS: Thirty-one (12.6%) patients were readmitted within 30 days of discharge following index rectal resection. The occurrence of anastomotic leaks, high-output stoma, and surgical site infections was significantly associated with readmission within 30 days (anastomotic leak OR 3.60, p = 0.02; high-output stoma OR 11.04, p = 0.003; surgical site infections OR 13.39, p = 0.01). Surgical site infections and high-output stoma maintained significant association on multivariate analysis (surgical site infections OR 10.02, p = 0.001; high-output stoma OR 9.40, p = 0.02). No significant difference was noted in the median length of stay or frequency of prolonged admissions (greater than 24 days) between readmitted and nonreadmitted patients. LIMITATIONS: The institutional database omits a number of socioeconomic factors and comorbidities that may influence readmission, limiting our capacity to analyze the relative contribution of these factors to our findings. CONCLUSIONS: An early postoperative care bundle to detect postoperative complications could prevent some unnecessary inpatient admissions following proctectomy. Key constituents should include early identification and management of stoma-related complications and surgical site infection. See Video Abstract at http://links.lww.com/DCR/A912.


Subject(s)
Patient Readmission , Postoperative Complications/epidemiology , Proctectomy , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Rectal Neoplasms/mortality , Rectal Neoplasms/pathology , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
5.
Ir J Med Sci ; 187(4): 1029-1038, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29423825

ABSTRACT

BACKGROUND: Appendectomy has for many years been the accepted treatment of appendicitis. In recent years, non-operative management of appendicitis (NOTA) has been reported as an effective treatment option. AIMS: We aimed to assess the perspectives of public hospital attendees regarding the diagnosis and treatment options for appendicitis. METHODS: We conducted a cross-sectional survey of outpatients over a 10-week period (December 2016-March 2017). The questionnaire contained an information sheet and consent form and included open, closed and multiple-choice questions. RESULTS: Two hundred forty-four participants (159 female, 85 male) were surveyed. A high level of awareness of appendicitis as a surgical emergency existed amongst the participants. The primary reason participants were reluctant to receive non-operative treatment was a fear of their appendix "bursting" if not removed. CONCLUSIONS: Participant knowledge levels were variable with many concerned that non-operated appendicitis would always perforate. Perceptions of treatment were variable with some believing surgery was an absolute requirement and others preferring antibiotics due to the belief that NOTA is complication-free.


Subject(s)
Appendicitis/therapy , Decision Making/ethics , Appendicitis/pathology , Cross-Sectional Studies , Female , Humans , Male , Treatment Outcome
6.
Melanoma Res ; 26(1): 66-70, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26460498

ABSTRACT

To analyse the patient demographics, tumour characteristics and follow-up data of patients with recurrence of melanoma following a negative sentinel lymph node biopsy. A retrospective review of a prospectively maintained melanoma database was conducted. Melanoma patients who had a negative sentinel lymph node were identified and we performed statistical analysis on their respective demographics, tumour histology characteristics and follow-up data. Of 164 patients studied, 40 (24%) had a recurrence of melanoma at a median of 39.5 months following diagnosis (range 1-92 months). Distant metastases were the most common form of disease recurrence (40% of all recurrences). Increasing tumour thickness was an independent predictor of recurrence on multivariate analysis while nodular histology approached significance. Median survival of 6 months was seen following disease recurrence (range 1-126 months). In the setting of a negative sentinel lymph node biopsy, there remains a risk of melanoma recurrence. Distant metastases were the most common form of recurrence. Disease recurrence occurred more frequently in those with thick primary tumours. Recurrences occurred at long intervals from diagnosis indicating the need to consider prolonged patient follow-up.


Subject(s)
Melanoma/epidemiology , Melanoma/pathology , Neoplasm Recurrence, Local/epidemiology , Sentinel Lymph Node Biopsy , Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Aged , False Negative Reactions , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Survival Analysis
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