Comparison of the clinical and economic outcomes between open and minimally invasive appendectomy and colectomy: evidence from a large commercial payer database

Background: Appendectomy and colectomy are commonly performed surgical procedures. Despite evidence demonstrating advantages with the minimally invasive surgical (MIS) approach, open procedures occur with greater prevalence. Therefore, there is still controversy as to whether the MIS approach is safer or more cost effective. Methods: A retrospective analysis was performed using a large commercial payer database. The data included information on 7,532 appendectomies and 2,745 colectomies. Data on the distribution of patient demographic and comorbidity characteristics associated with the MIS and open approaches were reviewed. The corresponding complication rates and expenditures were analyzed. Summary statistics were compared using chi-square tests, and generalized linear models were constructed to estimate expenditures while controlling for patient characteristics. Results: The patients undergoing MIS and open colectomy showed no significant variations in age distribution or marginal age differences for appendectomy. Significantly more patients experienced an infection postoperatively, and procedure-specific complications were more common in the open group for both procedures (P < 0.05). The postsurgical hospital stay was longer for the patients treated using the open techniques, differing an average of half a day for appendectomies and significantly more (4 days) for colectomy (P < 0.05). Readmission rates differed little between the two approaches. Procedures performed through an MIS approach were associated with lower expenditures than for the open technique, with differences ranging from $700 for appendectomy patients (P < 0.05) to$15,200 for colectomy patients (P < 0.05). Conclusions: Minimally invasive appendectomy and colectomy were associated with lower infection rates, fewer complications, shorter hospital stays, and lower expenditures than open surgery

A recombinant Fasciola gigantica 14-3-3 epsilon protein (rFg14-3-3e) modulates various functions of goat peripheral blood mononuclear cells

Background The molecular structure of Fasciola gigantica 14-3-3 protein has been characterized. However, the involvement of this protein in parasite pathogenesis remains elusive and its effect on the functions of innate immune cells is unknown. We report on the cloning and expression of a recombinant F. gigantica 14-3-3 epsilon protein (rFg14-3-3e), and testing its effects on specific functions of goat peripheral blood mononuclear cells (PBMCs). Methods rFg14-3-3e protein was expressed in Pichia pastoris. Western blot and immunofluorescence assay (IFA) were used to examine the reactivity of rFg14-3-3e protein to anti-F. gigantica and anti-rFg14-3-3e antibodies, respectively. Various assays were used to investigate the stimulatory effects of the purified rFg14-3-3e protein on specific functions of goat PBMCs, including cytokine secretion, proliferation, migration, nitric oxide (NO) production, phagocytosis, and apoptotic capabilities. Potential protein interactors of rFg14-3-3e were identified by querying the databases Intact, String, BioPlex and BioGrid. A Total Energy analysis of each of the identified interaction was performed. Gene Ontology (GO) enrichment analysis was conducted using Funcassociate 3.0. Results Sequence analysis revealed that rFg14-3-3e protein had 100% identity to 14-3-3 protein from Fasciola hepatica. Western blot analysis showed that rFg14-3-3e protein is recognized by sera from goats experimentally infected with F. gigantica and immunofluorescence staining using rat anti-rFg14-3-3e antibodies demonstrated the specific binding of rFg14-3-3e protein to the surface of goat PBMCs. rFg14-3-3e protein stimulated goat PBMCs to produce interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), corresponding with low levels of IL-4 and interferon gamma (IFN-γ). Also, this recombinant protein promoted the release of NO and cell apoptosis, and inhibited the proliferation and migration of goat PBMCs and suppressed monocyte phagocytosis. Homology modelling revealed 65% identity between rFg14-3-3e and human 14-3-3 protein YWHAE. GO enrichment analysis of the interacting proteins identified terms related to apoptosis, protein binding, locomotion, hippo signalling and leukocyte and lymphocyte differentiation, supporting the experimental findings. Conclusions Our data suggest that rFg14-3-3e protein can influence various cellular and immunological functions of goat PBMCs in vitro and may be involved in mediating F. gigantica pathogenesis. Because of its involvement in F. gigantica recognition by innate immune cells, rFg14-3-3e protein may have applications for development of diagnostics and therapeutic interventions

Key mechanisms governing resolution of lung inflammation

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered

Enhanced recovery program implementation: an evidence-based review of the art and the science

© 2019, Society of American Gastrointestinal and Endoscopic Surgeons. Background: The benefits of enhanced recovery program (ERP) implementation include patient engagement, improved patient outcomes and satisfaction, better team relationships, lower per episode costs of care, lower public consumption of narcotic prescription pills, and the promise of greater access to quality surgical care. Despite these positive attributes, vast numbers of surgical patients are not treated on ERPs, and many of those considered “on pathway” are unlikely to be exposed to a majority of recommended ERP elements. Methods: To explain the gap between ERP knowledge and action, this manuscript reviewed formal implementation strategies, proposed a novel change adoption model and focused on common barriers (and corollary solutions) that are encountered during the journey to a fully implemented and successful ERP. Given the nature of this review, IRB approval was not required/obtained. Results: The information reviewed indicates that implementation of best practice is both a science and an art. What many surgeons have learned is that the “soft” skills of emotional intelligence, leadership, team dynamics, culture, buy-in, motivation, and sustainability are central to a successful ERP implementation. Conclusions: To lead teams toward achievement of pervasive and sustained adherence to best practices, surgeons need to learn new strategies, techniques, and skills

External validation of a prognostic model of preoperative risk factors for failure of restorative proctocolectomy

Aim The Cleveland Clinic has proposed a prognostic model of preoperative risk factors for failure of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis. The model incorporates four predictive variables: completion proctectomy, handsewn anastomosis, diabetes mellitus and Crohn's disease. The aim of the present study was to perform an external validation of this model in a new cohort of patients who had RPC. Method Validation was performed in a multicentre cohort of 747 consecutive patients who had an RPC between 1990 and 2015 in three tertiary-care facilities, using a Kaplan-Meier survival analysis and Cox regression analysis. The performance of the model was expressed using the Harrell concordance error rate. The primary outcome measure was pouch survival with maintenance of anal function. Results During the study period, 45 (6.0%) patients experienced failure at a median interval of 31 months (interquartile range 9-82 months) from the original RPC. Multivariable analysis showed handsewn anastomosis to be the only significant independent predictor. The Harrell concordance error rate was 0.42, indicating poor performance. Anastomotic leakage and Crohn's disease of the pouch were strong postoperative predictors for pouch failure and showed a significant difference in pouch survival after 10 years (P <0.001). Conclusion The poor performance of the Cleveland Clinic prognostic model makes it unsuitable for daily clinical practice. Handsewn anastomosis was associated with pouch failure in our cohort with relatively few events. A prediction model for anastomotic leakage or Crohn's disease of the pouch may be a better solution since these variables are strongly associated with pouch failur

Apoptotic cell death of human interstitial cells of Cajal

Interstitial cells of Cajal (ICC) are specialized mesenchyme-derived cells that regulate contractility and excitability of many smooth muscles with loss of ICC seen in a variety of gut motility disorders. Maintenance of ICC numbers is tightly regulated, with several factors known to regulate proliferation. In contrast, the fate of ICC is not established. The aim of this study was to investigate whether apoptosis plays a role in the regulation of ICC numbers in the normal colon. ICC were identified by immunolabelling for the c-Kit receptor tyrosine kinase and by electron microscopy. Apoptosis was detected in colon tissue by immunolabelling for activated caspase-3, terminal dUTP nucleotide end labelling and by ultrastructural changes in the cells. Apoptotic ICC were identified and counted in double-labelled tissue sections. They were identified in all layers of the colonic muscle. In the muscularis propria 1.5 ± 0.2% of ICC were positive for activated caspase-3 and in the circular muscle layer 2.1 ± 0.9% of ICC were positive for TUNEL. Apoptotic ICC were identified by electron microscopy. Apoptotic cell death is a continuing process in ICC. The level of apoptosis in ICC in healthy colon indicates that these cells must be continually regenerated to maintain intact networks

A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fissures

PURPOSE: The aim of this study was to determine the optimal dose and dosing interval of nitroglycerin ointment to heal chronic anal fissures. METHOD: A randomized, double-blind study of intra-anally applied nitroglycerin ointment (Anogesic(TM)) was conducted in 17 centers in 304 patients with chronic anal fissures. The patients were randomly assigned to one of eight treatment regimens (0.0, 0.1, 0.2, 0.4 percent nitroglycerin ointment applied twice or three times per day), for up to eight weeks. A dose-measuring device standardized the delivery of 374 mg ointment. Healing of fissures (complete reepithelialization) was assessed by physical examination using an observer unaware of treatment allocation. The subjects assessed pain intensity daily by completing a diary containing a visual analog scale for average pain intensity for the day, the worst pain intensity for the day, and pain intensity at the last defecation. RESULTS: There were no significant differences in fissure healing among any of the treatment groups; all groups, including placebo had a healing rate of approximately 50 percent. This rate of placebo response was inexplicably higher than previously reported in the literature. Treatment with 0.4 percent (1.5 mg) nitroglycerin ointment was associated with a significant (P < 0.0002) decrease in average pain intensity compared with vehicle as assessed by patients with a visual analog scale. The decreases were observed by Day 4 of treatment. At 8 weeks the magnitude of,the difference between 0.4 percent nitroglycerin and control was a 21 percent reduction in average pain. Treatment was well tolerated, with only 3.29 percent of patients discontinuing treatment because of headache. Headaches were the primary adverse event and were dose related. CONCLUSION: Nitroglycerin ointment did not alter healing but significantly and rapidly reduced the pain associated with chronic anal fissures