Outcomes of Laparoscopic vs Open Repair of Perforated Peptic Ulcers: An ACS-NSQIP Study.

BACKGROUND: Perforated peptic ulcer (PPU) is a surgical emergency needing swift operative resolution. While laparoscopic and open approaches are viable options, it remains unclear whether laparoscopic repair has significantly improved outcomes. We use a national surgical database to compare perioperative and 30-d postoperative (30POP) outcomes. MATERIALS AND METHODS: The 2016-2018 ACS-NSQIP database was used to create the patient cohort, using ICD-10 and CPT codes. An unmatched analysis identified factors that likely contributed to the laparoscopic versus open treatment allocation. Propensity score matching (PSM) was used to identify outcomes that were not explained by underlying differences in the patient cohorts. RESULTS: A total of 3475 patients were included: 3135 in open group (OG), 340 (~10%) in laparoscopic group (LG). After PSM to control for comorbidities and illness severity that differed between groups on univariate analysis, 288 patients remained in each group. Analysis of the matched cohorts revealed no statistically significant difference in mortality (5.9% OG versus 3.8% LG, P = 0.245). The LG had significantly longer operative times (92 versus 79 min, P = 0.003), shorter hospital stays (8.2 versus 9.4 d, P = 0.044) and higher probability of being discharged home (81% versus 73%, P = 0.017). 30POP outcomes were largely equivalent, except that OG had higher risk for bleeding (14.6% versus 8%, P = 0.012) and pneumonia (8.7% versus 4.5%, P = 0.044). CONCLUSIONS: While laparoscopic repairs take longer, they lead to shorter hospital stays and higher likelihood of discharge home. Further study to identify patients that are candidates for this technique is warranted.

Are we ready for bundled payments for major bowel surgery?

BACKGROUND: The Centers for Medicare & Medicaid Services (CMS) recently announced a new voluntary episode payment model for major bowel surgery. The purpose of this study was to examine the financial impact of bundled payments for major bowel surgery. METHODS: An institutional database was retrospectively queried for all patients who underwent major bowel surgery between July 2016 and June 2018. Procedures were categorized using MS-DRG coding: MS-DRG 329 (with MCC, major complications and comorbidity), MS-DRG 330 (with CC, complications and comorbidity), and MS-DRG 331 (without CC/MCC). RESULTS: A total of 745 patients underwent 798 procedures, with mean age 62.1 years and BMI 29.2 kg/m2. The median LOS was 4.0 days, with 12.5% of patients being discharged to a post-acute care facility for an average of 38.5 days. The mean hospital cost was $18,525. The mean payment to a post-acute care facility was $423 per day. The 90-day readmission rate was 8.6% at an average cost of $12,859 per readmission. Patients with major complications and comorbidity (MS-DRG 329) had higher CMS Hierarchical Condition Categories scores, longer LOS, higher costs, more required home health services or post-acute care facilities, and had higher 90-day readmissions. In a fee-for-service model, hospital reimbursements resulted in a negative margin of - 8.2% for MS-DRG 329, - 2.6% for MS-DRG 330, but a positive margin of 2.8% for MS-DRG 331. In a bundled payment model, the hospital would incur a loss of - 13.1%, - 11.1%, and - 1.9% for MS-DRG 329, 330, and 331, respectively. CONCLUSIONS: Patients undergoing major bowel surgery are often a heterogeneous population with varied pre-existing comorbid conditions who require a high level of complex care and utilize greater hospital resources. Further study is needed to identify areas of cost containment without compromising the overall quality of care.

IL-23 mediates murine liver transplantation ischemia-reperfusion injury via IFN-γ/IRF-1 pathway.

Interleukin-23 (IL-23) is a proinflammatory cytokine initially studied in autoimmune disease that has been more recently linked to innate immunity. We observed that the expression of IL-23 is upregulated during hypoxia in a hepatocyte and nonparenchymal cell (NPC) coculture system, as well as during ischemia-reperfusion (I/R) injury in the liver. Interferon regulatory factor-1 (IRF-1) is a transcription factor that induces expression of multiple inflammatory cytokines and has been shown to play a critical role in liver I/R injury. We observed that IL-23 signaling induces not only the IL-17/chemokine (C-X-C motif) ligand 2 (CXCL2) pathway but also the IFN-γ/IRF-1 pathway. Quantification of cytokine genes revealed increased liver expression of IL-17a, CXCL2, and IRF-1 messenger RNA during liver transplantation. Recombinant IL-23 treated hepatocytes, and NPC coculture led to IL-17, CXCL2, IFN-γ, and IRF-1 expression. With anti-IL-17 and anti-Ly6G antibody neutralization, neutrophil recruitment and IFN-γ production were decreased during warm I/R injury. Overexpression of IL-23 in vivo through use of an adenovirus vector also led to expression of IL-17, CXCL2, IFN-γ, and IRF-1. The increased expression of IL-23 also led to increased apoptosis in the liver. By neutralization of IL-23 through use of an anti-IL-23p19 antibody, we were able to attenuate liver damage in a wild-type but not a natural killer T (NKT) cell-deficient mouse. This suggests that IL-23 signaling shares a common pathway with NKT cells. In conclusion, IL-23 is induced early by I/R in the liver. Its signaling leads to activation of the IL-17/CXCL2 and IFN-γ/IRF-1 pathways, resulting in increased apoptosis and necrosis. NEW & NOTEWORTHY IL-23 is expressed early during cold ischemia-reperfusion (I/R), and this expression is associated with expression of IL-17 and chemokine (C-X-C motif) ligand 2. Neutralization of IL-23 during cold I/R can significantly reduce liver damage as well as decrease cytokine production and neutrophil infiltration in the liver. IL-23 appears to activate IFN-γ production in natural killer T cells within the liver which, in turn, activates interferon regulatory factor-1, a known inflammatory transcription factor during I/R injury.

Hepatocyte-specific high-mobility group box 1 deletion worsens the injury in liver ischemia/reperfusion: a role for intracellular high-mobility group box 1 in cellular protection.

UNLABELLED: High-mobility group box 1 (HMGB1) is an abundant chromatin-associated nuclear protein and released into the extracellular milieu during liver ischemia-reperfusion (I/R), signaling activation of proinflammatory cascades. Because the intracellular function of HMGB1 during sterile inflammation of I/R is currently unknown, we sought to determine the role of intracellular HMGB1 in hepatocytes after liver I/R. When hepatocyte-specific HMGB1 knockout (HMGB1-HC-KO) and control mice were subjected to a nonlethal warm liver I/R, it was found that HMGB1-HC-KO mice had significantly greater hepatocellular injury after I/R, compared to control mice. Additionally, there was significantly greater DNA damage and decreased chromatin accessibility to repair with lack of HMGB1. Furthermore, lack of hepatocyte HMGB1 led to excessive poly(ADP-ribose)polymerase 1 activation, exhausting nicotinamide adenine dinucleotide and adenosine triphosphate stores, exacerbating mitochondrial instability and damage, and, consequently, leading to increased cell death. We found that this was also associated with significantly more oxidative stress (OS) in HMGB1-HC-KO mice, compared to control. Increased nuclear instability led to a resultant increase in the release of histones with subsequently more inflammatory cytokine production and organ damage through activation of Toll-like receptor 9. CONCLUSION: The lack of HMGB1 within hepatocytes leads to increased susceptibility to cellular death after OS conditions.

Cellular-specific role of toll-like receptor 4 in hepatic ischemia-reperfusion injury in mice.

UNLABELLED: Ischemia-reperfusion (I/R) injury is a process whereby an initial hypoxic insult and subsequent return of blood flow leads to the propagation of innate immune responses and organ injury. The necessity of the pattern recognition receptor, Toll-like receptor (TLR)4, for this innate immune response has been previously shown. However, TLR4 is present on various cell types of the liver, both immune and nonimmune cells. Therefore, we sought to determine the role of TLR4 in individual cell populations, specifically, parenchymal hepatocytes (HCs), myeloid cells, including Kupffer cells, and dendritic cells (DCs) subsequent to hepatic I/R. When HC-specific (Alb-TLR4(-/-) ) and myeloid-cell-specific (Lyz-TLR4(-/-) ) TLR4 knockout (KO) mice were subjected to warm hepatic ischemia, there was significant protection in these mice, compared to wild type (WT). However, the protection afforded in these two strains was significantly less than global TLR4 KO (TLR4(-/-) ) mice. DC-specific TLR4(-/-) (CD11c-TLR4(-/-) ) mice had significantly increased hepatocellular damage, compared to WT mice. Circulating levels of high-mobility group box 1 (HMGB1) were significantly reduced in Alb-TLR4(-/-) mice, compared to WT, Lyz-TLR4(-/-) , CD11c-TLR4(-/-) mice and equivalent to global TLR4(-/-) mice, suggesting that TLR4-mediated HMGB1 release from HCs may be a source of HMGB1 after I/R. HCs exposed to hypoxia responded by rapidly phosphorylating the mitogen-activated protein kinases, c-Jun-N-terminal kinase (JNK) and p38, in a TLR4-dependent manner; inhibition of JNK decreased release of HMGB1 after both hypoxia in vitro and I/R in vivo. CONCLUSION: These results provide insight into the individual cellular response of TLR4. The parenchymal HC is an active participant in sterile inflammatory response after I/R through TLR4-mediated activation of proinflammatory signaling and release of danger signals, such as HMGB1.

Early Experiences With Bundled Payments for Care Improvement for Major Bowel Surgery.

BACKGROUND: Bundled Payment (BP) models are becoming more common in surgery. We share our early experiences with Bundled Payments for Care Improvement for major bowel surgery. METHODS: Patients undergoing major bowel surgery between January and October 2021 were identified using Medicare Severity-Diagnosis Related Group (MS-DRG) codes. Major drivers of cost in a BP model are reported and compared to the Fee-For-Service (FFS) payment model. RESULTS: A total of 202 cases (173 FFS vs 29 BP) were analyzed. The mean BP cost per Clinical Episode was $28,340. Eleven patients (38%) in the BP model had costs greater than the Target Price. The drivers of cost in the BP model were 59% acute care facility, 17% physician services, 9% post-acute care facilities, 8% other, and 7% readmissions. Clinical Episode of care costs varied considerably by MS-DRG case complexity. Robotic surgery increased costs by 35% (mean increase $3724, P < .01). The 90-day readmission rate was 17% for a mean cost of $11,332 per readmission. Three patients (10%) were discharged to a skilled nursing facility at an average cost of $11,009, while fifteen patients (52%) received home health services at a mean cost of $2947. Acute care facility costs were similar in the BP vs FFS groups (mean difference $1333, P = .22). CONCLUSIONS: Patients undergoing major bowel surgery are a heterogeneous population. Physicians are ideally positioned to deliver high-value, patient-centered care and are crucial to the success of a BP model. The post-acute care setting is a key component of improving efficiency and quality of care.

Analysis of 10-year trends in Medicare Physician Fee Schedule payments in surgery.

BACKGROUND: Medicare expenditures have steadily increased over the decades, and yet Medicare Physician Fee Schedule payments for individual services have declined. We examine trends in Medicare Physician Fee Schedule payments for office visits, inpatient visits, and surgical procedures. METHODS: The Medicare Physician Fee Schedule Look-Up Tool was queried for payment data for office visits, inpatient visits, and surgical procedures between 2013 and 2023. All data were adjusted for inflation using the Consumer Price Index. Trends in payments were calculated for 5 common procedures in each surgical specialty. Trends in aggregate national health expenditures were compared to Medicare Physician Fee Schedule payments for physician services from 2013 to 2021. RESULTS: The Consumer Price Index increased by 29.3% from 2013 to 2023. Inflation-adjusted per-visit Medicare Physician Fee Schedule payments decreased by 12.2% for outpatient office visits, 19.1% for inpatient visits, and 22.8% for surgical procedures from 2013 to 2023. This varied by surgical specialty: vascular (-25.8%), endocrine (-22.0%), general surgery (-27.0%), thoracic (-19.2%), surgical oncology (-22.1%), breast (-22.4%), urology (-2.2%), neurosurgery (-22.8%), obstetrics/gynecology (-19.9%), and orthopedics (-24.7%). Adjusted for inflation, national health expenditures increased by 33.9% for physician services from 2013 to 2021. In comparison, Medicare Physician Fee Schedule payments over the same time period 2013 to 2021 increased by 1.3% for outpatient office visits but decreased by 10.6% for inpatient visits and 9.8% for surgical procedures. CONCLUSION: Controlling rising national health expenditures is important and necessary, but 10 years of declining Medicare Physician Fee Schedule payments on a per-procedure basis in surgery would suggest that this strategy alone may not achieve those goals and could ultimately threaten access to quality surgical care. Surgeons must advocate for permanent payment reforms.

Socially vulnerable patients are more likely to fail outpatient management of symptomatic cholelithiasis.

BACKGROUND: Symptomatic cholelithiasis is a common surgical problem, with many patients requiring multiple gallstone-related emergency department (ED) visits before cholecystectomy. The Social Vulnerability Index (SVI) identifies vulnerable patient populations. This study aimed to assess the association between social vulnerability and outpatient management of symptomatic cholelithiasis. METHODS: Patients with symptomatic cholelithiasis-related ED visits were identified within our health system from 2016 to 2022. Clinical outcomes data were merged with SVI census track data, which consist of 4 SVI subthemes (socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation). Multivariate analysis was used for statistical analysis. RESULTS: A total of 47,292 patients presented to the ED with symptomatic cholelithiasis, of which 6103 patients (13.3 %) resided in vulnerable census tract regions. Of these patients, 13,795 (29.2 %) underwent immediate cholecystectomy with a mean time to surgery of 35.1 h, 8250 (17.4 %) underwent elective cholecystectomy at a mean of 40.6 days from the initial ED visit, and 2924 (6.2 %) failed outpatient management and returned 1.26 times (range, 1-11) to the ED with recurrent biliary-related pain. Multivariate analysis found social vulnerability subthemes of socioeconomic status (odds ratio [OR], 1.29; 95 % CI, 1.09-1.52) and racial and ethnic minority status (OR, 2.41; 95 % CI, 2.05-2.83) to be associated with failure of outpatient management of symptomatic cholelithiasis. CONCLUSION: Socially vulnerable patients are more likely to return to the ED with symptomatic cholelithiasis. Policies to support this vulnerable population in the outpatient setting with timely follow-up and elective cholecystectomy can help reduce delays in care and overutilization of ED resources.

Interferon regulatory factor-2 is protective against hepatic ischemia-reperfusion injury.

Interferon regulatory factor (IRF)-1 is a nuclear transcription factor that induces inflammatory cytokine mediators and contributes to hepatic ischemia-reperfusion (I/R) injury. No strategies to mitigate IRF1-mediated liver damage exist. IRF2 is a structurally similar endogenous protein that competes with IRF1 for DNA binding sites in IRF-responsive target genes and acts as a competitive inhibitor. However, the role of IRF2 in hepatic injury during hypoxic or inflammatory conditions is unknown. We hypothesize that IRF2 overexpression may mitigate IRF1-mediated I/R damage. Endogenous IRF2 is basally expressed in normal livers and is mildly increased by ischemia alone. Overexpression of IRF2 protects against hepatic warm I/R injury. Furthermore, we demonstrate that IRF2 overexpression limits production of IRF1-dependent proinflammatory genes, such as IL-12, IFNß, and inducible nitric oxide synthase, even in the presence of IRF1 induction. Additionally, isograft liver transplantation with IRF2 heterozygote knockout (IRF2(+/-)) donor grafts that have reduced endogenous IRF2 levels results in worse injury following cold I/R during murine orthotopic liver transplantation. These findings indicate that endogenous intrahepatic IRF2 protein is protective, because the IRF2-deficient liver donor grafts exhibited increased liver damage compared with the wild-type donor grafts. In summary, IRF2 overexpression protects against I/R injury by decreasing IRF1-dependent injury and may represent a novel therapeutic strategy.

Hospital-Based Same-Day Compared to Overnight-Stay Mastectomy: An American College of Surgeons National Surgical Quality Improvement Program Analysis.

Background: Enhanced Recovery after Surgery for mastectomy has resulted in increased use of outpatient same-day mastectomy (SDM). Whether SDM leads to increased readmissions or reoperations is not well documented. This study examines national data to compare outcomes of SDM to an overnight stay. Methods: We analyzed the American College of Surgeons National Surgical Quality Improvement Program Participant Use Data File from 2016 to 2018 for all mastectomy cases. Cases with a length of stay (LOS) >1 day were excluded. Cases were then categorized into 2 LOS cohorts: SDM vs 1-day LOS. Results: A total of 22,642 cases (80.8% 1-day LOS vs 19.2% SDM) were identified for the final analysis. Patients in the 1-day LOS group were more likely to be older (57.9 vs 54.0 years, P<0.01), be female (98.0% vs 79.8%, P<0.01), and have greater comorbidity (38.1% vs 30.7% American Society of Anesthesiologists classification 3 or 4, P<0.01) compared to the SDM group. Multivariate analysis demonstrated no difference in risk for 30-day wound complications between the SDM and 1-day LOS groups. The risks for 30-day medical complications (1.60 odds ratio [OR], 95% CI 1.06-2.42, P=0.02), reoperations (1.46 OR, 95% CI 1.17-1.81, P<0.01), and readmissions (1.60 OR, 95% CI 1.25-2.05, P<0.01) were higher in the 1-day LOS group. Even after excluding patients undergoing reoperation on the day of surgery, the risk for reoperations (2.3% vs 3.3%, P<0.01) remained higher in the 1-day LOS group. Characteristics associated with 1-day LOS were hypertension, steroid use, diabetes, dyspnea, dependent functional status, bilateral procedures, and breast reconstruction. Conclusion: We demonstrate that SDM is a safe procedure, with no increase in risk for 30-day postoperative complications. Appropriate patients should be offered SDM.

High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity.

The mobilization and extracellular release of nuclear high mobility group box-1 (HMGB1) by ischemic cells activates inflammatory pathways following liver ischemia/reperfusion (I/R) injury. In immune cells such as macrophages, post-translational modification by acetylation appears to be critical for active HMGB1 release. Hyperacetylation shifts its equilibrium from a predominant nuclear location toward cytosolic accumulation and subsequent release. However, mechanisms governing its release by parenchymal cells such as hepatocytes are unknown. In this study, we found that serum HMGB1 released following liver I/R in vivo is acetylated, and that hepatocytes exposed to oxidative stress in vitro also released acetylated HMGB1. Histone deacetylases (HDACs) are a family of enzymes that remove acetyl groups and control the acetylation status of histones and various intracellular proteins. Levels of acetylated HMGB1 increased with a concomitant decrease in total nuclear HDAC activity, suggesting that suppression in HDAC activity contributes to the increase in acetylated HMGB1 release after oxidative stress in hepatocytes. We identified the isoforms HDAC1 and HDAC4 as critical in regulating acetylated HMGB1 release. Activation of HDAC1 was decreased in the nucleus of hepatocytes undergoing oxidative stress. In addition, HDAC1 knockdown with siRNA promoted HMGB1 translocation and release. Furthermore, we demonstrate that HDAC4 is shuttled from the nucleus to cytoplasm in response to oxidative stress, resulting in decreased HDAC activity in the nucleus. Together, these findings suggest that decreased nuclear HDAC1 and HDAC4 activities in hepatocytes following liver I/R is a mechanism that promotes the hyperacetylation and subsequent release of HMGB1.

Critical role of interferon regulatory factor-1 in murine liver transplant ischemia reperfusion injury.

Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates gene expression during immunity. We hypothesized that IRF-1 plays a pivotal role in liver transplant (LTx) ischemia/reperfusion (I/R) injury. Mouse orthotopic LTx was conducted after 24 hours cold storage in University of Wisconsin (UW) solution in wildtype (WT) C57BL/6 and IRF-1 knockout (KO) mice. IRF-1 deficiency in liver grafts, but not in recipients, resulted in significant reduction of hepatocyte apoptosis and liver injury, as well as improved survival. IRF-1 mRNA up-regulation was typically seen in graft hepatocytes in WT-->WT LTx. Deficiency of IRF-1 signaling in graft resulted in significantly reduced messenger RNA (mRNA) levels for death ligands and death receptors in hepatocytes, as well as decreased caspase-8 activities, indicating that IRF-1 mediates death ligand-induced hepatocyte death. Further, a smaller but significant IRF-1 mRNA up-regulation was seen in WT graft nonparenchymal cells (NPC) and associated with interferon gamma (IFN-gamma) mRNA up-regulation exclusively in NPC. IFN-gamma mRNA was significantly reduced in IRF-1 KO graft. Thus, IRF-1 in graft hepatocytes and NPC has distinct effects in hepatic I/R injury. However, LTx with chimeric liver grafts showed that grafts lacking hepatocellular IRF-1 had better protection compared with those lacking IRF-1 in NPC. The study identifies a critical role for IRF-1 in liver transplant I/R injury.

Does routine postoperative contrast radiography improve outcomes for patients with perforated peptic ulcer? A multicenter retrospective cohort study.

BACKGROUND: Perforated peptic ulcer is a morbid emergency general surgery condition. Best practices for postoperative care remain undefined. Surgical dogma preaches practices such as peritoneal drain placement, prolonged nil per os, and routine postoperative enteral contrast imaging despite a lack of evidence. We aimed to evaluate the role of postoperative enteral contrast imaging in postoperative perforated peptic ulcer care. Our primary objective was to assess effects of routine postoperative enteral contrast imaging on early detection of clinically significant leaks. METHODS: We conducted a multicenter retrospective cohort study of patients who underwent repair of perforated peptic ulcer between July 2016 and June 2018. We compared outcomes between those who underwent routine postoperative enteral contrast imaging and those who did not. RESULTS: Our analysis included 95 patients who underwent primary/omental patch repair. The mean age was 60 years, and 54% were male. Thirteen (14%) had a leak. Eighty percent of patients had a drain placed. Nine patients had leaks diagnosed based on bilious drain output without routine postoperative enteral contrast imaging. Use of routine postoperative enteral contrast imaging varied significantly between institutions (30%-87%). Two late leaks after initial normal postoperative enteral contrast imaging were confirmed by imaging after a clinical change triggered the second study. Two patients had contained leaks identified by routine postoperative enteral contrast imaging but remained clinically well. Duration of hospital stay was longer in those who received routine postoperative enteral contrast imaging (12 vs 6 days, median; P = .000). CONCLUSION: Routine postoperative enteral contrast imaging after perforated peptic ulcer repair likely does not improve the detection of clinically significant leaks and is associated with increased duration of hospital stay.

Isolated skeletal muscle metastasis following successful treatment of laryngeal cancer: case report.

Skeletal muscle metastases from tumors are a rare occurrence and can present difficult management decisions. We report here on a patient that had been previously treated for squamous cell laryngeal cancer with surgical resection and adjuvant systemic chemotherapy that presented with a metastasis to the rectus abdominis muscle without evidence of recurrent disease at the primary site. After a metastatic workup with PET/CT scan suggested this to be an isolated lesion, surgical excision with negative margins was performed based upon limited treatment options secondary to the location of the tumor and his favorable prognosis suggested by his pathological staging at the time of the initial resection. Here we discuss the incidence of distant metastases from laryngeal cancer and appropriate screening methods. Additionally, skeletal muscle metastases and treatment considerations are discussed.

How Does a New General Surgery Residency Program's Junior Residents Impact Hospital Efficiency and Productivity?

OBJECTIVE: The general surgery workforce deficit is projected to grow to 15% to 21% by 2050. An estimated 6.6% increase to existing general surgery residency (GSR) programs is needed to meet this shortfall. The purpose of this study was to examine the impact of a new GSR program on efficiency and productivity at a regional healthcare center. STUDY DESIGN: An institutional database was retrospectively queried for all GSR related procedures between July 2015 and June 2018. Procedures done prior to GSR initiation (pre-GSR) were compared to those done after (post-GSR). Univariate and multivariate analyses were performed. RESULTS: We reviewed 10,617 procedures (6365 pre-GSR vs. 4252 post-GSR). Patients had lower preoperative Hierarchical Condition Category scores in the post-GSR group (0.71 vs. 0.58, p < 0.01). Operative times increased post-GSR (101.7 vs. 109.1 minutes, p < 0.01), but length of stay decreased (6.4 vs. 5.5 days, p = 0.01). Thirty-day readmissions (4.0% vs. 3.4%, p = 0.11) were comparable, but reoperations significantly decreased post-GSR (10.1% vs. 8.6%, p = 0.01). Average hospital costs remained unchanged ($10,765 vs. $10,140, p = 0.12). Multivariate analysis revealed no statistical difference in operative times, length of stay, 30-day readmissions and reoperations, and hospital costs between the 2 groups. Subset analysis based on surgical service also showed no statistical difference. Productivity increased on the general surgery service post-GSR (7.1 vs. 7.8 cases per day, p = 0.02). Patient satisfaction increased post-GSR (76% vs. 81%, p = 0.31), but without statistical significance. CONCLUSION: The initiation of a new GSR program did not negatively impact operative times, length of stay, 30-day readmissions and reoperations, hospital costs, case volume, or patient satisfaction.

Bundled Payments for Appendectomy: a Model of Financial Implications to Institutions.

BACKGROUND: Bundled payments are increasingly becoming common in surgery, yet little is known regarding their potential impact on reimbursements for patients presenting with acute appendicitis. This study examines the financial impact of bundled payments for acute appendicitis. METHODS: This was a retrospective review of all open or laparoscopic appendectomies between July 2014 and June 2017. Patients that were not candidates for surgery were not included in this review. RESULTS: Of the total 741 patients, 42.1% were diagnosed with complicated acute appendicitis. The median length of stay was 1 day (range, 0 to 21 days). The median hospital cost was $4183 (range, $2075 to $71,023). The 90-day readmission rate was 3.2%, with a mean cost of $5025 per readmission (range, $1595 to $10,795). Length of stay, hospital costs, and 90-day readmissions were significantly higher for complicated versus uncomplicated acute appendicitis. In our current fee-for-service model, hospital reimbursements resulted in margins of - 4.0% to 24.6% depending on the severity of disease. If we assume that bundled payments do not reimburse for readmissions, we estimate that our hospital would incur losses of - 5.7% for patients with acute appendicitis with localized peritonitis and - 20.2% for patients with acute appendicitis with generalized peritonitis. CONCLUSIONS: As bundled payments become more common, hospitals may incur significant losses for acute appendicitis under a model that does not reflect the heterogeneous nature of patients requiring appendectomies. These losses can range up to - 20.2% for complicated cases. Improving clinical outcomes by reducing readmissions may mitigate some of these anticipated losses.

Arginase blockade protects against hepatic damage in warm ischemia-reperfusion.

BACKGROUND: Liver ischemia reperfusion (I/R) injury is associated with profound arginine depletion due to arginase release from injured hepatocytes. Nitric oxide (NO), shown to have protective effects in I/R, is produced by nitric oxide synthase (NOS) from the substrate arginine. The purpose of this study was to determine if nor-NOHA, a novel arginase inhibitor, would be able to increase circulating arginine levels and decrease hepatic damage following warm I/R. METHODS: C57BL/6 mice underwent partial liver warm I/R and were treated intraperitoneally with either nor-NOHA (100mg/kg) or saline. Serum and tissue samples were collected to measure liver enzyme levels, amino acids, and inflammatory mediators. The agent nor-NOHA (100mg/kg) was administered 15 min before ischemia and immediately after reperfusion. Serum amino acid analysis was performed using HPLC. RESULTS: Arginase activity after hepatic I/R peaked at 3-6h after reperfusion and resulted in a 10-fold drop in circulating arginine levels. Treatment with nor-NOHA inhibited arginase activity and reversed the arginine depletion after I/R while simultaneously increasing serum nitric oxide. In addition, circulating citrulline, a product of NOS activity, was increased in nor-NOHA-treated animals compared to controls. Inhibition of arginase also resulted in protection from hepatic I/R-induced damage in association with markedly lower hepatic TNF, IL-6, and inducible NOS mRNA levels compared to controls. CONCLUSION: Arginase blockade represents a potentially novel strategy to combat liver injury under conditions of arginine deficiency. This protection may be mediated through the arginine-NO pathway.

Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury.

Endogenous ligands released from damaged cells, so-called damage-associated molecular pattern molecules (DAMPs), activate innate signaling pathways including the TLRs. We have shown that hepatic, warm ischemia and reperfusion (I/R) injury, generating local, noninfectious DAMPs, promotes inflammation, which is largely TLR4-dependent. Here, we demonstrate that increasing dendritic cell (DC) numbers enhance inflammation and organ injury after hepatic I/R. High-mobility group box 1 (HMGB1), a NF released by necrotic cells or secreted by stimulated cells, is one of a number of ligands promoting TLR4 reactivity. Augmentation of DC numbers in the liver with GM-CSF hydrodynamic transfection significantly increased liver damage after I/R when compared with controls. TLR4 engagement on hepatic DC was required for the I/R-induced injury, as augmentation of DC numbers in TLR4 mutant (C3H/HeJ) mice did not worsen hepatic damage. It is interesting that TLR4 expression was increased in hepatic DC following HMGB1 stimulation in vitro, suggesting a mechanism for the increased liver injury following I/R. It thus appears that functional TLR4 on DC is required for I/R-induced injury. Furthermore, HMGB1 may direct the inflammatory responses mediated by DC, at least in part, by enhancing TLR4 expression and reactivity to it and other DAMPs.