Ccr2 Dependent Monocytes Exacerbate Intestinal Inflammation and Modulate Gut Serotonergic Signaling Following Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) leads to acute gastrointestinal dysfunction and mucosal damage, resulting in feeding intolerance. Ccr2+ monocytes are crucial immune cells that regulate the gut's inflammatory response via the brain-gut axis. Using CCR2KO mice, we investigated the intricate interplay between these cells to better elucidate the role of systemic inflammation after TBI. METHODS: A murine-controlled cortical impact model was utilized, and results were analyzed on post-injury days (PID) 1 and 3. The experimental groups included (1) Sham C57Bl/6 wild-type (WT), (2) TBI WT, (3) Sham CCR2KO and (4) TBI CCR2KO. Mice were euthanized on PID 1 and 3 to harvest the ileum and study intestinal dysfunction and serotonergic signaling using a combination of quantitative real-time PCR (qRT-PCR), immunohistochemistry, FITC-dextran motility assays, and flow cytometry. Student's t-test and one-way ANOVA were used for statistical analysis, with significance achieved when p < 0.05. RESULTS: TBI resulted in severe dysfunction and dysmotility of the small intestine in WT mice as established by significant upregulation of inflammatory cytokines iNOS, Lcn2, TNFα, and IL1ß and the innate immunity receptor toll-like receptor 4 (Tlr4). This was accompanied by disruption of genes related to serotonin synthesis and degradation. Notably, CCR2KO mice subjected to TBI showed substantial improvements in intestinal pathology. TBI CCR2KO groups demonstrated reduced expression of inflammatory mediators (iNOS, Lcn2, IL1ß, and Tlr4) and improvement in serotonin synthesis genes, including tryptophan hydroxylase 1 (Tph1) and dopa decarboxylase (Ddc). CONCLUSION: Our study reveals a critical role for Ccr2+ monocytes in modulating intestinal homeostasis after TBI. Ccr2+ monocytes aggravate intestinal inflammation and alter gut-derived serotonergic signaling. Therefore, targeting Ccr2+ monocyte-dependent responses could provide a better understanding of TBI-induced gut inflammation. Further studies are required to elucidate the impact of these changes on brain neuroinflammation and cognitive outcomes. STUDY TYPE: Original Article (Basic Science, level of evidence N/A).

Chest vs. neck anastomotic leak post esophagectomy for malignancy: rate, predictors, and outcomes.

Background: Anastomotic leak is a major contributor to comorbidity and mortality following esophagectomy. We sought to assess rate and predictors of leak after esophagectomy and compare outcomes of chest versus neck anastomotic leaks. Methods: A retrospective review was performed utilizing National-Surgical-Quality-Improvement-Program data from 2016-2019 for patients undergoing esophagectomy for malignancy. Preoperative characteristics and postoperative outcomes were compared. Patients were classified into two groups: Ivor Lewis esophagectomy [ILE, chest leak (CL)] and transhiatal esophagectomy (THE)/McKeown esophagectomy [ME, neck leak (NL)]. Multivariable regression models were constructed to determine predictors of each type of leak and postoperative complications. Results: A total of 1,665 patients underwent esophagectomy with 14.1% reported post-operative leak, 61% of patients underwent ILE while 39% underwent THE or ME. Of patients who underwent ILE, 13.8% had CL with complications including significantly higher length of stay and mortality compared to patients without leak. Independent predictors of CL included: diabetes, hypertension, advanced disease stage, chronic steroid use, and operative time. Ninety-five patients (14.6%) who underwent either THE or ME had NL with similar complications. Diabetes, pre-operative white blood cell (WBC), and operative time were independent predictors for NL. On multivariable regression, CL was associated with greater odds of requiring intervention compared with NL. Conclusions: Post-esophagectomy CL and NL are associated with higher morbidity and mortality. Diabetes and operative time were independent predictors for both leaks while steroid use, hypertension, and advanced disease stage predicted CL. CL was associated with greater odds of needing an intervention, but contrary to conventional wisdom, was not associated with higher morbidity or mortality.

New insights into the pathogenesis of necrotizing enterocolitis and the dawn of potential therapeutics.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disorder in premature infants that causes significant morbidity and mortality. Research efforts into the pathogenesis of NEC have discovered a pivotal role for the gram-negative bacterial receptor, Toll-like receptor 4 (TLR4), in its development. TLR4 is activated by dysbiotic microbes within the intestinal lumen, which leads to an exaggerated inflammatory response within the developing intestine, resulting in mucosal injury. More recently, studies have identified that the impaired intestinal motility that occurs early in NEC has a causative role in disease development, as strategies to enhance intestinal motility can reverse NEC in preclinical models. There has also been broad appreciation that NEC also contributes to significant neuroinflammation, which we have linked to the effects of gut-derived pro-inflammatory molecules and immune cells which activate microglia in the developing brain, resulting in white matter injury. These findings suggest that the management of the intestinal inflammation may secondarily be neuroprotective. Importantly, despite the significant burden of NEC on premature infants, these and other studies have provided a strong rationale for the development of small molecules with the capability of reducing NEC severity in pre-clinical models, thus guiding the development of specific anti-NEC therapies. This review summarizes the roles of TLR4 signaling in the premature gut in the pathogenesis of NEC, and provides insights into optimal clinical management strategies based upon findings from laboratory studies.

Management of pediatric appendicitis during the COVID-19 pandemic: A nationwide multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has impacted timely access to care for children, including patients with appendicitis. This study aimed to evaluate the effect of the COVID-19 pandemic on management of appendicitis and patient outcomes. METHODS: A multicenter retrospective study was performed including 19 children's hospitals from April 2019-October 2020 of children (age≤18 years) diagnosed with appendicitis. Groups were defined by each hospital's city/state stay-at-home orders (SAHO), designating patients as Pre-COVID (Pre-SAHO) or COVID (Post-SAHO). Demographic, treatment, and outcome data were obtained, and univariate and multivariable analysis was performed. RESULTS: Of 6,014 patients, 2,413 (40.1%) presented during the COVID-19 pandemic. More patients were managed non-operatively during the COVID-19 pandemic compared to before the pandemic (147 (6.1%) vs 144 (4.0%), p < 0.001). Despite this change, there was no difference in the proportion of complicated appendicitis between groups (1,247 (34.6%) vs 849 (35.2%), p = 0.12). COVID era non-operative patients received fewer additional procedures, including interventional radiology (IR) drain placements, compared to pre-COVID non-operative patients (29 (19.7%) vs 69 (47.9%), p < 0.001). On adjusted analysis, factors associated with increased odds of receiving non-operative management included: increasing duration of symptoms (OR=1.01, 95% CI: 1.01-1.012), African American race (OR=2.4, 95% CI: 1.3-4.6), and testing positive for COVID-19 (OR=10.8, 95% CI: 5.4-21.6). CONCLUSION: Non-operative management of appendicitis increased during the COVID-19 pandemic. Additionally, fewer COVID era cases required IR procedures. These changes in the management of pediatric appendicitis during the COVID pandemic demonstrates the potential for future utilization of non-operative management.

Complicated jejunal diverticulitis: A case report and review of literature.

Jejunal diverticulitis is an uncommon pathology wherein a delay in diagnosis can lead to significant morbidity and mortality. We report a case of such diverticula requiring operative management, after patient failed non-operative management, likely due to advanced jejunal inflammation from a delay in diagnosis and subsequent management.

Utilization of Supplemental Regional Anesthesia in Lobectomy for Lung Cancer in the United States: A Retrospective Study.

Background: Pulmonary lobectomy is the standard of care for the treatment of early-stage non-small cell lung cancer. This study investigated the rate of utilization of supplemental anesthesia in patients undergoing video-assisted thoracoscopic surgery (VATS) or open lobectomy using a national database and assessed the effect of regional block (RB) on postoperative outcomes. Methods: Patients who underwent lobectomy for lung cancer between 2014-2019 were identified in the American College of Surgeons National Surgical Quality Improvement Program. The patients' primary mode of anesthesia and supplemental anesthesia were recorded. Preoperative characteristics and postoperative outcomes were compared between 2 surgical groups: those who underwent general anesthesia (GA) alone versus GA with RB. Multivariable regression analyses were performed on the outcomes of interest. Results: In total, 13,578 patients met the study criteria, with 87% undergoing GA and the remaining 13% receiving GA and RB. The use of neuraxial anesthesia decreased over the years, while RB use increased up to 20% in 2019. Age, body mass index, and preoperative comorbidities were comparable between groups. Patients who underwent VATS were more likely to receive RB than those who underwent thoracotomy. RB was most often utilized by thoracic surgeons. An adjusted analysis showed that RB use was associated with shorter hospital stays and a reduced likelihood of prolonged length of stay, but a higher rate of surgical site infections (SSIs). Conclusion: In a large surgical database, there was underutilization of supplemental anesthesia in patients undergoing lobectomy for lung cancer. RB utilization was associated with a shorter length of hospital stay and an increase in SSI incidence.

Trends in open lobectomy outcomes for lung cancer over the last 15 years: national cohort.

OBJECTIVE: Adoption of thoracoscopic lobectomy has been increasing in the US; however, open lobectomy (OL) is still performed in half of the cases. Postoperative care and enhanced recovery after surgery (ERAS) pathways have evolved and improved outcomes. The study aims to evaluate postoperative outcomes of OL over the last 15 years. METHODS: Patients who underwent lobectomy for lung cancer between 2005 and 2019 were identified in the National Surgical Quality Improvement Program and divided into three groups; pre-ERAS (2005-2011), transitional period (2012-2015), and wider ERAS implementation (2016-2019). Preoperative characteristics and postoperative outcomes were compared and multivariable regression analysis was constructed to assess independent predictors of outcomes. RESULTS: OL was comprised of 40% of lobectomies for lung cancer. 10,021 patients met inclusion criteria. 49% were males and mean age was 67. Patients who belonged to the (2016-2019) period group had significantly higher comorbidities and ASA classification. General surgeons performed < 10% of OL in 2016-2019 compared to over 30% during 2005-2011. Patients in the 2016-2019 period were less likely to experience unplanned intubation, surgical site infections, and sepsis. Mortality was also significantly lower than the previous groups (1.9% vs 2.0% and 2.8%, p = 0.05). The rate of discharge to facility as well as length of hospital stays improved over the years. The surgeon specialty served as an independent predictor for length of stay, unplanned intubation, and home discharge. CONCLUSION: The outcomes of OL are improving over the years. Increasing number of these surgeries being performed by dedicated thoracic surgeons and ERAS pathways are likely helping improve outcomes.

Closing Contaminated Fascial Defects With Synthetic Mesh and a Vacuum-Assisted Closure Device.

BACKGROUND: The use of synthetic mesh is considered too high risk, and therefore, not an option when closing a contaminated abdominal fascial defect. This study evaluated the clinical outcomes when using synthetic mesh combined with vacuum-assisted closure (VAC) dressing to close these facial defects. MATERIALS AND METHODS: From 2010 to 2016, a retrospective review was performed, including 34 patients in a single rural trauma center who underwent a damage control laparotomy in the presence of a contaminated or infected field. Definitive abdominal closure with a bridging polypropylene mesh along with the application of a VAC dressing was done in all cases. Data collection included baseline demographics, operative indication, postoperative complications, mortality and length of follow up. RESULTS: Median age of the patients was 67 y (IQR 40-87 y), with 22 (65%) being male at the time of operation. The median duration of clinical follow-up was 15.15 mo. The observed complications included three fistulas, two hernias, nine draining sinus tracts, and three mesh explanations with an overall complication rate of 41.1%. Although the absolute observed fistula rate was 8.8% (3 cases), the adjusted mesh-related fistulas formation rate after chart review was 0.0%. No mortalities were attributed directly to mesh-related complication. CONCLUSIONS: This study found no mesh-related fistulas when using a synthetic mesh along with a VAC dressing for abdominal closure in a contaminated field. These results may provide a platform for further study regarding the safety of this technique.