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Anastomotic leaks after colorectal surgery is associated with increased morbidity and mortality. Understanding the impact of anastomotic leaks and their risk factors can help the surgeon avoid any modifiable pitfalls. The diagnosis of an anastomotic leak can be elusive but can be discerned by the patient's global clinical assessment, adjunctive laboratory data and radiological assessment. The use of inflammatory markers such as C-Reactive Protein and Procalcitonin have recently gained traction as harbingers for a leak. A CT scan and/or a water soluble contrast study can further elucidate the location and severity of a leak. Further intervention is then individualized on the spectrum of simple observation with resolution or surgical intervention.

Amyand’s hernia, an incarcerated appendix inside an inguinal hernia, accounts for

Histone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.

Utilization of robotic proctectomy (RP) for rectal cancer has steadily increased since the inception of robotic surgery in 2002. Randomized control trials evaluating the safety of RP are in process to better understand the role of robotic assistance in proctectomy. This study aimed to characterize the trends in the use of RP for rectal cancer, and to compare oncologic outcomes with center-level RP volume. 8107 patients with rectal adenocarcinoma who underwent RP were identified in the National Cancer Database (2010–2015). Logistic regression was used to evaluate associations between center-level volume and conversion to open proctectomy, margin status, lymph node yield, 30- and 90-day post-operative mortality, and overall survival. The utilization of RP increased from 2010 to 2015. On multivariate regression, lower center-level volume of RP was associated with significantly higher rates of conversion to open, positive margins, inadequate lymph node harvest (≥ 12), and lower overall survival. The present study was limited by its retrospective design and lack of information regarding disease-specific survival. This series suggests a volume–outcome relationship association; patients who have robot-assisted proctectomies performed at low-volume centers are more likely to have poorer overall survival, positive margins, inadequate lymph node harvest, and require conversion to open surgery. While these data demonstrate the increased adoption of robot-assisted proctectomy, an understanding of the appropriateness of this intervention is still lacking. As with any new intervention, further information from ongoing randomized controlled trials is needed to better clarify the role of RP in order to optimize patient outcomes.

To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28 minutes warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.

Summary: Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this “balancing act” remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a “default” Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.

The asymmetric total synthesis of (-)-bipinnatin J and its conversion into (+)-intricarene through a transannular 1,3-dipolar cycloaddition is described. In addition, the conversion of (-)-bipinnatin J into (+)-rubifolide and (+)-isoepilophodione B is reported. Biosynthetic relationships among furanocembranoids and the possible role of 1,3-dipolar cycloadditions in biosynthesis are discussed. [reaction: see text]