E-Only Articles
Linalool: a novel natural anti-inflammatory agent?: Commentary on “Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model”
Proinflammatory states are widely implicated in both acute and chronic disease processes. Severe acute systemic inflammation is at least partially responsible for shock and acute lung injury, and therapeutic options to curb the proinflammatory responses are limited. Sustained release of proinflammatory mediators by macrophages and other leukocyte subtypes is the hallmark of autoimmune illnesses. In addition to nonspecific immunosuppressants, targeted therapies to reduce inflammation via inhibition of cytokine release are available for some of these illnesses, including Crohn disease and rheumatoid arthritis.Intestinal alkaline phosphatase prevents the systemic inflammatory response associated with necrotizing enterocolitis
Necrotizing enterocolitis (NEC) represents a heterogeneous group of pathologic processes in the intestines of neonates who are commonly premature with very low birth weights. It is characterized by an intense inflammatory response and has mortality rates as high as 20%–40% [1,2]. Despite the established relationship between necrotizing enterocolitis and a proinflammatory cascade, the pathophysiology is still not completely understood. The involvement of enteral feedings, compromised intestinal perfusion, and bacterial invasion are commonly accepted factors [3].Importance of erythropoietin in septic encephalopathy
Erythropoietin (EPO) is a 31-kDa glycoprotein that has long been studied for its role in hematopoiesis. However, more recent evidence suggests that in addition to its biological functions in the hematopoietic system, EPO may have significant activity in the brain [1–3]. More specific functions in the brain have been proposed, including EPO as a neuroprotective agent against excitotoxicity and apopotosis, as well as EPO enhancing the proliferation and mobilization of neuronal stem cells [4,5].The Iliad and the Odyssey of metallic foreign body extraction: commentary on “Novel methods of removing metallic foreign body from human soft tissue: a report of 7390 cases”
Surgeons have been extracting metallic foreign bodies (MFB) for centuries. Perhaps the earliest literary account comes from Homer's epic poem The Iliad (ca BC 800), based on events of the Trojan War from Greek mythology. Makaon operated on an arrow wound to the abdomen of King Menelaus by extracting the arrow, sucking blood from the wound to remove poison, and applying a salve [1]: The shaft he drew, but left the head behind. Straight the broad belt with gay embroidery graced, He loosed; the corslet from his breast unbraced; Then suck'd the blood, and sovereign balm infused, Which Chron gave, and Aesculapius used [2].Radicicol, a Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis
Sepsis complex syndromes remain active challenges in critical care medicine because of a deficiency in understanding the molecular basis and cellular signaling network of such infections. We hope that the 21st century will witness a revolution in discovering and targeting the cellular and molecular roots of this clinical entity. Severe sepsis with multiple organ dysfunction remains the most common cause of mortality in noncardiac intensive care units and is ranked as the 10th leading cause of death in the US [1].The long and winding road to immune tolerance
No matter how many new immunosuppressive medications reach the market, the “Holy Grail” of transplantation has always been (and according to some will continue to “always” be) the induction of donor-specific immunologic tolerance. In this effort to modulate the immune system, there have been a multitude of different approaches and candidates at the cellular or molecular level. Dendritic cells (DC), as possibly the most effective antigen presenting cells, appear to play a critical role in moderating the immune response.Strategies to prevent sepsis-induced intensive care unit–acquired weakness: are there any options? Commentary on “Comparison of melatonin and oxytocin in the prevention of critical illness polyneuropathy in rats with surgically induced sepsis”
Intensive care unit-acquired weakness (ICUAW) is one of the leading causes of morbidity in critically ill patients and a significant risk factor for the development of chronic critical illness. In 2008, 727,000 patients were hospitalized for sepsis, with mortality rate of 17% at an estimated cost of $14.6 billion [1]. The risk of critical illness neuromuscular abnormalities in patients with sepsis, multiorgan failure, or prolonged mechanical ventilation is reported to be as high as 46% [2].Commentary on “Defining and predicting surgeon utilization at Forward Surgical Teams in Afghanistan”
In a recently published paper in the Journal of Surgical Research, Remick et al. [1] discuss contrasts between two Forward Surgical Teams deployed to Afghanistan during Operation Enduring Freedom during two separate time periods. Forward Surgical Teams are currently the smallest unit available to the US Army to provide resuscitative surgery in the field. These units, and variations, have been pushed farther afield in an effort to provide far-forward resuscitative capacity for our injured service members in the conflict in the Middle East.Angiotensin II as a limiting agent to intracellular calcium signaling in inflammatory states
Angiotensin II, the end product of the renal angiotensin system, is well known for its role in increasing peripheral vascular resistance and subsequent elevation in blood pressure in a clinical setting. The regulatory effect of angiotensin II on growth factors and inflammatory cytokines in an immunologic setting is less known but equally important aspect of this protein molecule. In a recently published article in the Journal of Surgical Research, Lo et al. has expanded on this topic by exploring the role of angiotensin II.Commentary: Empiric antibiotics pending bronchoalveolar lavage data in patients without pneumonia significantly alters the flora but not the resistance profile if a subsequent pneumonia develops
Ventilator-associated pneumonia (VAP), defined as pneumonia that occurs within 48–72 h of endotracheal intubation, has been reported to occur in up to 52% of critically ill patients [1]. VAP is associated with increased morbidity, mortality, the length of hospital stay, and excess costs [2]. Given the magnitude of the problem, there has been an impetus to identify processes of care that are linked to outcome such as appropriate antibiotic coverage and timing in patients with suspected VAP. In 2005, the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) published the consensus guidelines for the management of VAP.Radical gastrectomy with para-aortic lymphadenectomy for carcinoma? The controversy continues. Commentary on Risk Factors for Metastasis to Para-Aortic Lymph Nodes in Gastric Cancer: A Single Institution Study in China. Journal of Surgical Research
Gastric cancer is the fourth most common cancer worldwide and the second leading cause of cancer death. The highest incidence of gastric cancer is in Eastern Asia. China has 463,000 new cases a year, whereas the United States as an annual incidence of 21,000 cases [1]. Intestinal type gastric cancer is more prevalent in high-risk areas and is influenced by environmental factors. Because the incidence and histology are variable by region, there remains significant worldwide controversy regarding management of the disease.Selective occlusion of the portal vein while maintaining hepatic artery blood flow during partial hepatectomy: a new method for preventing ischemia-reperfusion injury?
The liver is an essential multifunctional organ with diverse vital functions in nutrient metabolism, blood and bile formation, detoxification, and hormone production. Liver function can be impaired by drug and alcohol abuse, food and environmental toxins, metabolic disorders, viral infections, and congenital defects. Primary liver cancer and liver metastases, primarily from colorectal cancer, can also cause life-threatening damage to the liver [1]. Depending on comorbidities, tumor size, and the segmental distribution of tumors in the liver, the techniques of ablation, resection, or liver transplantation remain the most important and successful treatment modalities for primary and secondary liver cancer [2,3].A blood test for acute rejection after renal transplantation? Commentary on “Osteopontin level correlates with acute cellular renal allograft rejection”
End-stage renal disease affects over 500,000 patients each year in the United States. Currently, over 92,000 people wait on the kidney transplant list in the United States alone, where approximately 16,000 transplants occur annually [1]. With such a discrepancy between supply and demand, graft survival is critical. Yet, even with advances in transplantation technique and immunosuppression, year one acute rejection rates remain between 10% and 20% [2]. Acute rejection begins subclinically and progression may lead to irreversible organ damage or graft loss.Suberoylanilide hydroxamic acid (SAHA) as an agent to attenuate Toll-like receptor 4–induced septic shock
Severe sepsis and septic shock are still associated with high mortality despite the advancement of antibiotics and critical care. Macrophages detect bacterial lipopolysaccharide (LPS) by a mechanism mediated by Toll-like receptor 4 (TLR4). This receptor causes activation of proinflammatory cascade and production of proteins and cytokines, such as myeloid differentiation primary response gene 88 (MyD88), interleukin (IL)-1 (including IL-1 receptor-associated kinase [IRAK]-1), tumor necrosis factor receptor-associated factor 6, and nuclear factor-κB (NF-κB), which can lead to robust and potentially exaggerated immune response of the body.Commentary on: “Temporary rapid bowel ligation as a damage control adjunct”
I have read with great interest the recently published article by Wang et al. [1]. The authors state strongly in the title of the article that temporary rapid bowel ligation as a damage control adjunct improves survival in a hypothermic traumatic shock swine model with multiple bowel perforations. There are major flaws in the design, statistical analysis, and interpretation of the study that completely undermine this statement. Reading their article critically actually indicates the opposite.Commentary: 17-β-estradiol reappropriates mass lost to the hypermetabolic state in thermally injured rats
Severe burns are among the most common causes of death from unintentional injury [1], and they remain an important subject in trauma and critical care medicine. The profound hypermetabolic and hypercatabolic states that are characteristic of severe thermal injury lead to extensive protein wasting, manifested as skeletal muscle breakdown, lean body mass loss, and negative nitrogen balance with subsequent compromised functional and structural changes of essential body organs [2,3]. These changes occur in response to the release of proinflammatory cytokines and counter regulatory hormones that dramatically impair the anabolic states.Age-related differences in hepatic ischemia/reperfusion: gene activation, liver injury, and protective effect of melatonin
Despite the fact that melatonin's discovery was over 50 y ago, it was not recognized as a free radical scavenger and antioxidant until the 1991 by Ianas et al. [1]. Melatonin can neutralize hydroxyl radical, hydrogen peroxide, peroxynitrite anion, nitric oxide, and hypochlorous acid [2]. After Sewerynek et al. showed that melatonin protects the liver against ischemia reperfusion injury (IRI) in 1996 many other experiments have been performed [3]. However, melatonin has not been tested yet in a liver transplant model.Is acute appendicitis in the weather forecast?
Acute appendicitis remains the most common abdominal surgical emergency [1]. In the United States alone, approximately 280,000 appendectomies are performed each year [2], and approximately 11 of every 10,000 Americans will develop acute appendicitis in their lifetime [3]. Despite the frequency with which this disease occurs, the exact etiology in most cases remains elusive. In monitoring changes in the epidemiology of acute appendicitis around the world, there have been many theories, which have raised more questions than answers.Cardiotrophin-1, an antiinflammatory cytokine; is there a therapeutic role in orthotopic liver transplantation?
Living donor liver transplantation was introduced in 1988 [1–3]. Since its first clinical application, living donor liver transplantation has been gradually accepted [4] for patients with end-stage liver disease. In recent years, living donor or cadaveric split liver transplantation has been a valuable alternative in solving the problem of organ shortage and has shown significantly improved clinical outcomes [5]. With reduction of graft size, the chance of primary graft nonfunction is increased.Genomics and transplantation: a brave new world is (almost) here
The era that we live in appears to be one that is dominated by genomic medicine, as the amount of genomic data has increased exponentially over the last several years, thus providing specific targets at the gene level for intervention in a variety of pathophysiological processes [1,2]. This has led to a shift in how we approach different biological mechanisms, as the challenge of understanding the human genome offers the possibility of a personalized approach to the individual patient with the unique genomic data.Commentary on “Combined treatment with regulatory T cells and vascularized bone marrow transplantation creates mixed chimerism and donor-specific tolerance to vascularized composite allografts without cytoreductive conditioning”
Transplantation of vascularized composite allografts (VCAs) could significantly affect the liver of the approximately 7 million Americans every year. These Americans would benefit from transplantation because they had undergone or need to undergo reconstructive surgery as the result of oncologic procedures, congenital anomalies, and trauma [1]. Just as important, it may also help bring us a step closer to the “Holy Grail” of transplantation, which is the induction of donor-specific immunologic tolerance.The role of exogenous adenosine triphosphate administration for the prevention of ischemia-reperfusion injury in skeletal muscle
Organ preservation solutions are essential for the temporary storage of tissue prior to transplantation or reimplantation. The depletion of oxygen stores occurs within a few seconds. Stored energy in the form of creatine phosphate (CP) and adenosine triphosphate (ATP) is depleted. Anaerobic glycolysis then occurs followed by an attempt to maintain normal cellular function. However, glycolysis cannot maintain tissue survival for long. Metabolic waste accumulates and the cellular pH decreases. Mitochondrial ATP generation is blocked because of a lack of molecular oxygen, and insufficient supply of NAD+ also causes the Krebs cycle to cease function.Commentary on: Lipid peroxidation in machine perfusion of older donor kidneys
It is a universally accepted fact that kidney transplantation improves quality of life and patient survival in patients with end-stage renal disease [1]. However, the success of renal transplantation has generated its biggest challenge, which is none other than the growing disparity between available organs on the one hand and the increasing need on the other hand. According to data from the United Network for Organ Sharing (UNOS), the annual increase of patients on the transplant waiting list is approximately five times the number of transplantation procedures, leading to a 6% mortality rate for patients on the waiting list for a renal transplant [2,3].Commentary on: Age-related differences in hepatic ischemia/reperfusion: gene activation, liver injury, and protective effect of melatonin
Ischemia/reperfusion (I/R) injury represents a process of blood deprivation during the ischemia period followed by the release of a high number of a variety of mediators during the reperfusion period, which can potentially lead to cellular and, eventually, organ dysfunction. This basic mechanism is critical in a variety of different fields of surgery, including trauma, vascular, and transplantation surgery, with the liver being one of the organs most frequently involved. Finding ways to ameliorate the I/R injury observed in liver transplantation or resection can go a long way towards improving their respective results, as well as towards increasing the number of transplants by being able to improve the quality of available hepatic grafts.Cbfa1/Runx2-transduced adult adipose stem cells on biodegradable scaffolds for segmental bone defect repair
Segmental bone defects can be caused by various pathologic conditions such as trauma, nonunion fractures, cancer treatment–related surgery for osteosarcomas and bone metastases, bacterial infections, inflammation, or congenital defects [1,2]. Depending on the amount and characteristics of the segmental bone loss, repair and regeneration can pose a clinical challenge for surgeons. In cases where autogenous or allogeneic bone grafting is not possible due to patient characteristics or the size or availability of the required bone transplant, modern techniques of skeletal tissue engineering can provide vital support for successful healing and reconstruction [3].
