Therapeutic evaluation of immunomodulators in reducing surgical wound infection.

Despite many advances in infection control practices, including prophylactic antibiotics, surgical site infections (SSIs) remain a significant cause of morbidity, prolonged hospitalization, and death worldwide. Our innate immune system possesses a multitude of powerful antimicrobial strategies which make it highly effective in combating bacterial, fungal, and viral infections. However, pathogens use various stealth mechanisms to avoid the innate immune system, which in turn buy them time to colonize wounds and damage tissues at surgical sites. We hypothesized that immunomodulators that can jumpstart and activate innate immune responses at surgical sites, would likely reduce infection at surgical sites. We used three immunomodulators; fMLP (formyl-Methionine-Lysine-Proline), CCL3 (MIP-1α), and LPS (Lipopolysaccharide), based on their documented ability to elicit strong inflammatory responses; in a surgical wound infection model with Pseudomonas aeruginosa to evaluate our hypothesis. Our data indicate that one-time topical treatment with these immunomodulators at low doses significantly increased proinflammatory responses in infected and uninfected surgical wounds and were as effective, (or even better), than a potent prophylactic antibiotic (Tobramycin) in reducing P. aeruginosa infection in wounds. Our data further show that immunomodulators did not have adverse effects on tissue repair and wound healing processes. Rather, they enhanced healing in both infected and uninfected wounds. Collectively, our data demonstrate that harnessing the power of the innate immune system by immunomodulators can significantly boost infection control and potentially stimulate healing. We propose that topical treatment with these immunomodulators at the time of surgery may have therapeutic potential in combating SSI, alone or in combination with prophylactic antibiotics.

Association between perioperative allogeneic red blood cell transfusion and infection after clean-contaminated surgery: a retrospective cohort study.

BACKGROUND: Allogeneic red blood cell (RBC) transfusion can induce immunosuppression, which can then increase the susceptibility to postoperative infection. However, studies in different types of surgery show conflicting results regarding this effect. METHODS: In this retrospective cohort study conducted in a tertiary referral centre, we included adult patients undergoing clean-contaminated surgery from 2014 to 2018. Patients who received allogeneic RBC transfusion from preoperative Day 30 to postoperative Day 30 were included into the transfusion group. The control group was matched for the type of surgery in a 1:1 ratio. The primary outcome was infection within 30 days after surgery, which was defined by healthcare-associated infection, and identified mainly based on antibiotic regimens, microbiology tests, and medical notes. RESULTS: Among the 8098 included patients, 1525 (18.8%) developed 1904 episodes of postoperative infection. Perioperative RBC transfusion was associated with an increased risk of postoperative infection after controlling for 27 confounders by multivariable regression analysis (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.39-1.84; P<0.001) and propensity score weighing (OR: 1.64; 95% CI: 1.45-1.85; P<0.001) and matching (OR: 1.70; 95% CI: 1.43-2.01; P<0.001), and a dose-response relationship was observed. The transfusion group also showed higher risks of surgical site infection, pneumonia, bloodstream infection, multiple infections, intensive care admission, unplanned reoperation, prolonged postoperative length of hospital stay, and all-cause death. CONCLUSIONS: Perioperative allogeneic RBC transfusion is associated with an increased risk of infection after clean-contaminated surgery in a dose-response manner. Close monitoring of infections and enhanced prophylactic strategies should be considered after transfusion.

Incidental COVID-19 in a heart-kidney transplant recipient with malnutrition and recurrent infections: Implications for the SARS-CoV-2 immune response.

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.

Toll-like receptors: exploring their potential connection with post-operative infectious complications and cancer recurrence.

Cancer is the leading cause of death in North America. Despite modern advances in cancer therapy, many patients will ultimately develop cancer metastasis resulting in mortality. Surgery to resect early stage solid malignancies remains the cornerstone of cancer treatment. However, surgery places patients at risk of developing post-operative infectious complications that are linked to earlier cancer metastatic recurrence and cancer mortality. Toll-like receptors (TLRs) are evolutionarily-conserved sentinel receptors of the innate immune system that are activated by microbial products present during infection, leading to activation of innate immunity. Numerous types of solid cancer cells also express TLRs, with their activation augmenting their ability to metastasize. Similarly, healthy host-tissue TLRs activated during infection induce a prometastatic environment in the host. Cancer cells additionally secrete TLR activating ligands that activate both cancer TLRs and host TLRs to promote metastasis. Consequently, TLRs are an attractive therapeutic candidate to target infection-induced cancer metastasis and progression.

Surgical Upper Extremity Infections in Immunosuppressed Patients: A Comparative Analysis With Diagnosis and Treatment Recommendations for Hand Surgeons.

Background: Immunosuppression is encountered in patients with oncologic, transplant, and autoimmune disorders. The purpose of this study is to provide guidance for physicians treating surgical hand and upper extremity (UE) infections in immunosuppressed (IS) patients. Methods: We retrospectively reviewed our database of patients presenting with UE infections over 3 years. IS patients were matched randomly to non-IS patients. Patient background, infection presentation, surgical evaluation, and microbiology variables were recorded. Infection variables included mechanism, location, and type. Outcomes included inpatient length of stay (LOS) and need for repeat drainage. Results: We identified 35 IS and 35 non-IS out of 409 UE infection patients. Patients most commonly had a hematologic malignancy (34%) as their IS class, and the most frequent immunosuppressive medication was glucocorticoids (57%). IS patients were more likely to be older and less likely to have a history of drug abuse or hepatitis C virus infections. IS infections were more likely to have idiopathic mechanisms, more likely to involve deeper anatomy such as joints, bone, tendon sheath, or muscle/fascia, and less likely to present with leukocytosis. IS cultures more commonly exhibited atypical Mycoplasma or fungus. There was no difference between IS and non-IS patients regarding LOS or recurrent drainage. Conclusions: Mechanism and white blood cell count are less reliable markers of infection severity in IS patients. Physicians treating infections in IS patients should maintain a higher suspicion for deeper involved anatomy and atypical microbiology. Nonetheless, with careful inpatient management and closer surveillance, outcomes in IS patients can approach that of non-IS patients.

Updates in penile prosthesis infections.

Inflatable penile prostheses are an important tool in the treatment of medically refractory erectile dysfunction. One of the major complications associated with these prostheses is infections, which ultimately require device explanation and placement of a new device. Over the past several decades, significant work has been done to reduce infection rates and optimize treatment strategies to reduce patient morbidity. This article reviews the current state of knowledge surrounding penile prosthesis infections, with attention to the evidence for methods to prevent infection and best practices for device reimplantation.

Perioperative immune function and pain control may underlie early hospital readmission and 90 day mortality following lung cancer resection: A prospective cohort study of 932 patients.

BACKGROUND: Mortality following lung cancer resection has been shown to double between 30 and 90 days and readmission following surgery is associated with an increased risk of mortality. The aim of this study was to describe the causes of readmission and mortality and enable the identification of potentially modifiable factors associated with these events. METHODS: Prospective cohort study at a United Kingdom tertiary referral centre conducted over 55 months. Binary logistic regression was used to identify factors associated with death within 90 days of surgery. RESULTS: The 30 day and 90 day mortality rates were 1.4% and 3.3% respectively. The most common causes of death were pneumonia, lung cancer and Acute Respiratory Distress Syndrome/Multi Organ Failure. Potentially modifiable risk factors for death identified were: Postoperative pulmonary complications (Odds ratio 6.1), preoperative lymphocyte count (OR 0.25), readmission within 30 days (OR 4.2) and type of postoperative analgesia (OR for intrathecal morphine 4.8). The most common causes of readmission were pneumonia, shortness of breath and pain. CONCLUSIONS: Postoperative mortality is not simply due to fixed factors; the impacts of age, gender and surgical procedure on postoperative survival are reduced when the postoperative course of recovery is examined. Perioperative immune function, as portrayed by the occurrence of infection and lower lymphocyte count in the immediate perioperative period, and pain control method are strongly associated with 90 day mortality; further studies in these fields are indicated as are studies of psychological factors in recovery. CLINICAL REGISTRATION NUMBER: ISRCTN00061628.

Early Postoperative Anti-TNF Therapy Does Not Increase Complications Following Abdominal Surgery in Crohn's Disease.

BACKGROUND: The impact of postoperative anti-TNF therapy on infectious complications following Crohn's disease surgery remains controversial. Use of anti-TNF therapy 2-4 weeks postoperatively appears safe, but safety of use within 2 weeks is unknown. AIMS: We sought to evaluate the effect of anti-TNF therapy initiated within 2 weeks of abdominal surgery in patients with Crohn's disease. METHODS: We conducted a retrospective review of adult Crohn's disease patients undergoing abdominal surgery between 2004 and 2011. Infectious and non-infectious complications were compared between patients exposed to anti-TNF therapy within 2 weeks or between 2 and 4 weeks postoperatively and to those without exposure using chi-squared and regression analysis. RESULTS: Three hundred thirty-one abdominal surgeries were included; 241 were without anti-TNF exposure, 46 received postoperative anti-TNF within 2 weeks of surgery, and 44 received anti-TNF therapy 2-4 weeks after surgery. Patients who received anti-TNF therapy within 2 weeks of surgery, those initiated between 2 and 4 weeks of surgery, and those who did not receive anti-TNF therapy within 4 weeks of surgery had no significant difference in rates of infectious complications (22%, 32%, 33%, p = 0.332). Rates of non-infectious complications (4%, 9%, 14%, p = 0.143), mortality (0%, 0%, 3%, p = 0.105), hospital readmission (17%, 16%, 15%, p = 0.940), and reoperation (11%, 11%, 16%, p = 0.563) were also similar between groups. CONCLUSIONS: Use of early anti-TNF therapy within 2 weeks or between 2 and 4 weeks following abdominal surgery did not increase risk of postoperative surgical infections in Crohn's patients.

Volatile Anesthetic Attenuates Phagocyte Function and Worsens Bacterial Loads in Wounds.

BACKGROUND: Previously we have shown that volatile anesthetic isoflurane attenuated neutrophil recruitment and phagocytosis in mouse sepsis and skin inflammation models. The objectives of this study were to test ex vivo function of neutrophils in patients who underwent cardiac catheterization under volatile anesthesia versus intravenous anesthesia (IA), and also to assess the effect of anesthesia on surgical site infections (SSIs) using mouse model to understand the clinical relevance of anesthesia-induced immunomodulation. METHODS: Whole blood from patients who underwent cardiac catheterization procedures either by volatile anesthesia or IA was collected and subjected to phagocytosis assay and a lipopolysaccharide-induced tumor necrosis factor-α assay. Mouse SSI with Staphylococcus aureus USA300 was created, and the effect of isoflurane and propofol exposure (short or long exposure) on bacterial loads was tested. RESULTS: Neutrophil phagocytosis was significantly attenuated after the induction of volatile anesthesia in patients, but not by IA. Monocyte phagocytosis was not affected by the anesthesia regimen. Bacterial loads following SSIs were significantly higher in mice receiving long, but not short, isoflurane exposure. Propofol exposure did not affect bacterial loads. DISCUSSION: Neutrophil phagocytosis can be affected by the type of anesthesia, and preclinical model of SSIs showed potential clinical relevance. The effects of anesthesia regimen on SSIs in patients needs to be studied extensively in the future.

The perioperative dynamics of IL-7 following robot-assisted and open colorectal surgery.

Interleukin-7 is critical for T-cell development and displays antimicrobial and antitumor properties. It is referred to as a "critical enhancer of protective immunity". However, there is no information on interleukin-7 dynamics following colorectal surgery. Moreover, although robot-assisted surgery is gaining popularity, data on the immune response to it is almost non-existent. In this prospective non-randomized case-control study we found interleukin-7 dynamics to differ following robot-assisted and open approach and to affect postoperative immunity. Linear increases were seen in the robotic group while a cubic pattern with a maximum at 8 h in the open one. Low preoperative interleukin-7 was associated with developing surgical site infection. In turn, higher preoperative interleukin-7 was associated with preserved immune function: less pronounced drop in lymphocyte count and higher Δlymphocyte/Δneutrophil ratio in patients undergoing robotic surgery. The changes in other cytokines, namely, interleukin-12(p70), TNFα, interferon-γ, and interleukin-10 were independently associated with interleukin-7 dynamics. In turn, relative changes in interleukin-7 were independent predictors of changes in interferon-γ, key cytokine of favourable Th1 immune response. Taken together, we demonstrated different perioperative dynamics of interleukin-7, which may contribute to favourable outcomes following robotic colorectal surgery including lower incidence of surgical site infections, milder surgery-induced lymphopenia, and beneficial interferon-γ dynamics.

Bilateral acute retinal necrosis after bilateral cataract surgery in an immunocompromised patient: a case report.

PURPOSE: To report a case of bilateral varicella zoster virus (VZV)-associated acute retinal necrosis (ARN) occurring after both eyes sequential cataract surgery in an elderly immunocompromised patient. METHODS: Medical records and investigation results of the patient were reviewed. RESULTS: Patient experienced floaters and blurring of vision in both eyes 4 weeks after her second uncomplicated cataract surgery. Clinical signs of granulomatous keratic precipitates, prominent vitritis, retinitis and vascular thrombosis were noted in both eyes. Aqueous samples from both eyes were positive for VZV. Disease was treated with intravitreal foscarnet bilaterally and 10 days of systemic intravenous acyclovir (10 mg/kg) followed by oral valaciclovir 1 g three times daily. Final visual acuity at 4 months after initial presentation was 20/60 in both eyes with no retinal detachment noted. CONCLUSIONS: Cataract surgery may have been the trigger for bilateral VZV-associated ARN. Immunocompromised patients can develop ARN and require close observation after cataract surgery. This is, to our knowledge, the first report of bilateral ARN following routine cataract surgery.

[Clinical experience with various techniques integrated treat the wounded with gunshot fractures of limbs]. / Klinicheskii opyt primeneniya razlichnykh metodik kompleksnogo lecheniya ranenykh s ognestrel'nymi perelomami kostei konechnostei.

AIM: To increase an efficiency of complex treatment of patients with diaphyseal gunshot fractures of long bones by introduction of modern minimally invasive surgical techniques of internal osteosynthesis into clinical practice of civil health care and to improve the outcomes in victims. MATERIAL AND METHODS: Prospective comparative clinical trial included 104 victims from the Republic of Yemen with gunshot wounds of limbs of various severity for the period 2009-2011. There were diaphyseal fractures of long bones of limbs associated with soft tissue injuries. Men were predominant (80.7%). Age ranged from 15 to 80 years (mean 38,5 ± 5,7 years). Various surgical techniques of simultaneous and staged treatment were used for gunshot fractures of long bones of limbs. Additional immune therapy was prescribed to prevent infectious complications in the most severe cases. RESULTS AND DISCUSSION: Victims were comprehensively treated according to different staged treatment: conventional surgical treatment with external fixation devices or early primary minimally invasive functionally stable osteosynthesis with LCP/BIOS plates were applied for low-energy fractures; in case of high-energy fractures the first stage included external fixation devices deployment followed by their subsequent replacement during delayed minimally invasive osteosynthesis. The essence of improvement is pursuit to simultaneous minimally invasive surgery by using of current plates for osteosynthesis and preventive immunotherapy of immune dysfunction to eliminate infectious complications. As a result, we obtained 2-fold decrease of surgical invasiveness (r≤0,01) and hospital-stay (r≤0,01). Repeated osteosynthesis was not made. Also 4-fold and 40-fold reduction of infectious and noninfectious complications was observed. This management was accompanied by reduced rehabilitation tine and significantly improved quality of life. CONCLUSION: Improved technique and algorithm of complex treatment of diaphyseal gunshot fractures of long bones of limbs were described. Early minimally invasive functionally stable osteosynthesis with modern implants and non-specific immune prevention of infectious complications are more effective and economically justified compared with conventional treatment including external fixation devices without immunoactive therapy.

Prograf produces more benefits for CYP3A5 low expression patients in early stage after kidney transplantation.

OBJECTIVE: This study is to analyze concentration changes of the prolonged-release and shorter-acting formulation of tacrolimus in patients with different CYP3A5 genotypes after kidney transplantation. METHODS: A single-factor retrospective analysis was performed in patients underwent allogeneic kidney transplantation with postoperative administration of Advagraf or Prograf in our hospital from May 2013 to June 2014. The CYP3A5 genotypes were determined, and tacrolimus trough concentrations in whole blood were measured within 28days after transplantation. The rates of acute rejection rate, chronic rejection and infection were recorded and compared after one year follow-up after surgery. RESULTS: The study included 106 patients administered Advagraf (45 cases) or Prograf (61 cases). The low expression genotype of CYP3A5 was detected in 40 (37.7%) patients. A higher dose of Advagraf was required to increase the tacrolimus trough concentrations within 21days after transplantation. Moreover, a higher dose for Advagraf than Prograf was required to increase the tacrolimus trough concentrations in low expression patients. In the low expression patients, Prograf more frequently achieved the target tacrolimus trough concentrations within seven days after transplantation (five days: 7.14% vs. 84%, P=0.001; seven days: 33.33% vs. 77.78%, P=0.001). The patient and kidney graft survival rates one year after transplantation both were 100%. The estimated glomerular filtration rate showed no significant difference between different CYP3A5 phenotypes or formulations of tacrolimus (P>0.05). However, the incidence of infections was higher in the Advagraf group in low expression patients (P<0.05). CONCLUSION: Tacrolimus of different formulations had different impact on patients with different CYP3A5 genotypes after kidney transplantation.

Infected Nonhealing Wound in a Kidney Transplant Recipient: Successful Treatment With Topical Homologous Platelet-Rich Gel.

Impaired would healing is a known adverse effect of chronic immunosuppression. Solid-organ transplant recipients undergoing major abdominal surgery have an increased risk of wound-related complications compared with the general population. In this subset of patients, surgical site infections and wound dehiscence must be aggressively treated to avoid sepsis, graft loss, and death. Recently, topical application of platelet-rich plasma has been proposed as an alternative therapeutic option to enhance wound healing in difficult cases. Unfortunately, randomized controlled trials evaluating the efficacy of platelet-rich plasma compared with standard or advanced wound management are lacking, and the literature mostly refers to anecdotal reports in patients with no evidence of wound infection. This report documents a kidney transplant recipient who experienced spontaneous bladder rupture because of gangrenous cystitis. After an exploratory laparotomy and bladder repair, the patient developed a deep surgical site infection by multidrug resistant Acinetobacter baumannii and extensive wound dehiscence. Advanced wound management and vacuum-assisted closure therapy were ineffective. Topical homologous platelet-rich gel was used resulting in significant wound healing, without infections or immunologic complications.

Prognostic Nutritional Index Predicts Short-Term Postoperative Outcomes After Bowel Resection for Crohn's Disease.

BACKGROUND: Bowel resection is required in the majority of patients with Crohn's disease (CD) during their lifetime. The Prognostic Nutritional Index (PNI) is a useful tool for predicting postoperative outcomes in patients undergoing cancer surgery. We examined the ability of the PNI to predict short-term outcomes in patients with CD-related bowel resection. MATERIALS AND METHODS: Seventy-three patients who underwent bowel resection for CD were retrospectively enrolled in the study. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mL). Patients were divided into 2 groups: PNI <40 (n = 30) and PNI ≥40 (n = 43). RESULTS: A significant difference was found in body mass index (17.9 ± 2.4 vs 19.2 ± 2.2, P = .018) between the 2 groups. Postoperative overall and infectious complications occurred more frequently in patients with PNI <40 than in those with PNI ≥40 (50.0% and 46.7% vs 23.3% and 16.3%, P = .018 and P = .005, respectively). In the univariate analysis, body mass index <18.5, penetrating behavior, open surgery, and PNI <40 were associated with an increased risk of overall complications and infectious complications. In the multivariate analysis, only PNI <40 was an independent prognostic factor for infectious complications (odds ratio: 3.846, 95% confidence interval: 1.145-12.821). CONCLUSIONS: Preoperative PNI is a useful predictor of postoperative infectious complications in patients with CD-related bowel resection.

Innate lymphoid cells: a paradigm for low SSI in cleft lip repair.

BACKGROUND: Cleft lip and palate reconstructions demonstrate significantly lower surgical site infection rates compared with clean-contaminated cases, prompting investigation into the pathophysiology causing this discrepancy. Recent studies have identified a new group of innate lymphocytes called innate lymphoid cells (ILCs), located in barrier surfaces of the skin, airways, and intestine. Our objectives were to explore for the first time the presence of ILCs in the vermillion of neonates and young children undergoing cleft lip reconstruction and characterize their composition by measuring the three classes of ILCs. MATERIALS AND METHODS: Lip tissue samples were collected from 13 subjects undergoing vermillion resection during cleft lip reconstructive surgery. Preparative, transmission electron microscopy, and analytical flow cytometry were performed. The functionality of ILCs was tested in terms of their capacity to produce type 1 (IFN-γ/TNF-α), type 2 (IL-5/IL-13), and type 3 (IL-17/IL-22) cytokines. Data were analyzed using Student t test or the analysis of variance to establish significance (P < 0.05) among groups for all other data. RESULTS: All three classes of ILCs were detected and visualized in the tissue samples. In all samples, the level of ILC2 subset was significantly higher than the other two ILC subsets (P < 0.01), followed by the ILC1 subset, which was present in significantly higher levels than the ILC3 subset (P < 0.05). CONCLUSIONS: Our data place ILCs for the first time in the interface of oral mucosal immunity, tissue microenvironment, and homeostasis during and after tissue development, possibly explaining lower infection rates in cleft lip or palate reconstructions.

Incidence of surgical site infection in postoperative patients at a tertiary care centre in India.

OBJECTIVE: A prospective observational was carried out to calculate the incidence of surgical site infections (SSI) along with the main risk factors and causative organisms in postoperative patients at a tertiary care setting in Mumbai. METHOD: A total number of 1196 patients between June 2011 to March 2013 admitted to the general surgical ward or surgical ICU of our hospital were included in the study. Post laproscopy patients and organ space SSIs were excluded. Patient data were collected using a preformed pro forma and a wound Southampton score tabulated and checked repeatedly until suture removal of patient. Regular follow-up was maintained until at least 30 days postoperatively. RESULTS: The study showed a SSI rate of 11%. Risk factors associated with a higher incidence of SSI were found to be age (>55 years), diabetes mellitus (especially uncontrolled sugar in the perioperative period), immunocompromised patients (mainly HIV and immunosuppressive therapy patients), surgeon skill (higher in senior professors compared with junior residents), nature of the cases, (emergency surgeries), placement of drains, wound class (highest in dirty wounds), type of closure (multilayer closure), prolonged duration of hospital stay, longer duration of surgery (>2 hours), type of surgery (highest in cholecystectomy). The highest rates of causative organisms for SSIs found were Staphylococcus aureus, Escherichia coli and Klebsiella ssp. CONCLUSION: Prevention of SSIs requires a multipronged approach with particular emphasis on optimising preoperative issues, adhering religiously to strict protocols during the intraoperative period and addressing and optimising metabolic and nutritional status in postoperative period.

The Significance and Challenges of Monocyte Impairment: For the Ill Patient and the Surgeon.

BACKGROUND: Trauma, major elective surgery, and overt sepsis can lead to a cascade of immunological change. A subset of these patients will have a degree of immune suppression that leads to hyporesponsive innate defenses, increasing the risk of infective co-morbidity and death. This article is an overview of monocyte impairment in the high-risk surgical patient. Specifically, our primary focus is on observations made pertaining to monocyte function and pathophysiological mechanisms underpinning this impairment. Clinical factors influencing monocyte function are also discussed. METHODS: A Pubmed search was conducted to review aspects of monocyte impairment in the surgical patient. Search terms included "monocyte impairment," "immunoparalysis," and "endotoxin tolerance" cross-referenced against terms including "trauma," "major surgery," and "sepsis." RESULTS: Findings revealed a broad variety of monocyte defects reported in surgical patients. They ranged from altered cytokine responses, particularly ex vivo TNF-α production, to impaired antigen presentation such as depressed HLA-DR expression. The latter is the most commonly described marker of secondary infection and death. Studies of underlying mechanisms have commonly utilized a model of endotoxin tolerance with in vitro monocytes, revealing a complex array of dysregulated pathways. For our purposes, endotoxin tolerance and monocyte impairment are sufficiently similar entities to permit further study as a single subject. In the high risk patient, microRNAs (also referred to as miRNA or miR) are emerging as potential biomarkers that may modify such pathways. Creation of a reliable impaired human monocyte model could be important to all such considerations. CONCLUSION: Impairment of monocyte function continues to be predictive of nosocomial infection, multi-organ failure, and death in some surgical patients. However, the optimal marker that could identify a patient as high risk early enough, and whether it might guide potential therapy, still is yet to be proven.

Do smokers have greater risk of delayed and non-union after fracture, osteotomy and arthrodesis? A systematic review with meta-analysis.

OBJECTIVES: Systematic review and meta-analysis of published observational cohort studies. To quantify the increased risk smokers have of experiencing a delayed and/or non-union in fractures, spinal fusion, osteotomy, arthrodesis or established non-unions. SETTING: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Allied and Complementary Medicine Database (AMED) and Web of Science Core Collection from 1966 to 2015. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Observational cohort studies that reported adult smokers and non-smokers with delayed and/or non-union or time to union of the fracture, spinal fusion, osteotomy, arthrodesis or established non-union were eligible. DATA EXTRACTION AND OUTCOME MEASURES: 2 authors screen titles, abstracts and full papers. Data were extracted by 1 author and checked independently by a second. The relative risk ratios of smoking versus non-smoking and the mean difference in time to union patients developing a delayed and/or non-union were calculated. RESULTS: The search identified 3013 articles; of which, 40 studies were included. The meta-analysis of 7516 procedures revealed that smoking is linked to an increased risk of delayed and/or non-union. When considered collectively, smokers have 2.2 (1.9 to 2.6) times the risk of experiencing delayed and/or non-union. In all the subgroups, the increased risk was always ≥1.6 times that of non-smokers. In the patients where union did occur, it was a longer process in the smokers. The data from 923 procedures were included and revealed an increase in time to union of 27.7 days (14.2 to 41.3). CONCLUSIONS: Smokers have twice the risk of experiencing a non-union after fracture, spinal fusion, osteotomy, arthrodesis or treatment of non-union. Time to union following fracture, osteotomy, arthrodesis or treatment of an established non-union is longer in smokers. Smokers should be encouraged to abstain from smoking to improve the outcome of these orthopaedic treatments.