American Burn Association Clinical Practice Guidelines on Burn Shock Resuscitation.

This Clinical Practice Guideline (CPG) addresses the topic of acute fluid resuscitation during the first 48 hours following a burn injury for adults with burns ≥20% of the total body surface area (%TBSA). The listed authors formed an investigation panel and developed clinically relevant PICO (Population, Intervention, Comparator, Outcome) questions. A systematic literature search returned 5978 titles related to this topic and after 3 levels of screening, 24 studies met criteria to address the PICO questions and were critically reviewed. We recommend that clinicians consider the use of human albumin solution, especially in patients with larger burns, to lower resuscitation volumes and improve urine output. We recommend initiating resuscitation based on providing 2 mL/kg/% TBSA burn in order to reduce resuscitation fluid volumes. We recommend selective monitoring of intra-abdominal and intraocular pressure during burn shock resuscitation. We make a weak recommendation for clinicians to consider the use of computer decision support software to guide fluid titration and lower resuscitation fluid volumes. We do not recommend the use of transpulmonary thermodilution-derived variables to guide burn shock resuscitation. We are unable to make any recommendations on the use of high-dose vitamin C (ascorbic acid), fresh frozen plasma (FFP), early continuous renal replacement therapy, or vasopressors as adjuncts during acute burn shock resuscitation. Mortality is an important outcome in burn shock resuscitation, but it was not formally included as a PICO outcome because the available scientific literature is missing studies of sufficient population size and quality to allow us to confidently make recommendations related to the outcome of survival at this time.

Surviving Sepsis After Burn Campaign.

INTRODUCTION: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes. METHODS: The International Society for Burn Injuries (ISBI) reached out to regional or national burn organizations to recommend members to participate in the program. Two members of the ISBI developed specific "patient/population, intervention, comparison and outcome" (PICO) questions that paralleled the 2021 Surviving Sepsis Campaign [1]. SSABC participants were asked to search the current literature and rate its quality for each topic. At the Congress of the ISBI, in Guadalajara, Mexico, August 28, 2022, a majority of the participants met to create "statements" based on the literature. The "summary statements" were then sent to all members for comment with the hope of developing an 80% consensus. After four reviews, a consensus statement for each topic was created or "no consensus" was reported. RESULTS: The committee developed sixty statements within fourteen topics that provide guidance for the early treatment of sepsis in burn patients. These statements should be used to improve the care of sepsis in burn patients. The statements should not be considered as "static" comments but should rather be used as guidelines for future testing of the best treatments for sepsis in burn patients. They should be updated on a regular basis. CONCLUSION: Members of the burn community from the around the world have developed the Surviving Sepsis After Burn Campaign guidelines with the goal of improving the outcome of sepsis in burn patients.

American Burn Association (ABA) Burn Care Quality Platform (BCQP) and Large Data Set Analysis Considerations: A Practical Guide to Investigating Clinical Questions in Burns via Large Data Sets.

The Burn Care Quality Platform (BCQP) consolidates data previously collected from the National Burn Repository and the Burn Quality Improvement Program into a single registry. Its data elements and their associated definitions are tailored to create consistency across other national trauma registries, namely the National Trauma Data Bank implemented by the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP). The BCQP now includes 103 participating burn centers and has captured data from 375,000 total patients as of 2021. With 12,000 patients entered under the current data dictionary, the BCQP represents the largest registry of its kind. On behalf of the American Burn Association Research Committee, the aim of this whitepaper is to provide a succinct overview of the BCQP, showcasing its unique features, strengths, limitations, and relevant statistical considerations. This whitepaper will highlight the resources available to the burn research community and offer insight on proper study design when preparing to conduct a large data set investigation for burn care. All recommendations herein were formulated through the consensus of a multidisciplinary committee and based on the available scientific evidence.

Association Between Health Insurance and Outcomes After Traumatic Brain Injury: A National ACS-TQP-PUF Database Study.

INTRODUCTION: According to the US Census Bureau, roughly 8.6% of the population lacks health care coverage. Increasing evidence suggests that insurance status plays a role in outcomes after trauma. However, its role in the setting of traumatic brain injury (TBI) remains poorly understood. METHODS: The Trauma Quality Programs Participant Use Files were queried from 2017 to 2019. All patients with isolated TBI were identified. Isolated TBI was defined as: 1) Head Abbreviated Injury Scale (AIS) > 3 and 2) AIS <3 in all other anatomical regions. Patients dead on arrival, with Head AIS = 6, or missing key data were excluded. Demographic and clinical information was compared between those with and without insurance. Multivariate regressions were used to assess associations between insurance status and TBI outcomes (inhospital mortality, discharge to facility, total ventilator days, Intensive Care Unit length of stay (ICU LOS), and hospital LOS). RESULTS: In total, 199,556 patients met inclusion criteria; 18,957 (9.5%) were uninsured. Compared to the insured, uninsured TBI patients were younger with a greater proportion of males. Uninsured patients were less severely injured and less comorbid. Uninsured patients had shorter unadjusted LOS in the ICU and hospital. Yet, uninsured patients experienced greater unadjusted inhospital mortality (12.7% versus 8.4%, P < 0.001). When controlling for covariates, lack of insurance was significantly associated with increased likelihood of mortality (OR 1.62; P < 0.001). This effect was most noticeable in patients with Head AIS = 4 (OR 1.55; P < 0.001) and Head AIS = 5 (OR 1.80; P < 0.001). Lack of insurance was also significantly associated with decreased likelihood of discharge to facility (OR 0.38), decreased ICU LOS (Coeff. -0.61), and decreased hospital LOS (Coeff. -0.82; all P < 0.001). CONCLUSIONS: This study demonstrates that insurance status is independently associated with outcome disparities after isolated TBI. Despite the Affordable Care Act (ACA) reform, lack of insurance appears significantly associated with inhospital mortality, decreased likelihood of discharge to facility, and decreased time spent in the ICU and hospital.

Inter-facility transfers for burn patients with concomitant traumatic injuries.

Burn patients with concomitant traumatic injuries suffer increased morbidity and mortality. Complex care coordination is necessary for these patients, and the prevalence of resulting inter-facility transfers has not yet been quantified by literature. This study examined the outcomes for traumatically injured burn patients to identify the occurrence of trauma system transfers in this group. The National Trauma Data Bank was reviewed from the years 2007-2016 for 6,565,577 patients with traumatic, burn, and concomitant burn & traumatic injuries. There were 5068 patients with both traumatic and burn injuries, 145,890 patients with burn injuries, and 6,414,619 patients with traumatic injuries. Trauma/burn patients were more often admitted to the ICU from the ED at a rate of 35.5% compared to 27.1% for burn and 19.4% for trauma (P < 0.001). For disposition when discharged from the hospital, trauma/burn patients required more inter-facility transfers at a rate of 2.5% compared to 1.7% for burn and 1.3% for trauma (P < 0.001). For level I trauma centers, 5.5% of trauma/burn, 7.1% of burn, and 0.5% of trauma patients required inter-facility transfers. For level II trauma centers, 29.1% of trauma/burn, 47.0% of burn, and 2.8% of trauma patients required inter-facility transfers. Among level I and level II trauma centers, patients with only burns and burn patients with concomitant traumatic injuries required more inter-facility transfers, and level II trauma centers required more inter-facility transfers for all patients. Quantifying these findings is the first step toward improving triage decisions and allocation of health care resources while expediting appropriate care.

Burn Shock and Resuscitation: Review and State of the Science.

Burn shock and acute fluid resuscitation continue to spark intense interest and debate among burn clinicians. Following a major burn injury, fluid resuscitation of burn shock is life-saving, but paradoxically can also be a source of increased morbidity and mortality because of the unintended consequence of systemic edema formation. Considerable research over the past two decades has been devoted to understanding the mechanisms of edema formation, and to develop strategies to curb resuscitation fluids and limit edema development. Recognition of burn endotheliopathy - injury to the endothelium's glycocalyx layer- is one of the most important recent developments in our understanding of burn shock pathophysiology. Newer monitoring approaches and resuscitation endpoints, along with alternative resuscitation strategies to crystalloids alone, such as administration of albumin, or plasma, or high dose ascorbic acid, have had mixed results in limiting fluid creep. Clear demonstration of improvements in outcomes with all of these approaches remains elusive. This comprehensive review article on burn shock and acute resuscitation accompanies the American Burn Association's State of the Science meeting held in New Orleans, LA on November 2-3, 2021 and the Proceedings of that conference published in this journal.

The impact of the Affordable Care Act's medicaid expansion on patients admitted for burns: An analysis of national data.

INTRODUCTION: The first states began implementing the Medicaid expansion provisions of the Patient Protection and Affordable Care Act (ACA) in 2014. Studies have yet to address its impact on burn patients. METHODS: Burn patients in geographic regions that expanded Medicaid coverage were compared to patients in regions that did not expand Medicaid before and after implementation of the ACA using bivariate statistics and a difference-in-differences model. A multivariable logistic regression was used to identify factors associated with having Medicaid insurance. The primary outcome of this study was the rate of Medicaid insurance. RESULTS: Of 25,331 discharges, we found greater increases in Medicaid coverage after the ACA in the Medicaid expander regions (23.4-40.2%) compared to the non-expander regions (18.5-20.1%). The difference-in-differences estimate between the expander and non-expander regions was 0.15 (95% CI: 0.11-0.18, p < 0.001). Patients admitted in expander regions were more likely to be insured by Medicaid (OR 1.57 [95%CI 1.21-2.05]), as were patients of Black race (OR 1.25 [95%CI 1.19-1.32), Hispanic ethnicity (OR 1.29 [95%CI 1.14-1.46]), and female sex (OR 1.59 [95%CI 1.11-2.27]). We also found a significant interaction between time period (pre-ACA/post-ACA) and expander region location (OR 2.10 [95%CI 1.67-2.62]). CONCLUSIONS: The Medicaid expansion provision of the ACA led to increased Medicaid coverage among burn patients which was significantly higher in areas with widespread implementation of the expansion.

Outcomes after ultramassive transfusion in the modern era: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era. METHODS: An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality. RESULTS: The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%). CONCLUSION: Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication. LEVEL OF EVIDENCE: Prognostic, level III.

An Assessment of Research Priorities to Dampen the Pendulum Swing of Burn Resuscitation.

On June 17 to 18, 2019, the American Burn Association, in conjunction with Underwriters Laboratories, convened a group of experts on burn resuscitation in Washington, DC. The goal of the meeting was to identify and discuss novel research and strategies to optimize the process of burn resuscitation. Patients who sustain a large thermal injury (involving >20% of the total body surface area [TBSA]) face a sequence of challenges, beginning with burn shock. Over the last century, research has helped elucidate much of the underlying pathophysiology of burn shock, which places multiple organ systems at risk of damage or dysfunction. These studies advanced the understanding of the need for fluids for resuscitation. The resultant practice of judicious and timely infusion of crystalloids has improved mortality after major thermal injury. However, much remains unclear about how to further improve and customize resuscitation practice to limit the morbidities associated with edema and volume overload. Herein, we review the history and pathophysiology of shock following thermal injury, and propose some of the priorities for resuscitation research. Recommendations include: studying the utility of alternative endpoints to resuscitation, reexamining plasma as a primary or adjunctive resuscitation fluid, and applying information about inflammation and endotheliopathy to target the underlying causes of burn shock. Undoubtedly, these future research efforts will require a concerted effort from the burn and research communities.

The end of the assembly line: Shifting patterns of automotive burns.

INTRODUCTION: As recently as 2006, carburetor flash burns comprised as much as 27% of admissions for car-related burns, despite the fact carburetors were last installed in pre-1990 automobiles. The prevalence of this injury pattern is related to the estimated 14 million cars on the road today that were manufactured prior to that year. The aim of this study was to investigate modern sources of automotive burns and describe any new trends in automotive burn-related epidemiology. MATERIALS AND METHODS: A retrospective review was conducted of all burn admissions from the years 2009-2013 to identify patients who suffered automotive-related burns. Pediatric patients (<18 years old) were excluded. Demographic information including age, gender, mechanism of injury, occupation, TBSA, number of operations, and length of hospital stay were recorded. RESULTS: From 2009-2013, the burn center saw 83 admissions for automotive-related burns. 14.5% of patients were mechanics. The most common injury pattern was from radiator burns (47%), followed by gasoline related burns (30%). There were only two carburetor burns (2.4%). 67.4% of patients were treated for less than two hospital days and there was one death (1.2% mortality). CONCLUSION: Despite the removal of carburetors from engines and a decrease in this specific mechanism, a significant morbidity remains with gasoline-inflicted burns. More public awareness is needed for the safe removal of radiator caps and handling of chemicals in overheating engines.

Damage control hip disarticulation: two-stage operation with index creation of a large medial flap for the septic hip.

BACKGROUND: Although rarely performed, hip disarticulation (HD) is usually used for the patient with a non-viable leg who is also in extremis. HD was first used for trauma and infection; however, the technique was perfected during the age of hindquarter amputation for osteosarcomas. The operation performed by most surgeons today is still based on the oncological principles of high vessel control and ligation. When this approach has been used in the overwhelmingly infected or mangled extremity, it has resulted in high mortality rates. During the last 20 years, the concept of damage control operation has been embraced by emergency surgeons in all fields. We sought to extrapolate this concept and to apply it to the non-viable lower extremity. METHODS: We describe a new concept of damage control HD, review the technique and discuss our consecutive series of nine patients who underwent the procedure for trauma or necrotizing infection without flap dehiscence or mortality. RESULTS: All patients survived to hospital discharge. At time of discharge or at follow-up, six of the nine patients were able to transfer to a wheelchair. DISCUSSION: Proper disarticulations for infection need to address these two operative and postoperative issues: damage control debridement with creation of sufficient flap size and thorough postoperative wound care.Level IV.

Association of the Risk of a Venous Thromboembolic Event in Emergency vs Elective General Surgery.

Importance: Trauma patients have an increased risk of venous thromboembolism (VTE), partly because of greater inflammation. However, it is unknown if this association is present in patients who undergo emergency general surgery (EGS). Objectives: To investigate whether emergency case status is independently associated with VTE compared with elective case status and to test the hypothesis that emergency cases would have a higher risk of VTE. Design, Setting, and Participants: This retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program database from January 1, 2005, to December 31, 2016, for all cholecystectomies, ventral hernia repairs (VHRs), and partial colectomies (PCs) to obtain a sample of commonly encountered emergency procedures that have elective counterparts. Emergency surgeries were then compared with elective surgeries. The dates of analysis were January 1 to 31, 2019. Main Outcomes and Measures: The primary outcome was VTE at 30 days. A multivariable analysis controlling for age, sex, body mass index, bleeding disorder, disseminated cancer, laparoscopy approach, and surgery type was performed. Results: There were 604 537 adults undergoing surgical procedures over 12 years (mean [SD] age, 55.3 [16.6] years; 61.4% women), including 285 847 cholecystectomies, 158 500 VHRs, and 160 190 PCs. The rate of VTE within 30 days was 1.9% for EGS and 0.8% for elective surgery, a statistically significant difference. Overall, 4607 patients (0.8%) had deep vein thrombosis, and 2648 patients (0.4%) had pulmonary embolism. A total of 6624 VTEs (1.1%) occurred in the cohort. As expected, when VTE risk was examined by surgery type, the risk increased with invasiveness (0.5% for cholecystectomy, 0.8% for VHR, and 2.4% for PC; P < .001). On multivariable analysis, EGS was independently associated with VTE (odds ratio [OR], 1.70; 95% CI, 1.61-1.79). Also associated with VTE were open surgery (OR, 3.38; 95% CI, 3.15-3.63) and PC (OR, 1.86; 95% CI, 1.73-1.99). Conclusions and Relevance: In this cohort study, emergency surgery and increased invasiveness appeared to be independently associated with VTE compared with elective surgery. Further study on methods to improve VTE chemoprophylaxis is highly recommended for emergency and more extensive operations to reduce the risk of potentially lethal VTE.

Variations of the lung microbiome and immune response in mechanically ventilated surgical patients.

Mechanically ventilated surgical patients have a variety of bacterial flora that are often undetectable by traditional culture methods. The source of infection in many of these patients remains unclear. To address this clinical problem, the microbiome profile and host inflammatory response in bronchoalveolar lavage samples from the surgical intensive care unit were examined relative to clinical pathology diagnoses. The hypothesis was tested that clinical diagnosis of respiratory tract flora were similar to culture positive lavage samples in both microbiome and inflammatory profile. Bronchoalveolar lavage samples were collected in the surgical intensive care unit as standard of care for intubated individuals with a clinical pulmonary infection score of >6 or who were expected to be intubated for >48 hours. Cytokine analysis was conducted with the Bioplex Pro Human Th17 cytokine panel. The microbiome of the samples was sequenced for the 16S rRNA region using the Ion Torrent. Microbiome diversity analysis showed the culture-positive samples had the lowest levels of diversity and culture negative with the highest based upon the Shannon-Wiener index (culture positive: 0.77 ± 0.36, respiratory tract flora: 2.06 ± 0.73, culture negative: 3.97 ± 0.65). Culture-negative samples were not dominated by a single bacterial genera. Lavages classified as respiratory tract flora were more similar to the culture-positive in the microbiome profile. A comparison of cytokine expression between groups showed increased levels of cytokines (IFN-g, IL-17F, IL-1B, IL-31, TNF-a) in culture-positive and respiratory tract flora groups. Culture-positive samples exhibited a more robust immune response and reduced diversity of bacterial genera. Lower cytokine levels in culture-negative samples, despite a greater number of bacterial species, suggest a resident nonpathogenic bacterial community may be indicative of a normal pulmonary environment. Respiratory tract flora samples were most similar to the culture-positive samples and may warrant classification as culture-positive when considering clinical treatment.

Patient Safety Indicators for Judging Hospital Performance.

Patient Safety Indicators (PSIs) were originally intended for use as a screen for quality of care but are now being used to rank hospitals and to modify hospital reimbursement. PSI data are dependent on accuracy of clinical documentation and coding. Information on whether a PSI event is inherent to the nature of the operation or posed a significant impact on the outcome is lacking. Cases for one year at a single academic center were queried. Cases with target PSIs were included (n = 136). Cases were evaluated for both the inherent nature and significance of injury. Both patient safety officers agreed that the PSI event was inherent to the disease process, and thus, the procedure and was not a marker of patient safety (false positive) in 11.8% to 33.3% of cases. Both reviewers agreed that the events were not clinically significant in 11.8% to 30.4% of cases. This study found high false-positive rates and only moderate interrater reliability for 3 PSIs. PSIs as currently reported are not reliable enough to be utilized for ranking.

The effect of tobacco use on outcomes of laparoscopic and open inguinal hernia repairs: a review of the NSQIP dataset.

BACKGROUND: As the effort to reduce postoperative morbidity and mortality continues, the search for modifiable patient risk factors to reduce complications is ongoing. Tobacco use is associated with impaired wound healing, but its effect on inguinal hernia repair has not been studied in a large population. An ACS-NSQIP dataset was used to evaluate the effect of tobacco use on outcomes of inguinal hernia repairs. METHODS: The ACS-NSQIP dataset was queried for patients who underwent open or laparoscopic inguinal hernia repairs, by primary procedure CPT codes, between years 2009-2012. Tobacco use was registered, as defined by the ACS-NSQIP, in two ways: current smoking (within the past 12 months), or history of smoking (having ever smoked). Univariate and multivariate analyses were used to investigate outcome variables for 30-day morbidity by type of smoking status, while adjusting for preoperative risk factors. RESULTS: During the study period, 90,162 patients underwent inguinal hernia repair. 76 % of the cases were open compared to 24 % laparoscopic. The population was overwhelmingly male, 91 %, compared to 9 % female. The average age of patients was 42.5 years. Of the available data (69 % of patients), 38.5 % had a history of smoking. 18 % had smoked within the 12 months prior to surgery (current smokers). Their average number of pack years was 27.2 (SD 24.0) compared to 4.5 pack years (SD 14.7) for those who had not smoked 12 months prior to surgery (historical smokers). Using Fisher's exact test, having ever smoked was found to be significantly associated with pneumonia (p = 0.0008) and return to the operating room (p = 0.010). This relationship held when preoperative variables were controlled for using logistic regression (pneumonia, p = 0.002; return to the operating room, p = 0.002). When preoperative variables were controlled for and logistic regression was performed for current smokers, there was also a significant association with pneumonia (p = 0.005) and return to the operating room (p = 0.01). CONCLUSION: Current smoking status is a modifiable risk of patients undergoing laparoscopic and open inguinal hernia repair. Failure to quit smoking prior to surgical repair is associated with complications like pneumonia and return to the operating room.

The effect of tobacco use on outcomes of laparoscopic and open ventral hernia repairs: a review of the NSQIP dataset.

INTRODUCTION: Tobacco smoking is a known risk factor for complications after major surgical procedures. The full effect of tobacco use on these complications has not been studied over large populations for ventral hernia repairs. This effect is more important as the preoperative conditioning, and optimization of patients is adopted. We sought to use the prospectively collected ACS-NSQIP dataset to evaluate respiratory and infectious complications for patients undergoing both laparoscopic and open ventral hernia repairs. METHODS: The ACS-NSQIP dataset was queried for patients who underwent open or laparoscopic ventral hernia repairs, by primary procedure CPT codes, between years 2009-2012. Smoking use was registered as defined by the ACS-NSQIP, as both a current smoker (within the prior 12 months) or as a history of smoking (having ever smoked). Univariate and multivariate analyses were used to investigate postoperative complications for 30-day morbidity and mortality by smoking status while adjusting for preoperative risk factors. RESULTS: The majority of cases were open, 82 %, compared to laparoscopic 18 %. Sex was evenly distributed with 58 % female and 42 % male; however, there was a difference in the distribution of current smokers (p = 0.03). On analysis there were significantly more respiratory complications (p = 0.0003) and infectious complications (p < 0.0001). When controlling for sex, age, and type of surgery, using logistic regression, there were associations between smoking in the prior 12 months and respiratory complications, including pneumonia (p < 0.0001), and re-intubation (p < 0.0001). Similar associations were seen on logistic regression if a patient ever smoked; including pneumonia (p < 0.0001), re-intubation (p < 0.0001), and failure to wean (p < 0.0001). CONCLUSION: Smoking tobacco, both current and historical use, leads to an increase in both respiratory and infectious complications. As more centers try to preoperatively condition patients for elective hernia repairs, it is important to note that patients may never return to the baseline outcomes of patients who never smoked.

Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death.

In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1). Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer.

OBJECTIVE: There are little clinical data assessing the antineoplastic effect of metformin in patients with non-small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non-small cell lung cancer, metformin exposure is associated with improved survival. METHODS: An institutional database was used to identify patients with stage I or II non-small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. RESULTS: A total of 215 patients with stage I and II non-small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. CONCLUSIONS: Metformin exposure in diabetic patients with early-stage non-small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic role for metformin in the treatment of non-small cell lung cancer.

Primary Anastomosis versus Ostomy after Colon Resection during Debulking of Ovarian Carcinomatosis: A NSQIP Analysis.

Ovarian carcinomatosis poses a dilemma for the surgeon. When resecting colon for tumor invasion, one must decide between diversion and primary anastomosis (PA). We examined the National Surgical Quality Improvement Program to determine whether PA associated with more complications than ostomy. The National Surgical Quality Improvement Program dataset was queried for patients with ovarian carcinomatosis between 2007 and 2012. Current Procedural Terminology codes were used to further identify patients undergoing colectomy with PA or ostomy. Logistic regression was used to evaluate 30-day morbidity and mortality. The 1013 ovarian carcinomatosis patients who underwent elective colon surgery were divided into primary repair (n = 453, 43.5%) or ostomy (n = 586, 56.5%) groups. Preoperative demographics were similar; however, ostomy patients had more severe preoperative laboratory derangements. The 30-day mortality and postoperative transfusion requirements were higher in the ostomy group. On multivariate analysis controlling for confounders, the differences were no longer significant. In conclusion, 30-day mortality and postoperative complications were increased in the ostomy group. Given the laboratory derangements in this group, this may reflect tendency to allocate ostomies to more ill patients. Primary repair in a selected population does not worsen outcomes. Prospective evaluation would help determine the impact of PA in the ovarian carcinomatosis population.

Angiogenesis Biomarkers May Be Useful in the Management of Patients With Indeterminate Pulmonary Nodules.

BACKGROUND: Low-dose computed tomography (CT) lung cancer screening is known to have a high false positive rate. This study aims to survey biomarkers of angiogenesis for those capable of assigning clinical significance to indeterminate pulmonary nodules detected through CT imaging studies. METHODS: An institutional database and specimen repository was used to identify 193 patients with stage I non-small cell lung cancer (T1N0M0) and 110 patients with benign solitary pulmonary nodules detected by CT imaging studies. All specimens were evaluated in a blinded manner for 17 biomarkers of angiogenesis using multiplex immunoassays. Biomarker performance was calculated through the Mann-Whitney rank sum U test and a receiver operator characteristic analysis. These data were used to refine our previously reported multi-analyte classification panel, which was then externally validated against an independent patient cohort (n = 80). RESULTS: A total of 303 patients were screened for 17 biomarkers of angiogenesis. Median nodule size was 1.2 cm for benign cases and 1.8 cm for non-small cell lung cancer, whereas median smoking histories were 25 and 40 pack-years, respectively. Differences in serum concentrations of heparin-binding epidermal growth factor (HB-EGF), epidermal growth factor (EGF), vascular (V)EGF-A, VEGF-C, and VEGF-D were strongly significant (p ≤ 0.001) while follistatin, placental growth factor (PLGF), and bone morphogenic protein (BMP)-9 were significant (p ≤ 0.05) between patients with benign and malignant nodules. Our previously reported multi-analyte classification panel was refined to include interleukin (IL)-6, IL-10, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF)-α, insulin-like growth factor binding protein (IGFBP)-5, IGFBP-4, IGF-2, stromal cell-derived factor (SDF)-1(α+ß), HB-EGF, and HGF resulting in improved accuracy and a validated negative predictive value of 96.4%. CONCLUSIONS: Angiogenesis biomarkers may be useful in discriminating stage I NSCLC from benign pulmonary nodules.