Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.

BACKGROUND & AIMS: While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. METHODS: Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-ß, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. RESULTS: In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. CONCLUSION: Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.

Factors affecting mortality after penetrating cardiac injuries: 10-year experience at urban level I trauma center.

BACKGROUND: Despite the lethality of injuries to the heart, optimizing factors that impact mortality for victims that do survive to reach the hospital is critical. METHODS: From 2003 to 2012, prehospital data, injury characteristics, and clinical patient factors were analyzed for victims with penetrating cardiac injuries (PCIs) at an urban, level I trauma center. RESULTS: Over the 10-year study, 80 PCI patients survived to reach the hospital. Of the 21 factors analyzed, prehospital cardiopulmonary resuscitation (odds ratio [OR] = 30), scene time greater than 10 minutes (OR = 58), resuscitative thoracotomy (OR = 19), and massive left hemothorax (OR = 15) had the greatest impact on mortality. Cardiac tamponade physiology demonstrated a "protective" effect for survivors to the hospital (OR = .08). CONCLUSIONS: Trauma surgeons can improve mortality after PCI by minimizing time to the operating room for early control of hemorrhage. In PCI patients, tamponade may provide a physiologic advantage (lower mortality) compared to exsanguination.

Reassessing the cardiac box: A comprehensive evaluation of the relationship between thoracic gunshot wounds and cardiac injury.

BACKGROUND: High-energy missiles can cause cardiac injury regardless of entrance site. This study assesses the adequacy of the anatomic borders of the current "cardiac box" to predict cardiac injury. METHODS: Retrospective autopsy review was performed to identify patients with penetrating torso gunshot wounds (GSWs) 2011 to 2013. Using a circumferential grid system around the thorax, logistic regression analysis was performed to detect differences in rates of cardiac injury from entrance/exit wounds in the "cardiac box" versus the same for entrance/exit wounds outside the box. Analysis was repeated to identify regions to compare risk of cardiac injury between the current cardiac box and other regions of the thorax. RESULTS: Over the study period, 263 patients (89% men; mean age, 34 years; median injuries/person, 2) sustained 735 wounds (80% GSWs), and 239 patients with 620 GSWs were identified for study. Of these, 95 (34%) injured the heart. Of the 257 GSWs entering the cardiac box, 31% caused cardiac injury, whereas 21% GSWs outside the cardiac box (n = 67) penetrated the heart, suggesting that the current "cardiac box" is a poor predictor of cardiac injury relative to the thoracic non-"cardiac box" regions (relative risk [RR], 0.96; p = 0.82). The regions from the anterior to posterior midline of the left thorax provided the highest positive predictive value (41%) with high sensitivity (90%) while minimizing false-positives, making this region the most statistically significant discriminator of cardiac injury (RR, 2.9; p = 0.01). CONCLUSION: For GSWs, the current cardiac box is inadequate to discriminate whether a GSW will cause a cardiac injury. As expected, entrance wounds nearest to the heart are the most likely to result in cardiac injury, but, from a clinical standpoint, it is best to think outside the "box" for GSWs to the thorax. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Penetrating cardiac injuries: A 36-year perspective at an urban, Level I trauma center.

BACKGROUND: This study evaluates patterns of injuries and outcomes from penetrating cardiac injuries (PCIs) at Grady Memorial Hospital, an urban, Level I trauma center in Atlanta, Georgia, over 36 years. METHODS: Patients sustaining PCIs were identified from the Trauma Registry of the American College of Surgeons and the Emory Department of Surgery database; data of patients who died prior to any therapy were excluded. Demographics and outcomes were compared over three time intervals: Period 1 (1975-1985; n = 113), Period 2 (1986-1996; n = 79), and Period 3 (2000-2010; n = 79). RESULTS: Two hundred seventy-one patients (86% were male; mean age, 33 years; initial base deficit = -11.3 mEq/L) sustained cardiac stab (SW, 60%) or gunshot wounds (GSW, 40%). Emergency department thoracotomy was performed in 67 (25%) of 271 patients. Overall mortality increased in the modern era (Period 1, 27%, vs. Period 2, 22%, vs. Period 3, 42%; p = 0.03) along with GSW mechanisms (Period 1, 32%, vs. Period 2, 33%, vs. Period 3, 57%; p = 0.001), GSW mortality (Period 1, 36%, vs. Period 2, 42%, vs. Period 3, 56%; p = 0.04), and multichamber injuries (Period 1, 12%, vs. Period 2, 10%, vs. Period 3, 34%; p< 0.001). In Period 3, GSWs (n = 45) resulted in multichamber injuries in 28 patients (62%) and multicavity injuries in 19 patients (42%). Surgeon-performed ultrasound accurately identified pericardial blood in 55 of 55 patients in Period 3. CONCLUSIONS: Increased frequency of GSWs in the past decade is associated with increased overall mortality, multichamber injuries, and multicavity injuries. Ultrasound is sensitive for detection of PCI. LEVEL OF EVIDENCE: Therapeutic study, level IV; epidemioligc study, level III.

Risk factors for rising incidence of esophageal and gastric cardia adenocarcinoma.

INTRODUCTION: In the last 30 years, the incidence of esophageal and gastric cardia adenocarcinoma has steadily increased. The increase in incidence is approximately seven-fold, which is a more substantial increase than that of several malignancies, including melanoma, breast cancer, and prostate cancer. DISCUSSION: The rising incidence has led to a steady increase in mortality from 2 to 15 deaths per 100,000 in the last three decades. The etiologic factors involved in the development of these malignancies include gastroesophageal reflux disease, Barrett's esophagus, acid-suppressive medication use, obesity, and tobacco use. This article discusses the contribution of these etiologic risk factors to this increase in incidence.