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.
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-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract 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 2003-2012, ...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 CPR (OR= 30), scene time > 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 = 0.08). Conclusion 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.
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.
...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).
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.
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.
Therapeutic study, level IV; epidemioligc study, level III.
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.
Background Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; ...adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.
Anorexia nervosa (AN) is characterized by severe dietary restriction or other weight loss behaviors and exhibits the highest mortality rate of any psychiatric disorder. Therapeutic renourishment in ...AN is founded primarily on clinical opinion and guidelines, with a weak evidence base. Genetic factors do not fully account for the etiology of AN, and non-genetic factors that contribute to the onset and persistence of this disease warrant investigation. Compelling evidence that the intestinal microbiota regulates adiposity and metabolism, and more recently, anxiety behavior, provides a strong rationale for exploring the role of this complex microbial community in the onset, maintenance of, and recovery from AN. This review explores the relationship between the intestinal microbiota and AN and a potential role for this enteric microbial community as a therapy for this severe illness.
Endothelial progenitor cells play an important role in neovascularization of ischemic flaps, a process that is significantly impaired in diabetes. This is the first investigation into the effects of ...flap ischemia on circulating and bone marrow-derived endothelial progenitor cells. Potential mechanisms for impaired vasculogenesis in diabetes are also investigated.
Circulating and bone marrow-derived endothelial progenitor cells were isolated from wild-type (n = 24) and diabetic mice (n = 24) with ischemic flaps (days 0, 1, 3, and 7). The number and vasculogenic function of primitive and definitive endothelial progenitor cells were determined by fluorescence-activated cell sorting analysis, culture assay, and vasculogenic colony-forming assay.
Ischemia mobilized endothelial progenitor cells (25 +/- 0.5 cells per high-power field at day 7 versus 9.0 +/- 0.6 cells per high-power field, p < 0.01) and enhanced the vasculogenic potential of circulating primitive endothelial progenitor cells (23 +/- 3.2 at day 3 versus 14 +/- 0.8, p < 0.01) relative to baseline. In the bone marrow, endothelial progenitor cell number and vasculogenic potential peaked at day 3 (2.1 +/- 0.3 x 10(5) cells versus 1.3 +/- 0.1 x 10(5) cells, p < 0.05; 36 +/- 1.9 versus 27 +/- 1.6, p < 0.05, respectively). In diabetes, circulating endothelial progenitor cell mobilization (5.8 +/- 0.4 cells per high-power field versus 9.0 +/- 0.6 cells per high-power field, p < 0.01) and vasculogenic potential (36 +/- 1.7 versus 43 +/- 2.6, p < 0.05) were impaired relative to the wild-type animals. Bone marrow-derived endothelial progenitor cell number was normal in diabetic animals, but the vasculogenic potential of these cells was significantly impaired (5.7 +/- 0.8 day 1 versus 13.4 +/- 2.5, p < 0.05).
Flap ischemia induces phenotypic changes in bone marrow-derived endothelial progenitor cells that subsequently traffic through the circulation. The vasculogenic potential of endothelial progenitor cells at various stages of differentiation is impaired in diabetes and thus may account for impaired ischemia-induced vasculogenesis observed clinically.
The costs of cancer care in the US continue to increase and may have serious consequences for patients. We hypothesize that even cancer patients treated with curative-intent surgery alone experience ...substantial financial burden.
A questionnaire was administered to adult cancer patients who were treated with curative-intent surgery. Survey items included a validated instrument for measuring financial toxicity, the COST score. Demographic variables and survey responses were examined using Chi-square and Fisher exact tests. A multivariate general linear model was performed to examine the relationship between age and COST score.
COST scores varied widely. 30% of respondents had a COST score of ≤24 (high burden). Younger participants reported more financial burden (p = 0.008). Respondents reported that financial factors influenced their decisions regarding surgery (14%) and caused them to skip recommended care (4.7%). Cancer care influenced overall financial health (38%) and contributed to medical debt (26%).
Curative-intent cancer care places a substantial portion of patients at risk for financial toxicity even when they don't require chemotherapy. Interventions should not be limited to patients receiving chemotherapy.
•Financial toxicity is common, even amongst patients who do not require chemotherapy.•Costs of care influence surgical decision making for some cancer patients.•Younger patients with curative intent surgery are at higher risk for financial toxicity.•One fifth of respondents indicated they wished they had known more about the costs prior to surgery.
Abstract Introduction Learning procedural skills as a medical student has evolved, as task trainers and simulators are now ubiquitous. It is yet unclear whether they have supplanted bedside teaching ...or are adjuncts to it, and whether faculty or residents are responsible for student skills education in this era. In this study we sought to characterize the experience and opinions of both medical students and faculty on procedural skills training. Methods Surveys were sent to clinical medical students and faculty at UNC Chapel Hill. Opinions on the ideal learning environment for basic procedural skills, as well as who serves as primary teacher, were gathered using a 4-point Likert scale. Responses were compared via Fisher exact test. Results A total of 237 students and 279 faculty responded. Third-year students were more likely to report simulation as the primary method of education (64%), compared to either fourth-year students (35%; P < 0.0001) or faculty (43%; P = 0.0018). Third- and fourth-year students were also more likely to report interns as a primary teacher (15% and 10%, respectively) as opposed to faculty (2%), and less likely to suggest faculty were the primary teacher (30% and 21%, respectively, versus 35%), P < 0.0001. Residents were the primary teachers for all three groups (55%, 70%, and 63% respectively). Conclusions Our data suggest that both medical students and faculty recognize the utility of simulation in procedural skills training, but vary in the degree to which they think simulation is or should be the primary instructional tool. Both groups suggest residents are the primary teacher of these skills.
An open book pelvis fracture with 5 cm displacement of the right hemipelvis was noted on pelvis X-ray (Fig. 1). Because the patient was hypotensive with a positive FAST and pulseless extremity, he ...was immediately transferred to the operating room. ...THP is associated with a high energy mechanism causing significant damage to softtissues, nerves, and vasculature.
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