Hyperglycemic Hyperosmolar State During Induction Chemotherapy for Acute Lymphoblastic Leukemia.

We present the case of a 16-year-old boy who presented with fatigue, polyuria, and polydipsia while on chemotherapy for his relapsed acute lymphoblastic leukemia (ALL). Blood gas examination confirmed the diagnosis of hyperosmolar hyperglycemic state. The etiology for his hyperglycemia was most likely a result of oral glucocorticoid therapy combined with asparaginase therapy-both are a cornerstone of induction chemotherapy for ALL. The patient was aggressively rehydrated with saline, and medications were administered to correct his hyperkalemia. He was then slowly brought to euglycemia with a continuous infusion of insulin. Although hyperosmolar hyperglycemic state is rare during the treatment of ALL, frontline providers should be aware of this diagnosis because of the significant risk of hypovolemic shock and death if correction of hyperglycemia occurs prior to complete fluid resuscitation.

Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays.

BACKGROUND: Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA). METHODS: This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival. RESULTS: One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2-11), TEG: 4.5 (2-8)] (P = 0.317), but more plasma units [CCA: 2.0 (0-4), TEG: 0.0 (0-3)] (P = 0.022), and more platelets units [CCA: 0.0 (0-1), TEG: 0.0 (0-0)] (P = 0.041) in the first 2 hours of resuscitation. CONCLUSIONS: Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: cancer and Leukemia Group B study 10 002.

To improve long-term outcomes for Burkitt leukaemia/lymphoma (BL) or aggressive lymphomas in adults, we assessed the benefit of adding rituximab and filgrastim support to a dose-dense modified chemotherapy regimen from the Cancer and Leukemia Group B (CALGB) 9251 trial. One hundred and five patients (aged 19-79 years) were enrolled; 27% were >60 years old; 47% had high or high-intermediate risk by International Prognostic Index (IPI) criteria. Common severe toxicities included stomatitis/upper gastrointestinal toxicity (69%), renal insufficiency (10%), neurological events (25%) and pulmonary events (18%). Seven died from treatment-related causes (one central nervous system bleed, four infections, two respiratory failure); five were >60 years old. Results in this adult population are encouraging as complete response (CR) was observed in 83% and 4-year event-free (EFS) and overall survivals (OS) were 74% and 78%, respectively. Results compare favourably to our prior chemotherapy alone study (CALGB 9251) but despite this, high-risk patients still had worse outcomes. In conclusion, short duration, intensive chemo-immunotherapy is feasible and should be considered in adults with BL as it results in high remission rates and durable remissions.

Inter-Hospital Transfer Is an Independent Risk Factor for Hospital-Associated Infection.

Background: Regionalization of surgical care shifts higher acuity patients to larger centers. Hospital-associated infections (HAIs) are important quality measures with financial implications. In our ongoing efforts to eliminate HAIs, we examined the potential role for inter-hospital transfer in our cases of HAI across a multihospital system. Hypothesis: Surgical patients transferred to a regional multihospital system have a higher risk of National Healthcare Safety Network (NHSN)-labeled HAIs. Patients and Methods: The analysis cohort of adult surgical inpatients was filtered from a five-hospital health system administration registry containing encounters from 2014 to 2021. The dataset contained demographics, health characteristics, and acuity variables, along with the NHSN defined HAIs of central line-associated blood stream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), and Clostridioides difficile infection (CDI). Univariable and multivariable statistics were performed. Results: The surgical cohort identified 92,832 patients of whom 3,232 (3.5%) were transfers. The overall HAI rate was 0.6% (528): 86 (0.09%) CLABSI, 133 (0.14%) CAUTI, and 325 (0.35%) CDI. Across the three HAIs, the rate was higher in transfer patients compared with non-transfer patients (CLABSI: n = 18 (1.3%); odds ratio [OR], 4.79; CAUTI: n = 25 (1.8%); OR, 4.20; CDI: n = 37 (1.1%); OR, 3.59); p < 0.001 for all. Multivariable analysis found transfer patients had an increased rate of HAIs (OR, 1.56; p < 0.001). Conclusions: There is an increased risk-adjusted rate of HAIs in transferred surgical patients as reflected in the NHSN metrics. This phenomenon places a burden on regional centers that accept high-risk surgical transfers, in part because of the downstream effects of healthcare reimbursement programs.

Markers of Futile Resuscitation in Traumatic Hemorrhage: A Review of the Evidence and a Proposal for Futility Time-Outs during Massive Transfusion.

The reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility.

A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701.

BACKGROUND: Rituximab combined with chemotherapy has improved the survival of previously untreated patients with follicular lymphoma (FL). Nevertheless, many patients neither want nor can tolerate chemotherapy, leading to interest in biological approaches. Epratuzumab is a humanized anti-CD22 monoclonal antibody with efficacy in relapsed FL. Because both rituximab and epratuzumab have single-agent activity in FL, the antibody combination was evaluated as initial treatment of patients with FL. METHODS: Fifty-nine untreated patients with FL received epratuzumab 360 mg/m2 with rituximab 375 mg/m2 weekly for 4 induction doses. This combination was continued as extended induction in weeks 12, 20, 28, and 36. Response assessed by computed tomography was correlated with clinical risk factors, [18F]fluorodeoxyglucose positron emission tomography findings at week 3, Fcγ polymorphisms, immunohistochemical markers, and statin use. RESULTS: Therapy was well-tolerated, with toxicities similar to expected with rituximab monotherapy. Fifty-two (88.2%) evaluable patients responded, including 25 complete responses (42.4%) and 27 partial responses (45.8%). At 3 years follow-up, 60% of patients remain in remission. Follicular Lymphoma International Prognostic Index (FLIPI) risk strongly predicted progression-free survival (P = .022). CONCLUSIONS: The high response rate and prolonged time to progression observed with this antibody combination are comparable to those observed after standard chemoimmunotherapies and further support the development of biologic, nonchemotherapeutic approaches for these patients.

Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: results of Cancer and Leukemia Group B Study 19802.

BACKGROUND: Cancer and Leukemia Group B (CALGB) Study 19802, a phase 2 study, evaluated whether dose intensification of daunorubicin and cytarabine could improve disease-free survival (DFS) in adults with acute lymphoblastic leukemia (ALL) and whether high-dose systemic and intrathecal methotrexate could replace cranial radiotherapy for central nervous system (CNS) prophylaxis. METHODS: One hundred sixty-one eligible, previously untreated patients ages 16 to 82 years (median age, 40 years) were enrolled, and 33 (20%) were aged ≥60 years. RESULTS: One hundred twenty-eight patients (80%) achieved complete remission (CR). Dose intensification of daunorubicin and cytarabine was feasible. At a median follow-up of 10.4 years for surviving patients, the 5-year DFS rate was 25% (95% confidence interval, 18%-33%), and the overall survival (OS) rate was 30% (95% confidence interval, 23%-37%). Patients aged <60 years who received the 80 mg/m(2) dose of daunorubicin had a DFS of 33% (95% confidence interval, 22%-44%) and an OS of 39% (95% confidence interval, 29%-49%) at 5 years. Eighty-four patients (52%) relapsed, including 9 patients (6%) who had isolated CNS relapses. The omission of cranial irradiation did not result in higher than historic CNS relapse rates. CONCLUSIONS: Intensive systemic, oral, and intrathecal methotrexate dosing permitted the omission of CNS irradiation in adult patients with ALL. This intensive approach using higher doses of daunorubicin and cytarabine failed to result in an overall improvement in DFS or OS compared with historic CALGB studies. Future therapeutic strategies for adults with ALL should be tailored to specific age and molecular genetic subsets.

Doxorubicin, vinblastine, and gemcitabine (CALGB 50203) for stage I/II nonbulky Hodgkin lymphoma: pretreatment prognostic factors and interim PET.

To reduce doxorubicin, bleomycin, vinblastine and dacarbazine toxicity, the Cancer and Leukemia Group B conducted a phase 2 trial of doxorubicin, vinblastine, and gemcitabine for newly diagnosed, nonbulky stages I and II Hodgkin lymphoma. Ninety-nine assessable patients received 6 cycles of doxorubicin 25 mg/m(2), vinblastine 6 mg/m(2), and gemcitabine 800 mg/m(2) (1000 mg/m(2) in first 6) on days 1 and 15 every 28 days. Computed tomography (CT) and positron emission tomography (PET) were performed before and after 2 and 6 cycles. Complete remission (CR)/CR unconfirmed was achieved in 72 of 99 patients (72.7%) and partial remission in 24 of 99 patients (24.2%). The CR rate was 81% when using PET criteria. Two patients have died of Hodgkin lymphoma progression. Median follow-up for nonprogressing patients is 3.3 years. The progression-free survival (PFS) at 3 years was 77% (95% confidence interval, 68%-84%). The relapse rate was less than 10% for patients with favorable prognostic factors. The 2-year PFS for cycle 2 PET-negative and -positive patients was 88% and 54%, respectively (P = .0009), compared with 89% and 27% for cycle 6 PET-negative and -positive patients (P = .0001). Although the CR rate and PFS were lower than anticipated, patients with favorable prognostic features had a low rate of relapse. Cycle 2 PET and cycle 6 PET were predictive of PFS.

Benchmarking outcomes in the critically injured trauma patient and the effect of implementing standard operating procedures.

OBJECTIVE: To determine and compare outcomes with accepted benchmarks in trauma care at 7 academic level I trauma centers in which patients were treated on the basis of a series of standard operating procedures (SOPs). BACKGROUND: Injury remains the leading cause of death for those younger than 45 years. This study describes the baseline patient characteristics and well-defined outcomes of persons hospitalized in the United States for severe blunt trauma. METHODS: We followed 1637 trauma patients from 2003 to 2009 up to 28 hospital days using SOPs developed at the onset of the study. An extensive database on patient and injury characteristics, clinical treatment, and outcomes was created. These data were compared with existing trauma benchmarks. RESULTS: The study patients were critically injured and were in shock. SOP compliance improved 10% to 40% during the study period. Multiple organ failure and mortality rates were 34.8% and 16.7%, respectively. Time to recovery, defined as the time until the patient was free of organ failure for at least 2 consecutive days, was developed as a new outcome measure. There was a reduction in mortality rate in the cohort during the study that cannot be explained by changes in the patient population. CONCLUSIONS: This study provides the current benchmark and the overall positive effect of implementing SOPs for severely injured patients. Over the course of the study, there were improvements in morbidity and mortality rates and increasing compliance with SOPs. Mortality was surprisingly low, given the degree of injury, and improved over the duration of the study, which correlated with improved SOP compliance.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909.

BACKGROUND: In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. DESIGN AND METHODS: Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. RESULTS: Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. CONCLUSIONS: Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma.

Initial experiences with point-of-care rapid thrombelastography for management of life-threatening postinjury coagulopathy.

BACKGROUND: Massive transfusion (MTP) protocol design is hindered by lack of accurate assessment of coagulation. Rapid thrombelastography (r-TEG) provides point-of-care (POC) analysis of clot formation. We designed a prospective study to test the hypothesis that integrating TEG into our MTP would facilitate goal-directed therapy and provide equivalent outcomes compared to conventional coagulation testing. STUDY DESIGN AND METHODS: Thiry-four patients who received more than 6 units of red blood cells (RBCs)/6 hours who were admitted to our Level 1 trauma center after r-TEG implementation (TEG) were compared to 34 patients admitted prior to TEG implementation (Pre-TEG). Data are presented as mean±SEM. RESULTS: Emergency department pre-TEG versus TEG shock, and coagulation indices, were not different: systolic blood pressure (94 mmHg vs. 101 mmHg), temperature (35.3°C vs. 35.9°C), pH (7.16 vs. 7.11), base deficit (-13.0 vs. -14.7), lactate (6.5 vs. 8.1), international normalized ratio (INR; 1.59 vs. 1.83), and partial thromboplastin time (48.3 vs. 57.9). Although not significant, patients with Injury Severity Score range 26 to 35 were more frequent in the pre-TEG group. Fresh-frozen plasma (FFP):RBCs, platelets:RBCs, and cryoprecipitate (cryo):RBC ratios were not significantly different at 6 or 12 hours. INR at 6 hours did not discriminate between survivors and nonsurvivors (p=0.10), whereas r-TEG "G" value was significantly associated with survival (p=0.03), as was the maximum rate of thrombin generation (MRTG; mm/min) and total thrombin generation (TG; area under the curve) (p=0.03 for both). Patients with MRTG of more than 9.2 received significantly less components of RBCs, FFP, and cryo (p=0.048, p=0.03, and p=0.04, respectively). CONCLUSION: Goal-directed resuscitation via r-TEG appears useful for management of trauma-induced coagulopathy. Further experience with POC monitoring could result in more efficient management leading to a reduction of transfusion requirements.

Effect of damage control surgery on major abdominal vascular trauma.

BACKGROUND: In 1982, we reported our experience with abdominal vascular trauma, highlighting the critical role of hypothermia, acidosis, and coagulopathy. Damage control surgery was subsequently introduced to address this "lethal triad." The purpose of the present study was to evaluate the outcomes from our most recent 6-year experience compared with a cohort from 30 years ago. METHODS: Patients with major abdominal vascular injuries were examined, and the most recent 6-year period was compared with archived data from a similar 6-year period three decades ago. RESULTS: The number of patients with major abdominal vascular injuries decreased from 123 patients in 1975 to 1980 to 64 patients in 2004 to 2009. The mean initial pH decreased from 7.21 to 6.96 (1975 to 1980 versus 2004 to 2009) for patients with overt coagulopathy. Despite increasingly protracted acidosis, mortality attributable to refractory coagulopathy decreased from 46% to 19% (1975 to 1980 versus 2004 to 2009, chi-square = 4.36, P = 0.04). No significant difference was found in mortality from exsanguinating injuries (43% versus 62%, 1975 to 1980 versus 2004 to 2009, chi-square = 1.96, P = 0.16). The prehospital transport times were unchanged (22 versus 20 min, 1975 to 1980 versus 2004 to 2009). Despite the administration of additional clotting factors and the advent of damage control surgery, the overall mortality remained largely unchanged (37% versus 33%, 1975 to 1980 versus 2004 to 2009, chi-square = 0.385, P = 0.53). CONCLUSIONS: The adoption of damage control surgery, including the implementation of a massive transfusion protocol, was associated with a reduction in mortality for abdominal vascular injuries due to coagulopathy; however, patients have continued to die of exsanguination.

Leiomyosarcoma of the somatic soft tissues.

Leiomyosarcomas of the somatic soft tissues are tumors of smooth muscle origin that occur in the extremities. These lesions are commonly high-grade tumors that carry a poor prognosis. Recommended treatment often includes wide excision and chemotherapy or radiation therapy. Sixty-five patients were followed for a mean of 4.1 years. The mean maximum tumor diameter was 7 cm, and approximately 70% of all patients had tumors deep to fascia. Including all stages of disease, the overall 1-, 2-, and 5-year survival rates were 91%, 87%, and 68%, respectively. Mitotic rate and tumor depth were significant predictors of development of recurrent disease and metastatic disease. Tumor size was another predictor of recurrent disease. The mitotic rate and AJCC stage were also important predictors of overall survival. Patients with deep lesions, histologic grade 3 disease/higher mitotic rates, and advanced stage of disease had a poorer prognosis and thus were more likely to undergo adjuvant chemotherapy. Future clinical studies may help determine if knowledge of these predictors can help guide treatment and improve clinical outcomes.

Reduced-intensity conditioning allogeneic hematopoietic cell transplantation for patients with hematologic malignancies who relapse following autologous transplantation: a multi-institutional prospective study from the Cancer and Leukemia Group B (CALGB trial 100002).

We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic HCT (allo-HCT) using a reduced-intensity conditioning regimen of fludarabine 150 mg/m(2) plus intravenous busulfan 6.4 mg/kg. Both matched sibling (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD donors received more intensive graft-versus-host disease (GVHD) prophylaxis, including rabbit antithymocyte globulin (ATG) 10 mg/kg, mycophenolate mofetil, and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9-5.8), treatment-related mortality (TRM) at 6 months and 2 years was 8% and 23%, respectively. Neither TRM nor the rates of acute GVHD (aGVHD) were different in those with sibling or MUD donors. Donor CD3 cell chimerism >90% at day +30 was achieved more often in patients with MUD than with matched sibling donors, 70% versus 23% (P < .0001). Median event-free suvival was higher in patients who achieved early full donor chimerism (14.2 versus 8 months, P = .0395). Allo-HCT using this reduced-intensity conditioning regimen can be performed with low TRM in patients who have received a prior AHCT. Efforts to improve early donor CD3 chimerism may improve event-free survival.

Refractory postinjury thrombocytopenia is associated with multiple organ failure and adverse outcomes.

BACKGROUND: Postinjury multiple organ failure (MOF) remains the leading cause of morbidity and late mortality after severe trauma. Our previous work consistently identified an association between thrombocytopenia and progression to MOF. In addition, recent studies suggest that platelets play a critical role in postinjury hyperinflammation. Therefore, we hypothesized that postinjury thrombocytopenia is a marker for progression to MOF. METHODS: One thousand four hundred fifteen critically injured surgical intensive care unit patients surviving>48 hours were prospectively collected over 12 years. Variables studied included age, Injury Severity Score (ISS), red blood cell (RBC)/12 h, MOF (Denver MOF score), death, infectious complications, and noninfectious complications. Thrombocytopenia was defined as platelets<80k. Logistic regression was applied to identify independent predictors of MOF and death. RESULTS: Mean±standard error of the mean ISS, age, and RBC were 29.3±11.3; 37.4 years±16.6 years; and 4.4 units±5 units. MOF developed in 346 patients (24%) and 118 patients (8%) died. Thrombocytopenia occurred in 35% of patients within 48-hour postinjury and was associated with a significant increase in ISS, RBC transfused, and age. Logistic regression confirmed that thrombocytopenia was a major independent risk factor for all adverse outcomes with an odds ratio of 2.4 for developing MOF and 3.4 for death. After adjustment for these factors, a relative increase in platelet count from day 3 to day 10 was associated with a significantly lower likelihood of MOF and death. CONCLUSION: Early postinjury thrombocytopenia is an independent risk factor for MOF, death, and other complications. Following platelet count dynamics over the first several days postinjury can help predict which high-risk patient will develop these adverse outcomes.

Shifts in Attitudes and Intentions to Practice Following Medication-Assisted Treatment Training.

PURPOSE: The Idaho State University Physician Assistant (PA) program was one of the first PA programs in the country to incorporate medication-assisted treatment (MAT) into its curriculum. This manuscript documents the impact of the course. METHODS: In the spring and summer of 2018, 61 students and 12 local providers enrolled in an elective MAT course developed by Idaho State University. All completed the training. At the end of the course, only the students submitted reflective essays. RESULTS: A review and coding of the essays indicated that MAT education increased knowledge about addiction and resulted in self-reported decreases in negative attitudes towards people with addictions. CONCLUSION: PA programs can support communities' increased capacity to offer MAT. A widely available course appears to result in important gains in both knowledge and attitude.

Necrotizing pancreatitis: A review for the acute care surgeon.

BACKGROUND: Necrotizing pancreatitis is a common condition with high mortality; the acute care surgeon is frequently consulted for management recommendations. Furthermore, there has been substantial change in the timing, approach, and frequency of surgical intervention for this group of patients. METHODS: In this article we summarize key clinical and research developments regarding necrotizing pancreatitis, including current recommendations for treatment of patients requiring intensive care and those with common complications. Articles from all years were considered to provide proper historical context, and most recent management recommendations are identified. RESULTS: Epidemiology, diagnosis, treatment in the acute phase, and complications (both short-term and long-term) are discussed. Images of surgical interventions are included from our institutional experience. CONCLUSION: Necrotizing pancreatitis management remains heavily based on clinical judgement, although technological advances and clinical trials have made decision making more straightforward.

The Effect of Antithrombotics on Hematoma Expansion in Small- to Moderate-Sized Traumatic Intraparenchymal Hemorrhages.

BACKGROUND: Although pre-injury antithrombotic agents, including antiplatelets and anticoagulants, are historically associated with expansion of traumatic intraparenchymal hemorrhage (tIPH), the literature has poorly elucidated the actual risk of hematoma expansion on repeat computed tomography (CT). The objective was to determine the effect of antithrombotic agents on hematoma expansion in tIPH by comparing patients with and without pre-injury antithrombotic medication. METHODS: The volume of all tIPHs over a 5-year period at an academic Level 1 trauma center was measured retrospectively. The initial tIPH was divided into 3 equally sized quantiles. The third tercile, representing the largest subset of tIPH, was then removed from the study population because these patients reflect a different pathophysiologic mechanism that may require a more acute and aggressive level of care with reversal agents and/or operative management. Per institutional policy, all patients with small- to moderate-sized hemorrhages received a 24-hour stability CT scan. Patients who received reversal agents were excluded. RESULTS: Of the 105 patients with a tIPH on the initial head CT scan, small- to moderate-sized hemorrhages were <5 cm3. The size of tIPH on initial imaging did not statistically significantly differ between the antithrombotic cohort (0.7 ± 0.1 cm3) and the non-antithrombotic cohort (0.5 ± 0.1 cm3) (P = 0.091). Similarly, the volume of tIPH failed to differ on 24-hour repeat imaging (1.0 ± 0.2 cm3 vs. 0.6 ± 0.1 cm3, respectively, P = 0.172). Following a multiple linear regression, only history of stroke, not antithrombotic medications, predicted increased tIPH on 24-hour repeat imaging. CONCLUSIONS: In small- to moderate-sized tIPH, withholding antithrombotic agents without reversal may be sufficient.

Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma.

BACKGROUND: The existence of primary fibrinolysis (PF) and a defined mechanistic link to the "Acute Coagulopathy of Trauma" is controversial. Rapid thrombelastography (r-TEG) offers point of care comprehensive assessment of the coagulation system. We hypothesized that postinjury PF occurs early in severe shock, leading to postinjury coagulopathy, and ultimately hemorrhage-related death. METHODS: Consecutive patients over 14 months at risk for postinjury coagulopathy were stratified by transfusion requirements into massive (MT) >10 units/6 hours (n = 32), moderate (Mod) 5 to 9 units/6 hours (n = 15), and minimal (Min) <5 units/6 hours (n = 14). r-TEG was performed by adding tissue factor to uncitrated whole blood. r-TEG estimated percent lysis was categorized as PF when >15% estimated percent lysis was detected. Coagulopathy was defined as r-TEG clot strength = G < 5.3 dynes/cm. Logistic regression was used to define independent predictors of PF. RESULTS: A total of 34% of injured patients requiring MT had PF, which was associated with lower emergency department systolic blood pressure, core temperature, and greater metabolic acidosis (analysis of variance, P < 0.0001). The risk of death correlated significantly with PF (P = 0.026). PF occurred early (median, 58 minutes; interquartile range, 1.2-95.9 minutes); every 1 unit drop in G increased the risk of PF by 30%, and death by over 10%. CONCLUSIONS: Our results confirm the existence of PF in severely injured patients. It occurs early (<1 hour), and is associated with MT requirements, coagulopathy, and hemorrhage-related death. These data warrant renewed emphasis on the early diagnosis and treatment of fibrinolysis in this cohort.