Violent trauma recidivism: Does all violence escalate?

PURPOSE: Rates of trauma patients presenting with history of prior trauma range from 25 to 44%. Outcomes involving recidivists in the setting of intentional trauma, especially penetrating trauma, are conflicting. We hypothesized that if violence does escalate with successive incidence, then injuries due to successive violence should escalate or become increasingly severe with successive admissions. METHODS: The trauma registry from an urban level I adult and pediatric trauma center was queried for injuries due to blunt assault, stabbing, and firearm injury. Primary outcome measures were mortality, injury mechanism, and injury severity for each successive trauma admission. RESULTS: Victims of blunt assault and stabbing were more likely to become recidivists than victims of gun violence (OR 1.53, p < 0.001 and OR 1.57, p < 0.001). Violent re-injury became increasingly severe only in victims of repeated gun violence. Patients with gunshot as the mechanism at every admission are at highest risk for mortality (OR 13.48, p < 0.001). All but one mortality (95.8%) in the recidivist population occurred within 180 days of discharge from a prior injury. CONCLUSION: Recidivism for interpersonal violence results in a significant number of admissions to trauma centers. In our patient cohort, injury associated with successive blunt assaults did not worsen with subsequent admissions. Recidivism for gunshot wounds tends to be more severe and have a worse prognosis with each successive admission compared to outcomes associated with repeated stab wounds. Focused efforts should include rehabilitation efforts early in the post-injury period, especially in patients with a history of gunshot wounds.

Predictors of retained hemothorax after trauma and impact on patient outcomes.

PURPOSE: Hemo/pneumothoraces are a common result of thoracic injury. Some of these injuries will be complicated by retained hemothorax (RH), which has previously been shown to be associated with longer hospitalizations. It has been proposed that early versus delayed intervention with video-assisted thoracoscopic surgery can reduce the duration of mechanical ventilation, hospital and ICU LOS, and costs in patients with RH. However, little is known regarding the effect of RH on these outcomes relative to patients with uncomplicated hemo/pneumothoraces. The aim of our study was to characterize factors present on admission that may be associated with RH and assess the impact of RH on outcomes. METHODS: A retrospective chart review was conducted and included all patients who underwent tube thoracostomy (TT) for traumatic hemo/pneumothorax admitted to a single urban adult and pediatric level I trauma center from January 2008 to September 2013. RESULTS: The study cohort included 398 patients, 17.6 % developed RH. RH was associated with significantly longer total duration of TT drainage (p < 0.001), hospital LOS (p < 0.001), and total hospital charges (p < 0.001). These associations remained significant in a subgroup analysis excluding patients with traumatic brain injury. Patients with bilateral injuries (OR 4.25, p < 0.001) and patients intubated on the day of admission (OR 2.30, p = 0.002) were significantly more likely to develop RH. There was also a small, but highly significant, association between increasing ISS and the development of RH (OR 1.07, p < 0.001). CONCLUSIONS: Our study suggests patients requiring ventilator support on admission and those with bilateral injuries are at increased risk of developing RH. Early identification of patients at risk for RH may allow for earlier intervention and potential benefits to the patient.

Induction of Mx protein by interferon and double-stranded RNA in salmonid cells.

Mx protein is one of several antiviral proteins that are induced by the type I interferons (IFN), IFNalpha and beta, in mammals. In this work induction of a 76 kDa Mx protein by double-stranded RNA (dsRNA) or type I IFN-like activity in Atlantic salmon macrophages, Atlantic salmon fibroblast cells (AS cells) and in Chinook salmon embryo cells (CHSE-214) is reported. Type I IFN-like activity was produced by the stimulation of Atlantic salmon macrophages with the synthetic dsRNA polyinosinic polycytidylic acid (poly I:C). A correlation appeared to exist between Mx protein expression and protection against infectious pancreatic necrosis virus (IPNV) induced by IFN in CHSE-214 cells. Several observations in the present work suggest that, as in mammals, the induction of Mx protein by dsRNA in fish cells primarily occurs via induction of type I IFN. First, type I IFN-like activity but not poly I:C, induced Mx protein expression in CHSE-214 cells. These cells apparently lack the ability to produce IFN in response to poly I:C. Second, the putative IFN induced maximal Mx protein expression 48 h earlier than poly I:C in AS cells. Third, the peak expression of Mx protein in macrophages induced by poly I:C occurred after 48 h whereas peak in IFN-like activity was observed by 24 h after addition of poly I:C. The present work supports the notion of using Mx protein as a molecular marker for the production of putative type I IFN in fish.

Variability in methotrexate serum and cerebrospinal fluid pharmacokinetics in children with acute lymphocytic leukemia: relation to assay methodology and physiological variables.

Methotrexate (MTX) steady state concentrations were evaluated in 42 children who had received high-dose infusions (6-8 g/m2) for acute lymphocytic leukemia. Concentrations in serum and cerebrospinal fluid (CSF) measured by immunoassay were found to be highly variable. Reanalysis by a reference high-pressure liquid chromatography method ruled out analytical factors as a source of this variability. The correlation coefficient between the analytical methods was 0.77 for the serum data and 0.88 for the CSF data. The variability of serum and CSF concentrations was higher in younger patients (serum; P = 0.05 and CSF; P = 0.18), and the CSF concentration decreased with decreasing age and in later courses. Body surface area, body mass index, weight, and gender were not significantly related to MTX variability. We conclude that the pronounced pharmacokinetic variability seen during MTX infusions remains largely unexplained.

Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation. Nordic Society of Pediatric Haematology and Oncology (NOPHO).

In this population-based material from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2860 children below 15 years of age were diagnosed with acute lymphoblastic leukemia (ALL) from July 1981 to June 1998. The annual incidence was 3.9/100,000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification with multidrug chemotherapy, including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. The overall event-free survival (EFS) at 5 years has increased from 56.5 +/- 1.7% in the early 1980s to 77.6 +/- 1.4% during the 1990s. The main improvements were seen in children with non-high risk leukemia. In high-risk patients, progress has been moderate, especially in children with high WBC (> or =100 x 10(9)/l) at diagnosis. During the last time period (January 1992-June 1998), only 10% of the patients have received cranial irradiation in first remission, while 90% of the patients have received pulses of high dose methotrexate (5-8 g/m2) isolated or combined with high-dose cytosine arabinoside (total dose 12 g/m2) plus multiple intrathecal injections of methotrexate as CNS-targeted treatment, not translating into increased cumulative incidence of CNS relapse.

[Adults treated as children for acute lymphocytic leukemia--methotrexate, late effects and quality of life]. / Voksne behandlet for akutt lymfatisk leukemi som barn--metotreksat, seneffekter og livskvalitet.

From 1975 to 1980, 153 Norwegian children were diagnosed with acute lymphocytic leukaemia. In 1995, all 98 survivors were studied and compared to matched family controls. 132 children were treated with the national protocol. Of these, 93 (70.5%) were survivors at the time of the study. The remaining five survivors were treated with different treatment schemes. The national protocol included methotrexate infusions combined with intrathecal methotrexate as prophylactics against neuroleukaemia, instead of the irradiation. Neither doxorubicin nor cyclophosphamide were included. In this study, a questionnaire was used that covered demographic data, quality of life, and medical information the response rates were 96% (94 persons) for survivors and 92% (90 persons) for family controls. Information was also obtained for the remaining four survivors. No significant differences were found between survivors and controls with regard to quality of life and demographics, with one exception, Somatisation on the GHQ-28. Hospital records of all patients were checked for possible late effects. One case of serious sequela (hemiparesis during therapy) was found, probably related to methotrexate therapy. Seven other serious, possible sequelae were recorded, but probably not related to methotrexate. There were no cases of secondary malignant neoplasm.

On the prognostic value of systemic methotrexate clearance in childhood acute lymphocytic leukemia.

The prognostic value of systemic methotrexate clearance (ClMTX) during high-dose therapy was evaluated in a cohort of 42 children with acute lymphocytic leukemia (ALL). As part of an extensive chemotherapy protocol, they had received a total of 293 methotrexate (MTX) infusions in the 6-8 g/m2 dose range. At the termination of the study, when they had all been followed up for 3.5 years or more, 26 of these patients were still in continuous complete remission, whereas 16 had suffered relapse. The intrapatient variability in ClMTX during the eight courses was up to six-fold. In 67% of the patients, the maximum level of ClMTX reached at least twice the minimum value. The coefficients of variation for the intra- and interindividual variability in ClMTX were 9-57% and 26-41%, respectively. The cumulative probability of relapse, estimated by the Kaplan-Meier procedure, was increased for patients with a high ClMTX during the initial treatment course, but the difference was not significant on a 5% level. There was no significant relationship between high individual median ClMTX and subsequent relapse of ALL. However, ClMTX during the initial infusion, the time-dependent mean for ClMTX, and the individual patient's median ClMTX, were significant predictors for event-free survival in a Cox proportional hazards regression analysis. The present study demonstrates gross pharmacokinetic variability and unpredictable values of ClMTX in subsequent courses after standardized administration of MTX to paediatric patients with ALL. In spite of the association between ClMTX and prognosis shown by some of the analyses, estimates of ClMTX rates may not necessarily be related to disease outcome in a way that can be exploited to the benefit of the individual patient.

Magnetic resonance imaging and neurological evaluation after treatment with high-dose methotrexate for acute lymphocytic leukaemia in young children.

This study evaluates the occurrence of permanent cerebral white matter changes and neurological abnormalities in children treated at a young age for acute lymphocytic leukaemia. Our pilot treatment protocol did not include central nervous system irradiation, but intrathecal methotrexate and high-dose methotrexate infusions followed by very intensive folinic acid rescue. We examined 12 children in complete remission and off therapy 18 months to 9.5 years after their last methotrexate infusion. They were below 5 years of age at diagnosis and therefore expected to be at special risk of neurotoxic sequelae. Cerebral magnetic resonance imaging in the 11 cases thus evaluated did not reveal white matter abnormalities or other signal changes as signs of permanent treatment-related sequelae. We did not observe any pathological clinical neurological findings likely due to methotrexate.

Evaluation of serious adverse events in patients treated with protocols including methotrexate infusions.

During the period 1979 to 1992 we treated 141 children for various malignant diseases with protocols including methotrexate (MTX) infusions in doses ranging from 0.5 to 33.6 g/m2. During a total of 922 courses, there were no fatal complications associated with MTX treatment. Serum MTX concentration and pharmacokinetic data were monitored continuously during the infusions. In this study, we evaluated the occurrence of serious untoward reactions to MTX infusions. Impaired renal function with delayed drug elimination was seen in seven patients, all boys, especially after short infusion times. All recovered completely without any serious clinical symptoms. In three leukemia patients who later died from resistant disease, we observed late neurological disturbances and computer tomography (CT) brain scan abnormalities. Pharmacokinetic data from the patients with complications are described and confirm that serial MTX concentration monitoring is the most important early indicator of renal toxicity.

Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO).

Among a cohort of 981 children who were followed up 4.3-26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyosarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5-16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without (p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.

Reproduction following treatment for childhood leukemia: a population-based prospective cohort study of fertility and offspring.

Of all children diagnosed with leukemia in Denmark, Finland, Iceland, Norway, and Sweden, 981 had discontinued therapy before 1985 and had been followed up annually after cessation of therapy. Progeny was registered and fertility evaluated among survivors who passed age 18 years without a relapse (n = 299). By April 1989, 48 offspring were registered, one of whom had congenital anomalies. This was no more than expected from the incidence of birth defects in the general population. No childhood malignancies or genetic diseases have so far been diagnosed in the progeny. In the study group, none of the 19 female and 8 male survivors of myeloid leukemias had become parents, and only 4 fathers were reported among the 131 male survivors of acute lymphoblastic leukemia (ALL). However, 23 of the 149 females treated for ALL had delivered 41 children. Fertility was measured as cumulative rates of first birth by maternal age. In a Cox regression analysis, cases who had received prophylactic radiation of the central nervous system (CNS) had a lower first birth rate than those without radiation (rate ratio 0.39, 95% CI 0.15-1.00), indicating that doses of 18-24 Gy to the brain may possibly be a risk factor. By using the Norwegian birth cohort of 1966 as a control group, matching the median year of birth for the study subjects, the group of female ALL survivors as a whole was as likely as the general female population to have given birth up to the age of 23. The first generation of females successfully treated for childhood ALL seems to have a nearly normal reproductive pattern during young adulthood, without increased risk of congenital anomalies in the offspring. However, cranial radiation as CNS prophylaxis may possibly impair subsequent reproduction.

[Treatment considerations for children during terminal care]. / Behandlingsoverveielser hos barn ved livets avslutning.

There should be a special obligation to shield children with a terminal illness from pain and from the psychological suffering when death is approaching. In spite of this, the child has the right to be informed about the prognosis and decisions taken concerning treatment. We discuss the difficult question of informed consent in pediatrics. Who can make an informed consent on behalf of a minor? At which age should a child make its own decisions concerning medical treatment? In pediatrics there are certain circumstances where withdrawal of intensive medical care is justified. Examples are given from oncological and neuromuscular diseases, as well as from the neonatal period. We discuss how termination of intensive care could take place. The medical team should make the decision alone, but should never go against the parents' will. It is underlined that termination of intensive care in the above-mentioned circumstances is completely different from active euthanasia, which we strongly oppose.

Structural chromosome aberrations in lymphocytes from children previously treated for Wilms' tumor or Hodgkin's disease.

Nineteen children treated for Wilms' tumor (thirteen cases) or Hodgkin's disease (six cases) with cytostatic agents and/or radiotherapy were studied cytogenetically on lymphocytes cultivated from blood samples drawn after at least 1 year of complete remission after end of therapy. A reference group of children was matched for age, sex, and residence. The frequencies of sister chromatid exchange (5.4 versus 5.6 SCE/cell), and chromosome damage type gaps (6.6 versus 7.1%) and breaks (1.9 versus 1.9%) were not different in the two groups, but exchange type aberrations were more frequent in the patients (0.9 versus 0.06%). Fifty karyotypes were analyzed in all but two cases of Hodgkin's disease. The overall frequency of stable (3.1 versus 3.8%) and unstable (1.7 versus 1.4%) structural chromosome changes such as translocations, deletions, chromatid exchanges, and dicentrics were not different in the patient and the control groups. If the chromosome data reflect a general cancer risk, this risk cannot be considerably higher among the cancer-treated children.

Late relapses after treatment for acute lymphoblastic leukemia in childhood: a population-based study from the Nordic countries.

Seven late relapses of acute lymphoblastic leukemia occurring 5.5 to 12.3 years after cessation of therapy are reported in 986 patients who had discontinued treatment for leukemia acquired before the age of 15. The study covers patients from the five Nordic countries. Of the 434 patients with ALL who had passed 5 years of follow-up without recurrence, seven have subsequently relapsed so far; an estimated cumulative proportion of 6.9% within the 10 years. In addition, we report a girl 15.9 years old at diagnosis who relapsed 7.3 years after cessation of therapy. These findings confirm that "cure" of acute lymphoblastic leukemia treated in the 1970s cannot be considered definite, even 5 years after discontinuation of therapy.

Thyroid function in children after cytostatic treatment for acute leukemia.

Sixty-one children were examined for thyroid dysfunction as an adverse late effect after cessation of antileukemic treatment. The aim of the study was to contribute to clarifying which types of therapy can cause this endocrine disorder. Our treatment protocols do not include cranial irradiation as CNS prophylaxis, but we give relatively intensive intrathecal methotrexate treatment. The results indicate that this cytostatic regimen alone does not cause thyroid dysfunction as an adverse late effect.