Traumatic Injury Under COVID-19 Stay-at-Home Advisory: Experience of a New England Trauma Center.

BACKGROUND: With the onset of the COVID-19 pandemic and subsequent widespread stay-at-home advisories throughout early 2020, hospitals have noticed a decrease in illnesses unrelated to COVID-19. However, the impact on traumatic injury is relatively unknown. This study aims to characterize patterns of trauma during the COVID-19 pandemic at a Level I Trauma Center. MATERIALS & METHODS: A retrospective review was performed of adult trauma patients from March to June, in the years 2018 through 2020. Primary outcome was the number of trauma activations (volume). Secondary outcomes included activation level, mechanism of injury, mortality rate, and length of stay, and other demographic background. Trauma patterns of the 2018 and 2019 periods were combined as historical control, and compared to patterns of the biweekly-matched period of 2020. RESULTS: A total of 2,187 patients were included in analysis (Pre-COVID n = 1,572; COVID n = 615). Results were significant for decreased trauma volume but longer length of stay during COVID cohort, and for an increased proportion of males. No significant difference was found for other demographic variables, trauma mechanisms, or severity. Trauma volume patterns mirrored COVID rates in the state. CONCLUSIONS: Despite a decline in trauma volume, other trauma patterns including severity and mechanism remained unchanged during the COVID-19 period. The decreased volume was not associated with a markedly lower clinical workload, change in team structure, or provider coverage re-distribution. Our data suggests that trauma volume and severity remained high enough during COVID-19 peak to necessitate full staffing, which may provide guidance in the event of a pandemic resurgence.

An abbreviated Caprini model for VTE risk assessment in trauma.

The Caprini risk assessment model (RAM) is widely used to assess risk of venous thromboembolism (VTE). However, it is cumbersome with 31 variables and poses challenges with inter-rater reliability. This study aimed to determine if an abbreviated model could perform similarly in VTE risk assessment. We performed a retrospective review of trauma patients ≥ 18 years old and admitted for over 24 h at a Level I trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Using a p-value cutoff of < 0.05, the individual components of the original Caprini RAM most highly associated with VTE were identified and used to calculate an abbreviated Caprini score. Logistic regression assessed odds of inpatient VTE with the original or abbreviated Caprini RAMs. Receiver operating characteristic curves and c-statistics were generated to assess discriminatory ability. The study sample included 1279 patients. Ten risk factors were included in the abbreviated model (recent major surgery, length of surgery > 2 h, transfusion, restricted mobility > 72 h, central venous catheter, current major surgery, age, history of VTE, hip or leg fracture, and serious trauma). Compared to the original, the abbreviated model had a similar odds ratio (1.17 vs 1.07, both p-values < 0.001), c-statistic (0.747 vs 0.753), sensitivity (0.73 vs 0.76) and specificity (0.62 vs 0.61). An abbreviated Caprini RAM performs similarly to the original, may streamline workflow and allow for automation in electronic health records, potentially enhancing its use in resource limited settings.

A Weight- and Anti-Xa-Guided Enoxaparin Dosing Protocol for venous thromboembolism Prophylaxis in intensive care unit Trauma Patients.

BACKGROUND: Trauma patients are high risk for venous thromboembolism (VTE) and the optimal dosing strategy for prophylactic enoxaparin remains unknown. The purpose of this quality improvement project was to evaluate a weight-based and anti-Xa-guided enoxaparin dosing protocol in intensive care unit (ICU) trauma patients and to determine if the protocol led to reduced clinical VTE rates. MATERIALS AND METHODS: Adult trauma patients admitted for ≥ 48 hours to our surgical or neurosurgical ICUs who received ≥ 3 consecutive weight-based enoxaparin doses were eligible for inclusion into this pre-post implementation cohort study. Enoxaparin 30 mg every 12 hours was used for weight 50 to 100 kg and body mass index (BMI) < 40 kg/m2 and enoxaparin 40 mg every 12 hours for weight ≥ 100 kg or BMI ≥ 40 kg/m2. PRE cohort patients did not routinely receive anti-Xa level monitoring, while in the POST cohort, dosing was subsequently titrated to peak anti-Xa levels of 0.2 to 0.4 IU/mL. RESULTS: A total of 110 and 113 patients were included in the PRE and POST cohorts, respectively. Clinical VTE rates were similar between groups. In the POST cohort, 75% of patients achieved goal anti-Xa levels without dose titrations, while 12% of higher weight patients and 9.1% of lower weight patients required adjustment. When comparing weight quartiles, patients > 100 kg were more likely to have sub-prophylactic anti-Xa levels than those ≤ 69 kg. CONCLUSIONS: Our enoxaparin dosing protocol was safe and frequently achieved initial anti-Xa levels within goal, indicating that weight-based dosing alone may be sufficient. However, patients > 100 kg may benefit from anti-Xa monitoring as they are highest risk for sub-prophylactic levels despite higher initial enoxaparin dosing.

Detection of ethanol, cannabinoids, benzodiazepines, and opioids in older adults evaluated for serious injuries from falls.

BACKGROUND: In 2020, there were 36.7 million reported falls among older adults (65+) in the United States. Ethanol and other sedating substances may increase fall risk among older adults due to their effect on cognitive and physical function. We estimate the prevalence of these substances in blood specimens of older adults presenting with a fall injury at selected trauma centers. METHODS: The initial study collected blood specimens from May 2020 through July 2021 from adults undergoing a trauma team evaluation at selected United States Level 1 trauma centers. We limited our study to older adults evaluated after a fall (n = 1,365) and selected a random sample (n = 300) based on age, sex, and trauma-center quotas. Medical health records and blood specimens obtained at trauma center presentation were analyzed. We estimated the prevalence of ethanol, benzodiazepines, cannabinoids, and opioids in the blood specimens. Two-sample tests of binomial proportions and Chi-square two-tailed tests were used to compare prevalence estimates of substances by demographic characteristics. RESULTS: At least one substance was detected among 31.3% of samples analyzed. Prevalences of specific substances detected were 9.3% (95% CI: 6.0-12.6%) for benzodiazepines, 4.3% (95% CI: 2.0-6.7%) for cannabinoids, 8.0% (95% CI: 5.2-11.7%) for ethanol, and 15.0% (95% CI: 10.9-19.1%) for opioids. There were 18 deaths (6%; 95% CI: 3.6-9.3%). One-third of decedents had at least one substance detected in their blood. DISCUSSION: Opioids were the most frequently detected substance, followed by benzodiazepines, ethanol, and cannabinoids. Substance use prevalence was not uniform across demographics, with differences observed by sex and age. CONCLUSIONS: This study provides insight into the frequency of the presence of substances that may contribute to fall risk and serious injury among older adults. Screening older adults for substances that impair cognitive and physical function can enhance clinical fall prevention efforts.

Near Hanging: Evaluation and Management.

Prior to the COVID-19 pandemic, the incidence of self-harm was already on the rise. Hanging/suffocation accounted for 50% of the increase in suicide attempts and remains the second leading cause of death from self-harm in the United States. Studies on the management of near-hanging patients are lacking, and most published literature is retrospective. Following airway and circulation assessment, clinical examination and imaging, namely CT angiography, remain the standard for identifying the injuries associated with near hanging: cervical spine fracture, blunt cerebrovascular injury, laryngeal injury, and injury to the trachea and oropharynx. These injuries, however, are uncommon, and each occur in < 5% of patients in most series. In a large series of critically ill near-hanging patients, > 50% survived to hospital discharge; however, cardiac arrest predicted a poor outcome. The management of asphyxia-related arrest remains controversial. Targeted temperature management has only been studied in a single large multicenter trial, which was retrospective. Given the significant selection bias of targeted temperature management in the treatment of the most ill patients, no firm recommendations can be made. Finally, for survivors, the underlying mental health issues must be addressed to avoid recurrent suicide attempts. Thirty percent of patients in a large near-hanging series were admitted for their second suicide attempt.

Evaluation of phenobarbital for prevention of alcohol withdrawal in trauma patients.

BACKGROUND: Up to 30% of trauma patients experience alcohol withdrawal syndrome (AWS) during their hospital admission, which is associated with worse outcomes. While benzodiazepines and phenobarbital are the mainstay of AWS management, there are limited data on the prevention of AWS. The objective was to evaluate the safety and efficacy of phenobarbital for the prevention of AWS. METHODS: Adult patients admitted to a level 1 trauma center who received at least one dose of phenobarbital for the prevention of AWS between January 2019 and August 2021 were included. Patients were case matched to a control group managed with symptom-triggered therapy based on risk of AWS. Risk factors included sex, age, history of AWS/delirium tremens or withdrawal seizures, selected laboratory values, and screening questionnaires. The primary endpoint was the need for rescue therapy. Secondary endpoints included the time to rescue therapy, intensive care unit (ICU) length of stay (LOS), and hospital LOS. RESULTS: Overall, 110 patients were included with 55 patients in each group. The phenobarbital group had higher baseline Injury Severity Scores ( p = 0.03) and were more likely to be admitted to the ICU (44% vs. 24%; p = 0.03). The phenobarbital group required less rescue therapy (16% vs. 62%; p < 0.001) with a longer time to rescue therapy administration (26 vs. 11 hours; p = 0.01). The phenobarbital group had a longer hospital LOS (216 vs. 87 hours; p = 0.0001) but no difference in ICU LOS ( p = 0.36). There was no incidence of delirium tremens or seizures and no difference in intubation rates ( p = 0.68). There was no incidence of hypotension associated with phenobarbital. CONCLUSION: Patients managed with phenobarbital had a lower need for rescue therapy for AWS with no increased adverse effects. Further studies should evaluate a protocol to prevent alcohol withdrawal in the trauma population. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Decompressive laparotomy for refractory intracranial hypertension after traumatic brain injury.

BACKGROUND: Intracranial hypertension is a crucial modifiable risk factor for poor outcome after traumatic brain injury (TBI). Limited evidence suggests that decompressive laparotomy may be an effective treatment for refractory ICH in patients who have elevated intra-abdominal pressure. METHODS: Case report. RESULTS: We present a multi-trauma patient who sustained severe TBI in a motor vehicle collision. Intracranial pressure (ICP) was initially medically managed but became refractory to standard therapies. Emergent decompressive laparotomy performed in the surgical intensive care unit for abdominal compartment syndrome concomitantly improved the patient's ICP. CONCLUSIONS: Elevated intra-abdominal pressure can exacerbate intracranial hypertension in patients with TBI. Recognition of this condition and treatment with decompressive laparotomy may be useful in patients with intracranial hypertension refractory to optimal medical therapy.

Venous thromboembolism risk stratification in trauma using the Caprini risk assessment model.

INTRODUCTION: The Caprini risk assessment model is widely used for venous thromboembolism (VTE) but has limited data in trauma. The study objective was to determine if the Caprini risk assessment model could effectively risk stratify trauma patients. MATERIALS AND METHODS: We performed a retrospective review of trauma patients aged ≥18 years, admitted for greater than 24 h at a level one trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Multiple logistic regression assessed odds of inpatient VTE. RESULTS: A total of 1279 patients met study eligibility, with a total of 33 VTE (2.6%). When comparing those with VTE to those without, the mean age was lower (52.5 vs 59.5, p = 0.06, respectively), sex distribution was similar, but mean body mass index was higher (30.2 vs 27.4, p = 0.019, respectively). The mean Caprini score was 9.9, and 75.5% had a score >4, the traditional Caprini high-risk cutoff. The VTE group had a higher mean Injury Severity Score (17.8 vs 12.6, p = 0.011), and mean Caprini score (16.4 vs 9.8, p < 0.001). Multiple logistic regression found Caprini score, not Injury Severity Score, was associated with higher odds of VTE (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.10), after adjusting for Injury Severity Score, any missed doses of VTE chemoprophylaxis, and VTE prophylaxis type. CONCLUSIONS: Higher Caprini scores are associated with elevated odds of inpatient VTE within hospitalized trauma patients. These data support using the Caprini risk assessment model in the trauma population, which may aid in risk stratification.

SARS-CoV-2 Seroprevalence and Drug Use in Trauma Patients from Six Sites in the United States.

In comparison to the general patient population, trauma patients show higher level detections of bloodborne infectious diseases, such as Hepatitis and Human Immunodeficiency Virus. In comparison to bloodborne pathogens, the prevalence of respiratory infections such as SARS-CoV-2 and how that relates with other variables, such as drug usage and trauma type, is currently unknown in trauma populations. Here, we evaluated SARS-CoV-2 seropositivity and antibody isotype profile in 2,542 trauma patients from six Level-1 trauma centers between April and October of 2020 during the first wave of the COVID-19 pandemic. We found that the seroprevalence in trauma victims 18-44 years old (9.79%, 95% confidence interval/CI: 8.33 - 11.47) was much higher in comparison to older patients (45-69 years old: 6.03%, 4.59-5.88; 70+ years old: 4.33%, 2.54 - 7.20). Black/African American (9.54%, 7.77 - 11.65) and Hispanic/Latino patients (14.95%, 11.80 - 18.75) also had higher seroprevalence in comparison, respectively, to White (5.72%, 4.62 - 7.05) and Non-Latino patients (6.55%, 5.57 - 7.69). More than half (55.54%) of those tested for drug toxicology had at least one drug present in their system. Those that tested positive for narcotics or sedatives had a significant negative correlation with seropositivity, while those on anti-depressants trended positive. These findings represent an important consideration for both the patients and first responders that treat trauma patients facing potential risk of respiratory infectious diseases like SARS-CoV-2.

The effect of anticoagulation on outcomes after liver and spleen injuries: A research consortium of New England centers for trauma (ReCONECT) study.

BACKGROUND: Liver and spleen injuries are the most commonly injured solid organs, the effects of anticoagulation on these injuries has not yet been well characterized. STUDY DESIGN: Multicenter retrospective study. RESULT: During the 4-year study period, 1254 patients, 64 (5%) on anticoagulation (AC), were admitted with liver and/or splenic injury. 58% of patients had a splenic injury, 53% had a liver injury and 11% had both. Patients on AC were older than non-AC patients (mean age 60.9 vs. 38.6 years, p < 0.001). The most common AC drug was warfarin (70%) with atrial fibrillation (47%) the most common indication for AC. There was no significant difference in AAST injury grade between AC and non-AC patients (median grade 2), but AC patients required a blood product transfusion more commonly (58 vs 40%, p = 0.007) particularly FFP (4 vs 19%, p < 0.01). Among those transfused, non-AC patients required slightly more PRBC (5.7 vs 3.8 units, p = 0.018) but similar amount of FFP (3.2 vs 3.1 units, p = 0.92). The two groups had no significant difference in the rates of initial non-operative management (50% (AC) vs 56% (non-AC), p = 0.3)) or failure of non-operative management (7 vs 4%, p = 0.16). AC patients were more likely to be managed initially with angiography (36 vs 20%, p = 0.001) while non-AC patients with surgery (24% vs 13%, p = 0.04). There was no significant difference in LOS and mortality. CONCLUSION: The use of anticoagulation did not result in a difference in outcomes among patients with spleen and/or liver injuries.

Risks factors for significant injury after geriatric falls.

Elderly falls are a healthcare epidemic. We aimed to identify risk factors of serious falls by linking data on functional status from the Global Longitudinal Study of Osteoporosis in Women (GLOW) and our institutional trauma registry. 124 of 5,091 local women enrolled in GLOW were evaluated by our trauma team for injuries related to a fall during the study period. Median injury severity score was 9. The most common injuries were intertrochanteric femur fracture (n = 25, 9.8%) and skin contusion/hematoma to face (n = 12, 4.7%). Injured women were older than the uninjured cohort (median 80 versus 68 years), more likely to have cardiovascular disease and osteoarthritis, and less likely to have high cholesterol. Prospectively collected Short Form 36 (SF-36) baseline activity status revealed greater limitation in all assessed activities in women evaluated for fall-related injuries in our trauma center. In multivariable analysis, age (per 10 year increase) and two or more self-reported falls in the baseline survey were the strongest predictors of falling (both HR 2.4, p <0.0001 and p<0.001 respectively), followed by history of osteoarthritis (HR 1.6, p= 0.01). Functional status was no longer associated with risk of fall when adjusting for these factors. Functional status appears to be a surrogate marker for frailty. With the aging of the US population and long lifespan of American women, this finding has important implications for both fall prevention strategies and research intended to better understand why aging women fall as burdensome validated metrics may not be the best indicators of fall risk.

Imaging and Management of Thoracic Trauma.

Thoracic injury results from penetrating and blunt trauma and is a major contributor to overall trauma morbidity and mortality in the United States. Modern imaging algorithms utilize ultrasound, chest radiograph, and computed tomography with intravenous contrast to accurately diagnose and effectively treat patients with acute thoracic trauma. This review focuses on the etiologies, signs and symptoms, imaging, and management of several life-threatening thoracic injuries including tracheobronchial rupture, pulmonary parenchymal injury, hemothorax, pneumothorax, diaphragmatic rupture, and axial skeleton injury.

Multidetector CT Imaging of Bowel and Mesenteric Injury: Review of Key Signs.

In contemporary practice, multidetector computed tomography plays a critical role in the diagnostic evaluation of patients with suspected acute mesenteric and bowel trauma. Although less common than solid organ injuries, it may be seen in up to 5% of blunt trauma patients. Evaluation with CT remains challenging even with improvements in technology. The major imaging signs of mesenteric and bowel trauma and what is known about their applicability in clinical practice are reviewed here. Examples illustrate both the subtlety and variable significance of many of the key signs as well as how these are typically integrated into clinical practice.

Differences in characteristics of patients with and without known risk factors for hepatocellular carcinoma in the United States.

AIM: To examine the clinical characteristics of a subgroup of patients with hepatocellular carcinoma (HCC) and compare them to those with known risk factors. METHODS: We used the HCC database of 306 patients seen at our institution from January 1, 1995 to December 31, 2001. Of the 306 patients, 63 (20%, group 1) had no known risk factors (hepatitis C virus, hepatitis B virus, alcohol, hemochromatosis or cirrhosis from any cause) and 243 (group 2) had one or more risk factors. RESULTS: The median age was similar in both groups, but there were disproportionate numbers of younger (< 30 years old), older (> 80 years) patients, women (33% vs 18%), and Caucasians (81% vs 52%) in group 1 as compared to group 2. There were fewer Asians (2% vs 11%) and African Americans (13% vs 27%) in group 1. Abdominal pain (70% vs 37%) was more common while gastrointestinal bleeding (0% vs 11%) and ascites (4% vs 17%) were less common in group 1 compared to group 2. Group 1 had larger tumor burden (median size 9.4 cm vs 5.7 cm) at the time of presentation, but there were no differences in the site (right, left or bilateral lesions), or number of tumors between the two groups. CONCLUSION: HCC patients without identifiable risk factors have different characteristics and clinical presentation compared to those with known risk factors. Absence of cirrhosis and larger tumor burden may explain the differences in the presenting symptoms.

Selective Nonoperative Management of Abdominal Gunshot Wounds from Heresy to Adoption: A Multicenter Study of the Research Consortium of New England Centers for Trauma (ReCoNECT).

BACKGROUND: Selective nonoperative management (SNOM) of abdominal gunshot wounds is being practiced in certain trauma centers, but its broader acceptance in the surgical community is unknown. We hypothesized that SNOM has been adopted in New England as an acceptable method of abdominal gunshot wound management. STUDY DESIGN: We reviewed the medical records of abdominal gunshot wound patients admitted from January 1996 to June 2015, in 10 New England Level I and II trauma centers. Outcomes included the incidence, success, and failure of SNOM, and morbidity and mortality related to SNOM. RESULTS: Of 922 patients, 707 (77%) received immediate laparotomy (IMMLAP) and 215 (23%) were managed by SNOM. Compared with IMMLAP patients, those with SNOM had a lower median Injury Severity Score (16 vs 8; p < 0.001), lower incidence of complications (34.7% vs 8.5%; p < 0.001) and mortality (5.2% vs 0.5%; p = 0.002), and shorter ICU and hospital stays (median days 1 of 8 vs 0 of 2, respectively; p < 0.001). One SNOM patient died after 3 days due to a gunshot wound to the head. The overall incidence of SNOM increased from 18% before 2010 to 27% in the following years (p = 0.001). Eighteen patients (8.4%) had unsuccessful SNOM and underwent delayed laparotomy at an average of 12.5 hours (range 141 minutes to 48 hours) after arrival. Nine of them (4.2%) experienced complications that were not directly related to the delayed laparotomy, and none died. The rate of nontherapeutic laparotomies was 14.7% among IMMLAP and 5.5% among delayed laparotomy patients (p = 0.49). CONCLUSIONS: Selective nonoperative management of abdominal gunshot wounds, despite being a heresy only a few years ago, has now been established as an acceptable method of management in Level I and II trauma centers in New England.

Improving patient notification of solid abdominal viscera incidental findings with a standardized protocol.

BACKGROUND: The increasing use of computed tomography (CT) scans in the evaluation of trauma patients has led to increased detection of incidental radiologic findings. Incidental findings (IFs) of the abdominal viscera are among the most commonly discovered lesions and can carry a risk of malignancy. Despite this, patient notification regarding these findings is often inadequate. METHODS: We identified patients who underwent abdominopelvic CTs as part of their trauma evaluation during a recent 1-year period (9/2011-8/2012). Patients with IFs of the kidneys, liver, adrenal glands, pancreas and/or ovaries had their charts reviewed for documentation of the lesion in their discharge paperwork or follow-up. A quality improvement project was initiated where patients with abdominal IFs were verbally informed of the finding, it was noted on their discharge summary and/or were referred to specialists for evaluation. Nine months after the implementation of the IF protocol, a second chart review was performed to determine if the rate of patient notification improved. RESULTS: Of 1,117 trauma patients undergoing abdominopelvic CT scans during the 21 month study period, 239 patients (21.4%) had 292 incidental abdominal findings. Renal lesions were the most common (146 patients, 13% of all patients) followed by hepatic (95/8.4%) and adrenal (38/3.4%) lesions. Pancreatic (10/0.9%) and ovarian lesions (3/0.3%) were uncommon. Post-IF protocol implementation patient notification regarding IFs improved by over 80% (32.4% vs. 17.7% pre-protocol, p = 0.02). CONCLUSION: IFs of the solid abdominal organs are common in trauma patients undergoing abdominopelvic CT scan. Patient notification regarding these lesions is often inadequate. A systematic approach to the documentation and evaluation of incidental radiologic findings can significantly improve the rate of patient notification.

Epithelial-to-mesenchymal transition and integrin-linked kinase mediate sensitivity to epidermal growth factor receptor inhibition in human hepatoma cells.

Hepatocellular carcinoma (HCC) is associated with a poor prognosis due to late diagnoses and a lack of effective treatment options. Epidermal growth factor receptor (EGFR)-targeted therapies have been effective in other cancers. However, erlotinib and cetuximab have shown only modest efficacy in clinical trials of HCC. We examined epithelial-to-mesenchymal transition (EMT) as a determinant of sensitivity of HCC to EGFR inhibitors. A panel of 12 human hepatoma cell lines were classified as epithelial or mesenchymal based on their expression of E-cadherin and vimentin. The resulting classification correlated with a previous microarray analysis of human hepatoma cell lines whereby the mesenchymal cell lines were shown to have increased expression of genes involved in metastasis and invasion. Sensitivity to erlotinib, gefitinib, and cetuximab was assessed and the epithelial cell lines were found to be significantly more susceptible to all three agents. Analysis of the EGFR pathway showed that EMT status was independent of EGFR expression or downstream extracellular signal-regulated kinase activation and only the epithelial cell lines expressed ErbB3. Interestingly, mesenchymal cells resistant to EGFR inhibitors had increased AKT and signal transducer and activator of transcription-3 activation through elevated expression of integrin-linked kinase (ILK). Mesenchymal cell lines were therefore experimentally transformed with kinase-inactive ILK (KI-ILK) with a resulting decrease in ILK activity and activation of AKT. KI-ILK transformants showed increased sensitivity to EGFR inhibitors both in vitro and in an in vivo xenograft model. These data suggest that EMT predicts HCC sensitivity to EGFR-targeted therapies and that ILK is a novel target to overcome HCC resistance to EGFR inhibition.

HSV-1 viral oncolysis and molecular imaging with PET.

Viral oncolysis, the destruction of cancer cells by replicating viruses, is a new modality of cancer therapy. This strategy involves use of viruses that are either genetically engineered to replicate preferentially in neoplastic cells, or use of viruses that display innate tropism for neoplastic cells. These viruses may also be modified to deliver transgenes to destroy cancer cells. While numerous viruses may be used for this form of cancer therapy, HSV-1 is an attractive vector for viral oncolysis due to several characteristics including its high infectivity, ease of genetic engineering, large transgene capacity, and the availability of an effective medical treatment for Herpes simplex virus infections. The HSV-1 viral genome has been manipulated to generate replication conditional viruses which target cancer cells. Although these viruses are programmed to replicate preferentially in cancer cells, there is some unintended replication in normal cells. Currently, biopsy is the gold standard for monitoring the therapeutic effects of viral oncolysis. However, a non-invasive test capable of serial monitoring of therapy during the treatment period is required for both preclinical and clinical studies. Positron emission tomography (PET) using HSV thymidine kinase as the PET reporter gene offers the desired qualities of a non-invasive test which can be easily repeated to determine the location and magnitude of viral replication and tumor lysis. We review viral oncolysis, focusing on HSV-1 viral oncolysis and therapeutic monitoring by PET.

The correlation of deficits in IQ with midface and digit hypoplasia in children exposed in utero to anticonvulsant drugs.

OBJECTIVE: Children exposed during pregnancy to the anticonvulsant drugs phenytoin, phenobarbital, and carbamazepine as monotherapy and polytherapy have an increased frequency of midface and digit hypoplasia. Some children also have cognitive dysfunction. The hypothesis tested is that the anticonvulsant drug-exposed child with midface and digit hypoplasia is more likely to have cognitive dysfunction. METHODS: Children exposed to anticonvulsant drugs (n = 80) were recruited for a follow-up evaluation, which included testing cognitive function and a physical examination for head size, height, and the presence of midface and digit hypoplasia. Microcephaly, midface and digit hypoplasia, and major malformations were correlated with full scale (FSI), performance (PIQ) and verbal (VIQ) intelligence. RESULTS: The presence of the 3 anticonvulsant-exposed children with microcephaly had a deficit of 23.7 IQ points in FSI in comparison with the other children with a normal head size. Either midface or digit hypoplasia, after excluding the persons with microcephaly and with the Bonferroni correction, correlated significantly with deficits in VIQ (-12.7), PIQ (-10) and FSI (-12.8) IQ points ( P = .0061). There was no decrease in IQ in association with major malformations. CONCLUSION: The presence of midface and digit hypoplasia in a child exposed to anticonvulsant drugs in pregnancy is an indication for a systematic developmental evaluation.