Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin-Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study.

Background: Postdiarrheal hemolytic-uremic syndrome (D+HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is a serious condition lacking specific treatment. Host immune dysregulation and genetic susceptibility to complement hyperactivation are implicated in non-STEC-related HUS. However, genetic susceptibility to D+HUS remains largely uncharacterized. Methods: Patients with culture-confirmed STEC diarrhea, identified through the Centers for Disease Control and Prevention FoodNet surveillance system (2007-2012), were serotyped and classified by laboratory and/or clinical criteria as having suspected, probable, or confirmed D+HUS or as controls and underwent genotyping at 200 loci linked to nondiarrheal HUS or similar pathologies. Genetic associations with D+HUS were explored by multivariable regression, with adjustment for known risk factors. Results: Of 641 enrollees with STEC O157:H7, 80 had suspected D+HUS (41 with probable and 32 with confirmed D+HUS). Twelve genes related to cytokine signaling, complement pathways, platelet function, pathogen recognition, iron transport, and endothelial function were associated with D+HUS in multivariable-adjusted analyses (P ≤ .05). Of 12 significant single-nucleotide polymorphisms (SNPs), 5 were associated with all levels of D+HUS (intergenic SNP rs10874639, TFRC rs3804141, EDN1 rs5370, GP1BA rs121908064, and B2M rs16966334), and 7 SNPs (6 non-complement related) were associated with confirmed D+HUS (all P < .05). Conclusions: Polymorphisms in many non-complement-related genes may contribute to D+HUS susceptibility. These results require replication, but they suggest novel therapeutic targets in patients with D+HUS.

Can computed tomography replace or supplement autopsy?

Postmortem computed tomography (PMCT) has been integrated into the practice of many forensic pathologists. To evaluate the utility of PMCT in supplementing and/or supplanting medicolegal autopsy, we conducted a prospective double-blind comparison of abnormal findings reported by the autopsy pathologist with those reported by a radiologist reviewing the PMCT. We reviewed 890 cases: 167 with blunt force injury (BFI), 63 with pediatric trauma (under 5 years), 203 firearm injuries, and 457 drug poisoning deaths. Autopsy and radiology reports were coded using the Abbreviated Injury Scale and abnormal findings and cause of death (COD) were compared for congruence in consensus conferences with novel pathologists and radiologists. Overall sensitivity for recognizing abnormal findings was 71% for PMCT and 74.6% for autopsy. Sensitivities for PMCT/autopsy were 74%/73.1% for BFI, 61.5%/71.4% for pediatric trauma, 84.9%/83.7% for firearm injuries, and 56.5%/66.4% for drug poisoning deaths. COD assigned by reviewing PMCT/autopsy was correct in 88%/95.8% of BFI cases, 99%/99.5% of firearm fatalities, 82.5%/98.5% of pediatric trauma deaths, and 84%/100% of drug poisoning deaths of individuals younger than 50. Both autopsy and PMCT were imperfect in recognizing injuries. However, both methods identified the most important findings and are sufficient to establish COD in cases of BFI, pediatric trauma, firearm injuries and drug poisoning in individuals younger than 50. Ideally, all forensic pathologists would have access to a CT scanner and a consulting radiologist. This would allow a flexible approach that meets the diagnostic needs of each case and best serves decedents' families and other stakeholders.

Salmonella enterica serotype Enteritidis: increasing incidence of domestically acquired infections.

BACKGROUND: Salmonella enterica causes an estimated 1 million cases of domestically acquired foodborne illness in humans annually in the United States; Enteritidis (SE) is the most common serotype. Public health authorities, regulatory agencies, food producers, and food processors need accurate information about rates and changes in SE infection to implement and evaluate evidence-based control policies and practices. METHODS: We analyzed the incidence of human SE infection during 1996-2009 in the Foodborne Diseases Active Surveillance Network (FoodNet), an active, population-based surveillance system for laboratory-confirmed infections. We compared FoodNet incidence with passively collected data from complementary surveillance systems and with rates of SE isolation from processed chickens and egg products; shell eggs are not routinely tested. We also compared molecular subtyping patterns of SE isolated from humans and chickens. RESULTS: Since the period 1996-1999, the incidence of human SE infection in FoodNet has increased by 44%. This change is mirrored in passive national surveillance data. The greatest relative increases were in young children, older adults, and FoodNet sites in the southern United States. The proportion of patients with SE infection who reported recent international travel has decreased in recent years, whereas the proportion of chickens from which SE was isolated has increased. Similar molecular subtypes of SE are commonly isolated from humans and chickens. CONCLUSIONS: Most SE infections in the United States are acquired from domestic sources, and the problem is growing. Chicken and eggs are likely major sources of SE. Continued close attention to surveillance data is needed to monitor the impact of recent regulatory control measures.

A toxicology-based review of fentanyl-related deaths in New Mexico (1986-2007).

Since its approval in the United States, fentanyl has become increasingly popular for the medical management of pain and as a substance of abuse. Fentanyl is unique among the opioids in its widespread use with a transdermal delivery system, which contributes to its unique pharmacokinetics and abuse potential. We examined the demographics of deaths with fentanyl identified on toxicologic analysis and reviewed specific challenges in the laboratory detection of postmortem fentanyl levels. The New Mexico Office of the Medical Investigator database was searched for all cases from January 1986 through December 2007 with fentanyl reported as present or quantified. Those deaths with a cause of death identified as drug overdose were then analyzed separately. From 1986 to 2007, 154 cases were identified with fentanyl present in postmortem samples, with 96 of the cases identified as fentanyl-related drug overdoses. The number of fentanyl-related deaths has increased over the past 20 years, corresponding to both statewide increases in the medical use of fentanyl and the abuse of prescription opioids. The demographics of these fentanyl-related overdoses showed that subjects were more likely to be female, white non-Hispanic, and older than those in previously described overdose deaths. Several cases were identified with central and peripheral blood samples and antemortem and postmortem samples available for fentanyl quantification. Given the uncharacteristic demographics of fentanyl-related deaths and the complexity of the laboratory analysis of fentanyl, forensic scientists must use caution in both the detection and interpretation of fentanyl concentrations.

Drugs, detention, and death: a study of the mortality of recently released prisoners.

It has been theorized that drug abusers recently released from prison have an increased risk of fatal drug overdose. The objective of this study was to determine whether persons released from prison in the state of New Mexico have an increased risk of death due to unintentional drug overdose in the time immediately after release from prison. A total of 96 people were identified who had been released from prison and subsequently suffered an unnatural death in 2001 through 2003. Among those who had drug-caused deaths, there was a significantly increased risk of dying in the first 2 weeks after release versus the subsequent 10 weeks RR = 3.08 (P < 0.001, 95% CI: 1.83-5.16). For those who died in the first 2 months after release, there was an increased risk of fatal drug overdose compared with dying of other unnatural causes (P = 0.025). Of those who died of fatal drug overdoses within the first 2 months, the average incarceration time was significantly longer than those who lived longer than 2 months after release (P = 0.021) and they were more likely to have used opiates (P < 0.0001) and sedatives (P = 0.01). Prisoners are at an increased risk of a fatal unintentional drug overdose immediately after release. The time surrounding release provides an opportunity for education on the risks of accidental overdose and the development of interventions to mitigate these risks.

Unintentional drug overdose death trends in New Mexico, USA, 1990-2005: combinations of heroin, cocaine, prescription opioids and alcohol.

AIMS: To determine the contribution of heroin, prescription opioids, cocaine and alcohol/drug combinations to the total overdose death rate and identify changes in drug overdose patterns among New Mexico subpopulations. DESIGN: We analyzed medical examiner data for all unintentional drug overdose deaths in New Mexico during 1990-2005. Age-adjusted drug overdose death rates were calculated by sex and race/ethnicity; we modeled overall drug overdose death adjusting for age and region. FINDINGS: The total unintentional drug overdose death rate in New Mexico increased from 5.6 per 100 000 in 1990 to 15.5 per 100 000 in 2005. Deaths caused by heroin, prescription opioids, cocaine and alcohol/drug combinations together ranged from 89% to 98% of the total. Heroin caused the most deaths during 1990-2005, with a notable rate increase in prescription opioid overdose death during 1998-2005 (58%). During 1990-2005, the 196% increase in single drug category overdose death was driven by prescription opioids alone and heroin alone; the 148% increase in multi-drug category overdose death was driven by heroin/alcohol and heroin/cocaine. Hispanic males had the highest overdose death rate, followed by white males, white females, Hispanic females and American Indians. The most common categories causing death were heroin alone and heroin/alcohol among Hispanic males, heroin/alcohol among American Indian males and prescription opioids alone among white males and all female subpopulations. CONCLUSIONS: Interventions to prevent drug overdose death should be targeted according to use patterns among at-risk subpopulations. A comprehensive approach addressing both illicit and prescription drug users, and people who use these drugs concurrently, is needed to reduce overdose death.

Expression of the p16(INK4a) gene product in premalignant and malignant epithelial lesions of the gallbladder.

The sequence of molecular changes leading to neoplastic transformation in the gallbladder remains elusive. The aim of this study is to characterize the spectrum of nuclear p16 protein product immunohistochemical expression in tissue microarray cores taken from resected gallbladders, comprising histologically normal gallbladder epithelia (n = 29), dyplastic epithelia (n = 19), reactive atypia (n = 7), and gallbladder adenocarcinoma (n = 23). Nuclear staining for p16 was evaluated for intensity (range, 0-3) and distribution (range, 0-3), and a summary staining score (range, 0-6) was obtained. Pairwise comparisons were significant for increased p16 protein expression in dysplastic epithelium (6/19, 31.6%) and invasive carcinoma (9/23, 39.1%) when compared to normal epithelium (0/29, 0%) (P = .003 and P = .0006, respectively). A quantitative increase of nuclear expression of p16 in reactive atypia (1/7, 14%) when compared to normal was also statistically significant (P = .049). Our data demonstrate that nuclear p16 expression is absent in normal gallbladder epithelium and is a frequent event in high-grade dysplasia of the gallbladder and gallbladder adenocarcinoma.

Youth suicide in New Mexico: a 26-year retrospective review.

Although suicidal behavior in children and adolescents is a major public health problem, large-scale research on suicide in this population is uncommon. In this study, we reviewed autopsy and field reports for all pediatric suicide cases referred to the New Mexico Office of the Medical Investigator from 1979 to 2005. The age-adjusted suicide rate was 4.8 per 100,000. Psychologic stressors and parasuicidal behavior were identified in some cases. Seventy-six percent of suicides occurred in the victim's home or yard, and 25% left a suicide note. In 26% of cases, alcohol or other drugs were detected in postmortem. Gunshot wound was the most common method overall (58%), followed by hanging (30%). Although the age-adjusted suicide rate is higher in New Mexico than nationally, the trends in the population are similar. With a solid understanding of the circumstances, it may be possible to predict, and hopefully prevent, future cases of child and adolescent death.

The Role of Postmortem Computed Tomography in the Evaluation of Strangulation Deaths.

We explored the value of postmortem computed tomography (PMCT) to augment autopsy in evaluating strangulation fatalities. A literature search identified 16 studies describing autopsy findings in 576 deaths and two studies describing autopsy and PMCT findings in six deaths. Similar cases were identified from our institution, yielding 130 deaths with autopsy findings and 14 deaths with both autopsy and PMCT findings. The presence of laryngohyoid fracture and soft tissue hemorrhage was compared from autopsy and autopsy+PMCT cases. The detection rates of fractures in autopsy and autopsy+PMCT cases were not significantly different. PMCT identified all fractures observed at autopsy and five fractures not identified. While PMCT may not detect soft tissue injuries in decomposed remains or subtle internal hemorrhages in neck injury, it is equally able to detect bony injuries as autopsy and might surpass autopsy in detecting subtle fractures. We conclude PMCT is useful to supplement autopsy in strangulation cases.

"Med-X": a medical examiner surveillance model for bioterrorism and infectious disease mortality.

We created a model surveillance system (Med-X) designed to enable medical examiners and coroners to recognize fatal infections of public health importance and deaths due to bioterrorism. All individuals who died in New Mexico and fell under medical examiner jurisdiction between November 23, 2000, and November 22, 2002, were prospectively evaluated using sets of surveillance symptoms and autopsy-based pathologic syndromes. All infectious disease deaths were evaluated to identify the specific causative agent. Of 6104 jurisdictional cases, 250 (4.1%) met Med-X criteria, of which 141 (56.4%) had a target pathologic syndrome. Ultimately, 127 (51%) of the 250 cases were due to infections. The causative organism was identified for 103 (81%) of the infectious disease deaths, of which 60 (58.3%) were notifiable conditions in New Mexico. Flu-like symptoms, fever and respiratory symptoms, and encephalopathy or new-onset seizures had predictive values positive for fatal infections of 65%, 72%, and 50%, respectively, and are useful as autopsy performance criteria. Before the development of surveillance criteria, 37 (14.8%) of the cases ordinarily would not have been autopsied resulting in a 1% increase in autopsy workload. Med-X is an effective method of detecting infectious disease deaths among medical examiner cases. Uniform criteria for performing medical examiner autopsies and reporting cases to public health authorities enhance surveillance for notifiable infectious diseases and increase the likelihood of recognizing deaths related to bioterrorism.

Role of the Medical Examiner in Zika Virus and Other Emerging Infections.

CONTEXT: -Medical examiners and coroners have long been an integral component of public health, often being the first to recognize and describe emerging infectious diseases. Given their experience and access, medical examiners and coroners will provide valuable contributions to better understanding Zika virus infection and its sequelae. OBJECTIVE: -To review past examples of medical examiner/coroner involvement in recognition of emerging infectious diseases and describe how medical examiners and coroners will be critical in understanding the pathophysiology of Zika infections. DESIGN: -Review of the existing literature on the role of medical examiners and coroners in the identification of emergent infections and the available literature on Zika virus. RESULTS: -Medical examiners and coroners have played a crucial role in identifying numerous emerging infectious diseases such as hantavirus pulmonary syndrome and West Nile virus, and have the expertise and experience to aid in elucidating the pathophysiologic effects of Zika virus and tracking its distribution and risk factors. CONCLUSIONS: -Medical examiners and coroners will be a significant factor in the unified public health approach needed to mitigate the effects of Zika virus and other, heretofore unrecognized, infectious diseases.

Evaluation of Non-Natural Deaths among Veterans: New Mexico Medical Examiner-Investigated Deaths, 2002-2011.

While it is recognized that veterans have increased rates of depression, post-traumatic stress disorder (PTSD), suicide, and substance use disorders, rates of homicide and unintentional injury deaths in veterans have been minimally investigated. We evaluated all non-natural deaths in New Mexico veterans between 2002 and 2011 in comparison with non-natural deaths among non-veterans. We reviewed all decedents in New Mexico with a history of military service and investigated by the medical examiner, excluding natural deaths and deaths due to fall from standing height. The most common manner of death was unintentional injury (62%), most of these deaths due to motor vehicle accidents (29%) followed by unintentional overdose (26%). Suicide rates among veterans were consistently higher than the general population. The most common mechanism of suicide in men was gunshot wound (72%), and intentional overdose in women (49%). Services are needed for veterans that are tailored to all ages and both sexes.

Amended cause and manner of death certification: a six-year review of the New Mexico experience.

Little is known about the amendment of death certificates (DCs) issued by medical examiners and coroners. This retrospective study examined why, how, and with what frequency cause and manner of death were amended on DCs issued by forensic pathologists over a 6-year period at the New Mexico Office of the Medical Investigator. Approximately 1% of DCs had either cause or manner of death amendments, with arteriosclerotic cardiovascular disease and intoxicants the most commonly amended and resulting causes of death, respectively. There was a significant association between manner of death and number of DCs amended (p<0.001). By percent, natural and suicide DCs were the most frequently amended. The way in which manner of death changed was significantly associated with the amount of time elapsed between DCs (p=0.04). Toxicology was the most common reason for DC amendment.

Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico.

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population.

Suicidal Drug Overdoses in New Mexico: A 5-year Retrospective Review.

To better understand the changing toxicology trends in suicidal drug overdoses in the setting of an increased national trend of multidrug overdoses, a retrospective review of electronic records from New Mexico's Office of the Medical Investigator database was performed between 2008 and 2012 to assess the drug type and current risk factors in suicide deaths. Information on demographics, circumstances, suicide risk factors, toxicology findings, and death certificates was collected and analyzed. Three hundred and forty-two suicide cases of suicide overdoses were identified. Decedents were predominantly female (61.8%). Scene investigation revealed risk factors including suicide ideation (47.4%), previous suicide attempts (38%), and suicide note (38%). Psychiatric illness was present in 72% of cases, with depression being the most common illness. Chronic pain was seen in 27.2% of cases. Most deaths were attributed to multiple drugs (76%). Utilizing the toxicology information will assist in creating public awareness and provide a framework to support targeted efforts to attempt to prevent future suicides.

Unintentional methadone-related overdose death in New Mexico (USA) and implications for surveillance, 1998-2002.

AIMS: To determine death rates from methadone over time, to characterize methadone-related death and to discuss public health surveillance of methadone-related death. DESIGN: We analyzed medical examiner data for all unintentional drug overdose deaths in New Mexico, USA, between 1998 and 2002. MEASUREMENTS: Age-adjusted death rates for methadone-related death, logistic regression models for likelihood of methadone-related death among all unintentional drug overdose deaths and bivariate comparisons within methadone-related death. FINDINGS: Of 1120 drug overdose deaths during this period, there were 143 (12.8%) methadone-related deaths; the death rate decreased over the time period, averaging 1.6 per 100,000. Of 143 methadone-related deaths, 22.4% were due to methadone alone, 23.8% were due to methadone/prescription drugs (no illicit drugs), 50.3% were due to methadone/illicit drugs and 3.5% were due to methadone/alcohol. These groups were significantly different in demographics, health history and circumstances of death. Of 79 decedents (55.2%) with a known source of methadone, 68 obtained methadone through a physician prescription (31 for methadone maintenance treatment (MMT), 27 for managing pain and 10 had unknown reason for prescription). CONCLUSIONS: Methadone-related death rates and the proportion of methadone-related death among all drug overdose deaths decreased in New Mexico from 1998 to 2002. It is important for surveillance of methadone-related death to assess multiple drug causes, not just underlying cause. Also, methadone for pain management must be examined alongside MMT and when possible, methadone co-intoxication should be described in the context of other drugs causing death.

Noncorrelating Pap tests and cervical biopsies: histological predictors of subsequent correlation.

Lack of correlation between dysplastic cervicovaginal Papanicolaou (Pap) tests and subsequent cervical biopsies raises the concern that a significant squamous intraepithelial lesion (SIL) may go unconfirmed. Additional tissue sections of cervical biopsies may detect SILs after noncorrelation on initial sections. Complete step sectioning of paraffin blocks was undertaken on 111 noncorrelating biopsy specimens from 95 patients and selected slides were reviewed for the presence of SIL. The initial negative biopsy slides were evaluated for four histological features: chronic cervicitis, acute cervicitis, mucosal erosion, and squamous atypia. Twenty-seven biopsies (24.3%) demonstrated the presence of a SIL in deeper levels. The presence of squamous atypia was significantly associated with the presence of dysplasia deeper in the block (P < 0.002). Acute and chronic cervicitis was seen roughly equally. Additional tissue levels are a productive way of confirming SILs, and squamous atypia allows a refined selection of negative cervical biopsies most likely to reveal an SIL on review of deeper levels.

Lightning deaths: a retrospective review of New Mexico's cases, 1977-2009.

To better understand lightning deaths, a retrospective review of electronic records from New Mexico's Office of the Medical Investigator database was performed between 1977 and 2009 to update and assess current risk factors. Information on demographics, circumstances, autopsy, and death certificates were collected and analyzed. Fifty-four decedents were identified, ages 2-71 years old (mean 34 years old), 42 males and 12 females. Common racial/ethnic groups were non-Hispanic Whites and American Indians (together comprising 72% of all cases). Physical findings were often related to the heat carried by the electrical current including clothing alterations (29.6%) and burning of skin (53.7%). Most deaths occurred on weekend afternoons in summer months, associated with recreational activities or agricultural work, and rural locations (77.8%). Utilizing the demographic information, clustered events, and associated outdoor activities will assist in creating public awareness and provide a framework to support targeted warnings in an attempt to prevent future deaths.

An examination of the postmortem redistribution of fentanyl and interlaboratory variability.

Fentanyl is a synthetic opioid agonist used for pain control. Often administered as a transdermal patch, it is an interesting drug for study of postmortem redistribution. We hypothesized that fentanyl concentrations would increase over time after death, as measured in blood drawn on the day prior to autopsy and in blood drawn at the time of autopsy in ten cases where fentanyl patches were identified at the scene. Concentrations were compared, and heart blood to femoral blood ratios were calculated as markers of postmortem redistribution. Fentanyl concentrations measured in peripheral blood drawn the day of autopsy (peripheral blood 2 [PB2]) were higher than those drawn the day prior to autopsy (peripheral blood 1 [PB1]) with a mean ratio (PB2/PB1) of 1.80. The ratio of heart blood concentrations (HB) to femoral blood concentrations drawn at autopsy (PB2) had a mean ratio (HB/PB2) of 1.08. Some cases had blood from the same source analyzed at two different laboratories, and concentrations of fentanyl in those samples showed inter- and intralaboratory differences up to 25 ng/mL. Postmortem fentanyl concentrations may be affected by antemortem factors, postmortem redistribution, and laboratory variability. Forensic pathologists must use caution in interpreting fentanyl levels as part of death investigation.

Childhood fatalities in new Mexico: medical examiner-investigated cases, 2000-2010.

To better understand risk factors and populations at risk of childhood fatalities, a review of all records of childhood deaths (≤19 years) between 2000 and 2010 from New Mexico's statewide medical examiner was conducted. Annually, 313-383 childhood deaths were investigated (3820 total). Males and American Indians were overrepresented (62% and 20.4% of deaths, respectively). The most common manner of death was natural (44.8%), followed by accidental (31.4%), homicide (8.8%), suicide (8.8%), and undetermined (4.1%). Infants under 1 year of age accounted for 41.4% of deaths. Motor vehicle crashes were responsible for the majority of accidental deaths (69%), followed by unintentional overdoses (6.9%), and drowning (5.3%). Gunshot wounds, either intentional or unintentional, caused 10.7% of childhood deaths. Complete medico-legal investigation of childhood fatalities is needed to provide public health agencies with adequate data to evaluate and prevent childhood deaths.