Adverse medical complications: an under-reported contributory cause of death in New York City.

OBJECTIVES: The current death certification system in the USA fails to accurately track deaths due to adverse medical events. The aim of this study was to demonstrate the under-reporting of deaths due to adverse medical events due to limitations in the current death certification/reporting system, and the benefits of using the term 'therapeutic complication' as the manner of death. STUDY DESIGN: Retrospective review and comparison of death certificates and vital statistical coding. METHODS: The manner of death is certified as a therapeutic complication when death is caused by predictable complications of appropriate therapy, and would not have occurred but for the medical intervention. Based on medical examiner records, complications that caused or contributed to deaths over a five-year period were examined retrospectively. These fatalities were compared with deaths coded as medical and surgical complications by the New York City Bureau of Vital Statistics. RESULTS: The Medical Examiner's Office certified 2471 deaths as therapeutic complications and 312 deaths as accidents occurring in healthcare facilities. In contrast, the New York City Bureau of Vital Statistics reported 188 deaths due to complications of medical and surgical care. CONCLUSIONS: Use of the term 'therapeutic complication' as the manner of death identified nearly 14 times more deaths than were reported by the New York City Bureau of Vital Statistics. If these therapeutic complications and medical accidents were considered as a 'disease', they would rank as the 10th leading cause of death in New York City, surpassing homicides and suicides in some years. Nationwide policy shifts that use the term 'therapeutic complication' would improve the capture and reporting of these deaths, thus allowing better identification of fatal adverse medical events in order to focus on and assess preventative strategies.

Inhibition of Mycobacterium tuberculosis-induced signalling by transforming growth factor-ß in human mononuclear phagocytes.

Tuberculosis (TB) is associated with excessive production and bioactivation of transforming growth factor bets (TGF-ß) in situ. Here, modification of expression of components of plasminogen/plasmin pathway in human monocytes (MN) by inhibitors of TGF-ß signalling was examined. Smad3 siRNA effectively inhibited TGF-ß-induced urokinase plasminogen activator receptor (uPAR). Agents known to interfere with TGF-ß signalling, including the Smad inhibitors SIS3 and erythromycin derivatives, and ALK5 receptor inhibitor (SB 431542) in inhibition of uPAR expression in response to Mycobacterium tuberculosis (MTB) were examined. Inhibition by SIS3 only inhibited uPAR mRNA significantly. SIS3 may prove to be an effective adjunct to TB therapy.

Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation.

Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV-1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)-6, IL-8, interferon (IFN)-γ and transforming growth factor (TGF)-ß, and did not include other T helper type 1 (Th1) (IL-2, IL-15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL-6 and IL-8, less with TGF-ß, and not with IFN-γ. Among CD4 T cells, FoxP3-reactive CD25(hi) were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3(+) CD25(hi) CD4 T cells were positive for IL-8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV-1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL-6, IL-8, IFN-γ and TGF-ß and regulatory T cells (T(reg) ). A correlation in expansion of T(reg) with proinflammatory cytokines (IL-6 and IL-8) in pleural fluid was shown. T(reg) themselves may promote the inflammatory cytokine milieu through IL-8.

Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis.

Several lines of evidence suggest that host genetic factors controlling the immune response influence infection by Mycobacterium tuberculosis. The proinflammatory cytokine interleukin (IL)-1beta and its antagonist, IL-1Ra (IL-1 receptor agonist), are strongly induced by M. tuberculosis and are encoded by polymorphic genes. The induction of both IL-1Ra mRNA and secreted protein by M. tuberculosis in IL-1Ra allele A2-positive (IL-1Ra A2(+)) healthy subjects was 1.9-fold higher than in IL-1Ra A2(-) subjects. The M. tuberculosis-induced expression of mRNA for IL-1beta was higher in subjects of the IL-1beta (+3953) A1(+) haplotype (P = 0.04). The molar ratio of IL-1Ra/IL-1beta induced by M. tuberculosis was markedly higher in IL-1Ra A2(+) individuals (P < 0.05), with minor overlap between the groups, reflecting linkage between the IL-1Ra A2 and IL-1beta (+3953) A2 alleles. In M. tuberculosis-stimulated peripheral blood mononuclear cells, the addition of IL-4 increased IL-1Ra secretion, whereas interferon gamma increased and IL-10 decreased IL-1beta production, indicative of a differential influence on the IL-1Ra/IL-1beta ratio by cytokines. In a study of 114 healthy purified protein derivative-reactive subjects and 89 patients with tuberculosis, the frequency of allelic variants at two positions (-511 and +3953) in the IL-1beta and IL-1Ra genes did not differ between the groups. However, the proinflammatory IL-1Ra A2(-)/IL-1beta (+3953) A1(+) haplotype was unevenly distributed, being more common in patients with tuberculous pleurisy (92%) in comparison with healthy M. tuberculosis-sensitized control subjects or patients with other disease forms (57%, P = 0.028 and 56%, P = 0. 024, respectively). Furthermore, the IL-1Ra A2(+) haplotype was associated with a reduced Mantoux response to purified protein derivative of M. tuberculosis: 60% of tuberculin-nonreactive patients were of this type. Thus, the polymorphism at the IL-1 locus influences the cytokine response and may be a determinant of delayed-type hypersensitivity and disease expression in human tuberculosis.

HIV seroprevalence among suicide victims in New York City, 1991-1993.

OBJECTIVE: The authors sought to determine the HIV seroprevalence among suicide victims in New York City. METHOD: All suicides of city residents from 1991 through 1993 were studied. The crude proportion of all suicide victims who were HIV positive and the proportion adjusted to the age, gender, and racial/ethnic characteristics of the New York City population were determined. The demographically adjusted proportion was then contrasted with HIV seroprevalence estimates for the New York City general population. HIV-seropositive suicide victims were assessed for pathological findings suggestive of HIV-related illnesses. RESULTS: The crude proportion of all suicide victims who were HIV seropositive was 0.088, and the demographically adjusted proportion was 0.049. Over 90% of all HIV-positive suicide victims were aged 25 to 54 years, and almost 90% were men. Among black and Hispanic men aged 35 to 54 years who committed suicide, the proportion who were HIV seropositive was 0.252--the highest seropositive rate of any demographic group. More than two-thirds of HIV-seropositive suicide victims had no HIV-related pathology or AIDS-indicator conditions at autopsy. CONCLUSIONS: The demographically adjusted proportion of suicide victims who were HIV positive (approximately 0.038 to 0.059), contrasted with the HIV seroprevalence estimates for the New York City general population (approximately 0.014 to 0.032), the absence of HIV-related pathology among suicide victims, and the likelihood that many HIV-positive individuals had other risk factors for suicide, such as substance abuse, suggests that a positive HIV serostatus is associated, at most, with a modest elevation in suicide risk.

Lower risk of suicide during pregnancy.

OBJECTIVE: The authors determined the risk of suicide during pregnancy. METHOD: The autopsy reports of all female residents of New York City, 10-44 years old, who committed suicide from 1990 to 1993 were assessed for pregnancy. These data were compared with age-adjusted and race-adjusted standardized mortality ratios for women, which were calculated by using population data from the 1990 U.S. Census as well as data obtained from the New York City Health Department on the number of live births, spontaneous abortions, and induced abortions. RESULTS: The standardized mortality ratio for suicide during pregnancy was 0.33; that is, the number of suicides of pregnant women was only one-third of that expected. CONCLUSIONS: Despite the mood swings and stresses associated with pregnancy and impending childbirth, pregnant women have a significantly lower risk of suicide than women of childbearing age who are not pregnant.

Use of prescription psychotropic drugs among suicide victims in New York City.

OBJECTIVE: The authors examined the rate of prescription psychotropic drug use among suicide victims at the time of their death. METHOD: From a total of 1,970 suicides that occurred in New York City from 1990 to 1992, 1,635 cases that had a complete toxicologic analysis and an injury-death interval of 48 hours or less were assessed at autopsy for the presence of commonly prescribed antidepressants and neuroleptics. RESULTS: Prescription psychotropic medications were detected in only 16.4% (N = 268) of the suicide victims studied. Demographic factors associated with use of these drugs included female gender and white race. Poisoning accounted for 17.9% (N = 293) of all suicides studied, but antidepressants or neuroleptics were detected in less than half of these victims. Among all suicide victims in whom an antidepressant or neuroleptic was detected, almost half had used lethal methods other than poisoning. CONCLUSIONS: In this study, most individuals who committed suicide in New York City were not taking prescription psychotropic medications at the time of their death and either were not receiving pharmacotherapy or were noncompliant.

Human stress cardiomyopathy. Myocardial lesions in victims of homicidal assaults without internal injuries.

In order to clarify the relationship between stress and sudden death, we reviewed homicidal assaults that occurred in Cuyahoga County, Ohio (metropolitan Cleveland), over the preceding 30 years. Specifically, attention was focused on the autopsy and investigative findings relating to victims who died as a direct result of physical assault without sustaining internal injuries. Fifteen such victims were identified, and 11 of them showed cardiac changes (myofibrillar degeneration) consistent with "stress cardiomyopathy," comparable to lesions described in stressed animal experiments. Age matched and cardiac disease matched control subjects showed little or no evidence of such changes. Two victims survived for a time in the hospital, suffered arrhythmias throughout the hospital course, and had the described cardiac lesions at autopsy. We interpret our data as being strongly supportive of the theory of catecholamine mediation of these myocardial changes in man and of the lethal potential of stress through its effect on the heart.

Subtle fatal child abuse.

The majority of homicide victims in infancy and childhood have been either beaten or starved to death. However, the pathologist must recognize a much broader range of fatalities in early life for which an adult appropriately bears criminal responsibility. To emphasize the diversity and potential subtlety of homicide in infancy and childhood, we present six instances of fatal child abuse that illustrate the types of unusual physical and chemical assault and the covert negligence that kill children. Unfamiliarity with the law, lack of suspicion in approaching cases, and failure to utilize necessary techniques to establish the mechanism of death can obscure recognition of the homicidal nature of such fatalities.

Arterial dysplasia with ruptured basilar artery aneurysm: report of a case.

An 11 year old girl died unexpectedly as a result of spontaneous subarachnoid hemorrhage originating from a ruptured giant fusiform aneurysm of the basilar artery. The aneurysm had developed as a long standing complication of arterial fibromuscular dysplasia. This discussion describes the light and electron microscopic findings in the aneurysm and the histologic examination of abnormalities in the muscular arteries of the viscera.

Neuropathology of human immunodeficiency virus infection at different disease stages.

The authors studied the brains of 471 adults infected with human immunodeficiency virus type 1 (HIV-1): 123 asymptomatic carriers, 127 in an early stage of acquired immunodeficiency syndrome (AIDS) with pulmonary tuberculosis or bacterial infections, and 221 in fully developed AIDS with opportunistic infections or neoplasms. Lymphocyte infiltration of the leptomeninges and of perivascular spaces occurred at all stages, but the frequency was significantly higher in asymptomatic carriers. Microglial nodules appeared at all stages of disease; they were not an early indicator of HIV encephalitis (HIVE). The incidence of HIVE was unrelated to the stage of AIDS, suggesting that HIVE occurs before opportunistic infections and neoplasms. Drug abuse, such as cocaine and opiates, may enhance HIV replication and increase the incidence of HIVE in the early stage of AIDS. Opportunistic infections or lymphoma involved only the brain in 31.2% of persons with fully developed AIDS. Conversely, opportunistic infections or neoplasms involved only organs other than the brain in 55.7% of persons with fully developed AIDS. In 13.1% of persons with fully developed AIDS, opportunistic infections or neoplasms involved the brain and other organs. Multiple intracranial opportunistic infections and lymphoma coexisted in 4.1% of persons with fully developed AIDS. The authors identified cerebrovascular disease in 10.6% of asymptomatic carriers, 7.1% of early AIDS, and 5.0% of fully developed AIDS. The observed sequence of abnormalities may be useful in understanding the progression of HIV disease in the brain.

Cocaine induced intracerebral hemorrhage: analysis of predisposing factors and mechanisms causing hemorrhagic strokes.

We analyzed 26 autopsy cases of cocaine induced intracerebral hemorrhage and compared those findings with those of 26 autopsy cases of cocaine induced cerebral aneurysm rupture. The incidence of hypertensive cardiovascular disease (HCVD) was significantly higher in persons with intracerebral hemorrhage than in those with aneurysm rupture. Our findings suggest that HCVD predisposes to cocaine induced intracerebral hemorrhage. We propose that the foregoing relationship results from a cocaine induced alteration of cerebral autoregulation in the context of increased cerebral blood flow.

The contrecoup phenomenon. Reappraisal of a classic problem.

We describe briefly and comment upon the salient strengths and limitations of the major published theories that purport to explain the mechanism of contrecoup cerebrocortical contusions. Through the application of mechanical principles, we then present a modification, clarification, and expansion of selected aspects of several theories. Our final formulation emphasizes the injurious potential of nonuniform compressive stress and the relationship between brain lag and rotationally induced injury. The resulting theory remains faithful to the laws of physics while explaining the location and distribution of cerebrocortical contusions opposite the site of a moving head impact.

Postmortem diagnosis of myocardial disease by enzyme analysis of pericardial fluid.

The authors measured the activities of CK, LDH, and their isoenzymes in pericardial fluid to determine their usefulness in evaluating acute myocardial injury. Their prospective study reveals that these enzymes significantly are elevated in cardiac deaths in contrast to fatalities from noncardiac causes. Also, a group of healthy individuals who were victims of violent deaths and died from extracardiac injuries had enzyme elevations greater than those found in acute cardiac deaths, suggesting catecholamine-mediated myocardial injury (stress cardiomyopathy) as part of the physiologic response to trauma. Measurements of cardiac enzymes in pericardial fluid may prove useful in establishing the postmortem diagnosis of acute myocardial injury in instances when such injury is suspected but cannot be established by ordinary histologic methods. Studies such as this may help in defining the participation of myocardial injury as one of the lethal mechanisms in various causes of death.

Carboxyhemoglobin concentrations in flash fire victims: report of six simultaneous fire fatalities without elevated carboxyhemoglobin.

Eight people died in a traffic accident involving a tractor-trailer and ten autos. The accident caused a series of flash fires from ruptured gas tanks. Complete autopsies established that six of the victims died exclusively from thermal trauma; none showed an elevated blood carboxyhemoglobin concentration. Flash fire victims are exceptions to the axiom that elevation of blood carboxyhemoglobin is a sine qua non for concluding that a decedent recovered from the scene of a conflagration was alive in the fire.

HIV infection among victims of accidental fatal drug overdoses in New York City.

AIMS: To determine the factors associated with HIV seroprevalence rates for victims of drug overdoses. DESIGN: Descriptive epidemiologic survey of a complete 3-year sample of accidental fatal drug overdoses. SETTING: New York City (population 7,322,564). PARTICIPANTS: All people over 15 years of age (n = 2159) who died of accidental fatal drug overdoses during 1991-93. MEASUREMENTS: Using medical examiner data and logistic regression analyses were conducted to examine the association between HIV seroprevalence and gender, race, age and type of drug overdose. FINDINGS: There were 646 (29.9%) victims who were HIV positive. Women (37.5%) were more likely than men (27.9%) to be HIV positive. African-Americans (39.4%) had a higher rate of HIV infection than Latinos (27.5%), whites (19.2%) or Asians (8.3%). Victims residing in communities with higher levels of poverty had higher rates of HIV infection but poverty did not account for the high rates of HIV infection among African-Americans. The highest rates of HIV infection were found among victims aged 35-44 years (38.8%) and 45-54 years (33.7%). Dying from an opiate overdose was associated with a 2.4 times increase in the likelihood of being HIV positive. CONCLUSION: If opiate abuse continues to rise in the United States, HIV infection will increase in the next few years. Women who abuse drugs participate in risky sexual practices and are more likely than men to develop HIV infection from receptive sex as well as sharing of needles. Harm reduction programs should address risky sex as well as needle programs. There should be further study of why African-Americans who died of drug overdoses have the highest rates of HIV infection.

Contrecoup skull fractures.

The authors describe the frequency, pathological features, and significance of contrecoup fractures of the anterior cranial fossae, which occur commonly when falls with occipital or temporal impacts cause fatal head injuries.

Acute responses to blunt head trauma. Experimental model and gross pathology.

This study of blunt craniocerebral trauma describes an experimental model that involves delivery of forceful blows to the resting movable skulls of anesthetized cats. Injuries inflicted by this method included skull fractures in 81% of cases, epidural hemorrhages in 50%, subdural hemorrhages in 80%, subarachnoid hemorrhages in 100%, and brain contusions in 84%. In the majority of instances the subdural and epidural hemorrhages were thin films of blood that did not compress or distort the subjacent brain. The distribution of cerebral contusions was restricted to the cerebral parenchyma beneath the locus of cranial impact except for contusions associated with skull fractures. This experimental model recapitulates clinically realistic human cranial trauma and produces pathological lesions suitable for investigation of the pathophysiology of blunt head trauma.

A profile of homicides on the streets and in the homes of New York City.

Although prior research has found that homes containing firearms and illicit drug and ethanol users are more likely to be the scene of a homicide than homes that do not contain these elements, the authors studied homicides on the streets as well as in homes so as to assess the role of firearms, cocaine, and ethanol in both settings. Using the files of the Chief Medical Examiner, the authors reviewed all 4,468 homicides occurring in New York City in 1990 and 1991. The most frequent places of occurrence were the streets and other outdoor places (49.6 percent) and the victims' homes (19.3 percent). Firearms were the cause of death for 49.6 percent of homicides in the home and 80.3 percent of those on the streets. Use of cocaine and ethanol was found more frequently among victims killed on the streets than those killed at home. In addition, victims killed on the streets were more likely to be male, ages 15-24 years, and African American. Further research in regard to prevention and intervention strategies is needed, keeping in mind the different patterns of homicide on the streets compared with those occurring in other settings.

Forensic pathology and the autopsy.

Questionnaires sent to representative medicolegal jurisdictions in the United States showed that medicolegal necropsies comprise a substantial proportion of the total number of autopsies performed. Qualitative differences between customary hospital autopsies and their forensic counterparts include autopsy bias, the importance of trauma, biological variability, and medicolegal logic. Because of these differences, medicolegal autopsies have an important role to play in the education of undergraduate and graduate medical students and should be incorporated into the training programs of academic departments of pathology.