Contribution of nonsteroidal anti-inflammatory drugs to deaths associated with peptic ulcer disease: a prospective toxicological analysis of autopsy blood samples.

CONTEXT: Of the side effects occurring in temporal association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), peptic ulcer disease is reported most often. OBJECTIVES: To (1) provide information on the temporal association between fatal peptic ulcer presenting as sudden death and NSAID use prior to death, and (2) to examine the diagnostic efficiency of postmortem determination of NSAID levels using high-pressure liquid chromatography. DESIGN: Prospective autopsy study of all cases of sudden death associated with peptic ulcer disease from a total of 1139 medicolegal autopsies performed during a 12-month period. METHODS: Postmortem femoral blood samples were analyzed for NSAIDs using high-pressure liquid chromatography, and specimens of gastric and duodenal mucosa were examined for coexisting pathologic conditions. RESULTS: Twelve fatalities that occurred out of hospital as a result of peptic ulcer disease and presented as sudden death were identified. Autopsy blood samples were positive for NSAIDs in 7 cases (ibuprofen in 4 cases, levels 0.8 to 1.4 microg/mL; diclofenac in 2 cases, levels 0.6 and 1.6 microg/mL; and ketoprofen in 1 case, level 0.3 microg/mL). The ages of the affected individuals (3 men, 4 women) ranged from 43 to 60 years. No other drugs, including corticosteroids, anticoagulants, salicylic acid, and salicylates, were present. Microscopic examination revealed no pathologic antemortem mucosal conditions in any of the cases. CONCLUSIONS: For the postmortem elucidation of etiopathogenetic factors contributing to fatal peptic ulcer disease, high-pressure liquid chromatography to determine NSAID levels in autopsy blood samples is of considerable diagnostic benefit, especially when combined with histology. The number of cases of sudden death involving younger individuals dying as a result of peptic ulcer disease in temporal association with preceding use of NSAIDs seems to be underestimated from the clinical viewpoint due to the underrepresentation of out-of-hospital fatalities in the field of clinical pathology.     

Evaluation of esophageal varices by multidetector-row CT: correlation with endoscopic 'red color sign'

To evaluate the ability of multidetector-row CT (MDCT) to predict a risk of hemorrhage in patients with esophageal varices, a total of 40 MDCT scans were performed in 29 patients who had been diagnosed with esophageal varices by conventional upper gastrointestinal tract endoscopy. In 11 patients, MDCT was performed both before and after endoscopic injection sclerotherapy (EIS). Endoscopically, the red color sign (RC sign) was present in 28 scans. Of the 11 patients who underwent EIS, the RC sign disappeared after EIS in 9. The MDCT scans were obtained in the arterial, portal, and equilibrial phases, and the portal phase images were used in this study. Subsequently, the extent of esophageal varices was categorized into four MDCT scores. The variceal score, the maximum short axis of the varices, and the presence of palisade vein dilatation obtained from MDCT had significant correlation with endoscopic variceal forms, and the presence and severity of RC sign, respectively (p<0.01). All cases with a maximum minor axis of more than 4 mm showed positive RC sign. MDCT was useful in the evaluation of esophageal varices for predicting a risk of hemorrhage.     

Delayed rupture of spontaneous tear of the ascending aorta--report of two fatalities.

A spontaneous tear of the ascending aorta, with or without medial dissection, can cause sudden death from hemorrhage due to aortic rupture. Two representative cases are described. Review of the clinical history and pathological changes showed that the terminal event was delayed allowing healing and reactive changes to occur in the aortic wall. A pathologist confronted with a fatal case of aortic rupture should be aware that death is not always immediate. Recognition of this has medicolegal importance, particularly if medical management is questioned because of a missed clinical diagnosis.     

Prophylactic sclerotherapy before the first episode of variceal hemorrhage in patients with cirrhosis

The value of sclerotherapy as prophylaxis against the first episode of variceal hemorrhage has not been established. Therefore, we randomly assigned 133 patients with cirrhosis of the liver (of alcoholic origin in 66 percent), esophageal varices, and no previous intestinal bleeding to either prophylactic sclerotherapy (n = 68) or no prophylaxis (n = 65). The groups were comparable in hepatic function, endoscopic findings, and the pathogenesis of cirrhosis. All patients who subsequently had a first episode of variceal hemorrhage received sclerotherapy whenever possible. During a median follow-up of 22 months, variceal hemorrhage occurred in 28 percent of the patients receiving sclerotherapy and 37 percent of the controls (P = 0.3). Thirty-five percent of the sclerotherapy group and 46 percent of the control group died. The survival curves (Kaplan-Meier) of both groups were similar (P = 0.2). However, among patients with alcoholic and moderately decompensated cirrhosis (Child-Pugh group B), survival was significantly higher in those receiving sclerotherapy, although the risk of bleeding was only marginally reduced by this procedure. We conclude that prophylactic sclerotherapy does not significantly reduce the risk of bleeding from esophageal varices, but that a subgroup of patients with esophageal varices and moderately decompensated alcoholic cirrhosis may benefit from prophylactic sclerotherapy because of factors not solely attributable to prevention of an initial episode of variceal bleeding.     

Long-term Outcomes of Endoscopic Variceal Ligation to Prevent Rebleeding in Children with Esophageal Varices

After an episode of acute bleeding from esophageal varices, patients are at a high risk for recurrent bleeding and death. However, there are few reports regarding the long-term results of secondary prophylaxis using endoscopic variceal ligation (EVL) against variceal rebleeding in pediatrics. Thirty-seven, who were followed for over 3 yr post-eradication, were included in the study. The mean duration of follow up after esophageal variceal eradication was 6.4±1.9 yr. The mean time required to achieve the eradication of varices was 3.25 months. The mean number of sessions and O-bands needed to eradicate varices was 1.9±1.2 and 3.8±1.5, respectively. During the period before the first EVL treatment, 145 episodes of bleedings developed in 37 children. Over the 3 yr of follow-up after variceal eradication, only 4 episodes of rebleeding developed in 4 of 37 patients. The four rebleeding episodes consisted of an esophageal variceal bleed, a gastric variceal bleed, a duodenal ulcer bleed, and a bleed caused by hemorrhagic gastritis. There was no mortality during long-term follow up after variceal eradication. During long-term follow up after esophageal variceal eradication using solely EVL in children with esophageal variceal bleeds, rebleeding episodes and recurrence of esophageal varices were rare. EVL is a safe and highly effective method for the long-term prophylaxis of variceal rebleeding in children with portal hypertension.     

Prophylaxis of first variceal hemorrhage in patients with liver cirrhosis

Summary Prophylaxis of bleeding from esophageal varices is a very tempting concept at first glance, especially under the assumption of a high mortality associated with first variceal hemorrhage. Up to now four different measures have been tried for prophylaxis: portacaval shunt operation, devascularization procedures, sclerotherapy, and drugs. With the exception of portacaval shunts, ongoing controlled trials show a weak trend toward reduction of variceal bleeding and prolongation of survival in selected patients with compensated cirrhosis and large varices. However, prophylaxis of first variceal bleeding must still be regarded as experimental and should be restricted to controlled clinical studies.Abbreviations ICG Indocyanine-green - WHVP/FHVP-gradient Wedged hepatic venous pressure minus free hepatic venous pressure gradient     

Tuberculous esophagitis with erosion into aortic aneurysm

An 87-year-old woman with a known atherosclerotic thoracic aneurysm died suddenly from a massive esophageal hemorrhage. Prior to death, tuberculous esophagitis was diagnosed by biopsy. At autopsy, a fistulous tract was found extending from the esophagus to the aortic aneurysm; this fistula proved to be the site of fatal hemorrhage. The tract was surrounded by a granulomatous inflammatory reaction, in which acid-fast bacilli were found. To our knowledge, this is the first reported case of tuberculous esophagitis extending to an aortic aneurysm resulting in hemorrhage and death.     

Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding

BACKGROUND AND METHODS: We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices. This prospective, controlled trial included consecutive eligible patients who had large varices (>5 mm in diameter) that were at high risk for bleeding. The patients were assigned to either propranolol therapy, at a dose sufficient to decrease the base-line heart rate by 25 percent, or variceal ligation, to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment. RESULTS: Of the 89 patients, 82 of whom had cirrhosis of the liver, 44 received propranolol and 45 underwent variceal ligation. The mean (+/-SD) duration of follow-up in each group was 14+/-9 and 13+/-10 months, respectively. The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1. After 18 months, the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group (P=0.04). Twelve patients in the propranolol group and four in the ligation group had bleeding. Three of the four in the ligation group had bleeding before their varices had been obliterated. Nine patients in the ligation group had recurrent varices, a mean of 3.7 months after the initial treatment. Five patients in each group died; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group. There were no serious complications of variceal ligation; in the propranolol group, treatment was stopped in two patients because of side effects. CONCLUSIONS: In patients with high-risk esophageal varices, endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding.     

Unexpected sudden death of a 19-year-old female with congenital single coronary artery ostium during exertion

Coronary artery anomalies are associated often with myocardial ischemia or sudden cardiac death. A 19-year-old woman who participated in an exertive game lost consciousness upon one such exertion. She was taken to a hospital where she died on the same day. An autopsy revealed that she had bifurcated coronary arteries, which arose from one coronary ostium in the left sinus of Valsalva. The right coronary artery arose from the left sinus and traveled between the aorta and the pulmonary trunk. The heart as well as the cardiac conduction system depended exclusively on the single coronary artery ostium for oxygenated blood supply, and the unbalanced blood distribution on her exertion probably led to sudden cardiac death. The case highlights the medicolegal importance of unexpected sudden cardiac death related to an anomalous origin of the coronary arteries.     

晚期血吸虫病食管静脉曲张破裂不同出血量套扎术的治疗效果

目的探讨在不同出血量及肝功能状态下,食管曲张静脉套扎术（EVL）治疗食管曲张静脉破裂（EVB）出血的临床治疗效果。方法选择湘岳医院2005年1月至2010年12月收治的晚期血吸虫病并发EVB患者107例,在内科综合治疗基础上给予EVL。结果本组患者107例,肝功能Child分级与食管曲张静脉程度有等级相关关系,相关系数为0.728（P〈0.01）,与出血量呈正相关关系,相关系数为0.848（t=16.426,P〈0.01）。内科治疗＋套扎术治疗的有效率为97.87%,单纯内科治疗的有效率仅为12.15%,二者比较差异有统计学意义（P〈0.01）。结论肝功能损害越严重食管胃底静脉曲张程度就越大、出血量也越多。内科治疗＋套扎术治疗EVB的有效率明显优于单纯内科治疗。     

猝死37例死因分析

目的 分析不明原因死亡患者的疾病分布及尸检病理学特点。方法 收集不明原因死亡尸体107例，解剖结果显示37例为猝死，占35％，对其进行组织病理学检查。结果 37例猝死的疾病分布以心血管最常见，共16例，占43．2％，其次为呼吸系统、神经系统、消化系统疾病。结论 通过尸体解剖和病理学检查，为解决医疗纠纷和明确猝死死因提供科学的鉴定依据，对提高医疗质量起到积极的作用。     

Angioarchitectural study of esophageal varices

Summary Pathomorphological and angioarchitectural characteristics of esophageal varices, mainly of ruptured varices, were studied in autopsy cases. Contrast medium was injected into the esophageal vein in 25 among 75 cases with varices, and in 4 cases without varices as a control. Out of the 75 cases with varices, rupture was confirmed in 8 cases. Ruptured points were recognized at the oral end of the longitudinal veins (these veins were called sudare-like veins in this study) in the lamina propria at the lower end of the esophagus in all of the 8 cases. This ruptured area was called the critical area. By morphometric examination, dilatation of these sudare-like veins was the most obvious in severe varices, and these veins were observed to penetrate the muscularis mucosae to connect to the submucosal veins at the critical area. This area seemed to be of the greatest significance in the pathogenesis of spontaneous variceal rupture.     

Postmortem demonstration of portal vein collateral circulation (author's transl)]

Introduction: Postmortem investigation of esophageal varices and the portal system is difficult, because veins are collapsed at autopsy. The demonstration of varices is possible by illumination of the isolated mucous membrane or by puncturing esophageal varices and filing them with different materials. Material and methods: We use a 15% aqueous gelatine solution (if needed with additional barium sulfate for x-ray examination) which is supplemented by 40% formaldehyde (40 ml in 1 1 gelatine solution). The superior mesenteric vein is catheterized and filled by a clyster-pump. Results: The mixture of gelatine and formaldehyde hardens within a few minutes. The autopsy is delayed only about half an hour. Within this time the portal system is well outlined. This method can show exactly the drainage of the portal system into the inferior vena cava. In cases of portocaval shunt or of esophageal transsection the result of the operation can be verified. The localization of the bleeding source of esophageal varices can be demonstrated by escape of the filling mass.     

Studies in stinging insect hypersensitivity: postmortem demonstration of antivenom IgE antibody in possible sting-related sudden death

The purpose of this study was to extend previous findings of elevated antivenom IgE antibodies in sera from persons experiencing fatal insect sting reactions. Elevated IgE antibodies to at least one venom were measured in sera from four of six witnessed fatal cases of sting anaphylaxis; in one of two unwitnessed cases of sudden, unexpected death in which the circumstances suggested possible sting anaphylaxis; and in one unwitnessed death where autopsy findings of massive swelling of the pharynx and larynx suggested anaphylaxis. Conversely, no elevated IgE antibodies were measured in serum from a boy who received more than 40 yellow jacket stings with subsequent cardiopulmonary arrest, from which he was successfully resuscitated. Measurement of IgE antibodies in postmortem sera may not only provide confirmatory evidence of fatal anaphylaxis following witnessed insect stings, but also may provide useful additional data in unwitnessed deaths where the clinical history or autopsy findings suggest unexplained anaphylaxis.     

Hymenoptera venom-specific IgE antibodies in post-mortem sera from victims of sudden, unexpected death

There have been reports of elevated venom-specific IgE levels in post-mortem sera from patients experiencing fatal Hymenoptera stings so we hypothesized that other cases of sudden death may be due to unrecognized sting anaphyiaxis. Of 94 sera obtained post mortem from subjects who died unexpectedly during the summer months, 22 (23%) contained elevated levels of IgE antibody to at least one insect venom. The causes of death as determined by autopsy did not differ significantly among patients with or without elevated IgE antibody levels. An identical percentage of seropositivity was noted in 48 post-mortem sera from victims of sudden, unexpected death in the winter months. Conversely, only 6% of sera from 92 living blood donors contained elevated venom-specific IgE antibodies. The appreciable incidence of elevated IgE antibodies in the post-mortem groups suggests that sting anaphylaxis should be more highly considered as a possible cause of unexpected death.     

Radiological score for hemorrhage in the patients with portal hypertension

Goal: To analyze the risk factors from radiological indices for hemorrhage in the patients with portal hypertension and weight risk factors. Method: We retrospectively analyzed all cases of portal hypertension with hepatitis B from June 2008 to June 2014 in Nanjing Drum Tower hospital. Patients with hepatocellular carcinoma, portal vein thrombosis, or portal hypertension with other causes, such as autoimmune hepatitis, pancreatitis, or hematological diseases were excluded. Results: Ninety-eight patients were recruited and divided into hemorrhage and non-hemorrhage groups. There were no statistical differences in clinical indexes such as age, prothrombin time, serum albumin, serum creatinine, serum sodium, hemameba, and blood platelet count. However, the differences were statistically significant in total bilirubin, hemoglobin, and liver function with the p values of 0.023, 0.000, and 0.039 respectively. For radiological indices, hemorrhage was correlated with diameter of inferior mesenteric vein (P=0.0528), posterior gastric vein (P=0.0283), and esophageal varices scores (P=0.0221). Logistic procedure was used to construct the model with stepwise selection and finally inferior mesenteric vein, posterior gastric vein, esophageal varices, and short gastric vein were enrolled into the model. These veins were scored according to the diameters and the rates of hemorrhage were increased with the score. We then validated the model with 26 patents from July 2014 to December 2014. The AUC value was 0.8849 in ROC curves for this radiological model. Conclusions: A risk model was constructed including inferior mesenteric vein, esophageal varices, posterior gastric vein, and short gastric vein. This radiological scoring model may be a valuable indicator for hemorrhage of portal hypertension.     

Fatal anaphylaxis: postmortem findings and associated comorbid diseases.

BACKGROUND: Anaphylaxis is an infrequent cause of sudden death. Death often results from circulatory collapse, respiratory arrest, or both. OBJECTIVE: To investigate the causes of death, anatomical findings, and comorbid diseases in cases of fatal anaphylaxis. METHODS: This is a retrospective case review of 25 unselected cases of documented fatal anaphylaxis. Each case report contained details of the fatal reaction, a review of the medical record, and laboratory and autopsy findings. Serum tryptase concentrations were measured in 7 cases. RESULTS: The anaphylactic deaths included 7 reactions to medications, 6 to radiocontrast material, 6 to Hymenoptera stings, and 4 to foods. The mean age was 59 years. The anaphylactic reaction began within 30 minutes of exposure in 21 of 25 cases, with death occurring within 60 minutes in 13 of 25 cases. Urticaria occurred in only 1 of 25 cases. Anatomical findings consistent with anaphylaxis were present in 18 of 23 patients undergoing autopsy. At least 1 significant comorbid disease was identified in 22 of 25 cases. CONCLUSIONS: (1) Elderly patients with substantial comorbid conditions constituted a significant number of the anaphylactic fatalities; (2) the onset of severe anaphylaxis occurred in less than 30 minutes in nearly every case; (3) 18 of 23 cases were associated with specific anatomical findings of anaphylaxis; (4) self-administered epinephrine was used in just 1 of 5 cases; and (5) serum total tryptase concentrations were elevated markedly in 4 of 7 cases tested.     

Alcohol estimation at necropsy: epidemiology, economics, and the elderly.

AIMS: To gather data on blood alcohol concentrations in a forensic necropsy population and to analyse the information on trends that may predict where alcohol testing is going to prove cost-effective. METHODS: Alcohol assays were performed on blood, urine, and vitreous samples in 1620 consecutive medicolegal necropsy examinations. RESULTS: Alcohol was detected in only 7% of natural deaths from all causes and in four of 40 deaths categorised as unknown/obscure. Alcohol concentrations > or = 350 mg/100 ml were found in nine drug/alcohol abuse deaths (range 362-506 mg/100 ml), five accidental deaths (356-504 mg/100 ml), and one homicide victim (400 mg/100 ml). Those categorised as alcohol abusers were represented in all but one category of death (unknown/obscure deaths in males), showing that many true alcoholics die with their alcoholism rather than of it; 39% of males and 34% of females with histories of alcohol abuse had alcohol present in their blood at necropsy at concentrations > or = 50 mg/100 ml, v only 9% (male) and 6% (female) without such history. CONCLUSIONS: The study highlights the problems of elderly and "hidden" alcoholics and illustrates cases where routine assays would provide additional significant information. Routine alcohol testing is useful in all cases of suspected unnatural death but universal testing of forensic necropsies is not cost-effective.     

Chaos and predicting varix hemorrhage

Despite a wide array of mechanisms implicated in esophagogastric varix hemorrhage, predicting the onset of bleeding or even identifying the dominant factor in its causation has proved elusive. In this article we re-examine variceal pathophysiology and hypothesize that bleeding is rooted in turbulent portal system flow, a phenomenon embodied in the 'new' science of chaos and the principles of non-linear, rhythmic fluid dynamics. Analogous to forecasting the weather, predicting turbulent flow hinges on defining the initial physical conditions, and, like the field theory of quantum physics, depends on probabilities and instabilities rather than direct proportional analysis. Based on the complex regional and systemic hemodynamic forces and local physical properties underlying formation and perpetuation of esophagogastric varices, we propose, as with climatologic events, that a relatively minor or remote physiologic adjustment may set into motion a sequence of destabilizing splanchnic blood flow kinetics that ultimately causes a varix to erupt. In other words, the onset of varix bleeding derives from a sudden, erratic switch from disorganized but stable to disruptive turbulent variceal blood flow, and as a 'chaotic' phenomenon, is likely to remain for the foreseeable future highly unpredictable.     

Fatal disseminated adenovirus infections in immunocompromised patients

Adenovirus has emerged as an important pathogen in immunocompromised patients, in whom disseminated disease occurs frequently and is associated with a high mortality rate. In a retrospective review of 1,847 consecutive autopsies, we identified 84 cases where adenovirus infection was suspected clinically. Adenovirus infection was confirmed at autopsy in 8 (10%) of 84 cases; all were immunocompromised patients. Six (75%) of these cases had disseminated adenovirus infection that contributed to death. Pathologic findings attributed to adenovirus infection included pneumonia with or without intra-alveolar hemorrhage, hepatic necrosis, enterocolitis with or without mucosal hemorrhage, epicardial hemorrhage, and ulcerations of the larynx, trachea, and ileum. This work shows that severe and fatal adenovirus infections are not infrequent, particularly in the immunocompromised population. Both clinicians and pathologists must become aware of the pathogenicity of adenovirus in this patient population, including its potential for causing life-threatening hemorrhage.