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Background: Every year, more than 795,000 people in the United States have a stroke, and each year about 140,000 Americans die from strokes. Although there is abundant information on the epidemiology, risk factors, pathophysiology, and many clinical features of strokes, there is a lack of specific numerical quantitation on the neuroanatomical distribution of strokes. Methods: This retrospective study utilized de-identified reports of radiologic imaging to determine the neurovascular anatomical location of acute ischemic cerebral infarcts in a 637-bed regional hospital in a rural area during the one-year interval from October 1, 2018 through September 30, 2019. Results: During the one-year study period, there were 418 acute ischemic strokes, and 54.6% (228/418) were in the territory of a single large vessel. Of the single large vessel strokes, 62.3% (142/228) were in a middle cerebral artery (MCA) territory, 12.1% (29/228) in a posterior cerebral artery (PCA) territory, 8.8% (20/228) in a basilar artery distribution, 7.5% (17/228) in a posterior inferior cerebellar artery (PICA) distribution, 6.6% (15/228) in an anterior cerebral artery (ACA) distribution, 1.8% (4/228) in a superior cerebellar artery (SCA) distribution, and 0.4% (1/228) in an anterior inferior cerebellar artery (AICA) territory. Internal capsule lacunar strokes accounted for 17.7% (74/418) of the total, brainstem lacunar strokes for 8.1% (34/418) and thalamic lacunar strokes for 5% (21/418) of the infarctions. Watershed infarctions accounted for 2.9% (12/418) of the strokes, 9 in the MCA/PCA watershed area and 3 in the MCA/ACA watershed area. Conclusions: This pilot study illustrates a methodology for collecting data to substitute specific numerical quantitation for vague generalities about the neuroanatomical distribution of strokes. Such quantification can enable evidence-based data-driven improvements in the care of stroke patients.

Chronic kidney disease (CKD) is a progressive disease that affects millions of adults every year. Major risk factors include diabetes, hypertension, and obesity, which affect millions of adults worldwide. CKD is characterized by cellular injury followed by permanent loss of functional nephrons. As injured cells die and nephrons become sclerotic, remaining healthy nephrons attempt to compensate by undergoing various structural, molecular, and functional changes. While these changes are designed to maintain appropriate renal function, they may lead to additional cellular injury and progression of disease. As CKD progresses and filtration decreases, the ability to eliminate metabolic wastes and environmental toxicants declines. The inability to eliminate environmental toxicants such as arsenic, cadmium, and mercury may contribute to cellular injury and enhance the progression of CKD. The present review describes major molecular alterations that contribute to the pathogenesis of CKD and the effects of arsenic, cadmium, and mercury on the progression of CKD.

Amniotic fluid embolism is a rare, often fatal complication of labor and delivery. The classic presentation is the sudden onset of a triad of clinical manifestations: hypoxia, hypotension and coagulopathy. Understanding of the syndrome as an immunologically mediated, complicated and often catastrophic maternal response to fetal or placental antigens is coming into focus. New treatments such as extracorporeal membrane oxygenation (ECMO) and better use of old treatments such as transfusion offer hope, but the condition is often rapidly fatal, so saving the maternal and fetal lives depends on rapid recognition of the syndrome. This series of three cases illustrates the clinical features enabling the rapid recognition needed for successful treatment of amniotic fluid embolism syndrome.

Blood transfusion for chronic anemia can lead to acute or decompensated heart failure in patients who have fluid overload as part of their compensatory response and/or have intrinsic heart disease, and then it could be fatal in such clinical scenarios. This is the report of a case of profound chronic anemia in a young male patient, who was not transfused and then developed confusion followed by terminal cardiopulmonary arrest. Autopsy revealed severe trichuriasis to be the cause of the anemia, along with severe ascariasis, but minimal intrinsic brain disease. This supports the conclusion that anemia was the cause of the confusion, and the lesson that confusion may be a sign that the benefit of blood transfusion outweighs the risk in a patient with severe chronic anemia.

Illustrative cases of diseases that are difficult to suspect and diagnose can serve as useful reminders. Invasive pulmonary aspergillosis and adenovirus hepatitis are two such diseases, both revealed by autopsy in this case of Hodgkin lymphoma refractory to chemotherapy treated with allogeneic hematopoietic stem cell transplantation complicated by these two fatal infections. This patient was cured of Hodgkin lymphoma, Clostridioides difficile colitis and thrombotic thrombocytopenic purpura using the marvels of modern medicine. This case illustrates many features of aspergillosis and adenovirus hepatitis, shows the value of autopsy in revealing diagnoses, and illustrates the limits of modern medicine, which should serve as a mental spur in our efforts to advance medical science, to try to defeat the numerous demons of disease, who seem to keep outwitting us.

Background Adhesions are bands of tissue that form postoperatively after intra-abdominal surgery. Adhesions cause significant morbidity and despite ongoing research no agent or method has been shown to completely prevent adhesions. Human amnion-derived matrix is a complex tissue matrix derived from human placenta and has been used in other areas of surgery to promote healing and decrease scar tissue formation. Our hypothesis was that aerosolized human amnion-derived matrix particulate solution (HAMPS) applied during abdominal surgery would decrease adhesion formation in rats. Methods Twenty-four Sprague-Dawley rats were divided into 4 different groups. Group 1 was the control group (CG) which had cecal abrasion 20× with a surgical rasp to generate the adhesion model. Groups 2-4 were the treatment groups (TGs) and had cecal abrasion plus application of the HAMPS at concentrations of 6.25, 12.5, and 25 mg/cc, respectively. After 30 days, rats were euthanized and adhesion assessment performed. Results In all groups there were minimal adhesions noted at necropsy. Moderate inflammation was 33% in CG versus 11% in combined TGs. Average adhesion was 1.00 in CG versus 0.44 in combined TGs. This indicated an observational improvement in adhesions/inflammation in the TGs, although this did not reach statistical significance. There was a trend toward significance in the 12.5 mg/cc group alone ( P = .054). Conclusion Overall, HAMPS showed an observational decrease in adhesions in TGs although not statistically significant. There was a trend toward significance in the 12.5 mg group. Additional studies will have to be performed to further evaluate this subgroup.

Hepatic cirrhosis, diabetes mellitus and iron overload can each independently predispose to cryptococcosis. Hereditary hemochromatosis leads to all three of these predispositions. This report is the case of a patient with chronic hepatitis B virus infection and cirrhosis, who had markedly elevated serum ferritin and 99% transferrin saturation, and developed a leukemoid reaction. Autopsy revealed disseminated cryptococcosis for which the leukemoid reaction was a clue and possible hereditary hemochromatosis of which elevated ferritin and transferrin saturation can be clues. Hereditary hemochromatosis is an important diagnosis clinicians should never miss because early treatment with phlebotomy can be life-saving. Disseminated cryptococcosis can be rapidly diagnosed with serum cryptococcal antigen test and is treatable.

the case we report: mildly elevated INR, arterial hypoxemia with normal chest radiograph, and dilated inferior vena cava suggestive of elevated right atrial pressure, possibly due to elevated pulmonary arterial pressure from thrombosis or hyperviscosity-induced obstruction. These features are eerily similar to COVID-19 suggesting the possibility that EBV infection could cause seizures with pathophysiology similar to COVID-19. This article is protected by copyright. All rights reserved.

There is a growing need for increased efficiency in the sterilization of single use medical devices and other products that contain polymer components. Gamma radiation is widely used for devices suited for radiation sterilization; however, safety, throughput and cobalt-60 source availability are challenging the prospect of relying on gamma radiation to meet the anticipated needs of the industry. Use of electron beam (e-beam) and X-rays as alternatives to gamma for radiation sterilization have been hampered in part by a concern that these modalities may adversely affect polymer integrity and performance relative to the gamma method, for which the industry has had much more experience. To address this concern, the effects of sterilization-relevant doses of e-beam, X-ray and gamma radiation were directly compared using common medical device polymers found in two prototypical commercial devices currently sterilized using cobalt-60 gamma irradiation. The Becton, Dickinson and Company (BD) Vacutainer™ Plus tube contains low-density polyethylene and chlorobutyl rubber components, while the BD Vacutainer™ Push Button Blood Collection Set contains polypropylene homopolymer and polyolefin elastomer components. Injection-molded samples prepared from the polymers used in these products were exposed to target doses of 15, 35, 50 and 80 kGy using gamma, e-beam and X-ray radiation. Changes in coloration, tensile properties and hardness were measured for each condition, and the effects of e-beam and X-ray irradiation compared with the effects of gamma irradiation on these properties. Both e-beam and X-ray appear as viable alternatives to gamma irradiation for sterilization of the polymers tested.

Mucormycosis is an increasingly frequent, difficult to diagnose, difficult to treat, often fatal infection, especially in patients with hyperglycemia from uncontrolled diabetes. Type I (von Gierke) glycogen storage disease is due to inherited deficiency of enzymes in glycogen metabolism, which causes hypoglycemia. This report is the case of a patient with von Gierke disease and a missed diagnosis of pulmonary mucormycosis. This report illustrates the importance of having a high index of suspicion for mucormycosis in the appropriate clinical context.

Hypertrophic cardiomyopathy used to be regarded as a rare untreatable cause of sudden death in young male athletes. This report is the case of a middle-aged female patient with hereditary hypertrophic cardiomyopathy masked by superimposed pericarditis and revealed by autopsy. This case report illustrates how co-morbidity can hide a crucial diagnosis. This case report also illustrates the value of autopsy disclosing a familial disease that is increasingly recognized and dramatically more treatable than a few decades ago. Sudden death due to hypertrophic cardiomyopathy has become preventable, if the diagnosis is made soon enough. The lessons for patient care from this case include the importance of not missing the diagnosis of hypertrophic cardiomyopathy in female patients.

It is important not to miss a diagnosis of infective endocarditis. It is fatal if untreated and most often successfully treatable if recognized. We report a classic case of subacute bacterial endocarditis with Osler nodes and Janeway lesions due to viridans streptococci from an oral source of poor dentition, infecting a presumably abnormal mitral valve. The diagnosis was missed repeatedly by multiple different clinicians over the course of seven months. Detailed analysis of this case suggests some of the pitfalls that led to the delay in diagnosis. The infective endocarditis was masked by analgesic medication, inadequate physical examination, and narrow focus thinking. The images of this case can serve as a reminder of the features of infective endocarditis. The detailed history and discussion can provide potential lessons in how to not miss the diagnosis of infective endocarditis.

Effective sterilization methods for single-use devices are a growing need for the medical industry. Concerns with safety, throughput and source availability, however, prompt prudent contingency planning for gamma irradiation of devices suited for radiation sterilization. Electron beam (e-beam) and X-ray represent two alternatives to gamma radiation if they can be confirmed to be compatible with sterilization of the devices. To address this question, the effects of sterilization-relevant doses of e-beam and X-ray radiation are directly compared to the effects of gamma radiation using two prototypical commercial devices currently sterilized using cobalt-60 gamma radiation. These devices include components that comprise six distinct polymer materials commonly used in the medical device industry. The devices investigated are the Becton, Dickinson and Company (BD) VacutainerTM Plus tube, comprised of low-density polyethylene, chlorobutyl rubber, and polyethylene terephthalate components; and the BD VacutainerTM Push Button Blood Collection Set, containing polypropylene, polyolefin elastomer, and polyvinyl chloride components. Changes in functionality, discoloration and select mechanical properties of components of each device were measured following exposure to targeted doses of 15, 35, 50 and 80 kGy. A statistical analysis was performed to determine if the effects of e-beam or X-ray radiation differ from the effects of gamma radiation for the properties considered. No devices were found to fail the functional performance tests at any of the doses considered. Small, but statistically significant differences were observed in device discoloration from e-beam, X-ray and gamma radiation following processing for certain materials at certain dose levels. Both e-beam and X-ray irradiation appear as viable alternatives to gamma irradiation for sterilization of the medical devices and materials considered.

Hysterectomy is a common surgery and rarely fatal. Here, we present a case of hysterectomy with postoperative complications, leading to a fatal outcome. The autopsy revealed the cause of death and clinicopathologic correlation suggested multiple lessons for patient safety. Patient safety can be enhanced by appropriate boundaries in the care of physician-patients, proactive monitoring and prompt treatment of postoperative asthma, nasogastric suction for postoperative ileus associated with vomiting, and assessment of the patient situation by a good history and physical examination, going to see the patient in person.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. Early implementation of therapeutic plasma exchange (TPE) has decreased the mortality rate from >90% to

Context.—The causes of death for patients with lung cancer are inadequately described. Objective.—To categorize the immediate and contributing causes of death for patients with lung cancer. Design.—The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Results.—Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. Conclusions.—The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

Radiologic studies are anatomic studies lacking the natural full-color, 3D, and microscopic-level examination of autopsies, suggesting that autopsies might be able to serve as quality control for radiology.Cases in which complete or near-complete autopsies were performed at a university hospital in 2008 were reviewed, and antemortem radiologic diagnoses were compared with corresponding autopsy findings. Discrepancies between antemortem radiologic diagnoses and autopsy findings were categorized.For 729 of the 828 diagnoses reviewed in the study, the pathologic condition in question was thought to be present at the time that a radiologic study of the relevant anatomic region was performed. Of these 729 radiologic diagnoses, 201 (27.6%) were determined to be discrepant from the corresponding autopsy diagnoses (i.e., autopsy deemed correct), but many of these radiologic discrepancies were not of clinical significance. The radiologic error rate considers only the clinically relevant discrepancies categorized as "missed diagnosis" or "misinterpretation"; it was calculated to be 3.3%. Interestingly, 32 autopsy discrepancies (i.e., radiology deemed correct) were also identified in the study.The results of this study suggest that even in 2008 patients sometimes died with undiagnosed or misdiagnosed diseases. Radiologic diagnoses discrepant from autopsy findings were consistently identified in this study and show that autopsies can help radiologists sharpen their skills in interpreting radiologic studies and can perhaps serve as quality control for radiology. The results also suggest that radiology can serve as quality control for autopsy.

Toxoplasma gondii usually causes an asymptomatic and then latent infection in human adults; however, a potentially fatal disseminated form can occur in immunocompromised patients. Given that the diagnosis of acute Toxoplasma infection, as opposed to latent disease, relies on finding direct evidence of T. gondii infection in tissue, pathologic examination is critical. There have only been a few reports describing the cytomorphology of Toxoplasma in exfoliative cytology, and no reports of the findings in Thin Prep. In this report, we describe a fatal case of toxoplasmosis in a cardiac transplant patient that was diagnosed by respiratory cytopathology. Although the extracellular organisms were well visualized on the Wright-Giemsa stained cytospin, they were only faintly seen on the Pap-stained cytospin trapped within mucin and were not easily appreciated on the ThinPrep slides nor the HE stained cell block sections. An immunohistochemical stain for Toxoplasma performed on the cell block was strongly positive, and an autopsy performed on the patient confirmed disseminated infection. Our case illustrates that the diagnosis of Toxoplasma in exfoliative cytology specimens can be challenging since organisms are not well visualized on ThinPrep or Pap-stained material; therefore, Wright-Giemsa stained material can be particularly helpful.

Although mortality in individuals with hemophilia is 2- to 3-fold higher than the general population, ischemic heart disease mortality is 50–80% lower than the general population [1–5]. Moreover, hemophilia carriers whose factor VIII levels are low, but not deficient, also appear to have low death rates of ischemic cardiac disease [6]. Elevated circulating factor VIII levels [7], as well as fibrinogen [8] and von Willebrand factor [9], are considered risk factors for cardiovascular disease. Yet, it is possible that low factor VIII levels may reduce the likelihood of clot formation, even in the presence of cardiovascular risk factors, such as smoking or elevated cholesterol, and, thereby, decrease coronary thrombosis and myocardial infarction in individuals with hemophilia.

We compared the results of HFE genotype with tests for iron binding saturation (IBS) in 190 consecutive patients with liver disease using 2 IBS cutoff levels: 45% and 60%. Saturation was more than 45% in 117 patients (61.6%) and more than 60% in 89 (46.8%). The number of patients (10) with the highest-risk HFE genotype (C282Y homozygote) was higher than expected. Elevated IBS cannot be used to predict genotype. There was a modest association of C282Y homozygosity with increased IBS (7 of 10, saturation >45% and 6 of 10, >60%). There was poor correlation of elevated saturation with other genotypes containing 1 or more HFE variants. Patients with a wild-type genotype (lacking HFE variants) and elevated IBS were far more likely to have an iron binding capacity less than 250 µg/dL (

A 52-year-old-white male underwent double lung transplantation for severe emphysema due to alpha-1-antitrypsin deficiency and heavy tobacco use. Following a postoperative course complicated by renal insufficiency, pulmonary emboli, and Clostridium difficile colitis, he was discharged in stable condition. Two months later, he was admitted to a local hospital with a fever, abdominal pain, diarrhea, nausea, and dyspnea. Computerized tomography (CT) of the chest revealed bilateral pleural effusions. Sigmoidoscopy was grossly normal but biopsy demonstrated cytomegalovirus (CMV) colitis, and the patient was placed on intravenous ganciclovir. Over the next week, he became progressively hypoxemic and was transferred to the University of Pittsburgh Medical Center (post-transplant day 81) for further evaluation. His medications on transfer included: ganciclovir, prednisone, tacrolimus, dapsone, fluconazole, ondansetron, lansoprazole, digoxin, and coumadin.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. Early implementation of therapeutic plasma exchange (TPE) has decreased the mortality rate from90% to10%. However, fatalities still occur in these patients. The goal of this study was to characterize the causes of death and related postmortem findings in patients with TTP in the current era of emergent TPE to identify possible areas for improvement in the care of these patients. We analyzed clinical history, laboratory and histopathologic findings, and causes of death of patients with active TTP or TTP in clinical remission autopsied at our institution over 22 years. Of 18 patients, 15 had TTP judged to be a cause of death: it was an underlying cause of death in five cases, intermediate in three, and contributing in seven. The most common immediate causes of death were cardiac arrest and myocardial infarction. The most common TTP-related findings at autopsy were thrombi/emboli in heart (9), lung (11), brain (3), kidney (7), followed by hemorrhages in heart (7), lung (8), brain (2), kidney (7), and infarcts in heart (5), lung (4), brain (6) and kidney (3). Analysis of the cases with TTP as a cause of death suggests that the mechanism of death is commonly cardiac in origin. Proactive measures to monitor and protect the heart may be beneficial in these patients.

Background. Patients are at an increased risk for developing malignancies after transplantation. Lymphomas, skin malignancies, Kaposi's sarcomas, and cervical/vulvar neoplasms are the most common, but visceral malignancies are also well documented, with a reported frequency ranging from 1% to 6%. These visceral tumors represent a mix of neoplasms that were clinically occult at the time of transplantation and those that arise de novo after transplantation. Little information, however, is available on the frequency of clinically occult malignancies at the time of transplantation and their contribution to the number of posttransplant malignancies. Methods. A retrospective study was performed of all patients who received an organ transplant from January 1981 to June 1997 and died within 100 days, a time interval in which epithelial malignancies found at autopsy were presumed to have been present, but clinically occult, at the time of transplantation. Results. A total of 375 patients were studied who received the following organ transplants: 231 liver, 52 heart, 26 heart and lung, 32 lung, and 34 kidney. Eleven malignancies were identified for an overall frequency of 2.9% and included three thyroid carcinomas, three carcinoids of the small bowel, two lung carcinomas, one laryngeal carcinoma, one renal cell carcinoma, and one seminoma. Conclusion. The 2.9% frequency of malignancies seen in this study suggests that a small, but significant, number of patients have occult malignancies at the time of transplantation and that these occult tumors contribute substantially to the number of malignancies that present clinically after transplantation.