Molecular Mechanisms of Cellular Injury and Role of Toxic Heavy Metals in Chronic Kidney Disease.

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.

Where in the Brain do Strokes Occur? A Pilot Study and Call for Data.

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.

Autopsy as a quality control measure for radiology, and vice versa.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Educational Case: Hemolysis elevated liver enzymes and low platelets (HELLP syndrome).

Recommended management of patients with preeclampsia starts with a comprehensive clinical maternal and fetal evaluation, including maternal complete blood count, platelets, creatinine, LDH, liver enzymes, and urine test for proteinuria, along with fetal ultrasonographic evaluation and fetal antepartum testing.7 Subsequent management depends on the results of this evaluation and on gestational age. Continued observation is recommended for a woman with a preterm fetus if she has gestational hypertension or preeclampsia without severe features, until delivery at 37 weeks of gestation in the absence of abnormal antepartum testing, preterm labor, premature rupture of membranes, or vaginal bleeding.7 There are numerous conditions precluding such expectant management including severe hypertension refractory to treatment, persistent headaches refractory to treatment, epigastric or right upper pain refractory to treatment, visual disturbances, motor deficit, altered sensorium, stroke, myocardial infarction, new or worsening renal dysfunction, pulmonary edema, suspected acute placental abruption, vaginal bleeding in the absence of placenta previa, eclampsia, or HELLP syndrome.7.

Effects of X-Rays, Electron Beam, and Gamma Irradiation on Chemical and Physical Properties of EVA Multilayer Films.

Gamma-ray irradiation, using the cobalt-60 isotope, is the most common radiation modality used for medical device and biopharmaceutical products sterilization. Although X-ray and electron-beam (e-beam) sterilization technologies are mature and have been in use for decades, impediments remain to switching to these sterilization modalities because of lack of data on the resulting radiation effects for the associated polymers, as well as a lack of education for manufacturers and regulators on the viability of these sterilization alternatives. For this study, the compatibility of ethylene vinyl acetate (EVA) multilayer films with different ionizing radiation sterilization (X-ray, e-beam, and gamma irradiation) is determined by measuring chemical and physical film properties using high performance liquid chromatography, differential scanning calorimetry, Fourier-Transform InfraRed spectroscopy (FTIR), surface energy measurement, and electron spin resonance techniques. The results indicate that the three irradiation modalities induce no differences in thermal properties in the investigated dose range. Gamma and X-Ray irradiations generate the same level of reactive species in the EVA multilayer film, whereas e-beam generates a reduced quantity of reactive species.

Ascariasis, trichuriasis and fatal non-transfusion.

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.

Amniotic fluid embolism: lessons for rapid recognition and intervention.

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.

Vasculitis with a neuromuscular presentation and associated cancer revealed by autopsy.

Peripheral neuropathy is common, but rarely due to vasculitis. This report is the case of a 74-year-old woman with systemic vasculitis who presented with progressive arm and leg weakness associated with numbness. Autopsy revealed a colon cancer, which may have triggered the vasculitis. This case illustrates the association between vasculitis and malignancy. The best treatment of vasculitis in patients with cancer-associated vasculitis is usually treatment of the cancer, which often yields remission of the vasculitis. This case also illustrates the difficulty of suspecting vasculitis since the symptoms and signs are nonspecific and protean. It is important not to miss a diagnosis of vasculitis. It is often life-threatening. It is treatable. The critical step in the diagnosis of vasculitis is to think of it.

How could hypoglycemia-inducing glycogen storage disease lead to hyperglycemia-induced mucormycosis?

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.

Disseminated cryptococcosis and hemochromatosis: clues to diagnosis.

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 grim reaper evading modern medicine: aspergillosis, adenovirus, and Hodgkin lymphoma.

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.

Does Human Amnion Membrane Prevent Postoperative Abdominal Adhesions?

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.

Death from pan-resistant superbug.

Acinetobacter baumannii has emerged as a pan-resistant superbug causing fatal infections in vulnerable patients. This report is the case of an immunosuppressed transplant patient with a fatal pneumonia due to pan-resistant Acinetobacter baumannii. Alternative therapy for resistant Acinetobacter infection is currently the subject of intense interest and research. This report illustrates the features of this type of emerging infectious disease and reviews some of the novel approaches to treatment.

Hypertrophic cardiomyopathy masked by pericarditis.

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.

A Psychiatrist with Postoperative Anxiety After Hysterectomy: How Could This Be Fatal?

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.

Infective Endocarditis Masked by Narrow Focus Thinking, Inadequate Physical Examination and Analgesic Medication.

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.

Perioperative myocardial infarction: diagnostic clues and prevention.

The diagnosis of perioperative myocardial infarction can be missed if the pain is masked by postoperative analgesia and the possibility is not considered. This report is the case of a patient with a missed diagnosis of perioperative myocardial infarction. Myocardial injury and infarction from noncardiac surgery is currently the subject of intense interest and research. This report illustrates the importance of the diagnosis and suggests clues that can be used to make the diagnosis.

Pneumonia as a trigger for atrial fibrillation.

In a rural mountainous region on a Friday, a 78-year-old man was seen in his physician's office for leg edema and diagnosed with new onset atrial fibrillation. He was discharged home to start medications for atrial fibrillation and heart failure. He was hospitalized the next day with septic shock due to pneumococcal pneumonia. The new onset of atrial fibrillation requires a trigger acting on a vulnerable substrate. These triggers include acute conditions such as alcohol intoxication, myocardial infarction and pulmonary embolism. Pneumonia may act as a trigger causing the new onset of atrial fibrillation.