Acute Necrosis Research Articles

Predictors of Mortality During Initial Liver Transplant Hospitalization and Investigation of Causes of Death.

BackgroundLiver transplant (LT) remains a life-saving procedure with a high mortality rate. The present study investigated the causes of death and sought to identify predictive factors of mortality during the initial LT hospitalization.Material/MethodsWe retrieved data on first-time adult recipients who underwent LT between November 2017 and October 2019 receiving grafts from donation after citizen’s death. The risk factors for mortality during the initial LT hospitalization were confirmed by univariate analysis. We also analyzed the causes of death.ResultsWe enrolled 103 recipients, including 86 males and 17 females, with a mean age of 47.7 years. Thirty-eight (36.9%) recipients were labeled as non-cholestatic cirrhosis-related indications. Approximately 8% of all recipients had diabetes prior to LT. Induction therapy was used in 11 (10.7%) recipients, along with maintenance therapy. The median model for end-stage liver disease score at LT was 32.4 (21.4–38.4). The in-hospital mortality rate of LT recipients was 6.8% (7/103), and infections were responsible for most of the deaths (6/7). The 1 remaining death resulted from primary graft failure. Univariate analysis showed recipients with postoperative pneumonia (p<0.05), acute hepatic necrosis, and intensive care unit (ICU) stay ≥7 days (both p<0.01), postoperative bacteremia, creatinine on day 3 after LT>2 mg/dL, and alanine transaminase on day 1 after LT >1800 μmol/L (all P<0.001) were much more likely to die.ConclusionsIn-hospital mortality of LT recipients was high, due in large part to infections. Acute hepatic necrosis, prolonged post-transplant ICU stays, certain types of postoperative infections, and postoperative liver and kidney dysfunction were potential risk factors for in-hospital mortality of LT recipients.

Type 2 MI induced by a single high dose of isoproterenol in C57BL/6J mice triggers a persistent adaptive immune response against the heart.

Heart failure is the common final pathway of several cardiovascular conditions and a major cause of morbidity and mortality worldwide. Aberrant activation of the adaptive immune system in response to myocardial necrosis has recently been implicated in the development of heart failure. The ß‐adrenergic agonist isoproterenol hydrochloride is used for its cardiac effects in a variety of different dosing regimens with high doses causing acute cardiomyocyte necrosis. To assess whether isoproterenol‐induced cardiomyocyte necrosis triggers an adaptive immune response against the heart, we treated C57BL/6J mice with a single intraperitoneal injection of isoproterenol. We confirmed tissue damage reminiscent of human type 2 myocardial infarction. This is followed by an adaptive immune response targeting the heart as demonstrated by the activation of T cells, the presence of anti‐heart auto‐antibodies in the serum as late as 12 weeks after initial challenge and IgG deposition in the myocardium. All of these are hallmark signs of an established autoimmune response. Adoptive transfer of splenocytes from isoproterenol‐treated mice induces left ventricular dilation and impairs cardiac function in healthy recipients. In summary, a single administration of a high dose of isoproterenol is a suitable high‐throughput model for future studies of the pathological mechanisms of anti‐heart autoimmunity and to test potential immunomodulatory therapeutic approaches.

A prospective evaluation of hepatic parameters in congestive heart failure patients

Background: Heart failure is heterogeneous and complex clinical syndrome. Passive congestion of liver is associated with increase in direct and indirect serum bilirubin and elevated liver enzyme. Impaired perfusion due to decreased cardiac output is responsible for acute hepatocellular necrosis and serum aminotransferases will be elevated. Present study has been designed to study the prevalence of liver function abnormalities in heart failure patients, pattern of elevation of liver enzymes and correlation of liver function tests with etiology, duration and of heart failure.Methods: All patients enrolled for this study was evaluated clinically and echocardiographically. Various demographic parameters like age sex duration of disease were recorded on predesigned Performa.Results: Serum bilirubin was 3.76±1.62 mg/dl in class IV and least in class I that is 1.125±0.30 mg/dl. Serum AST was highest in class IV 154.64±24.96 IU and least in class I that is 36.21±12.65 IU (p=0.001). Serum ALT was highest in class IV 192.24±34.44 IU and least in class I that is 33.34±11.460 (p=0.001).Conclusions: From present study we can conclude that heart failure was common in fifth and sixth decade of life and there was male predominance. Congested hepatomegaly was common presentation jaundice and ascites was also common. Change in biochemical parameters was increased with severity and duration of heart disease.

ESTABLISH THE INITIAL PROCEDURE FOR DETECTING VIBRIO PARAHAEMOLYTICUS IN THE SHRIMP BY ONE STEP- PCR METHOD

Early Mortality Syndrome (EMS), also known as Acute Hepatopancreas Necrosis Disease (AHPND) in shrimps, has been identified as being caused by a strain of V. parahaemolyticus. This disease has caused enormous damage to the shrimp farming industry among countries in the world in general and Vietnam in particular. One of the main reasons for uncontrollable widespread disease is the process of identifying pathogens is slow and inaccurate, leading to no promptly preventive measurement. In order to enhance the ability to briefly detect disease and improve the current disease status, in this study the PCR process using two specific 16S rRNA and ldh primers has been developed to swiftly diagnose V. parahaemolyticus pathogen in shrimps with a detection threshold of 3.5x103 CFU/ml

Gastrointestinal mucormycosis due to Rhizopus microsporus following Streptococcus pyogenes toxic shock syndrome in an HIV patient: a case report

BackgroundGastrointestinal (GI) mucormycosis is a rare and often deadly form of mucormycosis. Delayed diagnosis can lead to an increased risk of death. Here, we report a case of GI mucormycosis following streptococcal toxic shock syndrome in a virologically suppressed HIV-infected patient.Case presentationA 25-year-old Thai woman with a well-controlled HIV infection and Grave’s disease was admitted to a private hospital with a high-grade fever, vomiting, abdominal pain, and multiple episodes of mucous diarrhea for 3 days. On day 3 of that admission, the patient developed multiorgan failure and multiple hemorrhagic blebs were observed on all extremities. A diagnosis of streptococcal toxic shock was made before referral to Siriraj Hospital – Thailand’s largest national tertiary referral center. On day 10 of her admission at our center, she developed feeding intolerance and bloody diarrhea due to bowel ischemia and perforation. Bowel resection was performed, and histopathologic analysis of the resected bowel revealed acute suppurative transmural necrosis and vascular invasion with numerous broad irregular branching non-septate hyphae, both of which are consistent with GI mucormycosis. Peritoneal fluid fungal culture grew a grayish cottony colony of large non-septate hyphae and spherical sporangia containing ovoidal sporangiospores. A complete ITS1–5.8S-ITS2 region DNA sequence analysis revealed 100% homology with Rhizopus microsporus strains in GenBank (GenBank accession numbers KU729104 and AY803934). As a result, she was treated with liposomal amphotericin B. However and in spite of receiving appropriate treatment, our patient developed recurrent massive upper GI bleeding from Dieulafoy’s lesion and succumbed to her disease on day 33 of her admission.ConclusionDiagnosis of gastrointestinal mucormycosis can be delayed due to a lack of well-established predisposing factors and non-specific presenting symptoms. Further studies in risk factors for abdominal mucormycosis are needed.

Acute ozone exposure can cause cardiotoxicity: Mitochondria play an important role in mediating myocardial apoptosis

ObjectiveTo clarify the cardiotoxicity induced by acute exposure to different concentrations of ozone in both gender rats and explore the underlying mechanisms. MethodsA total of 240 rats were randomly sorted into 6 groups with equal numbers of male and female rats in each group. The rats were subjected to ozone inhalation at concentrations of 0, 0.12, 0.5, 1.0, 2.0 and 4.0 ppm, respectively, for 6 h. After ozone exposure, function indicators, myocardial injury indexes and risk factors of cardiovascular disease in blood were assayed. ResultsHigh ozone exposure resulted in sustained ventricular tachycardia in male and female rats. Myocardial apoptosis in male rats started from 1.0 ppm ozone, and that in female rats started from 2.0 ppm ozone (p < 0.05). Caspase-9 increased significantly from 0.12 ppm ozone (p < 0.01) in both gender rats, while caspase-3 was initially activated at 0.5 ppm ozone. From 1.0 ppm ozone, mitochondrial cristae and myofilaments dissolved. The ratio of Bcl-2/Bax decreased significantly from 0.12 ppm and MRCC-IV decreased significantly from 2.0 ppm by ozone. ConclusionAcute ozone exposure can cause paroxysmal ventricular tachycardia in rats. Moreover, the changes of inflammatory factors in the heart tissues of female and male rats after ozone exposure were greater than those of oxidative stress. This study reported for the first time that 6 h ozone exposure does not cause acute cardiomyocyte necrosis, but promotes cardiomyocyte apoptosis in a mitochondrial-dependent manner. Ozone could regulate caspases-3 dependent cardiomyocyte apoptosis by affecting the balance between caspase-9 and XIAP.

Cardiopulmonary Lesions in Sheep Produced by Experimental AcuteClostridium PerfringensType D Enterotoxemia

Enterotoxemia caused by Clostridium perfringens type D is one of the most prevalent clostridial diseases of sheep. The lesions of the acute form of this disease, particularly the cerebral lesions, are well characterized; however, detailed descriptions of the cardiac and pulmonary lesions are lacking. Here we describe cardiopulmonary lesions in experimental acute type D enterotoxemia in sheep and determine the role of epsilon toxin (ETX) in the development of these lesions. Four groups of 6 sheep were intraduodenally inoculated with either a wild-type C. perfringens type D strain; its etx knockout mutant, which is unable to produce ETX; the etx mutant complemented with the wild-type etx gene, which regains the ETX toxigenic ability; or sterile culture medium as a control. All sheep were subjected to postmortem examination within 24 hours of inoculation. Lesion scores were compared between groups for pulmonary edema; hydrothorax; ascites; hydropericardium; endocardial, myocardial and epicardial hemorrhages; microscopic lesions of acute myocardial degeneration and necrosis; and myocardial, endocardial, and epicardial edema, hemorrhage, and inflammation. Only sheep inoculated with the wild-type and complemented ETX-toxigenic bacterial strains developed cardiopulmonary lesions, which were present in varying degrees of severity and proportions. These lesions were not present in sheep inoculated with the etx mutant or in the negative control. We conclude that severe acute cardiopulmonary lesions in sheep with experimental enterotoxemia are associated with the capacity of the strains to produce ETX. These changes are likely contributors to the clinical signs and even death of affected animals.

ORGANOPHOSPHORUS POISONING PRESENTING WITH ACUTE CORTICAL NECROSIS: A RARE COMPLICATION OF A COMMON DISORDER IN INDIAN SETTING

Organophosphorus poisoning in the form of insecticides and pesticides acts by inhibition of anticholinesterase activity at the neuromuscular junction leading to overstimulation of the nicotinic and muscarinic receptor. Renal involvement usually manifests as increased urination, urinary incontinence, strangury due to overstimulation of urinary bladder . Acute kidney injury in the form of acute cortical necrosis is an extremely rare complication of OP poisoning. Here we highlight a case 31 year old male who presented to Emergency with Dichlorvos poisoning with anuria due to cortical necrosis requiring hemodialysis with gradually improving renal function thus representing an uncommon complication of Organophosphorus poisoning thus making it as a rare and interesting presentation.&#x0D; Keywords: Organophosphorus poisoning, Acute cortical necrosis, Granular casts

S2672 Influenza a Virus as a Trigger for Autoimmune Hepatitis

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic liver disease caused by an immune-mediated destruction of the hepatocytes. Studies have shed the light on the important role of infections in triggering AIH as many viral infections and vaccines have been associated with it. We present an atypical case of AIH possibly triggered by Influenza A virus. To our knowledge, this is the first case report showing autoimmune hepatitis induced by influenza A virus. CASE DESCRIPTION/METHODS: A 52-year-old previously healthy female presented with new-onset jaundice after Influenza A viral infection. Initial laboratory investigations revealed an aspartate aminotransferase level of 1211 U/liter, an alanine aminotransferase level of 1506 U/liter, an alkaline phosphatase level of 305 U/liter, a total bilirubin level of 5.1, a direct bilirubin level of 3.4 and an international normalized ratio of 1. Serologic testing for hepatitis A, B, and C, HSV, CMV, and EBV were negative. Influenza A PCR was detected on nasopharyngeal sampling. Covid-19 test was negative. ASMA was positive with a titer of 1:80. ANA was positive with a titer of 1:80. Anti-mitochondrial antibody was negative. IgG, Alpha 1 antitrypsin, ceruloplasmin levels were within normal limits. No acetaminophen was detected in the blood. A CT abdomen showed normal biliary tree with no biliary strictures and no cirrhotic changes of the liver. Her liver biopsy showed acute hepatitis with moderate acute hepatocellular injury and hepatocellular necrosis with mixed portal infiltrates which include both plasma cells and eosinophils. Based on the revised International Autoimmune Hepatitis Group Scoring System for the Diagnosis of Autoimmune Hepatitis, her pretreatment score was 13 points. She was started on prednisone and had significant biochemical improvement. Her steroids were tapered and steroid sparing therapy with azathioprine was initiated. DISCUSSION: Influenza virus and vaccine have been proposed to cause autoimmune disease in the literature such as type 1 diabetes, narcolepsy, recurrent ITP, and multiple sclerosis. There has been an association as well between influenza vaccine and AIH. In a study published by Saski et al, they describe two cases of middle-aged women who developed autoimmune hepatitis after receiving influenza vaccine. We suggest that in our patient, the influenza A virus infection triggered autoimmune hepatitis. Autoimmune hepatitis should be considered in patients with persistently elevated liver enzymes following infections such as influenza.Figure 1.: Liver biopsy cores show findings suggestive of acute hepatitis. Dense portal inflammatory infiltrates are present, comprised of macrophages, lymphocytes, neutrophils, eosinophils and plasma cells. Piecemeal acute hepatocellular necrosis is also noted at the limiting plate (H&E, original magnification 10x).Figure 2.: Prominent bile stasis with sinusoidal Kupffer cell hyperplasia (H&E, original magnification 10x).

S2978 Intrathoracic Gastric Incarceration Following Laparoscopic Nissen Fundoplication

INTRODUCTION: Nissen fundoplication is the most performed surgical treatment for GERD. Given the complex anatomy of the EG junction, structural complications occur in up to 30% of cases following fundoplication. Our case is that of post fundoplication paraesophageal hernia with intrathoracic gastric incarceration. CASE DESCRIPTION/METHODS: A 57yo F with PMHx of GERD and type III paraesophageal hiatal hernia who had undergone laparoscopic surgery with primary diaphragm repair and Nissen fundoplication 7mo prior presented with acute onset of dysphagia and epigastric pain. CT revealed superoposterior migration of the Nissen wrap above the diaphragm and a well-circumscribed pouchlike sac to the left of the Nissen fundoplication containing an air-fluid level, without evidence of perforation. GI was consulted and the patient underwent EGD revealing a tight Nissen wrap that was barely traversable. The gastric mucosa was congested, inflamed, and ulcerated from the GE junction to the gastric body concerning for acute incarceration and necrosis. Surgery was urgently consulted, and the patient underwent emergent exploratory laparoscopy which revealed incarcerated herniation of the previously performed fundoplication into the chest. The fundus and upper body of the stomach were necrotic. Laparoscopic subtotal linear gastrectomy with mediastinal abscess drainage and closure of the diaphragmatic defect was performed followed by intraoperative EGD. The patient was discharged a few days later and is currently doing well. DISCUSSION: Nissen fundoplication is a widely accepted and commonly performed anti reflux surgical procedure. The gastric fundus is wrapped around the intraabdominal esophagus, after mobilizing the esophagus and reducing the hiatal hernia, if present. The rate of serious complications has been documented as less than 5%. Incarceration post fundoplication is usually a late diagnosis as it presents with non-specific symptoms of abdominal pain, nausea, and vomiting. EGD with comprehensive retroflexed examination of the fundoplication and barium esophagram are the primary tests to assess for structural complications. Paraesophageal hernia is one of the complications reported after laparoscopic Nissen fundoplication, and it requires emergency operation when associated with incarceration, obstruction, or strangulation of the stomach. There should be high index of suspicion for complications in patients with history of Nissen fundoplication for early detection, prompt treatment, and satisfactory outcomes.Figure 1Figure 2Figure 3

A RARE CASE OF FULMINANT MYOCARDITIS CAUSED BY MYCOPLASMA PNEUMONIAE SUCCESSFULLY TREATED WITH IVIG

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Fulminant myocarditis (FM) is a clinical condition which main characteristic is a rapidly progressive clinical course associated with hemodynamic compromise and high mortality risk.It is associated with an infectious process but rarely reported alongside Mycoplasma pneumoniae infection.It is unclear if the primary problem is ongoing damage from a virus, post-infectious inflammatory reactions, or both. Therefore,immunosuppressive therapy such as IVIG could be of potential benefit for treating FM.We report a rare case of FM caused by M.pneumoniae in a 27 y/o F showing improvement with IVIG therapy. CASE PRESENTATION: 27 y/o F with DM1 presented to ED with lethargy,hypotension,and tachycardia.Labwork showed DKA.She was intubated, transferred to the ICU and then started on insulin drip.On day 2, the she developed ST segment elevations,along with elevated troponin(11.86 ug/L).Echocardiogram showed EF of 42% along diffuse hypokinesis. Cardiac angiogram revealed nonobstructive CAD.On day 3, DKA resolved and patient was transitioned off insulin drip. Echocardiogram revealed worsened EF of 10-15%.Her workup showed positive M. pneumoniae IgM serology and doxycycline therapy was started, however she developed hemodynamic instability and was started on IVIG therapy.On day 4,she was weaned off vasopressor support and extubated.Repeat echocardiogram revealed EF>50% without wall motion abnormalities.Patient completed 2 days of IVIG therapy and was discharged after 8 days of hospitalization. DISCUSSION: Despite FM’s rareness, up to 12% of cases of sudden death in patients aged <40 years exhibit myocarditis.Our patient was admitted to the ICU with severe DKA, and within 24 hours she developed FM with positive M. pneumoniae IgM serology. M. pneumoniae is among the most common bacterial causes of respiratory tract infections and also associated with carditis. Myocarditis should be suspected in patients with or without cardiac signs and symptoms who present a rise in cardiac biomarker levels; changes in ECG or abnormalities of ventricular systolic function. Definitive diagnosis of myocarditis is achieved via endomyocardial biopsy(EMB).Yet, 2013 ACCF/AHA guidelines suggest excluding other causes of HF as EMB might be helpful when the results influence the management.Therefore,our patient underwent heart catheterization to rule out obstructive CAD upon the documented STEMI findings.IVIG therapy was started when she worsened hemodynamically.Yet, the use of IVIG for acute myocarditis should not be part of routine practice as its use is obscured by poor quality evidence making its use for infectious myocarditis debatable. CONCLUSIONS: The response to IVIG therapy suggests that the rapid decline of this case of infectious FM may be caused in part by an autoimmune process.Immunosuppressive treatment with IVIG in FM associated to M.pneumoniae may reduce the mortality rate and prevent irreversible myocardial injury. Reference #1: Veronese, G. (2018). Fulminant myocarditis: Characteristics, treatment, and outcomes. The Anatolian Journal Of Cardiology. https://doi.org/10.14744/anatoljcardiol.2017.8170 Reference #2: Tretjak, M., Verovnik, F., Vujkovac, B., Slemenik-Pusnik, C., & Noc, M. (2003). Severe Diabetic Ketoacidosis Associated With Acute Myocardial Necrosis. Diabetes Care, 26(10), 2959-2960. https://doi.org/10.2337/diacare.26.10.2959 Reference #3: Gupta, A., Ghimire, G., & Hage, F. (2013). Guidelines in review: 2013 ACCF/AHA Guideline for the Management of HF. Journal Of Nuclear Cardiology, 21(2), 397-399. https://doi.org/10.1007/s12350-013-9832-x DISCLOSURES: No relevant relationships by Sabree Abedrabo, source=Web Response No relevant relationships by Violeta Alvarez-Retamales, source=Web Response No relevant relationships by Mukul Bhattarai, source=Web Response No relevant relationships by Phyo Kyaw, source=Web Response No relevant relationships by Odalys Lara-Garcia, source=Web Response No relevant relationships by Suhayb Ranjha, source=Web Response No relevant relationships by Mingchen Song, source=Web Response

Rotavirus infection in a racing pigeon (Columba livia) in Great Britain during 2018

We report the first diagnosis of fatal rotavirus A (RVA) infection in a racing pigeon in Great Britain. In August 2018, a small group of racing pigeons (Columba livia) from...

S2857 Intestinal Behcet’s Disease Involving Terminal Ileum

INTRODUCTION: Behcet’s Disease (BD) is a rare, chronic, inflammatory vasculitis that affects several organ systems. Gastrointestinal involvement occurs in 3 to 25% of patients, with prevalence of 1–2/1,000,000 in the United States. We present a case of a patient with BD developing abdominal pain, diarrhea, and weight loss. CASE DESCRIPTION/METHODS: 57-year-old man with known oral and genital BD presented with fever, 1-week 15lb weight loss, abdominal pain and non-bloody diarrhea. He had been on infliximab, colchicine and prednisone. Laboratory studies exhibited iron deficiency anemia and leukopenia. Abdominal CT showed wall thickening of terminal ileum with fat stranding consistent with terminal ileitis. Tuberculosis, Cytomegalovirus and Histoplasma on serum were negative. Colorectal surgery was consulted, and in light of refractory ileitis patient underwent laparoscopic right hemicolectomy with ileocolic anastomosis. Histopathology demonstrated acute ischemic necrosis with ileal ulceration. After surgery, he was continued on low dose prednisone and infliximab infusions with resolution of intestinal symptoms. DISCUSSION: Intestinal BD presents with abdominal pain, anorexia, vomiting, diarrhea, dyspepsia, and bloody/non-bloody stools. Mucosal ulcerations are thought to be the underlying factor behind the symptoms, likely secondary to a combination of vein and venule vasculitis and large vessel involvement leading to ischemia and subsequent infarction. Diagnosis can be challenging given clinical similarities with Inflammatory Bowel Disease (IBD), however findings of vasculitis on biopsy favors intestinal BD over IBD. Imaging modalities are useful in its diagnosis including barium swallow, CT, and MRI which demonstrate colonic wall thickening. Endoscopy often reveals large deep punched out ulcers with discrete margins usually in the ileocecal region. Treatment is similar to IBD, including medical and surgical modalities. First line agents are sulfasalazine, mesalamine and corticosteroids. Second line are infliximab and adalimumab. Colectomy is indicated if medical therapy fails or with presence of bowel perforation, fistulae or GI bleeding. After surgery, recurrence is seen up to 40–80% of cases, with 80% requiring re-operation. Keep in mind that patients with history of BD can develop colitis.Image 1.: Pre-operative CT showing the coronal sequence of images. Notice the circumferentially thickened, irregular terminal ileum in the right lower quadrant. There is secondary luminal narrowing and adjacent fat stranding compatible with transmural involvement.Image 2.: Pre-operative CT as above. Image series.

Multiple extra-splanchnic venous thromboses - an unusual vascular complication of acute pancreatitis.

Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable clinical presentations. Splanchnic venous thrombosis is a well-known vascular complication of AP and commonly present as thrombosis of the splanchnic venous system: splenic vein (SplV), portal vein (PV) and superior mesenteric vein (SMV), either separately or in combinations. Involvement of extra-splanchnic vessels is rare and associated with morbidity and mortality. Vascular complications are late phenomena and usually associated with local complications of AP, namely acute fluid collections, necrotizing pancreatitis and walled-off pancreatic necrosis. Pathogenesis of venous thrombosis is multifactorial in which pancreatic inflammation and systemic inflammatory response play a key role. At present, there are no consensus guidelines on treatment and use of anticoagulation for venous thrombosis in the setting of AP. Limited literature suggests the use of anticoagulation in presence of PV with or without SMV thrombosis and extrasplanchnic vessel involvement. Literature on extra-splanchnic vessels involvement in acute pancreatitis is sparse. Here we present two cases with multiple extra-splanchnic vessels involvement and their management.

Spontaneous Necrotizing Hepatic Arteriopathy in Male Sprague-Dawley Rats.

Differentiating test article-related vascular changes from spontaneous findings is important for microscopic interpretation in drug safety evaluation studies intended for regulatory submission. Here, we report background spontaneous hepatic artery degeneration and necrosis in up to 20% of 3- to 9-month-old control male Sprague-Dawley rats in 23 individual safety studies. The vascular degeneration occurred in one cross section of a medium-sized hepatic artery near the hilus and ranged from acute intramural hemorrhage and fibrinoid necrosis to chronic fibrosis of the vascular wall with perivascular edema, hemorrhage, and inflammatory cell infiltrates. The cause was uncertain. Many microscopic features were consistent with systemic necrotizing arteriopathy (SNA) or polyarteritis; however, there was no change in arteries commonly affected in SNA/polyarteritis (mesenteric, pancreatic, or testicular arteries) and hepatic artery degeneration/necrosis occurred in younger rats which is unusual for SNA/polyarteritis. Spontaneous hepatic artery degeneration/necrosis represents a sporadic background finding that may be confused with a test article's toxicologic effect.

Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis

Background/ObjectivesAcute pancreatitis is complicated by local and systemic complications in 20–30% of the patients. Accurate prediction of severity may be important for clinical decision making. Our aim is to identify and compare the accuracy of laboratory biomarkers that predict severity and complications in adult patients. MethodsMedline, EMBASE, Web of Science and Cochrane Library (1993 to August 2020) were searched for studies with an unselected population of patients with acute pancreatitis, that contains accuracy data for ≥1 laboratory biomarker(s) and/or APACHE-II score for the prediction of a patient outcomes of interest during the first 48 h of admission. The primary outcome is moderate severe or severe acute pancreatitis (MSAP/SAP). Secondary outcomes are severe acute pancreatitis, pancreatic necrosis and organ failure. Risk of bias was assed using QUADAS-2. Biomarkers extracted from ≥3 unique sources, were analyzed using hierarchical summary receiver operating characteristic (HSROC) and bivariate model analysis. ResultsIn total, 181 studies were included in the qualitative analysis reporting on 29 biomarkers. For the primary outcome at admission, summary sensitivities and specificities were, respectively, 87% (95% CI 69–95%) and 88% (95% CI 80–93%) for IL-6 at a threshold of >50 pg/ml, 72% (95% CI 64–79%) and 76% (95% CI 67–84%) for an APACHE-II score of ≥8, and 53% (95% CI 35–71%) and 82% (95% CI 74–88%) for CRP >150 mg/l. HSROC curve analysis confirmed these results. ConclusionThis study indicates superiority of IL-6 for the early prediction of MSAP/SAP and may be used for to guide clinical decision making.

Bacteriological and histopathological analysis of Penaeus vannamei experimentally infected with Vibrio parahaemolyticus-AHPND strains.

Vibrio parahaemolyticus strains have been identified as the causative agent of acute hepatopancreas necrosis disease (Vp AHPND+) in shrimp. In the present work, a highly virulent (M0904) and less virulent (M0607) strain of Vp AHPND+ were used in experimental infections of Penaeus vannamei. Throughout the experiment, histopathological analyses were conducted on shrimp tissues, and samples from the bottom (B) and water column (WC) of each aquarium were taken to estimate bacterial growth. The first deaths of shrimp challenged with Vp M0904 occurred 4 h post-infection (hpi), reached 50% mortality at 17 hpi, and showed more acute pathological progression associated with AHPND despite both strains having similar bacterial densities from 0-4 hpi. The first deaths of shrimp inoculated with Vp M0607 occurred at 13 hpi, a difference of 9 h. These shrimps displayed reduction of reserve vacuoles in R and B cells of the hepatopancreas, and reached 50% mortality at 27 hpi. As bacterial growth in the WC and B in the first hours was similar for both strains, bacterial density was not a significant factor in Vp virulence. Since pirAB toxin is the causative agent of AHPND, it is possible that there is a threshold level at which the toxin damages hepatopancreatic tissues, so production or secretion of the toxin can be dependent of the Vp strain. We propose new AHPND stage: remission with 3 main routes for the disease outcome after the remission stage (re-infection, chronic effect and recuperation). Hepatopancreatic embryonic cells can be used as a biological indicator of this stage.

Acute Severe Pancreatitis and Bilateral Renal Cortical Necrosis

Acute Severe Pancreatitis and Bilateral Renal Cortical Necrosis

Adrenal Vascular Changes in COVID-19 Autopsies.

To the Editor.—For the past 2 months, New York City has been the epicenter of the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus). The disease (coronavirus disease 2019 [COVID-19]) most acutely and severely affects the lungs, requiring mechanical ventilation in a subset of cases. Other organs, including the heart, kidneys, liver, and gastrointestinal tract, can also be involved. The pathophysiology and the extent of multiorgan involvement is poorly understood. We report pathological findings in the adrenal glands of the first 5 postmortem examinations of patients with COVID-19 diagnosed on clinical grounds with confirmatory real-time polymerase chain reaction testing of nasopharyngeal swab. Two patients were brought to the emergency room in cardiac arrest and could not be resuscitated. Three were briefly hospitalized, 2 for 24 hours and 1 for 72 hours. There were 4 males and 1 female, ranging from 59 to 90 years of age and with the following co-morbidities: hypertension (5 of 5), diabetes (3 of 5), ischemic cardiomyopathy (3 of 5), chronic lung disease (2 of 5, 1 with chronic obstructive pulmonary disease and 1 with interstitial lung disease), prostate carcinoma (2 of 5), and recent spinal surgery (1 of 5). Blood cultures were negative in the 3 patients tested. On microscopic examination, acute fibrinoid necrosis of small vessels, mainly arterioles in adrenal parenchyma, adrenal capsule, and in the immediately adjacent periadrenal adipose tissue, was identified. Subendothelial vacuolization and apoptotic debris were present (Figure, A–C). No significant inflammation, adrenal parenchymal infarcts, or thrombi were appreciated. The vascular pathology was disproportionately conspicuous in adrenal and not as easily identified in other organs examined.Fibrinoid necrosis describes vessel wall necrosis with fibrin and serum protein accumulation conveying an eosinophilic amorphous appearance on histology. With Masson's trichrome stain, the amorphous fibrinoid material is red, unlike collagen that stains blue (Figure, D). Arteriolar hyalinosis is another term used to describe the accumulation of pink amorphous material in vessel walls. This is thought to relate to hypertension, but is not typically associated with vessel necrosis and endothelial apoptosis. Hyalinosis may explain some of the histopathology; however, many of the vessels we observed were either necrotic or associated with apoptosis. It is unclear if the adrenal vasculopathy is because of hypoxia, abnormal vascular reaction and blood flow patterns, direct viral cytopathic effect, an immune-mediated injury, or a combination of events. Acute fibrinoid necrosis is classically described in malignant hypertension (first by Volhard and Fahr1 in 1914), mainly in kidneys, and in immune-mediated vasculitides. While SARS-CoV-2 infection seems to more severely affect patients with a history of hypertension,2 most critically ill patients with COVID-19 need vasopressors for persistent hypotension.3 Two of 3 hospitalized patients described had recorded high blood pressure values and 1 was hypotensive on arrival. Localized fibrinoid necrosis is also mentioned in a report of pathological findings in SARS virus infection.4 SARS-CoV-2 virus gains entry to the cell via the angiotensin-converting enzyme 2 receptor,5 which is most abundant in lung alveolar cells, but also present in endothelia and other tissues, providing a possible mechanism for vascular injury.6Adrenal hormones are involved in modulating inflammatory responses7 and adrenal gland dysfunction has been described in patients with community-acquired pneumonia.8In general, adrenal function is not routinely assessed in an intensive care unit setting. The most common indication for corticosteroid administration in an intensive care unit is refractory hemodynamic shock. According to several critical care societies, acute respiratory distress syndrome management can include corticosteroids, as they may decrease the time on a ventilator and reduce mortality.9 Corticosteroids are also administered if there is suspicion of adrenal insufficiency or if they are indicated because of an underlying condition. Currently, the World Health Organization and major critical care and infectious diseases associations advise against routine corticosteroid use in COVID-19 patients, mainly out of concern for slowing viral clearance. However, early reports from China and Europe suggested that corticosteroids are useful in severe COVID-19 and some experts posit that severe cytokine release syndrome seen in some patients warrants the use of corticosteroids or other targeted immunosuppressants.9–12It is interesting to consider that adrenal insufficiency secondary to the vasculopathy described here may contribute to the cytokine storm observed in patients with severe COVID-19. Clinical studies to further assess adrenal function in COVID-19 may help in understanding the pathogenesis of disease in severely affected patients and hopefully lead to therapeutic protocols that may rescue an increased number of patients.

Temporal Acute Serum Estradiol and Tumor Necrosis Factor-α Associations and Risk of Death after Severe Traumatic Brain Injury.

Severe traumatic brain injury (TBI) activates a robust systemic response that involves inflammatory and other factors, including estradiol (E2), associated with increased deaths. Tumor necrosis factor-alpha (TNFα) is a significant mediator of systemic shock, and it is an extra-gonadal transcription factor for E2 production. The study objectives were to test the hypotheses: (1) a positive feedback relationship exists between acute serum TNFα and E2; and (2) acute concentrations of E2 and TNFα are prognostic indicators of death after severe TBI. This prospective cohort study included N = 157 adults with severe TBI. Serum samples were collected for the first five days post-injury. The TNFα and E2 levels were averaged into two time epochs: first 72 h (T1) and second 72 h post-injury (T2). A cross-lag panel analysis conducted between T1 and T2 TNFα and E2 levels showed significant cross-lag effects: T1 TNFα and T1 E2 were related to T2 E2 and T2 TNFα, respectively. Cox proportional hazards multi variable regression models determined that increases in T1 E2 (hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.15, 2.81), but not T2 E2 (HR = 0.91, 95% CI: 0.56, 1.47), were associated with increased risk of death. Increased T2 TNFα (HR = 2.47, 95% CI: 1.35, 4.53), and T1 TNFα (HR = 1.47, 95% CI: 0.99, 2.19), to a lesser degree, were associated with increased risk of death. Relationships of death with T2 TNFα and T1 E2 were mediated partially by cardiovascular, hepatic, and renal dysfunction. Both E2 and TNFα are systemic, reciprocally related biomarkers that may be indicative of systemic compromise and increased risk of death after severe TBI.