Acute Necrosis Research Articles

Effect Analysis of Nursing Method Based on Stratified Emergency Knowledge in Emergency Myocardial Infarction.

First aid is to give immediate first aid to patients who have suffered accidental injuries or sudden diseases before the emergency medical personnel arrive at the scene or are sent to the hospital for treatment; myocardial infarction is a severe and emergency of coronary heart disease. It is often because of coronary atherosclerosis, plaque rupture, bleeding, or thrombosis, which leads to the acute and complete occlusion of the coronary arteries and acute necrosis of the myocardium. This article aims to investigate the effectiveness of a stratified emergency care team assisted by multidisciplinary first aid knowledge in acute myocardial infarction first aid, hoping to reduce the probability of acute myocardial infarction through first aid and nursing care. Business process reengineering is a management idea that reached its heyday in the 1990s and is usually defined as achieving workflow and productivity through the reorganization and optimization of corporate strategies, value-added operational processes, and the systems, policies, organizations, and structures that support them. This article first outlines the concepts and steps of medical image registration, analyzes the characteristics of current medical image registration methods, and uses the two most commonly used medical registration methods today; in this study, the BPR theory was used to construct the AMI emergency care process in the hospital, which effectively reduced the emergency delay time of AMI patients, improved the patient's emergency response, and increased the efficiency of emergency nurses' rescue work. The experimental results in this paper show that the sensitivities of the first four groups of ST↑III > II, ST ↓ aVL > I, STV3 ↓ /STIII↑≤1.2, STI ↓ ≥0.05 mV are 82.1%, 80%, 75.3%, and 60.3%, respectively. Their sensitivities are relatively close, both are greater than 50%; among them, ST↑III > II has the highest sensitivity, which is 80%. In terms of specificity, ST↑III > II, ST ↓ aVL > I, STV3 ↓ /STIII↑≤1.2, and STI ↓ ≥0.05 mV were 82.1%, 89.2%, 82.7%, and 65.2%, respectively. ST ↓ ≥0.05 mV has the lowest specificity, and ST ↓ aVL > I has the highest specificity.

Intravenous Glu-plasminogen attenuates cholesterol crystal embolism-induced thrombotic angiopathy, acute kidney injury and kidney infarction.

Cholesterol crystal (CC) embolism causes acute kidney injury (AKI) and ischaemic cortical necrosis associated with high mortality. We speculated that sustaining the fibrinolytic system with Glu-plasminogen (Glu-Plg) could be a safe way to attenuate AKI and prevent ischaemic infarction upon CC embolism. We induced CC embolism by injecting CC into the left kidney artery of C57BL/6J mice. The primary endpoint was glomerular filtration rate (GFR). Starting as early as 2h after CC embolism, thrombotic angiopathy progressed gradually in the interlobular, arcuate and interlobar arteries. This was associated with a decrease of GFR reaching a peak at 18h, i.e. AKI, and progressive ischaemic kidney necrosis developing between 12-48h after CC injection. Human plasma Glu-Plg extracts injected intravenously 4h after CC embolism attenuated thrombotic angiopathy, GFR loss as well as ischaemic necrosis in a dose-dependent manner. No bleeding complications occurred after Glu-Plg injection. Injection of an intermediate dose (0.6mg/kg) had only a transient protective effect on microvascular occlusions lasting for a few hours without a sustained protective effect on AKI at 18-48h or cortical necrosis, while 1.5mg/kg were fully protective. Importantly, no bleeding complications occurred. These results provide the first experimental evidence that Glu-Plg could be an innovative therapeutic strategy to attenuate thrombotic angiopathy, AKI, kidney necrosis and potentially other clinical manifestations of CC embolism syndrome.

COVID-19 infection: from stress-related cortisol levels to adrenal glands infarction.

Cortisol is a key element in acute stress including a severe infection. However, in coronavirus-associated disease, 20% of subjects experience hypocortisolemia due to direct or immune damage of pituitary and adrenal glands. One extreme form of adrenal insufficiency is found in 2∕3 of cases with viral and post-viral adrenal infarction (AI) (with∕without adrenal hemorrhage) that is mostly associated with a severe coronavirus disease 2019 (COVID-19) infection; it requires prompt glucocorticoid intervention. Some reports are incidental findings at computed tomography (CT)∕magnetic resonance imaging (MRI) scans for non-adrenal complications like pulmonary spreading and others are seen on post-mortem analysis. This is a review of PubMed-accessible, English papers focusing on AI in addition to the infection, between March 1, 2020 and November 1, 2021. Exclusion criteria were acute adrenal insufficiency without the histopathological (HP) and∕or imaging report of adrenal enlargement, necrosis, etc., respective adrenal failure due to pituitary causes, or non-COVID-19-related adrenal events. We identified a total of 84 patients (different levels of statistical evidence), as follows: a retrospective study on 51 individuals, two post-mortem studies comprising nine, respectively 12 patients, a case series of five subjects, seven single-case reports. HP aspects include necrosis associated with ischemia, cortical lipid degeneration (+/- focal adrenalitis), and infarcts at the level of adrenal cortex, blood clot into vessels, acute fibrinoid necrosis in arterioles and capsules, as well as subendothelial vacuolization. Collateral potential contributors to adrenal damage are thrombotic events, coagulation anomalies, antiphospholipid syndrome, endothelial dysfunction, severe COVID-19 infection with multiorgan failure, etc. Clinical picture is variable from acute primary adrenal insufficiency to asymptomatic or mild evolution, even a retrospective diagnostic; it may be a part of long COVID-19 syndrome; glucocorticoid therapy for non-adrenal considerations might mask cortisol deficient status due to AI∕hemorrhage. Despite its rarity, the COVID-19-associated AI/hemorrhage represents a challenging new chapter, a condition that is essential to be recognized due to its gravity since prompt intervention with glucocorticoid replacement is lifesaving.

Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis, A Review of Pathogenesis, Clinical Features, Diagnosis and Treatment

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, acute conditions, potentially life-threatening, immune-mediated and often unpredictable.
 Characteristic for SJS and TEN is acute necrosis of the epidermis and mucous membranes, caused by the extensive death of keratinocytes. These syndromes are considered hypersensitivity reactions. They are most often caused by drugs. There have also been reports of SJS / TEN being caused by infection,
 SJS/TEN disease is very rare and due to its rarity there is no specific pharmaceutical algorythm. Supportive care and treatment of symptoms are very important. The most crucial part of non-pharmacologic treatment of SJS/TEN is the detection and cessation of the pharmaceutical that caused the disease.
 The aim of this literature review was to summarize current knowledge about the pathogenesis, clinical features, diagnosis and treatment of Stevens- Johnson Syndrom and Toxic Epidermal Necrolysis.
 Standard criteria were used to review the literature data. The search of articles in the PubMed and Google Scholar database was carried out using the following keywords: Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, cutaneous adverse drug reactions

842P A phase II trial of AU-011, an investigational, virus-like drug conjugate (VDC) for the treatment of primary indeterminate lesions and small choroidal melanoma (IL/CM) using suprachoroidal administration

Choroidal melanoma is the most common primary intraocular malignancy in adults. Many subjects with a melanocytic choroidal tumor of indeterminate malignancy (i.e., ‘indeterminate lesion’) or small choroidal melanoma (IL/CM) are monitored clinically or treated with radiotherapy, which may lead to severe and irreversible vision loss. AU-011 (belzupacap sarotalocan) is a virus-like drug conjugate (VDC) currently being investigated as a potential first-line vision-sparing treatment. The dual mechanism of action consists of AU-011 selectively binding to malignant melanoma cells, causing acute necrosis upon light activation and potential long term anti-tumor immunity. The current Phase 2 trial is designed to evaluate the safety and efficacy of AU-011 when administered via suprachoroidal (SC) injection. Trial design using SC administration and interim safety from the open-label dose escalation phase will be presented. Phase 2, multicenter trial being conducted at 22 ocular oncology sites in the US. The trial included 6 single- and multiple-dose escalation cohorts to be followed by a randomized confirmatory phase. In dose escalation, adult subjects received up to 3 cycles of 3 weekly AU-011 treatments via SC administration with a maximum dose of 80μg with 2 laser applications. Preliminary safety results include 17 subjects in the dose escalation phase. The most common adverse events (AE) related to drug or laser were anterior chamber inflammation in 4 subjects, conjunctival hyperemia, eye pain, and punctate keratitis in 2 subjects each. There were no dose-limiting toxicities, treatment-related serious or grade 3/4 AEs, vitritis or serious AEs of vision loss. Two subjects developed 5 serious AEs unrelated to treatment. Preliminary results indicate AU-011 to have a favorable safety profile, supporting its potential to be a first-line therapy for the treatment of IL/CM, especially in early-stage disease where observation may be commonly employed. Efficacy data including visual acuity and tumor control from the dose escalation phase will be reported later this year.

Retrospective case series: Necrotising fasciitis in 23 dogs.

Necrotising fasciitis (NF) is a rare, rapidly progressive subcutaneous bacterial infection. Few studies have characterised NF in dogs. To retrospectively describe clinical and laboratory findings, with treatments and outcomes, in dogs with NF. Twenty-three client-owned dogs treated at a veterinary teaching hospital between 1998 and 2021. Medical records and laboratory data from 23 dogs diagnosed with NF were reviewed. Male dogs were significantly over-represented (p= 0.003). The most common presenting complaint was sudden lameness. Infection occurred in one or two limbs in 19 of 23 dogs, with right hindlimbs most often affected (13 of 23). Pitting oedema was evident in 14 of 23 dogs. Antibiotic and nonsteroidal anti-inflammatory drugs were administered before presentation in nine and 13 of 23 dogs, respectively. Common clinicopathological abnormalities included hypoalbuminemia, hyponatremia, elevated liver enzymes, elevated creatine kinase, increased bands and lymphopenia. Streptococcus canis was isolated from 18 of 23 dogs. Histopathological features included acute necrosis and severe neutrophilic inflammation. Fifteen dogs were euthanised or died, while surgical intervention led to survival in eight of 23 dogs. Dogs presenting for acute swelling of a limb with oedema should have the diagnosis of NF considered and early surgical intervention might increase survival.

Integrated single-cell transcriptomics and proteomics reveal cellular-specific responses and microenvironment remodeling in aristolochic acid nephropathy

Aristolochic acid nephropathy (AAN) is characterized by acute proximal tubule necrosis and immune cell infiltration, contributing to the global burden of chronic kidney disease and urothelial cancer. Although the proximal tubule has been defined as the primary target of aristolochic acids I (AAI), the mechanistic underpinning of gross renal deterioration caused by AAI has not been explicitly explained, prohibiting effective therapeutic intervention. To this point, we employed integrated single-cell RNA-Seq, bulk RNA-Seq, and mass spectrometry–based proteomics to analyze the mouse kidney after acute AAI exposure. Our results reveal a dramatic reduction of proximal tubule epithelial cells, associated with apoptotic and inflammatory pathways, indicating permanent damage beyond repair. We found the enriched development pathways in other nephron segments, suggesting activation of reparative programs triggered by AAI. The divergent response may be attributed to the segment-specific distribution of organic anion channels along the nephron, including OAT1 and OAT3. Moreover, we observed dramatic activation and recruitment of cytotoxic T and macrophage M1 cells, highlighting inflammation as a principal contributor to permanent renal injury. Ligand-receptor pairing revealed that critical intercellular crosstalk underpins damage-induced activation of immune cells. These results provide potentially novel insight into the AAI-induced kidney injury and point out possible pathways for future therapeutic intervention.

Percutaneous Catheter Drainage in Acute Infected Necrotizing Pancreatitis: A Real-World Experience at a Tertiary Care Hospital in North India.

IntroductionOpen necrosectomy in acute infected necrotizing pancreatitis is associated with very high mortality and morbidity. Moreover, if it is performed before four weeks, the benefits are limited. In this study, we evaluated the safety and efficacy of percutaneous catheter drainage (PCD) in patients with acute infected necrotizing pancreatitis.MethodsIt was a single-center, observational study, where all consecutive patients with proven or probable infected acute necrotizing pancreatitis in whom PCD was performed were studied. The patients who failed to respond to PCD underwent open necrosectomy. Baseline characteristics and the outcome of all included patients, including complications of PCD, were studied.ResultsA total of 46 patients (males=36, females=10) underwent PCD over a period of 18 months. Fifteen (32.60%) patients succumbed to their illness. PCD benefitted a total of 31 (67.39%) patients; in 17 (36.95%) patients, it worked as a standalone therapy, while in 14 (30.43%) patients, additional surgery was required where it helped to delay the surgery. Median days at which PCD and surgery were performed were 17.5 days (range: 2-28 days) and 33 days (range: 7-70 days), respectively. Lower mean arterial pressure at presentation, presence of multiorgan failure, more than 50% necrosis, higher baseline creatinine and bilirubin levels, and an early surgery were markers of increased mortality. Three (6.5%) patients had PCD-related complications, out of which only one required active intervention.ConclusionPCD in infected acute pancreatic necrosis is safe and effective. In one-third of the patients, it worked as standalone therapy, and in the rest it delayed the surgery beyond four weeks, thereby preventing the complications associated with early aggressive debridement.

Retrospective Evaluation of Intravenous Enoxaparin Administration in Feline Arterial Thromboembolism.

Simple SummaryFeline arterial thromboembolism is a painful disease characterized by acute ischemic necrosis of one or more limbs due to cardiac diseases, hyperthyroidism, or neoplasia. Among others, medical treatment consists of preventing new thrombus formation primarily using heparin products, such as enoxaparin. This retrospective study reports clinical data, regain of perfusion, short-term outcome, and complications of 36 affected cats treated with a novel intravenous enoxaparin protocol. Furthermore, we aimed to report monitoring and management of the intravenous enoxaparin treatment for this disease. In our population, visible hemorrhage was rare. The most common causes of death/euthanasia were cardiac instability, acute kidney injury, neurological abnormalities, and limb necrosis. The hospital discharge rate was 47% overall and was significantly different between single limb (83%) and dual limb (29%) thromboembolism. Our study supports the intravenous use of enoxaparin in combination with oral clopidogrel for cats with thromboembolism as an alternative treatment method.Induction of a hypocoagulable state is imperative in the treatment of feline arterial thromboembolism. Publications in human medicine report the use of enoxaparin intravenously in selected cases. The aim of our retrospective study was to report the regain of perfusion, short-term outcome, and complications of cats treated with a novel intravenous enoxaparin protocol (1 mg/kg bolus injection followed by 3 mg/kg/day continuous infusion) combined with oral clopidogrel administration. The secondary aim was to report the monitoring of enoxaparin with anti-Xa activity. There were 36 cats included. The probability of reaching limb reperfusion was significantly (p = 0.0148) higher with anti-Xa activity within or above the target range compared to results below the target range (19/21, 90% versus 11/20, 55%). The complications observed were acute kidney injury (15/36, 42%), hemorrhage (2/36, 6%), and neurological signs (6/36, 17%). The most common causes of death/euthanasia were cardiac instability, acute kidney injury, neurological abnormalities, and limb necrosis. The hospital discharge rate was 83% (10/12) for single limb and 29% (7/24) for dual limb thrombosis; the difference was significant (p = 0.0039). The median hospitalization time for the survivors was 119.5 (95–480) h. Our study supports the use of intravenous continuous rate infusion of enoxaparin in combination with oral clopidogrel for cats with aortic thromboembolism. We report similar discharge rates and lower hemorrhage rates than previously reported with thrombolytic treatment.

Risk factors for new-onset diabetes mellitus following acute pancreatitis: a prospective study.

Acute pancreatitis (AP) is increasingly recognized as a major cause of diabetes, however, the frequency and risk factors associated with new-onset diabetes are not well established. We aimed to assess the frequency and risk factors associated with new-onset diabetes, the time of diabetes occurrence, and the difference between early and late-onset diabetes following an AP episode. This prospective study included adult patients with AP admitted to a tertiary referral center, followed-up for one year to assess the occurrence of postpancreatitis diabetes. Diabetes was defined in accordance with World Health Organization criteria and the severity of AP was assessed based on the 2012 revised Atlanta classification. Of 329 patients with AP, 29 (8.8%) were diagnosed with diabetes secondary to AP. Of these, 21 (6.37%) had early-onset diabetes (within one month after the acute episode) whereas 8 (2.42%) had late-onset diabetes (more than one month after the AP episode). Obesity and acute necrosis were more frequent in patients with new-onset diabetes compared to those without (55.2% vs. 33.4%, p=0.040 and 31% vs. 7.7%, p<0.01), and remained statistically significant in multivariate analysis. No statistically significant differences were found between these groups regarding sex, age, etiology and severity of AP. The patients with early-onset diabetes were older than those with late-onset (61 vs. 45 years old), in univariate and multivariate analysis (p=0.018 and p=0.038, OR=0.87). Less than 10% of patients with AP developed diabetes within 1 year, particularly obese patients and those with acute pancreatic necrosis of more than 50%. Patients aged over 61 years old developed diabetes in the first month after the acute episode of AP.

Neutrophil circadian rhythm is associated with different outcomes of acute kidney injury due to cholesterol crystal embolism.

Cholesterol crystal (CC) embolism can cause acute tissue infarction and ischemic necrosis via triggering diffuse thrombotic angiopathy occluding arterioles and arteries. Neutrophils contribute to crystal-induced immunothrombosis as well as to ischemic necrosis-related necroinflammation. We speculated that CC embolism-induced acute kidney injury (AKI) would be circadian rhythm-dependent and associated with cyclic differences in neutrophil function. Injection of CC into the left kidney induced thrombotic angiopathy progressing starting as early as 3 h after CC injection followed by a progressive ischemic cortical necrosis and AKI at 24 h. In C57BL/6J mice, circulating CD11b+Ly6G+ neutrophils were higher during the day phase [Zeitgeber time (ZT) 0–12] compared to the dark phase (ZT12-24). In the time frame of thrombus formation at ZT13, more neutrophils were recruited into the injured kidney 24 h later compared to CC embolism at ZT5. This effect was associated with an increased circulating number of CXCR2+ neutrophils as well as an upregulated kidney adhesion molecule and chemokine expression. These findings were associated with a significant increase in kidney necrosis, and endothelial injury at ZT13. Thus, the time of day has an effect also on CC embolism-related AKI in association with the circadian rhythm of neutrophil recruitment.

Histopathological Alterations in Liver and Kidney Tissues of Banded Gourami (Trichogaster fasciata) Exposed to Thiamethoxam

Thiamethoxam is a broad-spectrum pesticide used in Bangladesh to protect crops from pests. In several ways, this pesticide ends up in aquatic ecosystems. Researchers have detected its existence in waterbodies. However, the harmful effects on non-target aquatic residents are not well studied and reported. As a result, the study sought to investigate the effect of thiamethoxam on the liver and kidney tissues of banded gourami (Trichogaster fasciata) using histopathological observations. Fish were exposed to five sub-lethal concentrations (in triplicates) of thiamethoxam (9.37, 18.75, 37.5, 75, and 150 mg/L) and 0 mg/L (control) for 90 days. Fish livers and kidneys were sampled on days 30, 60, and 90 of thiamethoxam exposure. The histopathological changes observed in thiamethoxam exposed fish were autolysis, acute cellular swelling, vacuolation, necrosis, and fatty change in the liver, whereas irregular renal corpuscle and cellular degradation of tissue were also observed in the kidney. The present study reveals that thiamethoxam can affect the livers and kidneys of Banded Gourami; therefore, the usage of this insecticide in agriculture should be applied carefully and monitored to avoid entry into water bodies.

Validation of qPCR from a crude extract for the rapid detection of white spot syndrome virus.

White spot disease (WSD) has posed a serious threat to the China and the global shrimp aquaculture. In order to diagnose white spot syndrome virus (WSSV) early and prevent the spread and outbreak of WSD, it is necessary to establish a highly sensitive WSSV diagnosis method suitable for shrimp farming sites. In this study, a pre-amplification qPCR assay from the crude extract of samples heated lysis was established, which was further compared with the universal qPCR assay to verify the shrimp samples. The limit of detection (LOD) of pre-amplification qPCR assay and universal qPCR assay was 2.80 copies and 20.57 copies per reaction at 95% CI, respectively. It had good WSSV specificity and did not show cross-detection of infectious hypodermal and hematopoietic necrosis virus (IHHNV), hepatopancreatic parvovirus (HPV), Enterocytozoon hepatopenaei (EHP), acute hepatopancreas necrosis disease (AHPND), necrotizing hepatopancreatitis bacteria (NHPB), and decapod iridescent virus 1 (DIV1). A total of 36 shrimp samples were detected as WSSV DNA positive by pre-amplification qPCR with crude extract from samples heated lysis and universal qPCR with DNA extraction. The diagnostic sensitivity and specificity were 97.22% (85.5 ~ 99.9%, 95% CI) and 100% (81.5 ~ 100%, 95% CI), respectively. The agreement Kappa value was 0.959 (0.879 ~ 1, 95% CI), and the analysis results were basically consistent. Eliminating the tedious steps of extracting DNA and using pre-amplified qPCR to detect WSSV in shrimp, it is a good choice for aquaculture farms.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s10499-022-00920-9.

Acute intestinal necrosis due to multiple thrombosis in COVID-19 patient. Report of a case

BackgroundWhile thrombosis is a well-known complication of coronavirus disease 2019 (COVID-19) infection, reports on intestinal necrosis due to intestinal ischemia caused by thrombosis are extremely rare. We herein report a case of intestinal necrosis due to multiple thrombosis in a COVID-19 patient.Case presentationThe patient was a 64-year-old man. He was admitted to hospital after being diagnosed with COVID-19, the severity was classified as moderate II. Nasal High Flow™ management was conducted along with treatment with tocilizumab, remdesivir, and dexamethasone. Heparin was also administered due to high D-dimer values. As abdominal pain appeared from the 6th day of hospitalization, contrast-enhanced CT was performed, which confirmed multiple thrombosis in the aorta. However, no obvious intestinal ischemia was found. On the 10th day of hospitalization, the patient’s abdominal pain was exacerbated. Upon re-evaluation by CT, he was diagnosed with perforative peritonitis due to ileal ischemic necrosis and emergency surgery was performed. Intraoperative examination revealed perforation due to necrosis at multiple sites in the ileum; thus, partial ileectomy was carried out. Pathological findings also revealed discontinuous multiple intestinal necrosis due to the frequent occurrence of thrombosis. Following surgery, the patient recuperated and was discharged after ventilator management and multimodal therapy at the ICU.ConclusionsThrombosis due to COVID-19 complications is rare in the intestinal tract, but also occur. Its initial symptoms might not be captured by CT images, therefore caution is required.

Long-Term Sequelae of COVID-19 in Experimental Mice

We recently reported acute COVID-19 symptoms, clinical status, weight loss, multi-organ pathological changes, and animal death in a murine hepatitis virus-1 (MHV-1) coronavirus mouse model of COVID-19, which were similar to that observed in humans with COVID-19. We further examined long-term (12 months post-infection) sequelae of COVID-19 in these mice. Congested blood vessels, perivascular cavitation, pericellular halos, vacuolation of neuropils, pyknotic nuclei, acute eosinophilic necrosis, necrotic neurons with fragmented nuclei, and vacuolation were observed in the brain cortex 12 months post-MHV-1 infection. These changes were associated with increased reactive astrocytes and microglia, hyperphosphorylated TDP-43 and tau, and a decrease in synaptic protein synaptophysin-1, suggesting the possible long-term impact of SARS-CoV-2 infection on defective neuronal integrity. The lungs showed severe inflammation, bronchiolar airway wall thickening due to fibrotic remodeling, bronchioles with increased numbers of goblet cells in the epithelial lining, and bronchiole walls with increased numbers of inflammatory cells. Hearts showed severe interstitial edema, vascular congestion and dilation, nucleated red blood cells (RBCs), RBCs infiltrating between degenerative myocardial fibers, inflammatory cells and apoptotic bodies and acute myocyte necrosis, hypertrophy, and fibrosis. Long-term changes in the liver and kidney were less severe than those observed in the acute phase. Noteworthy, the treatment of infected mice with a small molecule synthetic peptide which prevents the binding of spike protein to its respective receptors significantly attenuated disease progression, as well as the pathological changes observed post-long-term infection. Collectively, these findings suggest that COVID-19 may result in long-term, irreversible changes predominantly in the brain, lung, and heart.

Histological Identification and Quantification of Eosinophils and Ascites in Leghorn Chickens Treated with High Oral Concentrations of NaCl-Pilot Study.

The purpose of this pilot study was to determine the role played by eosinophils in NaCl poisoning and right cardiac hypertrophy (ascitic syndrome) in Leghorn chickens, as well as the histological findings in the central nervous system (CNS), liver, and kidney. Moreover, the hypertrophy of the right ventricle index (HRVI) as an indicator of ascites was evaluated. Male SPF Leghorn birds at 28 days of age were submitted to two experiments. Food and water (FW) experiment: birds were treated with food plus 3.3% NaCl for the next 27 days and 1% NaCl in their drinking water from days 22 to 27. Water experiment (W): birds were treated with 1% NaCl in their drinking water for 5 days. In both experiments, the chickens exhibited loss of appetite, diuresis, and watery, green diarrhea during treatment days; at 24–27 td-FW and experiment W, the birds showed nervous signology (prostration, running movements, tremors, and comatose state). In the leukogram at 28 td-FW, an increase (p < 0.05) in heterophiles and basophils was observed. CNS eosinophilia was not observed in birds intoxicated with NaCl, though they did present demyelination in the brain and spinal cord, hepatic degeneration, mesangial proliferative glomerulopathy, and acute proximal renotubular necrosis.

Childhood Vasculitis Syndrome Mimicking Guillain Barre Syndrome

Background: Childhood vasculitis is a heterogeneous disorder, characterized by inflammation of the blood vessel walls. Multiple organs and/or tissues are affected, either simultaneously or successively. Vascular neuropathy occurs when the vasa nervorum is affected. Presentation includes mononeuritis multiplex, acute motor/motor-sensory axonal neuropathy, pure sensory neuropathy, and chronic inflammatory demyelinating polyneuropathy. Making a diagnosis is a challenge when neurological manifestations appear for the first time or are isolated. Clinical Description: A 12-year-old girl presented with acute pain and progressive weakness of both lower limbs for 12 days, followed by diffuse abdominal pain and low-grade fever. Salient neurological findings were diminished power and hyporeflexia in all limbs. Guillain–Barre syndrome was suspected in view of symmetric ascending paralysis and a suggestive nerve conduction study. The child had neutrophilic leukocytosis but sterile cultures. The successive development of inflammatory demyelinating polyneuropathy, persistent fever, vasculitic phenomena (hypertension, severe myalgia, rashes, multiple infarcts, acute renal cortical necrosis, and gangrene of the digit), and elevated acute-phase reactants was suggestive of a multisystemic small-vessel and medium-sized vasculitis syndrome, such as polyarteritis nodosa (PAN). A diagnosis of PAN was established based on the satisfaction of clinical criteria. Management: The patient was administered pulse methylprednisolone and oral steroids, with which there was a dramatic recovery. Monthly cyclophosphamide was continued in view of major systemic involvement. Conclusion: Early recognition and management of childhood vasculitis syndrome is associated with good outcomes.

Comparative Analysis of Early Clinical Features and Complications of Different Types of Acute Pancreatitis.

Background Acute pancreatitis (AP) is a common surgical acute abdomen. Different kinds of pancreatitis may have different pathophysiological characteristics each other. The objective of this research was to investigate the early clinical features and complications of different types of acute pancreatitis. Methods 787 AP patients admitted in the Huadu District People's Hospital of Guangzhou during January 2009 and December 2019 were analyzed retrospectively. Among 787 AP patients, 520 (66.1%) were biliary AP (group I), 69 (8.7%) were alcoholic AP (group II), and 198 (25.2%) were hypertriglyceridemic AP (group III). According to the local and systemic complications and mortality in the early stage, we compared and analyzed the clinical characteristics and prognosis of different types of pancreatitis. Results Mild acute pancreatitis accounted for the highest proportion (79.4%) in group I, while moderately severe acute pancreatitis in group II (36.2%) and severe acute pancreatitis in group III (62.6%). In terms of severity score of the pancreatitis, the average scores of BISAP, Ranson, APACHE-II, and MCTSI of the patients in group III were the highest (p < 0.01). The incidence of acute peripancreatic fluid collection and infectious pancreatic necrosis was the highest in group III. The incidences of acute necrotic collection, pancreatic pseudocyst, and walled-off necrosis in group III were significantly higher than those in the other two groups (p < 0.01). The incidences of systemic inflammatory response syndrome, sepsis, multiple organ failure, intra-abdominal hypertension, and mortality were highest in group III. Conclusions There is an upward trend of the incidence rate of hypertriglyceridemic AP in recent years; it has been gradually developed into the second type of acute pancreatitis which is second only to the acute biliary pancreatitis. It is worthy to pay more and more attentions to it due to the feature of its younger onset, high incidence of complications, and high mortality.

Poroptosis: A form of cell death depending on plasma membrane nanopores formation

SummaryImmunogenic cell death (ICD) in malignant cells can decrease tumor burden and activate antitumor immune response to obtain lasting antitumor immunity, leading to the elimination of distant metastases and prevention of recurrence. Here, we reveal that ppM1 peptide is capable of forming irreparable transmembrane pores on tumor cell membrane, leading to ICD which we name poroptosis. Poroptosis is directly dependent on cell membrane nanopores regardless of the upstream signaling of cell death. ppM1-induced poroptosis was characterized by the sustained release of intracellular LDH. This unique feature is distinct from other well-characterized types of acute necrosis induced by freezing-thawing (F/T) and detergents, which leads to the burst release of intracellular LDH. Our results suggested that steady transmembrane-nanopore-mediated subacute cell death played a vital role in subsequent activated immunity that transforms to an antitumor immune microenvironment. Selectively generating poroptosis in cancer cell could be a promise strategy for cancer therapy.

Inflammation depletes humoral immunity by limiting plasma cell access to the bone marrow survival niche

Abstract The survival of plasma cells (PCs) is directly correlated to the longevity of prophylactic titers against pathogens. The bone marrow contains hematopoietic and non-hematopoietic cells that contribute to the maintenance of PCs. Studies have shown that pathogens contain a variety of mechanisms that result in the depletion of bone marrow PCs and antibody titers. Most, if not all, forms of infection induce inflammation, however, the role of inflammation in bone marrow PC depletion is unclear. Here, we show that acute Tumor Necrosis Factor Alpha (TNFa) treatment can deplete pre-existing antibody titers in a variety of models. We also found that recombinant TNFa treatment limits PC retention in the bone marrow via adoptive transfer experiments. To determine if PC retention in the bone marrow was mediated in a cell-intrinsic or − extrinsic manner, we generated bone marrow chimeras with wild-type and TNFa receptor knockout mice. Results showed that TNFa signaling through TNFa receptor 1 in non-hematopoietic cells regulates PC retention in the bone marrow, indicating that this mechanism is cell-extrinsic. Another cell-extrinsic mechanism that we identified is TNFa regulation of syndecan-1, a cell surface proteoglycan found to regulate PC survival and motility. These findings demonstrate that inflammation limits PC access to the bone marrow survival niche, ultimately leading to the reduction of antibody titers and long-term humoral protection. Supported by grants from the NIH (R01 HLI141491) and the Eric Heyer M.D. Ph.D Translational Research Grant