Fulminant Form Research Articles

Massive intravascular hemolysis is an important factor in Clostridium perfringens-induced bacteremia.

Clostridium perfringens bacteremia is rare but often fatal. In particular, once bacteremia with massive intravascular hemolysis (MIH) occurs, the mortality rate is extremely high. However, because of its rarity, the detailed pathophysiology of this fulminant form of bacteremia is unclear. To elucidate the detailed pathogenesis of MIH, we retrospectively reviewed the data of all patients with C. perfringens bacteremia from two university hospitals from 2000 to 2014. The medical records and laboratory data of 60 patients with bacteremia, including 6 patients with MIH and 54 patients without MIH, were analyzed. Patients with MIH had higher rates of intense pain at onset, impaired consciousness, shock at presentation, hematuria, metabolic acidosis, and gas formation than patients without MIH. The antibiotic susceptibility of the clinical isolates was not significantly different between the two groups. All patients with MIH, although treated with appropriate antimicrobial agents, died within 26h of admission due to rapidly progressive acute lung injury or acute respiratory distress syndrome, and the median time from arrival at the hospital to death was only 4h and 20min. When clinicians observe intravascular hemolysis in blood samples from patients with characteristic symptoms of MIH, they should prepare for a severe disease outcome. The underlying pathophysiology of fulminant cases must be investigated.

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic.

Celiac disease (CD) comprises over 1% of the world’s population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines.

THE COURSE OF GENERALIZED FORMS OF MENINGOCOCCAL INFECTION IN CHILDREN OF THE LVIV REGION DURING 2011-2019

Relevance. Meningococcal infection (MI) is one of the most significant bacterial infections in children, it is characterized by life-threatening and unpredictable fulminant course in the structure of infectious diseases.
 Objective. To analyze the clinical and laboratory features of generalized forms of MI in children of Lviv region during 2011-2019.
 Materials and methods. Retrospective analysis of 254 case reports of patients with generalized forms of MI, hospitalized in regional infectious diseases clinical hospital during 2011 -2019 years, was conducted, as well as 14 protocols for post-mortem examination of deceased from generalized forms of MI children during 2011-2019. 203 medical records with confirmed diagnosis of the disease were selected.
 Results. Meningitis as a clinical form was diagnosed in 48 children (23.6%), meningoencephalitis in 6 (3%), meningococcemia − in 82 (40.4%), combined form − in 67 children (33%).
 In children aged 1 month to 1 year and aged 1 to 3 years the combined form of the disease occurred significantly more often than the isolated clinical form. Analysis of clinical symptoms and major laboratory parameters in various clinical forms of MI were exemplified.
 12 children from 5 months up to 4 years 10 months diagnosed with MI generalized form: meningococcemia fulminant form, and one 6-year-old child with purulent meningoencephalitis had died.
 Conclusions. Despite of gradual decrease of morbidity level and respectively amount of hospitalized patients throughout 2011-2019, a difficult course of generalized forms of MI with development of toxische Schocksyndrom in 77,9% in patients with meningoccocemia were observed. Mortality in meningococcemia was 8,1%, most of the deceased were children aged 3-5 years. Misdiagnosis at the primary level were observed in 14,3%.

Per-operative evaluation of destructive pattern of COVID associated rhinocerebral mucormycosis

<p><strong>Background:</strong> The rapid global spread of Coronavirus disease led to declaration of COVID-19 as a pandemic on March 11,2020. Secondary infections are reportedly common in hospitalized, severely ill COVID-19 patients, encompassing between 10 and 30% of cases, fungal being 10 times more common. Mucormycosis is amongst the most fulminant form of zygomycosis caused by mucorales species of the phylum zygomycota and currently referred as COVID associated mucormycosis (CAM). The aim of this study is to evaluate the extend and pattern of destruction in nose, paranasal sinus and orbit found during the surgical debridement of post COVID hyperglycemic patients of mucormycosis.</p><p><strong>Methods:</strong> This prospective observational study was done on a random sample of 86 patients who came to ENT OPD of a tertiary care centre of middle India with clinical, radiological or histological findings suggestive of CAM. These patients underwent aggressive surgical debridement followed by antifungals and strict control of diabetic mellitus. The extend and pattern of destruction caused by CAM in nose, paranasal sinus and orbit noticed peroperatively were analysed.</p><p><strong>Results:</strong> Out of the 86 patients who got operated, there are 62 males and 24 females patients aged from 28 to 86 years. The left side was involved in 41 patients, and the right side in 66 patients. Among the nasal involvement, middle turbinate (56) was maximally involved followed by inferior turbinate (52), superior turbinate (1), septum (17) with posterior septum mostly involved, floor of nose was involved in (4) patients. The orbit was involved in 28 cases in which lamina papyracea was eroded in all cases followed by inferior orbital wall, orbital muscles, optic nerve. Cribriform plate was eroded in 3 patients. The overall extent of involvement of mucormycosis is as follows maxilla (86), ethmoid (71), frontal (29), sphenoid (30), septum (17), orbit (28), alveolus (5), palate (10), intracranial (9), subcutaneous phycomycosis (10).</p><p><strong>Conclusions:</strong> Management of CAM is really challenging which needs a multidisciplinary approach that includes aggressive surgical debridement, aggressive medical therapy with Amphotericin B and correction of the predisposing factors primarily diabetics mellitus</p>

Персонифицированный подход к ранней диагностике молниеносной формы острого некротического панкреатита

The aim of the research. To develop an individual approach to diagnosis of the fulminant form of acute pancreatitis based on laboratory and instrumental research methods. Material and methods. Th e retrospective phase of the study (2016-2018) enrolled 31 patients diagnosed with severe acute pancreatitis (SAP) – the control group. These patients underwent analysis of the results of surgical treatment in order to determine the factors of adverse outcome of the disease. On this basis, a special category of patients was identified, requiring changes in existing diagnostics and surgical tactics depending on the course of the disease. At the prospective stage (2018-2020), a total of 27 patients diagnosed with SAP (the main group) were included. Results. For these patients, we introduced an individualised approach to diagnosis and performed comparative analysis of its effectiveness. The comparative analysis of both groups was carried out based on the main indicators of the patients’ initial condition. Th e distribution of patients between the compared groups had no statistical difference in the gender composition (χ 2 = 0.141, p> 0.05). Th e age of patients ranged from 24 to 83 years. The average age was 44.3 ± 12.6 years in the control group and 43.7 ± 14.4 years in the main group (Student’s t-test = 0.7, p > 0.05). No statistically significant differences were revealed between groups in each age category. Conclusion. In our study on patients with fulminant progression, we emphasised a combination of additional attributes. Th e analysis has revealed statistically significant differences between the “fulminant” and the “typical” progression in the occurrence rate of the combination of attributes.

Marburg Multiple Sclerosis Variant: Complete Remission with Very Early Administration of Mitoxantrone-A Case Report.

Marburg variant is a severe and fulminant pseudotumor form of multiple sclerosis (MS) with high morbidity and mortality rates. Because of its scarcity, it remains incompletely characterized and physicians’ experiences will influence the treatment. We report the inflammatory explosive case of a 31-year-old woman presenting with rapid neurological degradation of histology proven Marburg’s disease, successfully treated with early administration of Mitoxantrone (MITX). To our knowledge, it is the first case describing complete remission after MITX in a biopsy-proven condition.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

Recombinant myelin oligodendrocyte glycoprotein quality modifies evolution of experimental autoimmune encephalitis in macaques

Experimental autoimmune encephalitis (EAE) is a well-recognized model for the study of human acquired demyelinating diseases (ADD), a group of inflammatory disorders of the central nervous system (CNS) characterized by inflammation, myelin loss, and neurological impairment of variable severity. In rodents, EAE is typically induced by active immunization with a combination of myelin-derived antigen and a strong adjuvant as complete Freund's adjuvant (CFA), containing components of the mycobacterial wall, while myelin antigen alone or associated with other bacterial components, as lipopolysaccharides (LPS), often fails to induce EAE. In contrast to this, EAE can be efficiently induced in non-human primates by immunization with the recombinant human myelin oligodendrocyte glycoprotein (rhMOG), produced in Escherichia coli (E. coli), purified and formulated with incomplete Freund's adjuvant (IFA), which lacks bacterial elements. Here, we provide evidence indicating how trace amounts of bacterial contaminants within rhMOG may influence the course and severity of EAE in the cynomolgus macaque immunized with rhMOG/IFA. The residual amount of E. coli contaminants, as detected with mass spectrometry within rhMOG protein stocks, were found to significantly modulate the severity of clinical, radiological, and histologic hallmarks of EAE in macaques. Indeed, animals receiving the purest rhMOG showed milder disease severity, increased numbers of remissions, and reduced brain damage. Histologically, these animals presented a wider diversity of lesion types, including changes in normal-appearing white matter and prephagocytic lesions. Non-human primates EAE model with milder histologic lesions reflect more accurately ADD and permits to study of the pathogenesis of disease initiation and progression.The authors describe quantitatively and qualitatively different forms of experimental autoimmune encephalitis (EAE) in cynomolgus macaques. They found that bacterial contaminants within recombinant human myelin oligodendrocyte glycoprotein seemed to aggravate disease evolution. They provide anatomopathological features of fulminant and progressive forms of EAE, allowing them to distinguish specific factors influencing the evolution of this model of autoimmune demyelinating disease.

Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward

Hepatorenal syndrome (HRS) is a form of acute kidney injury (AKI) occurring in patients with advanced cirrhosis and is associated with significant morbidity and mortality. The pathophysiology underlying HRS begins with increasing portal pressures leading to the release of vasodilatory substances that result in pooling blood in the splanchnic system and a corresponding reduction in effective circulating volume. Compensatory activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and release of arginine vasopressin serve to defend mean arterial pressure but at the cost of severe constriction of the renal vasculature, leading to a progressive, often fulminant form of AKI. There are no approved treatments for HRS in the United States, but multiple countries, including much of Europe, use terlipressin, a synthetic vasopressin analogue, as a first-line therapy. CONFIRM (A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1), the third randomized trial based in North America evaluating terlipressin, met its primary end point of showing greater rates of HRS reversal in the terlipressin arm. However, due to concerns about the apparent increased rates of respiratory adverse events and a lack of evidence for mortality benefit, terlipressin was not approved by the Food and Drug Administration (FDA). We explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised, and consider the future role of terlipressin in this critical clinical area of continued unmet need.

P-40 SEVERE AUTOIMMUNE HEPATITIS: CORTICOSTEROID THERAPY OR EARLY ENROLLMENT TO LIVER TRANSPLANTATION

Autoimmune hepatitis can present in severe or fulminant acute form (SAH). Only 30-60% of these patients respond favorably to corticosteroids. There is no clarity on its indication and how to evaluate steroid therapy in SAH. To evaluate the early response to corticosteroid treatment in patients with SAH (defined as bilirubin> 10 mg / dL or hepatic encephalopathy). Retrospective study of 27 patients with SAH, who received corticosteroids, aged 44 years (20-74), 19 (70%) women. Non-responder (NR) was defined if the patient died or required liver transplantation. 8 patients (30%) were NR, age 49 years (21-72). Bilirubin 22.7 (15-43), INR 2.52 (1.7-3.1), MELD-Na 31 (23-38), UKELD 64 (58-66). Responders (R): 19 (70 %), age 46 years (20 -74). Bilirubin 16 (10-32), INR 1.6 (1-2.8), MELD-Na 23 (17-30), UKELD 59 (54-62). The control at 3 days of R vs NR respectively was bilirubin 10.6 vs 20.3, MELD-Na 19 vs 31, (p <0.001). The Lille in the R at 3, 7 and 14 days had a statistically significant difference with respect to the NR (p <0.005). The majority of SAH patients (70%) respond to steroid therapy. The favorable response at 3 days could be used as a therapeutic guide. The Lille score was a good predictor on the third day after starting corticosteroids. There was no additional benefit when applying it at 7 and 14 days. MELD-Na is a good predictor of evolution.

Pathogenic Characterization of Clostridium perfringens Strains Isolated From Patients With Massive Intravascular Hemolysis.

Sepsis caused by Clostridium perfringens infection is rare but often fatal. The most serious complication leading to poor prognosis is massive intravascular hemolysis (MIH). However, the molecular mechanism underlying this fulminant form of hemolysis is unclear. In the present study, we employed 11 clinical strains isolated from patients with C. perfringens septicemia and subdivided these isolates into groups H and NH: septicemia with (n = 5) or without (n = 6) MIH, respectively. To elucidate the major pathogenic factors of MIH, biological features were compared between these groups. The isolates of two groups did not differ in growth rate, virulence-related gene expression, or phospholipase C (CPA) production. Erythrocyte hemolysis was predominantly observed in culture supernatants of the strains in group H, and the human erythrocyte hemolysis rate was significantly correlated with perfringolysin O (PFO) production. Correlations were also found among PFO production, human peripheral blood mononuclear cell (PBMC) cytotoxicity, and production of interleukin-6 (IL-6) and interleukin-8 (IL-8) by human PBMCs. Analysis of proinflammatory cytokines showed that PFO induced tumor necrosis factor-α (TNF-α), IL-5, IL-6, and IL-8 production more strongly than did CPA. PFO exerted potent cytotoxic and proinflammatory cytokine induction effects on human blood cells. PFO may be a major virulence factor of sepsis with MIH, and potent proinflammatory cytokine production induced by PFO may influence the rapid progression of this fatal disease caused by C. perfringens.

A rare case of invasive fungal sinusitis by co-infection of two fungi in a post COVID-19 patient: a case report

&lt;p&gt;Invasive fungal rhinosinusitis is a disease of the paranasal sinuses and nasal cavity that typically affects immunocompromised patients in acute fulminant form. Early symptoms can often mimic rhino sinusitis while late symptoms can cause significant morbidity and mortality. With early diagnosis and treatment can increase the patient survival. This case report is of 73 years old diabetic post COVID-19 patients. The patient presented to us was having severe headache and facial pain confined to left side cheek area with loosening of teeth. The patient underwent nasal cavity and biopsy from the maxillary sinus (left side) under local anaesthesia, which confirmed the diagnosis of invasive fungal sinusitis suggestive of co-infection by 2 fungi, aspergillus flavus and mucor. Further, the patient underwent surgical debridement and started on liposomal amphotericin B and patient improved significantly.&lt;/p&gt;

Genetic Defects Affecting Lymphocyte Cytotoxicity in Epstein-Barr Virus-Associated T/NK-Cell Lymphoproliferative Diseases

Background: EBV-associated T/NK-cell lymphoproliferative diseases (EBV+T/NK-LPDs) are a variety of diseases that characterized by clonal expansion of the EBV-infected T or NK cells. In a broad sense, they have a vast spectrum from reactive to neoplastic processes, and from indolent to aggressive or fulminant forms. Such diseases have overlapping clinical manifestations, and are associated with poor outcomes, which usually lead to diagnostic confusion and treatment dilemma. The hallmark of those diseases was refractory elevated EBV DNA titers in target tissues, suggesting genetic defects of the anti-EBV immune response might involve in the pathogenesis.Methods: We retrospectively enrolled 127 adult patients with EBV+T/NK-LPDs, including EBV-associated hemophagocytic lymphohistiocytosis (EBV+HLH, n=43), chronic active EBV infection of T/NK-cell type (CAEBV-T/NK, n=27), extranodal NK/T-cell lymphoma of nasal type (ENKTL, n=19), and aggressive NK-cell leukemia (ANKL, n=38). Genomic DNA was isolated from peripheral blood mononuclear cells. Targeted high-throughput sequencing based on Ion Torrent Personal Genome Machine (PGM) together with Sanger sequencing were performed in all the samples, which covering the coding sequences in 13 genes associated with lymphocyte cytotoxicity. Those 13 genes included GZMB , PRF1 , UNC13D, STX11 , STXBP2 , RAB27A , LYST, AP3B1 , SH2D1A , XIAP , MAGT1 , ITK , and CD27 . Probably pathogenic germline variants were filtered by in silico methods and validated by pedigree studies.Results: A total of 282 probably germline variants were initially identified in this study. According to our filtering strategy, 35 variants were eventually evaluated to be probably pathogenic. Those 35 variants were detected 62 times totally, affecting 59 genes of 47 patients. Mutation patterns were demonstrated in Figure 1. Mutation frequency were 21/43 (49%) in EBV+HLH, 13/27 (49%) in CAEBV-T/NK, 5/19 (26%) in ENKTL, and 8/38 (21%) in ANKL. Of 62 detected mutations, 57 (93%) were overwhelmingly missense mutations, 4 were truncated mutations, and 1 was deep intronic mutation. 3/4 truncated mutations were detected in EBV+HLH. Mutations were most frequently detected in UNC13D , PRF1 , LYST , and ITK . No mutation was found in STX11 , SH2D1A or MAGT1 . All mutations were heterozygous or hemizygous. Monoallelic heterozygous mutations were quite frequent than expected, accounting for 93% (55/59) mutated genes. Only two mutated genes presented biallelic compound heterozygous, which were both detected in EBV+HLH. In addition, di/trigenic synergistic mutations were significantly common in EBV+HLH, accounting for 8/21 (38%) mutated EBV+HLH cases. However, di/trigenic mutations were rarely in other clinical categories.Conclusions: Genetic defects affecting lymphocyte cytotoxicity were prevalent in adult EBV+T/NK-LPDs, especially in EBV+HLH and CAEBV-T/NK. A majority of mutations detected in adult EBV+T/NK-LPDs were “milder” type of mutations represented monogenic, monoallelic, and missense, rather than “severer” type of mutations represented di/trigenic, biallelic, and truncated. Accumulation of partial genetic defects affecting lymphocyte cytotoxicity increases the likelihood of developing adult EBV+T/NK-LPDs, and the severity of genetic defects was associated with the clinical phenotype of onset. Those provided us a novel insight into the pathogenesis of EBV+T/NK-LPDs, and indicate that such spectrum of diseases might be partly a biologic continuum rather than completely discrete entities. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

What the Cardiologist Needs to Know About Cancer Immunotherapies and Complications.

Immunotherapies have transformed the current landscape for cancer treatment and demonstrated unparalleled improvements in survival rates. Now, a third of cancer patients are eligible for treatment with the most widely used class of immunotherapy, immune checkpoint inhibitors (ICIs). As more patients are treated with these novel agents, it is critical for both oncologists and subspecialists to establish a better understanding of the adverse events which can occur. The incidence of myocarditis associated with ICI therapy has been reported to be between 0.27 and 1.14%, 5 times that of myocarditis from other cancer therapies, and, of those patients, 20-50% develop a fulminant form. However, because of unclear risk factors, a broad clinical spectrum, and lack of specific noninvasive studies for diagnosis, the care of patients with ICI-associated cardiotoxicity can be challenging. Here, we have provided a brief overview of the current immunotherapy agents with a focus on the emerging evidence regarding diagnosis and management of cardiac adverse events.

Maladie de Wilson

AbstractWilson’s disease is a autosomal recessive inherited disorder that causes progressive copper overload. The ATP7B gene carried on chromosome 13 encodes an intracellular copper transporter ATP7B protein that allows cellular excretion of excess copper. In Wilson’s disease, the functional deficiency of ATP7B causes a failure in the elimination of copper from the bile, which then accumulates in the liver and is then released in free form into the bloodstream. Wilson’s disease is therefore an initially hepatic disorder which can progress to multisystem involvement with an accumulation of copper in the brain, eye, kidney, etc. if it is not diagnosed early. The first symptoms are most often hepatic in children and neurological in adults. The diagnosis is made on a bundle of clinical, biological and radiological arguments. Interpretation of the cupric balance, typically associating a decrease in ceruloplasminemia and total cupremia with an increase in 24-hour urinary copper excretion, can be difficult, justifying the determination of the free or exchangeable copper. The ratio of exchangeable copper/total copper or REC (relative exchangeable copper) is an excellent diagnostic biomarker. Molecular biology can confirm the diagnosis in 98 % of cases. The treatments combine a copper low diet, copper chelators or zinc salts. Liver transplantation is the treatment for fulminant liver forms and decompensated cirrhosis. This rare genetic disease has a good prognosis if treatment is started early and continued all lifelong. It is therefore important to know the clinical manifestations of the disease and the diagnostic tests in order to evoke it quickly and to then ensure regular clinical and laboratory monitoring of patients.

Compatibility of Novel Cardiogenic Shock Phenotypes from the Cardiogenic Shock Working Group (CSWG) with the SCAI Staging System

<h3>Purpose</h3> Cardiogenic shock (CS) is a heterogeneous syndrome that represents an acute and fulminant form of heart failure (HF). We (1) employed machine learning (ML) to identify distinct CS phenotypes which could help define treatment algorithms based on individual risk and (2) tested the correlation of the SCAI staging system. <h3>Methods</h3> We included data from 1957 CS patients from 2 cohorts: CSWG Registry, further grouped for myocardial infarction (CSWG-MI, n=408) and acute on chronic HF (CSWG-HF, n=480); and the Danish Retroshock Registry containing MI patients (DRR, n=1069). Independent consensus <i>k</i> means clustering derived phenotypes at admission in the CSWG-MI cohort that were then validated in the CSWG-HF and DRR cohorts. Patients were also categorized by the most severe SCAI stage reached during the hospitalization. <h3>Results</h3> The ML algorithms revealed 3 distinct clusters that we designated: ‘non-congested (I)', ‘cardio-renal (II)' and ‘cardio-metabolic (III)'. In-hospital mortality was 21% vs 29% vs 10%, 42% vs 46% vs 32%, and 55% vs 57% vs 54% among the CSWG-MI vs DDR vs CSWG-HF for Clusters I, II and III, respectively. Despite baseline differences among the overall cohorts, clusters presented similarly across the 3 cohorts. The risk of escalating to stage D or E shock was lowest in Cluster I and highest in Cluster III for both CS-MI and CS-HF patients. Within each phenotype, the SCAI staging (C-E) further stratified mortality (fig). <h3>Conclusion</h3> Using ML, we derived and externally validated 3 distinct CS phenotypes. SCAI stages and CSWG CS phenotypes identify patients at risk for in-hospital mortality.

Mucormycosis of the maxillary sinus in an immunocompetent woman with oro-antral fistula – a case report

Mucormycosis is a very rare fungal infection, characterized by vascular invasion, rapid progression and high mortality. Individuals suffering from systemic diseases influencing the immune system are predisposed to this infection which is caused by saprophytic fungi belonging to the class of Mucormycetes in the order of Mucorales. In this paper, we present an unusual case of mucormycosis of the maxillary sinus in an immunocompetent patient with oro-antral fistula. The infection may occur in either a fulminant or chronic form. In the patient described, the disease was chronic and characterized by a mild course with local symptoms. In the disseminated form of mucormycosis, the mortality rate is almost 100%. A definitively higher survival rate is observed in immunocompetent patients with a localized form of the infection. Diagnosis of the disease is very difficult because of its clinical and radiological similarity to the more common fungal infection, aspergillosis. Early diagnosis plays a key role in the course of treatment and allows to reduce the scope of surgical intervention. According to most authors, first line treatment should be the liposomal form of amphotericin B. Some also advise surgical treatment involving the removal of fungal masses. In the patient described, both surgical and pharmacological treatment was conducted resulting in the complete resolution of the fungal infection after 12 months.

Humoral immune responses mediate the development of a restrictive phenotype of chronic lung allograft dysfunction.

Understanding the distinct pathogenic mechanisms that culminate in allograft fibrosis and chronic graft failure is key in improving outcomes after solid organ transplantation. Here, we describe an F1 → parent orthotopic lung transplant model of restrictive allograft syndrome (RAS), a particularly fulminant form of chronic lung allograft dysfunction (CLAD), and identify a requisite pathogenic role for humoral immune responses in development of RAS. B6D2F1/J (H2-b/d) donor lungs transplanted into the parent C57BL/6J (H2-b) recipients demonstrated a spectrum of histopathologic changes, ranging from lymphocytic infiltration, fibrinous exudates, and endothelialitis to peribronchial and pleuroparenchymal fibrosis, similar to those noted in the human RAS lungs. Gene expression profiling revealed differential humoral immune cell activation as a key feature of the RAS murine model, with significant B cell and plasma cell infiltration noted in the RAS lung allografts. B6D2F1/J lung allografts transplanted into μMt–/– (mature B cell deficient) or activation-induced cytidine deaminase (AID)/secretory μ-chain (μs) double-KO (AID−/−μs−/−) C57BL/6J mice demonstrated significantly decreased allograft fibrosis, indicating a key role for antibody secretion by B cells in mediating RAS pathology. Our study suggests that skewing of immune responses determines the diverse allograft remodeling patterns and highlights the need to develop targeted therapies for specific CLAD phenotypes.

Use of polymerase chain reaction in verification and differential diagnosis of babesiosis pathogens

Today, Babesia is recognized as one of the most common blood parasites in the world, which in terms of the number of cases of invasion is second only to trypanosomes (the causative agent of African trypanosomiasis and Chagas’ disease). These microorganisms can cause parasitism in erythrocytes and hematopoietic organs. They cause an infectious process, the clinical course of which can vary from asymptomatic, subclinical, mild or moderate influenza-like forms – to severe progressive disease (fulminant form) with fatal outcome. Thus, the latter determines the significant burden of babesia for the leading branches of medicine, veterinary medicine and the economy as a whole. The presented work is devoted to the study of the prospects for verification of babesiosis causative agents by the polymerase chain reaction (PCR) method. Blood, erythrocyte suspension, homogenized tick-carriers of babesiosis, culture of Babesia spp. were used as research material (samples). In order to obtain an objective assessment, the PCR-diagnostics method was used in two formats – standard and multiplex (multi-primer). Multiple PCR testing of multiplex format using primers in model samples containing cells of different species of Babesia (B. microti, B. divergens, B. bovis, B. canis), allowed us to establish the level of reproducibility of the results of such studies, which ranged 94.6–96.4%, to determine the level of PCR sensitivity of the multiplex format for detection/identification of human pathogenic babesia (B. microti, B. divergens and B. venatorum). It is established that the advantages of the PCR-diagnostic method of babesiosis pathogens in the samples of the studied biomaterial were: speed of research (2–4 hours); high sensitivity, specificity, reproducibility of Babesia detection results, prospects of species identification, differentiation with apicomplex spores (Plasmodium falciparum, Toxoplasma). In view of the above, the PCR method is recommended for use in cases of persistent suspicion of babesiosis infection (in cases of negative results of microscopic/cytological studies, to identify asymptomatic, subclinical and chronic forms of babesiosis, verification of active invasion in seropositive individuals and for Babesia species and their differentiation).