Non-infectious Origin Research Articles

Viral myocarditis.

The term myocarditis describes inflammatory disorders of the heart muscle of varied infectious and non-infectious origins. It can be caused by any kind of infection, drugs, toxic substances, or be associated with autoimmune conditions. Viruses are the main causes at least in developed countries. Acute myocarditis most commonly results from an external inflammatory trigger inducing the host immune response, which may range from minimally transient response to fulminant overwhelming cellular infiltration. If the immune system does not eliminate the infectious pathogen early on, chronic infection develops with or without accompanying inflammation. Post-infectious autoimmunity may persist despite effective virus clearance. Since the pathological conditions take place at the cellular level, viral myocarditis and postinfectious autoimmunity can be suggested but not diagnosed clinically. All clinical methods including imaging techniques are misleading if infectious agents are involved. Accurate diagnosis demands simultaneous histologic, immunohistochemical and molecular biological workup of the tissue. If the primary infectious or immune-mediated causes of the disease are carefully defined by clinical and biopsy based tools, specific antiviral treatment options in addition to basic symptomatic therapy are available under certain conditions. These may allow a tailored cause-specific treatment that improves symptoms and prognosis of patients with acute and chronic disease.

Non-infectious events under the International Health Regulations (2005) in Europe--a case for syndromic surveillance.

The scope of the International Health Regulations of 2005 (IHR (2005)) has been expanded. The IHR (2005) are no longer limited to a specific set of infectious diseases, instead they prescribe detection and assessment of any event of potential public health concern regardless of its source or origin. We examine events of non-infectious origin that might fulfill the criteria of a potential public health emergency of international concern under the IHR (2005). These comprise predominately events related to food safety, but also events related to drug safety or of chemical or industrial origin. We argue that to identify these events and assess health effects related to them, existing disease surveillance systems should be augmented with less specific indicator-based syndromic surveillance strategies that use available routine health-related service data for monitoring purposes.

Markers for sepsis diagnosis in the forensic setting: state of the art.

Reliable diagnoses of sepsis remain challenging in forensic pathology routine despite improved methods of sample collection and extensive biochemical and immunohistochemical investigations. Macroscopic findings may be elusive and have an infectious or non-infectious origin. Blood culture results can be difficult to interpret due to postmortem contamination or bacterial translocation. Lastly, peripheral and cardiac blood may be unavailable during autopsy. Procalcitonin, C-reactive protein, and interleukin-6 can be measured in biological fluids collected during autopsy and may be used as in clinical practice for diagnostic purposes. However, concentrations of these parameters may be increased due to etiologies other than bacterial infections, indicating that a combination of biomarkers could more effectively discriminate non-infectious from infectious inflammations. In this article, we propose a review of the literature pertaining to the diagnostic performance of classical and novel biomarkers of inflammation and bacterial infection in the forensic setting.

Viral communities associated with human pericardial fluids in idiopathic pericarditis.

Pericarditis is a common human disease defined by inflammation of the pericardium. Currently, 40% to 85% of pericarditis cases have no identified etiology. Most of these cases are thought to be caused by an infection of undetected, unsuspected or unknown viruses. In this work, we used a culture- and sequence-independent approach to investigate the viral DNA communities present in human pericardial fluids. Seven viral metagenomes were generated from the pericardial fluid of patients affected by pericarditis of unknown etiology and one metagenome was generated from the pericardial fluid of a sudden infant death case. As a positive control we generated one metagenome from the pericardial fluid of a patient affected by pericarditis caused by herpesvirus type 3. Furthermore, we used as negative controls a total of 6 pericardial fluids from 6 different individuals affected by pericarditis of non-infectious origin: 5 of them were sequenced as a unique pool and the remaining one was sequenced separately. The results showed a significant presence of torque teno viruses especially in one patient, while herpesviruses and papillomaviruses were present in the positive control. Co-infections by different genotypes of the same viral type (torque teno viruses) or different viruses (herpesviruses and papillomaviruses) were observed. Sequences related to bacteriophages infecting Staphylococcus, Enterobacteria, Streptococcus, Burkholderia and Pseudomonas were also detected in three patients. This study detected torque teno viruses and papillomaviruses, for the first time, in human pericardial fluids.

Using CRP in neonatal practice

Objective: C-reactive protein (CRP) is the most widely used infection marker in neonatal practice. Combined with difficulty in early recognition of neonatal sepsis, the number of infants with risk factors for infection, and postnatal maladaptation of non-infectious origin; CRP is often used as a decision making tool for antibiotic therapy. We wished to examine practice regarding neonatal infection and use of CRP.Methods: We designed an online multiple choice questionnaire, asking senior clinicians for their response to realistic postnatal ward scenarios.Results: We had 91 replies, showing a great degree of variation, with no pattern emerging for experience, region, or even individual neonatal units. This was true even for situations covered by the guidelines that have an evidence basis.Conclusions: A recurring theme was duration of antibiotic therapy for an elevated CRP, and once levels are falling, when it is safe to stop treatment. Given a lack of good quality evidence, the National Institute of Clinical Excellence (NICE) guidelines are purposefully non-specific. Further research is required, and if incorporated in future national guidelines, should help promote more widespread use and so reduce potential over- and under-treatment of this patient subset. However, this also requires a greater willingness on the part of pediatricians to ensure practice is evidence based.

Use of procalcitonin and white blood cells as combined predictors of infection in cardiac surgery patients

The aim of this study is to identify a marker able to predict sepsis in cardiac surgery patients and to differentiate SIRS from infectious and non-infectious origin. The occurrence of sepsis after cardiac surgery increases the mortality risk. Sepsis may be mistaken for the cardiac surgery-associated systemic inflammatory response syndrome (SIRS) [1].

Medikamentöse Therapie der infektiösen Diarrhö

Diarrheal diseases are among the most common diseases worldwide. In this review the current treatment recommendations for acute (Part 1) and chronic (Part 2) infectious diarrhea are summarized and typical enteropathogens are discussed. The second part of the article describes chronic diarrhea, its related pathogens and treatment. In contrast to acute diarrhea which is mainly caused by viral and typical bacterial pathogens, chronic diarrhea has mainly non-infectious origins. Protozoal pathogens, such as Giardia lamblia and Entamoeba histolytica in particular are found and more rarely bacterial pathogens, such as Tropheryma whipplei. Opportunistic pathogens cause diarrhea in immunocompromised patients, such as in HIV patients. In these patients cytomegalovirus (CMV) colitis or infections with Cryptosporidium spp., Cyclospora cayetanensis, Isospora belli or microsporidia have to be considered. Besides targeted specific antimicrobial therapy, anti-retroviral drugs improving the underlying immunosuppression and thus the reconstitution of the adaptive immune response remain a cornerstone of the treatment in HIV-positive patients.

Sarcoidosis en pediatría: reporte de 7 casos

Sarcoidosis is a chronic granulomatous disease of non-infectious origin which can involve various target organs. Its prevalence is low and there have been only isolated cases reported in Colombia. Its etiology and pathophysiology are not well known. The clinical presentation and signs of the disease vary. When its onset is before five years of age it is recognized as early onset sarcoidosis, while if its onset is after five years of age it is called late onset sarcoidosis. In this case report all patients had a delayed diagnosis and they presented with a multiple organ involvement which required an immunosuppressive treatment. Of the 7 patients, 4 had a chronic course, 2 had remission, and 1 with frequent relapses of the disease. There was an unusual relationship of two patients with early onset disease who additionally presented with Ollier's disease.

Nutritional Indicators for Postoperative Morbidity in Elective Oncological Surgery

Objective: This study was to establish the nutritional risk factors for morbidity following cancer surgery to reduce the incidence of related postoperative complications. Therefore this study was undertaken to assess the morbidity and to identify nutritional risk factors following cancer surgery in Bangladeshi population. Method: This cross-sectional observational study included 312 patients with malignancy who were waiting for surgery or within 60 days of postoperative period were enrolled for the study from indoor of surgical oncology department, NICR&H. Then the patients were submitted for further study to evaluate the preoperative fitness in terms of nutrition assessment – both clinical and biological. All the clinical (pre & post-operative including complication, if any), investigation findings were recorded accordingly. Results: Statistical correlation was discovered between BMI and morbidity but no statistical correlation was found between WL >10% and major surgical complications of either infectious or noninfectious origin (p = NS). No statistically significant correlation was found between nutritional condition or oedema and surgical morbidity. Conversely, a substantial statistical correlation was found between skin thickness or Hb% or albumin <30 g/l and major surgical complications (either infectious or noninfectious) (p= S). Conclusion: The best nutritional factor for detecting the risk of MC is albumin levels below 30 g/l. DOI: http://dx.doi.org/10.3329/jss.v16i1.14441 Journal of Surgical Sciences (2012) Vol. 16 (1) : 3-10

Hyperpigmentation in North Sea dab Limanda limanda. II. Macroscopic and microscopic characteristics and pathogen screening

An increasing trend in the prevalence of hyperpigmentation in the common dab Limanda limanda from the North Sea prompted us to investigate the potential role of infectious agents as causes or contributing factors to the condition. Dab representing 3 severity grades of hyperpigmentation were sampled for virology, bacteriology, histopathology and ultrastructure assessments. No cytopathic effect was recorded during virology testing, and bacteriological results showed no differences between normal and hyperpigmented dab. Histopathological assessment showed that the most significant changes occurred in the dermis as a result of chromatophore hyperplasia, namely melanophores and iridophores, alongside loose melanin granules. Dermal lymphocytic infiltration occasionally expanding into the epidermis and the underlying musculature was more frequent in highly pigmented dab than in normal fish, suggesting an active immune response. Ultrastructure studies showed additional disruption of the epithelial layer, with loose melanin granules between cells and a number of single or aggregated melanocytes. Dab representing different grades of hyperpigmentation kept in the laboratory alongside normal fish for a monitoring period of 18 mo showed no changes in their pigment distribution pattern, nor occurrence of new pigment in the normal fish. The current investigation found no association of hyperpigmentation in the common dab with infectious agents; therefore, understanding the cause of the condition remains a challenge which can now more reliably focus on a non-infectious origin hypothesis.

Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis

Procalcitonin is a promising marker for identification of bacterial infections. We assessed the accuracy and clinical value of procalcitonin for diagnosis of sepsis in critically ill patients. We searched Medline, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct, from inception to Feb 21, 2012, and reference lists of identified primary studies. We included articles written in English, German, or French that investigated procalcitonin for differentiation of septic patients--those with sepsis, severe sepsis, or septic shock--from those with a systemic inflammatory response syndrome of non-infectious origin. Studies of healthy people, patients without probable infection, and children younger than 28 days were excluded. Two independent investigators extracted patient and study characteristics; discrepancies were resolved by consensus. We calculated individual and pooled sensitivities and specificities. We used I(2) to test heterogeneity and investigated the source of heterogeneity by metaregression. Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0 · 77 (95% CI 0 · 72-0 · 81) and specificity of 0 · 79 (95% CI 0 · 74-0 · 84). The area under the receiver operating characteristic curve was 0 · 85 (95% CI 0 · 81-0 · 88). The studies had substantial heterogeneity (I(2)=96%, 95% CI 94-99). None of the subgroups investigated--population, admission category, assay used, severity of disease, and description and masking of the reference standard--could account for the heterogeneity. Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment. Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, Thuringian Ministry for Education, Science and Culture, the Thuringian Foundation for Technology, Innovation and Research, and the German Sepsis Society.

Clinical characteristics and the usefulness of the QuantiFERON-TB Gold In-Tube test in hematologic patients with hepatic or splenic lesions

Background/AimsHepatic or splenic lesions in hematologic patients are not defined well because they are not easy to evaluate due to limitations of invasive procedures. Management typically depends on the clinical diagnosis with few microbiological data.MethodsWe reviewed the medical records of consecutive hematologic patients with hepatic or splenic lesions in the infectious diseases unit from April 2009 to December 2010 at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea.ResultsTwenty-six patients were identified. Their mean age was 46.0 ± 14.7 years, and 16 (61.5%) were male. Underlying diseases were acute myelogenous leukemia (n = 15, 57.7%) and myelodysplastic syndrome (n = 6, 23.1%). Among the nine nontuberculous infectious lesions, two bacterial, six fungal, and one combined infection were identified. The numbers of confirmed, probable, and possible tuberculosis (TB) cases were one, three, and four, respectively. Two patients had concurrent pulmonary TB. QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis Ltd.) was positive in seven cases, among which six were diagnosed with TB. The sensitivity and specificity of QFT-GIT were 75% and 81.3%. Nine (34.6%) were defined as noninfectious causes.ConclusionsCauses of hepatic or splenic lesion in hematologic patients were diverse including TB, non-TB organisms, and noninfectious origins. TB should be considered for patients not responding to antibacterial or antifungal drugs, even in the absence of direct microbiological evidence. QFT-GIT may be useful for a differential diagnosis of hepatosplenic lesions in hematologic patients.

STREM-1 in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis, effect of smoking and inflammation

Soluble TREM-1 (sTREM-1; Triggering receptor expressed on myelocytes) is a new inflammatory marker indicating the intensity of myeloid cells activation and the presence of infection caused by extracellular bacteria and mould.The aim of our work was to detect and compare the levels of sTREM-1 in bronchoalveolar lavage fluid (BALF) in patients with pulmonary sarcoidosis (PS) and other ILD of non-infectious origin. The sTREM-1 levels were assessed by ELISA in 46 patients suffering from ILD, out of them 22 with PS. The levels of BALF sTREM-1 in PS patients were higher than in control group of ILD patients of non-infectious origin, however, the difference was not statistically significant. Since all PS patients except one were non-smokers we compared non-smokers PS with non-smokers ILD patients and found four times higher levels of BALF sTREM-1 in PS patients (P = 0.001). We also recorded the effect of smoking, ILD smokers had higher sTREM-1 levels than non-smokers (P = 0.0019). Higher concentrations of sTREM-1 were detected in BALF of patients with lymphadenopathy and with elevated inflammatory markers in BALF. Our results show that BALF sTREM-1 could be a good inflammatory marker and could help in diagnosis and PS monitoring. Detection of sTREM-1 in BALF indirectly points to myeloid cells activation in the lungs and helps to complete the information about the number of myeloid cells commonly determined in BALF with additional information concerning the intensity of their activation. This is the first study that analyses BALF sTREM-1 levels in patients with PS (Tab. 8, Ref. 28). Text in PDF www.elis.sk.

Insights into imaging of aortitis

BackgroundAortitis is a subtype of the more general term “vasculitis”, an inflammatory condition of infectious or noninfectious origin involving the vessel wall. The term “vasculitis” refers to a broad spectrum of diseases with different aetiologies, pathophysiologies, clinical presentations and prognoses. The clinical manifestations are nonspecific, as are the laboratory findings such as pain, fever, weight loss, vascular insufficiency and elevated levels of acute phase reactants, as well as other systemic manifestations, and sometimes may mimic other entities. Thus, if not suspected as part of the initial differential diagnosis, aortitis can be overlooked during the workup of patients with constitutional symptoms and systemic disorders. Methods: Imaging is rarely used for the primary diagnosis, but imaging findings, although nonspecific, can help in the assessment of these patients and is often required for making the final diagnosis. Imaging can be critical in the initiation of appropriate management and therapy. Results: Noninvasive cross-sectional imaging modalities such as contrast-enhanced CT, magnetic resonance (MR) imaging, nuclear medicine and in particular positron emission tomography (PET) are the leading modalities in modern diagnostic imaging of aortitis for both the initial diagnosis and follow-up. Conclusion: This review focusses on the most common manifestations of aortitis with which radiologists should be familiar.Teaching Points• Aortitis is an inflammatory condition of infectious/noninfectious origin involving the vessel wall.• Imaging findings can help in the assessment of aortitis and are often crucial for the final diagnosis.• Contrast-enhanced CT, MRI and PET-CT are used for both the initial diagnosis and follow-up of aortitis.

CFTR, Mucins, and Mucus Obstruction in Cystic Fibrosis

Mucus pathology in cystic fibrosis (CF) has been known for as long as the disease has been recognized and is sometimes called mucoviscidosis. The disease is marked by mucus hyperproduction and plugging in many organs, which are usually most fatal in the airways of CF patients, once the problem of meconium ileus at birth is resolved. After the CF gene, CFTR, was cloned and its protein product identified as a cAMP-regulated Cl(-) channel, causal mechanisms underlying the strong mucus phenotype of the disease became obscure. Here we focus on mucin genes and polymeric mucin glycoproteins, examining their regulation and potential relationships to a dysfunctional cystic fibrosis transmembrane conductance regulator (CFTR). Detailed examination of CFTR expression in organs and different cell types indicates that changes in CFTR expression do not always correlate with the severity of CF disease or mucus accumulation. Thus, the mucus hyperproduction that typifies CF does not appear to be a direct cause of a defective CFTR but, rather, to be a downstream consequence. In organs like the lung, up-regulation of mucin gene expression by inflammation results from chronic infection; however, in other instances and organs, the inflammation may have a non-infectious origin. The mucus plugging phenotype of the β-subunit of the epithelial Na(+) channel (βENaC)-overexpressing mouse is proving to be an archetypal example of this kind of inflammation, with a dehydrated airway surface/concentrated mucus gel apparently providing the inflammatory stimulus. Data indicate that the luminal HCO(3)(-) deficiency recently described for CF epithelia may also provide such a stimulus, perhaps by causing a mal-maturation of mucins as they are released onto luminal surfaces. In any event, the path between CFTR dysfunction and mucus hyperproduction has proven tortuous, and its unraveling continues to offer its own twists and turns, along with fascinating glimpses into biology.

Simulation of Nonalcoholic Steatohepatitis in Rats

The new model of nonalcoholic steatohepatitis in rats is based on alimentary effects of hypercaloric diet including much cholesterol and beef fat. This model reproduces structural and functional disorders in the liver, including hepatocyte fatty degeneration, parenchymatous necrosis and fibrosis paralleled by dyslipidemia and is intended for studies of the mechanisms of formation, progress, and therapy of liver diseases of noninfectious origin.

C reactive protein: impact on peripheral tissue oxygenation and perfusion in neonates

ObjectiveC reactive protein (CRP) is a sensitive marker of acute inflammation of infectious and non-infectious origin. Aim was to use near-infrared spectroscopy (NIRS) to analyse peripheral oxygenation and perfusion in...

Mass Spectometry-Based Protein Patterns in the Diagnosis of Sepsis/Systemic Inflammatory Response Syndrome

Early differential diagnosis of systemic inflammatory reactions in critically ill patients is essential for timely implementation of lifesaving therapies. Despite many efforts made, reliable biomarkers to discriminate between infectious and noninfectious causes of systemic inflammatory response syndrome (SIRS) are currently not available. Recent advances in mass spectrometry-based methods have raised hopes that identification of spectral patterns from serum/plasma samples can be instrumental in this context. We compared protein expression patterns from patients with SIRS of infectious and noninfectious origin. Plasma samples from 166 patients obtained under rigorously standardized preanalytical conditions were applied to Q10 and CM10 ProteinChips. Protein profiles were used to train and develop decision tree classification algorithms. Discriminatory peaks were isolated and identified. Classification trees distinguished patients with noninfectious SIRS with organ dysfunction following open heart surgery using cardiopulmonary bypass from those with severe sepsis or septic shock with distinct sensitivities and specificities. Results were validated in a blinded test set in two independent experiments and in a second independently collected test set. Discriminatory peaks at 13.8 and 55.7 kd were identified as transthyretin and α1-antitrypsin; the third protein at m/z 4,798 was assigned to a proteolytic fragment of α1-antitrypsin. Taken together, our data demonstrate that plasma protein profiling allows reproducible discrimination between patients with infectious and noninfectious SIRS with high sensitivity and specificity. However, rigorous standardization as well as considering drug-related interferences is essential when interpreting protein profiling studies. Identification of discriminatory proteins suggests a direct link between infectious-related protease activity and a sepsis-specific diagnostic pattern for discrimination of patients with SIRS.

Bovine abortion Part 1: Still one of the most difficult diagnoses to make

Effective surveillance methods for brucellosis are in place worldwide. The diagnosis of sporadic bovine abortion cases remains difficult because emphasis is placed on infectious causes, which may be controlled to some extent by vaccination, whereas the majority are of non-infectious origin. This case study describes a pathology-based investigation of a sporadic abortion, presumably associated with neosporosis from laboratory results of previous episodes. A fetal cardiomyopathy was found, possibly associated with vitamin E/selenium deficiency, and evidence that it died during second-stage labour at 225 days gestation. The dam presented no evidence of Neospora caninum infection, but bulk milk serology suggested that control of leptospirosis was inadequate in this herd. DOI: 10.1111/j.2044-3870.2011.00065.x

Diagnostic Approaches for the Assessment of Equine Chronic Pulmonary Disorders

Even though the respiratory system is one of the most accessible organs for diagnostic testing, it is not always easy to define chronic lower airway disease in the horse. Diagnostic procedures performed by first opinion veterinarians in the field are often restricted to taking the history and performing clinical examination. Respiratory tract endoscopy, tracheal or bronchoalveolar lavage, and blood sampling are sometimes used but other specific ancillary examinations are seldom performed in stable settings. Therefore, our objectives were to evaluate the diagnostic value of different techniques and examination types routinely used in the diagnostic workup of chronic equine lower airway cases in both stable and clinical circumstances. Another aim of this study was to estimate the prevalence of different chronic pulmonary disorders among horses admitted to a Hungarian referral clinic. According to the conditional inference tree method, age of the horse, history, clinical examination, respiratory tract endoscopy, and bronchoalveolar lavage cytology proved to be the most valuable tools to define pathology. It was also concluded that in 22% of cases, more specific ancillary diagnostic modalities, unavailable for the field veterinarian, were needed to establish the final diagnosis. According to our study, the most frequently diagnosed chronic pulmonary disorders in Hungary are of noninfectious origin, principally recurrent airway obstruction. Regardless of the cause, and interestingly including recurrent airway obstruction as well, these diseases occur primarily during the warm months.