title: Development of treatment and clinical results in childhood AML in Austria (1993–2013)

text: BACKGROUND: Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials have been performed in Austria (AML-Berlin-Frankfurt-Münster (BFM) 93, AML-BFM 98, and AML-BFM 2004) in close cooperation with the international BFM study center. Herein, we review the pertinent patient characteristics, therapy, and outcome data. PATIENTS AND METHODS: From January 1993 to April 2013, 249 children and adolescents (193 protocol patients) diagnosed with AML were enrolled in the three BFM studies. Patients were mainly treated in one of five pediatric hematology/oncology centers distributed over Austria. RESULTS: Many characteristics and outcome parameters were not statistically different between the three trials. Almost similar proportions of patients were stratified into two risk groups: standard risk (SR) (approximately 37 % overall) and high-risk (HR) (61 %). MLL rearrangements were found in 23 % of patients overall as the most frequent genetic aberration subtype. Complete remission (CR) was achieved by 84–95 % of patients. The most important type of event was leukemic relapse (5-year cumulative incidence 40 ± 8 %, 21 ± 5 %, and 39 ± 6 %; p = 0.058), with a trend to a higher rate specifically in SR patients of study AML-BFM 2004 compared with AML-BFM 98. Importantly, the frequency of death from causes other than relapse sequelae declined over the years (AML-BFM 93: 5/42 12 %, AML-BFM 98: 5/57 9 %, and AML-BFM 2004: 5/94 5 %). Altogether, event-free survival at 5 years varied insignificantly (48 ± 8 %, 61 ± 7 %, and 50 ± 6 %; p = 0.406). Nevertheless, survival (pSU) apparently improved from BFM 93 to subsequent studies, both overall (57 ± 8 %, 75 ± 6 %, and 62 ± 6 %; p = 0.046) and regarding the HR group (5-year-probability of survival (pSU) 40 ± 10 %, 66 ± 8 %, and 52 ± 8 %; p = 0.039). CONCLUSION: Treatment of pediatric AML in Austria renders survival rates in the range of international best practice. However, unambiguous statistical comparison of treatment periods is eventually hampered by small numbers and inequalities of recruitment. Hence, only internationally collaborative trials will allow developing treatment further to achieve higher cure rates with fewer events.


title: N-acetylcysteine and neurodegenerative diseases: Basic and clinical pharmacology

text: Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer’s disease, Parkinson’s disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down’s syndrome have been associated with several mitochondrial alterations Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in cellular damage and programmed cell death. First, this review examines the mechanisms of action of N-acetylcysteine (NAC), an antioxidant and a free radical-scavenging agent that increases intracellular GSH, at the cellular level. NAC can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. The chemical properties of NAC include redox interactions particularly with other members of the group XIV elements (selenium, etc.) and ebselen, a lipid-soluble seleno-organic compound. Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule neurons. Recent findings on the protective effect of NAC against 4-hydroxynonenal (HNE)-induced toxicity in cerebellar granule neurons are summarized. Finally, the protective pharmacokinetics of NAC in humans and the possible usefulness of NAC for the treatment of neurodegenerative diseases are discussed with reference to basic and clinical studies.


title: Intracellular versus extracellular granzyme B in immunity and disease: challenging the dogma

text: The cytotoxic granzyme B (GrB)/perforin pathway has been traditionally viewed as a primary mechanism that is used by cytotoxic lymphocytes to eliminate allogeneic, virally infected and/or transformed cells. Although originally proposed to have intracellular and extracellular functions, upon the discovery that perforin, in combination with GrB, could induce apoptosis, other potential functions for this protease were, for the most part, disregarded. As there are 5 granzymes in humans and 11 granzymes in mice, many studies used perforin knockout mice as an initial screen to evaluate the role of granzymes in disease. However, in recent years, emerging clinical and biochemical evidence has shown that the latter approach may have overlooked a critical perforin-independent, pathogenic role for these proteases in disease. This review focuses on GrB, the most characterized of the granzyme family, in disease. Long known to be a pro-apoptotic protease expressed by cytotoxic lymphocytes and natural killer cells, it is now accepted that GrB can be expressed in other cell types of immune and nonimmune origin. To the latter, an emerging immune-independent role for GrB has been forwarded due to recent discoveries that GrB may be expressed in nonimmune cells such as smooth muscle cells, keratinocytes, and chondrocytes in certain disease states. Given that GrB retains its activity in the blood, can cleave extracellular matrix, and its levels are often elevated in chronic inflammatory diseases, this protease may be an important contributor to certain pathologies. The implications of sustained elevations of intracellular and extracellular GrB in chronic vascular, dermatological, and neurological diseases, among others, are developing. This review examines, for the first time, the multiple roles of GrB in disease pathogenesis.


title: Pyomyositis in Children

text: Primary pyomyositis in children is prevalent in the tropics and increasingly being recognised from temperate regions. Staphylococcus aureus remains the principle causative organism worldwide, while proportion of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is on rise. Commonly involved groups are around the pelvis and lower limbs. Clinical presentation depends on the stage of disease, most commonly a child presenting with limping with fever. Early diagnosis and management are crucial. The investigation of choice is MRI scan. Appropriate antibiotic treatment should be instituted at the earliest opportunity along with drainage. Majority of patients show excellent and complete recovery with no long-term complications once treatment is started early. A high level of awareness and suspicion of this condition is warranted from all paediatric clinicians.


title: T-cell lymphomas, a challenging disease: types, treatments, and future

text: T-cell lymphomas are rare and aggressive malignancies associated with poor outcome, often because of the development of resistance in the lymphoma against chemotherapy as well as intolerance in patients to the established and toxic chemotherapy regimens. In this review article, we discuss the epidemiology, pathophysiology, current standard of care, and future treatments of common types of T-cell lymphomas, including adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma, aggressive NK/T-cell lymphoma, and cutaneous T-cell lymphoma.


title: Characterization of proinflammatory cytokine production and CD14 expression by murine alveolar macrophage cell lines

text: Alveolar macrophages, which play a central role in lung defense, produce cytokines that help orchestrate local inflammatory responses. In sepsis and other pathological conditions, bacterial lipopolysaccharide endotoxin can induce alveolar macrophages (AM) to release proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1, and interleukin-6. Studying the mechanisms that control alveolar macrophage cytokine production may lead to better therapies for conditions involving inflammatory lung injury. We and others have noted significant differences between alveolar macrophages and peritoneal macrophages, but large numbers of human or murine alveolar macrophages are rarely available for detailed mechanistic studies. We have obtained three murine alveolar macrophage cell lines (AMJ2C8, AMJ2C11, and AMJ2C20) and have begun to characterize their cytokine responses to proinflammatory stimuli. We measured the effects of endotoxin, interferon gamma, and the combination of the two on production of tumor necrosis factor, interleukin-1 beta, and interleukin-6 in each line. We also studied the expression of the endotoxin receptor CD14 by these cells, and investigated the effect of serum on their endotoxin responsiveness. We show here that all three of the cell lines responded in a manner comparable to that of primary murine alveolar macrophages. Observed variations between these lines may reflect the documented heterogeneity seen in populations of primary alveolar macrophages. These cell lines should expand the repertoire of tools available to investigators studying regulation of murine alveolar macrophage responses.


title: Herpes simplex virus 2 infection: molecular association with HIV and novel microbicides to prevent disease

text: Infection with herpes simplex viruses is one of the most ancient diseases described to affect humans. Infection with these viruses produces vexing effects to the host, which frequently recur. Infection with herpes simplex viruses is lifelong, and currently there is no vaccine or drug to prevent or cure infection. Prevalence of herpes simplex virus 2 (HSV-2) infection varies significantly depending on the geographical region and nears 20 % worldwide. Importantly, HSV-2 is the first cause of genital ulcers in the planet. HSV-2 affects approximately 500 million people around the globe and significantly increases the likelihood of acquiring the human immunodeficiency virus (HIV), as well as its shedding. Thus, controlling HSV-2 infection and spread is of public health concern. Here, we review the diseases produced by herpes simplex viruses, the factors that modulate HSV-2 infection, the relationship between HSV-2 and HIV and novel therapeutic and prophylactic microbicides/antivirals under development to prevent infection and pathological outcomes produced by this virus. We also review mutations associated with HSV-2 resistance to common antivirals.


title: Cell-Specific Nitric Oxide Synthase-Isoenzyme Expression and Regulation in Response to Endotoxin in Intact Rat Lungs

text: Nitric oxide (NO) produced by NO synthase (NOS) serves as a ubiquitous mediator molecule involved in many physiologic lung functions, including regulation of vascular and bronchial tone, immunocompetence, and neuronal signaling. On the other hand, excessive and inappropriate NO synthesis in inflammation and sepsis has been implicated in vascular abnormalities and cell injury. At least three different NOS isoforms (neuronal/brain [bNOS], inducible [iNOS], and endothelial [eNOS]) have been described, which are all expressed in normal lung tissue. We investigated the cell-specific expression of bNOS, iNOS, and eNOS in perfused control rat lungs and lungs undergoing stimulation with endotoxin in the presence and absence of plasma constituents. Lung immunohistochemistry and quantitative evaluation of staining intensity showed endotoxin-induced increase in iNOS expression in particular in bronchial epithelial cells, cells of the bronchus-associated lymphoid tissue (BALT), alveolar macrophages, and vascular smooth muscle cells in a time- and dose-dependent fashion. In endothelial cells, which did not express iNOS at baseline, newly induced iNOS was found in response to endotoxin. In contrast, expression of eNOS was markedly suppressed under endotoxin challenge, particularly in bronchial epithelium, BALT, and alveolar macrophages but also in vascular smooth muscle cells and endothelial cells. eNOS expression in bronchial smooth muscle cells was not altered. In contrast to iNOS and eNOS, cellular expression of bNOS in epithelial cells, nerve fibers, BALT, and endothelial cells did not change in response to endotoxin. All changes in NOS regulation were found to be independent of plasma constituents. We conclude that endotoxin exerts a profound impact on the cell-specific NOS regulation in a large number of lung cell types. Prominent features include de novo synthesis or up-regulation of iNOS, in contrast to down-regulation of eNOS, which may well contribute to vascular abnormalities, inflammatory sequelae, and loss of physiologic functions in septic lung failure.


title: Bronchiolitis obliterans

text: Bronchiolitis obliterans in the adult patient is a relatively uncommon and vexing clinical entity. This confusion results because this pathologic finding occurs in a variety of diverse clinical settings. Bronchiolitis obliterans is a fibrotic process that primarily affects the small conducting airways. The lesion results from damage to the bronchiolar epithelium and the repair process leads to excessive proliferation of granulation tissue. The alveoli adjacent to the small airway are almost always involved; however, a considerable portion of the interstitium is usually spared. The findings in these patients may physiologically and radiographically mimic chronic obstructive pulmonary disease (COPD). On the other hand, some of the processes associated with bronchiolitis obliterans result in restrictive or mixed restrictive and obstructive ventilatory defects; consequently, they may be confused with other diffuse infiltrative lung disorders. This review will focus principally on bronchiolitis obliterans in adults, which, until recently, was considered rare. There has been heightened interest in this process in adults because of its association with the connective tissue diseases, its development following toxic fume exposure, its occurrence as a result of chronic graft versus host reactions, and the increasing recognition of patients with idiopathic forms of the disease that have an insidious onset often confused with more common problems such as COPD or idiopathic pulmonary fibrosis.


title: Non-traumatic Pulmonary Emergencies in the Deployed Setting

text: PURPOSE OF REVIEW: Pulmonary disorders accounted for up to 8% of the over 70,000 medical evacuations conducted from Iraq and Afghanistan in the past 15 years. This review of non-traumatic pulmonary emergencies provides an overview of deployed military medical treatment capabilities and highlights pulmonary emergencies requiring aeromedical evacuation from theater. RECENT FINDINGS: Recent studies have improved the epidemiologic evaluation of non-traumatic pulmonary disease, highlighted specific parenchymal diseases, and revealed infection pathologies unique to the deployed setting. Literature regarding possible chemical exposures in the current deployed environment remains limited. SUMMARY: Respiratory disorders requiring medical evacuation represent a wide variety of diseases. Complications such as pulmonary emboli, infectious pathogens, and hazardous chemical exposures threaten the deployed warfighter. Adequate medical care requires an understanding of these potential environmental exposures. This review serves as a general overview of this topic; however, more research regarding epidemiologic and environmental exposures is required.


title: Secondary necrosis in multicellular animals: an outcome of apoptosis with pathogenic implications

text: In metazoans apoptosis is a major physiological process of cell elimination during development and in tissue homeostasis and can be involved in pathological situations. In vitro, apoptosis proceeds through an execution phase during which cell dismantling is initiated, with or without fragmentation into apoptotic bodies, but with maintenance of a near-to-intact cytoplasmic membrane, followed by a transition to a necrotic cell elimination traditionally called “secondary necrosis”. Secondary necrosis involves activation of self-hydrolytic enzymes, and swelling of the cell or of the apoptotic bodies, generalized and irreparable damage to the cytoplasmic membrane, and culminates with cell disruption. In vivo, under normal conditions, the elimination of apoptosing cells or apoptotic bodies is by removal through engulfment by scavengers prompted by the exposure of engulfment signals during the execution phase of apoptosis; if this removal fails progression to secondary necrosis ensues as in the in vitro situation. In vivo secondary necrosis occurs when massive apoptosis overwhelms the available scavenging capacity, or when the scavenger mechanism is directly impaired, and may result in leakage of the cell contents with induction of tissue injury and inflammatory and autoimmune responses. Several disorders where secondary necrosis has been implicated as a pathogenic mechanism will be reviewed.


title: Hospital and intensive care unit management of decompensated pulmonary hypertension and right ventricular failure

text: Pulmonary hypertension and concomitant right ventricular failure present a diagnostic and therapeutic challenge in the intensive care unit and have been associated with a high mortality. Significant co-morbidities and hemodynamic instability are often present, and routine critical care unit resuscitation may worsen hemodynamics and limit the chances of survival in patients with an already underlying poor prognosis. Right ventricular failure results from structural or functional processes that limit the right ventricle’s ability to maintain adequate cardiac output. It is commonly seen as the result of left heart failure, acute pulmonary embolism, progression or decompensation of pulmonary hypertension, sepsis, acute lung injury, or in the perioperative setting. Prompt recognition of the underlying cause and institution of treatment with a thorough understanding of the elements necessary to optimize preload, cardiac contractility, enhance systemic arterial perfusion, and reduce right ventricular afterload are of paramount importance. Moreover, the emergence of previously uncommon entities in patients with pulmonary hypertension (pregnancy, sepsis, liver disease, etc.) and the availability of modern devices to provide support pose additional challenges that must be addressed with an in-depth knowledge of this disease.


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title: Extreme Efficiency of Airway Pressure Release Ventilation (APRV) in a Patient Suffering from Acute Lung Injury with Pandemic Influenza A (H1N1) 2009 and High Cytokines

text: The authors report a Japanese boy with severe pandemic influenza A(H1N1) 2009-associated pneumonia and deteriorating oxygenation. He dramatically recovered after the use of Airway Pressure Release Ventilation (APRV) mode. There was no improvement by using any conventional ventilation, however, APRV immediately led to an improvement of his clinical symptoms and laboratory findings.


National scientific medical meeting 1997 abstracts


title: Dynamics of pulmonary endothelial barrier function in acute inflammation: mechanisms and therapeutic perspectives

text: The lungs provide a large inner surface to guarantee respiration. In lung alveoli, a delicate membrane formed by endo- and epithelial cells with their fused basal lamina ensures rapid and effective gas exchange between alveolar and vascular compartments while concurrently forming a robust barrier against inhaled particles and microbes. However, upon infectious or sterile inflammatory stimulation, tightly regulated endothelial barrier leakiness is required for leukocyte transmigration. Further, endothelial barrier disruption may result in uncontrolled extravasation of protein-rich fluids. This brief review summarizes some important mechanisms of pulmonary endothelial barrier regulation and disruption, focusing on the role of specific cell populations, coagulation and complement cascades and mediators including angiopoietins, specific sphingolipids, adrenomedullin and reactive oxygen and nitrogen species for the regulation of pulmonary endothelial barrier function. Further, current therapeutic perspectives against development of lung injury are discussed.


title: Treatment of radiculomyelopathy in two patients with placenta-derived decidua stromal cells

text: Mesenchymal stromal cells may reverse acute inflammatory disorders. The placenta is important in feto-maternal tolerance. We have used placenta-derived decidua stromal cells (DSCs) to treat graft-versus-host disease and found an immunomodulatory and anti-inflammatory effect. We here report the use of DSCs in two patients with radiculomyelopathy. The first patient was a 73-year old man treated with parotidectomy and irradiation for lymphoma of the neck. Following a Yersinia infection, he developed a radiculomyelopathy in C3/C4 and could not elevate his arms. The second patient was a 34-year old woman who was admitted 8 months after allogeneic hematopoietic stem cell transplantation due to hemolysis, impaired sensorium below arcus, and difficulty in ambulation. Following intravenous infusion of DSCs (1 × 10(6)/kg/infusion), the first patient could elevate his arms to the facial level. He experienced recurrent paralysis after 6 months, and the efficacy of four additional DSC infusions, at subsequent occasions, were limited and transient. The second patient was treated with two doses of DSCs (1 × 10(6)/kg/infusion). After cell infusion, she was able to stand on one leg, sensation in the belly normalized, and she was discharged. These two cases suggest that DSCs may be useful in the treatment of neuroinflammatory disorders.


Abstracts for the 17th IPNA Congress, Iguaçu, Brazil, September 2016: Oral Presentations


title: The Diagnostic Yield, Safety, and Impact of Flexible Bronchoscopy in Non-HIV Immunocompromised Critically Ill Patients in the Intensive Care Unit

text: BACKGROUND: Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) have major roles in the evaluation of parenchymal lung diseases in immunocompromised patients. Given the limited evidence, lack of standardized practice, and variable perception of procedural safety, uncertainty still exists on what constitutes the best approach in critically ill patients with immunocompromised state who present with pulmonary infiltrates in the era of prophylactic antimicrobials and the presence of new diagnostic tests. OBJECTIVE: To evaluate the diagnostic yield, safety and impact of FB and BAL on management decisions in immunocompromised critically ill patients admitted to the intensive care unit (ICU). METHODS: A prospective, observational study of 106 non-HIV immunocompromised patients admitted to the intensive care unit with pulmonary infiltrates who underwent FB with BAL. RESULTS: FB and BAL established the diagnosis in 38 (33%) of cases, and had a positive impact on management in 44 (38.3%) of cases. Escalation of ventilator support was not required in 94 (81.7%) of cases, while 18 (15.7%) required invasive and 3 (2.6%) required non-invasive positive pressure ventilation after the procedure. Three patients (2.6%) died within 24 h of bronchoscopy, and 46 patients (40%) died in ICU. Significant hypoxemia developed in 5% of cases. CONCLUSION: FB can be safely performed in immunocompromised critically ill patients in the ICU. The yield can be improved when FB is done prior to initiation of empiric antimicrobials, within 24 h of admission to the ICU, and in patients with focal disease.


Otitis media mit akutem progressivem Lungenversagen?: Und warum sich ein Urinstatus lohnt


Stichwortregister zu Band 45 (2008)


European Association of Nuclear Medicine Congress: 20 – 24 August 1994, Düsseldorf, Germany


39. Gemeinsame Jahrestagung der Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin und der Österreichischen Gesellschaft für Allgemeine und Internistische Intensivmedizin: 20. bis 23. Juni 2007 in Köln Tagungspräsident: Prof. Dr. med. H.-J. Trappe, Herne


title: The pulmonary findings of Crimean–Congo hemorrhagic fever patients with chest X-ray assessments

text: BACKGROUND: Crimean–Congo hemorrhagic fever (CCHF), characterized by fever and/or hemorrhage, is a zoonotic viral disease with high mortality. The agent causing CCHF is a Nairovirus. The virus is typically transmitted to humans through tick bites. CCHF is a life-threatening disease observed endemically over a wide geographical regions in the world, and there is limited information about pulmonary findings in CCHF patients. PURPOSE: We aimed to investigate the pulmonary findings belonging to a large CCHF patient cohort and to determine if there is any relationship between laboratory findings and disease severity. MATERIALS AND METHODS: A total of 165 patients who were diagnosed with CCHF and examined through chest X-ray (CXR) due to respiratory symptoms at their first examination and/or during their hospitalization were included in this study. In addition to demographical and laboratory findings of the patients, chest X-rays were also examined. RESULTS: Of the 165 patients examined, 96 were male (58.2%) and 69 were female (41.8%). The mean age was 51.64 ± 17.95 years (4–81 years). Single and/or multiple pathological findings were detected in 93 patients (56.4%) as a result of chest X-ray during their first examination. On chest X-ray, consolidation in 74 patients (44.8%), pleural effusion in 64 patients (39.8%), ground glass opacity in 49 patients (29.7%), and atelectasis in 30 patients (18.2%) were detected. CONCLUSION: According to the results of our study, it can be suggested that radiological examination in lungs should be performed primarily with CXR and pulmonary involvement (pleural effusion and consolidation) affects survival in CCHF negatively.


title: Clinical outcomes in breast cancer patients with HIV/AIDS: a retrospective study

text: The purpose of the study is to describe what is the presentation of breast cancer in women with HIV, their tolerance to therapy, the most common complications of treatment and their outcomes. Retrospective chart review of patients with HIV diagnosed with breast cancer between January 1, 1989 and December 31, 2013 at the University of Miami/Jackson Memorial Hospital (UM/JMH) 47 females and 1 male were included in the analysis. The median age of diagnosis was 46 years (IQR 41–52) and 64 % of the women were premenopausal. Median CD4(+) count was 330 cells/µL (IQR 131–589 cells/µL). 41 % had AIDS at time of diagnosis. 94 % of patients presented with locoregional disease and 6 % with late stage breast cancer. 52 % had ER(+) tumors. 6 % had HER-2/neu tumor expression and 21 % had triple negative disease. The 5 year PFS was 50 % (95 % CI 34–64 %), the 5 year OS was 44 % (95 % CI 29–58 %), and the Breast cancer-specific survival was 57 % (95 % CI 40–70 %). Death was attributed to breast cancer in 22 patients, AIDS progression in 6 patients, other medical condition in 1, and for 4, the cause was unknown. Serious adverse events were documented in 46 % of patients treated with chemotherapy. Targeted therapy was well tolerated. Patients with HIV/AIDS and breast cancer pose a major challenge for oncologists. Surgery, radiation, and endocrine therapy are well tolerated. Standard dose chemotherapy can have life-threatening side effects which can be managed with growth factor support and antimicrobial prophylaxis. All cancer therapy can be given while continuing with antiviral therapy at full dose.


title: High-dose hydroxocobalamin in end-stage liver disease and liver transplantation

text: Distributive shock is a serious complication in patients with chronic or end-stage liver disease, and can be exacerbated by vasoplegia in this patient population. Vasoplegic syndrome (VS) is a state of shock refractory to catecholamines and vasopressin that is often multifactorial in liver failure patients, and can occur in any phase of liver transplantation (LT) [i.e., pre-transplantation, intraoperative, and post-transplantation]. Methylene blue (MB) has been a well-established pharmacologic therapy for VS. However, it has been known to cause dose-related toxicity. Hydroxocobalamin (HXC) is not currently FDA approved for the management of VS, but studies have demonstrated its ability to cause an increase in systolic blood pressure by hypothesized mechanisms with only minimal side effects. To date, only three other reports have demonstrated the use of HXC in LT patients, which highlighted its use both intraoperatively and post-transplantation. Our report illustrates the utility of HXC in four LT patients with VS. Two of these cases illustrate the usefulness of HXC in the pre-transplantation period, which has never been previously reported. HXC is a useful pharmaceutical agent in the management of VS, especially if contraindications to MB exist or in cases of MB-resistant vasoplegia. Further studies with large sample sizes are necessary to ascertain the optimal dosage of HXC in LT patients.


title: Avian flu: The wrath of birdzilla or polly got the sniffles?

text: The potential damage from an avian flu epidemic is huge, but unlikely. Currently, the virus affects birds and humans who handle dead birds. Only one case of suspected human-to-human transmission exists. If human-to-human transmission can occur with a new strain of the virus, we are susceptible to a pandemic. The many subtypes of influenza act and develop differently. The inflammatory response generated by the virus accounts for the illness. Vaccines are being developed, but the difficulties are real, and the time to success cannot be confidently stated. Lymphopenia, thrombocytopenia, and elevated liver enzymes are common. Treatment has to take into account societal issues as well as the individual health of every patient.


title: Conformational Fingerprinting Using Monoclonal Antibodies (on the Example of Angiotensin I-Converting Enzyme-ACE)

text: During the past 30 years my laboratory has generated 40+ monoclonal antibodies (mAbs) directed to structural and conformational epitopes on human ACE as well as ACE from rats, mice and other species. These mAbs were successfully used for detection and quantification of ACE by ELISA, Western blotting, flow cytometry and immunohistochemistry. In all these applications mainly single mAbs were used. We hypothesized that we can obtain a completely new kind of information about ACE structure and function if we use the whole set of mAbs directed to different epitopes on the ACE molecule. When we finished epitope mapping of all mAbs to ACE (and especially, those recognizing conformational epitopes), we realized that we had obtained a new tool to study ACE. First, we demonstrated that binding of some mAbs is very sensitive to local conformational changes on the ACE surface—due to local denaturation, inactivation, ACE inhibitor or mAbs binding or due to diseases. Second, we were able to detect, localize and characterize several human ACE mutations. And, finally, we established a new concept—conformational fingerprinting of ACE using mAbs that in turn allowed us to obtain evidence for tissue specificity of ACE, which has promising scientific and diagnostic perspectives. The initial goal for the generation of mAbs to ACE 30 years ago was obtaining mAbs to organ-specific endothelial cells, which could be used for organ-specific drug delivery. Our systematic work on characterization of mAbs to numerous epitopes on ACE during these years has lead not only to the generation of the most effective mAbs for specific drug/gene delivery into the lung capillaries, but also to the establishment of the concept of conformational fingerprinting of ACE, which in turn gives a theoretical base for the generation of mAbs, specific for ACE from different organs. We believe that this concept could be applicable for any glycoprotein against which there is a set of mAbs to different epitopes.


title: Intensivmedizinische Betreuung von Patienten nach Stammzelltransplantation

text: Within the hematologic therapy procedures, stem cell transplantation (SCT) represents the most extensive and invasive intervention. Those patients have certain risks for several bacterial, viral, as well as fungal infections during the different stages of transplantation. Especially in allogenic transplantation, discrimination of non-infectious, mostly immunologic complications like graft-versus-host reactions or VOD (veno-occlusive disease) is crucial, and often represents a therapeutic challenge. An adequate intensive care therapy of these patients can only be achieved with the knowledge of the specific complications of SCT. This review starts with an overview of the SCT stages with their corresponding infectious and noninfectious complications, followed by the discussion of organ specific pulmonary, renal, cardiac, gastrointestinal, hepatic and neurological complications of stem cell transplantation.


title: Impact of combination therapy with aminoglycosides on the outcome of ICU-acquired bacteraemias

text: Pharmacodynamic studies report on the rapid bactericidal activity of aminoglycosides, conferring them as being of theoretical interest for bacteraemia treatment. We assessed this issue in a retrospective study of patients with intensive care unit (ICU)-acquired bacteraemias. To determine the impact of aminoglycosides in antimicrobial combination on the outcome of patients with bacteraemia, we performed a monovariate analysis and a logistic regression analysis comparing patients treated with or without aminoglycosides. Forty-eight bacteraemias in 48 patients were included. Eighteen patients received aminoglycosides. Baseline characteristics as well as adaptation and adequation of antibiotherapy did not differ in patients who did or did not receive aminoglycosides. Patients who received aminoglycosides had longer time alive away from the ICU (11.3 ± 8.9 (10 [0–20]) vs. 3.2 ± 6.6 (0 [0–2] days; p = 0.002) and free from mechanical ventilation (12.5 ± 9.3 (14 [0–21] vs. 5.5 ± 9.2 (0 [0–10] days; p = 0.02) on day 28. The ICU mortality was 16% in the aminoglycoside group versus 46% (p = 0.03). In the multivariate analysis, patients treated with aminoglycosides were 6 times less likely to die than those treated without aminoglycosides (confidence interval [CI] = [1.3–28.9]; p = 0.02). Our study supports the hypothesis that combination short-term antibiotherapy with an aminoglycoside for ICU-acquired bacteraemias could increase survival.


docid: dpgvvvwy

title: Interklinisch transport van ernstig zieke of gewonde kinderen

text: De zorg voor ernstig zieke of gewonde kinderen is in Nederland gecentraliseerd in acht gespecialiseerde afdelingen voor pediatrische intensive care (PICU) die gezamenlijk ongeveer 100 bedden hebben. Deze acht PICU’s verzorgen een regio waarbinnen overname en transport van kinderen van 0 tot 18 jaar gegarandeerd is.


Flumazenil reverses diazepam-induced neonatal apnoea and hypotonia


title: Ambulant erworbene Pneumonie: Wie viel Diagnostik muss sein?

text: Diagnostic tools are essential for the physician to reach a correct diagnosis of community-acquired pneumonia, to determine the pathogen, and to estimate the prognosis of individual patients. X-ray of the chest remains the “gold standard” for identification of pneumonia. Modern inflammatory markers such as C-reactive protein and in the future procalcitonin are essential for the differential diagnosis and follow-up. The microbiology tests include, besides classic bacterial cultures, urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila. A simple prognostic score has been developed to help the physician to decide if the patient needs hospitalization.


title: Role of early diagnosis for a noninvasive treatment of pulmonary thromboembolism in leukemic children

text: Pulmonary thromboembolism (PTE) in leukemic children undergoing intensive chemotherapy should be promptly recognized so that specific therapy can be started. Our experience with the two cases reported here has led us to propose guidelines for the treatment of initial PTE in a pediatric hematology unit. Two children with leukemia developed PTE, the first during the relapse for acute lymphoblastic leukemia and the second at the onset of acute promyelocytic leukemia. In both cases, the diagnosis of PTE was based on clinical assessment of sudden acute respiratory failure with positive pulmonary perfusional scintigraphy in spite of a negative chest X-ray. The subintensive supervision consisted of instrumental monitoring with the assistance of an intensive care anesthetist. The clinical monitoring was based on the serial registration of respiratory rate, cardiac rate, SaO(2) and body temperature. The thrombolytic therapy, together with heparin prophylaxis, was successfully administered in the hematology ward without the need for intensive care support (i.e. mechanical ventilation). The success of the treatment was documented by the criterion of a return to the normal cardiorespiratory parameters a few hours after the start of the thrombolytic treatment. Furthermore, a chest CT scan in case 1 and an arteriography in case 2 confirmed the PTE-related hypoperfusion. On the basis of this experience, the authors point out that in the course of acute respiratory failure in leukemic children, the combination of a negative chest X-ray and a positive pulmonary perfusional scintigraphy (compared whenever possible with ventilatory scintigraphy) in the presence of a negative CT scan could be a reliable diagnostic tool for PTE. This pathology should be treated promptly and with specific therapy to avoid progression to a severe, massive PTE.


title: JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects

text: The Janus kinase/signal transduction and activator of transcription (JAK–STAT) signaling pathway is implicated in the pathogenesis of inflammatory and autoimmune diseases including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Many cytokines involved in the pathogenesis of autoimmune and inflammatory diseases use JAKs and STATs to transduce intracellular signals. Mutations in JAK and STAT genes cause a number of immunodeficiency syndromes, and polymorphisms in these genes are associated with autoimmune diseases. The success of small-molecule JAK inhibitors (Jakinibs) in the treatment of rheumatologic disease demonstrates that intracellular signaling pathways can be targeted therapeutically to treat autoimmunity. Tofacitinib, the first rheumatologic Jakinib, is US Food and Drug Administration (FDA) approved for rheumatoid arthritis and is currently under investigation for other autoimmune diseases. Many other Jakinibs are in preclinical development or in various phases of clinical trials. This review describes the JAK–STAT pathway, outlines its role in autoimmunity, and explains the rationale/pre-clinical evidence for targeting JAK–STAT signaling. The safety and clinical efficacy of the Jakinibs are reviewed, starting with the FDA-approved Jakinib tofacitinib, and continuing on to next-generation Jakinibs. Recent and ongoing studies are emphasized, with a focus on emerging indications for JAK inhibition and novel mechanisms of JAK–STAT signaling blockade.


title: Use of Drotrecogin Alfa (Activated) in Bariatric Surgery Patients with Severe Sepsis Syndrome: Experience in an Urban Community Teaching Hospital

text: Background: Severe sepsis syndrome (SSS) and septic shock have an associated mortality ranging from 31 to 60%. Drotrecogin alfa (activated), activated protein C (APC), has been shown in a recent trial to decrease mortality from 44 to 31% in patients with SSS and a high risk of death. We present 3 patients who developed SSS after bariatric surgery and were treated with APC as part of comprehensive therapy for sepsis. Methods: At our institution, patients must have SSS plus an APACHE II score ≥ 25 in order to receive APC. JL is a 43-year-old man who developed SSS (APACHE II score 26) after Roux-en-Y gastric bypass. ML is a 33-year-old man who developed SSS (APACHE II=28) because of a distal obstruction 2.5 years after gastric bypass surgery. TQ was a 35-year-old man who developed SSS (APACHE II=35) in the setting of laparoscopic banding. Results: After receiving 90% of the 96-hour infusion, JL developed ecchymoses and a decrease in his platelet count; thus, the drug was stopped. ML received a full 96-hour infusion. Both patients made a full recovery from their SSS and were successfully discharged from the hospital. TQ developed septic shock and expired despite all efforts. Conclusion: Weight alone should not be considered a contraindication to the use of APC. Close coordination between the intensivist and surgeon is recommended for bariatric surgery patients with SSS, so that a rapid determination can be made as to the patient's risk of death and eligibility to receive APC.


title: Fatal Mycoplasma pneumoniae pneumonia in a previously healthy 18-year-old girl

text: A case of fatal Mycoplasma pneumoniae pneumonia in a previously healthy 18-year-old girl is reported. On hospital day 9, the antibody titer to M. pneumoniae was 1:512 in the complement fixation test and 1:5120 in the microparticle agglutination assay. After five weeks in the intensive care unit, the patient died from necrotizing hemorrhagic pneumonia with multi-organ failure. No significant superinfections occurred during ICU treatment. Corticosteroids (hospital day 8 onward) did not influence the course of the disease. It is noteworthy that, as in some previously reported cases, the clinical state deteriorated during presumably adequate antibiotic treatment (2 days before admission onward), and despite documented eradication of the pathogen from the respiratory tract (PCR from bronchoalveolar fluid on hospital day 22 was negative). However, the illness had lasted for several days before admission to the hospital, therefore the potentially beneficial effect of antibiotic treatment at an early stage of the disease cannot be assessed. Clearly, in default of other treatment options, correct diagnosis and early treatment of mycoplasma community-acquired pneumonia seems mandatory. This is the third case of fatal mycoplasma pneumonia reported from Austria in recent years, making this topic worthy of further scientific attention.


title: Pulmonale Hypertonie und Rechtsherzversagen auf der Intensivstation

text: The management of pulmonary hypertension and right ventricular failure in hemodynamically unstable patients is one of the most challenging situations in critical care medicine. Inadequate therapy, e.g. aggressive fluid resuscitation or invasive ventilation, may even harm patients with pulmonary hypertension. Identifying the underlying etiology therefore remains the primary focus for initiating successful management of patients with decompensated pulmonary hypertension and right ventricular failure. Pulmonary embolism requires immediate restoration of pulmonary vascular patency. The body of evidence from studies is scarce and favors dobutamine, NO inhalation, and intravenous prostacyclin. However, the use of other vasoactive substances, inotropes, and supportive measures has been successful in individual patients; it should be guided by the expected effects on the pulmonary vasculature or right ventricle, and should be adapted to the patient’s concomitant diseases.


title: Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling

text: Arctigenin, a bioactive component of Arctium lappa (Nubang), has anti-inflammatory activity. Here, we investigated the effects of arctigenin on lipopolysaccharide (LPS)-induced acute lung injury. Mice were divided into four groups: control, LPS, LPS + DMSO, and LPS + Arctigenin. Mice in the LPS + Arctigenin group were injected intraperitoneally with 50 mg/kg of arctigenin 1 h before an intratracheal administration of LPS (5 mg/kg). Lung tissues and bronchoalveolar lavage fluids (BALFs) were collected. Histological changes of the lung were analyzed by hematoxylin and eosin staining. Arctigenin decreased LPS-induced acute lung inflammation, infiltration of inflammatory cells into BALF, and production of pro-inflammatory cytokines. Moreover, arctigenin pretreatment reduced the malondialdehyde level and increased superoxide dismutase and catalase activities and glutathione peroxidase/glutathione disulfide ratio in the lung. Mechanically, arctigenin significantly reduced the production of nitric oxygen and inducible nitric oxygen synthase (iNOS) expression, enhanced the expression of heme oxygenase-1, and decreased the phosphorylation of mitogen-activated protein kinases (MAPKs). Arctigenin has anti-inflammatory and antioxidative effects on LPS-induced acute lung injury, which are associated with modulation of MAPK, HO-1, and iNOS signaling.


title: 5. Das akute Lungenversagen — eine kritische Analyse

text: The Adult Respiratory Distress Syndrome (ARDS) is a clinical syndrome with acute progressive lung function deterioration based on increased pulmonary permeability and caused mostly by non-pulmonary lesions (like sepsis or polytrauma), occasionally also by pulmonary diseases (like pneumonia) or intoxications (e.g. by paraquat). In the complex, interactive pathomechanisms (e.g. complement activation, stimulation of the arachidon metabolism) with release of numerous damaging mediators the massive accumulation of neutrophils in the lung plays an important role.


title: Clinical Profile of Atypical Manifestations of Dengue Fever

text: OBJECTIVES: To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. METHODS: All children (0–12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. RESULTS: Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. CONCLUSIONS: The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of dengue fever as lack of timely detection and management could be fatal. Impaired consciousness was the most ominous atypical manifestation of severe dengue infection.


title: Thy-1 depletion and integrin β3 upregulation-mediated PI3K-Akt-mTOR pathway activation inhibits lung fibroblast autophagy in lipopolysaccharide-induced pulmonary fibrosis

text: Lipopolysaccharide (LPS)-induced autophagy inhibition in lung fibroblasts is closely associated with the activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K-Akt-mTOR) pathway. However, the underlying mechanism remains unknown. In this study, we demonstrated that LPS activated the PI3K-Akt-mTOR pathway and inhibited lung fibroblast autophagy by depleting thymocyte differentiation antigen-1 (Thy-1) and upregulating integrin β3 (Itgb3). Challenge of the human lung fibroblast MRC-5 cell line with LPS resulted in significant upregulation of integrin β3, activation of the PI3K-Akt-mTOR pathway and inhibition of autophagy, which could be abolished by integrin β3 silencing by specific shRNA or treatment with the integrin β3 inhibitor cilengitide. Meanwhile, LPS could inhibit Thy-1 expression accompanied with PI3K-Akt-mTOR pathway activation and lung fibroblast autophagy inhibition; these effects could be prevented by Thy-1 overexpression. Meanwhile, Thy-1 downregulation with Thy-1 shRNA could mimic the effects of LPS, inducing the activation of PI3K-Akt-mTOR pathway and inhibiting lung fibroblast autophagy. Furthermore, protein immunoprecipitation analysis demonstrated that LPS reduced the binding of Thy-1 to integrin β3. Thy-1 downregulation, integrin β3 upregulation and autophagy inhibition were also detected in a mouse model of LPS-induced pulmonary fibrosis, which could be prohibited by intratracheal injection of Thy-1 overexpressing adeno-associated virus (AAV) or intraperitoneal injection of the integrin β3 inhibitor cilengitide. In conclusion, this study demonstrated that Thy-1 depletion and integrin β3 upregulation are involved in LPS-induced pulmonary fibrosis, and may serve as potential therapeutic targets for pulmonary fibrosis.


title: Indikationen und Komplikationen der Plasmapherese im Rahmen der Intensivmedizin

text: The last two decades have seen a marked change in the role of plasmapheresis in the intensive care unit (ICU). Initially regarded as highly effective in treating virtually any immunological disease, insights in pathophysiology and results from controlled trials have left only a few indications validated. To date, plasmapheresis is indicated for acute treatment of severe immunological disorders either unresponsive to immunosuppression or requiring large volumes of human plasma for therapy. In the future, more specific and less cumbersome methods of immunosuppression and immunomodulation might further limit indications of plasmapheresis. In this review, current indications and side-effects of plasmapheresis in the ICU setting are summarized.


docid: bejrttyk

title: Severe Combined Immunodeficiency (SCID) in Canadian Children: A National Surveillance Study

text: PURPOSE: Severe Combined Immune Deficiency (SCID) is universally fatal unless treated with hematopoietic stem cell transplantation (HSCT). Following the identification of disseminated Bacille Calmette-Guérin (BCG) infections in Canadian First Nations, Métis and Inuit (FNMI) children with unrecognized primary immune deficiencies, a national surveillance study was initiated in order to determine the incidence, diagnosis, treatment and outcome of children with SCID in Canada. METHODS: Canadian pediatricians were asked to complete a monthly reporting form if they had seen a suspected SCID case, from 2004 to 2010, through the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID criteria, more detailed data, including demographics and clinical information about investigations, treatment and outcome was collected. RESULTS: A total of 40 cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The proportion of SCID cases that were FNMI (17.5 %) was almost three times higher than was expected on the basis of proportion of the pediatric population estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per 100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The mean age at diagnosis for all SCID cases was 4.2 months (range 1–583 days). There were 12 deaths (30 %; 95 % CI 18–46 %); seven died of confirmed or suspected infections before they could receive an HSCT. CONCLUSIONS: The frequency of SCID cases in FNMI children is higher than in the general Canadian pediatric population. The high mortality rate, due primarily to infection, suggests that early diagnosis by newborn screening followed by HSCT could significantly benefit children with SCID.


title: Pulmonary defense and the human cathelicidin hCAP-18/LL-37

text: Antimicrobial peptides form an important component of the innate immune system. The cathelicidin family, a key member of the antimicrobial peptide defenses, has been highly conserved throughout evolution. Though widespread in mammals, there is currently only one identified human example, hCAP-18/LL-37. The cathelicidins have been found to have multiple functions, in addition to their known antimicrobial and lipopolysaccharide-neutralizing effects. As a result, they profoundly affect both innate and adaptive immunity. Currently, antimicrobial peptides are being evaluated as therapeutic drugs in disease states as diverse as oral mucositis, cystic fibrosis, and septic shock. One such peptide, the cathelicidin hCAP-18/LL-37, is reviewed in detail in the context of its role in lung physiology and defense.


title: Clinical aspects of 2009 pandemic influenza A (H1N1) virus infection in Austria

text: PURPOSE: To describe the clinical features, risk factors for severe disease and effectiveness of oseltamivir in patients with 2009 pandemic influenza A (H1N1) virus infection. METHODS: In a prospective, cross-sectional, multicentre study, data on 540 patients with confirmed 2009 H1N1 infection from seven Austrian hospitals were collected using a standardised online case-history form. RESULTS: The median age of the patients was 19.3 years (range 26 days–90.8 years); point-of-care testing yielded false-negative results in 60.2% of the 176 cases tested. The most common symptoms were fever, cough, fatigue and headache. Overall, 343 patients (63.5%) were hospitalised, 49 (9.1%) were admitted to an intensive care unit (ICU) and 14 (4.1%) died. Case fatality rates were highest (9.1%) in those aged 65 years or older. Factors significantly associated with a higher risk for ICU admission included age, neurological disease, adipositas, and both interstitial pathology and lobular pathology on chest X-ray. No association with pregnancy, malignancy or immunosuppressive therapy was detected. Antiviral treatment significantly reduced the duration of fever by 0.66 days and lowered the risk of ICU admission, but had no significant benefit on survival. CONCLUSIONS: During the 2009 H1N1 influenza pandemic, elderly or obese patients and those with neurological disease had an increased risk for severe H1N1 infection in Austria. Pregnancy was not associated with a higher risk for severe disease in the later phase of the 2009 H1N1 pandemic. Antiviral treatment provided a minimal effect on the symptoms of influenza but reduced the risk of admission to an ICU.


title: Clinical Impact of Non-Congenital Zika Virus Infection in Infants and Children

text: PURPOSE OF REVIEW: While the Zika virus (ZIKV) has been noted for its distinct neurotropism and identified as a significant cause for a congenital infection syndrome, there has been increased recognition of the importance to better understand the clinical impact of non-congenital ZIKV infection in infants and children. This article reviews reports of perinatal and breast milk transmission of ZIKV and summarizes current clinical outcome data of pediatric non-congenital ZIKV infection. RECENT FINDINGS: Perinatal transmission and presence of infective ZIKV particles in breast milk have been reported. Most symptomatic non-congenital ZIKV infection in infants and children is mild and self-limited, but long-term follow-up studies are lacking. SUMMARY: The mechanism and impact of perinatal and breast milk transmission is unclear. The current WHO infant feeding guidelines in areas of ZIKV transmission support breastfeeding. Unless any scientific data raise concern regarding transmission via breastfeeding, the current guidelines should continue to be followed. Prospective population-based cohort studies to investigate maternal, perinatal, infant, and child outcomes are needed.


title: Demographic profile and outcome analysis of a tertiary level pediatric intensive care unit

text: Objective : To study the profile and outcome of children admitted to a tertiary level pediatric intensive care unit (PICU) in India.Methods : Prospective study of patient demographics, PRISM III scores, diagnoses, treatment, morbidity and mortality of all PICU admissions.Results : 948 children were admitted to the PICU. Mean age was 41.48 months. Male to female ratio was 2.95:1. Mean PRISM III score on admission was 18.50. Diagnoses included respiratory (19.7%), cardiac (9.7%), neurological (17.9%), infectious (12.5%), trauma (11.7%), other surgical (8.8%).196 children (20.68%) required mechanical ventilation. Average duration of ventilation was 6.39 days. 27 children (30.7 children /1000 admissions) had acute respiratory distress syndrome. Gross mortality was 6.7% (59 patients). PRISMIII adjusted mortality was directly proportional to PRISMIII scores. 49.5% of nonsurvivors had multiorgan failure. Average length of PICU stay was 4.52 +/−2.6 days. Complications commonly encountered Were atelectasis (6.37%), accidental extubation (2%), and pneumothorax (0.9%). Incidence of nosocomial infections was 16.86%.Conclusion : Our data appears to be similar with regards to PRISMIII scores and adjusted mortality, length of the PICU stay, and duration of ventilation, to previously published western data. Multiorgan failure remains a major cause of death. As expected, Dengue and malaria were common. Incidence of nosocomial infections was somewhat high. Interestingly, more boys got admitted to the PICU as compared to girls. Clearly more studies are required to assess the overall outcomes of critically ill children in India


title: Infectious Diseases Causing Diffuse Alveolar Hemorrhage in Immunocompetent Patients: A State-of-the-Art Review

text: Diffuse alveolar hemorrhage (DAH) represents a syndrome that can complicate many clinical conditions and may be life-threatening, requiring prompt treatment. It is recognized by the signs of acute- or subacute-onset cough, hemoptysis, diffuse radiographic pulmonary infiltrates, anemia, and hypoxemic respiratory distress. DAH is characterized by the accumulation of intra-alveolar red blood cells originating most frequently from the alveolar capillaries. It must be distinguished from localized pulmonary hemorrhage, which is most commonly due to chronic bronchitis, bronchiectasis, tumor, or localized infection. Hemoptysis, the major sign of DAH, may develop suddenly or over a period of days to weeks; this sign may also be initially absent, in which case diagnostic suspicion is established after sequential bronchoalveolar lavage reveals worsening red blood cell counts. The causes of DAH can be divided into infectious and noninfectious, the latter of which may affect immunocompetent or immunodeficient patients. Pulmonary infections are rarely reported in association with DAH, but they should be considered in the diagnostic workup because of the obvious therapeutic implications. In immunocompromised patients, the main infectious diseases that cause DAH are cytomegalovirus, adenovirus, invasive aspergillosis, Mycoplasma, Legionella, and Strongyloides. In immunocompetent patients, the infectious diseases that most frequently cause DAH are influenza A (H1N1), dengue, leptospirosis, malaria, and Staphylococcus aureus infection. Based on a search of the PubMed and Scopus databases, we review the infectious diseases that may cause DAH in immunocompetent patients.


title: Vaccination against pandemic H1N1 (2009) in patients after allogeneic hematopoietic stem cell transplantation: a retrospective analysis

text: PURPOSE: Limited data are available on immunologic responses to primary pandemic H1N1 (2009) vaccination in recipients of allogeneic hematopoietic stem cell transplantation (HSCT) recipients. In 2009 serologic responses to either pandemic H1N1 (2009) vaccine (n = 36) or pandemic H1N1 (2009) infection (n = 2) were studied in 38 HSCT recipients. METHODS: Responses were measured with a standard hemagglutination-inhibition assay. Fourteen patients had active chronic graft-versus-host disease (cGvHD) at the time of vaccination/infection and seven patients had cGvHD in remission; 11 patients had no immunosuppressive therapy, and 27 patients were on immunosuppressive therapy. Nineteen patients (53%) responded to pandemic H1N1 (2009) vaccination. Two patients had pandemic H1N1 (2009) infection without prior vaccination, and one patient had severe pandemic H1N1 (2009) infection with acute respiratory distress syndrome despite prior single vaccination. RESULTS: Non-responders to pandemic H1N1 (2009) vaccination more often had cGvHD (65 vs. 53%) and received second- or third-line therapy (53 vs. 11%), while responders mostly had first-line therapy for cGvHD. While vaccine responders had no or single agent immunosuppressive therapy, non-responders frequently received moderate or intense immunosuppressive therapy. All vaccine recipients previously treated with rituximab were non-responders. CONCLUSIONS: In summary, the overall response to pandemic H1N1 (2009) vaccination in HSCT recipients was modest. Patients receiving combined immunosuppressive therapy for steroid-refractory cGvHD barely responded to pandemic H1N1 (2009) vaccination.


title: Eosinophilia-myalgia syndrome induced by excessive L-tryptophan intake from cashew nuts

text: Eosinophilia is characterized by more than 0.5 × 10(9) eosinophils per liter in the full blood count. A wide range of conditions, from asthma to parasitic infections, autoimmune diseases, and certain forms of cancer, have been known to trigger abnormally high amount of eosinophils. It is essential to reach the correct diagnosis and treat the underlying disease aggresively. Definition of the eosinophilia-myalgia syndrome was offered in 1980s by Centers for Disease Control and Prevention for surveillance purposes, and criteria were revised in 2001, with high specificity. We report a case of 59-year old female who started a special weight-reducing diet regimen that included excessive cashew nut ingestion. Several months after she has presented with periferal blood eosinophilia and constitutional symptoms. Detailed work-up has not found elements for haematological, systemic autoimmune, neoplastic or infectious disease. She was diagnosed with eosinophilia-myalgia syndrome due to extreme L-tryptophan intake, a compound found in the cashew nut’s oil. She responded well to cashew nut withdrawal and steroid therapy. In the follow-up period she remained stable with normal eosinophil count and there was not a need for any specific therapy.


title: Inhibition on angiotensin-converting enzyme exerts beneficial effects on trabecular bone in orchidectomized mice

text: BACKGROUND: This study aimed to study the osteo-preservative effects of captopril, an inhibitor on angiotensin-converting enzyme (ACE), on bone mass, micro-architecture and histomorphology as well as the modulation of captopril on skeletal renin-angiotensin system (RAS) and regulators for bone metabolism in mice with bilateral orchidectomy. METHODS: The orchidectomized (ORX) mice were orally administered with vehicle or captopril at low dose (10 mg/kg) and high dose (50 mg/kg) for six weeks. The distal femoral end, the proximal tibial head and the lumbar vertebra (LV) were stained by hematoxylin and eosin, Safranin O/Fast Green and masson-trichrome. Micro-computed tomography was performed to measure bone mineral density (BMD). RESULTS: Treatment with captopril increased trabecular bone area at distal metaphysis of femur, proximal metaphysis of tibia and LV-4, moreover, high dose of captopril significantly elevated trabecular BMD of LV-2 and LV-5. The mRNA expressions of renin receptor, angiotensinogen, carbonic anhydrase II, matrix metalloproteinase-9, and tumor necrosis factor-alpha were significantly decreased in tibia of ORX mice following treatment with captopril. The administration with captopril enhanced the ratio of OPG/RANKL mRNA expression, the mRNA expression of transforming growth factor-beta and the protein expression of bradykinin receptor-1. CONCLUSIONS: The inhibition on ACE by captopril exerts beneficial effects on trabecular bone of ORX mice. The therapeutic efficacy may be attributed to the regulation of captopril on local RAS and cytokines in bone.


title: The clinical differences between dengue and scrub typhus with acute respiratory failure in southern Taiwan

text: BACKGROUND: For both dengue and scrub typhus, acute respiratory failure (ARF) is a serious complication. The present study was carried out in order to investigate the clinical courses and outcomes of adult dengue and scrub typhus patients with ARF, and to identify the clinical differences between adult dengue and scrub typhus patients with ARF. METHODS: We conducted a retrospective study of the serologically confirmed adult dengue or scrub typhus patients admitted between 1998 and 2008 at Kaohsiung Chang Gung Memorial Hospital. A total of 980 dengue and 102 scrub typhus adult patients were included in our study. RESULTS: Eighteen of the 980 adult dengue patients and 8 of the 102 adult scrub typhus patients had ARF. There were significant differences that existed for eschar (P = 0.001; dengue 0%; scrub 62.5%), cough (P = 0.016; dengue 55.6%; scrub typhus 100%), white blood cell (WBC) count [P = 0.026; dengue 7.40 ± 5.74; scrub typhus 11.84 ± 4.95 (×10(3)/μL)], platelet count [P = 0.008; dengue 42.2 ± 33.9; scrub typhus 104.1 ± 93.3 (×10(9)/L)], prothrombin time (PT) [P = 0.007; dengue 12.82 ± 1.36; scrub typhus 10.74 ± 0.98 (s)], activated partial thromboplastin time (APTT) [P = 0.002; dengue 50.81 ± 10.08; scrub typhus 37.44 ± 4.06 (s)], blood urea nitrogen (BUN) [P < 0.001; dengue 64.6 ± 43.2; scrub typhus 20.9 ± 9.1 (mg/dL)], creatinine [P < 0.001; dengue 3.77 ± 3.37; scrub typhus 1.05 ± 0.37 (mg/dL)], admission day (A-day) [P = 0.027; dengue 2.9 ± 1.3; scrub typhus 5.4 ± 2.6 (days)], and ventilator duration [P = 0.022; dengue 9.4 ± 14.0; scrub typhus 14.8 ± 10.4 (days)] between both groups. CONCLUSIONS: This study provides relatively rare data regarding the clinical differences between adult dengue and scrub typhus patients with ARF.


title: The relationship between extravascular lung water and oxygenation in three patients with influenza A (H1N1)-induced respiratory failure

text: This case series reports the correlation between extravascular lung water (EVLW) and the partial arterial oxygen pressure/fractional inspiratory oxygen (PaO(2)/FiO(2)) ratio in three patients with severe influenza A (H1N1)-induced respiratory failure. All patients suffered from grave hypoxia (PaO(2), 26–42 mmHg) and were mechanically ventilated using biphasic airway pressure (PEEP, 12–15 mmHg; FiO(2), 0.8–1) in combination with prone positioning at 12 hourly intervals. All patients were monitored using the PICCO(®) system for 8–11 days. During mechanical ventilation, a total of 62 simultaneous determinations of the PaO(2)/FiO(2) ratio and EVLW were performed. A significant correlation between EVLW and the PaO(2)/FiO(2) ratio (Spearman-rho correlation coefficient, –0.852; p < 0.001) was observed. In all patients, a decrease in EVLW was accompanied by an improvement in oxygenation. Serum lactate dehydrogenase levels were elevated in all patients and significantly correlated with EVLW during the intensive care unit stay (Spearman-rho correlation coefficient, 0.786; p < 0.001). In conclusion, EVLW seems increased in patients with severe H1N1-induced respiratory failure and appears to be closely correlated with impairments of oxygenatory function.


Leukotrienes: Biosynthesis, Metabolism, and Pathophysiologic Significance


title: Hemophagocytic lymphohistiocytosis in a patient with Sjögren’s syndrome: case report and review

text: Hemophagocytic lymphohistiocytosis (HLH) is a very rare syndrome with a mortality up to 95% of cases if not treated. It is characterised by an excessive activation of the immune system that leads to a disproportionate and destructive inflammatory response. The high mortality rates are in part due to a delay in the diagnosis, and therefore clinicians must maintain a high index of suspicion. When the treatment is started early, the survival rate reaches around 55% of cases. HLH usually presents with persistent fever, pancytopenia, and organomegaly and is associated with very high levels of serum ferritin. In this manuscript, we present the case of a patient with primary Sjögren's syndrome who developed HLH after an acute infection by Cytomegalovirus. We will describe and discuss the pathogenesis, differential diagnosis and a pragmatic approach to the treatment for this critically important and, when diagnosed early, potentially curable syndrome.


title: Severe bronchiolitis in children

text: Bronchiolitis is a common, acute, contagious lower respiratory tract illness of infants and young children. The majority of cases are secondary to respiratory syncytial virus. There are a number of risk factors for severe disease, including children less than six weeks of age and patients with atopy and/or asthma. The management requires vigilant monitoring and high-quality supportive care, including impressive use of fluids and nutritional support. Further research on anti-virals is essential to prevent respiratory syncytial virus induced bronchiolitis. Fortunately, the prognosis for the majority of normal infants who develop bronchiolitis is good.


title: Novel observations during extracorporeal membrane oxygenation in patients with ARDS due to the H1N1 pandemic influenza

text: We report four patients with novel observations during extracorporeal membrane oxygenation support (ECMO). ECMO was initiated because of severe ARDS due to the primary H1N1 pandemic influenza pneumonia. Two patients had excessive conjugated hyperbilirubinemia and two had unproportional depletion of the coagulation factor IX. Pathogenetic mechanisms and clinical relevance of the noticed phenomena are discussed.


title: Intravascular large B-cell lymphoma with diffuse FDG uptake in the lung by (18)FDG-PET/CT without chest CT findings

text: We report a rare case of intravascular large B-cell lymphoma (IVLBCL) with diffuse fluorodeoxyglucose (FDG) uptake in the lung by (18)FDG-positron emission tomography/computed tomography (PET/CT). CT showed nodular shadow, whereas diffuse FDG uptake in PET/CT suggested IVLBCL in the lung. A random skin biopsy provided histological evidence of IVLBCL. The patient responded well to combination chemotherapy. Only two cases of IVLBCL in which diffuse pulmonary FDG uptake was demonstrated have been reported previously. FDG-PET/CT plus random skin biopsy may be useful for the early diagnosis of IVLBCL with pulmonary involvement even without convincing radiological findings in the lung.


Onkologische Notfälle


title: Severe Proctitis, Perforation, and Fatal Rectal Bleeding Secondary to Cytomegalovirus in an Immunocompetent Patient: Report of a Case

text: Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality in immunocompromised patients. In immunocompetent individuals, the infection is usually subclinical but it can sometimes be life threatening. We describe a case of fatal CMV proctitis in a 71-year-old man following an Ivor–Lewis esophagectomy. After surgery he developed renal failure, methicillin-resistant Staphylococcus aureus pneumonia, and acute respiratory distress syndrome. He recovered but developed melena and massive fresh rectal bleeding. Sigmoidoscopy revealed severe proctitis and a biopsy was consistent with ischemia. Despite undergoing a proctectomy he continued to bleed and died despite every effort. The final histological examination of the rectum revealed a CMV infection.


title: Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma

text: Intravenous brentuximab vedotin (ADCETRIS(®)) is a targeted antibody-drug conjugate (ADC) active against CD30-positive cancer cells such as those associated with classical Hodgkin lymphoma (HL). In noncomparative, phase 2 trials and in the real-world setting, salvage therapy with brentuximab vedotin resulted in high objective response (complete plus partial remission) rates in patients with relapsed or refractory CD30-positive HL, including as retreatment in patients who had an objective response to previous brentuximab vedotin therapy and subsequently relapsed. These beneficial outcomes were durable during long-term follow-up. As consolidation therapy after autologous haematopoietic stem cell transplant (ASCT) in the multinational, phase 3 AETHERA trial, brentuximab vedotin prolonged progression-free-survival (PFS) compared with placebo at a median follow-up of 30 months (primary analysis), with a 43% reduction in the risk of disease progression or death. The beneficial effects of brentuximab vedotin consolidation therapy were maintained during long-term follow-up. In the clinical trial and real-world setting, brentuximab vedotin had an acceptable tolerability and safety profile, with most adverse events manageable with dose reductions and/or delays [including peripheral sensory neuropathy (PSN) and neutropenia]. With a paucity of treatments available for many patients with relapsed or refractory HL, brentuximab vedotin represents an important option for the management of patients who have failed high-dose chemotherapy/ASCT or at least two prior chemotherapy regimens and as post-ASCT consolidation therapy in patients who are at increased risk/high-risk of relapse or progression after ASCT.


Journal of Artificial Organs 2017: the year in review: Journal of Artificial Organs Editorial Committee


title: Immune response in Dobrava-Belgrade virus infections

text: Dobrava-Belgrade virus (DOBV) is a hantavirus that causes a disease in humans known as hemorrhagic fever with renal syndrome. Hallmarks of hantaviral infections are increased vascular permeability due to dysregulation of the endothelial cell barrier and acute thrombocytopenia. In order to gain insight into the immune response in DOBV infections, the serum levels of 27 cytokines in 24 hospitalized Greek HFRS patients were evaluated. Compared to the control group, significantly higher IL-1ra, IL-6, IL-8, IL-9, IL-10, GM-CSF, IP-10, MIP-1b, TNF-α and VEGF levels were found in severe cases, while in non-severe cases, IL-13 and TNF-α levels were significantly higher (p < 0.05). In all groups, IP-10 was increased and RANTES was decreased. Significant and time- (after onset of illness) dependent differences among fatal, severe and non-severe cases were seen. VEGF was positively associated with disease severity. A strong immune response was seen during the first week of illness, especially in severe cases, while the response in non-severe cases was weaker and delayed. The Th1 response was strong in non-severe cases and weak in the fatal case, while a mixed Th1/Th2 immune response was seen in the survivors of severe disease.


title: Clinical Insights into Diffuse Alveolar Hemorrhage in Antiphospholipid Syndrome

text: PURPOSE OF REVIEW: Diffuse alveolar hemorrhage (DAH) is a rare but devastating manifestation of antiphospholipid syndrome (APS) patients with or without other systemic autoimmune diseases. Data regarding diagnosis and treatment are limited to case series. We review diagnostic and therapeutic strategies employed in APS patients with DAH and discuss our experience in managing these complex patients. RECENT FINDINGS: Pulmonary capillaritis likely contributes to the pathogenesis, however is only observed in half of the biopsies. Corticosteroids induce remission in the majority of patients, however almost half recur and require a steroid-sparing immunosuppressive to maintain remission. Cyclophosphamide- or rituximab-based regimens achieve the highest remission rates (50%); other strategies include intravenous immunoglobulin, plasmapheresis, mycophenolate mofetil, and/or azathioprine. SUMMARY: Given the rarity of DAH in APS, treatment is guided by interdisciplinary experience. Why certain patients achieve full remission with corticosteroids while others require immunosuppressive agents is unknown; future research should focus on the pathophysiology and optimal management.


Glyco XIII: XIIIth International Symposium on Glycoconjugates


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title: Conservation of T cell epitopes between seasonal influenza viruses and the novel influenza A H7N9 virus

text: A novel avian influenza A (H7N9) virus recently emerged in the Yangtze River delta and caused diseases, often severe, in over 130 people. This H7N9 virus appeared to infect humans with greater ease than previous avian influenza virus subtypes such as H5N1 and H9N2. While there are other potential explanations for this large number of human infections with an avian influenza virus, we investigated whether a lack of conserved T-cell epitopes between endemic H1N1 and H3N2 influenza viruses and the novel H7N9 virus contributes to this observation. Here we demonstrate that a number of T cell epitopes are conserved between endemic H1N1 and H3N2 viruses and H7N9 virus. Most of these conserved epitopes are from viral internal proteins. The extent of conservation between endemic human seasonal influenza and avian influenza H7N9 was comparable to that with the highly pathogenic avian influenza H5N1. Thus, the ease of inter-species transmission of H7N9 viruses (compared with avian H5N1 viruses) cannot be attributed to the lack of conservation of such T cell epitopes. On the contrary, our findings predict significant T-cell based cross-reactions in the human population to the novel H7N9 virus. Our findings also have implications for H7N9 virus vaccine design.


title: Risk factors and clinical significance of invasive infections caused by levofloxacin-resistant Streptococcus pneumoniae

text: PURPOSE: Fluoroquinolones are recommended for the treatment of pneumonia. The recognition of risk factors for invasive levofloxacin-resistant Streptococcus pneumoniae is important for the design of treatment. METHODS: A retrospective review of cases of invasive pneumococcal infections in adults was undertaken. Epidemiologic data, predisposing factors, clinical variables, and outcome were recorded from previously established protocols. Antimicrobial susceptibility was determined by disk diffusion and the Etest method. Serotyping was performed by latex agglutination and Quellung reaction. RESULTS: Twenty patients with infection caused by levofloxacin-resistant pneumococci [minimum inhibitory concentration (MIC) ≥2 μg/ml] were compared with 102 patients harboring levofloxacin-susceptible strains; 80 % of levofloxacin-resistant pneumococci were resistant to ≥3 antibiotics but susceptible to penicillin. Most levofloxacin-resistant strains (80 %) belonged to serotype 8. In comparison, only 8 % of levofloxacin-susceptible pneumococci belonged to serotype 8. In the multivariate analysis, residence in public shelters [odds ratio (OR) 26.13; p 0.002], previous hospitalization (OR 61.77; p < 0.001), human immunodeficiency virus (HIV) infection (OR 28.14; p = 0.009), and heavy smoking (OR 14.41; p = 0.016) were associated with an increased risk of infection by levofloxacin-resistant pneumococci. Mortality caused by levofloxacin-resistant and levofloxacin-susceptible pneumococci was 35 and 14 %, respectively. Among HIV-positive individuals infected with levofloxacin-resistant pneumococci 44 % died, but only 12.5 % of HIV-positive patients with levofloxacin-susceptible strains died. CONCLUSIONS: We observed the emergence of serotype 8 as the main cause of invasive disease caused by levofloxacin-resistant S. pneumoniae. HIV-positive patients seem to be prone to infection caused by multidrug-resistant serotype 8 and have a high mortality rate.


title: Pandemic H1N1 (2009) and renal failure: the experience of the Irish national tertiary referral centre

text: INTRODUCTION: H1N1 influenza A, was first described in April 2009. A significant cohort of patients from this outbreak developed acute respiratory distress syndrome or pneumonia. H1N1 has since been transmitted across the world. Little has been described on the renal complications of this illness. METHODS: A retrospective review of all patients admitted to our institution with H1N1 infection was carried out from July to November 2009. Renal biochemistry, need for renal replacement therapy and hospital outcome was recorded. RESULTS: Thirty-four patients with H1N1 were admitted. Average length of admission was 10 days (3–84). Eleven patients (32%) developed acute kidney injury (AKI) as defined by the RIFLE criteria (creatinine range 120–610). Four patients required renal replacement therapy, for a range of 10–52 days. Seven patients developed AKI that responded to volume resuscitation. The commonest cause of AKI was sepsis with acute tubular necrosis. CONCLUSION: This study highlights the significance and frequency of renal complications associated with this illness.


title: Adverse reactions to targeted and non-targeted chemotherapeutic drugs with emphasis on hypersensitivity responses and the invasive metastatic switch

text: More than 100 drugs are used to treat the many different cancers. They can be divided into agents with relatively broad, non-targeted specificity and targeted drugs developed on the basis of a more refined understanding of individual cancers and directed at specific molecular targets on different cancer cells. Individual drugs in both groups have been classified on the basis of their mechanism of action in killing cancer cells. The targeted drugs include proteasome inhibitors, toxic chimeric proteins and signal transduction inhibitors such as tyrosine kinase (non-receptor and receptor), serine/threonine kinase, histone deacetylase and mammalian target of rapamycin inhibitors. Increasingly used targeted vascular (VEGF) and platelet-derived endothelial growth factor blockade can provoke a range of pathological consequences. Many of the non-targeted drugs are cytotoxic, suppressing haematopoiesis as well as provoking cutaneous eruptions and vascular, lung and liver injury. Cytotoxic side effects of the targeted drugs occur less often and usually with less severity, but they show their own unusual adverse effects including, for example, a lengthened QT interval, a characteristic papulopustular rash, nail disorders and a hand–foot skin reaction variant. The term hypersensitivity is widely used across a number of disciplines but not always with the same definition in mind, and the terminology needs to be standardised. This is particularly apparent in cancer chemotherapy where anti-neoplastic drug-induced thrombocytopenia, neutropenia, anaemia, vascular disorders, liver injury and lung disease as well as many dermatological manifestations sometimes have an immune basis. The most insidious of all adverse consequences of targeted therapies, however, are tumour adaptation, increased malignancy and the invasive metastatic switch seen with anti-angiogenic drugs that inhibit the VEGF-A pathway. Adverse reactions to 44 non-targeted and 33 targeted, frequently used, chemotherapeutic drugs are presented together with discussions of diagnosis, premedications, desensitizations and importance of understanding the mechanisms underlying the various drug-induced reactions. There is need for wide-ranging acceptance of what constitutes a hypersensitivity reaction and for allergists to be more involved in the diagnosis, treatment and prevention of chemotherapeutic drug-induced hypersensitivity reactions.


title: Hand-assisted Laparoscopic Splenectomy and Devascularization of the Upper Stomach in the Management of Gastric Varices

text: BACKGROUND: Bleeding from esophagogastric varices is the major cause of death in patients with portal hypertension. Although esophageal varices can be treated with endoscopic procedures, the treatment for gastric varices is still controversial. The aim of this study was to describe a surgical technique and our preliminary results of hand-assisted laparoscopic Hassab’s procedure. METHODS: Between February 2002 and May 2005, we performed 7 cases of gastric varices with this type of operation. The patients included 4 men and 3 women who ranged in age from 23 to 74 years (underlying liver disease: 5 case of liver cirrhosis, 1 case of polycystic disease, 1 case of extrahepatic portal vein obstruction). After splenctomy was performed, we devascularized the vessels of the upper stomach and the esophagus 5 cm away from the esophago-cardia junction. RESULTS: The operative time ranged from 132 to 290 minutes. Intraoperative blood loss was estimated to be from 50 ml to 475 ml. The weight of removed spleen ranged from 110 g to 800 g. During the follow-up period, all gastric varices disappeared and no bleeding from varicose veins was observed. All patients had hypersplenism with thrombocytopenia before surgery (mean: 11.1 ± 7.4 × 10(4)/ml), which was improved postoperatively (mean: 30.8 ±19.0 × 10(4)/ml). This data were statistically significant (P = 0.033). One patient died of aspiration pneumonia related to postoperative pyloric stricture. CONCLUSIONS: Although there is no agreement concerning the best treatment of gastric varices, the hand-assisted laparoscopic Hassab’s operation is a safe, moderately invasive method, and its outcome appears to be equal to that of other open procedures.


title: Treatment of Paraneoplastic Cerebellar Degeneration

text: Paraneoplastic cerebellar degeneration is an uncommon autoimmune disorder characterized clinically by progressive, ultimately incapacitating ataxia and pathologically by destruction of cerebellar Purkinje cells, with variable loss of other cell populations. The disorder is most commonly associated with gynecological and breast carcinomas, small cell carcinoma of the lung, and Hodgkin’s disease and in most cases comes on prior to identification of the underlying neoplasm. The hallmark of paraneoplastic cerebellar degeneration is the presence of an immune response reactive with intracellular proteins of Purkinje or other neurons or, less commonly, against neuronal surface antigens. Evidence-based treatment strategies for paraneoplastic cerebellar degeneration do not exist; and approaches to therapy are thus speculative. Diagnosis and treatment of the underlying neoplasm is critical, and characterization of the antibody response involved may assist in tumor diagnosis. Most investigators have initiated treatment with corticosteroids, plasma exchange, or intravenous immunoglobulin G. Cyclophosphamide, tacrolimus, rituximab, or possibly mycophenolate mofetil may warrant consideration in patients who fail to stabilize or improve on less aggressive therapies. Plasma exchange has been of questionable benefit when used alone but should be considered at initiation of treatment to achieve rapid lowering of circulating paraneoplastic autoantibodies. Because the course of illness is one of relentless neuronal destruction, time is of the essence in initiating treatment. Likelihood of clinical improvement in patients with longstanding symptoms and extensive neuronal loss is poor.


title: Role of MicroRNA in Endothelial Dysfunction and Hypertension

text: PURPOSE OF REVIEW: Hypertension is either a cause or a consequence of the endothelial dysfunction and a major risk factor for cardiovascular disease (CVD). In vitro and in vivo studies established that microRNAs (miRNAs) are decisive for endothelial cell gene expression and function in various pathological conditions associated with CVD. This review provides an overview of the miRNA role in controlling the key connections between endothelial dysfunction and hypertension. RECENT FINDINGS: Herein we summarize the present understanding of mechanisms underlying hypertension and its associated endothelial dysfunction as well as the miRNA role in endothelial cells with accent on the modulation of renin-angiotensin-aldosterone-system, nitric oxide, oxidative stress and on the control of vascular inflammation and angiogenesis in relation to endothelial dysfunction in hypertension. In particular, latest insights in the identification of endothelial-specific microRNAs and their targets are added to the understanding of miRNA significance in hypertension. SUMMARY: This comprehensive knowledge of the role of miRNAs in endothelial dysfunction and hypertension and of molecular mechanisms proposed for miRNA actions may offer novel diagnostic biomarkers and therapeutic targets for controlling hypertension-associated endothelial dysfunction and other cardiovascular complications.


title: Zoonosis: Update on Existing and Emerging Vector-Borne Illnesses in the USA

text: PURPOSE OF REVIEW: This review describes mosquito- and tick-borne diseases found in the Western Hemisphere. It focuses on emerging diseases and recent geographic shifts in the presence of disease vectors. RECENT FINDINGS: Mosquito and tick vectors have become more widespread as environmental conditions have become more favorable. Zika recently has emerged as a concern for fetal anomalies. West Nile Virus has become widespread. Lyme disease and other tick-borne diseases are more prevalent in areas previously inhospitable to these ticks. SUMMARY: Healthcare providers must consider the possibility of mosquito- and tick-borne diseases in broader geographic areas and council patients traveling to endemic areas on precautions against these diseases. Treatment for suspected cases of serious tick-borne illnesses should not be delayed pending culture results.


title: Critical care management of the lung transplant recipient

text: Lung transplantation provides the prospect of improved survival and quality of life for patients with end stage lung and pulmonary vascular diseases. Given the severity of illness of such patients at the time of surgery, lung transplant recipients require particular attention in the immediate post-operative period to ensure optimal short-term and long-term outcomes. The management of such patients involves active involvement of a multidisciplinary team versed in common post-operative complications. This review provides an overview of such complications as they pertain to the practitioners caring for post-operative lung transplant recipients. Causes and treatment of conditions affecting early morbidity and mortality in lung transplant recipients will be detailed, including primary graft dysfunction, cardiovascular and surgical complications, and immunologic and infectious issues. Additionally, lung donor management issues and bridging the critically ill potential lung transplant recipient to transplantation will be discussed.


title: Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients

text: The purpose of this study was to assess the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for the diagnosis of severe respiratory diseases based on interpretation of sequencing results. BALF samples were harvested and used for mNGS as well as microbiological detection. Infectious bacteria or fungi were defined according to relative abundance and number of unique reads. We performed mNGS on 35 BALF samples from 32 patients. The positive rate reached 100% in the mNGS analysis of nine immunocompromised patients. Compared with the culture method, mNGS had a diagnostic sensitivity of 88.89% and a specificity of 74.07% with an agreement rate of 77.78% between these two methods. Compared with the smear method and PCR, mNGS had a diagnostic sensitivity of 77.78% and a specificity of 70.00%. In 13 cases, detection results were positive by mNGS but negative by culture/smear and PCR. The mNGS findings in 11/32 (34.4%) cases led to changes in treatment strategies. Linear regression analysis showed that diversity was significantly correlated with interval between disease onset and sampling. Dynamic changes in reads could indirectly reflect therapeutic effectiveness. BALF mNGS improves sensitivity of pathogen detection and provides guidance in clinical practice. Potential pathogens can be identified based on relative abundance and number of unique reads. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03734-5) contains supplementary material, which is available to authorized users.


title: Delivery Systems for Pulmonary Gene Therapy

text: Delivery of therapeutic genes to the lungs is an attractive strategy to correct a variety of pulmonary dysfunctions such as cystic fibrosis, alpha-1 antitrypsin deficiency, pulmonary hypertension, asthma, and lung cancer. Different delivery routes such as intratracheal instillation, aerosol and intravenous injection have been utilized with varying degrees of efficiency. Both viral and non-viral vectors, with their respective strengths and weaknesses, have achieved significant levels of transgene expression in the lungs. However, the application of gene therapy for the treatment of pulmonary disease has been handicapped by various barriers to the delivery vectors such as serum proteins during intravenous delivery, and surfactant proteins and mucus in the airway lumen during topical application of therapeutic genes. Immune and cytokine responses against the delivery vehicle are also major problems encountered in pulmonary gene therapy. Despite these shortcomings much progress has been made to enhance the efficiency, as well as lower the toxicity of gene therapy vehicles in the treatment of pulmonary disorders such as cystic fibrosis, lung cancer and asthma.


title: Hematopoietic stem cell transplantation for severe aplastic anemia—experience of an institute in Taiwan

text: Hematopoietic stem cell transplantation (HSCT) is an accepted treatment strategy for patients with severe aplastic anemia (SAA). We report our experience in a general hospital in Taiwan. From March 1985 to July 2001, 79 consecutive SAA patients, 46 male and 33 female, with a median age of 22 (4–43) years, received 80 courses of transplantation. Cyclophosphamide and total body radiation were used for the conditioning regimen, and cyclosporine-A and methotrexate for graft-versus-host disease (GVHD) prevention. Patients were followed for a median of 39 months (from 8 days to 194 months). Myeloid and platelet engraftment occurred in a median of 15 (8–27) days and 18 (8–77) days, respectively. Three patients had primary and three patients secondary graft failure. Five patients (6.8%) had grade II–IV acute GVHD in 73 evaluable patients. Chronic GVHD occurred in 23 (34.8%) patients, with extensive stage in six. Only two patients had CMV disease. The projected 3- and 5-year overall survival rates estimated by the Kaplan-Meier method were 76.08 and 74.13%, respectively. Age at transplant, non-sibling donor, mononuclear cell dose, grade II–IV acute GVHD, interval from diagnosis to transplant, and red blood cell and platelet transfusion before transplant were poor prognostic factors for overall survival by univariate analysis. Grade II–IV acute GVHD was the only prognostic factor affecting overall survival after multivariate Cox regression analysis (P=0.040). In conclusion, SAA patients receiving HSCT have good long-term survival. The low incidence of acute GVHD in our patients may be related to ethnicity.


title: Chinese society of cardiology expert consensus statement on the diagnosis and treatment of adult fulminant myocarditis

text: Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock, with mortality rates as high as 50%–70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial (NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time, we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes (i) mechanical life support (applications of mechanical respirators and circulatory support systems, including intraaortic balloon pump and extracorporeal membrane oxygenation, (ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and (iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis.