2017 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference


title: Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells

text: Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR) is a type II transmembrane protein which has been reported to bind a variety of pathogens as well as participate in immunoregulation. But the association between the level of DC-SIGNR and lung cancer is unknown. To investigate the clinical diagnostic significance of DC-SIGNR in lung cancer, we investigated serum DC-SIGNR levels in 173 lung cancer patients and 134 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results showed that serum DC-SIGNR levels in lung cancer patients were lower than that in healthy controls (P = 0.0003). A cut-off value of 3.8998 ng/L for DC-SIGNR predicted the presence of lung cancer with 78.03 % sensitivity and 49.25 % specificity (area under the curve = 0.6212, P = 0.0003). Strikingly, serum DC-SIGNR levels were significantly higher in lung cancer patients with brain metastasis compared to those without metastasis (P = 0.0283). Moreover, the serum concentrations of DC-SIGNR in lung cancer patients also correlated significantly with serum natural killer cells percentage (P = 0.0017). In addition, immunohistochemistry assay demonstrated that the expression of DC-SIGNR in lung tissues of 31 lung cancer patients and 13 tuberculosis patients was significantly lower than that in 18 normal lung tissues (P = 0.0418, 0.0289), and there is no significant difference between tuberculosis tissues and lung cancer tissues (P = 0.2696). These results suggest that DC-SIGNR maybe a promising biological molecule that has the potential for clinical research of lung cancer, whereas its underlying roles are needed to be investigated in further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11010-015-2465-4) contains supplementary material, which is available to authorized users.


title: Oseltamivir in seasonal, pandemic, and avian influenza: a comprehensive review of 10-years clinical experience

text: Oseltamivir (Tamiflu®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) is an orally administered antiviral for the treatment and prevention of influenza A and B infections that is registered in more than 100 countries worldwide. More than 83 million patients have been exposed to the product since its introduction. Oseltamivir is recommended by the World Health Organization (WHO) for use in the clinical management of pandemic and seasonal influenza of varying severity, and as the primary antiviral agent for treatment of avian H5N1 influenza infection in humans. This article is a nonsystematic review of the experience gained from the first 10 years of using oseltamivir for influenza infections since its launch in early 2000, emphasizing recent advances in our understanding of the product and its clinical utility in five main areas. The article reviews the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, including information on special populations such as children and elderly adults, and the co-administration of oseltamivir with other agents. This is followed by a summary of data on the effectiveness of oseltamivir treatment and prophylaxis in patients with all types of influenza, including pandemic (H1N1) 2009 and avian H5N1 influenza. The implications of changes in susceptibility of circulating influenza viruses to oseltamivir and other antiviral agents are also described, as is the emergence of antiviral resistance during and after the 2009 pandemic. The fourth main section deals with the safety profile of oseltamivir in standard and special patient populations, and reviews spontaneously reported adverse event data from the pandemic and pre-pandemic periods and the topical issue of neuropsychiatric adverse events. Finally, the article considers the pharmacoeconomics of oseltamivir in comparison with vaccination and usual care regimens, and as a component of pandemic influenza mitigation strategies.


title: Liver Resection for Hepatocellular Carcinoma in Patients with Renal Dysfunction

text: BACKGROUND: The aim of this study was to evaluate the feasibility of liver resection in hepatocellular carcinoma (HCC) patients with preoperative renal dysfunction (RD). METHODS: Data from 735 patients undergoing primary liver resection for HCC between 2002 and 2014 were analyzed. Short- and long-term outcomes were compared between the RD group, defined by a preoperative estimated glomerular filtration rate of <45 mL/min/1.73 m(2), and the non-RD group. RESULTS: Sixty-two patients had RD. The incidence of postoperative pleural effusion (24 vs. 11%; P = 0.007) and major complications (Clavien–Dindo III–V; 31 vs. 15%; P = 0.003) were significantly higher in RD patients. In RD patients with Child-Pugh A, 90-day mortality rate (1.9%) and median survival time (6.11 years) were comparable to that of non-RD patients. In contrast, RD patients with Child-Pugh B had a very high 90-day mortality rate (22.2%), and a significant shorter median survival time compared to non-RD patients (1.19 vs. 4.84 years; P = 0.001). CONCLUSIONS: Liver resection for Child-Pugh A patients with RD is safe and has comparable oncological outcomes compared to non-RD patients. However, selection of liver resection candidates from Child-Pugh B patients with RD should be stricter. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00268-018-4698-3) contains supplementary material, which is available to authorized users.


title: Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation

text: We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-β(2)-glycoprotein-1 (β(2)GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.


title: Radiological prognostic factors in patients with pandemic H1N1 (pH1N1) infection requiring hospital admission

text: The aim of this study was to determine the radiologic findings associated with admission to the intensive care unit (ICU) and the development of acute respiratory distress syndrome (ARDS) in patients with pH1N1 infection. One hundred and four patients (15–96 years) with laboratory-confirmed pH1N1 infection seen at the Emergency Department from July to December 2009 who underwent chest radiographs were studied. Radiographs were evaluated for consolidation, ground-glass opacities, interstitial patterns, distribution, and extent of findings. Eighty-seven (83.7%) of the patients were managed in the ward, and 17 (16.3%) patients eventually required admission to the ICU. All patients admitted to the ICU showed abnormalities on the initial radiograph. The presence of consolidation, multifocal, diffuse, and bilateral involvement on the initial radiograph was associated with a statistically higher risk of requiring ICU admission (p < 0.001). There were no significant differences regarding age, sex, and presence of underlying comorbidities. Evolution to ARDS was found in eight cases that necessitated ICU care. All of them had on the initial radiograph patchy multifocal consolidations (p < 0.001) with bilateral lesions in six cases. A higher number of lung zones involved and consolidation on the initial chest radiograph as well as a rapid progression of the radiological abnormalities were identified in patients requiring ICU admission and development of ARDS. Initial chest radiographs show acute abnormalities in all patients with severe disease. The findings of a multifocal patchy consolidation pattern with bilateral or diffuse lung involvement on admission should alert of the impending severity of disease and the risk of necessitating ICU admission


title: Clinical characteristics of Stenotrophomonas maltophilia infection in hematopoietic stem cell transplantation recipients: a single center experience

text: BACKGROUND: Recipients of hematopoietic stem-cell transplantation (HSCT) are at high risk for infections caused by Stenotrophomonas maltophilia. METHODS: We conducted a retrospective analysis of all infections caused by S. maltophilia in HSCT recipients in a single center in Israel during a 4 year period. RESULTS: Of 570 patients undergoing HSCT, 19 patients with an invasive S. maltophilia infection were identified. Sixteen had allogeneic HSCT and 3 had autologous HSCT. Seventeen patients (90%) had an indwelling central venous catheter (CVC) at the time of infection. S. maltophilia infections were detected in three clinical settings: as a complication of prolonged neutropenia (n = 9), as a CVC-related non-neutropenic infection occurring after CVC manipulation (n = 8) and as a respiratory tract infection (n = 2). Eleven patients (58%) had a polymicrobial infection. Ten patients (52.6%) received carbapenems during the previous month. The treatment for all patients included broad spectrum antibiotics, which were switched according to susceptibilities upon identification of the isolates. All isolates were susceptible in vitro to TMP-SMX. CVCs were removed in 12 patients (70%). Six patients, all after allogeneic HSCT, died. The CVC was removed in only two of the five patients with CVCs who died. CONCLUSIONS: Stenotrophomonas maltophilia is an emerging nosocomial pathogen in HSCT recipients, both in the early neutropenic phase and in the non-neutropenic phase. It is commonly associated with the presence and manipulation of an indwelling CVC. Removal of the CVC in addition to appropriate antibiotic therapy (TMP-SMX) is crucial for infection control.


title: Perioperative considerations of the patient with malaria

text: PURPOSE: Malaria is a life-threatening infectious disease caused by the Plasmodium parasite. Increased global travel has resulted in an escalation in the number of imported cases seen in developed countries. Patients with malaria may present for surgery in both endemic and non-endemic countries. This article reviews the perioperative considerations when managing patients with malaria. SOURCE: A literature review of anesthesia, perioperative care, and malaria-related articles was performed using the MEDLINE(®), EMBASE™, and Web of Science databases to identify relevant articles published in English during 1945-2014. Of the 303 articles matching the search criteria, 265 were excluded based on title and abstract. Eleven of the remaining 38 articles were relevant to anesthesia/perioperative care, and 27 articles were identified as having direct relevance to critical care medicine. PRINCIPAL FINDINGS: The majority of imported malaria cases are caused by the falciparum species, which is associated with the greatest degree of morbidity and mortality. Various organ systems may be impacted as a consequence of changes in the structure and function of parasitized erythrocytes. Preoperative assessment should focus on establishing the species of malaria, the severity of disease, assessing the degree of end-organ impairment, and initiating treatment of malaria prior to surgery. Intravenous artesunate is the treatment of choice for severe falciparum malaria. Quinine is a second-line agent but has a narrow therapeutic index and particularly hazardous side effects. Intraoperatively, attention should focus on fluid management, dynamics of cerebral blood flow, and avoidance of hypoglycemia. Postoperative care of severe cases should ideally take place in a critical care unit as there may be ongoing requirements for multi-organ support, including renal replacement therapy, ventilation, and/or inotropic support. The safety of neuraxial anesthesia has not been well studied in the setting of malaria. CONCLUSIONS: Malaria remains one of the most devastating infectious diseases worldwide. Multiple organ systems can be impacted as a consequence of changes in structure and function of parasitized erythrocytes. Safe perioperative management requires a sound knowledge of all these potential system effects.


title: Impact of Preexisting Circulating Effector T cells on the Outcome of ABO-Incompatible Adult LDLT

text: Our aim was to clarify the significance of phenotype of circulating CD8 T(+) cells on the outcome of ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). Twenty-six recipients undergoing ABO-I LDLT and 92 undergoing ABO-compatible (ABO-C) LDLT were classified into three groups according to preoperative proportion of CD8 T(+) cells: naive-dominant (group I), effector memory-dominant (group II), and effector-dominant (group III) recipients. The clinical courses were analyzed. The results showed that in ABO-C groups I and II and in ABO-I group I, effector cells remained above the pretransplant levels after tacrolimus administration. However, in ABO-C group III and ABO-I groups II and III, effector cells were down-regulated for a prolonged period, along with markedly decreased perforin expression and frequent life-threatening complications. ABO-I group II and group III recipients had higher infection rates. It was concluded that recipients with preexisting high effector CD8 T(+) cells are unfavorable candidates for ABO-I LDLT.


title: G-CSF mobilised granulocyte transfusions in 32 paediatric patients with neutropenic sepsis

text: INTRODUCTION: In this retrospective, uncontrolled, observational study, the effect of granulocyte colony-stimulating factor (G-CSF)-stimulated granulocyte transfusions (GTX) in neutropenic paediatric patients with sepsis was evaluated. PATIENTS AND METHODS: Granulocytes were collected from unrelated, ABO group-matched and cytomegalic-antibody compatible donors. For neutrophil mobilization, donors received a single subcutaneous dose of glycosylated G-CSF (Lenograstim, Chugai Pharma, Japan) plus oral dexamethasone (8 mg). In total, 168 (range 1–19 per patient) GTX were transfused in 32 children with a median age of 7.4 (0.25 to 16) years. RESULTS: The underlying diseases comprised predominantly haematooncological malignancies (31 children). In 15 of 32 patients, neutropenia was related to allogeneic stem cell transplantation. All children suffered from sepsis based on international criteria (fever, tachycardia, respiratory rate >2 SD above normal in the context of a suspected or proven infection). In ten children bacteria were isolated, in six children a fungal infection was diagnosed and four sepsis episodes were caused by viral infections. GTX contained a median neutrophil number of 6.3 (range 1.9–13.9)×10(10) per transfusion and obtained a sustained haematological response after GTX. Nineteen out of 32 children survived the neutropenic sepsis, particularly nine out of 11 patients with bacterial sepsis. DISCUSSION: In contrast to the non-survivors, we observed a significant decrease in the C-reactive protein levels shortly after initiation of the GTX treatment in the surviving patients. A clear-cut benefit of GTX for children with neutropenic sepsis cannot be concluded from these data, but in children with (severe) bacterial sepsis refractory to antibiotic treatment, GTX were feasible, safe and could reduce mortality rates in this subgroup of patients.


title: Non-Hepatic Abdominal Surgery in Patients with Cirrhotic Liver Disease

text: Cirrhotic liver disease is an important cause of peri-operative morbidity and mortality in general surgical patients. Early recognition and optimization of liver dysfunction is imperative before any elective surgery. Patients with MELD <12 or classified as Child A have a higher morbidity and mortality than matched controls without liver dysfunction, but are generally safe for elective procedures with appropriate patient education. Patients with MELD >20 or classified as Child C should undergo transplantation before any elective procedure given mortality exceeds 40%. Laparoscopic procedures are feasible and safe in cirrhotic patients.


title: Clinical study of Japanese spotted fever and its aggravating factors

text: Twenty-eight patients with Japanese spotted fever were clinically investigated. The diagnosis was determined by confirming an increase of specific antibody. All patients were treated with minocycline, and all recovered, excluding one patient with a fulminant course. Fever and exanthema were observed in all patients, and an eschar was pointed out in 20 (71%) patients. The platelet count was 10 × 10(4)/μl or lower in 8 (28%) patients. The fibrin degradation product (FDP)-level was abnormally high, 10 μg/ml or more, in 16 (57%) patients. The creatine kinase (CK) value was high in 14 of 22 patients, suggesting the presence of myositis. The leukocyte count, FDP, C-reactive protein, and soluble interleukin 2 receptor (sIL2-R) levels were significantly higher in severe cases. In the group without concomitant steroid therapy, mean times of 54.7 h and 101.4 h were required to reduce the temperature to 38°C and 37°C or lower, respectively, after the initiation of tetracycline treatment. There were 6 severe cases: 1 with disseminated intravascular coagulation, 2 with multiorgan failure, 1 with acute respiratory distress syndrome, and 2 with meningoencephalitis. These severe cases formed a group that required 6 or more days to initiate therapy after the onset (P < 0.005 vs non-severe group), showing that delay in diagnosis and therapy is the major cause of aggravation. In the 2 patients complicated by multiorgan failure, the sIL2-R level, produced by activated lymphocytes, was 10 000 U/ml or higher, suggesting that an sIL2-R level of more than 10 000 U/ml can be used as a marker of poor prognosis. It may be better that moderate to severe cases are treated with minocycline plus short-term steroid therapy.


Dengue, HIV and thrombocytopenia


title: Characterization of Angiotensin Converting Enzyme-2 (ACE2) in Human Urine

text: Angiotensin converting enzyme-2 (ACE2) is a recently described membrane-bound carboxypeptidase identified by its homology to ACE, the enzyme responsible for the formation of the potent vasoconstrictor angiotensin II (Ang II). ACE2 inactivates Ang II and is thus thought to act in a counter-regulatory fashion to ACE. ACE2 is highly expressed in epithelial cells of distal renal tubules, and recent evidence indicates that expression is increased in a range of renal diseases. A soluble form of ACE, generated by proteolytic cleavage of the membrane-bound form, has been shown to be present in urine; although evidence for a similar release of ACE2 has been reported in cell culture, it is not yet known whether this occurs in vivo. The present study has identified ACE2 in human urine, both by a sensitive fluorescence-based activity assay and by Western immunoblot. Levels of ACE2 were surprisingly higher than ACE, which may reflect preferential targeting of the enzyme to the luminal surface of the renal epithelium. Future studies will determine whether increased expression of ACE2 in renal diseases are reflected in higher urinary levels of this novel enzyme.


title: Influenza heute und in Zukunft

text: Every year, influenza causes seasonal epidemics and is responsible for increased morbidity and mortality worldwide. In general, clinical signs include fever, respiratory symptoms and myalgia. Human influenza viruses include influenza viruses A/H1N1, A/H3N2, A/H1N1pdm09, influenza virus B and influenza virus C. Wild waterfowl are the natural reservoir of influenza A virus. On a sporadic basis novel viruses can emerge from the zoonotic reservoir and cross the species barrier. In such events clinical presentation in humans can range from mild (e.g. conjunctivitis) to severe pneumonia and acute respiratory distress syndrome (ARDS). In early 2013, a novel avian influenza A virus H7N9 emerged in China and the clinical presentation included bilateral pneumonia with ARDS and a high case fatality rate. In this article a summary is given on diagnosis, therapy and prophylaxis of influenza and on future developments.


ARDS Caused by Herpes Simplex Virus Late After Stem Cell Transplant


title: Extracorporeal Life Support: Four Decades and Counting

text: Extracorporeal membrane oxygenation (ECMO) or extracorporeal life support (ECLS) is a form of heart lung bypass that is used to support neonates, pediatrics, and adult patients with cardiorespiratory failure for days or weeks till organ recovery or transplantation. Venoarterial (VA) and venovenous (VV) ECLS are the most common modes of support. ECLS circuit components and monitoring have been evolving over the last 40 years. The technology is safer, simpler, and more durable with fewer complications. The use of neonatal respiratory ECLS use has been declining over the last two decades, while adult respiratory ECLS is growing especially since the H1N1 influenza pandemic in 2009. This review provides an overview of ECLS evolution over the last four decades, its use in neonatal, pediatric and adults, description of basic principles, circuit components, complications, and outcomes as well as a quick look into the future.


title: A randomized study of imipenem compared to cefotaxime plus piperacillin as initial therapy of infections in granulocytopenic patients

text: The objective of the presented, randomized study was to compare the efficacy of antimicrobial monotherapy with imipenem (3×0.5g/d) to a combination therapy with cefotaxime (3×2g/d) plus piperacillin (3×4g/d) for empirical treatment of infections in neutropenic patients. In 165 patients, 237 infectious episodes were evaluable. The overall response rate of patients treated with cefotaxime plus piperacillin was 67/115 (58%), of those treated with impienem 66/122 (54%). In patients not responding to the initial therapy regimen within 2 or 3 days, the antimicrobial therapy was modified. After therapy modification 85/100 patients were cured. Fever of unknown origin (FUO) showed the most favourable course compared to other infection types, with a response in 46/59 (78%) and in 35/50 (70%) cases, respectively. In comparison, pneumonias were successfully treated in only 3/21 (14%) and 7/37 (19%) cases. Even including patients with modified therapy, only 66% (21/32) of pneumonia episodes responded. The unfavourable results in pneumonias is mainly due to the high rate of 13 systemic mycoses in this group (22%). Overall, a similar response was observed in patients treated with cefotaxime plus piperacillin in comparison with imipenem. In primary bacteremias however, an advantage was observed in patients treated with imipenem (20/27; 74%) compared with cefotaxime plus piperacillin (11/23; 48%).


title: Sepsis mediators

text: During sepsis, the plasma levels of numerous inflammatory markers are enhanced. Some of these markers are the mediators responsible for the syndromes observed during sepsis as well as for organ dysfunction and eventually death. Their role has been demonstrated in experimental models that employed either transgenic and gene-targeted animals or the use of neutralizing agents. Accordingly, anaphylatoxins generated after complement system activation, factors of coagulation and fibrinolysis, proinflammatory cytokines, chemokines, proteases, lipid mediators, nitric oxide, and cell markers of stress (eg, high mobility group box-1) have been shown to contribute to the deleterious events observed during sepsis. On the other hand, the counterregulation of the inflammatory process, which involves mediators such as anti-inflammatory cytokines and some neuromediators, can jeopardize the immune status of the host and render the patients more sensitive to nosocomial infections.


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title: Extrakorporale Herz- und Lungenersatzverfahren: „Extracorporeal membrane oxygenation“, „extracorporeal life support“ und „pumpless extracorporeal lung assist“

text: The use of extracorporeal support systems in cardiac and/or pulmonary failure is an established treatment option. Although scientific evidence is limited there is an increasing amount of data from individual studies, e.g. Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial 2010, suggesting that extracorporeal membrane oxygenation (ECMO) as a veno-venous pump-driven system is a life-saving procedure in severe respiratory failure. Initially established as a rescue option for postcardiotomy cardiac failure extracorporeal life support (ECLS) as a pump-driven veno-arterial cardiovascular support system is increasingly being used in cardiogenic shock after myocardial infarction, as bridging to transplantation or as part of extended cardiopulmonary resuscitation. The pumpless extracorporeal lung assist (pECLA) as an arterio-venous pumpless system is technically easier to handle but only ensures sufficient decarboxylation and not oxygenation. Therefore, this method is mainly applied in primarily hypercapnic respiratory failure to allow lung protective ventilation. Enormous technical improvements, e.g. extreme miniaturization of the extracorporeal assist devices must not obscure the fact that this therapeutic option represents an invasive procedure frequently associated with major complications. With this in mind a widespread use of this technology cannot be recommended and the use of extracorporeal systems should be restricted to centers with high levels of expertise and experience.


title: LOX-1 and Angiotensin Receptors, and Their Interplay

text: The renin-angiotensin system (RAS) plays an important role in regulating blood pressure, water-salt balance and the pathogenesis of cardiovascular diseases. Angiotensin II (Ang II) is the physiologically active mediator and mediates the main pathophysiological actions in RAS. Ang II exerts the effects by activating its receptors, primarily type 1 (AT1R) and type 2 (AT2R). Most of the known pathophysiological effects of Ang II are mediated by AT1R activation. The precise physiological function of AT2R is still not clear. Generally, AT2R is considered to oppose the effects of AT1R. Lectin-like oxidized low-density lipoprotein scavenger receptor-1 (LOX-1) is one of the major receptors responsible for binding, internalizing and degrading ox-LDL. The activation of LOX-1 has been known to be related to many pathophysiological events, including endothelial dysfunction and injury, fibroblast growth, and vascular smooth muscle cell hypertrophy. Many of these alterations are present in atherosclerosis, hypertension, and myocardial ischemia and remodeling. A growing body of evidence suggests the existence of a cross-talk between LOX-1 and Ang II receptors. Their interplays are embodied in the reciprocal regulation of their expression and activity. Their interplays are involved in a series of signals. Recent studies suggests that reactive oxygen species (ROS), nitric oxide (NO), protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) are important signals responsible for their cross-talk. This paper reviews these aspects of dyslipidemia and RAS activation.


title: Blood culture fluorescence rates predict severity and mortality of invasive pneumococcal pneumonia

text: Invasive pneumococcal pneumonia is associated with high rates of mortality. Clinical assessment tools have poor sensitivity for predicting clinical outcomes. Molecular measurements of bacterial load correlate closely with clinical outcome but require specialist facilities and expertise. This study describes how routine blood culture testing can estimate bacterial load and predict clinical outcome for invasive pneumococcal pneumonia. Between December 2009 to March 2014, clinical and laboratory data were collected for 50 patients with Streptococcus pneumoniae bacteraemia secondary to community-acquired pneumonia. Fluorescence rates (FR) were calculated from growth curves generated by BACTEC blood culture analysers by dividing change in fluorescence units (FU), measured at the first point of detectable fluorescence and at the point of automated BACTEC positivity, by time in hours. The mean age of the patients was 70.6 years (49.6–86.3). Forty patients survived invasive pneumococcal disease and ten patients died. These two groups did not significantly differ by demographic or clinical characteristics. The mean FR for the non-survival group (3.62 × 10(−3) FU/h) was significantly higher (p < 0.001) than that of the survival group (1.73 × 10(−3) FU/h). FR did not vary by serotype. We determined that an FR of 2.59 × 10(−3) FU/h might represent a useful threshold for predicting high mortality risk with a sensitivity of 91 % and a specificity of 97 %. Our FR calculation uses cheap and accessible routine blood culture techniques to predict mortality in a small retrospective cohort study. In patients admitted to hospital with pneumococcal bacteraemia and, potentially, other organisms, this single tool could guide early escalation of clinical care.


title: Clinical and imaging correlates of EEG patterns in hospitalized patients with encephalopathy

text: To identify the relationship between pathologic electroencephalographic (EEG) patterns, clinical and neuroradiological abnormalities, and outcome in hospitalized patients with acute encephalopathy. This 5-year cohort study was performed at an academic tertiary care center. EEGs in 154 patients with altered mental status were classified according to five predefined patterns: Isolated continuous slowing of background activity (theta, theta/delta, and delta activity) and patterns with slowing background activity with episodic transients [i.e., triphasic waves (TWs) or frontal intermittent delta activity (FIRDA)]. Clinical characteristics, blood tests and neuroimaging were compared among groups. Associations between EEG patterns and structural and non-structural abnormalities were calculated. Glasgow Outcome Score >3 at discharge was defined as favorable and 1–3 as unfavorable outcome. In multivariable analyses, theta was associated with brain atrophy (OR 2.6, p = 0.020), theta/delta with intracerebral hemorrhages (OR 6.8, p = 0.005), FIRDA with past cerebrovascular accidents (OR 2.7, p = 0.004), TWs with liver or multi-organ failure (OR 6, p = 0.004; OR 4, p = 0.039), and delta activity with alcohol/drug abuse with or without intoxication, and HIV infection (OR 3.8, p = 0.003; OR 9, p = 0.004). TWs were associated with death (OR 4.5, p = 0.005); theta/delta with unfavorable outcomes (OR 2.5, p = 0.033), while patients with FIRDA had favorable outcomes (OR 4.8, p = 0.004). In encephalopathic patients, well-defined EEG patterns are associated with specific pathological conditions and outcomes, suggesting that mechanistic hypotheses underlie these abnormal EEG patterns. To clarify the respective contributions of non-structural and structural abnormalities to encephalopathy reflected in specific EEG patterns, prospective studies using continuous EEG monitoring during the acute onset of encephalopathy are needed.


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title: The abstracts of the 26th congress of ESCTAIC, Timisoara, Romania, September 22–24 2016


title: Imaging pulmonary disease in AIDS: state of the Art

text: The spectrum of pulmonary diseases in AIDS including infections and neoplasms that affect the lungs are reviewed. Characteristic plain film and CT findings are illustrated.


title: Herpes simplex virus 1 pneumonia: conventional chest radiograph pattern

text: The aim of this study was to describe the findings on plain chest radiographs in patients with herpes simplex virus pneumonia (HSVP). The study was based on 17 patients who at a retrospective search have been found to have a monoinfection with herpes simplex virus. The diagnosis was established by isolation of the virus from material obtained during fiberoptic bronchoscopy (FOB) which also included broncho-alveolar lavage and tissue sampling. Fourteen patients had a chest radiograph performed within 24 h of the date of the FOB. Two radiographs showed no abnormalities of the lung parenchyma. The radiographs of the other 12 patients showed lung opacification, predominantly lobar or more extensive and always bilateral. Most patients presented with a mixed airspace and interstitial pattern of opacities, but 11 of 14 showed at least an airspace consolidation. Lobar, segmental, or subsegmental atelectasis was present in 7 patients, and unilateral or bilateral pleural effusion in 8 patients, but only in 1 patient was it a large amount. In contradiction to the literature which reports a high correlation between HSVP and acute respiratory distress syndrome (ARDS), 11 of 14 patients did not meet the pathophysiological criteria for ARDS. The radiologist may suggest the diagnosis of HSVP when bilateral airspace consolidation or mixed opacities appear in a susceptible group of patients who are not thought to have ARDS or pulmonary edema. The definite diagnosis of HSV pneumonia can be established only on the basis of culture of material obtained by broncho-alveolar lavage.


title: Diabetic lung disease: fact or fiction?

text: Diabetes mellitus is a chronic, progressive, incompletely understood metabolic disorder whose prevalence has been increasing steadily worldwide. Even though little attention has been paid to lung disorders in the context of diabetes, its prevalence has recently been challenged by newer studies of disease development. In this review, we summarize and discuss the role of diabetes mellitus involved in the progression of pulmonary diseases, with the main focus on pulmonary fibrosis, which represents a chronic and progressive disease with high mortality and limited therapeutic options.


title: Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease

text: We report on 12 patients with chronic granulomatous disease transplanted with hematopoietic stem cells from matched unrelated (n = 9) or matched sibling donors (n = 3). The most common infectious complication was pulmonary aspergillosis, which nine patients had previously developed. Only 5 of 12 individuals had normal lung function prior to transplantation. At a mean follow-up of 53 months 9 of the 12 patients are alive including 7 of 9 following matched unrelated donor (MUD) transplantation. One patient died from ARDS, another from systemic BK virus infection, the third from complications of chronic graft-versus-host disease. Seven of nine surviving patients have normal lung function now. HSCT from a MUD is an option worth considering when no matched family donor is available. Restricted lung function prior to HSCT does not appear to be a limiting factor for such treatment.


title: Neuropathological alterations in drug abusers: The involvement of neurons, glial, and vascular systems

text: Because the effects of drug abuse on the cellular elements of the human brain have not been studied systematically, an investigation was performed using histology, immunohistochemistry, and morphometry. The main cortical and subcortical brain areas of 50 polydrug deaths were analyzed as compared with controls. In the brains of drug abusers, a significant neuronal loss was present. Interestingly, the number of glial fibrillary acidic protein (GFAP)-positive astrocytes was reduced. the numerical density of perivascular and parenchymal microglia was increased in the white matter and in most subcortical regions. In the white matter there were widespread β-amyloid precursor protein deposits. Furthermore, there was a prominent vascular hyalinosis, endothelial cell proliferation, and a loss of immunoreactivity for collagen type IV within the vascular basal lamina. The neuronal loss seems to be the result of a direct impairment of nerve cells and, indirectly, to a damage of astrocytes, axons, and the microvasculature. The reduction of GFAP-positive astrocytes is also indicative of a drug-induced damage. The axonal injury suggests a toxic-metabolic drug effect, whereas the concomitant activation of microglia is indicative of a long-standing progressive process. The noninflammatory vasculopathy can be considered as the morphological substrate of a disturbed blood-brain barrier. Our findings demonstrate that drugs of abuse initiate a cascade of interacting toxic, vascular, and hypoxic factors that finally result in widespread disturbances within the complex network of central nervous system cell-cell interactions.


title: Modulation of Airway Responsiveness to Acetylcholine by Nitric Oxide in a Rabbit Model

text: Nitric oxide (NO) is an important mediator in the regulation of bronchial muscle tone and airway responsiveness. We investigated the influence of exogenous NO on airway responsiveness to acetylcholine aerosols (ACH) in normal and in hyperresponsive rabbits. White New Zealand rabbits were anesthetized, intubated, and breathed room air spontaneously. Responses of respiratory parameters in ACH challenge tests were measured. In group A the influence of NO on ACH infusion-induced airway constriction was measured. Airway responses to aerosols from 0.25 to 8.0% ACH solutions in saline were measured with 150 and 300 ppm NO inhalation (groups B and C) and compared with the same animals' responses without NO. Moreover, we examined the influence of NO synthase inhibition on airway responsiveness (group D) and the modulatory effect of NO in hyperresponsive animals (group E). 300 ppm NO inhalation significantly decreased the bronchoconstrictor response to intravenously administered ACH (group A). However, the baseline value of dynamic elastance (E(dyn)) was only marginally lower under the influence of 300 ppm NO. During inhalation of 150 or 300 ppm NO, responses to nebulized 2.0% and less ACH solutions remained nearly unaltered. Responses to aerosols of 4.0 and 8.0% diminished significantly (groups B and C). Following 40 min of aerosolized N-nitro-l-arginine-methyl ester (l-NAME) solution (a NO synthase inhibitor, 1.2 mM) inhalation, the response of E(dyn) to ACH increased significantly in group D. In group E, animals inhaled 500 mg/m(3) ammonium persulfate (APS), an oxidant with various industrial applications, after the first ACH challenge test (0.2, 1.0, and 2.0% ACH). After 2 h of APS exposure, the ACH-induced broncho constriction was increased significantly in the challenge test. After another 2 h of APS inhalation, the airway responsiveness to ACH was tested under the influence of 300 ppm NO. NO significantly decreased the response to ACH to almost the same level as before APS exposure. The results indicate that responses to high ACH concentrations as well as an APS-induced increase in ACH responsiveness were effectively reduced by high concentrations of inhaled NO.


title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat

text: In the present study, we evaluated the protective effect of oral insulin (OI) on intestinal mucosa following lipopolysaccharide-induced intestinal damage in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats, LPS-rats that were treated with lipopolysaccharide (LPS), and LPS-INS rats that were treated with OI given in drinking water 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, enterocyte apoptosis, and mucosal expression of Toll-like receptor 4 (TLR4) were determined 24 h after the last LPS injection. LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPS- animals. LPS rats demonstrated 50% increase in TLR4 expression in jejunum compared to sham animals. Treatment with OI resulted in a three-fold increase in TLR4 expression in jejunum, compared to LPS animals. In conclusion, OI improves intestinal recovery after LPS endotoxemia in a rat.


title: Human avian influenza A (H5N1) virus infection in China

text: Highly pathogenic influenza A (H5N1) virus causes a widespread poultry deaths worldwide. The first human H5N1 infected case was reported in Hong Kong Special Administrative Region of China in 1997. Since then, the virus re-emerged in 2003 and continues to infect people worldwide. Currently, over 400 human infections have been reported in more than 15 countries and mortality rate is greater than 60%. H5N1 viruses still pose a potential pandemic threat in the future because of the continuing global spread and evolution. Here, we summarize the epidemiological, clinical and virological characteristics of human H5N1 infection in China monitored and identified by our national surveillance systems.


docid: hjbsqkgs

title: IL-27 is Elevated in Acute Lung Injury and Mediates Inflammation

text: Cytokines play a critical role in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here we investigated whether IL-27 was elevated in patients with ALI/ARDS and its potential clinical significance. Bronchoalveolar lavage (BAL) and serum samples were obtained from 58 ALI/ARDS patients, and 25 control healthy volunteers. IL-27 and other inflammatory mediators were measured in BAL and serum by ELISA. Besides, a mouse model of cecal ligation and puncture (CLP)-induced lung inflammation/injury was established, and serum, BAL fluid and tissues were collected for analyses in the presence or absence of IL-27 neutralizing antibodies. BAL IL-27 was found to be significantly higher in patients with ALI/ARDS than that in controls, particularly of pulmonary origin; serum IL-27 was also significantly higher. Increased IL-27 was associated with markers of inflammation, and correlated with disease severity of patients in ALI/ARDS. In a mouse model of CLP-induced lung inflammation/injury, elevated IL-27 levels were observed in the lung, serum, and BAL fluids. IL-27 neutralizing antibody treatment reduced pulmonary inflammation and lung injury and improved mouse survival in response to CLP. Therefore, IL-27 is a critical cytokine in ALI/ARDS and inhibition of IL-27 may open a promising approach for ALI/ARDS patients.


docid: mwtqxwbw

title: SOCS-1 Suppresses Inflammation Through Inhibition of NALP3 Inflammasome Formation in Smoke Inhalation-Induced Acute Lung Injury

text: Smoke inhalation leads to acute lung injury (ALI), a devastating clinical problem associated with high mortality rates. Suppressor of cytokine signaling-1 (SOCS-1) is a negative regulator of proinflammatory cytokine signaling. We have found that adenoviral gene transfer of SOCS-1 ameliorates smoke inhalation-induced lung injury in C57BL/6 mice. We also found that the release of adenosine triphosphate (ATP) was increased post smoke exposure, while oxidized ATP, an inhibitor of purinergic P2X7 receptor, suppressed smoke-induced NALP3 inflammasome assembly, caspase-1 activation, and K(+) efflux. Similar to oxidized ATP, high protein level of SOCS-1 dampened the formation of NALP3 inflammasome and the activation of caspase-1 and IL-1β induced by smoke exposure in mouse alveolar macrophages. In conclusion, SOCS-1 relieves smoke inhalation-induced pulmonary inflammation and injury by inhibiting NALP3 inflammasome formation.


title: Surgical Resection and Prognostic Analysis of 142 Cases of Hilar Cholangiocarcinoma

text: Surgical resection for hilar cholangiocarcinoma is the only curative option, but low resectability rate and poor survival outcomes remain a challenge. This study was to assess the surgical resection for hilar cholangiocarcinoma and analyze the prognostic factors influencing postoperative survival. One hundred forty-two patients with hilar cholangiocarcinoma who underwent surgical resection between January 2006 and December 2014 were analyzed retrospectively based on clinicopathological and demographic data. Univariate and multivariate analysis against outcome were employed to identify potential factors affecting prognosis. Ninety-five patients were performed with R0 resection with median survival time of 22 months; whereas, 47 patients underwent non-R0 resection (R1 = 20, R2 = 27) with that of 10 months. Of these 95 patients, 19 underwent concomitant with vascular resection and reconstruction and 2 patients underwent pancreaticoduodenectomy. 64.8% patients (n = 92) underwent combined with hepatectomy. The one-year, three-year, and five-year survival rates after R0 resection were 76.3, 27.8, 11.3%, respectively, which was significantly better than that after non-curative resection (P = 0.000). Multivariate analysis revealed that non-curative resection (RR: 2.414, 95% CI 1.586–3.676, P = 0.000), pathological differentiation (P = 0.015) and preoperative serum total bilirubin above 10 mg/dL (RR: 1.844, 95% CI 1.235–2.752, P = 0.003) were independent prognostic factors. Aggressive curative resection remains to be the optimal option for hilar cholangiocarcinoma. Non-curative resection, pathological differentiation, and preoperative serum total bilirubin above 10 mg/ dL were associated with dismal prognosis.


title: T-cell large granular lymphocyte leukemia: an Asian perspective

text: To characterize T-cell large granular leukemia in Asia, 22 Chinese patients from a single institute were reported, together with an analysis of 88 Asian and 272 Western patients identified from the literature. In our cohort, anemia due to pure red cell aplasia (PRCA) occurred in 15/22 (68%) of cases, being the most common indication for treatment. Neutropenia was only found in 8/22 (36%) cases, and recurrent infections, the most important clinical problem in Western patients, were not observed. None of our cases presented with rheumatoid arthritis. These clinical features were consistently observed when compared with the 88 other Asian patients. Combined data from our cohort and other Asian cases showed that Asian patients, compared with Western patients, had more frequent anemia (66/110, 60% versus 113/240, 47%; p = 0.044), attributable to a much higher incidence of PRCA (52/110, 47% versus 6/143, 4%; p < 0.001). However, Western patients presented more frequently than Asian patients with neutropenia (146/235, 62% versus 33/110, 30%; p < 0.001) and splenomegaly (99/246, 40% versus 16/110, 15%; p < 0.001). Notably, Western patients were about eight to ten times more likely than Asian patients to have rheumatoid arthritis (73/272, 27% versus 4/106, 4%; p < 0.001) and recurrent infections (81/272, 30% versus 3/107, 3%; p < 0.001). These clinicopathologic differences have important implications on disease pathogenesis and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00277-009-0895-3) contains supplementary material, which is available to authorized users.


title: Characterization of viral genomic mutations in novel influenza A (H7N9)-infected patients: the association between oseltamivir-resistant variants and viral shedding duration

text: Since February 2013, human infections with the novel influenza A H7N9 virus have occurred in eastern China. It is important to detect mutations in viral genes and analyze the clinical features of patients and viral shedding duration related to neuraminidase inhibitor (NAI) resistance. We collected clinical specimens from 31 hospitalized H7N9 patients and sequenced NA, PB2, HA, and M gene fragments. Of the 31 identified patients, 7 (22.6%) carried the R292K substitution in NA, 30 (96.8%), 3 (9.7%), and 5 (16.1%) carried E627K, Q591K, and D701N mutations in PB2, respectively, and 2 (6.5%) carried both E627K and D701N mutations in PB2. All 26 identified patients harbored Q226L mutations and possessed only a single arginine (R) at cleavage sites in the HA and a S31N mutation in M2. Among 7 NA-R292K mutated patients, 3 died and 4 were discharged. There was no significant difference in the days that patients started oseltamivir treatment after symptom onset between NA-R292K mutant and NA-R292 wild-type patients (median days, 7 vs 6, P = 0.374). NA-R292K mutant patients had a significantly longer duration of viral shedding than NA-R292 wild-type patients after oseltamivir treatment (median days, 10 vs 5, P = 0.022). The mutation of R292K in NA conferring the potential ability of oseltamivir resistance resulted in prolonged viral duration and poor outcome and should be taken into consideration in the clinical management of infected patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-019-01678-8) contains supplementary material, which is available to authorized users.


title: Immunosuppressed patients with pandemic influenza A 2009 (H1N1) virus infection

text: The purpose of this paper was to prospectively characterize the clinical manifestations and outcomes of confirmed influenza A 2009 (H1N1) virus infection in immunosuppressed patients with hospital admission and compare them with those of a general population. A multicenter prospective cohort study was carried out. All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009 (H1N1) virus infection from June 12, 2009 to November 11, 2009 were included. Risk factors for complicated influenza infection were studied in immunosuppressed patients. Overall, 559 patients were included, of which 56 were immunosuppressed, nine with solid or hematological malignancies, 18 with solid-organ transplant recipients, 13 with corticosteroid therapy, and six with other types of immunosuppression. Clinical findings at diagnosis were similar in both groups. Nineteen immunosuppressed patients had pneumonia (33.9%). Immunosuppressed patients with pandemic influenza had bacterial co-infection more frequently (17.9% vs. 6.4%, p = 0.02), specifically, gram-negative bacilli and Staphylococcus aureus infections. Mortality was higher in immunosuppressed patients (7.1% vs. 1.8%, p < 0.05). The only modifiable risk factor of complicated influenza A 2009 (H1N1) was delayed antiviral therapy. In immunosuppressed patients, influenza A 2009 (H1N1) virus infection has higher mortality than in non-immunosuppressed individuals. Bacterial co-infection is common in complicated cases.


Invasive streptococcal infections


title: Drug Antioxidant Effects: A Basis for Drug Selection?

text: A free radical is any species capable of independent existence that contains one or more unpaired electrons. Free radical reactions have been implicated in the pathology of more than 50 human diseases. Radicals and other reactive oxygen species are formed constantly in the human body, both by deliberate synthesis (e.g. by activated phagocytes) and by chemical side- reactions. They are removed by enzymic and nonenzymic antioxidant defence systems. Oxidative stress, occurring when antioxidant defences are inadequate, can damage lipids, proteins, carbohydrates and DNA. A few clinical conditions are caused by oxidative stress, but more often the stress results from the disease. Sometimes it then makes a significant contribution to the disease pathology, and sometimes it does not. Several antioxidants are available for therapeutic use. They include molecules naturally present in the body [superoxide dismutase (SOD), α-tocopherol, glutathione and its precursors, ascorbic acid, adenosine, lactoferrin and carotenoids] as well as synthetic antioxidants [such as thiols, ebselen (PZ51), xanthine oxidase inhibitors, inhibitors of phagocyte function, iron ion chelators and probucol]. The therapeutic efficacy of SOD, α- tocopherol and ascorbic acid in the treatment of human disease is generally unimpressive to date although dietary deficiencies of the last two molecules should certainly be avoided. Xanthine oxidase inhibitors may be of limited relevance as antioxidants for human use. Exciting preliminary results with probucol (antiatherosclerosis), ebselen (anti-inflammatory), and iron ion chelators (in thalassaemia, leukaemia, malaria, stroke, traumatic brain injury and haemorrhagic shock) need to be confirmed by controlled clinical trials. Clinical testing of N-acetylcysteine in HIV-1-positive subjects may also be merited. A few drugs already in clinical use may have some antioxidant properties, but this ability is not widespread and drug- derived radicals may occasionally cause significant damage.


title: Long-Term Neurocognitive Function of Pediatric Patients with Severe Combined Immune Deficiency (SCID): Pre- and Post-Hematopoietic Stem Cell Transplant (HSCT)

text: BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is the only cure for patients with severe combined immunodeficiency (SCID). The purpose of this study was to evaluate long-term neurodevelopment of patients with SCID following myeloablative chemotherapy and HSCT. MATERIALS AND METHODS: Sixteen pediatric patients diagnosed with SCID were tested using the Bayley Scales of Infant Development and the validated Vineland Adaptive Behavior Scales (VABS) pre- and 1-year post-HSCT. Three years post-HSCT, there were 11 patients available for testing and four patients available 5 years post-HSCT. Patients greater than 3 years of age were administered the Wechsler Preschool and Primary Scale of Intelligence. Both raw scores and scaled scores were analyzed. RESULTS: There was a significant decrease 1 year post-HSCT in the Bayley Mental Developmental Index (MDI) [92.5 (pre) vs. 70.81 (1 year post), p < 0.0001] and the VABS [99.73 (pre) vs. 79.87 (1 year post), p = <0.0001]. There was a significant decrease over time in the MDI [95.00 (pre) vs. 72.64 (1 year post) vs. 71.82 (3 years post), p < 0.0001], but no significant change between 1 and 3 years post-HSCT. There was no change in the Bayley Psychomotor Development Scale (PDI) [82.4 (pre) vs. 84.8 (1 year post), p = 0.68]. The PDI scores decreased over time [86.29 (pre) vs. 86 (1 year post) vs. 74.14 (3 years post), p = 0.045]. Although there was a decrease in scaled scores, there was not a loss of skills. Analysis of raw scores showed that there was an increase in the raw test scores, which indicated that these children acquired developmental skills, but at a slower rate than normal infants and toddlers. Younger children had a more significant decrease in adaptive scores compared with older children. CONCLUSIONS: These findings may reflect the effects of the isolation and prolonged hospitalization that characterizes the immediate post-transplant period. Patients miss out on social interactions and learning opportunities that normally occur at their respective stages of development. These restrictions keep patients from acquiring developmentally appropriate cognitive skills as well as gross and fine motor developmental milestones. Longitudinal follow-up will be important to quantify acquisition of skills.


title: Another case of “European hantavirus pulmonary syndrome” with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages

text: Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.


title: Protective Effects of Neural Crest-Derived Stem Cell-Conditioned Media against Ischemia-Reperfusion-Induced Lung Injury in Rats

text: Current treatments for ischemia-reperfusion (IR)-induced acute lung injury are limited. Mesenchymal stem cell-conditioned medium (CM) has been reported to attenuate lung injury. Neural crest stem cells (NCSCs), a type of multipotent stem cells, are more easily obtained than mesenchymal stem cells. We hypothesize that NCSC-CM has anti-inflammatory properties that could protect against IR-induced lung injury in rats. In this study, NCSC-CM was derived from rat NCSCs. Typical acute lung injury was induced by 30-min ischemia followed by 90-min reperfusion in adult male Sprague–Dawley rats. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected to analyze the degree of lung injury after the experiment. NCSC-CM was administered before ischemia and after reperfusion. NCSC-CM treatment significantly attenuated IR-induced lung edema, as indicated by decreases in pulmonary vascular permeability, lung weight gain, wet to dry weight ratio, lung weight to body weight ratio, pulmonary arterial pressure, and protein level in BALF. The levels of tumor necrosis factor-α and interleukin-6 in the BALF were also significantly decreased. Additionally, NCSC-CM improved lung pathology and neutrophil infiltration in the lung tissue, and significantly suppressed nuclear factor (NF)-κB activity and IκB-α degradation in the lung. However, heating NCSC-CM eliminated these protective effects. Our experiment demonstrates that NCSC-CM treatment decreases IR-induced acute lung injury and that the protective mechanism may be attributable to the inhibition of NF-κB activation and the inflammatory response. Therefore, NCSC-CM may be a novel approach for treating IR-induced lung injury.


title: Association of surfactant protein B gene polymorphisms (C/A-18, C/T1580, intron 4 and A/G9306) and haplotypes with bronchopulmonary dysplasia in chinese han population

text: This study aimed to investigate the association between surfactant protein B (SP-B) polymorphisms and bronchopulmonary dysplasia (BPD) in Chinese Han infants. We performed a casecontrol study including 86 infants with BPD and 156 matched controls. Genotyping was performed by sequence specific primer-polymerase chain reaction (PCR) and haplotypes were reconstructed by the fastPHASE software. The results showed that significant differences were detected in the genotype distribution of C/A-18 and intron 4 polymorphisms of SP-B gene between cases and controls. No significant differences were detected in the genotype distribution of C/T1580 or A/G9306 between the two groups. Haplotype analysis revealed that the frequency of A-del-C-A haplotype was higher in case group (0.12 to 0.05, P=0.003), whereas the frequency of C-inv-C-A haplotype was higher in control group (0.19 to 0.05, P=0.000). In addition, a significant difference was observed in the frequency of C-inv-T-A haplotype between the two groups. It was concluded that the polymorphisms of SP-B intron 4 and C/A-18 could be associated with BPD in Chinese Han infants, and the del allele of intron 4 and A allele of C/A-18 might be used as markers of susceptibility in the disease. Haplotype analysis indicated that the gene-gene interactions would play an important part in determining susceptibility to BPD.


title: Prognostic importance of pretransplant disease status for posttransplant outcomes in patients with adult T cell leukemia/lymphoma

text: Adult T cell leukemia/lymphoma (ATL) is an aggressive T cell lymphoma with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be a curative treatment for ATL, a significant proportion of allo-HSCT recipients suffer from relapse/progression of ATL. Here we aimed to clarify the risk factors for and outcomes after posttransplant relapse/progression. We retrospectively reviewed 76 patients with ATL who received allo-HSCT at our institute. At the time of allo-HSCT, disease status was complete response in 17 patients, partial response in 29, stable disease (SD) in 18, and progressive disease (PD) in 12. In multivariate analysis, SD/PD at allo-HSCT, lymphoma subtype, reduced-intensity conditioning regimen, and time from diagnosis to allo-HSCT were associated with risk of relapse/progression. After allo-HSCT, 26 patients had relapse/progression at a median of 66 days (range, 13–2064 days). The 2-year overall survival rate after relapse/progression was only 19%. Compared with acute-type, lymphoma-type experienced local recurrence more frequently (1/15 acute vs. 7/11 lymphoma, P < 0.01) and had a significantly longer OS after relapse/progression (median; 112 days in acute vs. 554 days in lymphoma, P < 0.01). Since the prognosis of patients with ATL who experienced relapse/progression after allo-HSCT was poor, strategies to reduce the risk of these outcomes are warranted.


Heat shock protein 70 and the acute respiratory distress syndrome


title: Pulmonary complications of liver transplantation: radiological appearance and statistical evaluation of risk factors in 300 cases

text: The aim of this study was to evaluate the incidence, radiographic appearance, time of onset, outcome and risk factors of non-infectious and infectious pulmonary complications following liver transplantation. Chest X-ray features of 300 consecutive patients who had undergone 333 liver transplants over an 11-year period were analysed: the type of pulmonary complication, the infecting pathogens and the mean time of their occurrence are described. The main risk factors for lung infections were quantified through univariate and multivariate statistical analysis. Non-infectious pulmonary abnormalities (atelectasis and/or pleural effusion: 86.7 %) and pulmonary oedema (44.7 %) appeared during the first postoperative week. Infectious pneumonia was observed in 13.7 %, with a mortality of 36.6 %. Bacterial and viral pneumonia made up the bulk of infections (63.4 and 29.3 %, respectively) followed by fungal infiltrates (24.4 %). A fairly good correlation between radiological chest X-ray pattern, time of onset and the cultured microorganisms has been observed in all cases. In multivariate analysis, persistent non-infectious abnormalities and pulmonary oedema were identified as the major independent predictors of posttransplant pneumonia, followed by prolonged assisted mechanical ventilation and traditional caval anastomosis. A “pneumonia-risk score” was calculated: low-risk score ( < 2.25) predicts 2.7 % of probability of the onset of infections compared with 28.7 % of high-risk ( > 3.30) population. The “pneumonia-risk score” identifies a specific group of patients in whom closer radiographic monitoring is recommended. In addition, a highly significant correlation (p < 0.001) was observed between pneumonia-risk score and the expected survival, thus confirming pulmonary infections as a major cause of death in OLT recipients.


title: Zoonotic Influenza and Human Health—Part 2: Clinical Features, Diagnosis, Treatment, and Prevention Strategies

text: PURPOSE OF REVIEW: Zoonotic influenza viruses are those influenza viruses that cross the animal-human barrier and can cause disease in humans, manifesting from minor respiratory illnesses to multiorgan dysfunction. The increasing incidence of infections caused by these viruses worldwide has necessitated focused attention to improve both diagnostic as well as treatment modalities. In this second part of a two-part review, we discuss the clinical features, diagnostic modalities, and treatment of zoonotic influenza, and provide an overview of prevention strategies. RECENT FINDINGS: Illnesses caused by novel reassortant avian influenza viruses continue to be detected and described; most recently, a human case of avian influenza A(H7N4) has been described from China. We continue to witness increasing rates of A(H7N9) infections, with the latest (fifth) wave, from late 2016 to 2017, being the largest to date. The case fatality rate for A(H7N9) and A(H5N1) infections among humans is much higher than that of seasonal influenza infections. Since the emergence of the A(H1N1) 2009 pandemic, and subsequently A(H7N9), testing and surveillance for novel influenzas have become more effective. Various newer treatment options, including peramivir, favipiravir (T-705), and DAS181, and human or murine monoclonal antibodies have been evaluated in vitro and in animal models. SUMMARY: Armed with robust diagnostic modalities, antiviral medications, vaccines, and advanced surveillance systems, we are today better prepared to face a new influenza pandemic and to limit the burden of zoonotic influenza than ever before. Sustained efforts and robust research are necessary to efficiently deal with the highly mutagenic zoonotic influenza viruses.


title: Mechanical ventilation of mice

text: Due to growing interest in murine functional genomics research, there is an increasing need for physiological stable in vivo murine models. Of special importance is support and control of ventilation by artificial respiration, which is difficult to execute as a consequence of the small size of the animal and the technically demanding breathing pattern. In addition, numerous genetically altered mice show depressed spontaneous ventilation or impaired respiratory responses. After an introduction in murine respiratory physiology we describe options for ventilatory support, its monitoring and the potential side effects. This review will provide an overview on current possibilities in the field of airway support in mouse research.


title: Letaler Verlauf einer Varizella-Zoster-Sepsis bei einem 22-jährigen Patienten

text: Infection with Varicella zoster virus (VZV) usually occurs in children up to 15 years with mild symptoms. We present a case of a 22-year old man with a fatal varicella zoster infection. He developed fulminant hepatitis with acute liver failure and an acute respiratory distress syndrom (ARDS). In this article the general aspects of VZV infection are discussed. Treatment options and previous publications are reviewed.


title: Pulmonary Toxoplasmosis, a Rare but Severe Manifestation of a Common Opportunistic Infection in Late HIV Presenters: Report of Two Cases

text: Pulmonary toxoplasmosis is rare, particularly in the era of highly active antiretroviral therapy (HAART). Here, we describe two severe cases in patients not known to be HIV-infected. In both patients, early diagnosis and therapy led to a favourable outcome. Pulmonary toxoplasmosis should be considered in the differential diagnosis in potentially HIV-infected patients with respiratory symptoms.


title: Glutathione and inflammatory disorders of the lung

text: Glutathione (GSH) is an essential tripeptide present in most eukaryotic cells. Because of its sulfhydryl group, GSH is a versatile molecule capable of protecting cells against oxidants and toxic xenobiotics. However, it also plays key roles in multiple metabolic pathways, such as the synthesis of certain leukotrienes, proteins, and DNA precursors as well as the activation of enzymes, the regulation of immune responses and others. Not only is GSH synthesized by cells for local use but it also participates in an elaborate intercellular exchange process regulated by theγ-glutamyl cycle. Extracellular GSH in plasma and in alveolar epithelial lining fluid is thus subject to variations according to the degree of expression ofγ-glutamyl cycle enzymes and the rate of consumption of GSH by electrophilic molecules. Bronchoalveolar lavage has allowed us to observe many of these variations of GSH within the extracellular environment of the normal and diseased human lung. Studies of lung GSH have lead to a better understanding of pathogenic processes and have stimulated investigations of novel therapeutic approaches in lung inflammatory disorders.


title: Primary Immunodeficiency Disorders in Kuwait: First Report from Kuwait National Primary Immunodeficiency Registry (2004–2006)

text: Primary immunodeficiency disorders are heterogeneous group of illnesses that predispose patients to serious complications. Registries for these disorders have provided important epidemiological data and shown both racial and geographical variations. The clinical features of 76 patients with primary immunodeficiency disorders registered in Kuwait National Primary Immunodeficiency Registry from 2004 to 2006 were recorded. Ninety-eight percent of the patients presented in childhood. The prevalence of these disorders in children was 11.98 in 100,000 children with an incidence of 10.06 in 100,000 children. The distribution of these patients according to each primary immunodeficiency category is: combined T and B cell immunodeficiencies (21%), predominantly antibody immunodeficiency (30%), other well defined immunodeficiencies (30%), diseases of immune dysregulation (7%), congenital defects of phagocyte number, function or both (8%), and complement deficiencies (4%). The consanguinity rate within the registered patients was 77%. The patients had a wide range of clinical features affecting different body systems. Primary immunodeficiency disorders are prevalent in Kuwait and have a significant impact into the health system.


title: Apelin-12 and its structural analog enhance antioxidant defense in experimental myocardial ischemia and reperfusion

text: This study investigated the effects of peptide apelin-12 (H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH, A12) and its novel structural analog (H-(N(α)Me)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe-OH, AI) on myocardial antioxidant enzyme activities, lipid peroxidation, and reactive oxygen species formation in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury. Isolated working rat hearts were subjected to global ischemia and reperfusion. Infusion of 140 μM A12 or AI before global ischemia improved cardiac function recovery; increased the activity of Cu,Zn superoxide dismutase (Cu,Zn SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); decreased malondialdehyde (MDA) content in reperfused heart; and reduced the formation of hydroxyl radical adduct of the spin trap 5,5-dimethyl-1-pyrroline-N-oxide in the myocardial effluent during early reperfusion compared with these indices in control. Anesthetized open-chest rats were subjected to the left anterior descending coronary artery occlusion and coronary reperfusion. Peptide A12 or its analog AI was injected intravenously at the onset of reperfusion at a dose of 0.35 μmol/kg. Treatment with A12 or AI significantly limited infarct size and reduced the activity of lactate dehydrogenase and creatine kinase MB isoenzyme in blood plasma at the end of reperfusion compared with control. These effects were accompanied by complete recovery of Cu,Zn SOD, CAT, and GSH-Px activities; and decrease in MDA content in the area at risk by the end of reperfusion. The study concluded that C-terminal fragment of native peptide apelin-12 and its synthesized analog is involved in the upregulation of cardiac antioxidant defense systems and attenuation of lipid peroxidation in myocardial I/R injury.


title: What’s new in surfactant?: A clinical view on recent developments in neonatology and paediatrics

text: Surfactant therapy has significantly changed clinical practice in neonatology over the last 25 years. Recent trials in infants with respiratory distress syndrome (RDS) have not shown superiority of any natural surfactant over another. Advancements in the development of synthetic surfactants are promising, yet to date none has been shown to be superior to natural preparations. Ideally, surfactant would be administered without requiring mechanical ventilation. An increasing number of studies investigate the roles of alternative modes of administration and the use of nasal continuous positive airway pressure to minimise the need for mechanical ventilation. Whether children with other lung diseases benefit from surfactant therapy is less clear. Evidence suggests that infants with meconium aspiration syndrome and children with acute lung injury/acute respiratory distress syndrome may benefit, while no positive effect of surfactant is seen in infants with congenital diaphragmatic hernia. However, more research is needed to establish potential beneficial effects of surfactant administration in children with lung diseases other than RDS. Furthermore, genetic disorders of surfactant metabolism have recently been linked to respiratory diseases of formerly unknown origin. It is important to consider these disorders in the differential diagnosis of unexplained respiratory distress although no established treatment is yet available besides lung transplantation for the most severe cases. Conclusion: Research around surfactant is evolving and recent developments include further evolution of synthetic surfactants, evaluation of surfactant as a therapeutic option in lung diseases other than RDS and the discovery of genetic disorders of surfactant metabolism. Ongoing research is essential to continue to improve therapeutic prospects for children with serious respiratory disease involving disturbances in surfactant.


title: Radiologic imaging of the transplanted bowel

text: BACKGROUND: The radiologic evaluation of the transplanted bowel is largely unknown and rather complex because it involves several techniques that depend on indications and times that have not been fully defined. METHODS: From December 2000 to November 2002 in the Section of Radiology I of the University of Modena and Reggio Emilia (Modena, Italy), 11 patients with transplanted bowel were studied with different methods: traditional radiologic evaluation with contrast agent (all patients), evaluation of transit time with radiopaque markers (five patients), ultrasonographic (US) evaluation of the intestinal wall and Doppler US of the vascular axes (five patients), computed tomographic (CT) evaluation (all patients), and magnetic resonance (MR) evaluation of the bowel and the vascular axes (five patients). Traditional contrast examination enabled evaluation of the gastroesophageal transit and cardia functionality; anatomy and integrity of the anastomoses (proximal and distal); time of gastric emptying; morphology, tone, and kinesis of the transplanted small bowel loops and time of global transit. The study of transit with radiopaque markers was carried out in five patients to define the time of transit through the entire transplanted bowel, confirm recovery of intestinal motility, and identify possible abnormalities. The US examination was carried out in five patients to evaluate the morphology, thickness, and echo structural features of the intestinal loops. Color Doppler was performed to visualize the superior mesenteric artery and a wall arteriole of the sampled loop. CT examination was performed 2 to 4 weeks after surgery to evaluate the anatomy of the transplanted organs, arterial and venous anastomoses in case of complications identified with other methods or suspected, and periodically in the follow-up of patients who underwent transplantation due to Gardner syndrome. The protocol for MR evaluation of the bowel included coronal single-shot fast spin-echo T2-weighted sequences, axial and/or sagittal single-shot fast spin-echo T2-weighted sequences, coronal fast multiplanar spoiled gradient-echo (FMP- SPGR) sequences, coronal FMPSPGR sequences with and without administration of intravenous paramagnetic contrast agent, and axial or sagittal FMPSPGR fat-saturated sequences performed after dynamic gadolinium administration. RESULTS AND CONCLUSION: The study of transit with radiopaque markers was useful in patients with chronic intestinal pseudo-obstruction because it identified recovery and normalization of motility. Traditional contrast examination of the gastrointestinal tract continues to play an important role in transplanted patients because it is a simple examination that allows evaluation of the graft anatomy and recovery of motility of the residual native bowel and the transplanted loops. Moreover, it plays a crucial role in early detection of major postoperative complications such as intestinal obstruction, perforation, fistulas, and anastomotic complications (stenosis and dehiscence). CT examination is crucial for the detection of fluid collections, abscesses, and fistulas because it can serve as a guide of drainage and during follow-up of patients with Gardner syndrome can be used to investigate all possible sites in which desmoids might arise in addition to their relation to the graft. Because patients with transplanted bowel are generally rather a young population of reproductive age and because of technologic advances, MR may represent an effective method that does not use ionizing radiation and can therefore substitute for traditional radiologic evaluation. US represents a quick examination technique that is easily available and well tolerated by patients, and it has a role to play in the follow-up of transplanted patients and in the identification of major postoperative complications. However, its role in monitoring possible rejection remains to be defined with studies on wider and more representative samples.


title: The Role of Interleukin-8 and its Receptors in Inflammatory Lung Disease: Implications for Therapy

text: Neutrophils have been implicated in the pathogenesis of many inflammatory lung diseases, including the acute respiratory distress syndrome, chronic obstructive pulmonary disease and asthma. The CXC chemokine interleukin (IL)-8, is a potent neutrophil recruiting and activating factor and the detection of IL-8 in clinical samples from patients with these diseases has led clinicians to believe that antagonism of IL-8 may be a practicable therapeutic strategy for disease management. Work over the last decade has concentrated on both the molecular mechanisms by which IL-8 is produced in the inflammatory setting and also on the manner in which IL-8 activates the neutrophil. Expression of the IL-8 gene appears to be controlled by several components of the inflammatory milieu. Whilst lipopolysaccharide, IL-1β and tumor necrosis factor-α are capable of augmenting IL-8 production, IL-10 is a potent inhibitor of IL-8 synthesis and appears to play an auto-regulatory role. Regulation of the IL-8 gene is under the control of nuclear factor κB which appears to be a primary target for corticosteroid-mediated repression of IL-8 production. IL-8 exerts is effects on neutrophils by binding with high affinity to two receptors on its cell surface, the chemokine receptors CXCR1 and CXCR2. These closely related receptors belong to the superfamily of G-protein coupled receptors, proteins that historically have proved amenable to antagonism by small molecules. The recent descriptions in the literature of highly potent small molecule antagonists of CXCR2 and their success in blocking in vivo trafficking of neutrophils suggest that antagonsim of IL-8 at the receptor level is a viable therapeutic strategy. Clinical trials of such compounds will ultimately provide crucial information currently lacking and will define whether or not IL-8 blockade provides future therapy in pulmonary disease.


title: Urine samples as a possible alternative to serum for human immunodeficiency virus antibody screening

text: The detection of specific antibodies against human immunodeficiency virus (HIV) was tested by dot blot enzyme immunoassay in 95 urine samples from 72 individuals infected with HIV and 23 seronegative individuals. Western blot of paired serum samples from these same individuals was used as the gold standard. The dot blot tested had a sensitivity of 97.2% and a specificity of 100%; only two samples from HIV-infected individuals at Centers for Disease Control (CDC) stages II and IV were non-reactive. Reactive and discrepant samples (serum/urine) were confirmed by Western blot, which had a sensitivity of 98.6% and a specificity of 100%. The most commonly observed Western blot reactivity pattern in urine samples included bands against three groups of HIV structural proteins (ENV, POL, and GAG). The results indicate that urine can be used in screening for HIV antibodies in epidemiological studies of high-prevalence populations, though it is not recommended for individualized diagnostic purposes.


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title: Influence of viral load in the outcome of hospitalized patients with influenza virus infection

text: The role of viral load in the outcome of patients requiring hospital admission due to influenza is not well established. We aim to assess if there is an association between the viral load and the outcome in hospitalized patients with a confirmed influenza virus infection. A retrospective observational study including all adult patients who were hospitalized in our center with a confirmed influenza virus infection from January to May 2016. Viral load was measured by real-time reverse-transcriptase–polymerase chain reaction (rRT-PCR) cycle threshold (Ct) value on upper respiratory tract samples. Its value was categorized into three groups (low Ct, ≤ 20; intermediate Ct, > 20–30; and high Ct, > 30). Two hundred thirty-nine patients were included. Influenza A/H1N1pdm09 was isolated in 207 cases (86.6%). The mean Ct value was 26.69 ± 5.81. The viral load was higher in the unvaccinated group when compared with the vaccinated patients (Ct 25.17 ± 5.55 vs. 27.58 ± 4.97, p = 0.004). Only 27 patients (11.29%) presented a high viral load. Patients with a high viral load more often showed abnormal findings on chest X-ray (p = 0.015) and lymphopenia (p = 0.097). By contrast, there were no differences between the three groups (according to viral load), in associated pneumonia, respiratory failure, need for mechanical ventilation, sepsis, or in-hospital mortality. Our findings suggest that in patients admitted to the hospital with confirmed influenza virus infection (mostly A/H1N1pdm09), a high viral load is associated with a higher presence of abnormal findings on chest X-ray but not with a significant worse prognosis. In these cases, standardized quantitative PCR could be useful.


title: Macrophage activation syndrome in 13 children with systemic-onset juvenile idiopathic arthritis

text: BACKGROUND: Macrophage activation syndrome (MAS) is a severe, potentially life-threatening condition induced by chronic rheumatic diseases, especially systemic-onset juvenile idiopathic arthritis (SoJIA) in childhood. This study aimed to analyze the clinical and laboratory characteristics of systemic-onset juvenile idiopathic arthritis (SoJIA) with macrophage activation syndrome (MAS) in 13 patients. METHODS: Clinical and laboratory data of 13 SoJIA patients with MAS treated in our hospital from January 2003 to October 2007 were analyzed. RESULTS: In the 13 patients, 9 were boys and 4 girls aged from 5 months to 12 years. Clinical manifestations were of no typical characteristics including persistent fever, anemia, arthritis, hepatosplenomegaly, lymph-adenopathy, dysfunction of the liver, abnormal fat metabolism, and hemophagocytic cells in the bone marrow. Two patients experienced acute respiratory distress syndrome, two had mutiorgan failure, and three died. The perforin A91V (NCBI:SNP rs35947132) gene in 6 patients was normal. Glucocorticoid and immunoimpressive therapy were effective in all patients and plasmapheresis used in one severe patient was also effective. CONCLUSIONS: MAS is a serious complication of JIA, especially systemic-onset juvenile idiopathic arthritis. It is essentially important to recognize and treat MAS earlier in order to lower the mortality.


title: Allogeneic bone marrow transplantation with matched unrelated donors for patients with hematologic malignancies using a preparative regimen of high-dose cyclophosphamide and fractionated total body irradiation

text: Allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling donor is effective therapy for patients with bone marrow failure states and those with hematologic malignancies. However, only a minority of them will have an HLA-identical sibling donor; unrelated donors, matched or partially mismatched, have been used successfully for patients lacking a related donor. Even though results with allogeneic transplants using unrelated donors are encouraging, the incidence of complications including graft-versus-host disease (GVHD) and graft rejection or late graft failure is increased compared to identical sibling transplants. The combination of cyclophosphamide and total body irradiation (TBI) has been used as an effective preparative regimen for allogeneic transplants, however, the total dosage and dosing schedule of both the cyclophosphamide and TBI has varied significantly among studies. To decrease the rate of graft rejection and late graft failure with volunteer donors, we evaluated a preparative regimen of high-dose cyclophosphamide (200 mg/kg over 4 consecutive days, days −8, −7, −6, −5) followed by fractionated TBI (1400 cGy administered in eight fractions over 4 days, days −4, −3, −2, −1). GVHD prophylaxis included FK506 and methotrexate. From July 1993 to January 1996, 43 adult patients, median age 38 years (range 18–58 years), were treated with this preparative regimen. Seventeen patients had low-risk disease and 26 had high-risk disease. Thirty-one donor/recipient pairs were matched for HLA-A, -B, and -DR by serology and molecular typing. Seven additional pairs were minor mismatched at the HLA-A or HLA-B loci. Four other donor/recipient pairs were HLA-A,-B, and -DR identical by serology but allele mismatched at either DRB1 or DQB. Forty patients were evaluable for myeloid engraftment. Engraftment occurred in all 40 patients at a median of 19 days. There were no cases of graft rejection or late graft failure. Nephrotoxicity was the primary adverse event with 26 patients (60%) experiencing a doubling of their creatinine. Hepatic veno-occlusive disease occurred in seven patients, six of whom had high-risk disease. All patients who had relapsed or refractory disease prior to BMT achieved a complete remission following BMT. Six patients transplanted for high-risk disease relapsed a median of 377 days post-BMT. None of the patients with low-risk disease have relapsed following transplant; the Kaplan–Meier survival for those patients with low-risk disease is 62% and 37% for those patients transplanted with high-risk disease (P = 0.0129). The median Karnofsky performance status is 100% (range 70–100%). Therefore, a preparative regimen of high-dose cyclophosphamide and fractionated TBI is an acceptable regimen for patients receiving an allograft from unrelated donors.


title: Roles of Nitric Oxide in Surgical Infection and Sepsis

text: This review will summarize the pathobiology of NO in surgical sepsis and infection.


38. Gemeinsame Jahrestagung der Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin und der Österreichischen Gesellschaft für Allgemeine und Internistische Intensivmedizin: 14.–17. Juni 2006 in Saarbrücken, Tagungspräsident: Prof. Dr. med. G.W. Sybrecht, Homburg/Saar


title: The effect of granulocyte-macrophage colony stimulating factor (rGM-CSF) on macrophage function in microbial disease

text: Clinical Research Consultants, 24 Webergasse, 4058 Basle, Switzerland The haematopoietic growth factor, GM-CSF, has well-documented stimulatory effects on monocyte and macrophage functions. These effects include enhanced proliferation of their progenitor cells, increased endocytosis and metabolism of mature cells, increased function as antigen-presenting cells, and increased inhibition or killing of intracellular fungi, bacteria, protozoa and viruses. The major effect of GM-CSF on monocytes and macrophages is to enhance phagocytic and metabolic functions, including increased synthesis of molecules toxic to microbes, and to release other pro inflammatory cytokines. This results in inhibition and/or killing ofCandida albicans, Aspergillus, Cryptococcus, Pneumocystis, Leishmania, Mycohacteria, as well as other intracellular pathogens. GM-CSF also enhances the intracellular effectiveness of antiviral and antibacterial drugs. Viral replication may be increased in activated cells, therefore, when GM-CSF is used, a combination with appropriate antiviral drugs is recommended. Several reports in patients of successful management of microbial diseases which depend on macrophage function are now reviewed. These reports support the clinical value of GM-CSF in the management of patients with cancer and chemotherapy related monocyte/macrophage dysfunction and presumed or documented microbial disease.


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title: Kontinuierliches Stuhldrainagesystem im intensivtherapeutischen Bereich

text: The relevance of nursing interventions for patients with fecal incontinence/defecation problems in intensive care medicine is very often underestimated. Fecal incontinence can either be a symptom of a disease, an epiphenomenon or a primary disease. Fecal incontinence negatively influences the ability of affected intensive patients to care for themselves. Fecal incontinence and diarrhea often occur together, which in return restricts the patient’s mobility. Improperly treated fecal incontinence can result in infections (e.g., skin disorders, existing catheter sores), secondary healing can be delayed (e.g., bedsores, sores on the back or groin/genital area) and can also result in contamination of other areas (e.g., intestinal infection). In the past, many improvised techniques and materials have been used to drain feces for patients who are either immobile or critically ill with temporary or persistent fecal incontinence. Continuous and safe fecal drainage is often a problem. There is no basic standard nursing concept that can be recommended or verified. At present there are a number of continuous fecal drainage systems that have been launched on the market. Different indications and fields of application have been recommended when dealing with continuous fecal drainage. This article shows weaknesses and strengths of continuous fecal drainage, explains how each functions, and illustrates possible indications and contra-indications with each of these. Deployment options and limits are presented and summarized in an algorithm as a practical help for decision-making.


title: Differential Expression, Time Course and Distribution of Four PARs in Rats with Endotoxin-induced Acute Lung Injury

text: The hypothesis that the expression of protease-activated receptors (PARs) protein is regulated at the level of transcription and that PAR isoforms, PAR-1, PAR-2, PAR-3, and PAR-4, in lung tissue show different patterns of expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) was tested. Male Wistar rats were rendered endotoxemic by intra-peritoneal injection of LPS (15 mg/kg body weight). We examined the expression of protein and mRNA and the immunohistochemical localization of PAR isoforms in lung tissues 1, 3, 6, and 10 h after LPS administration. Induction of ALI by LPS was confirmed based on histopathological changes. LPS administration induced significant increases in the expression of PAR isoforms (protein) at the level of transcription in ALI. While the time course of PAR-1 and -2 expressions were different, those of PAR-3 and -4 were almost similar. An immunohistochemical analysis showed localization of PAR isoforms in the vascular endothelium, alveolar epithelium, and alveolar macrophages. However, the cellular distribution patterns of PAR isoforms were different. We conclude that LPS induces increase in protein expression of PAR isoforms at the level of transcription in rats with ALI. The differential expression patterns (over a time course) and distribution of PAR isoforms suggests a distinct role for each isoform in the pathogenesis of LPS-induced ALI.


title: Clinical significance and outcome of Aeromonas spp. infections among 204 adult patients

text: The objectives of this investigation were to analyze the clinical patterns, risk groups, prognostic factors, and mortality of infections caused by Aeromonas spp. This was a retrospective study of adult patients with Aeromonas spp. isolates attended at the Hospital del Mar in Barcelona, Spain, between January 2006 and December 2012. Epidemiological data, antimicrobial susceptibility, clinical patterns, underlying illnesses, type of infection, admission to the intensive care unit (ICU), number of episodes, coinfection, antimicrobial therapy, and evolution were analyzed. A total of 221 clinical samples from 204 patients were positive for Aeromonas spp. The mean age of the patients was 67.6 years. The main clinical form of presentation was gastrointestinal (78.4%). Malignancy was the main risk group in 69 (33.8%) patients, and 48 (23.5%) were previously healthy. Twenty-one patients (10.3%) were admitted to the ICU. Infections were acquired in the hospital in 52.5% of the patients, and 28.9% were polymicrobial. The overall mortality (after 1 year of follow-up from the first positive culture) was 26.5%. Univariate analysis identified an association between increased mortality and the following variables: age ≥80 years, hospitalization, admission to the ICU, malignancy, extraintestinal infection, and appropriate antimicrobial therapy. In the multivariate analysis, age ≥80 years [odds ratio (OR), 4.37 [95% confidence interval (CI), 1.68–11.35; p = 0.002]], admission to the ICU (OR, 6.59 [95% CI, 2.17–19.99; p = 0.001]), and malignancy (OR, 3.62 [95% CI, 1.32–9.90; p = 0.012]) were significantly associated with mortality. Aeromonas infections are mainly gastrointestinal. The 1-year follow-up mortality rate was high. Old age (age ≥80 years), admission to the ICU, and malignancy were identified as independent risk factors for mortality.


title: Management of Acute Liver Failure: A Pediatric Perspective

text: PURPOSE OF REVIEW: Pediatric acute liver failure is a rare, complex, rapidly progressing, and life-threatening illness. Majority of pediatric acute liver failures have unknown etiology. This review intends to discuss the current literature on the challenging aspects of management of acute liver failure. RECENT FINDINGS: Collaborative multidisciplinary approach for management of patients with pediatric acute liver failure with upfront involvement of transplant hepatologist and critical care specialists can improve outcomes of this fatal disease. Extensive but systematic diagnostic evaluation can help to identify etiology and guide management. Early referral to a transplant center with prompt liver transplant, if indicated, can lead to improved survival in these patients. SUMMARY: Prompt identification and aggressive management of pediatric acute liver failure and related comorbidities can lead to increased transplant-free survival and improved post-transplant outcomes, thus decreasing mortality and morbidity associated with this potential fatal condition.


title: Hantavirus pulmonary syndrome in the United States

text: Since the first outbreak of hantavirus pulmonary syndrome (HPS) in 1993, understanding of the vast distribution and potential impact of hantaviruses has grown. At least 277 cases of HPS have been documented in the United States. The full clinical spectrum has yet to be elucidated, and one outbreak suggested the possibility of person-to-person transmission. New research has identified the β-3 integrins as cellular receptors for hantaviruses and has determined the pivotal role of the immune system in pathogenesis. Rapid diagnosis has been facilitated by a new immunoblot assay to detect Sin Nombre virus infection. Treatment remains primarily supportive; however, a placebocontrolled trial of ribavirin is ongoing. Extracorporeal membrane oxygenation may be a potential therapy in severe cases; inhaled nitric oxide needs further study. Vaccines developed against hantaviruses associated with hemorrhagic fever and renal syndrome might be effective against HPS-associated strains.


title: Unusual and rare manifestations of dengue during a dengue outbreak in a tertiary care hospital in South India

text: Dengue is the most rapidly spreading mosquito-borne viral disease in the world, and as a larger proportion of the population is being affected, more unusual manifestations are being reported. Very few studies have documented unusual manifestations of dengue in South India. This prospective study was undertaken from July 2011 to June 2013 to document rare manifestations of dengue fever in 175 hospitalized patients. The clinical diagnosis was confirmed by the detection of NS1Ag, dengue IgM, or IgG by ELISA and/or a RT-PCR and CDC real-time PCR for dengue virus (DENV) RNA. The daily profiles of the hematological and biochemical investigations were followed and recorded. Unusual and rare manifestations of dengue were documented for 115 patients (66 %). Hepatitis was observed in 70 % of the cases. Pleural effusion was seen in 11 %, acute renal failure in 10 %, neurological complications such as encephalitis in 7.4 %, myocarditis in 9 %, and bleeding gastric ulcers in 3.4 % of the cases. DENV serotype 2 was more prevalent in patients with unusual manifestations of dengue in our study. The WHO classification system does not include unusual and rare manifestations; hence, it is essential to be aware of these manifestations and closely monitor them for better clinical management and outcome of patients.