title: Activin, neutrophils, and inflammation: just coincidence?

text: During the 26 years that have elapsed since its discovery, activin-A, a member of the transforming growth factor β super-family originally discovered from its capacity to stimulate follicle-stimulating hormone production by cultured pituitary gonadotropes, has been established as a key regulator of various fundamental biological processes, such as development, homeostasis, inflammation, and tissue remodeling. Deregulated expression of activin-A has been observed in several human diseases characterized by an immuno-inflammatory and/or tissue remodeling component in their pathophysiology. Various cell types have been recognized as sources of activin-A, and plentiful, occasionally contradicting, functions have been described mainly by in vitro studies. Not surprisingly, both harmful and protective roles have been postulated for activin-A in the context of several disorders. Recent findings have further expanded the functional repertoire of this molecule demonstrating that its ectopic overexpression in mouse airways can cause pathology that simulates faithfully human acute respiratory distress syndrome, a disorder characterized by strong involvement of neutrophils. This finding when considered together with the recent discovery that neutrophils constitute an important source of activin-A in vivo and earlier observations of upregulated activin-A expression in diseases characterized by strong activation of neutrophils may collectively imply a more intimate link between activin-A expression and neutrophil reactivity. In this review, we provide an outline of the functional repertoire of activin-A and suggest that this growth factor functions as a guardian of homeostasis, a modulator of immunity and an orchestrator of tissue repair activities. In this context, a relationship between activin-A and neutrophils may be anything but coincidental.


title: Persistent thrombocytopenia following dengue shock syndrome

text: Though thrombocytopenia is one of the hallmarks of dengue hemorrhagic fever/ dengue shock syndrome, persistence of the same is rare. We report an 11 year-old child with dengue shock syndrome, who developed persistent thrombocytopenia. The possible mechanisms are discussed.


docid: ouekkmhd

title: Utility of Coil-Assisted Retrograde Transvenous Obliteration II (CARTO-II) for the Treatment of Gastric Varices

text: PURPOSE: To investigate the technical feasibility, safety and clinical outcomes of coil-assisted retrograde transvenous obliteration II (CARTO-II) for gastric varices (GV). MATERIALS AND METHODS: Thirty-six consecutive patients who had undergone CARTO-II between June 2016 and April 2018 were included in the study. In the CARTO procedure, coil embolization of the drainage vein is performed “before” injection of the sclerosant to replace the use of balloon catheter. In the CARTO-II procedure, coil embolization of the drainage vein was performed “after” injection of the sclerosant to prevent migration of the sclerosant. CARTO-II was performed with ethanolamine oleate iopamidol, and the balloon catheter was immediately removed after coil placement. Technical and clinical success rates, number of coils used, presence or absence of severe complications, timing of the procedure, and rate of GV recurrence after the procedure were analyzed retrospectively. RESULTS: In all patients, GV sclerosis, coil placement and removal of the balloon catheter were successfully completed. The technical success rate was 100%. No patients experienced severe complications such as coil migration or pulmonary embolization. The mean number of metallic coils used per procedure was 3.36. Mean length of the procedure was 132.8 min. Contrast-enhanced computed tomography after CARTO-II confirmed complete variceal thrombosis in all cases. The recurrence rate of GV during follow-up was 2.8% (mean follow-up, 207 days). CONCLUSION: CARTO-II was feasible and safe and could be performed relatively quickly. The number of coils used and the rate of GV recurrence were both low. CARTO-II may have an important role to play in the management of GV.


docid: qatpvuhe

title: Lysophosphatidylcholine Abrogates the CR1 Preserving Effect of Surfactant on Quartz-Exposed Human Granulocytes

text: The effects of pulmonary surfactant on granulocytes were studied by flow cytofluorometry. Cells from hemolyzed blood were first activated by N-formyl-methionyl-leucyl-phenylalanine (fMLP) which mobilizes complement receptor 1 (CR1) from the intracellular pool to the cell surface. The reduced CR1 expression observed after quartz incubation was abolished by a porcine surfactant preparation containing phospholipids and the hydrophobic surfactant proteins. Phospholipids alone had no preservative capacity. However, addition of the surfactant proteins to the phospholipids did not restore the CR1 values to that of intact surfactant, probably due to changed protein structure during the purification procedure. Heating of surfactant at 37°C up to 72 h reduced the preservative effect of surfactant on CR1 expression. Congruent results of CR1 expression were achieved when 1–10% lysophosphatidylcholine was added to the surfactant preparations. Our results imply that lysophosphatidylcholine formed during storage of surfactant at elevated temperatures influences CR1 expression on granuloyctes.


title: Hypothermia Attenuates β1 Integrin Expression on Extravasated Neutrophils in an Animal Model of Meningitis

text: Brain injury in meningitis occurs in part as a consequence of leukocyte migration and activation. Leukocyte integrins are pivotal in the inflammatory response by mediating adhesion to vascular endothelium and extracellular matrix proteins. We have demonstrated that moderate hypothermia early in the course of meningitis decreases leukocyte sequestration within the brain parenchyma. This study examines whether hypothermia alters neutrophil integrin expression in a rabbit model of bacterial meningitis. Prior to the induction of meningitis, peripheral blood samples were obtained and the neutrophils isolated. Sixteen hours after inducing group B streptococcal meningitis, animals were treated with antibiotics, IV fluids, and mechanically ventilated. Animals were randomized to hypothermia (32–33°C) or normothermia conditions. After 10 hours of hypothermia or normothermia, neutrophils were isolated from the blood and cerebral spinal fluid (CSF), stained for β1 and β2 integrins, and analyzed using flow cytometry. Cerebral spinal fluid neutrophil β1 integrin expression was significantly decreased in hypothermic animals. Beta-1 integrins can assume a higher affinity or "activated" state following inflammatory stimulation. Expression of "activated" β1 integrins was also significantly decreased in hypothermic animals. Beta2 CSF neutrophil integrin expression was decreased in hypothermic animals, but failed to reach significance. These data suggest hypothermia may attenuate extravasated leukocyte expression of both total and "activated" β1 integrins.


title: Protein oxidation at the air-lung interface

text: Whilst performing its normal functions the lung is required to deal with a range of toxic insults. Whether these are infectious agents, allergens or air pollutants they subject the lung to a range of direct and indirect oxidative stresses. In many instances these challenges lead to oxidative alterations of peptides and proteins within the lung. Measurement of protein oxidation products permits the degree of oxidative stress to be assessed and indicates that endogenous antioxidant defences are overwhelmed. The range of protein oxidation products observed is diverse and the nature and extent of specific oxidation products may inform us about the nature of the damaging ROS and NOS. Recently, there has been a significant shift away from the measurement of these oxidation products simply to establish the presence of oxidative stress, to a focus on identifying specific proteins sensitive to oxidation and establishing the functional consequences of these modifications. In addition the identification of specific enzyme systems to repair these oxidative modifications has lead to the belief that protein function may be regulated through these oxidation reactions. In this review we focus primarily on the soluble protein components of within the surface liquid layer in the lung and the consequence of their undue oxidation.


title: Emergency versus elective living-donor liver transplantation: a comparison of a single center analysis

text: PURPOSE: We studied the risk factors for postoperative mortality between patients who underwent emergency or elective living-donor liver transplantation (LDLT). METHODS: Forty-seven patients underwent LDLT in our institute, 16 for emergencies and 31 as elective procedures. The emergency LDLT status was applied to cases in which the time period between referral to our institution and transplantation did not exceed 10 days, and in which liver failure was accompanied by the presence of any degree of hepatic encephalopathy. RESULTS: With regard to preoperative factors, age (P = 0.03), the model for end-stage liver disease score (P = 0.001), preoperative tracheal intubation (P = 0.001), ratio between arterial oxygen tension and fractional inspired oxygen (PaO(2)/FiO(2) ratio) (P = 0.03), steroid therapy use (P = 0.001), lymphocyte count (P = 0.02), and cases requiring hemodiafiltration (P = 0.001) differed significantly between the two groups. Postoperative pneumonia occurred more frequently in emergency LDLT patients than in elective LDLT patients (P = 0.006). Invasive pulmonary aspergillosis (IPA) was the main cause of postoperative death in emergency LDLT patients, and, in a univariate analysis, a preoperative status of high serum (1 → 3)-β-d-glucan (>20 pg/ml, P = 0.001), advanced age (>52 years, P = 0.02), and a low PaO(2)/FiO(2) ratio (<320, P = 0.01) were identified as factors predictive of IPA. CONCLUSION: Careful perioperative management, including preoperative investigation of aspergillosis and empiric antibiotic therapy, should be considered for emergency LDLT patients who fulfill IPA risk factors.


title: Microorganisms associated with respiratory syncytial virus pneumonia in the adult population

text: Respiratory syncytial virus (RSV) has been recognized as responsible for severe respiratory illness in adults, especially in the elderly. While pneumonia is commonly observed during RSV infection, the burden and epidemiology of bacterial superinfection is poorly understood. The aim of this study was to identify microorganisms associated with RSV-positive pneumonia in adults. A retrospective study was conducted during three consecutive winters (October to April 2013–2016) in the University Hospital of Lyon, France. During RSV circulation periods, a systematic RSV screening was performed by reverse-transcription PCR on all respiratory samples collected from adults. Records of RSV-positive patients were subsequently analyzed to identify radiologically confirmed pneumonia cases. Bacteria were identified by standard bacteriology cultures or urinary antigen screening and classified as potentially causative of pneumonia if quantification was above the specific threshold as defined by the European Manual of Clinical Microbiology. Overall, 14,792 adult respiratory samples were screened for RSV detection by PCR. In total, 292 had a positive RSV detection (2.0%) among which 89 presented with pneumonia including 27 bacterial superinfections (9.3%) with Streptococcus pneumonia, Haemophilus influenza, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis. Most patients were elderly (55.6%) and patients with comorbidities (77.8%). A more severe outcome was observed for RSV-bacteria-associated pneumonia compared with RSV pneumonia: length of stay was significantly longer (16 days vs 10 days) and ICU hospitalization more frequent (66.7% vs 21.0%) (p < 0.05). In conclusion, we did not observe major differences in the epidemiology of bacterial superinfections in RSV-positive pneumonia compared to reports on post-influenza pneumonia.


title: Macrolide-resistant Mycoplasma pneumoniae in children in Taiwan

text: The aim of this study was to estimate the prevalence of macrolide-resistant Mycoplasma pneumoniae in Taiwan and to compare the clinical courses of pediatric patients with macrolide-resistant (MR) M. pneumoniae and macrolide-susceptible (MS) M. pneumoniae infection. Patients were among the children admitted to Chang Gung Children’s Hospital with mycoplasmal pneumonia between February and December 2011. Detection for macrolide resistance was performed after informed consent was obtained. We retrospectively reviewed medical records and compared the clinical courses of two groups of patients of 73 children enrolled into our study. The rate of macrolide resistance in M. pneumoniae was 12.3 %. Longer hospital stay was observed in the MR patients than MS patients [median, 7 days vs. 5 days (P = 0.019)]. Clinical features or radiographic or laboratory findings are not helpful to differentiate MR from MS mycoplasmal pneumonia. Early diagnosis of MR mycoplasmal pneumonia is crucial for the best management of these patients and obviates the need for extensive etiological searches of these nonresponding cases.


title: Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies

text: We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100–110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6–28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II–IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (<80,000/mL) and lactic dehydrogenase (>500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.


title: Invasive Meningococcal Infection: Analysis of 110 cases from a Tertiary Care Centre in North East India

text: OBJECTIVES: To report an outbreak of invasive meningococcal disease from Meghalaya, in the north east India, from January 2008 through June 2009. METHODS: Retrospective review of case sheets was done. One hundred ten patients with invasive meningococcal disease were included for the study. RESULTS: Of the total patients, 61.8 % were boys and 38.2 % were girls (boy to girl ratio = 1.62:1). The average age of presentation was 8.48 ± 5.09 y. Meningococcal meningitis was seen in 61.8 % of cases, meningococcemia in 20 % and 18.2 % had both. Fever was the most common manifestation (100 %) followed by meningeal signs (78.2 %), headache (56.4 %), vomiting (53.6 %), shock (38.2 %), low Glasgow coma scale (GCS) (25.5 %), purpura and rashes (23.6 %), seizures (9.1 %), abdominal symptoms (4.5 %), irritability and excessive crying (4.5 %) and bulging anterior fontanalle (23 %) in those below 18 mo of age. Raised intracranial pressure (ICP) was the most common complication (28.2 %) followed by coagulopathy (16.4 %), hepatopathy (10 %), herpes labialis (9.1 %), syndrome of inappropriate ADH secretion (SIADH) (8 %), pneumonia (7 %), arthritis (6 %), purpura fulminans, respiratory failure, sixth nerve palsy and diabetes insipidus in 4.5 % each, subdural empyema, optic neuritis, ARDS and ARF in 1.8 % each, cerebral salt wasting syndrome, third nerve palsy, cerebritis and hearing impairment in 0.9 % each. Culture was positive in 35.5 %. Patients were treated initially with ceftriaxone and dexamethasone but later on with chloramphenicol due to clinical drug resistance. Mortality was 6.4 %. CONCLUSIONS: This is the first epidemic report of invasive meningococcal disease from the north east India. Chloramphenicol acts well in areas with penicillin or cephalosporin resistance. Mortality reduces significantly with early diagnosis and prompt intervention.


title: Elevated serum levels of decoy receptor 3 are associated with disease severity in patients with hemorrhagic fever with renal syndrome

text: Hemorrhagic fever with renal syndrome (HFRS) is an acute viral infectious disease characterized by fever, hemorrhage and renal failure. HFRS has become a serious public health problem in China. Unfortunately, the pathogenesis of HFRS has not been completely clarified. The aim of this study is to investigate the changes of decoy receptor 3 (DcR3) and to further explore its potential roles in HFRS. The levels of serum DcR3 were measured by sandwich ELISA. We found serum DcR3 levels increased significantly, which reached peak value during the oliguric phase and in the critical group. Moreover, serum DcR3 levels were closely related to the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and parameters reflecting kidney injury including BUN, creatinine (Cr) and proteinuria. This study indicates that high levels of serum DcR3 have associations with the disease stages, severity and degree of kidney damage. Meanwhile, our results suggest that DcR3 may play a dual role in HFRS pathogenesis. First, DcR3 is involved in the inflammatory cascade response resulting in capillary permeability and kidney injury in the early stage. Secondly, HTNV infection induced DcR3 expression at the convalescent phase may act as a feed-back mechanism in anti-inflammatory response. Thus, a study of DcR3 is essential for a better understanding of HFRS pathogenesis.


docid: bsuerphz

title: Outbreak of pandemic 2009 influenza A/H1N1 infection in the hematology ward: fatal clinical outcome of hematopoietic stem cell transplant recipients and emergence of the H275Y neuraminidase mutation

text: We report an outbreak of pandemic 2009 influenza A/H1N1 virus (2009 H1N1) infection that occurred in the hematology ward of our institution during the 2010–2011 influenza season. A total of seven hospitalized patients with hematologic tumors, including five recipients of hematopoietic stem cell transplantation (HSCT), successively developed rapid influenza detection test (RIDT)-positive influenza A; four patients had laboratory-confirmed 2009 H1N1 infection. Three HSCT recipients required mechanical ventilation support and two were admitted to the intensive care unit; they died of progressive respiratory failure despite receiving available anti-viral drugs. We implemented outbreak-control measures including transferal of RIDT-positive patients to a single-patient room and chemoprophylaxis with oseltamivir. We note that the H275Y neuraminidase mutation was detected in respiratory specimens from three patients, who were administered therapeutic or prophylactic dosages of oseltamivir. The present report demonstrates that the nosocomial 2009 H1N1 outbreak in the hematology ward led to fatal clinical outcomes and the emergence of a resistant virus at a markedly high rate.


title: Molecular recognition elements: DNA/RNA-aptamers to proteins

text: The review summarizes data on DNA/RNA aptamers, a novel class of molecular recognition elements. Special attention is paid to the aptamers to proteins involved into pathogenesis of wide spread human diseases. These include aptamers to serine proteases, cytokines, influenza viral proteins, immune deficiency virus protein and nucleic acid binding proteins. High affinity and specific binding of aptamers to particular protein targets make them attractive as direct protein inhibitors. They can inhibit pathogenic proteins and data presented here demonstrate that the idea that nucleic acid aptamers can regulate (inhibit) activity of protein targets has been transformed from the stage of basic developments into the stage of realization of practical tasks.


title: Nutritional Support to Prevent and Treat Multiple Organ Failure

text: Pseudomonas . Food antioxidants such as glutathione, vitamin E, and β-carotenes are important. Ingredients for the colonic mucosa are important. Approximately 10% of caloric need is satisfied by so-called colonic food (prebiotics), fermented at the level of the colonic mucosa to produce colonic mucosa nutrients and to prevent gut origin sepsis. More than 10 g of fiber per day is recommended. The fermenting flora (probiotic flora) is deranged owing to disease or antibiotic treatment, and resupply of flora is important. A new concept of ecoimmune nutrition is presented for enteral supply of mucosa-reconditioning ingredients: new surfactants, pseudomucus, fiber, amino acids such as arginine, and mucosa-adhering Lactobacillus plantarum 299.


A case of pancytopenia and splenomegaly: haematological disease?


title: Rare Benign Tumors of the Liver: Still Rare?

text: BACKGROUND: Benign liver tumors are common. They do not spread to other areas of the body, and they usually do not pose a serious health risk. In fact, in most cases, benign liver tumors are not diagnosed because patients are asymptomatic. When they are detected, it’s usually because the person has had medical imaging tests, such as an ultrasound (US), computed tomography (CT) scan, or magnetic resonance imaging (MRI), for another condition. MATERIALS AND METHODS: A search of the literature was made using cancer literature and the PubMed, Scopus, and Web of Science (WOS) database for the following keywords: “hepatic benign tumors”, “hepatic cystic tumors”, “polycystic liver disease”, “liver macroregenerative nodules”, “hepatic mesenchymal hamartoma”, “hepatic angiomyolipoma”, “biliary cystadenoma”, and “nodular regenerative hyperplasia”. DISCUSSION AND CONCLUSION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world; there is an increasing incidence worldwide. Approximately 750,000 new cases are reported per year. More than 75 % of cases occur in the Asia-Pacific region, largely in association with chronic hepatitis B virus (HBV) infection. The incidence of HCC is increasing in the USA and Europe because of the increased incidence of hepatitis C virus (HCV) infection. Unlike the liver HCC, benign tumors are less frequent. However, they represent a chapter always more interesting of liver disease. In fact, a careful differential diagnosis with the forms of malignant tumor is often required in such a way so as to direct the patient to the correct therapy. In conclusion, many of these tumors present with typical features in various imaging studies. On occasions, biopsies are required, and/or surgical removal is needed. In the majority of cases of benign hepatic tumors, no treatment is indicated. The main indication for treatment is the presence of significant clinical symptoms or suspicion of malignancy or fear of malignant transformation.


A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease


title: A surge of flu-associated adult respiratory distress syndrome in an Austrian tertiary care hospital during the 2009/2010 Influenza A H1N1v pandemic

text: We report on 17 patients with influenza A H1N1v-associated Adult Respiratory Distress Syndrome who were admitted to the intensive care unit (ICU) between June 11th 2009 and August 10th 2010 (f/m: 8/9; age: median 39 (IQR 29–54) years; SAPS II: 35 (29–48)). Body mass index was 26 (24–35), 24% were overweight and 29% obese. The Charlson Comorbidity Index was 1 (0–2) and all but one patient had comorbid conditions. The median time between onset of the first symptom and admission to the ICU was 5 days (range 0–14). None of the patients had received vaccination against H1N1v. Nine patients received oseltamivir, only two of them within 48 hours of symptom onset. All patients developed severe ARDS (PaO(2)/FiO(2)-Ratio 60 (55–92); lung injury score 3.8 (3.3–4.0)), were mechanically ventilated and on vasopressor support. Fourteen patients received corticosteroids, 7 patients underwent hemofiltration, and 10 patients needed extracorporeal membrane-oxygenation (ECMO; 8 patients veno-venous, 2 patients veno-arterial), three patients Interventional Lung Assist (ILA) and two patients pump driven extracorporeal low-flow CO(2)-elimination (ECCO(2)–R). Seven of 17 patients (41%) died in the ICU (4 patients due to bleeding, 3 patients due to multi-organ failure), while all other patients survived the hospital (59%). ECMO mortality was 50%. The median ICU length-of-stay was 26 (19–44) vs. 21 (17–25) days (survivors vs. nonsurvivors), days on the ventilator were 18 (14–35) vs. 20 (17–24), and ECMO duration was 10 (8–25) vs. 13 (11–16) days, respectively (all p = n.s.). Compared to a control group of 241 adult intensive care unit patients without H1N1v, length of stay in the ICU, rate of mechanical ventilation, days on the ventilator, and TISS 28 scores were significantly higher in patients with H1N1v. The ICU survival tended to be higher in control patients (79 vs. 59%; p = 0.06). Patients with H1N1v admitted to either of our ICUs were young, overproportionally obese and almost all with existing comorbidities. All patients developed severe ARDS, which could only be treated with extracorporeal gas exchange in an unexpectedly high proportion. Patients with H1N1v had more complicated courses compared to control patients.


docid: nvfdigln

title: Cushing’s syndrome complicated by multiple opportunistic infections

text: The case history of a 56-year-old man is described who suffered from severe adrenocorticotrophic hormone (ACTH)-dependent Cushing’s syndrome. The clinical course was complicated by simultaneous infections with Pneumocystis carinii, Staphylococcus aureus, Candida albicans, Aspergillus fumigatus and Herpes simplex, which proved to be fatal. A study of the literature shows that opportunistic infections in endogenous Cushing’s syndrome are associated with severe cortisol excess and carry a high mortality. Opportunistic infections are most prevalent in the ectopic ACTH syndrome, explained by the very high plasma cortisol concentrations in this condition. Infections with Aspergillus species, Cryptoccus neoformans, Pneumocystis carinii and Nocardia asteroides predominated. Cushing’s syndrome with a very high plasma cortisol concentration causes a severe immunocompromized state. Prompt evaluation of the cause of the hypercortisolism, initiation of cortisol lowering therapy, primary prophylaxis for Pneumocystis carinii infection when plasma cortisol exceeds 2500 nmol L(−1) and a search for concomitant infectious disease is recommended.


title: Surfactant protein B and A concentrations are increased in neonatal pneumonia

text: BACKGROUND: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and ill-defined factors. Surfactant proteins’ (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. METHODS: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-(13)C-PA)dipalmitoyl-phosphatidylcholine. RESULTS: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t(1/2) was significantly shorter in the pneumonia group (11.8 (5.5–19.8) h vs. 26.6 (19.3–63.6) h, P = 0.011). CONCLUSION: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease’s resolution is associated with the restoration of the normal ratio between SP-B and PL. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2015.123) contains supplementary material, which is available to authorized users.


docid: mnkwjplb

title: Novel Medical Treatments for Hypertension and Related Comorbidities

text: PURPOSE OF REVIEW: The purpose of this review is to summarize the most recent data available on advances in development of novel medical treatments for hypertension and related comorbidities. RECENT FINDINGS: Approximately half of all hypertensive patients have not achieved goal blood pressure with current available antihypertensive medications. Recent landmark studies and new hypertension guidelines have called for stricter blood pressure control, creating a need for better strategies for lowering blood pressure. This has led to a shift in focus, in recent years, to the development of combination pills as a means of achieving improved blood pressure control by increasing adherence to prescribed medications along with further research and development of promising novel drugs based on discovery of new molecular targets such as the counter-regulatory renin-angiotensin system. SUMMARY: Fixed-dose combination pills and novel treatments based on recently discovered pathogenic mechanisms of hypertension that have demonstrated promising results as treatments for hypertension and related comorbidities will be discussed in this review.


title: Akutes Leberversagen: Von der Epidemiologie und Pathogenese zur Therapie

text: Acute liver failure (ALF) is characterized by loss of liver function without pre-existing chronic liver disease. Drug toxicity and viral hepatitis have been identified as the main causes of ALF in Germany. The regeneration capability of the liver and overall prognosis are determined by the underlying etiology. Advances in intensive care medicine, supportive therapy, and transplantation surgery have improved the overall outcome of ALF over the last two decades. The clinical syndrome of ALF is mainly due to a release of inflammatory cytokines from necrotic hepatocytes, which lead to disastrous consequences in the immune system and hemodynamics. The main goals of supportive intensive care therapy in ALF are early identification and treatment of infections and the prevention and therapy of cerebral hypertension.


title: Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis

text: Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy.


title: Management of chickenpox in pregnant women: an Italian perspective

text: Chickenpox is a highly contagious disease caused by primary infection of varicella zoster virus (VZV). The disease is spread worldwide and is usually benign but, in some groups of population like pregnant women, can have a severe outcome. Due to a not optimal vaccination coverage, a relatively high number of childbearing-aged women in a European country such as Italy tested seronegative for VZV and so are currently at risk of acquiring chickenpox during pregnancy, especially if they live in contact with children for family or work reasons. Only few data are available about the risk of infection in this setting: the incidence of chickenpox may range from 1.5 to 4.6 cases/1000 childbearing females and from 1.21 to 6 cases/10,000 pregnant women, respectively. This review is aimed to focus on the epidemiology and the clinical management of exposure to chickenpox during pregnancy. Particular emphasis is given to the accurate screening of childbearing women at the time of the first gynecological approach — the females who tested susceptible to infection can be counseled about the risks and instructed on procedure should contact occur — and to the early prophylaxis of the at-risk exposure. Lastly, the achievement of adequate vaccination coverage of the Italian population remains a cornerstone in the prevention of chickenpox in pregnancy.


title: Intestinal transplantation in children: current status

text: Intestinal transplantation (IT) is the least common form of organ transplantation; however, it has shown exceptional growth and improvement in graft survival rates over the past two decades mainly due to better outcomes achieved during the first year of transplantation (76 % at 1 year), due to improvement in surgical techniques and the development of better immunosupressive therapies as we understand more about the relationship between the recipient and host immune system. There are still ongoing issues with chronic rejection and long-term survival. Intestinal transplantation is still an acceptable therapy for patients with intestinal failure (IF), but it is generally reserved for patients who develop severe and life-threatening complications despite standard therapies, or those who are not able to maintain a good quality of life. The purpose of this review is to describe the current status, indications, outcomes and advances in the field of intestinal transplantation.


title: Corticosteroids combined with continuous veno-venous hemodiafiltration for treatment of hantavirus pulmonary syndrome caused by Puumala virus infection

text: Reported here are two cases of hantavirus pulmonary syndrome caused by Puumala virus infection, which rapidly resolved after initiation of corticosteroid treatment combined with continuous veno-venous hemodiafiltration. These cases emphasize the role of the inflammatory response in the pathogenesis of hantavirus pulmonary syndrome.


title: Clinical features of the 2009 swine-origin influenza A (H1N1) outbreak in Japan

text: To clarify the clinical symptoms of the influenza A virus during the 2009 pandemic influenza outbreak, we describe the clinical features of outpatients diagnosed with type A influenza by use of the rapid influenza diagnostic test (RIDT) from September to December 2009. Questionnaires were used to collect prospective data on 1,122 cases with influenza-like illness at our medical institutions. The independent predictors of influenza A virus were identified on the basis of demographic features and the clinical symptoms of the patients who tested positive for influenza A virus in the RIDT test. Of the 1,122 cases tested, 389 (34.7%) were positive for the influenza A virus. The median age of the influenza-positive patients was 14, and 58.9% of the patients were male. The symptoms fever, cough, rhinorrhea, and headache were statistically dominant. A history of recent contact with persons suffering from influenza or influenza-like illness at home, school, or in the workplace was significantly more common in the positive group than in the negative group. Pneumonia was observed in 2 (0.5%) of the positive patients, but the symptoms were only severe enough to require hospitalization in 1 of the 2. No deaths were observed among the 389 RIDT-positive patients. Although the spread of influenza A virus was both rapid and extensive, mainly among children under the age of 18, it seemed to be mild. Appropriate interpretation of the RIDT on the basis of recent clinical information, and early treatment with antiviral drugs might help to prevent severe illness from influenza pandemics in the future.


title: Clinical Features of Severe Influenza A (H1N1) Virus Infection

text: OBJECTIVE: To highlight the clinical presentations of influenza A (H1N1) infection, for early diagnosis and recognition by the pediatricians. METHODS: In this retrospective study, the medical records of inpatients with influenza A (H1N1) infection between November 1, 2009 and May 31, 2011were reviewed. RESULTS: Eighty pediatric in-patients with median age 41.9 mo were studied. ARDS (11/80), pneumothorax (8/80), pleural effusion (7/80) and encephalopathy (7/80) were the most frequent complications. Six of 11 ARDS patients died;all of them were under 5 y. The median days of viral shedding was 11.4 d. Slight increase of Il-6, Il-10 and TNF-γ were revealed in some cases. CONCLUSIONS: During late stage of pandemic wave, the majority of patients were young children. Children with severe Influenza A (H1N1) are prone to develop complications, and die from ARDS. If influenza-like illness is accompanied by neurologic signs, influenza A (H1N1) virus infection should be considered. The viral shedding in children is longer than in adults.


title: Acute Respiratory Distress Syndrome after Rituximab Infusion

text: Rituximab, a humanized monoclonal antibody approved for malignant lymphoma, is being increasingly, effectively, and safely used for immune thrombocytopenic purpura (ITP) and other humoral autoimmune disorders. We report the case of a 43-year-old man with ITP refractory to steroids and intravenous immunoglobulin who developed acute respiratory distress syndrome (ARDS) after a single infusion of rituximab. Dyspnea, hypoxemia, and pleuritic chest pain occurred within 24 hours of rituximab administration, and there was no other apparent explanation. Progressive hypoxemia mandated endotracheal intubation 1 week after rituximab administration and led to death 4 weeks after admission. ARDS has been associated with the administration of other monoclonal antibodies, such as infliximab, gemtuzumab ozogamicin, and OKT3 and is believed to be directly mediated by release of proinflammatory cytokines. ARDS is rarely associated with rituximab infusion for lymphoproliferative disorders, but it should be considered by those administering rituximab, especially when a patient develops severe pulmonary symptoms soon after infusion.


title: Preventive Effect of Hochu-ekki-to on Lipopolysaccharide-Induced Acute Lung Injury in BALB/c Mice

text: This study was designed to investigate the effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in female BALB/c mice by the intranasal administration of 0.1 mg/kg LPS. The mice were divided into a group receiving normal feed and another group receiving feed mixed with TJ-41 at a dose of 1 g/kg/day for 8 weeks before LPS challenge. In the bronchoalveolar lavage fluid, the preadministration of TJ-41 caused significant reduction in the absolute number of total cells, neutrophils, and macrophages. The preadministration of TJ-41 significantly inhibited increases in the serum level of keratinocyte chemoattractant (KC), which is a murine chemotaxin for neutrophils that corresponds to human interleukin-8, with respect to its concentration at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the TJ-41-treated mice than in the control mice. These findings indicated that the preadministration of TJ-41 could show an inhibitory effect on ALI in this experimental murine system associated with the suppression of chemokine production.


CASE REPORT: Gastrointestinal Cryptococcosis Presenting as Spontaneous Jejunal Perforation in a Nonimmunocompromised Host


title: Inflammation in lung transplantation for CF: Immunosuppression and modulation of inflammation

text: Lung transplantation is an accepted therapy for selected individuals with end-stage lung disease due to cystic fibrosis (CF). Recent data show that CF recipients oflung transplantation have survival as good as those of any other diagnostic group. After transplantation, CF patients confront the major threats to life and health of graft infection and rejection. Inflammation is the common mediator of injury to the lung in both these instances. Graft infection after lung transplantation involves the same micro-organismsas are typical with CF as well as opportunistic agents. Prophylactic strategies and aggressive diagnosis via bronchoscopy are both critical in the effective treatment of post-transplant lung infections. Graft rejection involves the detection and recognition of foreign antigen and the subsequent activation of specific T-lymphocyte clones leading to inflammatory injury to the donor organ. Immunosuppression is used to prevent and/or modulate host response to the donor organ and titrated to serum therapeutic drug monitoring and transbronchial biopsy findings. Precise clinical monitoring and aggressive diagnostic approaches are crucial to minimizing graft injury and aggressive diagnostic approaches are crucial to minimizing graft injury and enhancing life after transplantation. Although most CF lung transplant recipients experience both graft infection and rejection and the 5-yr survival rate remains at approx 50%, improvement in diagnosis and therapy continue over time. With the introduction of new approaches to antimicrobial therapy, new immunosuppressant agents and promising strategies to promote immune tolerance, survival after lung transplantation is likely to improve in the coming decades.


title: Malaria und andere notfallmedizinische relevante Tropenerkrankungen mit dem Leitsymptom Fieber

text: BACKGROUND: For people returning from the tropics, malaria is the most common cause of fever. Plasmodium falciparum causes the most common and most dangerous form of malaria, called malignant tertian malaria or falciparum malaria. METHOD: Search and evaluation of the current literature. RESULTS AND CONCLUSION: Over 90 % of all malaria cases and malaria deaths occur in Africa, while the remaining cases are divided between India, Southeast Asia, Oceania, and Latin America. In Germany, between 513 and 613 cases of malaria have been reportet annually over the last 10 years according to the Robert Koch Institute, including 389–541 cases of potentially fatal falciparum malaria (Plasmodium falciparum). All fever patients who have been in to the tropics during the last 4 months must be tested for malaria. However, immigrants from tropical regions might develop malaria even years after their last trip to their former home country. Rapid diagnostic tests are now available—particularly for falciparum malaria. However, the occasional negative or false-positive results are possible. The treatment of malaria depends on the Plasmodium species, the clinical severity, and the region in which the infection was acquired.


European Society of Esophagology 2007


title: Pneumonia in patients with novel influenza A (H1N1) virus in Southeastern Turkey

text: The objective of this study was to describe the clinical characteristics and the radiological and laboratory findings of the hospitalised patients who had novel, laboratory-confirmed, swine-origin influenza A virus (S-OIV) infection with pneumonia. Between October and December 2009, 56 patients hospitalised for pneumonia who were tested for S-OIV infection were retrospectively evaluated. Thirty-three patients had positive S-OIV infections. In addition, 23 of the 56 patients who had negative test results for S-OIV infection were compared with the positive group. The mortality rate amongst the patients with S-OIV infection was 24.2%. Of the 33 patients, 42.4% had at least one underlying medical condition and 4 (12%) patients were pregnant or postpartum. Fourteen patients (42.4%) with S-OIV infection were followed up in an intensive care unit. The most common symptom was dyspnea. The mean peak body temperature during hospital stay (39.42 ± 0.70) was higher in this group than in the negative group (38.51 ± 1.05) (p = 0.001). Thrombocytopenia, increased creatine kinase and elevated lactate dehydrogenase levels were statistically significant. Bilateral infiltration was more common in the patients with S-OIV infection. Although some laboratory, radiological and clinical data show a significant difference between the patients with S-OIV pneumonia and the negative group, each patient presenting with signs of pneumonia during pandemia should be tested for Influenza A.


docid: kxecvnay

title: Acute Motor Axonal Neuropathy Associated with Pandemic H1N1 Influenza A Infection

text: BACKGROUND: Guillain–Barre syndrome (GBS) is a well known entity that has many infectious agents reported as antecedent events. The spectrum of GBS includes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), and some other variants like Miller-Fisher syndrome (MFS). METHODS: Patient with AMAN variant of GBS after severe bilateral pneumonia and ARDS due to the novel pandemic H1N1 influenza A virus is presented. RESULTS: 28-year-old white female was admitted to our Intensive Care Unit during the influenza pandemic because of severe ARDS due to bilateral pneumonia. The course of the disease was complicated with the new onset tetraplegia due to the AMAN variant of GBS. Treatment with plasma exchange was conducted and the patient had satisfactory recovery. CONCLUSION: We report a case of AMAN variant of GBS associated with proven H1N1 influenza A infection. This virus has not been reported previously as the agent of antecedent infection that induced this disorder. Risk factors for other causes of ICU neuromuscular weakness are usually present in the ICU patients and should not be the reason for reluctance in active quest for GBS. Once the diagnosis of GBS is established or suspected the treatment with plasma exchange or intravenous immune globulin is indicated.


title: Pulmonary Vasculature and Critical Asthma Syndromes: a Comprehensive Review

text: One of the important factors and consequences in persistent asthma is the change in the vasculature of the airways and lung parenchyma. These changes could contribute to worsening asthma control and predispose asthmatics to critical asthma syndromes. For many years, the contribution of vasculature to severe asthma was limited to discussion of small and medium vessel vasculitis commonly referred to as Churg − Strauss syndrome. This comprehensive review will explore the known mechanisms that are associated with remodeling of the vasculature in a variety of critical asthma presentations. Inflammation of pulmonary and bronchial small blood vessels may contribute significantly but silently to asthma pathobiology. Inflammation in the vasculature of the lung parenchyma can decrease lung capacity while inflammation in airway vasculature can decrease airflow. This review will provide a modern perspective on Churg–Strauss syndromes with a focus on phenotyping, mechanism, and ultimately modern therapeutic approaches. Vascular remodeling and airway remodeling are not mutually exclusive concepts in understanding the progression of asthma and frequency of acute exacerbations. Furthermore, the contribution of vascular leak, particularly in the parenchymal vasculature, has become an increasingly recognized component of certain presentations of poorly controlled, severe persistent asthmatic and during exacerbations. We highlight how these mechanisms can contribute to some the severe presentations of influenza infection in patients with a history of asthma. The ultimate aim of this review is to summarize the current literature concerning vasculitis and the contribution of airway and parenchymal vascular remodeling to presentation of persistent asthma and its consequences during acute exacerbations and critical asthma syndromes.


title: Extracorporeal lung support for patients who had severe respiratory failure secondary to influenza A (H1N1) 2009 infection in Canada

text: BACKGROUND: From March to July 2009, influenza A (H1N1) 2009 (H1N1-2009) virus emerged as a major cause of respiratory failure that required mechanical ventilation. A small proportion of patients who had this condition developed severe respiratory failure that was unresponsive to conventional therapeutic interventions. In this report, we describe characteristics, treatment, and outcomes of critically ill patients in Canada who had H1N1-2009 infection and were treated with extracorporeal lung support (ECLS). METHODS: We report the findings of a case series of six patients supported with ECLS who were included in a cohort study of critically ill patients with confirmed H1N1-2009 infection. The patients were treated in Canadian adult and pediatric intensive care units (ICUs) from April 16, 2009 to August 12, 2009. We describe the nested sample treated with ECLS and compare it with the larger sample. RESULTS: During the study period, 168 patients in Canada were admitted to ICUs for severe respiratory failure due to confirmed H1N1-2009 infection. Due to profound hypoxemia unresponsive to conventional therapeutic interventions, six (3.6%) of these patients were treated with ECLS in four ICUs. Four patients were treated with veno-venous pump-driven extracorporeal membrane oxygenation (vv-ECMO), and two patients were treated with pumpless lung assist (NovaLung iLA). The mean duration of support was 15 days. Four of the six patients survived (66.6%), one of the surviving patients was supported with iLA and the other three surviving patients were supported with ECMO. The two deaths were due to multiorgan failure, which occurred while the patients were on ECLS. INTERPRETATION: Extracorporeal lung support may be an effective treatment for patients who have H1N1-2009 infection and refractory hypoxemia. Survival of these patients treated with ECLS is similar to that reported for patients who have acute respiratory distress syndrome of other etiologies and are treated with ECMO.


title: New insights into the importance of aminopeptidase A in hypertension

text: The renin-angiotensin system (RAS) plays an important role in the maintenance of normal blood pressure and the etiology of hypertension; however, minimal attention has been paid to the degradation of the effector peptide, angiotensin II (AngII). Since aminopeptidase A (APA)-deficient mice develop hypertension APA appears to be an essential enzyme in the control of blood pressure via degradation of AngII. The robust hypertension seen in the spontaneously hypertensive rat (SHR) is due to activation of the RAS, and an accompanying decrease in kidney APA. Changes in APA have also been measured during the activation of the RAS in the Goldblatt hypertension model and Dahl salt-sensitive (DSS) rat. The DSS rat shows an elevation in renal APA activity at the onset of hypertension suggesting a protective role against elevations in circulating AngII, followed by decreased APA activity with advancing hypertension. Changes seen in human maternal serum APA activity during preeclampsia are similar to changes measured in renal APA in the DSS rat model. APA activity is higher than during normal pregnancy at the onset of preeclampsia, and with advancing preeclampsia (severe preeclampsia) declines below that seen during normal pregnancy. Serum APA activity is also increased during hormone replacement therapy (HRT), perhaps in reaction to elevated levels of AngII. Thus, it appears important to consider the relationship among activation of the RAS, circulating levels of AngII, and the availability of APA in hypertensive disorders.


title: Generation of an immortal differentiated lung type-II epithelial cell line from the adult H-2K(b)tsA58 transgenic mouse

text: This paper describes a new fully differentiated Type-II alveolar epithelial cell line designated T(7), derived from transgenic H-2K(b)-tsA58 mice, capable of being passaged as an immortalized cloned cell line in culture. H-2K(b)-tsA58 mice harbor a temperature-sensitive (ts) mutant of the simian virus 40 (SV40) large tumor antigen (T antigen) under the control of the γ-interferon (INF)-inducible mouse major histocompatibility complex H-2K(b) promoter. When cultured under permissive conditions (33°C and in the presence of γ-INF) cells isolated from H-2K(b)-tsA58 mice express the large T antigen, which drives the cells to proliferate. However, upon withdrawal of the γ-INF and transfer of the cells to a higher temperature (39°C), T antigen expression is turned off, the cells stop proliferating and differentiate. The T(7) cell line is a clonal cell line originally derived from a Type-II cell-rich fraction isolated from lungs of H-2K(b)-tsA58 mice. The T(7) cells form confluent monolayers, and have a polarized epithelial cell morphology with tight junctions and apical microvilli. In addition, the T(7) cells have distinct cytoplasmic lamellar bodies, which become more numerous and pronounced when the cells are grown under nonpermissive conditions. The T(7) cells synthesize and secrete phosphatidylcholine and the three surfactant proteins, SP-A, SP-B, and SP-C. The T(7) cell line is unique in that it is the first non-tumor-derived Type-II cell line capable of synthesizing and secreting the major components of surfactant. Based on the criteria studied, the T(7) cell line is phenotypically very similar to normal Type-II cells. The T(7) cell line, therefore, should prove a valuable experimental system to advance the study of the cell biology/physiology of surfactant metabolism and secretion as well as serve as a model for other studies of Type-II cell physiology.


40. Gemeinsame Jahrestagung der Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin (DGIIN) und der Österreichischen Gesellschaft für Allgemeine und Internistische Intensivmedizin (ÖGIAIM): 4. bis 7. Juni 2008, Congress Innsbruck Kongresspräsidenten: A. o. Univ.-Prof. Dr. Michael Joannidis, Innsbruck Prim. Prof. Dr. Christian Wiedermann, Bozen


title: Critical Care of the Liver Transplant Recipient

text: Patient survival following orthotopic liver transplantation has greatly increased following improvements in surgical technique, anesthetic care, and immunosuppression. The critical care of the liver transplant recipient has paralleled these improvements, largely thanks to input from multidisciplinary teams and institution-specific protocols guiding management and care. This article provides an overview of the approach to critical care of the postoperative adult liver transplant recipient outlining common issues faced by the intensivist. Approaches to extubation and hemodynamic assessment are described. The provision of appropriate immunosuppression, infection prophylaxis, and nutrition is addressed. To aid prompt diagnosis and treatment, intensivists must be aware of postoperative complications of bleeding, primary nonfunction, delayed graft function, vascular thromboses, biliary complications, rejection, and organ dysfunction.


title: Influenza pathogenicity during pregnancy in women and animal models

text: Pregnant women are at the highest risk to develop severe and even fatal influenza. The high vulnerability of women against influenza A virus infections during pregnancy was repeatedly highlighted during influenza pandemics including the pandemic of this century. In 2009, mortality rates were particularly high among otherwise healthy pregnant women. However, our current understanding of the molecular mechanisms involved in severe disease development during pregnancy is still very limited. In this review, we summarize the knowledge on the clinical observations in influenza A virus-infected pregnant women. In addition, knowledge obtained from few existing experimental infections in pregnant animal models is discussed. Since clinical data do not provide in-depth information on the pathogenesis of severe influenza during pregnancy, adequate animal models are urgently required that mimic clinical findings. Studies in pregnant animal models will allow the dissection of involved molecular disease pathways that are key to improve patient management and care.


title: Study of Acute Exogenous Lipoid Pneumonia

text: OBJECTIVE: To analyze the clinical and imagenological characteristics of acute Exogenous lipoid pneumonia (ELP), explore its risk factors, and assess the potential role of multiple bronchoalveolar lavages (BALs) and steroid therapy in the treatment of children with acute ELP. METHODS: Between May 2011 and July 2014, 33 pediatric patients with pneumonia caused by aspiration of oil-based substances were admitted to the Guangzhou Women and Children’s Medical Center, Guangdong, China. Data on the demographics of these patients, as well as that on clinical presentations, imagenological characteristics, history of ingestion, laboratory observations, treatment protocol, response to therapy, BAL findings, and treatment outcomes were collected. RESULTS: The study group consisted of 23 boys (69.7 %) and 10 girls (30.3 %), with ages ranging from 4 mo to 4 y. They were admitted to the hospital 2 h to 13 d after ingesting the oil-based substance. By the time of admission, most patients presented with respiratory distress and other symptoms, including tachypnea (n = 21), cough (n = 25), mild fever (n = 18), progressive dyspnea (n = 12), and pneumorrhagia (n = 5); six patients received mechanical ventilation because of complicated respiratory distress syndrome. The most common laboratory observations were leukocytosis (25 of 33, 75.8 %), neutrophilia (23 of 33, 69.7 %), and anemia (8 of 33, 24.2 %). Serum biochemical examination showed elevated sedimentation rates (24 of 33, 72.7 %), lactate dehydrogenase levels (18 of 33, 54.5 %), and C-reactive protein levels (17 of 33, 51.5 %). The most common finding on computed tomography (CT) scans was areas of consolidation. Within the follow-up duration of 2 wk to 6 mo, all patients with clinical symptoms of ELP experienced remission, and none died. The CT scans of most of the cases were normal by 1 to 3 mo, except for two patients who showed complete improvement 6 mo after treatment. CONCLUSIONS: It was found that multiple BALs combined with steroid therapy result in significant improvement of clinical, radiologic, and laboratory parameters in children with acute ELP. Further, some traditional practices may predispose children to ELP, even in the absence of underlying risk factors. Finally, pneumorrhagia and acute respiratory distress syndrome may be the main complications of acute ELP in children.


title: Molecular mechanisms in the early phase of hemorrhagic shock

text: Hemorrhagic shock (HS) results in the initiation of an inflammatory cascade that is critical for survival following successful resuscitation. We identified a complex sequence of molecular events including shock-dependent and reperfusion-dependent responses that offer a new comprehensive approach for consequences of HS. Shock-dependent initializing mechanisms include the induction of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and CD14 and play a catalyzing role for subsequent phenotypic changes following resuscitation. The early immediate response genes iNOS and COX-2 promote the inflammatory response by the rapid and excessive production of nitric oxide (NO) and prostaglandins. The transcription factor hypoxia-inducible factor-1 (HIF-1) may regulate the induction of iNOS during the ischemic phase of shock. NO is an important signaling molecule which is involved in redox-sensitive mechanisms including the downstream activation of nuclear factor (NF)-κB. NO-dependent NF-κB activation promotes the induction of inflammatory cytokine expression during the reperfusion phase. Peroxynitrite-mediated direct toxicity and NO-mediated inflammatory toxicity contribute to organ injury. Patients suffering consequences of severe HS are susceptible to systemic inflammation, organ injury, and mortality if physiologic and therapeutic mechanisms are ineffective in limiting the activation of the inflammatory cascade.


Procalcitonin, a marker of bacterial infection


docid: qpjvmwmp

title: Predictors of Mortality in Hospitalized Children with Pandemic H1N1 Influenza 2009 in Pune, India

text: OBJECTIVE: To analyse the factors associated with increased mortality among Indian Children with H1N1. METHODS: Data were abstracted from available hospital records of children less than 12 y of age, who were admitted to Sassoon General Hospital in Pune, India, with confirmed pandemic 2009 H1N1 influenza infection from August 2009 through January 2010. Logistic regression analysis was used to identify clinical characteristics associated with mortality. RESULTS: Of 775 pediatric cases admitted with Influenza Like Illness (ILI), 92 (11.8%) had confirmed H1N1 influenza infection. The median age of HIN1 cases was 2.5 y; 13 (14%) had an associated co-morbid condition. Median duration of symptoms was 4 d (interquartile range (IQR), 3–7 d). All 92 H1N1 cases received oseltamivir and empiric antimicrobials on admission. Intensive care unit (ICU) admission was required for 88 (96%) children, and 20 (23%) required mechanical ventilation.Fifteen children (16%) died; mortality was associated with presence of diffuse alveolar infiltrate on admission chest radiography (odds ratio (OR) 45, 95%CI :5.4–370; p < 0.001), use of corticosteroids in ARDS in children who required mechanical ventilation (OR 8.12, 95%CI: 2.44–27.05; p = 0.001), SpO(2) <80% on admission (OR 32.8, 95% CI: 5.8–185.5; p < 0.001) and presence of ARDS (OR 345.3, 95% CI :33.5–3564.1; p < 0.001). Necropsy from all children who died showed 9 (60%) had ARDS pattern and necrotizing pneumonitis, diffuse hemorrhage and interstitial pneumonia (n = 4 each, 27%) with gram positive organisms consistent with severe viral and bacterial co-infection. CONCLUSIONS: Hypoxia, ARDS and use of corticosteroids in children with ARDS who were mechanically ventilated were the factors associated with increased odds of mortality. Necropsy also suggested bacterial co-infection as a risk factor.


title: Ventilator Associated Pneumonia in Pediatric Intensive Care Unit: Incidence, Risk Factors and Etiological Agents

text: OBJECTIVES: To study the incidence, etiology and risk factors associated with ventilator associated pneumonia (VAP) in children. METHODS: This prospective cohort study was conducted on patients admitted to the Pediatric Intensive Care Unit (PICU) of a tertiary care institute of North India, from June 2012 through March 2014, who received mechanical ventilation for more than 24 h. All enrolled children were assessed daily for development of ventilator associated pneumonia (VAP) using the case definition given by Centers for Disease Control and Prevention (CDC). Chest radiograph and microbiologic samplings were performed in children suspected to have VAP. Risk factors associated with VAP were calculated by doing bivariate and multivariate analysis. RESULTS: A total of 128 patients were screened and 86 were enrolled (median age 30 mo 95% CI 4.0–84.0; 72% boys). The most common admitting diagnosis was sepsis (16%) followed by acyanotic congenital heart disease with pneumonia (14%) and the most common indication for ventilation was respiratory failure (45.3%). The incidence of VAP according to CDC criteria was 38.4%, while the incidence of microbiologically confirmed VAP was 24.4%. The incidence of ventilator associated tracheobronchitis (VAT) was found to be 11.6%. Acinetobacter was the most frequently isolated organism (47%) followed by Pseudomonas (28%), Klebsiella (15%), E. coli (5%) and Enterobacter (5%). Risk factors for VAP on bivariate analysis were use of proton pump inhibitor (PPI) (p = 0.027, OR 5.2, 95% CI 1.1–24.3), enteral feeding (p < 0.001, OR 6.5, 95% CI 2.1–19.4) and re-intubation (p = 0.024, OR 3.3 and 95% CI 1.1–9.6). On multivariate analysis, use of PPI (p = 0.03, OR 8.47, 95% CI 1.19–60.33) and enteral feeding (p < 0.001, OR 12.2, 95% CI 2.58–57.78) were identified as independent risk factors for VAP. CONCLUSIONS: Ventilator associated pneumonia is an important complication in children receiving mechanical ventilation in PICU and Gram negative bacilli (Acinetobacter and Pseudomonas) being the important causative agents. Ventilator associated tracheobronchitis is an emerging entity; recognition and treatment of same might prevent the development of VAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12098-018-2662-8) contains supplementary material, which is available to authorized users.


title: Septicemia due toStreptococcus mitis in neutropenic patients with acute leukemia

text: Eight neutropenic patients with acute lymphocytic or nonlymphocytic leukemia had septicemia due to different strains ofStreptococcus mitis (St. mitis), a microorganism not commonly recognized as a special pathogen in leukemic patients. Four of the patients had been treated with high-dose cytosine arabinoside as part of the cytostatic regimen, six had a central venous line and four patients had oral lesions prior to the infection. Selective gut decontamination consisted of co-trimoxazole/colistin in five patients and quinolones in three patients. The first three patients died, either due to interstitial pneumonia with the adult respiratory distress syndrome (ARDS), or due to infection-triggered disseminated intravascular coagulation despite prompt empiric antibiotic therapy including vancomycin. The other patients improved after empiric supplementation of penicillin G (30 Mega/day) to the antibiotic regimen. Beginning ARDS in two of these patients dramatically responded to high-dose steriods. We conclude thatSt. mitis is a major pathogen in neutropenic leukemic patients. Infection appears to occur independently of acute leukemic cell type, regimen of selective gut decontamination, venous access, visible oral lesions or treatment with highdose cytosine arabinoside. The clinical course of our patients raises questions about the value of commonly recommended empiric antibiotic regimens, which were clearly ineffective to control infections withSt. mitis in this patient group. Our data indicate that immediate antibiotic therapy with penicillin G is indicated and may be life-saving for suspectedSt. mitis infections in neutropenic leukemic patients.


title: Role of interleukin-8 in community-acquired pneumonia: Relation to microbial load and pulmonary function

text: In pneumonia local phagocyte activation is crucial for clearing of pathogenic microorganisms. In this context alveolar macrophage interleukin-8 secretion, phagocyte oxidative response and concentrations of lavage proteins were quantified, including interleukin-8, in 31 patients with pneumonia, 13 age matched patients with peripheral lung consolidation and six healthy volunteers; these findings were related to the impairment of gas exchange and the bacterial load in the alveolar space. Increased interleukin-8 levels were found in bronchoalveolar lavage fluid (BALF) and in alveolar macrophage supernatants from patients with pneumonia (214 ng/10(5) AM±121 vs 71 ng/10(5) AM±35 and 66 ng/10(5) AM±30, p<0.05). Interleukin-8 release from alveolar macrophages correlated with the upregulated spontaneous luminol enhanced oxidative response of pulmonary phagocytes but not with the neutrophil count in BALF. In pneumonia patients a significant difference was found between patients with 10(4) or more colony forming units (CFU)/ml BALF of one pathogen and patients with less CFU or nonspecific microbiological results (261 ng/10(5) AM±89 vs 179 ng/10(5) AM±81 and 7.5 ng/ml BALF±17 vs 0.44 ng/ml BALF±1, p<0.05). Further, a negative correlation between interleukin-8 release of alveolar macrophages and the arterial pO(2) at the time of BALF could be demonstrated (r=−0.47, p<0.05). The results demonstrate local cellular activation in community-acquired pneumonia, which is related to the bacterial load in the alveolar space and to impairment of gas exchange. This is consistent with the hypothesis that pulmonary phagocytes play a central role in the pathogenesis of bacterial pneumonia, contributing not only to bacterial clearing but also to local tissue damage.


title: Relative Adrenal Insufficiency in the Critical Care Setting: Debunking the Classic Myth

text: BACKGROUND: Classic teaching states that chronic adrenal insufficiency is associated with hyponatremia, hyperkalemia, hypercalcemia, hypoglycemia, and eosinophilia. We hypothesize that these diagnostic markers do not predict relative adrenal insufficiency (RAI) in the critically ill or injured patient. METHODS: Chart review of surgical, trauma, and medical patients admitted over 7 years to a critical care unit was performed to evaluate cortisol levels drawn for suspicion of RAI, which was defined as a cortisol concentration <25 mcg/dl. Laboratory parameters were defined as hyponatremia <135 mmol/l, hyperkalemia >5.3 mmol/l, hypercalcemia >2.55 mmol/l (10.2 mg/dl), hypoglycemia <3.89 mmol/l (70 mg/dl), and eosinophilia >5%. RESULTS: A total of 212 patients had cortisol levels drawn. Fifty-seven percent were male and their mean age was 59 years. Fifty-three percent had RAI. Average cortisol level was 30.5 μg/dl. No significant differences were seen in mean potassium, sodium, calcium, or glucose levels between RAI and non-RAI patients. Few patients had laboratory values consistent with RAI. In fact, many with RAI had opposite findings: 75% had hypernatremia, 90% had hypokalemia, 100% had hypocalcemia, and 97% had hyperglycemia. Eosinophilia was statistically significant (P = 0.026). CONCLUSION: Hyponatremia, hyperkalemia, hypercalcemia, and hypoglycemia do not predominate in RAI and laboratory values are of minimal value in predicting patients with RAI.


title: Double umbilical cord blood transplantation for children and adolescents

text: Umbilical cord blood transplantation (UCBT) with two units has been conducted with promising results in adults to overcome the limitation of low cell numbers. In an attempt to improve the outcomes, double UCBT was performed in children and adolescents. Sixty-one patients, including 44 acute leukemia, and 17 other hematologic diseases, received double UCBT. Donor-type engraftment achieved in 82% of patients. Except one patient with persistent mixed chimerism of two units, other 49 patients showed dominancy of one unit and only the CFU-GM was significant factor influencing dominancy. The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received transplant in first or second CR (68.6%) was significantly better than in those with advanced disease (22.2%) (P = 0.007). Among the factors influencing outcomes, low cell dose difference between two units (TNC difference/TNC of large unit <15%) were associated with higher TRM, relapse, and lower EFS. Double UCBT was a promising modality of transplant in children and adolescence. However, engraftment and other results were not so satisfactory yet. To improve the outcomes, development of new selection guideline, probably including cell dose difference between two units and technology to enhance engraftment and reduce transplantation-related mortality are warranted.


title: Rodent animal models: from mild to advanced stages of diabetic nephropathy

text: Diabetic nephropathy (DN) is a secondary complication of both type 1 and type 2 diabetes, resulting from uncontrolled high blood sugar. 30–40 % of diabetic patients develop DN associated with a poor life expectancy and end-stage renal disease, causing serious socioeconomic problems. Although an exact pathogenesis of DN is still unknown, several factors such as hyperglycemia, hyperlipidemia, hypertension and proteinuria may contribute to the progression of renal damage in diabetic nephropathy. DN is confirmed by measuring blood urea nitrogen, serum creatinine, creatinine clearance and proteinuria. Clinical studies show that intensive control of hyperglycemia and blood pressure could successfully reduce proteinuria, which is the main sign of glomerular lesions in DN, and improve the renal prognosis in patients with DN. Diabetic rodent models have traditionally been used for doing research on pathogenesis and developing novel therapeutic strategies, but have limitations for translational research. Diabetes in animal models such as rodents are induced either spontaneously or by using chemical, surgical, genetic, or other techniques and depicts many clinical features or related phenotypes of the disease. This review discusses the merits and demerits of the models, which are used for many reasons in the research of diabetes and diabetic complications.


title: CT of parenchymal and bronchial tuberculosis

text: Tuberculosis (TB) remains a common disease in the World. Its incidence has risen steadily since 1985, despite a preexisting continuous decreasing of its frequency due to an effective chemotherapy. Nonwhite people, socioeconomically disadvantaged, chronically debilitated groups and AIDS patients are the most concerned. Chest radiography remains the first imaging modality to evaluate TB. Widely radiographic appearances can be encountered, including normal chest X-ray. CT can be useful in all stages of the disease, particularly when clinical and radiological findings are in disagreement and/or when imaging findings are equivocal. CT should be proposed at the end of an effective antituberculous treatment to better subsequently detect fine lesions suggestive of reactivation TB.


title: Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution

text: Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-016-0569-y) contains supplementary material, which is available to authorized users.


docid: nvzcgpyb

title: Anti-inflammatory effects of Reduning Injection (热毒宁注射液) on lipopolysaccharide-induced acute lung injury of rats

text: OBJECTIVE: To evaluate the protective effects of Reduning Injection (热毒宁注射液, RDN), a patent Chinese medicine, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and its underlying mechanisms of action. METHODS: Sixty male Sprague-Dawley rats were randomly divided into 6 groups, including normal control, model, dexamethasone (DEX, 5 mg/kg), RDN-H (720 mg/kg), RDN-M (360 mg/kg) and RDN-L (180 mg/kg) groups, with 10 rats in each group. Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX. At 6 h after LPS challenge, lung tissues and bronchoalveolar lavage fluid (BALF) were collected, and the number of inflammatory cells was determined. The right lungs were collected for histopathologic examination, measurement of gene and protein expressions, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities. RESULTS: In vivo pretreatment of RDN (360, 720 mg/kg) significantly reduced the weight of wet to dry (W/D) ratio of lung, protein content in BALF, and led to remarkable attenuation of LPS-induced histopathological changes in the lungs. Meanwhile, RDN enormously decreased BALF total inflammatory cells, especially neutrophil and macrophage cell numbers. Moreover, RDN increased SOD activity, inhibited MPO activity, alleviated LPS-induced tumor neurosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression in lung tissues. Furthermore, RDN (720 mg/kg) efficiently weakened nuclear factorkappa B (NF-κB) gene and protein expression. CONCLUSION: Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration, lowering MPO activity, TNF-α and iNOS gene expression by inhibiting NF-κB activity in LPS-induced ALI.


title: Chloroquine relieves acute lung injury in rats with acute hemorrhagic necrotizing pancreatitis

text: This study preliminarily investigated the mechanism by which chloroquine (CQ) relieves acute lung injury (ALI) complicated in acute hemorrhagic necrotizing pancreatitis (AHNP). Sixty male Wistar rats were randomized into sham-operated group (group A, n=10), AHNP group (group B, n=10), L-arginine-treated group (group C, n=10), L-N-nitro-L-arginine methyl ester (NAME)-treated group (group D, n=10), CQ-treated group (group E, n=10) and CQ+L-NAME-treated group (group F, n=10). TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide (NO) concentration was reduced, as compared with those in the group A (P<0.05 or P<0.01). Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated (P<0.05 or P<0.01). In the group E, TLR4 expression was substantially lower and NO concentration higher than those in the group B (P<0.05 or P<0.01). However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E (P<0.05 or P<0.01). It was concluded that TLR4 may play an important role in the pathogenesis and development of ALI complicated in AHNP. CQ could relieve ALI by decreasing the TLR4 expression and increasing the NO release.


title: Über eine ungewöhnliche Vaccine-Infektion bei einem Neugeborenen

text: Es wird über eine Vaccineinfektion bei einem Säugling berichtet, der am 20. Lebenstag unter dem Bilde einer Virussepsis starb und versucht, an Hand des klinischen Verlaufes und des Sektionsbefundes den Gang der Infektion zu klären.


title: Das akute Leberversagen

text: Acute liver failure represents a serious life-threatening event comparable to acute heart failure with cardiogenic shock or acute renal failure. Underlying acute liver diseases leading to hepatic failure differ between different geographic regions and in their incidence rates. In Europe etiological agents like viruses, drugs and toxins predominate over other much rarer causes. The different noxious agents lead to hepatocellular necrosis and/or apoptosis with loss of liver cell specific functions subsequent to a fall of functioning hepatocytes below a critical number. The syndrome is clinically characterized by the rapid onset of hepatic encephalopathy within 7 days after a first manifestation of liver disease (fulminant liver disease). Liver failure in patients with preexisting chronic liver disease is largely defined by the time which elapses between the occurrence of jaundice and encephalopathy (hyperacute, acute, subacute liver failure). The acute loss of liver specific functions is accompanied by a number of severe life-threatening complications like cerebral edema, circulatory failure, infections, renal failure and defective coagulation. Management of patients with fulminant liver disease requires a profound knowledge of hepatology and intensive care medicine. A close cooperation with a liver transplant unit is an absolute prerequisite for successful therapy. Permanent or temporary auxiliary liver replacement by a healthy human liver allows for a survival of 60 to 70% of patients selected for such a transplant procedure. Progress has been made in the temporary substitution of specific liver cell functions bridging the time period between liver failure and resumption of hepatocellular functions or availability of a donor liver. Different artificial livers have been designed and introduced into clinical trials. However, further evaluation is urgently needed.


title: Nutritional regulation of glutathione in stroke

text: In contrast to cardiovascular disease, the impact of nutritional status on the prevention and outcome of stroke has received limited investigation. We present a mechanism based on animal studies, clinical data, and epidemiological data by which protein-energy status in the acute stroke and immediate postinjury periods may affect outcome by regulating glutathione (GSH), a key component of antioxidant defense. As cysteine is the limiting amino acid for GSH synthesis, the GSH concentration of a number of nonneural tissues has been shown to be decreased by fasting, low-protein diets, or diets limiting in sulfur amino acids. The mechanism may also be relevant in brain since GSH in some brain regions is responsive to dietary sulfur amino acid supply and to the pro-cysteine drug, L-2-oxothiazolidine-4-carboxylate. The latter is an intracellular cysteine delivery system used to overcome the toxicity associated with cysteine supplementation. These findings may provide the mechanism to explain both the inverse correlation between dietary protein and stroke mortality and the documented association between suboptimal protein-energy status and diminished functional status following a stroke. Future investigations should examine the role of nutritional intervention in neuroprotective strategies aimed at improving stroke outcome. Pharmacological interventions such as L-2-oxothiazolidine-4-carboxylate should be investigated in animal models of stroke, as well as the impact of nutritional status on the response to these agents. Finally, micronutrient deficiencies that may accompany protein-energy malnutrition, such as selenium, should also be investigated for their role in antioxidant defense in cerebral ischemia.


title: Gonadotropin Stimulation Increases the Expression of Angiotensin-(1–7) and Mas Receptor in the Rat Ovary

text: We have previously shown the presence of immunoreactive angiotensin-(1–7) [Ang-(1–7)] in rat ovary homogenate and its stimulatory effect on estradiol and progesterone production in vitro. In the current study, we investigated the presence and cellular distribution of Ang-(1–7) and the Mas receptor, the expression of Mas and angiotensin-converting enzyme 2 (ACE2) messenger RNA (mRNA), and the enzymatic activity in the rat ovary following gonadotropin stimulation in vivo. Immature female Wistar rats (25 days old) were injected subcutaneously (SC) with equine chorionic gonadotropin (eCG, 20 IU in 0.2 mL) or vehicle 48 hours before euthanasia. Tissue distributions of Ang-(1–7), Mas receptor, and ACE2 were evaluated by immunohistochemistry, along with angiotensin II (Ang II) localization, while the mRNA expression levels of Mas receptor and ACE2 were evaluated by real-time polymerase chain reaction (PCR). In addition, we determined the activity of neutral endopeptidase (NEP), prolyl endopeptidase (PEP), and ACE by fluorometric assays. After eCG treatment, we found strong immunoreactivity for Ang-(1–7) and Mas primarily in the theca-interstitial cells, while Ang II appeared in the granulosa but not in the thecal layer. Equine chorionic gonadotropin treatment increased Mas and ACE2 mRNA expression compared with control animals (3.3- and 2.1-fold increase, respectively; P < .05). Angiotensin-converting enzyme and NEP activities were lower, while PEP activity was higher in the eCG-treated rats (P < .05). These data show gonadotropin-induced changes in the ovarian expression of Ang-(1–7), Mas receptor, and ACE2. These findings suggest that the renin-angiotensin system (RAS) branch formed by ACE2/Ang-(1–7)/Mas, fully expressed in the rat ovary and regulated by gonadotropic hormones, could play a role in the ovarian physiology.


title: Chemokines as Molecular Targets for Therapeutic Intervention

text: Despite the youth of the chemokine field, many antagonists of chemokine function have already been identified and tested at the preclinical level. These include neutralizing antibodies, peptidyl and non-peptidyl antagonists and non-specific immunosuppressive agents. These early studies suggest that chemokine agonists have the potential to regulate many diseases, ranging from HIV-1 infection and tumor growth to acute and chronic inflammation. Clinical application will depend on pharmaceutical development. Great strides have been made in defining structural domains of the chemokines involved in receptor binding and activation. The identification of receptors is rapidly progressing, but with 50 potential ligands and 15 characterized receptors, it is obvious that additional molecular studies are needed. The intriguing observation that several pathogens either use chemokine receptors as entry portals or produce chemokine decoys to subvert the immune system suggests that there is much to be learned about the immune system from studies of “virokines.” Future studies should lead to the discovery and design of more effective inhibitors and antagonists with therapeutic benefit.


title: Group A streptococcal sepsis

text: The fulminant nature of group A streptococcal sepsis poses impressive challenges from diagnostic and therapeutic perspectives. Most patients are seen early in the course of infection by primary care providers or emergency department physicians and sent home, only to return in 12 to 24 hours with fully developed group A streptococcal sepsis. Early diagnosis is imperative, but the clinician must have a high index of suspicion. Often, the diagnosis is established only after aggressive interventional management has begun. This review emphasizes salient clinical features and provides general recommendations for critical care management.


title: Protective effect of acacetin on sepsis-induced acute lung injury via its anti-inflammatory and antioxidative activity

text: Sepsis is a clinical syndrome with no effective protective or therapeutic treatments. Acacetin, a natural flavonoid compound, has anti-oxidative and anti-inflammatory effects which can potentially work to reduce sepsis. We investigated the potential protective effect of acacetin on sepsis-induced acute lung injury (ALI) ALI and dissect out the underlying mechanisms. Mice were divided into five groups: a sham group, a sepsis-induced ALI group, and three sepsis groups pre-treated with 20, 40, and 80 mg/kg body weight of acacetin. We found that acacetin significantly attenuated sepsis-induced ALI, in histological examinations and lung edema. Additionally, acacetin treatment decreased protein and inflammatory cytokine concentration and the number of infiltrated inflammatory cells in BALF compared with that in the non-treated sepsis mice. Pulmonary myeloperoxidase (MPO) activity was lower in the acacetin-pre-treated sepsis groups than in the sepsis group. The mechanism underlying the protective effect of acacetin on sepsis is related to the regulation of certain antioxidation genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), superoxide dismutases (SODs), and heme oxygenase 1 (HO-1).Taken together, our results indicate that acacetin pre-treatment inhibits sepsis-induced ALI through its anti-inflammatory and antioxidative activity, suggesting that acacetin may be a potential protective agent for sepsis-induced ALI.


docid: sbfomkcv

title: Antifibrotic Therapies: Will We Ever Get There?

text: Progressive hepatic fibrosis is the final common pathway for most chronic liver injuries, leading to cirrhosis with risk of liver failure and hepatocellular carcinoma. It is now recognized that fibrosis is a dynamic process, and may be reversible prior to the establishment of advanced architectural changes to the liver. The most effective antifibrotic strategy is to cure the underlying disease process before advanced fibrosis has developed. Unfortunately, this is often not possible, and specific antifibrotic therapies are needed. Advances in the understanding of the pathogenesis of liver fibrosis have identified several potential novel therapeutic targets, but unfortunately clinical development has been disappointing. One major limitation has been the often prolonged natural history of fibrosis compared to experimental models, and difficulties in accurate noninvasive fibrosis assessment, thus making clinical trial design difficult. In this review, we highlight the most promising current antifibrotic strategies.


title: Clinical course and end-of-life care in patients who have died after allogeneic stem cell transplantation

text: PURPOSE: Allogeneic stem cell transplantation may cure approximately 50% of patients, however, a significant part of the other half might benefit from a high-quality palliative care medicine at the end of life. Somatic, psychic and spiritual needs of these patients may differ from those of patients suffering from incurable solid tumours and are not comprehensively evaluated so far. METHODS: To address this question, data from charts of 123 patients who have died after allogeneic stem cell transplantation were extracted. In detail, the time line of the clinical course, the symptoms, the administered drugs and other applied procedures were analysed. RESULTS: Approximately one half of the patients, who have died after stem cell transplantation, did not live more than 5 months. Two-thirds of patients died within 14 months after SCT. 28.5% of the patients could not be discharged after transplantation. However, a significant proportion had a low ECOG-score (0–1) prior to death, indicating a high degree of mobility. Major symptoms were weakness, fatigue and need for aid at daily activities. Severe pain, dyspnoea and obstipation, as known from patients suffering from advanced solid tumours, were rare. In consequence, use of opioids seemed to be less frequent than in patients with solid tumours. Measures of intensive care and i.v.-drug administration were applied to a significant proportion of patients. CONCLUSION: The present investigation indicates that the somatic, psychic and spiritual end-of-life-care after allogeneic stem cell transplantation could be optimised. A significant problem for the transplantation team seems to be the realisation of necessity to switch the curative concept into a palliative ambition. Requirements are a subsequent prospectively conducted investigation and an intensification of cooperation between transplant and palliative care teams.


title: Influence of hilar deposition in the evaluation of the alveolar epithelial permeability on (99m)Tc-DTPA aerosol inhaled scintigraphy

text: PURPOSE: We investigated whether hilar radioaerosol deposition affects the clearance rate of technetium-99m-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) from peripheral alveolar regions. MATERIALS AND METHODS: A total of 38 patients underwent (99m)Tc-DTPA inhalation lung scintigraphy. Six region of interest (ROI) patterns were adopted: ROI 1 was outlined around the entire hemithorax, and ROIs 2–6 were outlined around the hemithorax but excluded square ROIs of different size in the hilar region. Half-times (T(½)) were calculated with time-activity curves using onecompartment and two-compartment analyses. The T(½) of ROIs 1–5 were plotted against the T(½) of ROI 6, and regression lines were obtained with the least-squares method. The absolute values of the differences between surveyed values and regression line were calculated. The Wilcoxon test for trend and a single linear regression model were used to determine statistical significance. RESULTS: There were significant reductions in the absolute values of the differences between surveyed values and regression line from ROIs 1–5 by one-component analysis and the fast component of two-compartment analysis (P < 0.001). CONCLUSION: Our results suggest that the deposition of radioaerosol in the hilar region affects the clearance rate of (99m)Tc-DTPA from the alveoli in damaged lungs. The hilar region should be excluded from ROIs when alveolar epithelial permeability is evaluated.


title: Infektiöse obere Luftwegsobstruktion: Ein pädiatrischer Notfall

text: Infectious diseases of the upper airway can lead to emergency situations with partial up to complete obstruction and respiratory insufficiency, especially in infants and toddlers. This necessitates a cool-headed and calm approach; however, at times a prompt intervention is required by the primary care physician. Important questions concerning patient history include the onset of symptoms, severity and duration of fever and for orientation possible previously known respiratory problems since birth or in the first weeks afterwards (e.g. congenital malformations of the larynx or trachea). The examination should begin by careful observation of the child’s position of comfort and by noting all vital signs. A child with inspiratory or biphasic stridor at rest already has some degree of airway obstruction that can progress to complete obstruction over time. Systemic steroids and inhalation of nebulized epinephrine (adrenaline) are the best therapeutic options for viral laryngotracheobronchitis, which is the most common cause of acute stridor in childhood. Rare differential diagnoses, such as bacterial tracheitis, epiglottitis (supraglottitis), retropharyngeal and parapharyngeal infections necessitate disease-specific management.


title: Rapidly progressive interstitial lung disease due to anti-MDA5 antibodies without skin involvement: a case report and literature review

text: Anti-MDA5 antibodies have been strongly associated with rapidly progressive interstitial lung disease (RP-ILD) in dermatomyositis (DM) patients, especially in the clinically amyopathic subset (CADM). We present a case of anti-MDA5 antibody-associated RP-ILD in a patient with arthritis but with no other clinical signs suggestive of DM or CADM successfully treated with a combination of cyclophosphamide, cyclosporine and corticoids. A review of the literature was also done. Despite its rarity, anti-MDA5 antibody-associated ILD should be suspected in cases of RP-ILD even without other signs of DM or CADM as prompt and aggressive treatment could improve prognosis.


title: Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract

text: Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36–0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients’ gut microbiota may also contribute to ileostomy’s therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00277-019-03754-3) contains supplementary material, which is available to authorized users.