Type I IFN signaling limits hemorrhage-like disease after infection with Japanese encephalitis virus through modulating a prerequisite infection of CD11b+Ly-6C+ monocytes.

BACKGROUND: The crucial role of type I interferon (IFN-I, IFN-α/ß) is well known to control central nervous system (CNS) neuroinflammation caused by neurotrophic flaviviruses such as Japanese encephalitis virus (JEV) and West Nile virus. However, an in-depth analysis of IFN-I signal-dependent cellular factors that govern CNS-restricted tropism in JEV infection in vivo remains to be elucidated. METHODS: Viral dissemination, tissue tropism, and cytokine production were examined in IFN-I signal-competent and -incompetent mice after JEV inoculation in tissues distal from the CNS such as the footpad. Bone marrow (BM) chimeric models were used for defining hematopoietic and tissue-resident cells in viral dissemination and tissue tropism. RESULTS: The paradoxical and interesting finding was that IFN-I signaling was essentially required for CNS neuroinflammation following JEV inoculation in distal footpad tissue. IFN-I signal-competent mice died after a prolonged neurological illness, but IFN-I signal-incompetent mice all succumbed without neurological signs. Rather, IFN-I signal-incompetent mice developed hemorrhage-like disease as evidenced by thrombocytopenia, functional injury of the liver and kidney, increased vascular leakage, and excessive cytokine production. This hemorrhage-like disease was closely associated with quick viral dissemination and impaired IFN-I innate responses before invasion of JEV into the CNS. Using bone marrow (BM) chimeric models, we found that intrinsic IFN-I signaling in tissue-resident cells in peripheral organs played a major role in inducing the hemorrhage-like disease because IFN-I signal-incompetent recipients of BM cells from IFN-I signal-competent mice showed enhanced viral dissemination, uncontrolled cytokine production, and increased vascular leakage. IFN-I signal-deficient hepatocytes and enterocytes were permissive to JEV replication with impaired induction of antiviral IFN-stimulated genes, and neuron cells derived from both IFN-I signal-competent and -incompetent mice were vulnerable to JEV replication. Finally, circulating CD11b+Ly-6C+ monocytes infiltrated into the distal tissues inoculated by JEV participated in quick viral dissemination to peripheral organs of IFN-I signal-incompetent mice at an early stage. CONCLUSION: An IFN-I signal-dependent model is proposed to demonstrate how CD11b+Ly-6C+ monocytes are involved in restricting the tissue tropism of JEV to the CNS.

Spontaneous rupture of pyogenic liver abscess with subcapsular hemorrhage mimicking ruptured hepatocellular carcinoma: A case report.

RATIONALE: Spontaneous rupture of PLA (pyogenic liver abscess) is an extremely rare and life-threatening event. Ruptured PLA is very difficult to distinguish from malignant HCC (hepatocellular cancer) rupture or cholangiocarcinoma rupture on CT (computed tomography) scan. PATIENT CONCERNS: We describe the case of a 71-year-old man with fever, right upper abdominal pain, nausea with intermittent vomiting, and general fatigue. He had no medical or surgical history. DIAGNOSIS: CT scan showed a hypodense mass in right hepatic lobe and MRI (magnetic resonance imaging) revealed a heterogenous mass of ∼6 cm in segment VI of the liver and heterogenous fluid in the subcapsular region. We made a tentative diagnosis of HCC rupture with subcapsular hemorrhage based on these findings. INTERVENTION: After improving the patient's condition by administering empirical therapy consisting of intravenous antibiotics and fluids, we performed surgical exploration. Gross examination of the abdomen showed that almost the entire right hepatic lobe was hemorrhagic and affected by peritonitis. Therefore, we performed right hepatectomy. The intraoperative frozen biopsy revealed suspicious PLA with marked necrosis, neutrophil infiltration, and hemorrhagic rupture, although no malignant tissue or fungus was observed. The postoperative secondary pathology report confirmed the diagnosis of PLA with hemorrhagic rupture. OUTCOMES: The patient was discharged 13 days after the operation. Follow-up CT was performed 5 months after discharge and revealed no abnormal findings. LESSONS: A high index of suspicion is key to preventing misdiagnosis of ruptured PLA and improving prognosis. Furthermore, even if rupture of the PLA is initially localized, delayed peritonitis may occur during medical treatment. Therefore, vigilant monitoring is essential.

A salivary metabolite signature that reflects gingival host-microbe interactions: instability predicts gingivitis susceptibility.

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.

Clinical Characteristics of Rapidly Progressive Fatal Hemorrhagic Pneumonia Caused by Stenotrophomonas maltophilia.

Objective Hemorrhagic pneumonia due to Stenotrophomonas maltophilia (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. Methods This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. Patients All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. Results The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). Conclusion Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation.

Polytrauma independent of therapeutic intervention alters the gastrointestinal microbiome.

BACKGROUND: This study characterizes the gastrointestinal (GI) microbiome in a pre-clinical polytrauma hemorrhage model. METHODS: Rats (n = 6) were anesthetized, hemorrhaged 20% of their blood volume, and subjected to a femur fracture and crush injuries to the small intestine, liver, and limb skeletal muscle without resuscitation. Fecal samples were collected pre-injury and 2 h post-injury. Purified DNA from the samples underwent 16s rRNA sequencing for microbial quantification. Bacterial diversity analysis and taxonomic classification were performed. RESULTS: Following injury, the gut microbial composition was altered with a shift in beta diversity and significant differences in the relative abundance of taxa. The relative abundance of the families Lachnospiraceae and Mogibacteriaceae was increased at 2 h, while Barnesiellaceae and Bacteroidaceae were decreased. Alpha diversity was unchanged. CONCLUSIONS: The GI microbiome is altered in rats subjected to a polytrauma hemorrhage model at 2 h post-injury in the absence of antibiotics or therapeutic interventions.

Bacteria prevalence in a large Italian population sample: a clinical and microbiological study.

The present study detects those bacterial species which are more strongly related to bleeding on probing, suppuration and smoking in periodontal-affected patients. Nine hundred and fifty-one patients with periodontal diseases were admitted to the Department of Periodontology and Implantology, Dental School of Bologna University where they underwent microbiological tests for six periodontal pathogens (Actinomyces actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, Fusobacterium nucleatum and Tannerella forsythia). Cluster analysis explored the variables that mostly influence both the presence and absolute\relative bacterial load. Logistic regression and multivariate linear regression quantifies these relations. The probability of recovering bacteria belonging to the Red Complex is greater by 25-48% in presence of bleeding on probing. When probing depth is less than 3 mm the probability of presence of each bacterial species is inferior in comparison with depth >6 mm both for Red Complex (of 20-37%), the Orange complex (of 41-61%) and Actinomyces actinomycetemcomitans (46%). Total bacterial cell count increases with pocket depth above all for the Red Complex. As Treponema Denticola and Tannerella Forsytia presence is associated with bleeding on probing and Prevotella intermedia presence with suppuration and smoking. The examination of these three as indicators of periodontitis evolution is suggested.

Characterization of Seven Outbreaks of Hemorrhagic Hepatopathy Syndrome in Commercial Pullets Following the Administration of a Salmonella Enteritidis Bacterin in California.

Between April 2013 and April 2015, seven flocks belonging to three different major commercial egg producers inCalifornia experienced a mild increase in mortality 2 to 3 wk after administration of Salmonella Enteritidis bacterins. Strains of chickens involved were H&N (flock A1, A2, B2, C1, C2, and C3) and Lohmann white (flock B1). Vaccination was administered individually through injection either in the breast muscles or subcutis in the legs between 11 and 18 wk of age in all flocks. Clinical signs ranged from inapparent to lameness, reluctance to walk, greenish diarrhea, and retching-like symptoms. The mortality ranged from 0.16% to 1.38% per week, with the highest peaks occurring usually 2 to 3 wk postvaccination, and then declined rapidly. Postmortem examinations revealed enlarged livers with disseminated hemorrhages and pale foci of necrosis. Also, severe extensive hemorrhages in the intestine, heart, and proventriculus were observed in a few birds. Various degrees of productive, exudative giant cell granulomatous myositis were observed invading deeply the muscles and subcutis at the site of vaccination. The myositis was always associated with optically empty vacuoles positive for neutral lipids by Oil Red O stain. Droplets of Oil Red O material were also noticed in the affected livers and intestines. Congo red stain highlighted the presence of amyloid in moderate to severe amounts in the breast muscles and moderate amounts in livers, spleens, and intestines. Salmonella antigens were detected in the injection sites and livers by immunohistochemical staining. No viruses or toxic substances were recovered from the liver, spleen, intestine, and pectoral muscles, and the few bacteria isolated were interpreted as secondary postmortem invaders. In addition, livers and bile tested for hepatitis E virus were negative by reverse-transcriptase polymerase chain reaction.

Gingipains: Critical Factors in the Development of Aspiration Pneumonia Caused by Porphyromonas gingivalis.

Aspiration pneumonia is a life-threatening infectious disease often caused by oral anaerobic and periodontal pathogens such as Porphyromonas gingivalis. This organism produces proteolytic enzymes, known as gingipains, which manipulate innate immune responses and promote chronic inflammation. Here, we challenged mice with P. gingivalis W83 and examined the role of gingipains in bronchopneumonia, lung abscess formation, and inflammatory responses. Although gingipains were not required for P. gingivalis colonization and survival in the lungs, they were essential for manifestation of clinical symptoms and infection-related mortality. Pathologies caused by wild-type (WT) P. gingivalis W83, including hemorrhage, necrosis, and neutrophil infiltration, were absent from lungs infected with gingipain-null isogenic strains or WT bacteria preincubated with gingipain-specific inhibitors. Damage to lung tissue correlated with systemic inflammatory responses, as manifested by elevated levels of TNF, IL-6, IL-17, and C-reactive protein. These effects were unequivocally dependent on gingipain activity. Gingipain activity was also implicated in the observed increase in IL-17 in lung tissues. Furthermore, gingipains increased platelet counts in the blood and activated platelets in the lungs. Arginine-specific gingipains made a greater contribution to P. gingivalis-related morbidity and mortality than lysine-specific gingipains. Thus, inhibition of gingipain may be a useful adjunct treatment for P. gingivalis-mediated aspiration pneumonia.

Vesiculobullous and hemorrhagic erythema migrans: uncommon variants of a common disease.

BACKGROUND: The diagnosis of Lyme disease relies on the accurate diagnosis of erythema chronicum migrans (ECM) because serologic tests, culture, and polymerase chain reactions are often inaccurate. Although ECM is classically associated with a targetoid rash, there are many variants of this lesion. These variants of ECM are often initially diagnosed as cellulitis or spider bite reactions and treated with oral antibiotics. Inappropriate treatment further delays the diagnosis of Lyme disease, leading to late complications. METHODS: We present four cases of vesiculobullous and hemorrhagic ECM, a less common variant of ECM. RESULTS: All four patients had a history of exposure to wooded areas in Massachusetts during the summer months. In these patients, ECM presented with central vesicles and bullae with hemorrhage, crusting, and in some cases necrosis. Serologic testing was positive in three of the four cases at presentation. In one case, microscopic examination of a skin biopsy showed epidermal spongiosis with parakeratosis, focal necrosis, papillary dermal edema, erythrocyte extravasation, and a superficial and deep perivascular lymphocytic infiltrate with neutrophils and eosinophils of the dermis. No fungal organisms or bacteria were identified. All four patients were treated with doxycycline with complete resolution of symptoms. CONCLUSIONS: It is important to recognize the vesiculobullous and hemorrhagic variants of ECM in order to minimize the provision of inappropriate antibiotic treatment for other diagnoses. Early diagnosis of ECM and the initiation of appropriate antibiotics may prevent late complications of Lyme disease.

Diffuse alveolar hemorrhage in a patient with acute poststreptococcal glomerulonephritis caused by impetigo.

We herein report a case of pulmonary renal syndrome with nephritis in a 17-year-old boy with diffuse alveolar hemorrhage (DAH) associated with acute poststreptococcal glomerulonephritis (APSGN). The patient exhibited hemoptysis two weeks after developing impetigo, and DAH was diagnosed on bronchoscopy. Respiratory failure progressed, and high-dose methylprednisolone therapy was administered; the respiratory failure regressed immediately after the onset of therapy. Streptococcus pyogenes was detected in an impetigo culture, and, together with the results of the renal biopsy, a diagnosis of APSGN was made. This case demonstrates the effects of high-dose methylprednisolone therapy in improving respiratory failure.

Does cervical ureaplasma/mycoplasma colonization increase the lower uterine segment bleeding risk during cesarean section among patients with placenta previa? A cross-sectional study.

OBJECTIVE: The underlying inflammation of endometrium may impede normal implantation of placenta during pregnancy. Our objective is to show cervical colonization of ureaplasma and/or mycoplasma as a marker of endometritis in pregnancies complicated with placenta previa that can be a risk factor for placenta accreta and peripartum hemorrhage. PATIENTS AND METHODS: Cervical cultures for ureaplasma urealyticum and mycoplasma genitalium have been taken from the endocervical region of the cervix of the patients. Subsequent uterine lower segment bleeding suggesting placenta implantation defects have been evaluated during cesarean section. RESULTS: Of 25 patients: ten (40%) had negative cervical cultures for cervical mycoplasma and/or ureaplasma, 9 (36%) were found to be culture positive for cervical ureaplasma, 1 (4%) was found to be culture positive for cervical mycoplasma. Half of the 10 patients with positive cervical cultures for ureaplasma or mycoplasma and 6 of (40%) 15 patients with negative results had experienced lower uterine segment bleeding during cesarean section. CONCLUSIONS: Bacterial colonization of cervix in particular with ureaplasma and/or mycoplasma is found to be strongly associated with placenta previa. Before a planned pregnancy, treatment of this infection with appropriate antibiotics is necessary to prevent underlying uterine endometritis that increases the risk for abnormal implantation of placenta.

[Comparative evaluation of efficacy of histological and cytological methods of H. pylori primary diagnosis in pyloroduodenal ulcer complicated by hemorrhage].

In 48 patients, suffering gastroduodenal ulcer disease, complicated by hemorrhage, cytological and histological investigations were conducted to reveal helicobacter infection. There was established, that sensitivity, specificity and accuracy of smears--the gastric mucosa imprints--cytological investigation exceeds such of histological investigation of biopsies. In more than 80% patients, in whom pyloroduodenal ulcer, complicated by hemorrhage, was diagnosed, Helicobacter pylori (H. pylori) was revealed in gastric mucosa.

Acquired hemophilia A in a patient associated with community-acquired pneumonia.

Acquired hemophilia A (AHA) is a rare disease induced by autoantibodies to factor VIII (FVIII) and may be correlated with pregnancy, underlying malignancies, autoimmune diseases or drug administration. An 81-year-old man who presented with cough, expectoration, hemoptysis and multiple ecchymoses was diagnosed with community-acquired pneumonia by computed tomography scan. Respiratory symptoms were ameliorated after the application of antibiotics. Despite repeated infusion of fresh frozen plasma and cryoprecipitate, his prolonged activated partial thromboplastin time (APTT) maintained in the 75-110-s range and ecchymoses were not ameliorated. Then, he was transferred to the department of hematology. Based on a prolonged APTT, decreased level of FVIII and presence of antibodies against FVIII, the patient was diagnosed with AHA. Then the patient was treated with activated prothrombin complex concentrates, prednisone and intravenous immunoglobulin, resulting in a complete remission of the bleeding, recovering the FVIII level and negativity for FVIII antibody titers. Here, we investigate this novel case retrospectively and review the relevant literature.

Isolation of an X-factor-dependent but porphyrin-positive Escherichia coli from urine of a patient with hemorrhagic cystitis.

An Escherichia coli isolate was recovered from a 92-year-old female patient with urinary tract infection. Gram-stained preparation of the urine sediment manifested some gram-negative rod-shaped cells, and the urine specimen culture yielded nonhemolytic colonies on sheep blood agar plate. However, no visible colonies appeared on modified Drigalski agar plate. The isolate was finally identified as an X-factor-dependent E. coli. The interesting finding was that the isolate revealed a positive reaction for porphyrin test despite the requirement of hemin. This finding suggested that some pyrrol-ring-containing porphyrin compounds or fluorescent porphyrins had been produced as chemical intermediates in the synthetic pathway from δ-amino-levulinic acid (ALA), although the isolate should be devoid of synthesizing hems from ALA. This was the first clinical isolation of such a strain, indicating that the E. coli isolate should possess incomplete synthetic pathways of hems from ALA.

Tuberculous pericarditis presenting as massive haemorrhagic pericardial effusion.

Tuberculous pericarditis is an exceedingly rare but a well-described extra-pulmonary manifestation of tuberculosis (TB) infection in Hong Kong. An 82-year-old woman with a known history of diabetes mellitus, hypertension and hyperlipidaemia was admitted for congestive heart failure. Routine echocardiographic study during admission revealed a massive pericardial effusion (~4 cm in thickness) but with no tamponade effect. Pericardiocentesis was performed and 1.6 L of heavily blood stained fluid was drained. All tumour and auto-immune markers were unremarkable. A whole body positron emission tomography-computer tomography (PET-CT) scan was then performed and showed an increased fluorodeoxyglucose uptake in the entire pericardium with no sources of possible malignancy identified. Rapid acid fast bacilli culture and Genprobe examination of the pericardial fluid then demonstrated the growth of Mycobacterium tuberculosis. She was started on anti-TB medications and tolerated them well. Follow-up echocardiographic study showed no re-accumulation of pericardial fluid.

External fistulous wound with Pseudomonas aeruginosa infection and massive bleeding following rupture of pulmonary suppuration.

We present a 54-year old man with a pulmonary infectious cavity continuing to a cutaneous fistula. Before he was admitted to our hospital, he had undergone open-window surgery for a left thoracic empyema due to the rupture of pulmonary suppuration of the left upper lobe. He had then undergone thoracoplasty with the plombage of the cavity using left pectoralis major muscle. However, this procedure had failed and the external fistulous wound remained infected by Pseudomonas aeruginosa and occasional massive bleeding from the cavity occurred. He underwent en bloc left upper lobectomy for the external fistulous wound. The pedicled left latissimus dorsi muscle flap was transposed to fill the dead space and reinforce the bronchial stump. He remained in good health and did not experience intrathoracic infection or haemoptysis.

Fatal hemorrhagic pneumonia caused by Stenotrophomanas maltophilia in a patient with non-Hodgkin lymphoma.

Stenotrophomonas maltophilia is increasingly emerging as a multiresistant pathogen in the hospital environment. In immunosuppressed patients, this bacterium may cause severe infections associated with sepsis and multiple organ dysfunction. We report on a 57-year-old woman treated with intensive chemotherapy for non-Hodgkin lymphoma who developed severe neutropenia, hemorrhagic pneumonia, and acute respiratory failure, which led to her death within 36 h of onset of pneumonia. Postmortem examination revealed bilateral extensive intraalveolar hemorrhage associated with severe infection by the gram-negative bacterium Stenotrophomonas maltophilia. In vitro susceptibility testing showed resistance to carbapenem, cephalosporines and aminoglycosides, but sensitivity to minocycline, ciprofloxacin, levofloxacin, and trimethoprim/sulfamethoxazole (cotrimoxazole). Early diagnosis and adequate antibiotic treatment were difficult, as the clinical course was rapid and fulminant, and this bacterium is resistant to multiple antibiotics. To improve prognosis in such cases, it will be necessary to develop an effective prophylactic strategy for high-risk patients.

Real-time PCR improves Helicobacter pylori detection in patients with peptic ulcer bleeding.

BACKGROUND AND AIMS: Histological and rapid urease tests to detect H. pylori in biopsy specimens obtained during peptic ulcer bleeding episodes (PUB) often produce false-negative results. We aimed to examine whether immunohistochemistry and real-time PCR can improve the sensitivity of these biopsies. PATIENTS AND METHODS: We selected 52 histology-negative formalin-fixed paraffin-embedded biopsy specimens obtained during PUB episodes. Additional tests showed 10 were true negatives and 42 were false negatives. We also selected 17 histology-positive biopsy specimens obtained during PUB to use as controls. We performed immunohistochemistry staining and real-time PCR for 16S rRNA, ureA, and 23S rRNA for H. pylori genes on all specimens. RESULTS: All controls were positive for H. pylori on all PCR assays and immunohistochemical staining. Regarding the 52 initially negative biopsies, all PCR tests were significantly more sensitive than immunohistochemical staining (p<0.01). Sensitivity and specificity were 55% and 80% for 16S rRNA PCR, 43% and 90% for ureA PCR, 41% and 80% for 23S rRNA PCR, and 7% and 100% for immunohistochemical staining, respectively. Combined analysis of PCR assays for two genes were significantly more sensitive than ureA or 23S rRNA PCR tests alone (p<0.05) and marginally better than 16S rRNA PCR alone. The best combination was 16S rRNA+ureA, with a sensitivity of 64% and a specificity of 80%. CONCLUSIONS: Real-time PCR improves the detection of H. pylori infection in histology-negative formalin-fixed paraffin-embedded biopsy samples obtained during PUB episodes. The low reported prevalence of H. pylori in PUB may be due to the failure of conventional tests to detect infection.