Determinants of worse liver-related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort.

OBJECTIVES: We aimed to study hepatitis D virus (HDV) prevalence and risk of progression to severe liver-related events (SLRE) in HBsAg positive people living with HIV (PLWH) in Italy; role of HDV-RNA copy levels, HCV coinfection and nadir CD4 counts were also investigated. METHODS: People living with HIV (PLWH) from Italian Foundation cohort Naïve antiretrovirals (ICONA) with available HBsAg and HDV Ab were enrolled. HBsAg, HDV Ab, HDV-RNA and HDV genotypes were tested. PRIMARY END-POINT: time from first HDV screening to Severe Liver Related Events (SLRE: decompensated cirrhosis, liver transplantation, HCC). Fine-grey regression models were used to evaluate the association of HDV Ab, HDV-RNA, HDV/HCV coinfection, CD4 nadir and outcome. Secondary end-points: time to SLRE or death; HDV Ab and HDV-RNA prevalence. RESULTS: A total of 152/809 (18.8%) HBsAg positive PLWH showed HDV Ab reactivity; 63/93 (67.7%) were HDV-RNA positive. Being male, persons who inject drugs (PWID), HCV Ab positive, with FIB-4 > 3.25 were independent factors of HDV Ab positivity. In a median follow-up of 5 years, 37 PLWH (4.1% at 5-year) developed SLRE and 97 (12.0%) reached the SLRE or death end-point. HDV-RNA positive (independently from HDV-RNA copy level) PLWH had a 4.6-fold (95%CI 2.0-10.5) higher risk of SLRE than HDV negatives. PLWH positive for both HCV Ab and HDV Ab showed the highest independent risk of SLRE (ASHR: 11.9, 95%CI: 4.6-30.9 vs. HCV neg/HDV neg). Nadir CD4 < 200/mL was associated with SLRE (ASHR: 3.9, 95% 1.0-14.5). CONCLUSIONS: One-fifth of the HBsAg positive PLWH harbour HDV infection, and are at high risk of progression to advanced liver disease. HCV contributes to worse outcomes. This population needs urgently effective treatments.

Primary central nervous system lymphomas in immunocompromised patients require specific response criteria.

PURPOSE: Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. METHODS: We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. RESULTS: We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15 mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. CONCLUSION: In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed.

Prevention of ICU-acquired infection with decontamination regimen in immunocompromised patients: a pre/post observational study.

PURPOSE: Although the proportion of immunocompromised patients admitted to the ICU is increasing, data regarding specific management, including acquired infection (ICU-AI) prophylaxis, in this setting are lacking. We aim to investigate the effect of multiple-site decontamination regimens (MSD) in immunocompromised patients. METHODS: We conducted a prospective pre-/post-observational study in 2 ICUs in Bretagne, western France. Adults who required mechanical ventilation for 24 h or more were eligible. During the study period, MSD was implemented in participating ICUs in addition to standard care. It consists of the administration of topical antibiotics (gentamicin, colistin sulfate, and amphotericin B), four times daily in the oropharynx and the gastric tube, 4% chlorhexidine bodywash once daily, and a 5-day nasal mupirocin course. RESULTS: Overall, 295 immunocompromised patients were available for analysis (151 in the post-implementation group vs 143 in the pre-implementation group). Solid organ cancer was present in 77/295 patients while immunomodulatory treatments were noticed in 135/295. They were 35 ICU-AI in 29/143 patients in the standard-care group as compared with 10 ICU-AI in 9/151 patients in the post-implementation group (p < 0.001). In a multivariable Poisson regression model, MSD was independently associated with a decreased incidence of ICU-AI (incidence rate ratio = 0.39; 95%CI [0.20-0.87] p = 0.008). There were 35/143 deaths in the standard-care group as compared with 22/151 in the post-implementation group (p = 0.046), this difference remained in a multivariable Cox model (HR = 0.58; 95CI [0.34-0.95] p = 0.048). CONCLUSION: In conclusion, MSD appeared to be associated with improved outcomes in critically ill immunocompromised patients.

Regulatory T cells in ischemic stroke.

Recent evidence shows that when ischemic stroke (IS) occurs, the BBB would be destructed, thereby promoting the immune cells to migrate into the brain, suggesting that the immune responses can play a vital role in the pathology of IS. As an essential subpopulation of immunosuppressive T cells, regulatory T (Treg) cells are involved in maintaining immune homeostasis and suppressing immune responses in the pathophysiological conditions of IS. During the past decades, the regulatory role of Treg cells has attracted the interest of numerous researchers. However, whether they are beneficial or detrimental to the outcomes of IS remains controversial. Moreover, Treg cells exert distinctive effects in the different stages of IS. Therefore, it is urgent to elucidate how Treg cells modulate the immune responses induced by IS. In this review, we describe how Treg cells fluctuate and play a role in the regulation of immune responses after IS in both experimental animals and humans, and summarize their biological functions and mechanisms in both CNS and periphery. We also discuss how Treg cells participate in poststroke inflammation and immunodepression and the potential of Treg cells as a novel therapeutic approach.

[A rare but increasing aetiology of febrile dyspnea in the elderly]. / Une dyspnée fébrile chez un patient âgé.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infectious disease well described in patients living with HIV (PLHIV) but that can occur in other immunosuppressed patients. Currently, its incidence decreases in PLHIV but increases in non-HIV immunosuppressed patients, particularly in case of hematological diseases. Thus, in elderly, the diagnosis of PJP should be evoked in case of subacute pneumonia rapidly evolving to an acute respiratory distress, with or without interstitial pneumonia at chest radiography, and a context of immunosuppression.

Early emergence of opportunistic infections after starting direct-acting antiviral drugs in HIV/HCV-coinfected patients.

Varicella-zoster virus and hepatitis B virus reactivations have been reported after starting interferon-free direct-acting antiviral agent (DAA) combinations. HIV/HCV-coinfected patients could be a high-risk group for the reactivation of latent infections. Because of these, we report the occurrence of severe infections after starting DAA regimens in HIV/HCV-coinfected patients. Individuals included in the HEPAVIR-DAA (NCT02057003) cohort were selected if they had received all-oral DAA combinations. A retrospective review of clinical events registered between the start of DAAs and 12 months after SVR12 was carried out. Overall, 38 (4.5%) of 848 patients presented infections. The incidence (95% confidence interval) of infections was 4.6 (3.3-6.3) cases per 100 person-years. The median (Q1-Q3) time to the infection since baseline was 23 (7.3-33) weeks. Five (13%) of the patients with infections died; four of them had cirrhosis. The frequency of previous AIDS was 21 (54%) for patients with infections and 324 (40%) for those without infections (P = 0.084). The median (Q1-Q3) nadir CD4 cell count of individuals with and without infections was 75 (53-178) and 144 (67-255) cells/µL, respectively (P = 0.047). Immunodepression-associated infections were observed in 9 (1.1%) patients. All of them had suppressed HIV replication with antiretroviral therapy. In conclusion, severe infections are relatively common among HIV/HCV-coinfected patients receiving all-oral DAA combinations. Some unusual reactivations of latent infections in patients with suppressed HIV replication seem to be temporally linked with DAA use.

Immunodepression after CPB: Cytokine dynamics and clinics after pediatric cardiac surgery - A prospective trial.

BACKGROUND: Corrective surgery for congenital heart defects is known to trigger a severe immune reaction. There has been extensive research on the effects of inflammation after cardiopulmonary bypass (CPB). Interestingly, monocytes are observed to be non-responsive to stimulation with lipopolysaccharide (LPS) under these conditions, indicating a state of immunodepression, which lays the ground for second hit infections after cardiosurgery with CPB. OBJECTIVES: The aim of this prospective study was to analyze immunodepression after pediatric cardiopulmonary bypass and to differentiate the effects of monocytic anergy on postoperative outcome. METHODS: In a prospective trial, we quantified the immune responses in 20 pediatric patients (median age 4.9months, range 2.3-38.2months; median weight 7.2kg, range 5.2-11.7kg) with congenital ventricular septal defect undergoing heart surgery with CPB. Ex vivo LPS-induced protein expression of IFN-γ, IL-1ß, IL-1Ra, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and MCP-1 was measured before (T1), immediately after (T2) and 4h after (T3) cardiopulmonary bypass surgery using Luminex technology. RESULTS: The innate immune system responds to CPB with an almost complete depression of monocytic function. Inflammatory IL-12, TNF-α, IL-1ß, IL-6, IL-8 and IFN-y are completely suppressed. IL-10, IL-1Ra and MCP-1 are still produced during suppression with IL-1Ra being overly secreted during reversion. Suppression of TNF-α expression after LPS-stimulation correlates closely with longer mechanical ventilation time (r=-0.619, p=0.004). CONCLUSION: Cardiosurgery with CPB causes a state of immunodepression making pediatric patients more vulnerable to second hit infections. MCP-1, IL-10, and IL-1Ra play an important role in monocyte recovery, eventually permitting new therapeutic options for controlling immunodepression and inflammation. Standardized glucocorticoid therapy should be evaluated carefully for each individual patient.

Multicentric experience with interferon gamma therapy in sepsis induced immunosuppression. A case series.

BACKGROUND: The sepsis-induced immunodepression contributes to impaired clinical outcomes of various stress conditions. This syndrome is well documented and characterized by attenuated function of innate and adaptive immune cells. Several pharmacological interventions aimed to restore the immune response are emerging of which interferon-gamma (IFNγ) is one. It is of paramount relevance to obtain clinical information on optimal timing of the IFNγ-treatment, -tolerance, -effectiveness and outcome before performing a RCT. We describe the effects of IFNγ in a cohort of 18 adult and 2 pediatric sepsis patients. METHODS: In this open-label prospective multi-center case-series, IFNγ treatment was initiated in patients selected on clinical and immunological criteria early (< 4 days) or late (> 7 days) following the onset of sepsis. The data collected in 18 adults and 2 liver transplanted pediatric patients were: clinical scores, monocyte expression of HLA-DR (flow cytometry), lymphocyte immune-phenotyping (flow cytometry), IL-6 and IL-10 plasma levels (ELISA), bacterial cultures, disease severity, and mortality. RESULTS: In 15 out of 18 patients IFNγ treatment was associated with an increase of median HLA-DR expression from 2666 [IQ 1547; 4991] to 12,451 [IQ 4166; 19,707], while the absolute number of lymphocyte subpopulations were not affected, except for the decrease number of NK cells 94.5 [23; 136] to 32.5 [13; 90.8] (0.0625)]. Plasma levels of IL-6 464 [201-770] to 108 (89-140) ng/mL (p = 0.04) and IL-10 from IL-10 from 29 [12-59] to 9 [1-15] pg/mL decreased significantly. Three patients who received IFNγ early after ICU admission (<4 days) died. The other patients had a rapid clinical improvement assessed by the SOFA score and bacterial cultures that were repeatedly positive became negative. The 2 pediatric cases improved rapidly, but 1 died for hemorrhagic complication. CONCLUSION: Guided by clinical and immunological monitoring, adjunctive immunotherapy with IFNγ appears well-tolerated in our cases and improves immune host defense in sepsis induced immuno suppression. Randomized clinical studies to assess its potential clinical benefit are warranted.

Alterations of the iNKT cell compartment in brain-injured patients.

BACKGROUND: Brain injury (BI) induces a state of immunodepression leading to pneumonia. We investigated the invariant natural killer T (iNKT) cell compartment. METHODS: This is an observational study in two surgical intensive care units (ICUs) of a single institution and a research laboratory. Clinical data and samples from a prospective cohort were extracted. Severe brain-injured patients (n = 33) and sex- and age-matched healthy donors (n = 40) were studied. RESULTS: We observed the presence of IL-10 in serum, a loss of IFN-γ and IL-13 production by peripheral blood mononuclear cells (PBMCs) following IL-2 stimulation, and downregulation of HLA-DR expression on both monocytes and B cells early after BI. Inversely, CD1d, the HLA class I-like molecule involved in antigen presentation to iNKT cells, was over-expressed on patients' monocytes and B cells. The antigen-presenting activity to iNKT cells of PBMCs was increased in the patients who developed pneumonia, but not in those who remained free of infection. Frequencies of iNKT cells among PBMCs were dramatically decreased in patients regardless of their infection status. Following amplification, an increased frequency of CD4+ iNKT cells producing IL-4 was noticed in the group of patients free of infection compared with those who became infected and with healthy donors. Finally, serum from BI patients inhibited the iNKT cells' specific response as well as the non-specific IL-2 stimulation of PBMCs, and the expression of the beta-2 adrenergic receptor was elevated at the surface of patients T lymphocytes. CONCLUSIONS: We observed severe alterations of the iNKT cell compartment, including the presence of inhibitory serum factors. We demonstrate for the first time that the decreased capacity to present antigens is not a generalized phenomenon because whereas the expression of HLA-DR molecules is decreased, the capacity for presenting glycolipids through CD1d expression is higher in patients.

Exercise-Induced Illness and Inflammation: Can Immunonutrition and Iron Help?

The main focus of this review is illness among elite athletes, how and why it occurs, and whether any measures can be taken to combat it or to prevent its onset. In particular, there is particular interest in exercise-induced immunodepression, which is a result of the immune system regarding exercise (e.g., prolonged, exhaustive exercise) as a challenge to its function. This promotes the inflammatory response. There is often a high incidence of illness in athletes after undertaking strenuous exercise, particularly among those competing in endurance events, not only mainly in terms of upper respiratory tract illness, but also involving gastrointestinal problems. It may well be that this high incidence is largely due to insufficient recovery time being allowed after, for example, a marathon, a triathlon, or other endurance events. Two examples of the incidence of upper respiratory tract illness in moderate versus endurance exercise are provided. In recent years, increasing numbers of research studies have investigated the origins, symptoms, and incidence of these bouts of illness and have attempted to alleviate the symptoms with supplements, sports foods, or immunonutrition. One aspect of the present review discusses iron deficiency, which has been primarily suggested to have an impact upon cell-mediated immunity. Immunonutrition is also discussed, as are new techniques for investigating links between metabolism and immune function.

Microcirculatory Changes in Experimental Models of Stroke and CNS-Injury Induced Immunodepression.

Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression is considered to contribute to increased susceptibility to infections after stroke. Different experimental models have contributed significantly to the current knowledge of stroke pathophysiology and its consequences. Each model causes different changes in the cerebral microcirculation and local inflammatory responses after ischemia. The vast majority of studies which focused on the peripheral immune response to stroke employed the middle cerebral artery occlusion method. We review various experimental stroke models with regard to microcirculatory changes and discuss the impact on local and peripheral immune response for studies of CNS-injury (central nervous system injury) induced immunodepression.

Modulation of the Endocannabinoid System Following Central Nervous System Injury.

Central nervous system (CNS) injury, such as stroke or trauma, is known to increase susceptibility to various infections that adversely affect patient outcomes (CNS injury-induced immunodepression-CIDS). The endocannabinoid system (ECS) has been shown to have immunoregulatory properties. Therefore, the ECS might represent a druggable target to overcome CIDS. Evidence suggests that cannabinoid type 2 receptor (CB2R) activation can be protective during the early pro-inflammatory phase after CNS injury, as it limits neuro-inflammation and, therefore, attenuates CIDS severity. In the later phase post CNS injury, CB2R inhibition is suggested as a promising pharmacologic strategy to restore immune function in order to prevent infection.

Neutrophil-to-Lymphocyte Ratio and Response to Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

BACKGROUND AND AIMS: The Neutrophil-to-Lymphocyte Ratio (NLR) is suggested as a readily available and inexpensive biomarker to predict prognosis of acute stroke. Experience with intravenous (IV) tissue plasminogen activator (tPA) treatment is limited. METHODS: Total 142 (80 female, age: 69 ± 13 yearr) consecutive acute stroke patients treated with IV tPA were evaluated. Admission and 24th hour lymphocyte, neutrophil, and monocyte counts were measured and the NLR was calculated. RESULTS: Average NLR elevated (by 3.47 ± 6.75) significantly from admission to 24th hour (P< .001). Total 52% of patients exerted good response to IV tPA (NIHSS ≤1 or decrease in NIHSS ≥4 at end of 24 hour), while 27% showed dramatic response (decrease in NIHSS ≥8 at end of 24 hour). The patients with "thrombolysis resistance" had significantly higher 24 hour Neutrophil-to-Lymphocyte Ratio (24h NLR) (P= .001). At the end of 3rd month, 46.5% of patients had favorable (modified Rankin's score, mRS 0-2) and 32.4% had excellent (mRS 0-1) outcome. Patients without favorable/excellent outcome had significantly higher 24h NLRs. Regression analysis indicated that post-tPA, but not admission NLR, was an independent negative predictor of excellent (ß =-.216, P= .006) and favorable (ß = -.179, P= .034) outcome after adjustment for age, hypertension, and admission NIHSS. Nine patients who developed symptomatic intracerebral hemorrhage had elevated pre-tPA (7.6 ± 7.39 versus 3.33 ± 3.07, P< .001) and 24h NLR (26.2 ± 18.6 versus 5.78 ± 4.47, P< .001). Of note, receiver operating characteristics analysis failed to detect any reliable NLR threshold for absence of tPA effectiveness/dramatic response, 3rd month good/excellent outcome or any type tPA-induced hemorrhage. CONCLUSIONS: As a marker of stroke-associated acute stress response, the NLR, which increases during the first 24 hours, is an epiphenomenon of poor prognosis. However, pretreatment NLR values have no importance in predicting IV tPA response.

[Eruptive disseminated superficial porokeratosis associated with acute hepatitis E]. / Porokératose éruptive superficielle disséminée associée à une hépatite virale E aiguë.

BACKGROUND: Porokeratosis (PK) is a rare form of dermatosis characterized by a keratinization disorder of unknown etiology. Herein we describe the first case associated with hepatitis E virus infection. PATIENTS AND METHODS: A 69-year-old patient with colorectal cancer treated with radiation and chemotherapy followed by surgery in April 2017 presented two months later with jaundice associated with annular keratotic lesions of the skin with a raised border. Blood tests revealed elevated liver enzymes and hyperbilirubinemia. Viral hepatitis E was diagnosed based on serology and viral PCR after other aetiologies such as obstruction, auto-immune disease and other viruses (HAV, HBV, HCV, HSV, HIV, EBV and CMV) had been ruled out. A skin biopsy showed a cornoid lamella. Disseminated superficial porokeratosis associated with hepatitis E infection was then diagnosed. DISCUSSION: The mechanism of PK is unknown and probably involves a combination of different factors. PK has been described in patients with treatment-induced immunosuppression, solid cancer or AIDS, sometimes promoted by HCV viral infection, but never with concomitant HEV infection. A combination of immunosuppression induced by radio-chemotherapy and HEV infection could have prompted the development of PK in our patient. CONCLUSION: We report the first case of eruptive disseminated superficial porokeratosis associated with hepatitis E infection. The exact role of hepatitis E infection in the development of PK is still unclear.

ß-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke.

BACKGROUND: Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a protective mechanism for secondary inflammatory injury as well as a contributor to infection complications. Although stroke-induced hyperactivation of the sympathetic system is proved to facilitate SIDS, the involved endogenous factors and pathways are largely elusive. In this study, we aim to investigate the function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS. METHODS: Splenic ARRB2 expression and the sympathetic system activity were detected after establishing transient models of middle cerebral artery occlusion (MCAO). In addition, a correlation between ARRB2 expression and the sympathetic system activity was analyzed using a linear correlation analysis. Any SIDS reflected in monocyte dysfunction was investigated by measuring inflammatory cytokine secretion and neurological deficit scores and infarct volume were tested to assess neurological outcome. Further, ARRB2 expression in the monocytes was knocked down in vitro by siRNAs. Following the stimulation of noradrenaline and lipopolysaccharide, cytokine secretion and the nuclear factor-κB (NF-κB) pathway were evaluated to gain insight into the mechanisms related to the contribution of ARRB2 to adrenergic-induced monocyte dysfunction. RESULTS: Splenic ARRB2 expression was significantly increased after stroke and also showed a significant positive correlation with the sympathetic system activity. Stroke-induced monocyte dysfunction resulted in an increase of the interleukin-10 (IL-10) level as well as a decrease of the interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels. Also, blockade of adrenergic-activity significantly reversed these cytokine levels, and blockade of adrenergic-activity improved stroke-induced neurological results. However, the improved neurological results had no significant correlation with ARRB2 expression. Furthermore, the in vitro results showed that the deficiency of ARRB2 dramatically repealed adrenergic-induced monocyte dysfunction and the inhibition of NF-κB signaling phosphorylation activity. CONCLUSIONS: ARRB2 is implicated in the sympathetic-triggered SIDS, in particular, monocyte dysfunction after stroke. Accordingly, ARRB2 may be a promising therapeutic target for the immunological management of stroke in a clinic.

Rush progression and fatal result of septic shock related to central line catheter infection in cirrhosis patient with brain stroke.

BACKGROUND: Catheter-related blood stream infection (CRBSI) is one of the most common intractable healthcare-associated infections because catheters can be easily contaminated by resistant bacteria, and is associated with a high mortality. Central lines are currently used for administering medication to patients with severe stroke, and may thus cause CRBSI. CASE PRESENTATION: A 71-year-old woman with cirrhosis presented with subarachnoid hemorrhage (SAH) that was treated by clipping surgery. On postoperative day (POD) 38, sudden high fever (40.3 °C) was detected; the patient died a few hours later. Blood and central line cultures were positive for Klebsiella pneumoniae that may have caused CRBSI and endotoxin shock. In this case, the duration from fever detection to death was notably short. Additionally, inflammatory markers such as white blood cells (WBC) or C-reactive protein (CRP) were almost within normal ranges, even a few hours after fever was detected and before death. Cirrhosis was considered to be the cause of these phenomena. CONCLUSION: The timely diagnosis and complete treatment of patients with liver cirrhosis who develop CRBSI are highly challenging. We suggest that clinicians should rigorously apply preventive measures and strengthen CRBSI monitoring, especially in cirrhosis-associated cases.

Neuroanatomical correlates of stroke-associated infection and stroke-induced immunodepression.

BACKGROUND: Infections represent the most frequent medical complications in stroke patients. Their main determinants are dysphagia and a transient state of immunodepression. We analyzed whether distinct anatomical brain regions were associated with the occurrence of stroke-associated infections or immunodepression. MATERIALS AND METHODS: In 106 patients with acute ischemic stroke, we evaluated the incidence of pneumonia, urinary tract infection, or other infections together with the characterization of biomarkers of immunodepression. Twenty control subjects served to provide reference values. Using voxel-based lesion-symptom mapping, the involvement of gray and white matter structures was correlated with clinical and laboratory findings in crude analyses and in volume adjusted models to rule out associations reflecting differences in the size of the infarction. RESULTS: Stroke-associated infection occurred in 22 (21%) patients and prevailed in patients with larger infarcts. Volume adjusted voxel-based lesion-symptom mapping revealed the involvement of the superior and middle temporal gyri, the orbitofrontal cortex, the superior longitudinal fasciculus and the inferior fronto-occipital fasciculus amongst infected patients. These associations were similar for pneumonia but not for urinary tract infections. Lymphopenia was associated with lesions of the superior and middle temporal gyri. Laterality did not influence stroke-associated infections or the presence of immunodepressive traits after volume control. The greatest overlap in the neuroanatomical correlates occurred between pneumonia and dysphagia. CONCLUSION: Infarct volume plays a relevant role in the occurrence of stroke-associated infections, but lesions in specific brain locations such as the superior and lateral temporal lobe and the orbitofrontal cortex are also associated with increased infectious risk, especially pneumonia.

Values of vanillylmandelic acid and homovanillic acid in the urine as potential prognostic biomarkers in ischaemic stroke patients.

BACKGROUND: Suitable biomarkers that have prognostic values are one of the key points of interest in ischaemic stroke. Increased sympathetic nervous system activity in ischaemic stroke causes multiple local and systemic effects that can be detrimental to the outcome. The mechanism of action is increased secretion and activity of catecholamines, whose end metabolic products are vanillylmandelic acid and homovanilic acid. Aim of our study was to determine whether these compounds can be used as potential prognostic biomarkers in ischaemic stroke, as a unique insight into the activity of the sympathetic nervous system. METHODS: Urine samples of 96 patients with ischaemic stroke and transitory ischaemic attacks were analysed. Values of vanillylmandelic and homovanillic acids in urine were tested using liquid chromatography on the first and third day post-stroke. Severity of stroke was determined using the NIHSS scale, while functional outcome was determined using the Modified Rankin Scale. RESULTS: Values of vanillylmandelic and homovanillic acids positively correlated with functional outcome of ischaemic stroke. Favorable outcomes correlated with decreased values, on contrary to increased values, which were associated with unfavourable outcomes. CONCLUSION: Determining the values of these compounds in the urine is an easily available prognostic tool for the ischaemic stroke outcome, while also influencing potential therapeutic changes.

Radiologic findings of Fusarium pneumonia in neutropenic patients.

In neutropenic patients, lungs are involved in 50%-80% of cases of fusariosis, but imaging of pulmonary fusariosis has been previously described as indistinguishable from other invasive mould diseases. Our attempt was to identify a radiological pattern that may distinguish pulmonary fusariosis from other mould diseases. We examined the CT findings of nine neutropenic haematology patients with invasive fusariosis. As control group for comparison, we examined 14 invasive mould diseases (11 aspergillosis, 3 mucormycosis) in haematology patients with similar underlying disease and timing of CT imaging. Chest-CT in invasive fusariosis showed small airways (7/9) or peribronchial (5/9) infiltrates, less frequently macronodular consolidations (4/9) with hypodense sign, but without halo sign or occluded-vessel sign. The control group presented macronodular consolidations with occluded-vessel sign in all of the cases; the halo and the hypodense signs were observed, respectively, in 100% and 82% of aspergillosis, and in 67% and 100% of mucormycosis. Sinusitis was documented by CT in 7/7 fusariosis, 2/2 mucormycosis and 5/7 aspergillosis; maxillary and ethmoid sinuses were involved in 7/7 fusariosis, in most of the cases with hyperdense opacification (rarely observed in the controls). We concluded that no radiological findings can discriminate between different mould infections, but invasive fusariosis should be suspected if chest-CT demonstrates pulmonary infiltrates with the hypodense sign, but without the halo or the occluded-vessel signs. Suspicion is greater in the presence of hyperdense maxillary and ethmoid sinusitis.

Cholinergic Pathway Suppresses Pulmonary Innate Immunity Facilitating Pneumonia After Stroke.

BACKGROUND AND PURPOSE: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive. METHODS: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, α7 nicotinic acetylcholine receptor-deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity. RESULTS: Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using α7 nicotinic acetylcholine receptor-deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung. CONCLUSIONS: Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury.