Quantitative PCR to diagnose Pneumocystis pneumonia in immunocompromised non-HIV patients

The utility of quantitative Pneumocystis jirovecii PCR in clinical routine for diagnosing Pneumocystis pneumonia (PCP) in immunocompromised non-HIV patients is unknown. We analysed bronchoalveolar lavage fluid with real-time quantitative P. jirovecii PCR in 71 cases with definitive PCP defined by positive immunofluorescence (IF) tests and in 171 randomly selected patients with acute lung disease. In those patients, possible PCP cases were identified by using a novel standardised PCP probability algorithm and chart review. PCR performance was compared with IF testing, clinical judgment and the PCP probability algorithm. Quantitative P. jirovecii PCR values >1,450 pathogens·mL(-1) had a positive predictive value of 98.0% (95% CI 89.6-100.0%) for diagnosing definitive PCP. PCR values of between 1 and 1,450 pathogens·mL(-1) were associated with both colonisation and infection; thus, a cut-off between the two conditions could not be identified and diagnosis of PCP in this setting relied on IF and clinical assessment. Clinical PCP could be ruled out in 99.3% of 153 patients with negative PCR results. Quantitative PCR is useful for diagnosing PCP and is complementary to IF. PCR values of >1,450 pathogens·mL(-1) allow reliable diagnosis, whereas negative PCR results virtually exclude PCP. Intermediate values require additional clinical assessment and IF testing. On the basis of our data and for economic and logistical limitations, we propose a clinical algorithm in which IF remains the preferred first test in most cases, followed by PCR in those patients with a negative IF and strong clinical suspicion for PCP.

Bipolar disorder susceptibility region on chromosome 3q29 not confirmed in a case-control association study

We identified a bipolar disorder (BPD) susceptibility region on chromosome 3q29 in a genome-wide linkage scan (Bailer et al. 2002 (Biol Psychiatry 52: 40), NPL-score 4.09) and follow-up linkage analysis (Schosser et al. 2004 (J Psychiatr Res 38(3): 357), NPL-scores >3 with five markers). These findings were supported by further fine-mapping of this region (Schosser et al. 2007 (Eur Neuropsychopharmacol 17(6-7): 501)), finding NPL-scores >3.9 with SNPs (single nucleotide polymorphisms) spanning a region of 3.46 Mbp in BPD families. Since genetic association studies are more powerful than linkage studies for detecting susceptibility genes of small effect size, we aimed to replicate these findings in an independent case-control sample collected in London (UK) and Vienna (Austria).

Is Acute Fibrinous and Organizing Pneumonia the Expression of Immune Dysregulation?

INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a recently described histologic pattern of diffuse pulmonary disease. In children, all cases reported to date have been fatal. In this study, we describe the first nonfatal AFOP in a child and review the literature. DESCRIPTION: A 10-year-old boy developed very severe aplastic anemia (VSAA) after being admitted to our hospital with a fulminant hepatic failure of unknown origin. A chest computed tomography scan revealed multiple lung nodules and a biopsy of a pulmonary lesion showed all the signs of AFOP. Infectious workup remained negative. We started immunosuppressive therapy with antithymocyte globulin and cyclosporine to treat VSAA. Subsequent chest computed tomography scans showed a considerable diminution of the lung lesions but the VSAA did not improve until we performed hematopoietic stem cell transplantation 5 months later. CONCLUSIONS: Aplastic anemia is associated with a variety of autoimmune syndromes. The sequence of events in our patient suggests that the hepatic failure, AFOP, and the VSAA may all have been part of an autoimmune syndrome. AFOP could be the result of immune dysregulation in this pediatric case with favorable outcome after immunosuppressive therapy and hematopoietic stem cell transplantation.

Acute cardiac disorder or pneumonia and concomitant presence of pulmonary embolism

Purpose To determine the frequency of apparent acute pulmonary embolism (PE) and of concomitant disease in computed tomography pulmonary angiography (CTPA); to compare the frequency of PE in patients with pneumonia or acute cardiac disorder (acute coronary syndrome, tachyarrhythmia, acute left ventricular heart failure or cardiogenic shock), with the frequency of PE in patients with none of these alternative chest pathologies (comparison group). Methods Retrospective analysis of all patients who received a CTPA at the emergency department (ED) within a period of four years and 5 months. Results Of 1275 patients with CTPA, 28 (2.2%) had PE and concomitant radiologic evidence of another chest disease; 3 more (0.2%) had PE and an acute cardiac disorder without radiological evidence of heart failure. PE was found in 11 of 113 patients (10%) with pneumonia, in 5 of 154 patients (3.3%) with an acute cardiac disorder and in 186 of 1008 patients (18%) in the comparison group. After adjustment for risk factors for thromboembolism and for other relevant patient’s characteristics, the proportion of CTPAs with evidence of PE in patients with an acute cardiac disorder or pneumonia was significantly lower than in the comparison group (OR 0.13, 95% CI 0.05–0.33, p<0.001 for patients with an acute cardiac disorder, and OR 0.45, 95% CI 0.23–0.89, p = 0.021 for patients with pneumonia). Conclusion The frequency of PE and a concomitant disease that can mimic PE was low. The presence of an acute cardiac disorder or pneumonia was associated with decreased odds of PE.

Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study

To examine whether acute dysglycaemia predicts death in people admitted to hospital with community acquired pneumonia.

Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection

BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10 to 20% during the initial infection and increases substantially with the need for mechanical ventilation. It was suggested that in these patients corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality. OBJECTIVES: To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air). SEARCH STRATEGY: We searched Medline (January 1980-December 2004), EMBASE (January 1985-December 2004) and The Cochrane Library (Issue 4, 2004) without language restrictions to identify randomised controlled trials that compared adjunctive corticosteroids to control in HIV-infected patients with PCP. We further reviewed the reference lists from previously published overviews, we searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts of the field, and searched reference lists of identified publications for citations of additional relevant articles. SELECTION CRITERIA: Trials were considered eligible for this review if they compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, used random allocation, and reported mortality data. We excluded trials in patients with no or mild hypoxemia (arterial oxygen partial pressure >70 mmHg or an alveolar-arterial gradient <35 mmHg on room air) and trials with a follow-up of less than 30 days. DATA COLLECTION AND ANALYSIS: Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups by using a random effects model. MAIN RESULTS: Six studies were included in the review and meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval [CI], 0.32-0.98) at 1 month and 0.68 (95% CI, 0.50-0.94) at 3-4 months of follow-up. To prevent 1 death, numbers needed to treat are 9 patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.38 (95% CI, 0.20-0.73) in favour of adjunctive corticosteroids. AUTHORS' CONCLUSIONS: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but evidence from this review suggests a beneficial effect for patients with substantial hypoxemia.

Ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve: accuracy of a selective new technique confirmed by anatomical dissection

BACKGROUND: Ilioinguinal and iliohypogastric nerve blocks may be used in the diagnosis of chronic groin pain or for analgesia for hernia repair. This study describes a new ultrasound-guided approach to these nerves and determines its accuracy using anatomical dissection control. METHODS: After having tested the new method in a pilot cadaver, 10 additional embalmed cadavers were used to perform 37 ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerve. After injection of 0.1 ml of dye the cadavers were dissected to evaluate needle position and colouring of the nerves. RESULTS: Thirty-three of the thirty-seven needle tips were located at the exact target point, in or directly at the ilioinguinal or iliohypogastric nerve. In all these cases the targeted nerve was coloured entirely. In two of the remaining four cases parts of the nerves were coloured. This corresponds to a simulated block success rate of 95%. In contrast to the standard 'blind' techniques of inguinal nerve blocks we visualized and targeted the nerves 5 cm cranial and posterior to the anterior superior iliac spine. The median diameters of the nerves measured by ultrasound were: ilioinguinal 3.0x1.6 mm, and iliohypogastric 2.9x1.6 mm. The median distance of the ilioinguinal nerve to the iliac bone was 6.0 mm and the distance between the two nerves was 10.4 mm. CONCLUSIONS: The anatomical dissections confirmed that our new ultrasound-guided approach to the ilioinguinal and iliohypogastric nerve is accurate. Ultrasound could become an attractive alternative to the 'blind' standard techniques of ilioinguinal and iliohypogastric nerve block in pain medicine and anaesthetic practice.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection: a meta-analysis of randomised controlled trials

BACKGROUND: The objective of this study was to review the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with Pneumocystis jiroveci pneumonia (PCP) and substantial hypoxemia (arterial oxygen partial pressure <70 mmHg or alveolar-arterial gradient >35 mmHg on room air). METHODS: We conducted a systematic search of the literature for randomised trials published up to December 2004. Selected trials compared adjunctive corticosteroids with placebo or usual care in HIV-infected patients with PCP and reported mortality data. Two teams of reviewers independently evaluated the methodology and extracted data from each primary study. RESULTS: Six studies were included in the meta-analysis. Risk ratios for overall mortality for adjunctive corticosteroids were 0.54 (95% confidence interval [CI], 0.38-0.79) at 1 month and 0.67 (95% CI, 0.49-0.93) at 3-4 months of follow-up. Numbers needed to treat, to prevent 1 death, are 9 patients in a setting without highly active antiretroviral therapy (HAART) available and 22 patients with HAART available. Only the 3 largest trials provided data on the need for mechanical ventilation with a risk ratio of 0.37 (95% CI, 0.20-0.70) in favour of adjunctive corticosteroids. CONCLUSION: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but our results suggest a beneficial effect for patients with substantial hypoxemia.

Fatal sepsis in an AIDS patient during therapy for Pneumocystis carinii pneumonia

The case of a patient with a newly diagnosed HIV infection and Pneumocystis carinii pneumonia is presented. Despite treatment with high-dose trimethoprim/sulfamethoxazole (TMP/SMX) and prednisone with initial improvement, the patient acutely deteriorated with severe acidosis and died on the 4th day of hospitalization. Cryptococcus neoformans grew the next day in broncheoalveolar lavage (BAL) and blood culture. As simultaneous presence of more than one opportunistic infection can occur in these patients, systematic workup for other common opportunistic infections must be performed.

[Community-acquired pneumonia--pathogens and assessment]

Pneumonia is one of the most important infectious diseases, both in terms of incidence as well as potential severity. Streptococcus pneumoniae remains the most prevalent etiologic agent, accounting for about two-thirds of bacteremic cases. Diagnostic procedures include chest radiography, blood culture, Gram staining and culture of expectorated sputum, urine antigen assays for Legionella pneumophila and pneumococci, and asservation of an initial serum sample for comparative serologic investigations. Molecular biology techniques continue to gain importance for the diagnosis of Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionellae and viral respiratory infections, however, their availability at present is mainly restricted to research and reference laboratories.