Follow-up of patients with urinary tract infections discharged from the emergency department: a mixed methods study.

OBJECTIVES: To evaluate the quality of culture follow-up after emergency department (ED) discharge in patients with urinary tract infections (UTIs). METHODS: This convergent mixed methods study included an observational cohort study and a qualitative interview study in UTI patients discharged from the ED of a Dutch university hospital. The primary outcomes of the observational study were the proportion of patients requiring adjustment of antibiotic therapy after culture review, and the proportion of patients in whom these adjustments were made. Logistic regression identified factors associated with these outcomes. Interviews assessed patient experiences and transcripts were analysed using inductive thematic content analysis. Integration of the results informed recommendations for high-quality follow-up. RESULTS: Out of 455 patients, 285 (63%) required culture-based treatment adjustments. In most patients, no adjustments were made (239/285, 84%). De-escalation was most frequently omitted (98%), followed by discontinuation of antibiotics (92%). A mean of 7.1 (SD  3.8) antibiotic days per patient could have been avoided in 103 patients. Patients with diabetes were less likely to require adjustments (aOR   0.50, 95%-CI  0.29-0.85). Patients with moderate or severe renal impairment (aOR  4.1, 95%-CI  1.45-11.33; aOR  4.2, 95%-CI   1.50-11.94) or recurrent UTIs (aOR  5.0, 95%-CI  2.27-11.18) were more likely to have received necessary adjustments. Twelve interviews also revealed varying degrees of follow-up. Three themes were identified: 'information and communication', 'coordination and accessibility of care' and 'individual needs and preferences'. Recommendations for high-quality follow-up advocate a person centred approach. CONCLUSIONS: This study highlights the importance of urine culture follow-up after ED discharge, mainly to reduce unnecessary antibiotic treatment, promote de-escalation and improve patient experience.

Low-risk Staphylococcus aureus bacteremia patients do not require routine diagnostic imaging: A multicenter retrospective cohort study.

BACKGROUND: Risk stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low- or high-risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. METHODS: We performed a retrospective cohort study in seven Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. The primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both the actual therapy administered and by linking a retrospectively adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival, and factors associated with performing of diagnostic imaging. RESULTS: Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%) imaging findings during patient admission had been interpreted as metastatic infections that should extend duration of treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-days relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; aOR 0.749 (95% CI 0.373-1.504). CONCLUSION: Our study advocates risk stratification for the management of patients with SAB. Prerequisites are follow-up blood cultures, bedside ID consultation, along with critically reviewing disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.

Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

OBJECTIVES: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). METHODS: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. RESULTS: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. CONCLUSIONS: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

The impact of implementing an endocarditis team in comparison to the classic heart team in a tertiary referral centre.

BACKGROUND: Infective endocarditis (IE) is a complex disease for which the European Society of Cardiology guideline recommends a dedicated multidisciplinary endocarditis team (ET) approach since 2015. It is currently unknown whether this ET approach is beneficial compared to a classic heart team approach including bedside consultation by an infectious disease specialist in Western Europe. METHODS: This retrospective single centre, observational cohort study was conducted at the Radboudumc, a tertiary referral centre in the Netherlands. Consecutive patients treated for IE were included from September 2017 to September 2018 before implementation of a dedicated ET and from May 2019 to May 2020 afterwards. RESULTS: In total, 90 IE patients (45 patients before and 45 patients after the implementation of the ET) were included. No significant differences were found in diagnostic workup, surgical treatment (surgery performed 69% vs. 71%, p = 0.82), time to surgery because of an urgent indication (median 4 vs. 6 days, p = 0.82), in-hospital complications (53% vs. 67%, p = 0.20), and 6-month mortality (11% vs. 13%, p = 0.75) between IE patients treated before and after the implementation of the ET. CONCLUSION: Formalization of the recommended multidisciplinary endocarditis team might not significantly improve the complication rate nor the short term outcome.

[Chloroquine for COVID-19: a hype or not?] / Chloroquine bij covid-19.

In March the CEO of Tesla, Elon Musk, posted a Tweet about the possible effects of chloroquine for COVID-19. Celebrities and mainstream media joined the discussion and promoted (hydroxy-)chloroquine to a true hype and the miracle cure for COVID-19. Police surveillance was needed to protect the producer of chloroquine in the Netherlands. Was (hydroxy-)chloroquine just a hype? The first European study had many methodological issues, a misleading conclusion and was published without the peer review process. It took several weeks before better designed studies showed that (hydroxy-)chloroquine was not effective for COVID-19, after which the use of this medicine was no longer recommended. It is understandable that in a pandemic there is a high need for an effective cure, but physicians should have waited until effectiveness was demonstrated. In our opinion, the use of (hydroxy-)chloroquine for COVID-19 was indeed a hype.

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands.

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called 'endocarditis team' in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

[Medication and comedication in COVID-19 patients]. / Geneesmiddelen bij COVID-19.

This paper discusses the possible effects of comedication on COVID-19 and the current treatment options for this infection. It is very doubtful that comedication has a disadvantageous effect on the course of the disease. NSAIDs should be avoided in any patient with a possible severe disease, because of potential side effects. Inhibitors of the renin-angiotensin aldosterone system should be continued when there is a solid indication, and stopped in case of hemodynamic problems. There is no preference for either ACE inhibitors or angiotensin II receptor inhibitors. Currently, chloroquine and remdesivir are possible treatment options. There is no sound evidence for either treatment. Chloroquine has side effects (nausea, QT prolongation) and there are several drug interactions. The treatment should be reconsidered in the event of side effects and when inferior medication for comorbidity must be prescribed because of possible interactions. Lopinavir/ritonavir is not effective. Supportive care is at present the mainstay of the treatment.

Management of infected pancreatic necrosis in the intensive care unit: a narrative review.

BACKGROUND: Severe acute pancreatitis is marked by organ failure and (peri)pancreatic necrosis with local complications such as infected necrosis. Infection of these necrotic collections together with organ failure remain the major causes of admission to an intensive care unit (ICU) in acute pancreatitis. Appropriate treatment of infected necrosis is essential to reduce morbidity and mortality. Overall knowledge of the treatment options within a multidisciplinary team-with special attention to the appropriate use of antimicrobial therapy and invasive treatment techniques for source control-is essential in the treatment of this complex disease. OBJECTIVES: To address the current state of microbiological diagnosis, antimicrobial treatment, and source control for infected pancreatic necrosis in the ICU. SOURCES: A literature search was performed using the Medline and Cochrane libraries for articles subsequent to 2003 using the keywords: infected necrosis, pancreatitis, intensive care medicine, treatment, diagnosis and antibiotic(s). CONTENT: This narrative review provides an overview of key elements of diagnosis and treatment of infected pancreatic necrosis in the ICU. IMPLICATIONS: In pancreatic necrosis it is essential to continuously (re)evaluate the indication for antimicrobial treatment and invasive source control. Invasive diagnostics (e.g. through fine-needle aspiration, FNA), preferably prior to the start of broad-spectrum antimicrobial therapy, is advocated. Antimicrobial stewardship principles apply: paying attention to altered pharmacokinetics in the critically ill, de-escalation of broad-spectrum therapy once cultures become available, and early withdrawal of antibiotics once source control has been established. This is important to prevent the development of antimicrobial resistance, especially in a group of patients who may require repeated courses of antibiotics during the prolonged course of their illness.

Nationwide survey of hospital antibiotic stewardship programs in France.

OBJECTIVE: We aimed to evaluate the current state of antibiotic stewardship (ABS) in French public and private acute care hospitals. METHODS: We conducted a cross-sectional online questionnaire survey. The selection of participating hospitals was performed through a stratified random sampling procedure among all French public and private hospitals with acute care beds. RESULTS: 97/215 (45%) hospitals participated. A formal ABS program was implemented in 84% (80/95) of hospitals. A person officially in charge of this program (i.e., ABS program leader) was present in almost all participating hospitals (99%, 95/96) and s/he coordinated a multidisciplinary ABS team in 42% (40/96) of cases. The median time spent on ABS activities was 1.7, 1.6, and 0.8hours/week/100 acute care beds for infectious disease (ID) specialists, pharmacists, and microbiologists respectively; 27% (7/26) of ID specialists/other clinicians, 58% (15/26) of pharmacists, and 80% (16/20) of microbiologists received no salary support for the stewardship activities conducted as part of the team. Local guidelines (94%, 88/94), electronic medical records (85%, 80/94), and an antibiotic restriction policy (92%, 82/89) were implemented in almost all hospitals. Reports on antibiotic consumption and local resistance rates were available in 100% (91/91) and 84% (76/91) of hospitals, respectively. CONCLUSION: Despite the existence of national requirements, hospital ABS programs are not fully implemented in France, mainly because of inadequate institutional support and funding.

[Antibiotic prophylaxis and (pre-)dental implant surgery]. / AB-profylaxe en (pre)implantologische chirurgie.

Recent literature indicates that in a healthy patient, who has sufficient bone volume to allow implant placement, it is justified to refrain from prophylactic administration of antibiotics. The patient should, however, rinse with chlorhexidine digluconate 1 day prior to treatment and at least 1 week postoperatively. In the case of an immune-compromised patient, a single antibiotic gift is indicated 1 hour before the procedure (2 grams of amoxicillin orally or 2 grams of cefazoline intravenously). In the case of a healthy patient, antibiotic (AB) prophylaxis is also indicated if autologous bone, a bone filler or membranes are applied. Although AB prophylaxis is not necessary when harvesting extraoral bone grafts, it is indicated because the harvested bone is applied intraorally in the same treatment session. The question whether postoperative administration of antibiotics is still needed remains open.

Comparison of antimicrobial stewardship programmes in acute-care hospitals in four European countries: A cross-sectional survey.

Antimicrobial stewardship programmes (ASPs) are designed to improve antibiotic use. A survey was systematically developed to assess ASP prerequisites, objectives and improvement strategies in hospitals. This study assessed the current state of ASPs in acute-care hospitals throughout Europe. A survey containing 46 questions was disseminated to acute-care hospitals: all Dutch (n = 80) and Slovenian (n = 29), 215 French (25%, random stratified sampling) and 62 Italian (49% of hospitals with an infectious diseases department, convenience sampling) acute-care hospitals, for a Europe-wide assessment. Response rates for the Netherlands (Nl), Slovenia (Slo), France (Fr) and Italy (It) were 80%, 86%, 45% and 66%. There was variation between countries in the prerequisites met and the objectives and improvement strategies chosen. A formal ASP was present mainly in the Netherlands (90%) and France (84%) compared with Slovenia (60%) and Italy (60%). Presence of an antimicrobial stewardship (AMS) team ranged from 42% (Fr) to 94% (Nl). Salary support for AMS teams was provided in 68% (Fr), 51% (Nl), 33% (Slo) and 12% (It) of surveyed hospitals. Quantity of antibiotic use was monitored in the majority of hospitals, ranging from 72% (Nl) to 100% (Slo and Fr) of acute-care hospitals. Participating countries varied substantially in the use of 'prospective monitoring and advice' as a strategy to improve AMS objectives. ASP prerequisites, objectives and improvement activities vary considerably across Europe, with room for improvement. Stimulating appropriate system prerequisites throughout Europe, e.g. by introducing staffing standards and financial support for ASPs, seems a first priority.

A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis.

Candida vaginitis is a frequent clinical diagnosis with up to 8% of women experiencing recurrent vulvovaginal candidiasis (RVVC) globally. RVVC is characterized by at least three episodes per year. Most patients with RVVC lack known risk factors, suggesting a role for genetic risk factors in this condition. Through integration of genomic approaches and immunological studies in two independent cohorts of patients with RVVC and healthy individuals, we identified genes and cellular processes that contribute to the pathogenesis of RVVC, including cellular morphogenesis and metabolism, and cellular adhesion. We further identified SIGLEC15, a lectin expressed by various immune cells that binds sialic acid-containing structures, as a candidate gene involved in RVVC susceptibility. Candida stimulation induced SIGLEC15 expression in human peripheral blood mononuclear cells (PBMCs) and a polymorphism in the SIGLEC15 gene that was associated with RVVC in the patient cohorts led to an altered cytokine profile after PBMC stimulation. The same polymorphism led to an increase in IL1B and NLRP3 expression after Candida stimulation in HeLa cells in vitro. Last, Siglec15 expression was induced by Candida at the vaginal surface of mice, where in vivo silencing of Siglec15 led to an increase in the fungal burden. Siglec15 silencing was additionally accompanied by an increase in polymorphonuclear leukocytes during the course of infection. Identification of these pathways and cellular processes contributes to a better understanding of RVVC and may open new therapeutic avenues.

Incidence and microbiology of post-operative infections after radical cystectomy and ureteral stent removal; a retrospective cohort study.

BACKGROUND: Post-operative infections are frequent after radical cystectomy with urinary diversion surgery (UDS). Reduction of post-operative infections necessitates appropriate peri-operative antimicrobial prophylaxis targeting causative bacteria. We assessed the incidence and microbiology of infections in the 30-day post-operative period after UDS and investigated effectiveness of the currently used peri-operative antibacterial prophylaxis. METHODS: Retrospective cohort study of all patients undergoing UDS in a tertiary university medical center from January 2014 until September 2016. Antibiotic prophylaxis consisted of cefazolin plus metronidazol according to the Dutch national guideline. Primary outcome was the incidence of post-operative infections within 30 days. Risk factors for post-operative infections and antimicrobial susceptibility profiles of cultured bacteria were also assessed. RESULTS: 147 patients were included. 69 patients (46.9%) had 82 post-operative infections, 27 of which were patients with bacteremia (18.4%). Highest incidence of infections was on day 4-5 and on day 8-10 postoperatively. The second peak was associated with ureteral stent removal. 4.8% of 147 study patients developed bacteremia 24 h after stent removal, which counted for 25.9% of all bacteremia episodes found in this study. Enterobacteriaceae were cultured in 67.9% of blood cultures and were only highly susceptible to ciprofloxacine, piperacillin-tazobactam (90%), meropenem and gentamicin (100%). Multivariate logistic regression analysis showed orthotopic Hautmann neobladder to be associated with increased infections complications: odds ratio 4.1 (95% confidence interval 1.6-10.5), p = 0.03. CONCLUSIONS: The incidence of infections after radical cystectomy is high and particularly ureteral stent removal was associated with both bacteremia and complicated urinary tract infections. Based on the results of this study, antibiotic prophylaxis might need to be broadened for patients undergoing radical cystectomy. Further research is required to investigate whether current guidelines need to be altered concerning administration of antibiotic prophylaxis just before stent removal.

A survey on antimicrobial stewardship prerequisites, objectives and improvement strategies: systematic development and nationwide assessment in Dutch acute care hospitals.

Background: Stewardship guidelines define three essential building blocks for successful hospital antimicrobial stewardship programmes (ASPs): stewardship prerequisites, stewardship objectives and improvement strategies. Objectives: We systematically developed a survey, based on these building blocks, to evaluate the current state of antimicrobial stewardship in hospitals. We tested this survey in 64 Dutch acute care hospitals. Methods: We performed a literature review on surveys of antimicrobial stewardship. After extraction and categorization of survey questions, five experts merged and rephrased questions during a consensus meeting. After a pilot study, the survey was sent to 80 Dutch hospitals. Results: The final survey consisted of 46 questions, categorized into hospital characteristics, stewardship prerequisites, stewardship objectives and stewardship strategies. The response rate was 80% (n = 64). Ninety-four percent of hospitals had established an antimicrobial stewardship team, consisting of at least one hospital pharmacist and one clinical microbiologist. An infectious diseases specialist was present in 68% of the teams. Nine percent had dedicated IT support. Forty-one percent of the teams were financially supported, with a median of 0.6 full-time equivalents (FTE; 0.1-1.8). The majority of hospitals performed monitoring of restricted antibiotic agents (91%), dose optimization (65%), bedside consultation (56%) and intravenous-to-oral switch (53%). Fifty-eight percent of the hospitals provided education to residents and 28% to specialists. Conclusions: The survey provides information on the progress that is being made in hospitals regarding the three building blocks of a successful ASP, and provides clear aims to strengthen ASPs. Ultimately, these data will be related to national data on antibiotic consumption and resistance.

Human resources required for antimicrobial stewardship teams: a Dutch consensus report.

SCOPE: Antimicrobial stewardship teams are responsible for implementing antimicrobial stewardship programmes (ASP). However, in many countries, lack of funding challenges this obligation. A consensus procedure was performed to investigate which structural activities need to be performed by Dutch stewardship teams and how much time (and thus full-time equivalent (FTE) labor) is needed to perform these activities. METHODS: In 2015, an electronic survey, based on a nonsystematic literature search and interviews with seven experienced stewardship teams, was sent to 21 stewardship teams that performed an ASP. This was followed by a semistructured face-to-face consensus meeting. Fourteen stewardship teams completed the survey (18% of Dutch acute-care hospitals), and 13 participated in the consensus meeting. RECOMMENDATIONS: The hours needed each year are dependent on hospital size and number of stewardship objectives monitored. If all activities are performed at a minimal base (one stewardship objective; minimal staffing standard), time investment was estimated to be 1393 to 2680 hours annually in the early phase, corresponding with 0.87 (300 beds) to 1.68 FTE (1200 beds), with a further increase to minimally 1.25 to 3.18 FTE in the following years with three stewardship objectives monitored (optimal staffing standards during the first few years of implementing an ASP). This consensus on required human resources provides a directive for structural financial support of stewardship teams in the Dutch context. Some stewardship activities (and related time investments) might be specific to the Dutch context and hospital setting. To develop standards for other settings, our methodology could be applied.

Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related neuropathological conditions.

HIV in the central nervous system (CNS) mainly infects microglial cells which are known to express toll-like receptors (TLRs). This paper aimed to study the role of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV-infected rhesus macaques with and without neurological sequelae, as well as in HIV-infected patients with and without cognitive impairments and Alzheimer's disease (AD) patients and matched controls. CSF cytokines and chemokines levels were analyzed in macaques as markers of neuroinflammation, while neopterin and S100B CSF concentrations were measured in HIV-infected patients as microglial and astrocyte marker, respectively. We found detectable levels of sTLR2 and sTLR4 in CSF of macaques and humans. Furthermore, CSF sTLR2 and sTLR4 concentrations were higher in SIV-infected macaques with neurological sequelae compared to those without neurological complications (p = 0.0003 and p = 0.0006, respectively). CSF IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels were elevated in macaques with neurological sequelae, and a positive correlation was found between CSF levels of sTLR2/4 and IL-8 and MCP-1. Also in humans, elevated CSF sTLR4 levels were found in HIV-infected patients with cognitive impairments compared to HIV-infected patients with normal cognition (p = 0.019). Unlike CSF S100B levels, neopterin correlated positively with sTLR2 and sTLR4. No difference was found in plasma and CSF sTLR2 and sTLR4 levels between AD patients and control subjects (p = 0.26). In conclusion, CSF sTLR2 and sTLR4 may play a role in HIV/SIV-related neuroinflammation and subsequent neuropathology.

Circulating galectin-3 in infections and non-infectious inflammatory diseases.

Recent studies point to a dual role for galectin-3 as both a circulating damage-associated molecular pattern and a cell membrane-associated pattern recognition receptor. The aim of this study was to assess the potential of circulating galectin-3 for discriminating between infections and non-infectious inflammatory disorders on the one hand, and between fungal and bacterial infections on the other. Galectin-3 and C-reactive protein (CRP) were measured in the plasma of 127 patients with either non-infectious inflammatory disorders (gout, autoinflammatory syndrome or pancreatitis) or an infection (viral lower respiratory tract infection, bacterial sepsis or candidaemia). Circulating galectin-3 concentrations were increased in patients with infections when compared with healthy volunteers or patients with non-infectious inflammatory diseases. At cut-off values with a specificity of 95%, the sensitivity of galectin-3 (>20.6 ng/ml) to discriminate between an infection and non-infectious inflammation was higher than that of CRP (>156 mg/l): 43% [95% confidence interval (CI) 33-53%] versus 27% (95% CI 19-37%), p = 0.03. After exclusion of patients with CRP <156 mg/l, galectin-3 concentration >20.6 ng/ml could identify 41 % (95% CI 29-53%) of the patients with an infection at the cost of one false-positive with non-infectious inflammation. Using this sequential approach, 57% of the patients with an infection could be selected. Galectin-3 concentrations were similar in patients with bacterial and Candida sepsis, while being lower in viral respiratory infections. Although galectin-3 does not discriminate between bacterial and Candida sepsis, the sequential use of CRP and galectin-3 in distinguishing infectious diseases from non-infectious inflammation may be superior to CRP alone.

Pulmonary infection, and not systemic inflammation, accounts for increased concentrations of exhaled nitric oxide in patients with septic shock.

Nitric oxide (NO) is a key mediator in the pathophysiology of septic shock that can be measured in exhaled breath. To assess whether a pulmonary infection itself or systemic inflammation is responsible for NO production, we determined exhaled NO in ventilated patients with respiratory and non-respiratory septic shock and compared it with the concentration in ventilated intensive care patients without systemic inflammation. In addition, the change of NO production over time and correlations with haemodynamic instability were evaluated. The controls without systemic inflammation, as witnessed by the absence of systemic inflammatory response syndrome criteria and low levels of interleukin-6, had similar concentrations of NO as the patients with non-respiratory septic shock. The respiratory sepsis patients exhaled more NO than the non-respiratory sepsis patients (p = 0.05), and a time dependent decline in time in both groups (p = 0.04). Exhaled NO did not correlate with markers of disease severity, systemic inflammation and haemodynamic instability. These data indicate that the infected lungs are the source of exhaled NO.

Cardiac involvement in hypereosinophilic syndrome.

Hypereosinophilic syndrome is a heterogeneous group of disorders characterised by hypereosinophilia and organ involvement of varying intensity. We describe involvement of the heart in patients with hypereosinophilic syndrome,and the diagnostic and therapeutic clinical management of these patients.

Complete remission of MDS RAEB following immunosuppressive treatment in a patient with Sweet's syndrome.

We report on a patient with myelodysplastic syndrome (MDS), classified as refractory anaemia with excess of blasts-2, and histiocytoid Sweet's syndrome. The skin lesions disappeared after initiation of corticosteroids and doxycycline. Remarkably, two months later a complete remission of the MDS occurred. Fourteen months later both the skin lesions and the MDS relapsed. Antileukaemic activity following reversion of the impaired cellular immunity due to an increased number of natural killer cells in his bone marrow may be responsible for this rare event. Inhibition of T-cell mediated myelosuppression by corticosteroids or a proapoptotic effect of doxycycline may have attributed as well.