Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronisation therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life, clinical, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were nonsignificant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = 0.03; adjusted Pinteraction = 0.33) and diabetics (Pinteraction = 0.01; adjusted Pinteraction = 0.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

[A descriptive study of psychiatric care and pre-sentencing psychiatric reports in a French high-security prison]. / Parcours de soins et expertises psychiatriques pré-sentencielles : une étude descriptive au centre pénitentiaire de Château-Thierry.

CONTEXT: The high prevalence of psychiatric disorders among people in prison is well documented, and several hypotheses have been proposed to explain this overrepresentation. In France, the decrease in the number of people found by the judge to be not criminally responsible on account of mental disorder after a psychiatric expertise could play a crucial role. The Château-Thierry prison is a high-security correctional facility where prisoners whose integration into a "standard" prison is complicated because of behavioural problems, reside. We conducted the first study to describe the judicial and healthcare trajectories of people incarcerated in this facility. METHOD: All the people incarcerated in the Château-Thierry prison between May and September 2019 were included in this cross-sectional study. In addition to sociodemographic characteristics, data on the psychiatric care before and during incarceration as well as information on the judicial and prison history were collected. We also analyzed all the pre-sentencing psychiatric reports in order to collect the degree of discernment determined by the psychiatrist expert for each included individual. RESULTS: Sixty-eight (97%) of the 70 people detained at the Château-Thierry prison during the study period were included and 92 pre-sentencing psychiatric reports were analyzed. The population studied was exclusively male, with an average age of 40 years, low socio-economic status and frequent criminal history (79%). About half of them (46%) had already been hospitalized in a psychiatric community hospital prior to incarceration, and 79% have been hospitalized in a psychiatric facility during their incarceration. Disciplinary sanctions were frequent (72%) as well as convictions for offenses committed while in prison (57%). When at least one pre-sentencing psychiatric report was carried out (29 persons had a single psychiatric forensic evaluation and 27 ones had multiple evaluations), at least one psychiatric expert had concluded to a diminished (but not lack of) criminal responsibility in almost half of the cases (44%). CONCLUSION: This study shows the extent to which people incarcerated in the Château-Thierry prison are affected by psychiatric disorders. It also highlights the difficulties of coping with the prison environment for people suffering from psychiatric disorders. Finally, it raises the question of the lack of diversion programs for the individuals in France with mental health problems whose responsibility has been considered as full or diminished.

Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

[Health care delivery and psychiatric hospitalizations in the prisons of the North of France: An observational study]. / Offre de soins et recours aux hospitalisations psychiatriques en milieu pénitentiaire : une étude observationnelle dans le Nord de la France.

BACKGROUND: In French prisons, psychiatric care for inmates is organized into three levels: ambulatory care within each jail in "unités sanitaires en milieu pénitentiaire" (USMP: sanitary units in correctional settings), day hospitalizations in the 28  services médico-psychologiques régionaux (SMPR, "regional medical-psychological services") and full-time hospitalizations in one of the nine "unités d'hospitalisation spécialement aménagées" (UHSA: specially equipped hospital units). Despite high prevalence of mental disorders among French prisoners, the efficiency of these specialized psychiatric care units has been insufficiently studied. The main goal of this study is to describe full-time psychiatric hospitalizations for inmates in the twenty prisons located in the North of France. METHODS: We conducted a descriptive study based on medical and administrative data and survey results. The following data were collected for each prison regarding 2016: 1) number and occupancy rates for mental health professionals and 2) psychiatric hospitalization rates (in the UHSA of Lille-Seclin and the general psychiatric hospitals). RESULTS: Provision of care is incomplete: the vacancy rate in the health units studied reaches 40 %. Moreover, access to UHSA is unequal: it varies pronouncedly according to the location of the prison; only inmates in prisons close to the UHSA benefit from satisfactory access. CONCLUSION: Access to psychiatric care for inmates remains problematic in France, particularly due to a lack of mental health professionals in USMPs, the overload of patients in UHSAs and the distance of theses facilities from certain prisons and jails.

[Mental health care in French correctional facilities during the Covid-19 pandemic]. / Prisons confinées : quelles conséquences pour les soins psychiatriques et la santé mentale des personnes détenues en France ?

OBJECTIVE: The impact of the Covid-19 pandemic on the 11 million people currently incarcerated worldwide is the subject of many concerns. Prisons and jails are filled with people suffering from many preexisting medical conditions increasing the risk of complications. Detainees' access to medical services is already limited and overcrowding poses a threat of massive contagion. Beyond the health impact of the crisis, the tightening of prison conditions worries. On March 16, 2020, in France, the lockdown measures have been accompanied by specific provisions for prisons: all facilities have suspended visitations, group activities and external interventions. Over 10,000 prisoners have been released to reduce the prison population and the risk of virus propagation. These adjustments had major consequences on the healthcare system in French prisons. The objectives of this article are to describe the reorganization of the three levels of psychiatric care for inmates in France in the context of Covid-19 pandemic and to have a look at the impact of lockdown measures and early releases on mental health of prisoners. METHODS: This work is based on a survey conducted in April 2020 in France among psychiatric healthcare providers working in 42 ambulatory units for inmates and in the 9 full-time inpatient psychiatric wards exclusively for inmates called "UHSAs" (which stands for "unités hospitalières spécialement aménagées", and can be translated as "specially equipped hospital units"). A review of the international literature on mental healthcare system for inmates during the Covid-19 epidemic has also been performed. RESULTS: The Covid-19 epidemic has been rather contained during the period of confinement in French prisons but the impact of confinement measures on the prison population is significant. The three levels of psychiatric care for inmates have implemented specific measures to ensure continuity of care, to support detainees during Coronavirus lockdown and to prevent an infection's spread. Among the most important are: limitation of medical consultations to serious and urgent cases, creation of "Covid units", cancellation of voluntary psychiatric hospitalizations, reinforcement of preventive hygiene measures and reshuffling of medical staff. Prolonged confinement has consequences on mental health of detainees. Currently, mental health workers are facing multiple clinical situations such as forced drug and substance withdrawal (linked to difficulties in supplying psychoactive substances), symptoms of anxiety (due to concerns for their own and their relatives' well-being) and decompensation among patients with severe psychiatric conditions. Early releases from prison may also raise some issues. People recently released from prison are identified as at high risk of death by suicide and drug overdose. The lack of time to provide the necessary link between health services within prisons and health structures outside could have serious consequences, emphasizing the well-known "revolving prison doors" effect. DISCUSSION: The current lockdown measures applied in French jails and prisons point out the disparities between psychiatric care for inmates and psychiatric care for general population. Giving the high vulnerability of prison population, public health authorities should pay more attention to health care in prisons.

Structural validity of the Dutch version of the disability of arm, shoulder and hand questionnaire (DASH-DLV) in adult patients with hand and wrist injuries.

BACKGROUND: Fractures of the hand and wrist are one of the most common injuries seen in adults. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire has been developed as a patient-reported assessment of pain and disability to evaluate the outcome after hand and wrist injuries. Patient reported outcomes (PROs) can be interpreted as pain, function or patient satisfaction. To be able to interpret clinical relevance of a PRO, the structural validity and internal consistency is tested. The Dutch version of the DASH has not yet been validated. The aim of this study was to evaluate the structural validity and the internal consistency of the existing Dutch version of the DASH. The relevance of reporting subscale scores was investigated. METHODS: This study was a retrospective analysis of cross-sectional data of 370 patients with an isolated hand or wrist injury. Adult patients aged 18 to 65 years treated conservatively or surgically were included. Patients unable to understand or read the Dutch language were excluded. Confirmatory factor analysis was used to investigate the structural validity, while Cronbach's alpha and coefficient omega were used to assess internal consistency. RESULTS: All investigated models (a single factor model, a 3-correlated factor, and a bifactor model) were associated with a good model fit. Both the single factor and the 3-correlated factor model were associated with factor loadings of at least 0.70. In addition, the covariance between the factors in the 3-correlated factor model was positive (at least 0.89) and statistically significant (p < 0.001). In the bifactor model, the additional value of subscales was limited as the items loaded high on the general factor but low on the subscale factors. CONCLUSION: This study indicates that the Dutch version of the DASH should be considered as an unidimensional trait. A single score should be reported.

Optimized acoustic biochip integrated with microfluidics for biomarkers detection in molecular diagnostics.

The development of integrated platforms incorporating an acoustic device as the detection element requires addressing simultaneously several challenges of technological and scientific nature. The present work was focused on the design of a microfluidic module, which, combined with a dual or array type Love wave acoustic chip could be applied to biomedical applications and molecular diagnostics. Based on a systematic study we optimized the mechanics of the flow cell attachment and the sealing material so that fluidic interfacing/encapsulation would impose minimal losses to the acoustic wave. We have also investigated combinations of operating frequencies with waveguide materials and thicknesses for maximum sensitivity during the detection of protein and DNA biomarkers. Within our investigations neutravidin was used as a model protein biomarker and unpurified PCR amplified Salmonella DNA as the model genetic target. Our results clearly indicate the need for experimental verification of the optimum engineering and analytical parameters, in order to develop commercially viable systems for integrated analysis. The good reproducibility of the signal together with the ability of the array biochip to detect multiple samples hold promise for the future use of the integrated system in a Lab-on-a-Chip platform for application to molecular diagnostics.

[Plasma cell myeloma in the stomach?]. / Plasmazellmyelom im Magen?

The detection of a diffuse infiltrate of heterogeneous small B-cells in the lamina propria mucosae invading the epithelium and destroying the glandular tissue by discrete aggregates of three or more marginal zone B-cells above the basal membrane (so-called lymphoepithelial lesions) is suspicious of a mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach. The demonstration of a monoclonal B-cell population by immunohistochemistry, in situ hybridization or PCR excludes a benign lymphatic lesion. In the differential diagnosis with other small B-cell lymphomas in the stomach, a panel of five different immunohistochemical markers is useful to diagnose a small lymphocytic lymphoma (CD5 and CD23 positive), a mantle cell lymphoma (CD5 and cyclin D1 positive) or a follicular lymphoma (BCL2 and CD10 positive). The presence of the translocation t(11;18)(q21;q21) or the API2/MALT1 rearrangement could give further information about the clinical course and the prognosis of a gastric MALT lymphoma.

The significance of pretransplant donor-specific antibodies reactive with intact or denatured human leucocyte antigen in kidney transplantation.

Antibodies recognizing denatured human leucocyte antigen (HLA) can co-react with epitopes on intact HLA or recognize cryptic epitopes which are normally unaccessible to HLA antibodies. Their specificity cannot be distinguished by single antigen beads (SAB) alone, as they carry a mixture of intact and denatured HLA. In this study, we selected pretransplant sera containing donor-specific HLA class I antibodies (DSA) according to regular SAB analysis from 156 kidney transplant recipients. These sera were analysed using a SAB preparation (iBeads) which is largely devoid of denatured HLA class I, and SAB coated with denatured HLA class I antigens. A total of 241 class I DSA were found by regular SAB analysis, of which 152 (63%) were also found by iBeads, whereas 28 (11%) were caused by reactivity with denatured DNA. Patients with DSA defined either by regular SAB or iBeads showed a significantly lower graft survival rate (P = 0·007) compared to those without HLA class I DSA, whereas reactivity to exclusively denatured HLA was not associated with decreased graft survival. In addition, DSA defined by reactivity to class I SAB or class I iBeads occurred more frequently in female patients and in patients with historic HLA sensitization, whereas reactivity to denatured HLA class I was not associated with any of these parameters. Our data suggest that pretransplant donor-specific antibodies against denatured HLA are clinically irrelevant in patients already sensitized against intact HLA.

[Polypoid dysplasia in inflammatory bowel disease: differential diagnosis and further diagnostic and therapeutic approaches]. / Polypoide Dysplasie bei chronisch-entzündlicher Darmerkrankung: Differenzialdiagnose und weiteres diagnostisch-therapeutisches Vorgehen.

Polypoid dysplasia in inflammatory bowel disease (IBD) is categorized as DALM (dysplasia associated lesion or mass) or ALM (adenoma-like mass). DALMs are etiologically related to the underlying inflammatory disease, have a high risk of cancer and remain an indication for colectomy. Sporadic adenomas occur coincidentally according to the adenoma-carcinoma sequence. They are adequately treated by polypectomy. More recently, a special group of lesions has been termed as "adenoma-like DALM" which shows a morphological overlap with sporadic adenomas in spite of arising against the background of chronic IBD. Adenoma-like DALMs may possess a lower risk of malignancy in contrast to non-adenoma-like DALMs. They may be treated adequately by polypectomy and continued monitoring if the lesion has been excised completely and there is no evidence of flat dysplasia elsewhere in the colon.

[Microscopic colitis: histopathological review with a clinicopathological correlation]. / Mikroskopische Kolitis: Histopathologische Übersicht mit klinisch-pathologischer Korrelation.

Microscopic colitis is a clinicopathological entity which, in addition to typical symptoms such as watery diarrhea, is characterized by its specific histopathology. Since colonoscopy yields normal findings, microscopic colitis belongs in a histological domain. The term encompasses two forms: lymphocytic and collagenous colitis. Histologically, lymphocytic colitis shows an increase in intraepithelial lymphocytes of more than 20 lymphocytes per 100 surface colonocytes, while collagenous colitis is characterized by a thickened subepithelial collagen layer of more than 10 µm. Specific stains help in the quantification of both. Since microscopic colitis does not always affect the entire colon and the number of intraepithelial lymphocytes varies physiologically, obtaining stepwise biopsies of the colon (with information on location where possible) is recommended. A thickened collagen layer is relatively specific for collagenous colitis, whereas intraepithelial lymphocytosis is also found in other diseases. Therefore, to make a correct diagnosis, it is important to correlate histological findings with clinical symptoms, including the main symptom of watery diarrhea.

[Endoscopic-bioptic diagnostics, surveillance of and therapy for gastrointestinal diseases according to guidelines]. / Leitlinienorientierte endoskopisch-bioptische Diagnostik, Uberwachung und Therapie von Magen-Darm-Erkrankungen.

The present review summarises the detailed recommendations for an optimal endoscopic-bioptic diagnostic procedure, endoscopic surveillance of and therapy for gastrointestinal diseases. The recommendations are mainly based on the S 3-guidelines and have been developed by histopathologists and gastroenterologists in interdisciplinary work. The material has been arranged according to topographic regions of the gastrointestinal tract and clinical problems. The focus is placed on diagnostic and surveillance of Barrett's oesophagus, therapy and postoperative treatment for early gastrointestinal carcinoma, management of colon polyps and endoscopic surveillance of inflammatory bowel disease. Treatment recommendations for both ulcerative colitis and Crohn's disease as well as low-grade and high-grade intraepithelial neoplasia and polypoid neoplasia are currently being intensively discussed. Thus we examine this controversial discussion in detail. Furthermore, the recent guidelines for Helicobacter pylori (H. pylori) and gastric MALT-lymphoma diagnostics are included in this survey. To allow the gastroenterologist a time-sparing overview during practical work, most of the recommendations are presented in itemised form and summarised in tables and figures at the end of the discussion.

Course of behaviour problems of children with cerebral palsy: the role of parental stress and support.

BACKGROUND: Cerebral palsy (CP) is a well-recognized neurodevelopmental condition persisting through the lifespan. In many individuals with CP, motor disorders are accompanied by other disturbances, including emotional and behavioural problems. Little is known on the course of such problems, also in relation to possible exacerbating or mitigating factors. Aims of this study were to test whether parental stress and support, apart from the severity of CP of the child, played a significant role in the course of behaviour problems. METHOD: The participants aged 9, 11 and 13 were assessed (baseline) and followed up after 1, 2 and 3 years. Situational and relational sources of support and stress for the primary caregiver were rated with a questionnaire: (CBCL), behaviour problems with the Child Behaviour Checklist. Physicians rated motor ability using the Gross Motor Function Classification System. RESULTS: Behaviour problems of children with CP started significantly higher than in the general population, but diminished over the 3-year period. Older children showed less problems overall, and girls showed less externalizing problems than boys. Children with the most severe CP had more externalizing problems; effects on internalizing problems were not significant. Across time, an excess of stress vs. support related to parents' socio-economic and living situation and to parents' social relationships was positively related to total behaviour problems, internalizing and externalizing behaviours of children. CONCLUSIONS: Levels of behaviour problems are elevated but diminish during adolescence for children with CP. Severity of CP plays a role as well as the family context in terms of the stress and support that caregivers experience.

[Gastric MALT-type lymphoma. Pathology, pathogenesis, diagnostics and therapy]. / Magenlymphome vom MALT-Typ. Pathologie, Pathogenese, Diagnostik und Therapie.

Helicobacter pylori infection plays a central role in the development of gastric MALT-type (mucosa-associated lymphoid tissue) lymphoma. Infection results in chronic H. pylori gastritis and stimulates together with antigens or autoantigens proliferation of B-lymphocytes which is the basis for the neoplastic transformation. Histology of MALT-type lymphoma is architecturally similar to the physiological MALT. Invasion and destruction of the gastric epithelium with development of so-called lympho-epithelial lesions is the most important diagnostic criterion. Cytologically MALT-lymphoma resembles centrocytes and monocytes. For definitive lymphoma diagnosis and for the differential diagnosis from other small cell lymphomas in the stomach immunohistochemistry can be helpful. The phenotype of MALT-type lymphoma is identical to non-neoplastic B-lymphocytes of the marginal zone (CD20+, CD5-, CD10- and CD23-). Individual therapy is strongly dependent from histological type and lymphoma stadium. Therapy modalities are H. pylori eradication, radiochemotherapy, surgery or a combination of these. Aim of the therapy is the complete lymphoma regression and cure of the disease.

[Gastric leishmaniasis. A rare type of gastritis]. / Gastrale Leishmaniose. Ein seltener Gastritistyp.

Gastric leishmaniasis was diagnosed in a 43-year-old HIV infected patient by histopathology as an accidental diagnostic finding. Leishmania HIV co-infections have increasingly been reported recently as a result of intensive travelling and an increase in geographical extension. Nevertheless, Leishmania gastritis is a rare disease which can occur without clinical symptoms and in the absence of endoscopic abnormalities. In this case microscopic detection of the pathogen in macrophages of the gastric mucosa resulted in the correct diagnosis.

Metabolomics (liver and blood profiling) in a mouse model in response to fasting: a study of hepatic steatosis.

A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major changes were observed using different techniques. High performance thin layer chromatography (HPTLC)-measurements of liver-homogenates indicated a significant rise of FC with 192%, triacylglycerols (TG) with 456% and cholesterol esters (CE) with 268% after 24 h of starvation in comparison with the control group. Reversed phase liquid chromatography coupled to mass spectrometry measurements (LC-MS) of liver homogenate indicated that the intensity of Phosphatidylcholine (PC) in the 24-h starvation group dropped to 90% of the value in the control group while the intensity of CE and TG increased to 157% and 331%, respectively, of the control group. Interestingly, a 49:4-TG with an odd number of C atoms appeared during starvation. This unique triacylglycerol has all characteristics of a biomarker for detection of hepatic steatosis. These observations indicate that in mammals liver lipid profiles are a dynamic system which are readily modulated by environmental factors like starvation.

Gastric extranodal marginal zone B-cell lymphomas of MALT type exclusively express Toll-like receptor 4 in contrast to other lymphomas infiltrating the stomach.

BACKGROUND: Development and growth of extranodal marginal zone B-cell lymphomas (eMZBCLs) of mucosa-associated lymphoid tissue (MALT) type are thought to be highly dependent on Helicobacter pylori and autoantigens. Receptors mediating these effects are not characterised so far. Toll-like receptors (TLRs) recognise bacterial proteins and autoantigens, which results in inflammatory reactions and influences tumour development and growth. MATERIALS AND METHODS: TLR4, 5 and 9 expressions were evaluated by immunohistology and confocal microscopy in gastric eMZBCL in comparison to other lymphomas infiltrating the stomach. RESULTS: TLR4 was exclusively expressed on the cell surface in all eMZBCL (n = 19) and not in chronic lymphocytic leukaemia (CLL, n = 12) or mantle cell lymphoma (MCL, n = 10). TLR5 was strongly expressed in CLL and weak in some eMZBCL (15 of 19), but not in MCL. TLR4, 5 and 9 were negative in all the three lymphoma entities. CONCLUSIONS: Exclusive TLR4 expression may enable eMZBCL to interact with H. pylori and autoantigens. Blockade of TLR4 might be a new approach for therapy of eMZBCL of MALT type.

Reduced leucocyte cholesteryl ester transfer protein expression in acute coronary syndromes.

OBJECTIVE: Cholesterol ester transfer protein (CETP) plays an important role in HDL cholesterol metabolism. Leucocytes, including monocyte-derived macrophages in the arterial wall synthesize and secrete CETP, but its role in atherosclerosis is unclear. The aim of the current study was to investigate the effect of acute coronary syndromes (ACS) on leucocyte CETP expression. RESEARCH DESIGN: Peripheral blood mononuclear cells (PBMCs) were freshly isolated from hospitalized ACS patients displaying Braunwald class IIIB unstable angina pectoris (UAP) on admission (t = 0) and at 180 days post inclusion (t = 180) for analysis of CETP expression. In addition, to prove the potential correlation between leucocyte CETP and ACS the effect of acute myocardial infarction on leucocyte CETP expression was studied in CETP transgenic mice. RESULTS: Upon admission, UAP patients displayed approximately 3-6 fold (P < 0.01) lower CETP mRNA and nearly absent CETP protein expression in PBMCs, as compared to healthy age-/sex-matched controls. Interestingly, CETP mRNA and protein levels were significantly elevated in PBMCs isolated from UAP patients (both stabilized and refractory) at t = 180 as compared to t = 0 (P < 0.01), which was correlated with a reduced inflammatory status after medical treatment. In agreement with the data obtained in UAP patients, markedly down-regulated leucocyte CETP mRNA expression was observed after coronary artery ligation in CETP transgenic mice, which also correlated with increased serum amyloid A levels. CONCLUSIONS: We are the first to report that episodes of UAP in humans and myocardial infarction in CETP transgenic mice are associated with reduced leucocyte CETP expression. We propose that the impairment in leucocyte CETP production is associated with an enhanced inflammatory status, which could be clinically relevant for the pathogenesis of ACS.

Triggering receptor expressed on myeloid cells-1 (TREM-1) expression on gastric epithelium: implication for a role of TREM-1 in Helicobacter pylori infection.

In Helicobacter pylori gastritis gastric epithelium plays a central role in the innate immunity to H. pylori. However, epithelial receptors interacting with H. pylori have been poorly characterized so far. Recently a new triggering receptor expressed on myeloid cells-1 (TREM-1) has been identified on human neutrophils and monocytes. On these cells TREM-1 triggers innate immunity by stimulating the secretion of interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha and thus amplifies bacterial-induced inflammation. In this study expression and function of TREM-1 in gastric epithelium exposed to H. pylori has been investigated. TREM-1 mRNA and protein were expressed on gastric epithelial cell lines as demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence activated cell sorter analysis. Gastric epithelial TREM-1 expression was up-regulated directly by H. pylori and was independent of epithelial IL-8 induced by H. pylori. Immunohistochemistry and tissue RT-PCR demonstrated significantly stronger TREM-1 expression in H. pylori gastritis compared with the non-inflamed gastric mucosa supporting in vivo that epithelial TREM-1 is up-regulated during H. pylori infection. Stimulation of gastric epithelial TREM-1 receptor resulted in IL-8 up-regulation on mRNA and protein level, as shown by real-time PCR and immunoassay. This is the first study localizing TREM-1 on gastric epithelium. Functional data suggest that TREM-1 expressed on gastric epithelium amplifies inflammation of the underlying gastric mucosa by up-regulation of IL-8.