Injectable autologous chondrocyte implantation in acetabular cartilage defects: 2-year minimum clinical and MRI results.

INTRODUCTION: Early results using injectable autologous chondrocyte implantation (ACI) for the treatment of full thickness acetabular cartilage defects have been promising. However, so far there is no information on radiological results after injectable ACI using spheroids. The purpose of this sturdy was to (1) investigate the quality of tissue repair on MRI and (2) investigate the correlation between the MRI results and clinical results at a minimum follow-up of 24 months after third generation ACI in full thickness acetabular cartilage defects. It was hypothesized that ACI shows good MRI results in patients with large full thickness acetabular cartilage defects 24 months after surgery. It was also hypothesized that there is a correlation between postoperative clinical and MRI morphological results at a minimum follow-up of 24 months. STUDY DESIGN: Retrospective case series. MATERIALS AND METHODS: Patients with ACI for full thickness acetabular cartilage defects > 2 cm2 were evaluated by preoperative and postoperative clinical scoring tools including the modified Harris Hip Score (mHHS), the International Hip Outcome Tool (iHOT-33), and the Subjective Hip Value (SHV) as well as a high resolution indirect arthro-MRI 24 months after surgery utilizing an identical imaging protocol for all patients. The magnetic resonance observation of cartilage repair tissue (MOCART) scoring system was used to classify the repair tissue on MRI. Demographic patient data was evaluated for influencing factors for pre- and postoperative clinical as well as radiological results. RESULTS: Thirty six consecutive patients (5 women/31 men, average age 32.9 years) had undergone two stage ACI procedure. The average size of the cartilage defect was 5.0 (2-6) cm2. The average follow-up was 29.9 (24-42) months. Four patients were not available for the final follow-up (follow-up rate 89%). The postoperative average MOCART score was 82.2 (± 14.2). MOCART score showed medium correlation of the item defect fill and the postoperative mHHS (r = 0.384, p = 0.043). There was no correlation of the other items or the total score with postoperative results. The patients showed significant improvement in the outcome measurements between preoperative and postoperative in the mHHS, the iHOT-33, and the SHV. CONCLUSIONS: Despite the large acetabular cartilage defects included in this study, ACI showed good MRI results with complete defect fill in 87.5% after a minimum 24-month follow-up. Statistically significant correlation of MRI and clinical results could only be seen with the item defect fill. Further research with longer follow-up is needed to evaluate the long-term results of ACI in acetabular cartilage defects.

Outcome of transcatheter edge-to-edge mitral valve repair in patients with diabetes mellitus: Results from a real-world cohort.

BACKGROUND: There are only limited data on patients with diabetes undergoing transcatheter edge-to-edge repair (TEER) in real-world settings. Previous data indicated patients with diabetes to have a worse prognosis. This study sought to evaluate safety and efficacy of TEER in patients with diabetes in a real-world cohort. METHODS: In this monocentric study 340 consecutive patients with severe primary and secondary mitral regurgitation (MR) undergoing TEER were included. Immediate results of the procedure, intrahospital and one-year outcome were compared between patients with and without diabetes. RESULTS: Diabetes was present in 109 patients (32%). Patients with diabetes were younger (77 y (71, 81) vs. 79 y (74, 83); p = 0.003), had more often ischemic cardiomyopathy (68% vs. 48%; p<0.001), previous coronary-artery bypass graft (35% vs. 20%; p = 0.002) and arterial hypertension (89% vs. 75%; p<0.001) compared to those without diabetes. Baseline NYHA class, type of MR (primary vs. secondary), left ventricular dimensions and function (ejection fraction: 37% (28, 50) vs. 40% (29, 55); p = 0.10) as well as severity of MR were not different between both groups. Success of the procedure (95% vs. 95%; p = 0.84), intrahospital mortality (5.5% vs. 4.8%; p = 0.98) and one-year follow-up regarding all-cause mortality (24.2% vs. 23.0%; p = 0.72), hospitalization for heart failure (37.4% vs. 31.0%, p = 0.23), NYHA class (p = 0.14) or MR severity (p = 0.59) did not differ between both groups. CONCLUSION: Our real-world data suggest that TEER seems to be similarly safe and effective in patients with severe MR and diabetes compared to those without diabetes.

Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.

BACKGROUND: Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT). METHODS: The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months. RESULTS: In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Dual-center experiences with interventional closure of patent foramen ovale: A medium-term follow-up study comparing two patient groups aged under and over 60 years.

BACKGROUND: Current guidelines recommend interventional closure of patent foramen ovale (PFO) in patients with cryptogenic ischemic stroke who are under 60 years of age. HYPOTHESIS: The hypothesis of this study was to compare follow-up results of PFO closure in patients over 60 years of age to those of patients under 60 years of age in order to determine whether the procedure is safe and effective for both age groups. METHODS: We included 293 patients who had a cryptogenic ischemic stroke and a PFO confirmed by transesophageal echocardiography (TEE) and who were scheduled for percutaneous closure of the PFO between 2014 and 2019. The device implantation was completed in all patients using an Amplatzer™, Occlutec™, or Cardia Ultrasept PFO occluder. RESULTS: Follow-up TEE examinations were performed at intervals of 1, 3, and 6 months after implantation. Patients were followed for a median of 3.6 ± 1.2 years. Recurrent ischemic stroke or transient ischemic attack, cardiac death, arrhythmias, and residual shunt were reported equally in both groups. CONCLUSIONS: Interventional closure of PFO can be as safe and effective in patients over 60 years of age as it is in patients under 60 years of age regardless of the device used. In this older patient group, rigorous discussion and a case-by-case decision-making process including cardiologists and neurologists is warranted to ensure optimal procedure selection.

Correlation of the Subjective Hip Value with Validated Patient-Reported Outcome Measurements for the Hip.

BACKGROUND: The subjective hip value (SHV) was developed as a patient-reported outcome measurement (PROM) that is easily and quickly performed and interpreted. The SHV is defined as a patient's subjective hip measurement tool expressed as a percentage of an entirely normal hip joint, which would score 100%. The hypothesis is that results of the subjective hip value correlate with the results of the modified Harris hip score and the International Hip Outcome Tool in patients with hip-related diseases. METHODS: 302 patients completed the modified Harris hip score (mHHS), the International Hip Outcome Tool (iHot-33) as well as the SHV. The SHV consist of only one question: "What is the overall percent value of your hip if a completely normal hip represents 100%?". The patients were divided into five different groups depending on the diagnosis. Pearson correlation was used to evaluate the correlation between the different PROMs and linear regression analysis was used to calculate R2. RESULTS: 302 complete datasets were available for evaluation. There was a high correlation between the SHV and the iHOT-33 (r = 0.847; r2 = 0.692, p < 0.001) and the mHHS (r = 0.832; r2 = 0.717, p < 0.001). The SHV showed a medium (r = 0.653) to high (r = 0.758) correlation with the mHHS and the iHOT-33 in all diagnosis groups. CONCLUSION: The SHV offers a useful adjunct to established hip outcome measurements, as it is easily and quickly performed and interpreted. The SHV reflects the view of the patient and is independent of the diagnosis. Further research with prospective studies is needed to test the psychometric properties of the score.

Use of the Prostate Health Index and Density in 3 Outpatient Centers to Avoid Unnecessary Prostate Biopsies.

OBJECTIVES: We investigated the diagnostic efficacy of the prostate health index (PHI) and PHI density (PHID) to avoid unnecessary prostate biopsies in 3 urological practices. METHODS: In 122 patients, total prostate-specific antigen (PSA), free PSA (f-PSA), the quotient from total PSA and f-PSA (f-PSA%), and [-2]pro-PSA were measured in the serum; PHI, PHID, and PSA density (PSAD) were calculated prior to prostate biopsy. Tissue sampling via transrectal biopsy was indicated in case of suspicious PSA (progression and/or elevation of PSA) and/or suspicious digital rectal examination. PSAD, PHI, and PHID were not used for biopsy indication. The diagnostic efficacy was determined with receiver-operating characteristic (ROC)and decision curve analyses. RESULTS: Based on prostate biopsies, 38% (n = 46) of the cases had no prostate carcinoma (PCa), 21% (n = 26) no clinically significant (insignificant) PCa, and 41% (n = 50) had clinically significant PCa. ROC analyses of the PSA parameters showed higher diagnostic efficacy for PHI and PHID (AUC 0.722 and 0.739) than for f-PSA%, PSA, and PSAD (AUC 0.612, 0.595, and 0.698, respectively) regarding carcinoma diagnosis. With a combined use of PHI and PHID (cutoff >40 and >0.9, respectively), only 1 clinically significant PCa would have been missed (sensitivity 98%); in 24 (20%) patients, biopsy could have been avoided. CONCLUSION: The integration of PHI and PHID could improve the diagnostic efficacy of risk calculators to avoid unnecessary prostate biopsies. However, as a prerequisite, validation of cutoff values in prospective studies is urgently required.

Phenotypic Characterization of DFNB16-associated Hearing Loss.

HYPOTHESIS: We hypothesized that patients with DFNB16 caused hearing loss show characteristical audiological findings depending on genetic results. BACKGROUND: Hearing loss belongs to the most frequent congenital diseases. In 50-70% of individuals, hearing loss is caused by genetic defects. DFNB1 (deafness, neurosensory, autosomal-recessive) is the most frequently affected locus. Despite its great genetic heterogeneity, comprehensive analysis of genes like STRC, encoding stereocilin (DFNB16) is possible. The genetic architecture of the DFNB16 locus is challenging and requires a unique molecular genetic testing assay. The aim of the study is a systematic characterization of the audiological phenotype in DFNB16-positive patients. METHODS: Since 2011, 290 patients with suspicion of inherited hearing loss received a human genetic exploration. Eighty two DFNB1-negative patients advanced to further testing in the DFNB16 locus. STRC-positive patients obtained complete audiological diagnostic workup. Additionally, epidemiological data was collected. RESULTS: Nine of 82 (11%) of the examined patients (mean age 5 yr) showed mutations in the STRC (3 homozygous, 6 compound heterozygous). Aside from a moderate hearing loss in the pure tone audiogram, auditory brainstem response thresholds were 40-50 dB nHL. Otoacoustic emissions were detectable in only one patient. CONCLUSIONS: Examination of the DFNB16-locus should be a standard diagnostic test after negative DFNB1-gene screening result. Notably, DFNB16-associated hearing loss can be audiologically characterized as moderate sensorineural hearing loss in the main speech field with absent otoacoustic emissions. Our study is the first to correlate audiological findings with genetic results in patients with hearing loss due to STRC.

Injectable autologous chondrocyte implantation (ACI) in acetabular cartilage defects-three-year results.

To evaluate the clinical outcome after arthroscopic matrix-associated injectable autologous chondrocyte implantation (ACI) in patients with large full-thickness acetabular cartilage defects. ACI was performed in young patients with full-thickness acetabular cartilage defects ≥2 cm2 in a two-step arthroscopic procedure. The patients were followed closely with clinical examinations and pre- and postoperative scores. The modified Harris Hip Score (mHHS), iHOT33 questionnaire (iHOT33) and the Subjective Hip Value (SHV) were surveyed. Demographic patient data was evaluated for influencing factors for the pre- and postoperative results. Thirty-two consecutive cases (4 female, 28 male, mean age 33 years) were included. The average defect size was 4.9 (range: 2-6) cm2. They were followed at 6, 12, 24 and 36 months postoperatively. Patients had improved significantly from 64 to 91 points (P < 0.001) in the mHHS, from 44% to 86% (P < 0.001) in the iHOT33 and from 54% to 87% (P < 0.001) in the SHV. No surgery related complications were noted. Cell cultivation failed in two cases (7%) and the patients decided for a repeated harvesting of cartilage cylinders followed by a successful ACI. Patients age and size of the cartilage defect showed no significant correlation with the pre- or postoperative results. Injectable ACI is a reliable procedure treating full-thickness acetabular cartilage defects leading to promising results 3 years postoperatively with a significant increase in all scores despite large acetabular cartilage defects in the weight-bearing zone.

Is the evaluation of the anterior inferior iliac spine (AIIS) in the AP pelvis possible? Analysis of conventional X-rays and 3D-CT reconstructions.

INTRODUCTION: A hypertrophic AIIS has been identified as a cause for extraarticular hip impingement and is classified according to Hetsroni using 3D-CT reconstructions. The role of the conventional AP pelvis X-ray, which is the first standard imaging step for the evaluation of hip pain, has not been investigated yet. MATERIALS AND METHODS: AP pelvis X-rays and 3D-CT reconstructions of patients were evaluated regarding their morphology of the AIIS. The conventional X-rays were categorized into three groups according to the projection of the AIIS: above (A) or below (B) the acetabular sourcil or even exceeding the anterior acetabular rim (C). They were compared to the morphologic types in the 3D-CT reconstruction (Hetsroni type I-III). RESULTS: Ninety patients with an equal distribution of type A, B or C projection in the AP pelvis were evaluated and compared to the morphology in the 3D-CT reconstruction. The projection of the AIIS below the acetabular sourcil (B + C) showed only moderate sensitivity (0.76) and specificity (0.64) for a hypertrophic AIIS (Hetsroni type II + III), but if the AIIS exceeds the anterior rim, all cases showed a hypertrophic AIIS in the 3D-CT reconstructions (Hetsroni type II + III). CONCLUSIONS: Distinct differentiation of the AIIS morphology in the AP pelvis is not possible, but the projection of the AIIS below the anterior acetabular rim represented a hypertrophic AIIS in all cases and should, therefore, be critically investigated for a relevant AIIS impingement.

Injectable autologous chondrocyte transplantation for full thickness acetabular cartilage defects: early clinical results.

INTRODUCTION: Acetabular cartilage lesions are frequently seen in young patients with hip pain and have been identified as an important prognostic factor. New therapies have complemented abrasion and microfracture procedures. The aim of the study is to evaluate the early outcome of patients with arthroscopic injectable autologous chondrocyte transplantations (ACT) for full thickness acetabular cartilage defects. METHODS: A two-step procedure ACT was performed in patients with full thickness acetabular cartilage defects measuring ≥2 cm(2). The patients were closely followed with clinical examination, pre- and postoperative scores until the latest available follow-up of 3, 6, 12, and 24 months. RESULTS: 20 consecutive cases (4 female, 16 male, mean age 33 years) were included. No patients were lost at final follow-up. The average defect size was 5.05 (range 2-6) cm(2). The average follow-up was 12.05 (range 6-24) months. Three months postoperatively the preoperative scores improved significantly from a mean mHHS of 63-81 points (p = 0.009), iHOT33 of 44-66 % (p = 0.028) and subjective hip assessment (Subjective Hip Value, SHV) of 60-87 % (p = 0.007). After 12 months the results improved significantly to a mean mHHS of 93 points (p = 0.017), an iHOT33 of 79 % (p = 0.007) and an SHV of 82 % (p = 0.048) compared with the preoperative scores. DISCUSSION: The injectable matrix associated ACT is a reliable procedure, yielding promising early results with a significant increase of all scores evaluated in patients with full thickness acetabular cartilage defects.

Prediction of Outcomes in Patients with Chronic Ischemic Cardiomyopathy by Layer-Specific Strain Echocardiography: A Proof of Concept.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) has been established as a powerful tool for predicting mortality. However, its application is limited by availability and various contraindications. The aim of this study was to evaluate the predictive value of layer-specific myocardial deformation analysis as assessed by strain echocardiography for cardiac events in patients with chronic ischemic left ventricular dysfunction in comparison with CMR. METHODS: Three hundred ninety patients (mean age, 63 ± 4 years; 69% men; mean left ventricular ejection fraction [LVEF], 41 ± 7%) with chronic ischemic cardiomyopathy were prospectively enrolled and underwent strain echocardiography and CMR within 3 ± 1 days. LVEF, wall motion score index, and circumferential strain (CS), longitudinal strain, and radial strain for total wall thickness and for three myocardial layers (endocardial, midmyocardial, and epicardial) were determined by echocardiography. The extent of total myocardial scar (TMS) was determined by CMR. Follow-up was obtained for a mean of 4.9 ± 2.2 years. Cardiac events were defined as readmission for worsening of heart failure, ventricular arrhythmias, or death of any cause. The incremental value of LVEF, strain parameters, and TMS to relevant clinical variables was determined in nested Cox models. RESULTS: There were 133 cardiac events (34%). Baseline clinical data associated with outcomes were age (hazard ratio [HR], 1.27; P = .04), diabetes mellitus (HR, 1.52; P = .001), and renal insufficiency (HR, 1.77; P = .001) by multivariate analysis. The addition of LVEF, global and endocardial strain parameters, and TMS increased the predictive power, but endocardial CS (HR, 1.52; P < .01) caused the greatest increment in model power (χ(2) = 39.2, P < .001). Endocardial CS < -20% was found to be the optimal predictor of prognosis. CONCLUSIONS: Endocardial CS is a powerful predictor of cardiac events and appears to be a better parameter than LVEF, TMS by CMR, and other strain variables by echocardiography.

Myocardial deformation by strain echocardiography identifies patients with acute coronary syndrome and non-diagnostic ECG presenting in a chest pain unit: a prospective study of diagnostic accuracy.

OBJECTIVE: Clinical assessment often cannot risk stratify patients hospitalized with chest pain and non-diagnostic electrocardiography (ECG) or myocardial enzymes. An inappropriate admission of patients with non-cardiac chest pain is an enormous cost factor. METHODS: 2315 patients who presented in the chest pain unit (CPU) with symptoms suggestive of acute coronary syndrome (ACS) were screened. All patients with relevant changes in ECG or myocardial enzymes were excluded. 268 consecutive patients (mean 58 ± 7 years, 88 men) were prospectively included and underwent echocardiography for left ventricular ejection fraction (LVEF), wall motion score index (WMSI) and strain parameter and a coronary angiography (CA) within 2 ± 1 days after admission. RESULTS: Anatomically obstructive coronary artery disease (CAD) (≥70 % diameter stenosis) was present in 110 patients (41 %). The incremental value of LVEF, WMSI, and strain parameters to relevant clinical variables was determined in nested Cox models. Baseline clinical data associated with relevant CAD were age [hazard ratio (HR) 1.31, p = 0.03], arterial hypertension (HR 1.39, p = 0.03) and diabetes (HR 1.46, p = 0.001). The addition of endocardial global circumferential strain (GCS) (HR 1.57, p < 0.001) caused the greatest increment in model power (χ (2) = 43.4, p < 0.001). Optimal cut-off value was calculated as -21.7 % for GCS (sensitivity 87 %, specificity 76 %) to differentiate between these patients. CONCLUSIONS: In patients with suspected ACS but without ECG changes or myocardial enzyme abnormalities, myocardial deformation imaging can identify patients at risk. This approach may be applied to improve decision guidance at the CPU for fast discharge of patients with non-cardiac chest pain or prompt cardiological allocation of patients with CAD. CLINICAL TRIAL REGISTRATION: NCT 02357641.

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location.

AIMS: Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS: A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION: Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.

Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella.

Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria. We have identified a single-copy cathepsin B-like cysteine peptidase gene in the genome database of Eimeria tenella (EtCatB). Molecular modeling of the predicted protein suggested that it differs significantly from host enzymes and could be a good drug target. EtCatB was expressed and secreted as a soluble, active, glycosylated mature enzyme from Pichia pastoris. Biochemical characterization of the recombinant enzyme confirmed that it is cathepsin B-like. Screening of a focused library against the enzyme identified three inhibitors (a nitrile, a thiosemicarbazone, and an oxazolone) that can be used as leads for novel drug discovery against Eimeria. The oxazolone scaffold is a novel cysteine peptidase inhibitor; it may thus find widespread use.

The right ventricular response to high afterload: comparison between healthy persons and patients with transposition of the great arteries: a 2D strain study.

OBJECTIVE: To evaluate the contraction pattern of the systemic right ventricle (RV) in comparison to healthy controls. METHODS: 31 patients (14 female, mean age 21.5 ± 3.3 years) with congenital corrected (ccTGA) and surgical corrected (D-TGA) TGA and 31 age-matched healthy controls (17 female, mean age 23.1 ± 2.6 years) were included in the study. We compared the contraction pattern of the systemic RV with findings in the right and left ventricle (LV) of healthy controls. Echocardiograms were performed for all patients (19.3 ± 2.5 years after the operation) and all healthy controls. Using a novel computer software (GE Ultrasound, Horton, Norway) that allows automatic frame-by-frame tracking of accoustic markers during the heart cycle longitudinal and circumferential strain and strain rate were defined as parameters of myocardial deformation. RESULTS: In the systemic free RV wall, circumferential strain was greater than longitudinal strain (-25.6 ± 4.2% vs. -15.2 ± 3.9%, P < 0.001), opposite to the contraction pattern of the subpulmonary free RV wall (-17.7 ± 4.1% vs. -28.3 ± 3.3%, P < 0.001). Compared with controls, segmental analysis of the free RV wall resulted in lower systolic longitudinal and higher systolic circumferential strain and strain rate values. In the free LV wall, circumferential strain was lower than longitudinal strain (-19.1 ± 2.7% vs. -26.8 ± 4.5%, P < 0.001) in contrast to the data in the systemic free LV wall (-24.5 ± 3.1% vs. -16.7 ± 3.5%, P < 0.001). CONCLUSIONS: Myocardial deformation parameters were significantly different in systemic and normal RV indicating a dependency of myocardial deformation parameters on right ventricular afterload. The use of myocardial deformation imaging identified a shift from longitudinal to circumferential contraction pattern in the systemic RV in comparison to the LV. This might demonstrate a response to the systemic load creating a myocardial hypertrophy.

Inhibition of interleukin-6-transsignaling via gp130-Fc in hemorrhagic shock and sepsis.

BACKGROUND: Immune function after hemorrhagic shock and subsequent sepsis is characterized by an early proinflammatory burst of IL-6, and high IL-6 levels have been linked to high mortality after trauma and in sepsis. Trans-signaling is defined as the activation of cells that do not express the membrane bound IL-6 receptor by the complex of IL-6 and the soluble IL-6 receptor (sIL-6R). Gp130-Fc is able to bind the IL-6/sIL-6R complex, and beneficial effects of IL-6 blockade in chronic inflammatory diseases have been shown. The first aim of this study was to investigate the potential effect of a gp130 blockade via the gp130-Fc antibody causing impairment of IL-6 signaling. The second aim was to find out what role the IL-6/sIL-6R complex can play in the context of hemorrhagic shock and subsequent sepsis as an acute inflammatory disease. MATERIAL AND METHODS: Male CBA/J mice were subjected to hemorrhagic shock (35+/-5 mmHg for 90min and fluid resuscitation) or sham operation. At resuscitation each animal received either 0.5mg gp130-Fc or placebo (PL) i.p. At 48 h after resuscitation, both splenocytes and peritoneal macrophages (pMphi) were harvested or polymicrobial sepsis was induced by cecal ligation and puncture. Survival over 10 d was determined. Release of IL-6, TNF-alpha, and IL-10 of pMphi and release of IL-2, IL-10, and IFN-gamma of splenocytes was assessed by ELISA. Proliferation of splenocytes and their morphologic damage were determined. RESULTS: Binding of the IL-6/sIL-6R complex by gp130-Fc led to significant lower IL-6 levels compared with placebo treated animals. Placebo treated males showed depressed proinflammatory immune response (IL-2, IL-6) after hemorrhagic shock. While splenocyte proliferation was significantly reduced directly after hemorrhagic shock and restored after 48 h by gp130-Fc, pMphi cytokine release was not influenced. Finally, survival appeared to be unaffected. CONCLUSION: Transsignaling does not seem to play a pivotal role in the development of the immune dysfunction and mortality in our model of hemorrhage and subsequent sepsis.

Twenty-three neutrophil granulocytes in 10 high-power fields is the best histopathological threshold to differentiate between aseptic and septic endoprosthesis loosening.

AIMS: The histopathological diagnosis of infection in periprosthetic tissue from loose total joint endoprosthesis has been the subject of controversy. The aim was to define a histological criterion that would best differentiate between aseptic and septic endoprosthesis loosening. METHODS AND RESULTS: Neutrophilic granulocytes (NG) were enumerated histopathologically in 147 periprosthetic membranes obtained from aseptic and septic revision surgery, using periodic acid-Schiff (PAS) stains and CD15 immunohistochemistry. Cell numbers were correlated with the results of microbiological culture and the clinical diagnoses. Using receiver-operating characteristics, an optimized threshold was found at 23 NG in 10 high-power fields (HPF). Using this threshold, histopathological examination had a sensitivity of 73% and specificity of 95% when compared with microbiological diagnosis (area under the curve 0.881), and a sensitivity of 77% and specificity of 97% when compared with clinical diagnosis (area under the curve 0.891). CONCLUSIONS: We therefore recommend a counting algorithm with a threshold of > or =23 NG in 10 HPF (visual field diameter 0.625 mm) for the histopathological diagnosis of septic endoprosthesis loosening. If the enumeration of NG is difficult in conventional haematoxylin and eosin-stained slides, CD15 immunohistochemistry should be performed, whereas the PAS stain has not proven to be helpful.

Computer-assisted validation of the synovitis score.

Histopathological examination of synovial specimens can contribute to the diagnosis of chronic joint diseases. A so-called synovitis score has been introduced as a standardised grading system, based on the semi-quantitative evaluation of the three determining features of chronic synovitis: enlargement of synovial lining, density of synovial stroma and inflammatory infiltrate, giving a score between 0 and 9. The present study examines the reliability of this procedure by comparison with exact measurements using computer-assisted image analysis (CAIA). Seventy-one synovial specimens from patients with osteoarthritis (OA, n=22), psoriatic arthritis (PsA, n=7), rheumatoid arthritis (RA, n=35) and from a control group (Co, n=7) were evaluated using both the synovitis score and CAIA. The measurements were transformed to semi-quantitative values analogous to the synovitis score. The differences between the transformed CAIA scores and the pathologist's scores were 0 or +/-1 in 40 cases, whereas in 31 cases the difference was greater than 1 (correlation coefficient r=0.725). The CAIA scores differed significantly between Co and RA cases (p=0.000) as well as between OA and RA (p=0.000). We conclude that the synovitis score was validated by CAIA and can be regarded a reliable grading system that contributes to the diagnostic procedure of chronic joint inflammation.

Influence of sex and age on morphological organ damage after hemorrhagic shock.

Immune function after hemorrhagic shock (shock) and subsequent sepsis is proofed to be sex- and age-related, showing an enhanced immune function and better survival of young females and a deteriorating immune response in advanced age. However, it remains unclear if the observed sex- and age-related effects observed on the immune function mirror the histomorphological changes of the affected organs. To scrutinize a possible association, male and female CBA/J mice (young, 2-3 months; aged 18-19 months) were subjected to shock (35 + 5 mmHg for 90 min and fluid resuscitation) or sham operation. At 48 h after shock, histological specimen at definite sites were harvested (lung, small bowel, liver, and kidney) and immediately stored in 10% formalin. After paraffin embedding, hematoxylin-eosin stain and immunohistochemical stains (vascular cell adhesion molecule 1 [VCAM-1], cluster of differentiation 44 [CD44], signal transducers and activators of transcription 3 [STAT-3]) were performed. In both sexes, aged animals developed significantly increased (P < 0.05) tissue damage in all analyzed organs compared with young mice. Sex differences were noticed in the lungs of young mice, showing a significantly (P < 0.05) lower organ damage score in female animals. Sex-related differences were found for VCAM-1 and cluster of differentiation 44 expression, whereas age-related changes were observed for STAT-3. These results demonstrate that the severity of tissue damage caused by hemorrhagic shock is influenced by sex- and age-related effects. Variances in the VCAM-1 and STAT-3 expression suggest that improved immune function in female and young subjects may be responsible for less shock-induced tissue damage.