Diastolic exercise stress testing in heart failure with preserved ejection fraction: The DEST-HF study.

AIMS: Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry. METHODS AND RESULTS: We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg). CONCLUSIONS: We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive.

Impaired coagulation is a risk factor for clinical and radiologic deterioration in patients with traumatic brain injury and isolated traumatic subarachnoid hemorrhage.

BACKGROUND: Isolated traumatic subarachnoid hemorrhage (itSAH) is found in approximately 25% of all patients with mild traumatic brain injury (TBI). The aim of this study was to analyze the clinical course and identify risk factors for potential clinical and radiologic deterioration in consideration of impaired coagulation in patients with itSAH. METHODS: A retrospective analysis of 735 patients with TBI resulting in a pathologic computer-assisted tomography (CAT) was performed. Only those patients with itSAH and Glasgow Coma Scale (GCS) of greater than 8 points and follow-up CAT scan were included. Patients with hemorrhage in any other brain compartment (subdural, epidural, and intracerebral) were excluded. Impaired coagulation was operationally defined. RESULTS: Of the 735 patients, 89 met the inclusion criteria. The majority of these patients experienced mild TBI. The rate of radiologic expansion or conversion of the SAH was 28.1%. The rate of clinical deterioration was 6.7%. Neither the initial pattern of itSAH on different intracranial localizations nor the number of sulci involved in the itSAH was associated with clinical worsening. The rate of patients with impaired coagulation was 38%; 17.9% of all patients showed elevated international normalized ratio (INR). Radiologic and clinical deterioration was significantly associated with elevated INR. INR was shown to be independent of age in a logistic regression analysis. CONCLUSION: TBI patients with itSAH and impaired coagulation especially those who showed elevated INR are at risk of clinical and radiologic deterioration. Despite coagulation status, routine repetition of cranial CAT scan is advised in patients with itSAH to detect potential radiologic worsening, which if occurring should result in close clinical monitoring. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

Transcranial Doppler sonography as a potential screening tool for preanaesthetic evaluation: a prospective observational study.

CONTEXT: Intraoperative cervical spine rotation may compromise cerebral blood flow in susceptible individuals by distortion of cervical arteries. OBJECTIVE: To investigate the effect of five cervical spine positions on cerebral blood flow in the middle cerebral artery. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS: Fifty-six male and 24 female patients scheduled for general anaesthesia for routine surgery. Exclusion criteria were cranial spine pathology and cerebral vascular disease. INTERVENTIONS: Maximum rotation of the head to the left and right side with and without hyperextension, and hyperextension in the neutral position. MAIN OUTCOME MEASURES: Change of mean blood flow velocity in the middle cerebral artery measured by transcranial Doppler sonography. RESULTS: Age had a significant effect on mean blood flow velocity in the left middle cerebral artery in the neutral position (P = 0.047). There was a significant difference in mean blood flow velocity in the left middle cerebral artery between patients younger than 40 years and patients older than 59 years [61.2 (16.6) ml min(-1) vs. 47.7 (16.2) ml min(-1); P = 0.015]. There was a significant effect of head position on mean blood flow velocity in both the left and in the right middle cerebral arteries (P = 0.039 left, P = 0.025 right). Twenty patients had a decrease of more than 20% from their baseline mean blood flow velocity. CONCLUSION: Neck rotation and/or extension resulted in a significant change of blood flow in the middle cerebral artery.

Evaluation and development of a predictive model for ultrasound-guided investigation of neck metastases.

Ultrasound investigations for the correct identification of lymph node metastases depend on the experience and qualifications of the investigator; thus, model that provides better preoperative evaluation is desired. Data from 290 patients with an upcoming neck dissection were analyzed to compare the preoperative ultrasound assessment of neck metastases with the pathologically proven postoperative neck status. In total, 364 data sets with 200 malignant and 164 benign lymph nodes were explored. The minimal and maximal transverse diameters and their ratio were shown to be especially good parameters for sensitivity, whereas the echostructure and the presence of a hilum were good for specificity. A model incorporating the evaluated markers is presented. The model provides better judgement of neck lymph nodes in a more objective manner. Using logistic regression, five parameters were identified to predict metastases.

Imaging of acute heart-transplant rejection using 99m-Technetium labelled oligonucleotides against interleukin-2 mRNA in rats.

OBJECTIVES: Today, acute cardiac rejection is detected by endomyocardial biopsy, which harbours many risks. Thus, there is a necessity for less invasive methods. Since interleukin-2 (IL2) is over-expressed in acute graft rejection, we use radioactive DNA-fragments complementary to the mRNA of IL2 to detect graft rejection scintigraphically. METHODS: In a rat model of acute graft rejection, the oligonucleotide sequence complementary to the mRNA of IL2 is labelled with 99m-Technetium and injected intravenously. Scintigraphic and Geiger-counter activity of the transplants are evaluated and correlated with the current rejection classification of the International Society for Heart and Lung Transplantation (ISHLT). RESULTS: From the fourth postoperative day onwards, the scintigraphic images show a significant increase of radioactivity (p<0.05) in the rejected organs than in the accepted grafts. While scintigraphy is not significantly correlated with the standard rejections classification of the ISHLT, there is significant correlation between the ISHLT classification and radioactivity in the Geiger-counter analysis. CONCLUSIONS: Radioactively labelled anti-sense-oligonucleotides against mRNA of IL2 may be a promising approach for the detection of acute transplant rejection in vivo.

Histological grading in a large series of advanced stage ovarian carcinomas by three widely used grading systems: consistent lack of prognostic significance. A translational research subprotocol of a prospective randomized phase III study (AGO-OVAR 3 protocol).

While there is no doubt that histologic grading is applicable in early stage ovarian carcinoma, it is still in controversial discussion concerning advanced stage ovarian carcinoma. It was the aim of this study to assess the three most widely used grading systems for ovarian carcinoma in terms of prognostic significance, concordance rates, and reproducibility in a large number of advanced stage ovarian carcinomas of all types after standardized chemotherapy. Representative hematoxylin and eosin slides from 334 cases of stage IIB-IV ovarian carcinoma (prospective randomized, multi-center, phase III study) were used. The first round was grading of all cases according to FIGO, GOG, and Silverberg by one author. The second round (after 1 year) was 30 randomly selected cases graded by three authors. None of the three grading systems was prognostically significant (FIGO p = 0.38; GOG p = 0.70; Silverberg p = 0.92). The concordance rates between the three systems were as follows: FIGO/GOG 95.5%, kappa = 0.929; Silverberg/FIGO 69.9%, kappa = 0.533; Silverberg/GOG 66.8%, kappa = 0,481. Grading of advanced stage ovarian carcinomas was of no value for estimation of prognosis in this homogeneously treated patient group. Alternative methods should be defined, which might help to separate patients with high risk of tumor progression from others with low risk.

Effect of elevated PEEP on dynamic variables of fluid responsiveness in a pediatric animal model.

BACKGROUND: Previous studies have demonstrated that stroke volume variation (SVV), pulse pressure variation (PPV) and global end-diastolic volume (GEDV) can be used to predict the response to fluid administration. Currently, little information is available whether application of different levels of positive end-expiratory pressure (PEEP), especially in infants and neonates, affects their ability to predict fluid responsiveness. The aim of our study was to assess the effect of increasing PEEP levels on the predictive value of SVV, PPV and GEDV with respect to fluid responsiveness. METHODS: Stroke volume variation and PPV were monitored continously in 22 anesthetized piglets during changing PEEP levels (5 and 10 cmH(2)O) both before and after fluid loading (FL). GEDV was measured by transpulmonary thermodilution; cardiac output and stroke volume (SV) were measured by pulmonary artery thermodilution. A positive response to FL was defined as > or =15% increase in SV. RESULTS: Fluid loading induced significant changes in all hemodynamic variables except of heart rate and systemic vascular resistance. At PEEP 5 cmH(2)O, SVV, PPV and GEDV significantly correlated with volume induced percentage change in SV, whereas at PEEP 10 cmH(2)O, this correlation was abolished for PPV. As assessed by receiver operating characteristic curve analysis, SVV and GEDV, independent of PEEP level applied, were the best predictors of a positive response to FL [area under the curve: SVV = 0.88; GEDV = 0.80]. CONCLUSIONS: In this pediatric animal model, SVV and GEDV were sensitive and specific predictors of fluid responsiveness during increasing PEEP levels.

Retention of zirconia ceramic copings bonded to titanium abutments.

PURPOSE: The aim of this study was to evaluate the effect of 2 surface conditioning methods and 2 luting-gap sizes on the retention and durability of zirconia ceramic copings bonded to titanium abutments. MATERIALS AND METHODS: Zirconia ceramic copings (Camlog Biotechnologies, Winsheim, Germany) with a luting-gap size of either 30 microm or 60 microm were bonded to titanium abutments (Camlog Biotechnologies) using the composite resin cement Panavia F (Kuraray, Osaka, Japan). The bonding surfaces of the zirconia ceramic copings were either (a) pretreated with airborne particle abrasion and cleaned with alcohol or (b) just cleaned with alcohol, whereas the bonding surfaces of all titanium abutments had been abraded and cleaned. After the specimens had been stressed for either 1, 30, 60, or 150 days by water and thermal cycling, retention was measured. RESULTS: The surface conditioning method, luting-gap size, and storage time significantly (P = .001; 3-way analysis of variance [ANOVA]) influenced retention. Air abrasion increased the retention significantly. Failure modes were predominantly adhesive. Air-abraded copings bonded with 30-microm luting gap achieved significantly greater retention than those bonded with a 60-microm luting gap. CONCLUSION: Surface conditioning methods and the size of the luting gap have a significant influence on the retention of Camlog zirconia ceramic copings bonded to Camlog titanium abutments.

Early and medium-term results after on-pump and off-pump coronary artery surgery: a propensity score analysis.

BACKGROUND: Comparative publications on beating-heart off-pump coronary artery bypass grafting (OPCAB) surgery versus conventional coronary artery bypass grafting (CCAB) surgery frequently do not offer conclusive information because of investigator bias. METHODS: Trying to eliminate this problem, a propensity score analysis of the data of all CCAB patients (n = 517) and OPCAB patients (n = 133) operated on by the same surgeons during the same time period (1998 to 2001) was applied. After matching patients with similar propensity score values, 97 CCAB patients and 72 OPCAB patients entered the final analysis. RESULTS: Early results were similar in both groups: the 30-day mortality reached 1.4% in the CCAB group and 2.8% in the OPCAB group; strokes did not happen. Perioperative myocardial infarctions occurred in 4.1% of the CCAB patients and 4.3% of the OPCAB patients. Drainage blood loss in the first 24 hours after surgery (830 +/- 687 mL, CCAB group; and 909 +/- 678 mL, OPCAB group) was similar (p = 0.06) in both groups. Medium term results (freedom from percutaneous transluminal coronary angioplasty or reoperation, freedom from myocardial infarction, freedom from stroke, and the quality of life) also were not significantly different between the off-pump and on-pump groups after a mean follow-up of 27 +/- 11 months. CONCLUSIONS: Our results suggest that elective-surgery patients with coronary artery disease can be operated on either on-pump or off-pump with the same early and late mortality and morbidity.

Differential enhancement of collagen crosslink excretion in cases of osteosarcoma and chondrosarcoma.

Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are markers of collagen absorption and LP is specific for collagen type I in bone. In the present study we evaluated the concentration of HP and LP in urine of patients with osteosarcoma ( n=20; age range 16-49 years) and chondrosarcoma ( n=15; age range 18-70 years). The values were compared with those obtained from 74 healthy controls (age range 16-83 years). The range and upper limit of normal values (HP(max) and LP(max)) were measured in our control group. High performance liquid chromatography (HPLC) was used to determine concentrations of HP and LP (nmol/mmol creatinine). The average urinary HP concentrations were significantly increased in patients with osteosarcoma ( p=0.001) and chondrosarcoma ( p<0.001), whereas HP remained within the normal range in approximately half of the patients. The average urinary LP concentrations were not increased in osteosarcoma and chondrosarcoma patients as compared with the control group. Further studies in a large group of patients are necessary to evaluate whether HP might be a valuable marker of prognosis, and if its urinary concentration can be correlated to tumour burden.