Thoracic Endovascular Aortic Repair of Aortic Arch Pathologies with the Conformable Thoracic Aortic Graft: Early and 2 year Results from a European Multicentre Registry.

OBJECTIVE: To assess safety, effectiveness and clinical outcome of the conformable thoracic aortic endograft (CTAG) in the treatment of aortic arch pathologies. METHODS: Between October 2009 and December 2010, 100 consecutive patients (65 men; mean age 65 years) with aortic arch pathologies were treated with the CTAG device in five European centres. Indications were thoracic aortic aneurysm (n = 57), Type B dissection (n = 24), intramural haematoma (n = 4), penetrating aortic ulcer (n = 9), and traumatic transection (n = 6). Emergency procedures were performed in 33%. The proximal landing zone (LZ) was LZ 0 in 7%, LZ 1 in14%, LZ 2 in 43%, and LZ 3 in 36%. Data were collected prospectively and analysed for technical and clinical success. Conformability and deployment accuracy were analysed on intra-operative angiography and post-operative computed tomography. Mean follow up was 24 ± 19 months (range, 0.3-36 months). RESULTS: The 30 day, 1 and 2 year survival rates were 90%, 81%, and 74% respectively. The 2 year survival was 80% in the elective and 62% in the emergency groups (p = .20). The major 30 day complication rate was 34%: primary Type Ia endoleak affected 1%, retrograde dissection in 1%, and the paraplegia and stroke rates at 30 days were 4% and 11%. Age > 70 years was an independent predictor for mortality and complications. The primary technical success rate was 92%; device deployment was successful in 100% and accurate in 99%. Conformability to the aortic arch was achieved in 95%. CONCLUSION: The CTAG stent graft shows high deployment accuracy, good conformability, and clinical effectiveness in the treatment of aortic arch pathologies. However, thoracic endovascular aortic repair in the arch is associated with a relatively high stroke rate. Further studies with more patients and longer follow up are needed to evaluate the long-term results.

Liver resection for hepatocellular carcinoma in non-cirrhotic liver without underlying viral hepatitis.

BACKGROUND: Hepatocellular carcinoma (HCC) arising in normal liver parenchyma is rare and the outcome after hepatectomy is not well documented. METHODS: Between June 1998 and September 2003, 33 patients without viral hepatitis underwent resection for HCC in a non-cirrhotic, non-fibrotic liver. Data were analysed with regard to operative details, pathological findings including completeness of resection, and outcome as measured by tumour recurrence and survival. RESULTS: Twenty-three major hepatectomies and ten segmentectomies or bisegmentectomies were performed. After potentially curative resection, 19 of 29 patients were alive at a median follow-up of 25 months, with calculated 1- and 3-year survival rates of 87 and 50 per cent respectively. Survival was significantly better after resection of tumours without vascular invasion (3-year survival rate 89 versus 18 per cent; P = 0.024). Disseminated recurrence developed in nine of 29 patients, leading to death within 28 months of operation in all but one of the nine. CONCLUSION: These data justify hepatic resection for HCC arising in non-cirrhotic, non-fibrotic liver without underlying viral hepatitis. Liver transplantation is rarely indicated because the outcome is good after resection of tumours without vascular infiltration, whereas vascular invasion is invariably associated with diffuse extrahepatic recurrence.

Insulin sensitivity and coronary vasoreactivity: insulin sensitivity relates to adenosine-stimulated coronary flow response in human subjects.

OBJECTIVE: Diabetes is associated with coronary microvasculature abnormalities and impaired coronary flow reserve (CFR). CFR is the ratio of coronary flow under maximal vasodilation to basal flow and is a measure for coronary vasoreactivity. Insulin resistance is the central defect in the development of type 2 diabetes, preceding its onset by 10-20 years. Thus, the relationship between insulin sensitivity and CFR in nondiabetic subjects is particularly interesting. The aim of the study was to investigate this relationship. DESIGN: Cross-sectional study. PATIENTS: The study population consisted of 18 nondiabetic subjects without coronary artery stenosis on coronary angiography. We excluded patients with structural heart disease or with conditions affecting CFR or insulin sensitivity such as low density lipoprotein (LDL)-cholesterol > or = 4.14 mmol/l, smoking, hypertension or obesity with a body mass index (BMI) > 28 kg/m(2). MEASUREMENTS AND RESULTS: CFR was 3.1 +/- 0.8 (range 1.7-4.8), as assessed by intracoronary Doppler measurements in the left anterior descending coronary arteries after adenosine stimulation. Intravascular ultrasound revealed zero to moderate coronary atherosclerotic changes. Whole-body insulin sensitivity (M-value) was 7.5 +/- 2.9 mg/kg/min (range 2.2-12.6), as assessed by the hyperinsulinaemic-euglycaemic clamp test. Subjects with low CFR (< 3.0) had a significantly lower M-value than subjects with normal CFR (> 3.0) (6.0 +/- 2.5 vs. 9.0 +/- 2.5 mg/kg/min, P = 0.021). Univariate linear regression demonstrated a strong correlation between CFR and M-value (r = 0.76, P < 0.001). In multiple regression analysis, the significant association of CFR with M-value was independent of potential confounders (sex, age, BMI, LDL-cholesterol and plaque burden on intravascular ultrasound). Bootstrap analysis corroborated this finding. CONCLUSIONS: Whole-body insulin sensitivity relates to coronary vasoreactivity. Across a wide range of both insulin sensitivity and coronary flow reserve from markedly abnormal to normal values, an increase in insulin sensitivity appears to be associated with an increase in coronary flow reserve. Insulin resistance is therefore associated with coronary microvasculature abnormalities in nondiabetics.

How reliable is the allopurinol load in detecting carriers for ornithine transcarbamylase deficiency?

The allopurinol test aims to distinguish carriers and noncarriers for ornithine transcarbamylase (OTC) deficiency. We have evaluated the reliability of the test in at-risk females of known genotype. Results based on urine orotidine and/or orotic acid measurement were compared in terms of sensitivity and specificity. Retrospectively, we analysed the results of allopurinol tests in 42 women (22 confirmed heterozygotes and 20 noncarriers) from 23 pedigrees at risk of being carriers for OTC deficiency. Using a cut-off of 2 standard deviations above the mean of controls, the highest sensitivity (91%) was given by orotidine alone or in combination with orotic acid, but specificity was only 70% and 65%, respectively. We conclude that the value of the allopurinol test for detecting OTC carriers in at-risk females is limited. This needs to be recognized when counselling families. The test still has a role as a safe, quick, noninvasive screen of individuals at risk, but test results in possible carriers should be interpreted with caution. In the absence of other supportive evidence, confirmation by mutation analysis is required.

Optimal rocuronium dose for intubation during inhalation induction with sevoflurane in children.

BACKGROUND: We studied 120 children aged 2-7 yr in a prospective, randomized, assessor-blinded fashion to define the optimal rocuronium dose which provides a 95% probability of acceptable intubation conditions (ED95TI) during inhalation induction with sevoflurane. METHODS: After inhalation induction with 8% sevoflurane in 60% nitrous oxide and 40% oxygen, and loss of the eyelash reflex, we administered rocuronium (0.1, 0.15, 0.22, 0.3, or 0.6 mg kg-1) or placebo. We quantified neuromuscular function by stimulation of the ulnar nerve at 0.1 Hz to produce contraction of the adductor pollicis muscle using accelerometry. Intubation conditions were assessed 2 min after test drug injection. The optimal rocuronium dose was defined as the lowest dose, which allowed acceptable intubation conditions in 95% of children (ED95TI). RESULTS: Two minutes after injection of placebo or rocuronium, intubation conditions were acceptable in 35, 45, 80, 90, 95, and 100% of children, respectively. Rocuronium 0.07 [CI 0.02-0.11], 0.24 [0.19-0.31], and 0.29 [0.23-0.38] mg kg-1 provided 50, 90, and 95% probability of acceptable intubating conditions. When thumb acceleration was depressed by 50% or more, intubating conditions were considered acceptable in 97% of children. Recovery of the train-of-four ratio to 0.8 averaged 12 (7), 16 (7), 24 (7), 24 (8), and 50 (22) min after the respective dose of rocuronium. CONCLUSIONS: During inhalation induction with 8% sevoflurane in 60% nitrous oxide, rocuronium 0.29 mg kg-1 (ED95) optimizes intubation conditions for surgery of short duration.

A scheme for a dose-escalation study when the event is lagged.

Classical designs for clinical phase I trials assume that information about a dose-limiting event (DLE) is available for all the included patients, or advise not to treat new patients until the information is present. If a DLE occurs after a lag, however, information at the current time might not be sufficient to make clear-cut decisions according to these designs. In particular, if new patients are available, it is not clear whether to include them in the trial. We suggest a rule that decides on the accrual of each individual eligible patient. Simulation studies are presented that indicate an advantage over the standard 'three-at-once' design in the length of the study.

Health care providers on the World Wide Web: quality of presentations of surgical departments in Germany.

It is becoming increasingly common for health care providers to present information on the World Wide Web (WWW). Patients, as well as health care professionals, do not really know what they can expect today. Many quality criteria are proposed for the assessment of medical Internet sites focusing mainly on structure and content management. The objective of this study was to assess the quality of presentations by health care providers on the WWW and to detect strengths and weaknesses with regard to potential target groups, patients, colleagues, and students. A sample of 171 presentations was randomly selected in March 2000 from a collection of 469 surgical departments in Germany. Medical doctors undergoing a full-time training in medical informatics rated the presentations. A previously evaluated questionnaire was used to assess the presentations with regard to 12 criteria about content and technical features. For each criterion the categories 'very good', 'sufficient', and 'insufficient' could be used. Twenty medical doctors assessed 168 presentations with one to seven valuations per presentation. Three presentations could not be accessed at the time of evaluation. Sixty-eight per cent of the median values of each criterion were rated as insufficient. The only criteria rated sufficient or better in at least 50% were: employees/map, survey of offered medical services, navigation, and layout. University hospitals and heart centres achieved significantly better results than regional hospitals. In conclusion, the quality of provider information on the W WW is unsatisfactory. Most surgical departments do not provide information that could help patients to choose their physicians. The criteria set developed here could be a useful tool for a target-group-oriented self-assessment of provider presentations on the World Wide Web.

Early detection of prostate cancer in Germany: a study using digital rectal examination and 4.0 ng/ml prostate-specific antigen as cutoff.

OBJECTIVE: While international screening studies for prostate cancer are by now almost reaching the estimated number of recruitments mandatory for the necessary power to investigate an effect on mortality of prostate cancer, no statistical figures on the detection of prostate cancer in Germany - apart from historical data before the use of prostate-specific antigen (PSA) are available. In order to generate a database and to investigate the diagnostic efficacy of the primarily practice-based urological care system, a case finding study designed as a nationwide longitudinal early detection trial was initiated. METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years of age by digital rectal examination (DRE) and PSA with 4.0 ng/ml as cutoff. Data of family history and physical examination were collected by questionnaire. At this time participants were not aware of their PSA value. PSA was determined in the study center. Indication for sextant biopsy was a PSA value above 4.0 ng/ml or a suspicious lesion on DRE. Any indicated biopsy not performed had to be clarified. In a second questionnaire results of prostate biopsy, treatment and tumor status were documented. RESULTS: The mean age of the study population was 62 years (median 62). The PSA median was 1.4 ng/ml with 82.8% presenting with < 4.0 ng/ml, 12.8% with 4-10 ng/ml and 4.4% with >10 ng/ml. From 1,115 men (47.7%) biopsied, 262 cancers were detected resulting in a detection rate of 23.5%. While 399 men refused biopsy, further investigation was not recommended in 387 men by their urologist, because prostatitis or benign hyperplasia was thought to be the cause for elevated PSA. From the 143 patients undergoing radical prostatectomy, 93 (65%) cancers were organ confined. T(1c) cancers with elevated PSA > 10 ng/ml could be treated with curative intent in 44% only. The positive predictive value (PPV) was estimated to be 16% for DRE alone (14/90), 17% for PSA alone (143/819) and 51% for the combination of both (105/206). In that cohort, use of age-adjusted PSA values and PSA density increased the PPV of PSA testing nonsignificantly. CONCLUSIONS: Significant higher PPV indicated that utilizing a combination of both DRE and PSA is most effective in the early detection of prostate cancer. Unnecessary biopsies can be avoided using either age-adjusted PSA value or PSA density, but the PPV is not significantly changed and potentially curable cancer is missed in up to 25%. Given the substantial variability of the diagnostic approach despite the study design, uniform guidelines are necessary to ensure countrywide sufficient screening.

[Early detection of prostatic carcinoma in urologic practice with digital rectal examination and prostate-specific antigen. Early Detection Project Group]. / Früherkennung des Prostatakarzinoms in der urologischen Praxis mit digitaler rektaler Untersuchung und prostataspezifischem Antigen. Projektgruppe Früherkennung.

For the early detection of prostate cancer, a patient should undergo digital rectal examination (DRE) and PSA investigation. Follow-up of increased PSA levels detects nearly 80% of cancers. Positive predictive value of suspicious DRE and PSA is about 50%. Whereas in the first evaluation of this case-finding trial about 70% of the patients had organ-confined cancers, nearly all of the detected cancers in the follow-up investigation were organ confined. The increased number of organ-confined cancers detected in early periodical examinations can lead to a reduction of mortality and morbidity from prostate cancer.

Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT.

In order to evaluate the risk of cytomegalovirus (CMV) associated disease after allogeneic stem cell transplantation (SCT), 158 consecutive patients at risk for infection were analyzed. BMT was performed in 101 patients and peripheral blood stem cell transplantation (PBSCT) in 57 patients. CMV antigenemia was found in 57 cases (56%) after BMT and 27 cases (47%) after PBSCT, respectively. CMV antigenemia resistant to a 14-day course of GCV was found in 26 patients (26%) after BMT but in only four patients (7%) after PBSCT (P < 0.01). Eighteen patients (11%) developed CMV disease, 14 post BMT and four post PBSCT. Lethal CMV-related interstitial pneumonia (CMV-IP) occurred in 13 cases of whom 12 patients were bone marrow recipients (P = 0.04). The subgroup of seronegative patients with a CMV seropositive donor had a significantly lower risk of developing CMV antigenemia, GCV-resistant CMV antigenemia (P < 0.01) and CMV-related disease (P = 0.01). In conclusion, the incidence of persistent CMV antigenemia and CMV-IP was significantly reduced when allogeneic transplantation was performed with peripheral blood stem cells instead of bone marrow. These findings suggest that our previous in vitro data on improved immune reconstitution after allogeneic PBSCT as compared to allogeneic BMT have clinical relevance.

Influence of sodium butyrate on the induction of radiation-induced chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary (CHO) cells.

CHO cells were pre-treated with sodium butyrate (SB) for 24 h and then X-irradiated in G1. Metaphases were scored for the induction of chromosomal aberrations and sister chromatid exchanges (SCEs). The data were compared with those obtained after irradiation of cells not pre-treated with SB and showed that SB has different effects on the endpoints examined. The frequencies of dicentric chromosomes were elevated and of small acentric rings (double minutes, DMs) reduced. These results are discussed to be a consequence of conformational changes in hyperacetylated chromatin which could lead to more interchromosomal and to less intrachromosomal exchanges. SB itself induces a few SCEs but suppresses the induction of SCEs by X-rays. We assume that a minor part of radiation induced SCEs are 'false' resulting from structural chromosomal aberrations, such as inversions, induced in G1. Inversions are the symmetrical counterparts of DMs. If inversions are suppressed by SB treatment to a similar extent as DMs a small reduction of SCEs by SB can be expected.

[Early recognition of prostate carcinoma. Initial results of a prospective multicenter study in Germany. Project Group for Early Detection DGU-BDU Laboratory diagnosis Professional Circle]. / Früherkennung des Prostatakarzinoms. Erste Ergebnisse einer prospektiven multizentrischen Studie in Deutschland. Projektgrouppe Früherkennung DGU-BDU-Arbeitskreis Labordiagnostik.

To compare the efficacy of digital rectal examination (DRE) and serum prostate specific antigen (PSA) in early detection of prostate cancer, we initiated a prospective multicenter screening trial. In 12,542 men choosen at random with a mean age of 62 (+/- 7.5) a suspect DRE or a PSA level > 4.0 ng/ml was found in 2343 (20%). Of the presently performed 744 biopsies, 157 revealed diagnosis of prostate cancer. Although further biopsies as well as the follow up of the 12,542 men are still missing, combination of DRE and PSA value > 4.0 ng/ml appears to be superior to DRE alone with a positive predictive value of 50% versus 19% in early detection of prostate cancer.