Progression of coronary artery disease during long-term follow-up of the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II)

Background: This study evaluates cardiovascular risk factors associated with progression of coronary artery disease (CAD) in patientswith silent ischemia followingmyocardial infarction. Hypothesis: Coronary artery disease only progresses slowly with comprehensive risk factor intervention. Methods: A total of 104 of 201 patients (51.7%) of the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II) with baseline and follow-up coronary angiography were included. All patients received comprehensive cardiovascular risk factor intervention according to study protocol. Logistic regression was used to evaluate associationsbetween baseline cardiovascular risk factors and CAD progression. Results: The mean duration of follow-upwas 10.3 ± 2.4 years. At baseline, 77.9% of patients were smokers, 45.2% had hypertension, 73.1% had dyslipidemia, 7.7% had diabetes, and 48.1% had a family history of CAD. At last follow-up, only 27 patients of the initial 81 smokers still smoked, only 2.1% of the patients had uncontrolled hypertension, 10.6%of the patientshad uncontrolled dyslipidemia, and 2.1%of the patientshad uncontrolled diabetes. Coronary artery disease progression was found in up to 81 (77.9%) patients. Baseline diabetes and younger age were associatedwith increased odds of CAD progression.The time intervalbetween baseline and follow-up angiography was also associatedwith CAD progression. Conclusion: Coronary artery disease progressionwas highly prevalent in these patients despite comprehensive risk factor intervention. Further research is needed to optimize treatment of known risk factors and to identify other unknown and potentiallymodifiable risk factors.

Clinicopathologic correlations of silent corticotroph adenomas of the pituitary: report of four cases and literature review

Silent corticotroph adenomas (SCA) are rare pituitary tumors with histologic hallmarks of corticotroph differentiation, including ACTH immunoreactivity, but lacking clinical evidence of Cushing's syndrome. We report on four female patients, aged 19-66 years, each presenting with a nonfunctional macroadenoma. Leading symptoms were headache in two cases and visual field deficits in one. One patient was incidentally diagnosed while undergoing cranial MRI for an unrelated condition. Three patients had marked obesity; none of them presented constitutional signs of Cushing's syndrome. Serum cortisol levels were moderately elevated in the two patients systematically tested in this respect. Marginal to moderate hyperprolactinemia was present in two cases. Two patients also were shown to be deficient in either gonadotroph or thyrotroph axis, while a third had a combined insufficiency of both gonadotroph and thyrotroph axis. MRI scans revealed intratumoral hemorrhage and/or cystic change in three cases, as well as tumor-related occlusive hydrocephalus in one. The latter patient was biopsied only, while the remaining underwent gross total resection. Histologically, all four lesions were diagnosed as SCA subtype I displaying intense immunoreactivity for ACTH. In three tumors, scattered cells coexpressed PRL as well. In addition, Crooke's hyaline change was noted in a significant number of tumor cells and in residual non-neoplastic corticotrophs in one case each. With MIB-1 labeling indices of 1-3%, none of the tumors qualified as atypical adenoma. We conclude that SCAs are more likely to be discovered as expansile tumors, whose advanced local space-occupying character at surgery rather than an inherently aggressive growth potential may negatively influence the clinical outcome. Subtle morphologic evidence of corticotroph suppression in residual pituitary adjacent to tumor lends further support to literature data indicating minimal or intermittent functional activity in this tumor type.

Effects of percutaneous coronary interventions in silent ischemia after myocardial infarction: the SWISSI II randomized controlled trial

CONTEXT: The effect of a percutaneous coronary intervention (PCI) on the long-term prognosis of patients with silent ischemia after a myocardial infarction (MI) is not known. OBJECTIVE: To determine whether PCI compared with drug therapy improves long-term outcome of asymptomatic patients with silent ischemia after an MI. DESIGN, SETTING, AND PARTICIPANTS: Randomized, unblinded, controlled trial (Swiss Interventional Study on Silent Ischemia Type II [SWISSI II]) conducted from May 2, 1991, to February 25, 1997, at 3 public hospitals in Switzerland of 201 patients with a recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease. Follow-up ended on May 23, 2006. INTERVENTIONS: Percutaneous coronary intervention aimed at full revascularization (n = 96) or intensive anti-ischemic drug therapy (n = 105). All patients received 100 mg/d of aspirin and a statin. MAIN OUTCOME MEASURES: Survival free of major adverse cardiac events defined as cardiac death, nonfatal MI, and/or symptom-driven revascularization. Secondary measures included exercise-induced ischemia and resting left ventricular ejection fraction during follow-up. RESULTS: During a mean (SD) follow-up of 10.2 (2.6) years, 27 major adverse cardiac events occurred in the PCI group and 67 events occurred in the anti-ischemic drug therapy group (adjusted hazard ratio, 0.33; 95% confidence interval, 0.20-0.55; P<.001), which corresponds to an absolute event reduction of 6.3% per year (95% confidence interval, 3.7%-8.9%; P<.001). Patients in the PCI group had lower rates of ischemia (11.6% vs 28.9% in patients in the drug therapy group at final follow-up; P = .03) despite fewer drugs. Left ventricular ejection fraction remained preserved in PCI patients (mean [SD] of 53.9% [9.9%] at baseline to 55.6% [8.1%] at final follow-up) and decreased significantly (P<.001) in drug therapy patients (mean [SD] of 59.7% [11.8%] at baseline to 48.8% [7.9%] at final follow-up). CONCLUSION: Among patients with recent MI, silent myocardial ischemia verified by stress imaging, and 1- or 2-vessel coronary artery disease, PCI compared with anti-ischemic drug therapy reduced the long-term risk of major cardiac events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00387231.

Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study

AIMS: To determine the effect of anti-ischaemic drug therapy on long-term outcomes of asymptomatic patients without coronary artery disease (CAD) history but silent exercise ST-depression. METHODS AND RESULTS: In a randomized multicentre trial, 263 of 522 asymptomatic subjects without CAD but at least one CAD risk factor in whom silent ischaemia by exercise ECG was confirmed by stress imaging were asked to participate. The 54 (21%) consenting patients were randomized to anti-anginal drug therapy in addition to risk factor control (MED, n = 26) or risk factor control-only (RFC, n = 28). They were followed yearly for 11.2 +/- 2.2 years. During 483 patient-years, cardiac death, non-fatal myocardial infarction, or acute coronary syndrome requiring hospitalization or revascularization occurred in 3 (12%) of MED vs. 17 (61%) of RFC patients (P < 0.001). In addition, MED patients had consistently lower rates of exercise-induced ischaemia during follow-up, and left ventricular ejection fraction remained unchanged (-0.7%, P = 0.597) in contrast to RFC patients in whom it decreased over time (-6.0%, P = 0.006). CONCLUSION: Anti-ischaemic drug therapy and aspirin seem to reduce cardiac events in subjects with asymptomatic ischaemia type I. In such patients, exercise-induced ST-segment depression should be verified by stress imaging; if silent ischaemia is documented, anti-ischaemic drug therapy and aspirin should be considered.

Sudden cardiac death in patients with silent myocardial ischemia after myocardial infarction (from the Swiss Interventional Study on Silent Ischemia Type II [SWISSI II])

The occurrence of sudden cardiac death (SCD) in patients with silent ischemia after myocardial infarction (MI) and the factors facilitating SCD are unknown. This study aimed to determine the factors facilitating SCD in patients with silent ischemia after MI. In the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II), 201 patients with silent ischemia after MI were randomized to percutaneous coronary intervention (PCI) or medical management. The main end point of the present analysis was SCD. Multivariable regression models were used to detect potential associations between baseline or follow-up variables and SCD. During a mean follow-up of 10.3 +/- 2.6 years, 12 SCDs occurred, corresponding to an average annual event rate of 0.6%. On multivariate regression analysis, the decline in the left ventricular ejection fraction (LVEF) during follow-up was the only independent predictor of SCD (p = 0.011), other than age; however, the baseline LVEF was not. The decline in LVEF was greater in patients receiving medical management than in those who had received PCI (p <0.001), as well as in patients with residual myocardial ischemia or recurrent MI compared with patients without these findings (p = 0.038 and p <0.001, respectively). Compared with medical management, PCI reduced the rate of residual myocardial ischemia (p <0.001) and recurrent MI (p = 0.001) during follow-up. In conclusion, patients with silent ischemia after MI are at a substantial risk of SCD. The prevention of residual myocardial ischemia and recurrent MI using PCI resulted in better long-term LVEF and a reduced SCD incidence.

The silent loss of neuronavigation accuracy: a systematic retrospective analysis of factors influencing the mismatch of frameless stereotactic systems in cranial neurosurgery

BACKGROUND Neuronavigation has become an intrinsic part of preoperative surgical planning and surgical procedures. However, many surgeons have the impression that accuracy decreases during surgery. OBJECTIVE To quantify the decrease of neuronavigation accuracy and identify possible origins, we performed a retrospective quality-control study. METHODS Between April and July 2011, a neuronavigation system was used in conjunction with a specially prepared head holder in 55 consecutive patients. Two different neuronavigation systems were investigated separately. Coregistration was performed with laser-surface matching, paired-point matching using skin fiducials, anatomic landmarks, or bone screws. The initial target registration error (TRE1) was measured using the nasion as the anatomic landmark. Then, after draping and during surgery, the accuracy was checked at predefined procedural landmark steps (Mayfield measurement point and bone measurement point), and deviations were recorded. RESULTS After initial coregistration, the mean (SD) TRE1 was 2.9 (3.3) mm. The TRE1 was significantly dependent on patient positioning, lesion localization, type of neuroimaging, and coregistration method. The following procedures decreased neuronavigation accuracy: attachment of surgical drapes (DTRE2 = 2.7 [1.7] mm), skin retractor attachment (DTRE3 = 1.2 [1.0] mm), craniotomy (DTRE3 = 1.0 [1.4] mm), and Halo ring installation (DTRE3 = 0.5 [0.5] mm). Surgery duration was a significant factor also; the overall DTRE was 1.3 [1.5] mm after 30 minutes and increased to 4.4 [1.8] mm after 5.5 hours of surgery. CONCLUSION After registration, there is an ongoing loss of neuronavigation accuracy. The major factors were draping, attachment of skin retractors, and duration of surgery. Surgeons should be aware of this silent loss of accuracy when using neuronavigation.

Silent chronic osteomyelitis lasting for 30 years before outburst of symptoms

A 56-year-old male patient presented with left knee and thigh pain after suffering a knee contusion. History revealed a complex fracture of the distal femur 30 years prior to presentation. Initial blood tests upon admission showed elevated C reactive protein values. Subsequent imaging and biopsies showed a correlate to osteomyelitis, upon which the diagnosis of a late onset osteomyelitis as an outburst of silent chronic osteomyelitis was made. The patient was successfully treated surgically by means of aggressive debridement and discharged after confirmation of negative biopsies.

Building silent compartments at the nuclear periphery: a recurrent theme.

In eukaryotes, the genetic material is stored in the nucleus, which is enclosed in a double lipid bilayer, the nuclear envelope (NE). It protects the genome from physical stress and separates it from the rest of the cell. On top of this physical function, growing evidence shows that the nuclear periphery contributes to the 3D organization of the genome. In turn, tridimensional organization of chromatin in the nuclear space influences genome expression. Here we review recent findings on the function of this physical barrier in gene repression and latest models on how silent subnuclear compartments at the NE are built in yeast as well as in the nematode C. elegans and mammalian cells; trying to draw parallels between the three systems.

Cholestasis in a patient with gallstones and a normal gamma-glutamyl transferase

Cholestasis with normal gamma glutamyl transferase characterizes functional deficiencies in the gene ABCB11, which encodes the bile salt export pump (BSEP), a liver-specific adenosine triphosphate (ATP)-binding cassette transporter. Here we report the case of a patient presenting with features of benign recurrent intrahepatic cholestasis associated with a heterozygous mutation in the ABCB11 gene. Immunohistochemistry showed a gradual decrease of BSEP from zone 1 to zone 3 of the liver lobule, suggesting that the mutation identified here may predispose patients to cholestasis through a delocalization process of BSEP at the lobular level. (HEPATOLOGY 2013;57:2539-2541).

The silent services of the world ocean

The most recent comprehensive assessment carried out by the Intergovernmental Panel on Climate Change has concluded that “Human influence on the climate system is clear,” a headline statement that was approved by all governments in consensus. This influence will have long-lasting consequences for ecosystems, and the resulting impacts will continue to be felt millennia from now. Although the terrestrial impacts of climate change are readily apparent now and have received widespread public attention, the effects of climate change on the oceans have been relatively invisible. However, the world ocean provides a number of crucial services that are of global significance, all of which come with an increasing price caused by human activities. This needs to be taken into account when considering adaptation to and mitigation of anthropogenic climate change.

The Silent Reform of Swiss Federalism: The New Constitutional Articles on Education

This article examines the decision-making process leading to the new constitutional articles on education in Switzerland. It analyzes how actors from both state levels (Confederation and cantons) could reach consensus in a process that was prone to a "joint-decision trap". To that end, we hypothesize which factors may be conducive to a "problem-solving" style of policy-making in a compulsory negotiation system. Rich empirical material from various sources supports our theoretical arguments: We show that shared beliefs and a common frame of reference, the procedural separation between constitutional and distributional issues, neutral brokers, and informal structures were all beneficial to the success of the reform project.