Relationship between the logistic EuroSCORE and the Society of Thoracic Surgeons Predicted Risk of Mortality score in patients implanted with the CoreValve ReValving system--a Bern-Rotterdam Study

Background Surgical risk scores, such as the logistic EuroSCORE (LES) and Society of Thoracic Surgeons Predicted Risk of Mortality (STS) score, are commonly used to identify high-risk or “inoperable” patients for transcatheter aortic valve implantation (TAVI). In Europe, the LES plays an important role in selecting patients for implantation with the Medtronic CoreValve System. What is less clear, however, is the role of the STS score of these patients and the relationship between the LES and STS. Objective The purpose of this study is to examine the correlation between LES and STS scores and their performance characteristics in high-risk surgical patients implanted with the Medtronic CoreValve System. Methods All consecutive patients (n = 168) in whom a CoreValve bioprosthesis was implanted between November 2005 and June 2009 at 2 centers (Bern University Hospital, Bern, Switzerland, and Erasmus Medical Center, Rotterdam, The Netherlands) were included for analysis. Patient demographics were recorded in a prospective database. Logistic EuroSCORE and STS scores were calculated on a prospective and retrospective basis, respectively. Results Observed mortality was 11.1%. The mean LES was 3 times higher than the mean STS score (LES 20.2% ± 13.9% vs STS 6.7% ± 5.8%). Based on the various LES and STS cutoff values used in previous and ongoing TAVI trials, 53% of patients had an LES ≥15%, 16% had an STS ≥10%, and 40% had an LES ≥20% or STS ≥10%. Pearson correlation coefficient revealed a reasonable (moderate) linear relationship between the LES and STS scores, r = 0.58, P < .001. Although the STS score outperformed the LES, both models had suboptimal discriminatory power (c-statistic, 0.49 for LES and 0.69 for STS) and calibration. Conclusions Clinical judgment and the Heart Team concept should play a key role in selecting patients for TAVI, whereas currently available surgical risk score algorithms should be used to guide clinical decision making.

Risk of sequelae after Chlamydia trachomatis genital infection in women

Chlamydia trachomatis infection, the most common reportable disease in the United States, can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain. Although C. trachomatis is identified among many women who receive a diagnosis of PID, the incidence and timing of PID and long-term sequelae from an untreated chlamydial infection have not been fully determined. This article examines evidence reviewed as part of the Centers for Disease Control and Prevention Chlamydia Immunology and Control Expert Advisory Meeting; 24 reports were included. We found no prospective studies directly assessing risk of long-term reproductive sequelae, such as infertility, after untreated C. trachomatis infection. Several studies assessed PID diagnosis after untreated chlamydial infection, but rates varied widely, making it difficult to determine an overall estimate. In high-risk settings, 2%-5% of untreated women developed PID within the approximately 2-week period between testing positive for C. trachomatis and returning for treatment. However, the rate of PID progression in the general, asymptomatic population followed up for longer periods appeared to be low. According to the largest studies, after symptomatic PID of any cause has occurred, up to 18% of women may develop infertility. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with each recurrent episode. The present review critically evaluates this body of literature and suggests future research directions. Specifically, prospective studies assessing rates of symptomatic PID, subclinical tubal damage, and long-term reproductive sequelae after C. trachomatis infection; better tools to measure PID and tubal damage; and studies on the natural history of repeated chlamydial infections are needed.

Risk stratification of normotensive patients with acute symptomatic pulmonary embolism

Treatment guidelines recommend strong consideration of thrombolysis in patients with acute symptomatic pulmonary embolism (PE) that present with arterial hypotension or shock because of the high risk of death in this setting. For haemodynamically stable patients with PE, the categorization of risk for subgroups may assist with decision-making regarding PE therapy. Clinical models [e.g. Pulmonary Embolism Severity Index (PESI)] may accurately identify those at low risk of overall death in the first 3 months after the diagnosis of PE, and such patients might benefit from an abbreviated hospital stay or outpatient therapy. Though some evidence suggests that a subset of high-risk normotensive patients with PE may have a reasonable risk to benefit ratio for thrombolytic therapy, single markers of right ventricular dysfunction (e.g. echocardiography, spiral computed tomography, or brain natriuretic peptide testing) and myocardial injury (e.g. cardiac troponin T or I testing) have an insufficient positive predictive value for PE-specific mortality to drive decision-making toward such therapy. Recommendations for outpatient treatment or thrombolytic therapy for patients with PE necessitate further development of prognostic models and conduct of clinical trials that assess various treatment strategies.

Occurrence, risk factors, diagnosis and treatment of syphilis in the prospective observational Swiss HIV Cohort Study

Background: Annual syphilis testing was reintroduced in the Swiss HIV Cohort Study (SHCS) in 2004. We prospectively studied occurrence, risk factors, clinical manifestations, diagnostic approaches and treatment of syphilis. Methods: Over a period of 33 months, participants with positive test results for Treponema pallidum hemagglutination assay were studied using the SHCS database and an additional structured case report form. Results: Of 7244 cohort participants, 909 (12.5%) had positive syphilis serology. Among these, 633 had previously been treated and had no current signs or symptoms of syphilis at time of testing. Of 218 patients with newly detected untreated syphilis, 20% reported genitooral contacts as only risk behavior and 60% were asymptomatic. Newly detected syphilis was more frequent among men who have sex with men (MSM) [adjusted odds ratio (OR) 2.8, P < 0.001], in persons reporting casual sexual partners (adjusted OR 2.8, P < 0.001) and in MSM of younger age (P = 0.05). Only 35% of recommended cerebrospinal fluid (CFS) examinations were performed. Neurosyphilis was diagnosed in four neurologically asymptomatic patients; all of them had a Venereal Disease Research Laboratory (VDRL) titer of 1:≥32. Ninety-one percent of the patients responded to treatment with at least a four-fold decline in VDRL titer. Conclusion: Syphilis remains an important coinfection in the SHCS justifying reintroduction of routine screening. Genitooral contact is a significant way of transmission and young MSM are at high risk for syphilis. Current guidelines to rule out neurosyphilis by CSF analysis are inconsistently followed in clinical practice. Serologic treatment response is above 90% in the era of combination antiretroviral therapy.

What percentage of people in the general population satisfies the current clinical at-risk criteria of psychosis?

The clinical validity of at-risk criteria of psychosis had been questioned based on epidemiological studies that have reported much higher prevalence and annual incidence rates of psychotic-like experiences (PLEs as assessed by either self rating questionnaires or layperson interviews) in the general population than of the clinical phenotype of psychotic disorders (van Os et al., 2009). Thus, it is unclear whether “current at-risk criteria reflect behaviors so common among adolescents and young adults that a valid distinction between ill and non-ill persons is difficult” (Carpenter, 2009). We therefore assessed the 3-month prevalence of at-risk criteria by means of telephone interviews in a randomly drawn general population sample from the at-risk age segment (age 16–35 years) in the Canton Bern, Switzerland. Eighty-five of 102 subjects had valid phone numbers, 21 of these subjects refused (although 6 of them signaled willingness to participate at a later time), 4 could not be contacted. Sixty subjects (71% of the enrollment fraction) participated. Two participants met exclusion criteria (one for being psychotic, one for lack of language skills). Twenty-two at-risk symptoms were assessed for their prevalence and severity within the 3 months prior to the interview by trained clinical raters using (i) the Structured Interview for Prodromal Syndromes (SIPS; Miller et al., 2002) for the evaluation of 5 attenuated psychotic and 3 brief limited intermittent psychotic symptoms (APS, BLIPS) as well as state-trait criteria of the ultra-high-risk (UHR) criteria and (ii) the Schizophrenia Proneness Instrument, Adult version (SPI-A; Schultze-Lutter et al., 2007) for the evaluation of the 14 basic symptoms included in COPER and COGDIS (Schultze-Lutter et al., 2008). Further, psychiatric axis I diagnoses were assessed by means of the Mini-International Neuropsychiatric Interview, M.I.N.I. (Sheehan et al., 1998), and psychosocial functioning by the Scale of Occupational and Functional Assessment (SOFAS; APA, 1994). All interviewees felt ‘rather’ or ‘very’ comfortable with the interview. Of the 58 included subjects, only 1 (2%) fulfilled APS criteria by reporting the attenuated, non-delusional idea of his mind being literally read by others at a frequency of 2–3 times a week that had newly occurred 6 weeks ago. BLIPS, COPER, COGDIS or state-trait UHR criteria were not reported. Yet, twelve subjects (21%) described sub-threshold at-risk symptoms: 7 (12%) reported APS relevant symptoms but did not meet time/frequency criteria of APS, and 9 (16%) reported COPER and/or COGDIS relevant basic symptoms but at an insufficient frequency or as a trait lacking increase in severity; 4 of these 12 subjects reported both sub-threshold APS and sub-threshold basic symptoms. Table 1 displays type and frequency of the sub-threshold at-risk symptoms.

Implantation of the biodegradable polymer biolimus-eluting stent in patients with high SYNTAX score is associated with decreased cardiac mortality compared to a permanent polymer sirolimus-eluting stent: two year follow-up results from the "all-comers" LEADERS trial

Background: The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods and results: The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the “all-comers” LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046). Conclusions: The SXscore when applied to an “all-comers” patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Tumor budding score based on 10 high-power fields is a promising basis for a standardized prognostic scoring system in stage II colorectal cancer

Tumor budding is recognized by the World Health Organization as an additional prognostic factor in colorectal cancer but remains unreported in diagnostic work due to the absence of a standardized scoring method. This study aims to assess the most prognostic and reproducible scoring systems for tumor budding in colorectal cancer. Tumor budding on pancytokeratin-stained whole tissue sections from 105 well-characterized stage II patients was scored by 3 observers using 7 methods: Hase, Nakamura, Ueno, Wang (conventional and rapid method), densest high-power field, and 10 densest high-power fields. The predictive value for clinicopathologic features, the prognostic significance, and interobserver variability of each scoring method was analyzed. Pancytokeratin staining allowed accurate evaluation of tumor buds. Interobserver agreement for 3 observers was excellent for densest high-power field (intraclass correlation coefficient, 0.83) and 10 densest high-power fields (intraclass correlation coefficient, 0.91). Agreement was moderate to substantial for the conventional Wang method (κ = 0.46-0.62) and moderate for the rapid method (κ = 0.46-0.58). For Nakamura, moderate agreement (κ = 0.41-0.52) was reached, whereas concordance was fair to moderate for Ueno (κ = 0.39-0.56) and Hase (κ = 0.29-0.51). The Hase, Ueno, densest high-power field, and 10 densest high-power field methods identified a significant association of tumor budding with tumor border configuration. In multivariate analysis, only tumor budding as evaluated in densest high-power field and 10 densest high-power fields had significant prognostic effects on patient survival (P < .01), with high prognostic accuracy over the full 10-year follow-up. Scoring tumor buds in 10 densest high-power fields is a promising method to identify stage II patients at high risk for recurrence in daily diagnostics; it is highly reproducible, accounts for heterogeneity, and has a strong predictive value for adverse outcome.

High-grade supraclavicular soft tissue sarcoma as secondary malignancy after successful treatment of acute myeloid leukemia: case report and literature review

It is well known that the treatment protocols for hematopoetic neoplasms carry a high risk of long-term oncogenicity. However, few reports have been published of sarcomas as secondary malignancies. An unusual case report of a soft tissue sarcoma appearing as a secondary cancer is presented, with a review of the published data. The present report involves a soft tissue sarcoma of the neck that occurred 18 years after curative treatment of acute myeloid leukemia by induction chemotherapy and bone marrow transplantation. Consecutive graft-versus-host disease affected the cervical skin. Soft tissue sarcomas appearing as secondary tumors are rare in oncology. The presented case describes the appearance of a sarcoma 18 years after curative treatment of acute myeloid leukemia. This is only the second case of this type reported in published studies.

The significance of at-risk symptoms for psychosis in children and adolescents

The early detection and treatment of people at risk for psychosis is currently regarded as a promising strategy in fighting the devastating consequences of psychotic disorders. Currently, the 2 most broadly used sets of at-risk criteria, that is, ultra-high risk (UHR) and basic symptom criteria, were developed mainly in adult samples. We review the data regarding the presence and relevance of at-risk symptoms for psychosis in children and adolescents. The few existing studies suggest that attenuated psychotic symptoms (APS) and brief limited intermittent psychotic symptoms (BLIPS) do have some clinical relevance in young adolescents from the general population. Nevertheless, their differentiation from atypical psychotic symptoms or an emerging schizotypal personality disorder, as well as their stability and predictive accuracy for psychosis, are still unclear. Further, standard interviews for UHR criteria do not define a minimum age for the assessment of APS and BLIPS or guidelines as to when and how to include information from parents. APS and basic symptoms may be predictive of conversion to psychosis in help-seeking young adolescents. Nevertheless, the rate and timing, and thus the required observation time, need further study. Moreover, no study has yet addressed the issue of how to treat children and adolescents presenting with at-risk symptoms and criteria. Further research is urgently needed to examine if current at-risk criteria and approaches have to be tailored to the special needs of children and adolescents. A preliminary rationale for how to deal with at-risk symptoms for psychosis in clinical practice is provided.

'A rose is a rose is a rose', but at-risk criteria differ

Background: Over the last 15 years, efforts to detect psychoses early in their prodromal states have greatly progressed; meanwhile, ultra-high risk (UHR) criteria have been the subject of such consensus that parts of them have been proposed for inclusion in DSM-5 in terms of an attenuated psychosis syndrome. However, it is frequently unacknowledged that the definitions and operationalizations of UHR-related at-risk criteria, including the relevant attenuated psychotic symptoms, vary considerably across centers and time and, thus, between prediction studies. Methods: These variations in UHR criteria are described and discussed with reference to the rates of transition to psychosis, their prevalence in the general population and the proposed new operationalization of the attenuated psychosis syndrome. Results: A comparison of samples recruited according to different UHR operationalizations reveals differences in the distribution of UHR criteria and transition rates as well as in the prevalence rates of at-risk criteria in the general population. Conclusion: The evidence base for the introduction of such a new syndrome is weaker than the number of studies using supposedly equal UHR criteria would at first suggest. Thus, studies comparing the effects of different (sub-)criteria not only on transition rates and outcomes but also on other important aspects, such as neurocognitive performance and brain imaging results, are necessary. Meanwhile, the preliminary attenuated psychosis syndrome in DSM-5 should not follow an altogether new definition but, rather, the currently most reliable UHR definition, which must still demonstrate its reliability and validity outside specialized psychiatric services.

Clinical outcomes of patients with estimated low or intermediate surgical risk undergoing transcatheter aortic valve implantation

AimsTranscatheter aortic valve implantation (TAVI) is an established treatment alternative to surgical aortic valve replacement in high-risk and inoperable patients and outcomes among patients with estimated low or intermediate risk remain to be determined. The aim of this study was to assess clinical outcomes among patients with estimated low or intermediate surgical risk undergoing TAVI.Methods and resultsBetween August 2007 and October 2011, 389 consecutive patients underwent TAVI and were categorized according to the Society of Thoracic Surgeons (STS) score into low (STS < 3%; n = 41, 10.5%), intermediate (STS ≥3% and ≤8%, n = 254, 65.3%), and high-risk (STS > 8%; n = 94, 24.2%) groups for the purpose of this study. Significant differences were found between the groups (low risk vs. intermediate risk vs. high risk) for age (78.2 ± 6.7 vs. 82.7 ± 5.7 vs. 83.7 ± 4.9, P < 0.001), body mass index (28.1 ± 6.1 vs. 26.5 ± 4.9 vs. 24.4 ± 4.6, P < 0.001), chronic renal failure (34 vs. 67 vs. 90%, P < 0.001), all-cause mortality at 30 days (2.4 vs. 3.9 vs. 14.9%, P = 0.001), and all-cause mortality at 1 year (10.1 vs. 16.1 vs. 34.5%, P = 0.0003). No differences were observed with regards to cerebrovascular accidents and myocardial infarction during 1-year follow-up.ConclusionIn contemporary practice, TAVI is not limited to inoperable or STS-defined high-risk patients and should be guided by the decision of an interdisciplinary Heart Team. Compared with patients at calculated high risk, well-selected patients with STS-defined intermediate or low risk appear to have favourable clinical outcomes.

Changes in PESI scores predict mortality in intermediate-risk patients with acute pulmonary embolism

Although the Pulmonary Embolism Severity Index (PESI) accurately identifies 35% of patients with acute pulmonary embolism (PE) as being low risk, some patients deemed high risk by the PESI on admission might be treated safely in the outpatient environment. This retrospective cohort study included a total of 304 consecutive patients with acute PE, classified at the time of hospital admission into PESI class III. The PESI was recalculated 48 h after admission (PESI(48)) and each patient reclassified into the corresponding risk category. The primary outcome of the study was all-cause mortality between day 2 and day 30 after PE diagnosis. 26 (8.5%) patients (95% CI 5.4-11.7%) died between day 2 and day 30 after PE diagnosis. Investigators reclassified 83 (27.3%) patients (95% CI 22.3-32.3%) as low risk (classes I and II) at 48 h. 30-day mortality in these patients was 1.2% (95% CI 0-3.5%) as opposed to 11.3% (95% CI 7.1-15.5%) in those who remained high risk. The net improvement in reclassification was estimated at 54% (p<0.001). In a cohort of intermediate-risk patients with acute PE, calculation of the PESI(48) allows identification of those patients at very low risk of dying during the first month of follow-up.

Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG)

BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

Pulmonary hypertension in high-altitude dwellers: novel mechanisms, unsuspected predisposing factors

Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease states in general. Over the past decade, studies involving short-term hypoxic exposure have greatly advanced our knowledge regarding underlying mechanisms and predisposing events of hypoxic pulmonary hypertension. Studies in high altitude pulmonary edema (HAPE)-prone subjects, a condition characterized by exaggerated hypoxic pulmonary hypertension, have provided evidence for the central role of pulmonary vascular endothelial and respiratory epithelial nitric oxide (NO) for pulmonary artery pressure homeostasis. More recently, it has been shown that pathological events during the perinatal period (possibly by impairing pulmonary NO synthesis), predispose to exaggerated hypoxic pulmonary hypertension later in life. In an attempt to translate some of this new knowledge to the understanding of underlying mechanisms and predisposing events of chronic hypoxic pulmonary hypertension, we have recently initiated a series of studies among high-risk subpopulations (experiments of nature) of high-altitude dwellers. These studies have allowed to identify novel risk factors and underlying mechanisms that may predispose to sustained hypoxic pulmonary hypertension. The aim of this article is to briefly review this new data, and demonstrate that insufficient NO synthesis/bioavailability, possibly related in part to augmented oxidative stress, may represent an important underlying mechanism predisposing to pulmonary hypertension in high-altitude dwellers.

[Pregnancy in patients with rheumatoid arthritis and inflammatory spondylarthropathies]

The activity of a rheumatic disease can be influenced by pregnancy and puerperium. Prospective studies have shown an improvement in joint involvement in rheumatoid arthritis in two thirds to three quarters of pregnancies. After birth, an exacerbation is common. In spondylarthropathies there is no relevant change in disease activity. The fetal outcome is not impaired in patients with rheumatoid arthritis and inflammatory spondylarthropathies. Every pregnancy in women with a rheumatic disease should be considered as high-risk, and such pregnancies require close collaboration between rheumatologists and obstetricians.