Stringent Inclusion Criteria Research Articles

A prognostic scoring system for patients with multiple hepatocellular carcinomas treated by hepatectomy.

The selection criteria of hepatectomy for patients with multiple hepatocellular carcinomas (HCCs) remain controversial. A scoring system based on preoperative data and independent predictors of overall survival (OS) was developed in a primary cohort of 510 patients who underwent hepatectomy for multiple HCCs from 1998 to 2006, and validated in 177 patients who were operated from 2006 to 2009 at the Eastern Hepatobiliary Surgery Hospital. In the NDR scoring system, tumor number (N) > 3, total tumor diameter (D) > 8 cm, and a ratio of largest/smallest diameter (R) > 6 were independent predictors of OS. Its predictive accuracy as determined by the area under the curve (AUC, 0.718) was larger than the four conventional staging systems (0.524-0.662). It stratified postoperative OS into five levels (0-4 score). The 5-year OS rate of patients with a NDR score 0-2 was 46.5% versus 13.9% in those > 2 (P < 0.001). Patients with a score 0-2 therefore were recommended for hepatectomy. The feasibility of this NDR score 0-2 was compared with the previously reported criteria. If the two more stringent inclusion criteria were adopted, 45.5-75.7% of patients with a NDR score 0-2 would be excluded, but their 5-year OS rates were comparable to those within the criteria (44.7% vs. 52.1%, P = 0.083; 46.6% vs. 46.3%, P = 0.674). If the less stringent criteria were used, an additional 25.9% of patients received hepatectomy, but their 5-year OS rate was 13.9%. The NDR scoring system was more accurate in selecting patients with multiple HCCs for hepatectomy.

A critical review of the role of local excision in the treatment of early (T1 and T2) rectal tumors.

The optimal treatment of early (T1 and T2) rectal adenocarcinomas remains controversial. Local excision and radical resection with total mesorectal excision are the two surgical techniques for excising early rectal cancer. Each has their respective benefits, with local excision allowing for decreased operative morbidity and mortality while radical resection provides an oncologically complete treatment through lymphadenectomy. Local excision can be accomplished via transanal endoscopic microsurgery or transanal excision. There is no significant difference in the recurrence rates (21% vs. 33%) or overall survival (80% vs. 66%) between the two local excision modalities; however, transanal endoscopic microsurgery does allow for a higher rate of R0 resection. Current selection criteria for local excision include well to moderately differentiated tumors without high-risk features such as lymphovascular invasion, perineural invasion, or mucinous components. In addition, tumors should ideally be <3 cm in size, excised with a clear margin, occupy less than 1/3 of the circumference of the bowel and be mobile/nonfixed. Despite these stringent inclusion criteria, local excision continues to be plagued with a high recurrence rate in both T1 and T2 tumors due to a significant rate of occult locoregional metastases (20% to 33%). For both tumor groups, the recurrence rate in the local excision group is more than double compared to radical resection. However, the overall survival is not significantly different between those with and without metastases. With intense postoperative surveillance, these recurrences can be identified early while they are confined to the pelvis allowing for salvage surgical options. Recently, neoadjuvant therapy followed by local excision has shown favorable short and long-term oncological outcomes to radical resection in the treatment of T2 rectal cancer. Ultimately, the management of early rectal cancer must be individualized to each patient's expectations of quality and quantity of life. With informed consent, patients may be willing to accept a higher failure rate and an increased post-operative surveillance regimen to preserve a perceived increased quality of life.

The Role of Image Guided Biopsy Targeting in Patients with Atypical Small Acinar Proliferation

Men diagnosed with atypical small acinar proliferation are counseled to undergo early rebiopsy because the risk of prostate cancer is high. However, random rebiopsies may not resample areas of concern. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy offers an opportunity to accurately target and later retarget specific areas in the prostate. We describe the ability of magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy to detect prostate cancer in areas with an initial diagnosis of atypical small acinar proliferation. Multiparametric magnetic resonance imaging of the prostate and magnetic resonance imaging/transrectal ultrasound fusion guided biopsy were performed in 1,028 patients from March 2007 to February 2014. Of the men 20 met the stringent study inclusion criteria, which were no prostate cancer history, index biopsy showing at least 1 core of atypical small acinar proliferation with benign glands in all remaining cores and fusion targeted rebiopsy with at least 1 targeted core directly resampling an area of the prostate that previously contained atypical small acinar proliferation. At index biopsy median age of the 20 patients was 60 years (IQR 57-64) and median prostate specific antigen was 5.92 ng/ml (IQR 3.34-7.48). At fusion targeted rebiopsy at a median of 11.6 months 5 of 20 patients (25%, 95% CI 6.02-43.98) were diagnosed with primary Gleason grade 3, low volume prostate cancer. On fusion rebiopsy cores that directly retargeted areas of previous atypical small acinar proliferation detected the highest tumor burden. When magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detects isolated atypical small acinar proliferation on index biopsy, early rebiopsy is unlikely to detect clinically significant prostate cancer. Cores that retarget areas of previous atypical small acinar proliferation are more effective than random rebiopsy cores.

Germline CDKN2A mutations in Brazilian patients of hereditary cutaneous melanoma.

Approximately 10 % of all cutaneous melanoma cases occur in a familial context. The major susceptibility gene for familial melanoma is CDKN2A. In Latin America, genetic studies investigating melanoma predisposition are scarce. The aim of this work was to investigate germline CDKN2A point mutations and genomic rearrangements in a cohort of 59 Brazilian melanoma-prone patients. Screening of CDKN2A alterations was performed by sequencing and multiplex ligation probe amplification. Germline CDKN2A mutations affecting p16(INK4a) were detected in 8 unrelated probands (13.6 %), including 7 familial cases and one patient with multiple melanomas; 4 out of 8 mutation carriers met the criteria for familial melanoma and had multiple primary lesions. Although this study adds to the literature on melanoma susceptibility in Latin America, it is limited by the small size of the cohort. Our findings suggest that stringent inclusion criteria led to a substantially increased rate of CDKN2A mutation detection. This consideration should be taken into account when referring patients for genetic screening in a setting of limited budget, such as in developing countries.

SAT0401 Disease Activity in Psoriatic Arthritis: Comparison of the Discriminative Capacity and Construct Validity of Six Composite Indices in A Real-World

BackgroundTo date is known that an early and aggressive control of disease activity results in significantly better clinical, functional and radiographic outcomes in patients with psoriatic arthritis (PsA). A variety...

Recruitment and screening for a randomized trial investigating Roux-en-Y gastric bypass versus intensive medical management for treatment of type 2 diabetes.

Large-scale randomized clinical trials are needed to assess the role of Roux-en-Y gastric bypass (RYGB) in treating patients with type 2 diabetes mellitus (T2DM). Recruitment challenges must be understood. One hundred twenty participants were needed for a prospective randomized controlled trial investigating treatments for hyperglycemia and cardiovascular disease risk factors in patients with T2DM. The trial had two arms-intensive medical management plus a rigorous lifestyle intervention (LS/IMM) versus LS/IMM with RYGB. Medical inclusion criteria included glycosylated hemoglobin (HbA1c) ≥ 8.0 % while under the care of a physician and body mass index (BMI) 30.0-39.9 kg/m(2). Another inclusion criterion was expressed willingness to accept randomization and participate fully. Varied recruitment strategies were employed at four academic hospitals in the USA and Taiwan, including referrals, mass media, direct mail to patients drawn from a practice-based database, and direct mail to commercial mailing lists. Between February 2008 and December 2011, 2,648 candidates were phone-screened and 240 were screened on site; 120 participants were eventually randomized. Impediments included stringent medical inclusion criteria and a lack of equipoise (i.e., strong beliefs or preferences) among patients and their personal community-based physicians. To meet timeline requirements, the upper limit for BMI was increased from 34.9 to 39.9 kg/m(2) and an additional site was added. We successfully recruited 120 participants with poorly controlled T2DM and mild to moderate obesity. Participants had to be willing to accept randomization to either surgical or nonsurgical treatments. Recruitment took 4 years.

Treatment of painful Modic type I changes by vertebral augmentation with bioactive resorbable bone cement

Low back pain is one of the most common causes of seeking medical attention in industrialized western countries. End plate degenerative changes in the acute phase, formally referred to as Modic type I, represent a specific cause. The aim of this study is to evaluate the effectiveness of vertebral augmentation with calcium sulfate and hydroxyapatite resorbable cement in patients with low back pain resistant to conservative treatment whose origin can be recognized in Modic type I changes. From February 2009 to October 2013, 1,124 patients with low back pain without radicular symptoms underwent physical and imaging evaluation. Stringent inclusion criteria elected 218 to vertebral augmentation with resorbable cement. Follow-up period was 1 year. One hundred seventy-two (79 %) patients improved quickly during the first 4 weeks after treatment. Forty-two (19 %) patients showed a more gradual improvement over the first 6 months, and at 1 year, their pain level did not differ from that of the previous group. In both groups, pain did not resolved completely, but patients showed significant improvement in their daily life activities. Two (1 %) patients did not show any improvement. Two (1 %) patients died for other reasons. There were no complications related to the procedures. Vertebroplasty with bioactive resorbable bone cement seems to be an effective therapeutic option for patients with low back pain resistant to conservative treatment whose origin could be recognized in Modic type I end plate degenerative changes.

Influence of periodontitis on the experience of oral mucositis in cancer patients undergoing head and neck radiotherapy: a pilot study

Periodontitis and radiation-induced oral mucositis are both inflammatory conditions which may be associated through a common underlying dysregulation of the inflammatory response. This pilot study aimed to determine whether the severity of oral mucositis is associated with the severity of periodontitis in cancer patients undergoing head and neck radiotherapy. In this pilot study, 41 patients met the inclusion criteria. The severity of oral mucositis was measured according to the WHO system. The severity of periodontitis was assessed clinically and radiographically. Gingival crevicular fluid was sampled and levels of eight cytokines were determined using a multiplexed bead immunoassay. Associations between radiation-induced oral mucositis and periodontitis were analysed using logistic and linear regression. There was a trend towards a greater proportion of periodontitis patients in the mucositis groups (grades = 1-4) than in the non-mucositis group (grade = 0). However, due to the small sample size of this pilot study, these trends were not statistically significant. This pilot study did not demonstrate a positive statistical correlation between periodontitis experience and severity of radiation-induced oral mucositis. Nonetheless, a trend towards increased bone loss, pocket depth and clinical attachment levels was noted in patients with mucositis grades 1-4. Larger studies with more stringent inclusion criteria are now required to further investigate this possible relationship between periodontitis experience and severity of radiation-induced oral mucositis.

MTHFR Functional Genetic Variation and Methotrexate Treatment Response in Rheumatoid Arthritis: A Meta-Analysis

To date, functional MTHFR SNPs have been tested for their impact on low-dose methotrexate (MTX) response in small rheumatoid arthritis (RA) cohorts. We sought to test their effect in the single largest cohort studied to date, and undertook a meta-analysis utilizing stringent study inclusion criteria. RA patients treated with MTX monotherapy from the Yorkshire Early Arthritis Register (YEAR) were genotyped using RFLP assays, and tested for association with treatment efficacy. Studies for meta-analysis were screened by a set of stringent inclusion criteria. rs1801131 and rs1801133 were not associated with response to MTX in the YEAR cohort, nor did they affect the probability of achieving a low disease activity state. A meta-analysis of comparable studies found no association with these SNPs. MTHFR SNPs rs1801131 and rs1801133 are unlikely to have a clinically meaningful effect on the first 6 months of MTX treatment in early RA.

Candesartan Cilexetil 32 mg/Hydrochlorothiazide 25 mg in Unselected Patients with High or Very High Cardiovascular Risk: Efficacy, Safety, and Metabolic Impact

Safety and efficacy of the fixed-dose combination candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg has been demonstrated in a number of randomized clinical trials. Because stringent inclusion and exclusion criteria prohibit many high-risk patients from being investigated in clinical trials we aimed to assess the effectiveness, tolerability, and safety in a large unselected cohort of high-risk patients in primary care. The primary objective was the efficacy of candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in lowering the office-based blood pressure (BP). Secondary objectives were changes of metabolic parameters and safety. A multicenter, non-interventional study of patients with a BP ≥ 140 mmHg systolic and/or 90 mmHg diastolic and additional cardiovascular risk factors. Patients received the fixed-dose combination of candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg for 24 weeks. A total of 3,390 patients with a mean age of 61.7 ± 10.6 years, 57.8 % being male, and a mean body mass index of 29.7 kg/m(2) were documented. Of these, 70.9 % had at least one additional cardiovascular risk factor such as coronary artery disease (45.5 %) or diabetes mellitus (44.5 %). Baseline BP was 159.6 ± 15.3 over 93.5 ± 9.5 mmHg. BP at 24 weeks was reduced by 32.3 ± 15.8 systolic and 16.1 ± 10.2 mmHg diastolic compared with baseline (p < 0.001 each). Systolic BP (SBP) and diastolic BP (DBP) was normalized (<140/<90 mmHg) in 57.4 % of non-diabetic patients. An SBP <140 mmHg or SBP reduction of ≥ 20 mmHg was achieved by 77.9 % non-diabetic patients. Fasting plasma glucose (-5.9 mg/dL), glycosylated hemoglobin (-0.18 %), low-density lipoprotein cholesterol (-8.5 mg/dL) and triglycerides (-20.3 mg/dL) were reduced significantly, high-density lipoprotein was increased by 0.18 %, while potassium and creatinine levels remained stable. The proportion of patients with adverse drug reactions (ADRs) was 1.3 % (n = 61 events in 45 patients). There were ten serious ADRs in eight patients; four patients died without causal relationship to study drug. The results confirm previous randomized clinical trial data supporting the effectiveness, tolerability, and safety of this fixed-dose combination in an unselected patient population with high cardiovascular risk.

High mutation detection rates in cerebral cavernous malformation upon stringent inclusion criteria: one‐third of probands are minors

Cerebral cavernous malformations (CCM) are prevalent vascular malformations occurring in familial autosomal dominantly inherited or isolated forms. Once CCM are diagnosed by magnetic resonance imaging, the indication for genetic testing requires either a positive family history of cavernous lesions or clinical symptoms such as chronic headaches, epilepsy, neurological deficits, and hemorrhagic stroke or the occurrence of multiple lesions in an isolated case. Following these inclusion criteria, the mutation detection rates in a consecutive series of 105 probands were 87% for familial and 57% for isolated cases. Thirty-one novel mutations were identified with a slight shift towards proportionally more CCM3 mutations carriers than previously published (CCM1: 60%, CCM2: 18%, CCM3: 22%). In-frame deletions and exonic missense variants requiring functional analyses to establish their pathogenicity were rare: An in-frame deletion within the C-terminal FERM domain of CCM1 resulted in decreased protein expression and impaired binding to the transmembrane protein heart of glass (HEG1). Notably, 20% of index cases carrying a CCM mutation were below age 10 and 33% below age 18 when referred for genetic testing. Since fulminant disease courses during the first years of life were observed in CCM1 and CCM3 mutation carriers, predictive testing of minor siblings became an issue.

The technical hypothesis of motivational interviewing: a meta-analysis of MI's key causal model.

The technical hypothesis of motivational interviewing (MI) posits that therapist-implemented MI skills are related to client speech regarding behavior change and that client speech predicts client outcome. The current meta-analysis is the first aggregate test of this proposed causal model. A systematic literature review, using stringent inclusion criteria, identified 16 reports describing 12 primary studies. We used review methods to calculate the inverse-variance-weighted pooled correlation coefficient for the therapist-to-client and the client-to-outcome paths across multiple targeted behaviors (i.e., alcohol or illicit drug use, other addictive behaviors). Therapist MI-consistent skills were correlated with more client language in favor of behavior change (i.e., change talk; r = .26, p < .0001), but not less client language against behavior change (i.e., sustain talk; r = .10, p = .09). MI-inconsistent skills were associated with less change talk (r = -.17, p = .001) as well as more sustain talk (r = .07, p = .009). Among these studies, client change talk was not associated with follow-up outcome (r = .06, p = .41), but sustain talk was associated with worse outcome (r = -.24, p = .001). In addition, studies examining composite client language (e.g., an average of negative and positive statements) showed an overall positive relationship with client behavior change (r = .12, p = .006; k = 6). This meta-analysis provides an initial test and partial support for a key causal model of MI efficacy. Recommendations for MI practitioners, clinical supervisors, and process researchers are provided.

Neuroimaging essentials in essential tremor: a systematic review.

BackgroundEssential tremor is regarded to be a disease of the central nervous system. Neuroimaging is a rapidly growing field with potential benefits to both diagnostics and research. The exact role of imaging techniques with respect to essential tremor in research and clinical practice is not clear. A systematic review of the different imaging techniques in essential tremor is lacking in the literature.MethodsWe performed a systematic literature search combining the terms essential tremor and familial tremor with the following keywords: imaging, MRI, VBM, DWI, fMRI, PET and SPECT, both in abbreviated form as well as in full form. We summarize and discuss the quality and the external validity of each study and place the results in the context of existing knowledge regarding the pathophysiology of essential tremor.ResultsA total of 48 neuroimaging studies met our search criteria, roughly divided into 19 structural and 29 functional and metabolic studies. The quality of the studies varied, especially concerning inclusion criteria. Functional imaging studies indicated cerebellar hyperactivity during rest and during tremor. The studies also pointed to the involvement of the thalamus, the inferior olive and the red nucleus. Structural studies showed less consistent results.Discussion and conclusionNeuroimaging techniques in essential tremor give insight into the pathophysiology of essential tremor indicating the involvement of the cerebellum as the most consistent finding. GABAergic dysfunction might be a major premise in the pathophysiological hypotheses. Inconsistencies between studies can be partly explained by the inclusion of heterogeneous patient groups. Improvement of scientific research requires more stringent inclusion criteria and application of advanced analysis techniques. Also, the use of multimodal neuroimaging techniques is a promising development in movement disorders research. Currently, the role of imaging techniques in essential tremor in daily clinical practice is limited.

Clinical significance of neutrophil gelatinase-associated lipocalin (NGAL) in colorectal cancer: a meta-analysis

Growing evidence has implicated that neutrophil gelatinase-associated lipocalin (NGAL) plays a role in a spectrum of human cancers. Several observational studies from different parts of the world have been devoted to elucidate the clinical relationship between NGAL and colorectal cancer. This meta-analysis aimed to explore the overall accuracy of NGAL detection for the diagnosis and prognosis of colorectal cancer. Based on comprehensive literature screening on Pubmed, Ovid, and CNKI databases, our screening covered all published papers until March 2013. The relevant papers were selected according to some stringent inclusion criteria. Essential data were extracted from the recruited papers and further processed by systematic meta-analysis. The meta-analysis included 5 studies for diagnosis of colorectal cancer. Overall, the pooled sensitivity and specificity of all studies were 73% (95%CI=0.69-0.76) and 89% (95%CI=0.85-0.93). The pooled positive likelihood ratio and negative likelihood ratio were 5.41 (95%CI=3.85- 7.59) and 0.37 (95%CI=0.22-0.62). The pooled diagnostic odds ratios was 18.05 (95%CI=11.77-27.69). The area under the summary receiver operating characteristic curve for the diagnosis of colorectal cancer was 0.87. Meanwhile, 3 studies were included to evaluate the prognostic significance of NGAL overexpression in colorectal cancer patients. The pooled hazard ratio was 2.12 (95%CI=1.35-3.33). High level of NGAL predicted poor disease-free survival. Thus, NGAL is a potential biomarker for the diagnosis and prognosis of colorectal cancer.

Atypical sulcal anatomy in young children with autism spectrum disorder.

Autism spectrum disorder is associated with an altered early brain development. However, the specific cortical structure abnormalities underlying this disorder remain largely unknown. Nonetheless, atypical cortical folding provides lingering evidence of early disruptions in neurodevelopmental processes and identifying changes in the geometry of cortical sulci is of primary interest for characterizing these structural abnormalities in autism and their evolution over the first stages of brain development. Here, we applied state-of-the-art sulcus-based morphometry methods to a large highly-selective cohort of 73 young male children of age spanning from 18 to 108 months. Moreover, such large cohort was selected through extensive behavioral assessments and stringent inclusion criteria for the group of 59 children with autism. After manual labeling of 59 different sulci in each hemisphere, we computed multiple shape descriptors for each single sulcus element, hereby separating the folding measurement into distinct factors such as the length and depth of the sulcus. We demonstrated that the central, intraparietal and frontal medial sulci showed a significant and consistent pattern of abnormalities across our different geometrical indices. We also found that autistic and control children exhibited strikingly different relationships between age and structural changes in brain morphology. Lastly, the different measures of sulcus shapes were correlated with the CARS and ADOS scores that are specific to the autistic pathology and indices of symptom severity. Inherently, these structural abnormalities are confined to regions that are functionally relevant with respect to cognitive disorders in ASD. In contrast to those previously reported in adults, it is very unlikely that these abnormalities originate from general compensatory mechanisms unrelated to the primary pathology. Rather, they most probably reflect an early disruption on developmental trajectory that could be part of the primary pathology.

Outcomes of cancer patients who do not satisfy conventional clinical trial eligibility criteria (CTEC).

128 Background: Trials have stringent inclusion and exclusion criteria to maintain internal validity. However, study findings are often applied to patients in routine practice who do not meet CTEC. Our aim was to characterize the outcomes and magnitude of treatment benefit in these patients. Methods: Patients diagnosed with stage III colon cancer from 2006 and 2008, referred to 1 of 5 regional cancer centers in British Columbia, and assessed for adjuvant chemotherapy (AC) within 12 weeks of surgery were analyzed. Patients were considered trial-eligible (TE) if aged 18 to 79 years, ECOG 0/1, CEA &lt;10, did not receive prior chemotherapy or radiation, and had adequate blood counts and normal cardiac, liver and kidney function. All other patients were deemed trial-ineligible (TI). Results: A total of 820 patients were identified: median age was 69 years (range 60-76), 423 (52%) were men, 365 (45%) were ECOG 0/1 and 592 (72%) received AC. Among patients treated with AC, 370 (63%) were TE and 222 (37%) were TI. Compared to TI patients, those who were TE were younger (63 vs. 70 years, p &lt; 0.01) and more likely to receive combination regimens rather than single agent AC (56 vs. 33%, p &lt; 0.01). Outcomes were significantly different among patients who were TE, TI, and those who did not receive AC (Table). In multivariate analyses that adjusted for known prognostic factors such as age, ECOG and T and N stages, both TI patients and those not treated with AC had worse outcomes than TE patients (HR for colon cancer death 1.32, 95%CI 0.86-2.02 and 2.77, 95%CI 1.92-3.99, respectively, p trend &lt; 0.01; HR for all cause death 1.24, 95%CI 0.85-1.80 and 2.95, 95%CI 2.17-4.00, respectively, p trend &lt; 0.01). Conclusions: In this population-based cohort, colon cancer patients who did not fit CTEC were frequently treated with AC. Outcomes in this TI group were inferior to those in the TE group, but they were better than the subset that did not receive AC. Broadening CTEC to include a segment of the TI population should be considered as there appears to be benefit in selected individuals. [Table: see text]

Association between Polymorphisms in the Renin-Angiotensin-Aldosterone System Genes and Essential Hypertension in the Han Chinese Population

BackgroundRenin-angiotensin-aldosterone system (RAAS) is the most important endocrine blood pressure control mechanism in our body, genes encoding components of this system have been strong candidates for the investigation of the genetic basis of hypertension. However, previous studies mainly focused on limited polymorphisms, thus we carried out a case-control study in the Han Chinese population to systemically investigate the association between polymorphisms in the RAAS genes and essential hypertension.Methods905 essential hypertensive cases and 905 normotensive controls were recruited based on stringent inclusion and exclusion criteria. All 41 tagSNPs within RAAS genes were retrieved from HapMap, and the genotyping was performed using the GenomeLab SNPstream Genotyping System. Logistic regression analysis, Multifactor dimensionality reduction (MDR), stratified analysis and crossover analysis were used to identify and characterize interactions among the SNPs and the non-genetic factors.ResultsSerum levels of total cholesterol (TC) and triglyceride (TG), and body mass index (BMI) were significantly higher in the hypertensive group than in the control group. Of 41 SNPs genotyped, rs3789678 and rs2493132 within AGT, rs4305 within ACE, rs275645 within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate with hypertension. The MDR analysis demonstrated that the interaction between BMI and rs4305 increased the susceptibility to hypertension. Crossover analysis and stratified analysis further indicated that BMI has a major effect, and rs4305 has a minor effect.ConclusionThese novel findings indicated that together with non-genetic factors, these genetic variants in the RAAS may play an important role in determining an individual’s susceptibility to hypertension in the Han Chinese.

Impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial on Clinical Management of the Axilla in Older Breast Cancer Patients: A SEER-Medicare Analysis

American College of Surgeons Oncology Group (ACOSOG) Z0011 demonstrated that eligible breast cancer patients with positive sentinel lymph nodes (SLN) could be spared an axillary lymph node dissection (ALND) without sacrificing survival or local control. Although heralded as a ‘‘practice-changing trial,’’ some argue that the stringent inclusion criteria limit the trial’s clinical significance. The objective was to assess the potential impact of ACOSOG Z0011 on axillary surgical management of Medicare patients and examine current practice patterns. Medicare beneficiaries aged C66 years with nonmetastatic invasive breast cancer diagnosed from 2001 to 2007 were identified from the Surveillance, Epidemiology and End Results-Medicare database (n = 59,431). Eligibility for ACOSOG Z0011 was determined: SLN mapping, tumor\5 cm, no neoadjuvant treatment, breast conservation; number of positive nodes was determined. Actual surgical axillary management for eligible patients was assessed. Twelve percent (6,942/59,431) underwent SLN mapping and were node positive. Overall, 2,637 patients (4.4 % (2,637/59,431) of the total cohort, but 38 % (2,637/6,942) of patients with SLN mapping and positive nodes) met inclusion criteria for ACOSOG Z0011, had 1 or 2 positive lymph nodes, and could have been spared an ALND. Of these 2,637 patients, 46 % received a completion ALND and 54 % received only SLN biopsy. Widespread implementation of ACOSOG Z0011 trial results could potentially spare 38 % of older breast cancer patients who undergo SLN mapping with positive lymph nodes an ALND. However, 54 % of these patients are already managed with SLN biopsy alone, lessening the impact of this trial on clinical practice in older breast cancer patients.

Prevalence of Resistant Hypertension and Eligibility for Catheter-Based Renal Denervation in Hypertensive Outpatients

Studies of endovascular renal denervation (RDN) have demonstrated significant blood pressure reduction in eligible patients with resistant hypertension. These trials have used stringent inclusion and exclusion criteria in patient enrollment, potentially selecting for a small subset of patients with resistant hypertension. In this study, we examined the changes in estimated prevalence of resistant hypertension when using increasingly stringent definitions of resistant hypertension in a fixed population and assessed the generalizability of RDN when applying study criteria to a community-based hypertensive population. A retrospective chart review was done of hypertensive outpatients. Four increasingly stringent interpretations of the American Heart Association definition of resistant hypertension were used to calculate prevalence estimates. Patients eligible for RDN were identified using criteria from SYMPLICITY HTN-3. Demographic and clinical characteristics were compared. We identified 1,756 hypertensive outpatients; 55.0% were male, 53.9% were white, and subjects had a mean age of 66.6 ± 12.5 years and a body mass index (BMI) of 30.1 ± 10.7 kg/m(2). Only 14 (0.8%) were eligible for RDN. Among these patients, 10 (71.4%) were female and all were black, with a mean age of 69.9 ± 8.8 and BMI of 35.7 ± 6.6. Congestive heart failure was more common in patients eligible for RDN. Patients eligible for RDN based on published studies represent an exceedingly small proportion of the total hypertensive population. Further studies are necessary to determine if the benefits of RDN can be generalized to a broader range of hypertensive patients than those included in previous trials.

HeartWare ventricular assist device experience in the real world

We congratulate Wu et al. [1] for sharing their experience with the HeartWare ventricular assist device (HVAD), which is the largest published series so far. They were successful in demonstrating improvement not only in haemodynamic parameters but also in renal and liver function after device implantation. In comparison with previously published multicentre trials and single-centre experiences about the use of the HVAD [2–4], this series is unique due to liberalization of inclusion criteria, i.e. inclusion of destination therapy patients, younger ( 65 years) are similar to those in the 18–65 age group. Another noteworthy finding is the significant reduction in mean pulmonary vascular resistance (PVR) from 9 to 3 Wood units, which demonstrates the efficacy of LVADs, in this case HAVD, in reducing PVR and thus making patients, who were denied heart transplantation (HTx) previously due to high PVR, suitable for HTx. The series might be criticized for survival outcome (67% at 1 year) which is lower compared with the published 84–86% [2–4]. However, the stringent patient inclusion criteria in the previous trials differ markedly from those in the present series. Specifically, implantation for destination therapy (59% survival at 1 year) and BVAD (47% survival at 1 year) significantly influence their results and are responsible for overall lower survival. Also, the proportion of patients in INTERMACS level I and II published trials is only 22–29%, while it makes up two-thirds of the patients in this series. However, a relatively poor survival, 67% at 3 months and 67% at 1 year (suggestive of only early deaths in this group), is observed in INTERMACS level IV patients in this series. It will be much appreciated if authors could explain these results. Thrombosis in the LVAD pumps is an infrequent but annoying complication and the HVAD is not an exception with the reported incidence of pump thrombosis ranging from 2.1 to 9% [2–4].In the present series, the authors report device malfunctions in 12 (8.5%) cases. There is no consensus about the treatment of device thrombosis, with thrombolytic therapy being favoured as a first-line treatment by many, followed by device exchange which is associated with high mortality [5, 6]. Taking into consideration the large size of the cohort, it would be insightful if the authors could comment on their institutional protocol for the management of device thromboses especially whether thrombolysis was tried before device exchange and the success rate of both thrombolysis and surgery for device exchange.