Citations

Background and Purpose— The extent of potential consent bias in observational studies elucidating genetic and environmental contributions to ischemic stroke is largely unknown. The purpose of this study was to assess differences in stroke cohort characteristics between those who provided informed consent and those whose enrollment was authorized by surrogate decision makers. Methods— The Ischemic Stroke Genetics Study (ISGS) is a prospective, 5-center, case-control study of first-ever ischemic stroke. Demographic, clinical, and stroke characteristics were compared between cases enrolled by self versus by surrogate. Data from one site that limits enrollment only to those able to self-consent were also analyzed to compare those who enrolled with those not able to consent. Results— Overall, 10% (54 of 517) were enrolled using surrogate authorization. Self-consented and surrogate-authorized cases did not differ significantly in age, sex, or conventional risk factors. Surrogate-authorized cases had significantly more severe stroke deficits, larger infarcts, and infarcts localizing to left supratentorial regions. Similarly, at the site restricting enrollment, stroke severity and characteristics differed between self-consented individuals and those otherwise eligible but unable to provide consent. Conclusions— Failure to permit surrogate authorization in genetic studies of ischemic stroke may skew enrollment toward less severe strokes caused by smaller infarcts. This potential consent bias may undermine the ability to identify genetic determinants of risk and severity and suggests that surrogate enrollment in these studies can be ethically justifiable.

Purpose To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. Methods Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. Results High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. Conclusion The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes.

Abstract Purpose: MicroRNA (miRNA) is a new class of small, noncoding RNA. The purpose of this study was to determine if miRNAs are differentially expressed in hepatocellular carcinoma (HCC). Experimental Design: More than 200 precursor and mature miRNAs were profiled by real-time PCR in 43 and 28 pairs of HCC and adjacent benign liver, respectively, and in normal liver specimens. Results: Several miRNAs including miR-199a, miR-21, and miR-301 were differentially expressed in the tumor compared with adjacent benign liver. A large number of mature and precursor miRNAs were up-regulated in the adjacent benign liver specimens that were both cirrhotic and hepatitis-positive compared with the uninfected, noncirrhotic specimens (P < 0.01). Interestingly, all of the miRNAs in this comparison had increased expression and none were decreased. The expression of 95 randomly selected mRNAs was not significantly altered in the cirrhotic and hepatitis-positive specimens, suggesting a preferential increase in the transcription of miRNA. Comparing the miRNA expression in the HCC tumors with patient's survival time revealed two groups of patients; those with predominantly lower miRNA expression and poor survival and those with predominantly higher miRNA expression and good survival (P < 0.05). A set of 19 miRNAs significantly correlated with disease outcome. A number of biological processes including cell division, mitosis, and G1-S transition were predicted to be targets of the 19 miRNAs in this group. Conclusion: We show that a global increase in the transcription of miRNA genes occurs in cirrhotic and hepatitis-positive livers and that miRNA expression may prognosticate disease outcome in HCC.

✓Reconstruction of extensive nerve defects is hampered by the amount of autogenous nerve tissue available for transplantation and by donor site morbidity. Nerve allografts, being of foreign origin and potentially unlimited in supply, provide a solution to these problems. Studies have shown that nerve allotransplants require immunosuppression only until end-organ connections are made and that immunosuppressant therapy may be subsequently discontinued with no negative effect on functional outcome. Also, recent experimental and clinical focus has been on shorter periods of immunosuppression in order to reduce risk, even stopping immunosuppression after regeneration has reached the distal suture line rather than before recovery of end-organ connections. In the pediatric population, the increased disease burden and increased potential for nerve regeneration as well as the frequent availability of a living related donor make allografts all the more attractive as solutions to nerve reconstructive problems. Nevertheless, the risks of immunosuppression must not be underemphasized, and they deserve more attention in the current nerve transplantation literature. The authors report on a child who, at the age of 1 year, received a nerve allograft from a living related donor who was positive for Epstein–Barr virus (EBV). The child quickly developed a symptomatic EBV infection concurrent with immunosuppressant drug therapy. The immunosuppression regimen was stopped prematurely, and the patient suffered only a short illness, but the EBV infection could have developed into a life-threatening posttransplant lymphoproliferative disorder (PTLD). The patient is consequently predisposed to develop PTLD and will have to be monitored for the rest of his life. This case highlights the importance of considering the potentially fatal risks associated with this elective procedure. Future studies are needed to quantify and minimize this complication. Nevertheless, it should be weighed against the potential functional benefit from using nerve allografts.

Between 1986 and 2005, 22 patients (mean age, 14.7 years; range, 3-21) with renal hypertension underwent renal artery revascularization for 28 lesions, 23 with open repair (OR) and 5 with percutaneous transluminal renal angioplasty (PTRA). Thirty-day morbidity was 17% (4/23). Hypertension was cured in 13 (57%), improved in 8 (38%), and unchanged in 1 (5%). Renal function worsened in 1. At a mean follow-up of 4.9 years, 1-year patency rate was 94% and maintained for 5 years. Hypertension at 1 year was cured in 6 of 14 patients (43%; OR, 4; PTRA, 2) and improved in 8 (57%; OR, 7; PTRA, 1); hypertension at 5 years was cured in 50% and improved in 50%. Renal function remained unchanged in all patients who were followed. The authors conclude that both OR and PTRA benefit pediatric patients. PTRA for selected patients may be promising as a first line treatment or as a bridge to definitive OR in children with small arteries.

Questions remain as to whether pediatric sleep disordered breathing increases the risk for elevated blood pressure and blood pressure–dependent cardiac remodeling. We tested the hypothesis that activity-adjusted morning blood pressure surge, blood pressure load, and diurnal and nocturnal blood pressure are significantly higher in children with sleep disordered breathing than in healthy controls and that these blood pressure parameters relate to left ventricular remodeling. 24-hour ambulatory blood pressure parameters were compared between groups. The associations between blood pressure and left ventricular relative wall thickness and mass were measured. 140 children met the inclusion criteria. In children with apnea hypopnea index <5 per hour, a significant difference from controls was the morning blood surge. Significant increases in blood pressure surge, blood pressure load, and in 24-hour ambulatory blood pressure were evident in those whom the apnea hypopnea index exceeded 5 per hour. Sleep disordered breathing and body mass index had similar effect on blood pressure parameters except for nocturnal diastolic blood pressure, where sleep disordered breathing had a significantly greater effect than body mass index. Diurnal and nocturnal systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure predicted the changes in left ventricular relative wall thickness. Therefore, sleep disordered breathing in children who are otherwise healthy is independently associated with an increase in morning blood pressure surge, blood pressure load, and 24-hour ambulatory blood pressure. The association between left ventricular remodeling and 24-hour blood pressure highlights the role of sleep disordered breathing in increasing cardiovascular morbidity.