Locoregional control and survival after lymph node SBRT in oligometastatic disease

Stereotactic body radiotherapy (SBRT) has emerged as an effective option in oligo-metastatic cancer patients affected by lymph node metastases, but its use might be questioned due to risk of regional and distant dissemination through the lymph node chain. The primary aim of our study was to assess the loco-regional control following SBRT in this setting. Ninety-one patients undergoing SBRT for at least one lymph node metastasis from miscellaneous primary tumors were retrospectively evaluated for patterns of failure and toxicity. locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) at 4 years were 79 and 44%. Repeated use of local therapy after progression resulted in a median interval of 17 months until allocation to systemic therapy or supportive care. Forty-three percent of patients were alive at 4 years. Local failure, occurring in 15% of patients, was the only predictor of poor survival (HR: 3.06). Tumor diameter?≥?30 mm and urothelial primary tumor predicted for impaired local control (HR: 4.59 and 5.43, respectively). Metastases from pulmonary cancer showed a significant earlier distant dissemination (HR: 3.53). Only acute and late grade 1–2 toxicities were reported except for 1 case of G3 dysphagia. Loco-regional failure risk is low (18%) and justifies the use of local therapies for patients with oligometastatic disease. Durable disease remission can be achieved by iterative use of local approaches. Local control is correlated to improved OS. Diameter and primary tumor type may affect response to SBRT and risk for early metastatic dissemination.     

Cytokine expression profile in the bone‐anchored hearing system: 12‐week results from a prospective randomized,controlled study

Objective

To study the effect of implanting the percutaneous bone‐anchored hearing system (BAHS) itself and inflammation of the peri‐abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri‐implant skin inflammation.

Materials and Methods

During surgery and 12 weeks post‐implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL‐1β, IL‐6, IL‐8, TNFα, IL‐17, IL‐10, TGF‐ß, MIP‐1α, MMP‐9, TIMP‐1, COL1α1, VEGF‐A, FGF‐2 TLR‐2, and TLR‐4 was quantified using qRT‐PCR.

Results

Thirty‐five patients agreed to the surgery and 12‐week biopsy. Twenty‐two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft‐tissue preservation. Five biopsies were obtained during episodes of inflammation. The post‐implantation mRNA expression of IL‐1β (P = .002), IL‐8 (P = .003), MMP9 (P = .005), TIMP‐1 (P = .002), and COL1α1 (P < .001) was significantly up‐regulated. IL‐6 (P = .009) and FGF‐2 (P = .004) mRNA expression was significantly down‐regulated after implantation. Within patients, no difference between post‐implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL‐1β (P = .015) and IL‐17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12‐week follow‐up.

Conclusions

As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL‐8 and IL‐1β) is still relatively high compared with the baseline, steady‐state, expression. The up‐regulation of anabolic (COL1α1) and tissue‐remodeling (MMP‐9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL‐1β, IL‐17, and TNF‐α may be interesting markers associated with inflammation.     

Improving Handoff by Deliberate Cognitive Processing: Results from a Randomized Controlled Experimental Study

BackgroundAlthough a number of successful handoff interventions have been reported, the handoff process remains vulnerable because it relies on memory. The aim of this study was to investigate the effect of deliberate cognitive processing (i.e., analytical, conscious, and effortful thinking) on recall of information from a simulated handoff.MethodsThis two-phased experiment was executed in the Netherlands in 2015. A total of 78 pediatric residents were randomly divided into an intervention group (n = 37) and a control group (n = 41). In phase 1, participants received written handoffs from 8 patients. The intervention group was asked to develop a contingency plan for each patient, deliberately processing the information. The control group received no specific instructions. In phase 2, all participants were asked to write down as much as they recalled from the handoffs. The outcome was the amount and accuracy of recalled information, calculated by scoring for idea units (single information elements) and inferences (conclusions computed by participants based on two or more idea units).ResultsParticipants in the intervention group recalled significantly more inferences (7.24 vs. 3.22) but fewer correct idea units (21.1% vs. 25.3%) than those in the control group. There was no difference with regard to incorrectly recalled information.ConclusionOur study revealed that deliberate cognitive processing leads to creation of more correct inferences, but fewer idea units. This suggests that deliberate cognitive processing results in interpretation of the information into higher level concepts, rather than remembering specific pieces of information separately. This implies better understanding of patients’ problems.     

Normative comparisons for large neuropsychological test batteries: User-friendly and sensitive solutions to minimize familywise false positives

Introduction. In neuropsychological research and clinical practice, a large battery of tests is often administered to determine whether an individual deviates from the norm. We formulate three criteria for such large battery normative comparisons. First, familywise false-positive error rate (i.e., the complement of specificity) should be controlled at, or below, a prespecified level. Second, sensitivity to detect genuine deviations from the norm should be high. Third, the comparisons should be easy enough for routine application, not only in research, but also in clinical practice. Here we show that these criteria are satisfied for current procedures used to assess an overall deviation from the norm—that is, a deviation given all test results. However, we also show that these criteria are not satisfied for current procedures used to assess test-specific deviations, which are required, for example, to investigate dissociations in a test profile. We therefore propose several new procedures to assess such test-specific deviations. These new procedures are expected to satisfy all three criteria. Method. In Monte Carlo simulations and in an applied example pertaining to Parkinson disease, we compare current procedures to assess test-specific deviations (uncorrected and Bonferroni normative comparisons) to new procedures (Holm, one-step resampling, and step-down resampling normative comparisons). Results. The new procedures are shown to: (a) control familywise false-positive error rate, whereas uncorrected comparisons do not; (b) have higher sensitivity than Bonferroni corrected comparisons, where especially step-down resampling is favorable in this respect; (c) be user-friendly as they are implemented in a user-friendly normative comparisons website, and as the required normative data are provided by a database. Conclusion. These new normative comparisons procedures, especially step-down resampling, are valuable additional tools to assess test-specific deviations from the norm in large test batteries.     

From the Cover: Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine

Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thoracic region extends well into Hox10-expressing areas of the embryo, suggesting that these proteins are unable to block rib formation. Here, we show that this is not a result of the loss of rib-repressing properties by the snake proteins, but rather to a single base pair change in a Hox/Paired box (Pax)-responsive enhancer, which prevents the binding of Hox proteins. This polymorphism is also found in Paenungulata, such as elephants and manatees, which have extended rib cages. In vivo, this modified enhancer failed to respond to Hox10 activity, supporting its role in the extension of rib cages. In contrast, the enhancer could still interact with Hoxb6 and Pax3 to promote rib formation. These results suggest that a polymorphism in the Hox/Pax-responsive enhancer may have played a role in the evolution of the vertebrate spine by differently modulating its response to rib-suppressing and rib-promoting Hox proteins.     

Acculturation and the prevalence of depression in older Mexican Americans: baseline results of the Sacramento Area Latino Study on Aging

OBJECTIVE: To determine the association between acculturation, immigration, and prevalence of depression in older Mexican Americans. DESIGN: Cross-sectional analysis from a cohort study. SETTING: Urban and rural counties of the Central Valley of Northern California. PARTICIPANTS: One thousand seven hundred and eighty-nine Latinos recruited from a population-based sample (85% Mexican Americans) with a mean age of 70.6 (range 60-100; standard deviation (SD) = 7.13); 58.2% were women. MEASUREMENTS: Depressive symptoms were assessed with the Center for Epidemiologic Studies--Depression scale (CES-D). Acculturation was measured with the Acculturation Rating Scale for Mexican Americans--II. Psychosocial, behavioral, and medical histories were also obtained. RESULTS: The prevalence of depression (CES-D > or = 16) was 25.4%. Women were at greater risk (32.0%) than men (16.3%; male/female odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.90-3.09). The prevalence of depression was higher among immigrants (30.4%, OR = 1.70, 95% CI = 1.36-2.13), bicultural participants (24.2%, OR = 1.66, 95% CI = 1.24-2.24), and less-acculturated participants (36.1%, OR = 2.95, 95% CI = 2.22-3.93) compared with U.S.-born (20.5%) and more-acculturated groups (16.1%). When adjustments for education, income, psychosocial, behavioral, and health-problem factors were made, the least-acculturated participants were at significantly higher risk of depression than highly acculturated Mexican Americans (OR = 1.56, 95% CI = 1.06-2.31). CONCLUSIONS: These findings are consistent with previously reported estimates of a higher prevalence of depression for older Mexican Americans than non-Hispanic Caucasians and African Americans and are the first to report the prevalence and risk of depression for older U.S.-born and immigrant Mexican Americans. The high prevalence of depression of the least acculturated group may be related to cultural barriers encountered by immigrants and less-acculturated older Mexican Americans and to poorer health status.     

High relapse-free survival after preoperative and intraoperative radiotherapy and resection for sulcus superior tumors

STUDY OBJECTIVES: Relapse-free survival in patients with sulcus superior tumors. DESIGN: Prospective registration study. SETTING: Department of surgical oncology of a university hospital. PATIENTS: Twenty-one patients treated with preoperative radiotherapy (46 Gy), lobectomy and chest-wall resection, and intraoperative radiotherapy (10 Gy). RESULTS: After a median follow-up of 18 months, 18 patients (85%) were free from locoregional relapse, while 8 patients were still alive. CONCLUSIONS: The results show that this protocol can achieve excellent local tumor control and can even be used for palliative treatment.