Disclosing incidental findings in brain research: The rights of minors in decision‐making

MRI is used routinely in research with children to generate new knowledge about brain development. The detection of unexpected brain abnormalities (incidental findings; IFs) in these studies presents unique challenges. While key issues surrounding incidence and significance, duty of care, and burden of disclosure have been addressed substantially for adults, less empirical data and normative analyses exist for minors who participate in minimal risk research. To identify ethical concerns and fill existing gaps, we conducted a comprehensive review of papers that focused explicitly on the discovery of IFs in minors. The discourse in the 21 papers retrieved for this analysis amply covered practical issues such as informed consent and screening, difficulties in ascertaining clinical significance, the economic costs and burden of responsibility on researchers, and risks (physical or psychological). However, we found little discussion about the involvement of minors in decisions about disclosure of IFs in the brain, especially for IFs of low clinical significance. In response, we propose a framework for managing IFs that integrates practical considerations with explicit appreciation of rights along the continuum of maturity. This capacity‐adjusted framework emphasizes the importance of involving competent minors and respecting their right to make decisions about disclosure. J. Magn. Reson. Imaging 2013;38:1009–1013. © 2013 Wiley Periodicals, Inc.     

Cancer Risk Associated with Residential Proximity to Industrial Sites: A Review

In this study, the authors sought to review available epidemiologic studies of cancer risk and its association with residence in a neighborhood characterized by industrial sites and to discuss options for future study design. The authors attempted to identify all case-control studies published from January 1980 through July 1997 in which investigators examined exposure resulting from residential proximity to an industrial site neighborhood relative to an increased risk of lung, urinary tract, and lymphohematopoietic malignancies. During these years, some authors reported significant associations between lung cancer risk and residential proximity to (a) smelters, (b) complex industrial areas, and (c) other localized emission sources. There was some evidence that leukemia and lymphomas occurred in the neighborhoods that contained industrial sites.     

Endorectal coil MRI in local staging of rectal cancer

PURPOSE: The choice of the therapeutic strategies in patients affected with rectal cancer is strictly dependent by the tumor stage. So, in order to obtain an improvement in preoperative staging accuracy, new imaging modalities are now under investigation. The aim of this work is the evaluation of endorectal-coil MRI in the local staging of rectal cancer. MATERIAL AND METHODS: Fourty-three patients affected with histologically proven rectal cancer, have been evaluated by an high-field strength magnet (1.5 T). In 14/43 patients neoadjuvant pre-operative chemotherapy had been previously performed. In all cases axial SE T1w and FSE T2w sequences and coronal or sagittal FSE T2w sequences, with and without fat suppression, were performed. Basing upon the TNM staging system and the previously reported MRI signs the local extent of the tumor was evaluated, focusing about the rectal wall infiltration and the perirectal lymph nodes involvement. All the patients underwent surgery and a comparative evaluation of MRI and pathological staging was done. RESULTS: At MRI the tumor was detected in 38/43 patients. In evaluating wall infiltration the MRI results agreed with pathological results in 89% of patients and showed 92% accuracy in T1-T2 stage and 94% in T3. In evaluating perirectal lymph nodes metastases MRI showed 69% accuracy, 82% sensitivity and 55%specificity. DISCUSSION AND CONCLUSIONS: The poor accuracy of CT and body-coil MRI in evaluating wall involvement in patients with rectal cancer is mainly related to their inability to demonstrate the single layers of the rectal wall. So transrectal ultrasound is now the first choice modalitiy in local staging of rectal cancer. However transrectal ultrasound showed low sensitivity in detecting perirectal lymph nodes metastases and low accuracy in evaluating the patients previously undergone to neoadjuvant chemotherapy or radiotherapy. On the other hand the improvement of MRI sequences and the availability of the endorectal coils allowed to visualize the single layers of the rectal wall so making the endorectal-coil MRI a reliable imaging technique to stage rectal cancer. The results of our work demonstrate a good diagnostic accuracy of endorectal-coil MRI in local staging of rectal cancer, in particular the degree of rectal wall infiltration was well demonstrated, while the perirectal lymph nodes metastases were demonstrated with less accuracy. The long examination time, the costs and the movement-related artefacts are the main limits of MRI. In particular the movement-related artifacts sometime do not allow the visualization of the wall layers so lowering the diagnostic accuracy in demonstrating the tumor wall infiltration. In conclusion, even though endorectal coil MRI proved to be a reliable imaging technique in local staging of rectal cancer, at present we are not able to state what may be its real role in diagnostic evaluation of the patients with rectal cancer, in particular if compared to endorectal ultrasound. Further, comparative studies, based upon larger patients series are probably needed to draw a definitive conclusion.     

The challenge of basilar artery occlusion wake-up stroke: too late for intravenous thrombolysis?

We describe the case of a patient carried to our emergency department, with the wake-up finding of dysarthria, right hemiplegia and worsening consciousness impairment (NIHSS 12). After performing a CT angiography, which showed complete basilar occlusion, we determined the MR DWI-FLAIR mismatch to estimate the stroke onset time. Because of the favorable mismatch (DWI hyperintensity in the left pons, no FLAIR hyperintensity in the same region), the patient underwent thrombolysis with sudden neurological improvement. In addition, the DWI hyperintensity first observed in the left pons totally regressed after thrombolysis. Wake-up stroke constitutes about 14 % of all strokes, while the percentage of basilar artery occlusion wake-up strokes is still unknown. Although thrombolysis in patients with unknown-onset time is still an off-label therapy, basilar artery occlusion is a potentially fatal event. In our case we used RM DWI-FLAIR mismatch to rapidly estimate the stroke onset time and to treat the patient with an off-label but potentially effective and safe therapy.     

Sodium removal and sodium concentration during peritoneal dialysis: effects of three methods of sodium measurement.

BACKGROUND: Sodium removal (NaR) may have a major impact on the survival of peritoneal dialysis patients. The dialysate/plasma sodium concentration ratio (D/P(Na)) is an indirect index of transcellular water transport by aquaporin channels, and thus of ultrafiltration. Sodium concentration can be assessed by means of flame photometry (F), and direct (D-ISE) or indirect ion-selective electrodes (I-ISE), but these methods have different properties. I-ISE is being used increasingly in clinical laboratories. The aim of this study was to evaluate NaR and D/P(Na) using the three different measurement methods. METHODS: We performed peritoneal equilibration tests (PETs) in 44 peritoneal dialysis patients and calculated the NaR. We also calculated D/P(Na) during the test; plasma and dialysate sodium concentrations were measured by F, D-ISE and I-ISE. RESULTS: NaR was lower (P<0.001) with D-ISE (69+/-29 mmol) than with F (81+/-29 mmol) or I-ISE (79+/-28 mmol). D/P(Na) was also lower at baseline (0.92+/-0.02 vs 0.95+/-0.02 and 0.95+/-0.02; P<0.001), after 60 min (0.87+/-0.03 vs 0.90+/-0.03 and 0.90+/-0.03; P<0.001) and at the end of PET (0.88+/-0.04 vs 0.92+/-0.04 and 0.92+/-0.04; P<0.001) when measured by D-ISE in comparison with F and I-ISE, respectively. CONCLUSIONS: NaR and D/P(Na) were lower when measured by the D-ISE method compared with the F and I-ISE methods. NaR and D/P(Na) were similar when measured by F or I-ISE. I-ISE can be used reliably in the evaluation of NaR and D/P(Na) in everyday clinical practice of peritoneal dialysis.     

Absence of donor CD40 protects renal allograft epithelium and preserves renal function

Blocking the CD40‐CD154 pathway prevents allograft rejection and induces donor‐specific tolerance in various experimental models. However, the translation to clinical studies has been hampered by unexpected thromboembolic complications of CD154‐blocking antibodies. Thus, blocking CD40 instead is now considered as an alternative strategy. Here, we evaluated the role of donor CD40 in allospecific T‐cell responses in vitro and in an in vivo model for renal transplantation. Fully MHC‐mismatched allografts from CD40‐deficient donors displayed better renal function than wild type. These functional data correlated with a lower level of apoptosis in renal tubular epithelial cells and higher expression of PD‐L1, which is most probably because of a reduced Th17 response in recipients of a CD40‐deficient donor. This hypothesis was supported in vitro, where donor CD40 expression was important for the induction of direct allospecific T‐cell responses. Especially the induction of Th17 cells was critically dependent on donor CD40. IL‐17A in conjunction with interferon‐γ in turn rendered renal tubular epithelial cells to a more costimulatory state by upregulating CD40 and downregulating PD‐L1 expression. In conclusion, CD40 blockade not only reduces the allospecific T‐cell responses, but might also lead to protection of tubular epithelium from apoptosis and thereby preserve kidney allograft function.     

Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC)

Purpose

Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor.

Methods

Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n?=?44; age 60.64?±?13.78, mean?±?SD) and carcinoma patients (n?=?11; age 58.91?±?12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1–3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR).

Results

M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2?>?M3 and M3?>?M2) were observed, which differed in associated purinergic and histamine receptor expression.

Conclusions

M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.     

Early outcomes of colon laparoscopic resection in the elderly patients compared with the younger

Background

The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 75 years old (OP) compared with the outcomes of a younger populations (YP).

Methods

Forty elderly patients undergoing laparoscopic colectomy for colorectal cancer between 2007-2011 were studied, the patients are divided for gender, age, year of surgery, site of cancer, and comorbidity on admission and compared with 40 younger patients.

Results and discussion

Mean (standard deviation) age was 81.3 in OP and 68.3 YP Conversion rate was the same between the two groups. There was no difference in operative mean time . The overall mortality rate was 0% percent. The surgical morbidity rate was the same but there was an increased in cardiologic e bronchopneumonia complications in older population. Patients treated with laparoscopic approach had a faster recovery of bowel function and a significant reduction of the mean length of hospital stay not age related. Laparoscopy allowed a better preservation of postoperative independence status.

Conclusions

Laparoscopic colectomy for cancer in elderly patients is safe and beneficial including preservation of postoperative independence and a reduction of length of hospital stay.