Regression of Renal Disease by Angiotensin II Antagonism Is Caused by Regeneration of Kidney Vasculature

Chronic renal insufficiency inexorably progresses in patients, such as it does after partial renal ablation in rats. However, the progression of renal diseases can be delayed by angiotensin II blockers that stabilize renal function or increase GFR, even in advanced phases of the disease. Regression of glomerulosclerosis can be induced by angiotensin II antagonism, but the effect of these treatments on the entire vascular tree is unclear. Here, using microcomputed tomography and scanning electron microscopy, we compared the size and extension of kidney blood vessels in untreated Wistar rats with those in untreated and angiotensin II antagonist–treated Munich Wistar Frömter (MWF) rats that spontaneously develop kidney disease with age. The kidney vasculature underwent progressive rarefaction in untreated MWF rats, substantially affecting intermediate and small vessels. Microarray analysis showed increased Tgf-β and endothelin-1 gene expression with age. Notably, 10-week inhibition of the renin-angiotensin system regenerated kidney vasculature and normalized Tgf-β and endothelin-1 gene expression in aged MWF rats. These changes were associated with reduced apoptosis, increased endothelial cell proliferation, and restoration of Nrf2 expression, suggesting mechanisms by which angiotensin II antagonism mediates regeneration of capillary segments. These results have important implications in the clinical setting of chronic renal insufficiency.     

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial

Background

Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of ≈ 6 years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period.

Methods

Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan–Meier analysis and the log-rank test.

Results

The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3 years median follow-up, 39 primary BC-related recurrences occurred, 22 (19 %) of which occurred in the ALND arm and 17 (16 %) occurred in the SLNB arm (p = 0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8 %) and EFS (72.8 vs. 72.9 %) were not statistically different between the ALND and SLNB arms (p = 0.502 and 0.953, respectively).

Conclusions

SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

     

Palliative embolization for metastases of the spine

Background

To present palliative selective and superselective arterial embolization with N-butyl-cyanoacrylate for cancer patients with spinal metastases.

Materials and methods

We studied the files of 164 cancer patients (94 men and 70 women; mean age 57.6 years; range 35–81 years) treated from March 2003 to March 2013 with 178 selective arterial embolization procedures for metastases of the spine from variable primary cancers. We evaluated the technical success of the embolization procedure with post-procedural angiography, the clinical effect in pain relief, need for analgesics and tumor size reduction, and the embolization-related complications.

Results

Post-embolization angiography showed complete occlusion of the pathological feeding vessels in all procedures. Pain score and need for analgesics reduced by 50 % in 159 patients (97 %); no response was achieved in five patients with metastases of the sacrum. The mean duration of pain relief was 9.2 months (range 1–12 months). Metastatic tumor size reduced from a mean of 5.5 cm (range 3.5–7.5 cm) pre-embolization to a mean of 4.5 cm (range 3–5 cm) at the 6-month follow-up; the difference was not statistically significant. Ninety-three patients (56.7 %) experienced embolization-related complications the most common being post-embolization syndrome (80 patients, 48.8 %) followed by leg paresthesias (ten patients, 6 %), and rupture of a lumbar artery (one patient, 0.6 %).

Conclusion

Selective arterial embolization with N-butyl-cyanoacrylate should be considered for pain palliation of patients with metastases of the spine. However, pain relief is temporary, and complications, although minor may occur.

     

Midterm results of surgical treatment of displaced proximal humeral fractures in children

Purpose

To analyse the clinical outcomes of 26 children treated surgically for displaced proximal humerus fracture.

Materials and methods

From January 2008 to December 2012, 26 children/adolescents (14 boys, 12 girls) were treated surgically for displaced fractures at the proximal extremity of the humerus. Ten were grade III and 16 were grade IV according to the Neer–Horowitz classification with a mean age of 12.8 ± 4.2 years. Twenty young patients were surgically treated with a closed reduction and direct percutaneous pinning; six required an open approach. To obtain a proper analysis, we compared the Costant scores with the contralateral shoulder (Δ Costant).

Results

The mean follow-up period was 34 months (range 10–55). Two grade IV patients showed a loss in the reduction after percutaneous treatment. This required open surgery with a plate and screws. On average, the treated fractures healed at 40 days. The mean Δ Costant score was 8.43 (range 2–22). There was a statistically significant improvement in the mean Δ Costant score in grade III patients. In grade IV patients, there was a significant improvement in the mean Δ Costant score in those treated with open surgery versus mini-invasive surgery.

Conclusions

Our study shows excellent results with percutaneous k-wires. This closed surgery had success in these patients, and the excellent outcomes noted here lead us to prefer the mini-invasive surgical approach in NH grade III fractures. In grade IV, the best results were noted in patients treated with open surgery. We suggest an open approach for these patients.

Level of evidence

III.

     

Efficacy and safety of sublingual immunotherapy in children

Allergen immunotherapy (AIT) is currently the only available disease-modifying and aetiological treatment of IgE-mediated diseases. Sublingual allergen immunotherapy (SLIT) constitutes the preferred route of administration of AIT for respiratory allergies in Europe. Recently it has also been approved in the US. Further applications are currently under evaluation, such as IgE-mediated food allergy and IgE-mediated atopic dermatitis. The SLIT safety profile is overall favourable, although local adverse events, usually mild, are described. Most of the meta-analyses confirmed the efficacy of SLIT in reducing symptoms and medication intake in children with allergic diseases. AIT, as an immune-modulating treatment, can modify the natural history of the allergic diseases: reduction of the risk of development of asthma and bronchial hyperreactivity in patients with allergic rhinitis, and reduction of the onset of new sensitizations. A great interest is now devoted to the preventive effects of AIT and, consequently, to the optimal time of initiation.     

Learning from other diseases: protection and pathology in chronic fungal infections

Fungal commensals coexist in a complex milieu of bacteria within the human body. An increased understanding of the importance of microbiota in shaping the host’s immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. Metagenomics has revealed the complex interactions between fungal and bacterial commensals that, either directly or through the participation of the host immune system, impact on immune homeostasis at mucosal surfaces that, in turn, lead to secondary fungal infections. Metabolomics has captured the dialogue between the mammalian host and its microbiota. It appears that the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) plays a dominant role in the interplay between tryptophan catabolism by microbial communities, the host’s own pathway of metabolite production, and the activation of the aryl hydrocarbon receptor (AhR)/IL-22 axis, eventually impacting on mucosal immune homeostasis and host/fungal symbiosis. Thus, the regulatory loop involving AhR and IDO1 may be exploited for the development of multi-pronged host- and microbiota-directed therapeutic approaches for mucosal and systemic fungal diseases.     

Volume rendering based on magnetic resonance imaging: advances in understanding the three-dimensional anatomy of the human knee

The choice of medical imaging techniques, for the purpose of the present work aimed at studying the anatomy of the knee, derives from the increasing use of images in diagnostics, research and teaching, and the subsequent importance that these methods are gaining within the scientific community. Medical systems using virtual reality techniques also offer a good alternative to traditional methods, and are considered among the most important tools in the areas of research and teaching. In our work we have shown some possible uses of three-dimensional imaging for the study of the morphology of the normal human knee, and its clinical applications. We used the direct volume rendering technique, and created a data set of images and animations to allow us to visualize the single structures of the human knee in three dimensions. Direct volume rendering makes use of specific algorithms to transform conventional two-dimensional magnetic resonance imaging sets of slices into see-through volume data set images. It is a technique which does not require the construction of intermediate geometric representations, and has the advantage of allowing the visualization of a single image of the full data set, using semi-transparent mapping. Digital images of human structures, and in particular of the knee, offer important information about anatomical structures and their relationships, and are of great value in the planning of surgical procedures. On this basis we studied seven volunteers with an average age of 25 years, who underwent magnetic resonance imaging. After elaboration of the data through post-processing, we analysed the structure of the knee in detail. The aim of our investigation was the three-dimensional image, in order to comprehend better the interactions between anatomical structures. We believe that these results, applied to living subjects, widen the frontiers in the areas of teaching, diagnostics, therapy and scientific research.     

Reaching the covert, fragile side of patients: the case of narcissistic personality disorder

A multifaceted self allows selection of those sides that are most suited to a situation and an interpersonal context, thus improving adaptation. Patients suffering from personality disorders display a limited range of self-aspects, and their relationships are stereotyped and maladaptive. Another problem is that some of these sides scarcely reach consciousness and usually remain in the background. In the case of narcissistic personality disorder (NPD) the self-part that is fragile is unlikely to reach consciousness, so that people suffering from this disorder are impervious and detached. We present a case of a psychotherapist working with a woman suffering from NPD by facilitating the emergence of the fragile part of her self, hidden by angry and scornful characters. We demonstrate, moreover, how reaching such a self-part is associated with an improvement in the patient's interpersonal relationships outside the consulting room.