Diagnosis and treatment response in the asymmetric variant of chronic inflammatory demyelinating polyneuropathy

The objectives were to (a) assess the diagnostic value of testing clinically affected and unaffected limbs with nerve conduction studies (NCS) in patients with the asymmetric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant and to define the most useful strategy for diagnosis, and (b) describe treatment response and long‐term outcome. We performed a retrospective study and included patients with a multifocal distribution of symptoms and signs, who met the probable or definite EFNS/PNS diagnostic categories for CIDP. We included 34 patients and 32 NCS datasets were available. Of these 32 patients, 25 (78%) met the electrodiagnostic criteria for definite or probable CIDP and seven (22%) for possible CIDP. Patients fulfilling the possible electrodiagnostic criteria and a supportive criterion were considered as probable CIDP. NCS of the clinically affected forearm and leg led to a probable or definite diagnosis in 13 patients (41%). Measuring both arms up to Erb's point led to a probable or definite diagnosis in 25 patients (78%), after which NCS of both legs did not contribute to additional probable or definite diagnoses. In total, 30% of patients treated with dexamethasone and 94% of patients treated with intravenous immunoglobulins (IVIg) responded. IVIg withdrawal attempts were successful in 21% of patients. After measuring the clinically affected arm up to Erb's point, NCS of the unaffected arm to Erb's point has the highest additional diagnostic yield in patients with asymmetric CIDP. Patients seem to respond better to IVIg than to corticosteroids and long‐term treatment is often required, although IVIg withdrawal was successful in 21%.     

The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder characterized by the fibrosis of skin, heart, lung, and kidney as well. Excessive activation of fibroblasts is associated with higher expression of Notch1 and/or Notch3 genes. The constitutive expression of NOTCH genes was described in epithelial cells: epidermal keratinocytes, hair follicle cells and sebaceous glands. The NOTCH signalling pathway may be involved in the development of fibrosis, myofibroblast formation and the process of epithelial-mesenchymal transition. Activation of the NOTCH pathway leads to morphological, phenotypic and functional changes in epithelial cells. Furthermore, inhibition of Notch signalling prevent the development of fibrosis in different models, among them, bleomycin-induced fibrosis and in the Task-1 mause model. Molecular mechanisms, including the role of NOTCH signaling pathway, associated with fibrosis in SSc have not been completely recognized.     

Relapse following frontofacial advancement using the rigid external distractor

Multisutural synostosis may result in frontofacial hypoplasia. The aesthetic and function problems arising from this can be corrected by frontofacial advancement, either by monobloc or bipartition osteotomy. Significantly larger, safer advancements can be achieved using distraction osteogenesis when compared to conventional osteotomy. However, the stability of this technique has been questioned. A retrospective study of 21 patients with craniofacial dysostosis who underwent frontofacial advancement osteotomies using the rigid external distractor system was undertaken. Twelve were distracted on protocol 1 (24 hours after surgery at 1.5 mm/d). Nine were distracted on protocol 2 (7 days after surgery at 1 mm/d). A 6-week consolidation period was used. Changes in frontofacial advancement in the sagittal plane were measured preoperatively, immediately, at 6 months, and where possible thereafter annually using lateral cephalograms and three-dimensional computed tomography scans. The midface was distracted an average of 16.4 mm with a range of 12 to 22 mm as measured in the sagittal plain. Relapse was seen only in 3 of 21 patients, and all of these patients were distracted using protocol 1. Distraction osteogenesis of the frontofacial skeleton using the rigid external distractor frame is generally stable. In this series, a longer latency period and reduced distraction rate resulted in greater stability. Overdistraction in the growing infant is recommended to allow for completion of growth. Overdistraction is not needed to compensate for potential relapse.     

Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

Purpose

MCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as a relevant prognostic biomarker in a variety of cancers, including pituitary adenomas. The purpose of this study was to assess whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort of ACTH-immunopositive adenomas.

Methods

Tissue samples were obtained intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were assessed by immunohistochemical staining, while the expression of miR-106b-5p, miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR performed on RNA isolated from FFPE tissues.

Results

We have found a significant increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7 was ubiquitously overexpressed in Crooke’s cell adenomas. The expression of miR-93-5p was significantly elevated in invasive compared to noninvasive tumors. In addition, all four microRNAs from the miR-106b~25 cluster displayed marked upregulation in Crooke’s cell adenomas. Remarkably, MCM7 and miR-106b-5p both strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25 cluster expression was able to accurately differentiate invasive from noninvasive tumors and had a significant discriminatory ability to predict postoperative tumor recurrence/progression.

Conclusions

miR-106b~25 and its host gene MCM7 are potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas. Additionally, they are both significantly upregulated in rare Crooke’s cell adenomas and might therefore contribute to their aggressive phenotype.

     

Effect of exercise combined with glucagon‐like peptide‐1 receptor agonist treatment on cardiac function: A randomized double‐blind placebo‐controlled clinical trial

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon‐like peptide‐1 (GLP‐1) receptor agonist (GLP‐1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP‐1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] ?7.1 ± 1.6 to ?7.7 ± 1.8 cm/s, P = .01), but not in the liraglutide group (?7.1 ± 1.4 to ?7.0 ± 1.4 cm/s, P = .60; between groups, P = .02). Similarly, the mean ± s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 ± 0.4 to 1.2 ± 0.4, P = .003), but not in the liraglutide group (1.0 ± 0.3 to 1.0 ± 0.3, P = .87; between groups, P = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function.     

Whole pelvis radiotherapy for pathological node-positive prostate cancer

Purpose

The goal of this work was to investigate the oncological outcome of whole pelvis radiotherapy (wpRT) in pathologic pelvic lymph node-positive (pN1) prostate cancer (PCa), evaluate the location of relapse, and identify potential prognostic factors.

Patients and methods

All patients undergoing pelvic lymph node dissection (PLND) since the year 2000 at a single tertiary care center were evaluated. A total of 154 patients with pN1 PCa were treated with wpRT (39 in an adjuvant setting) and 2–3 years of androgen deprivation therapy (ADT). Kaplan–Meier analysis was performed to estimate biochemical recurrence-free survival (bRFS), clinical progression-free survival (cPFS), and prostate cancer-specific survival (CSS). Uni- and multivariate regression analyses were performed to identify prognostic factors.

Results

Estimated bRFS was 67%, cPFS was 71%, and CSS was 96% at 5 years. Median follow-up was 55 months (interquartile range 25–87). Multivariate analysis identified having only 1 positive lymph node, a shorter time between diagnosis and PLND, and older age as independent favorable prognostic factors for biochemical and clinical recurrence. The number of positive lymph nodes was prognostic for CSS (hazard ratio [HR] 1.34, 95% confidence interval 1.17–1.54) and OS (HR 1.22, 95% confidence interval 1.10–1.36). Bone metastases were the most frequent location of PCa relapse (n = 32, 64%).

Conclusions

Patients with pN1 PCa treated with wpRT and 2–3 years ADT have an encouraging 5?year CSS. Understaging of the disease extent may be the most important enemy in definitive pN1 PCa treatment.