Risk of Type 1 Diabetes Progression in Islet Autoantibody-Positive Children Can Be Further Stratified Using Expression Patterns of Multiple Genes Implicated in Peripheral Blood Lymphocyte Activation and Function

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates. RT-PCR analyses of the top-27 candidate genes confirmed 5 genes (BACH2, IGLL3, EIF3A, CDC20, and TXNDC5) associated with differential progression and implicated in lymphocyte activation and function. Multivariate analyses of these five genes in the discovery and validation data sets identified and confirmed four multigene models (BI, ICE, BICE, and BITE, with each letter representing a gene) that consistently stratify high- and low-risk subsets of AbP subjects with hazard ratios >6 (P < 0.01). The results suggest that these genes may be involved in T1D pathogenesis and potentially serve as excellent gene expression biomarkers to predict the risk of progression to clinical diabetes for AbP subjects.     

The influence of non‐HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Non‐HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti‐angiotensin II type 1‐receptor‐activating antibodies (anti‐AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti‐AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti‐AT1R antibodies in 117 consecutive renal transplant recipients in pre‐ and post‐transplant screening. Anti‐AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti‐AT1R(+) group. The patients with anti‐AT1R Abs >9 U/ml lost their graft more often. Biopsy‐proven AR was described in 4/27 (15%) pts in the anti‐AT1R(+) group and 13/90 (14.4%) in the anti‐AT1R(?) group, but more severe cases of Banff IIB or antibody‐mediated rejection (AMR) were more often observed in anti‐AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti‐AT1R(+) (P = 0.009). Patients with anti‐AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti‐AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti‐AT1R‐positive ones lost the graft. Our study suggests monitoring of anti‐AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.     

Femoral and iliac vein stenoses after prolonged femoral vein catheter insertion.

BACKGROUND/AIMS: Catheterization of the femoral vein is a safe and recommended method of temporary access for haemodialysis. In some patients, however, because of the lack of other possibilities, it is necessary to maintain long-term femoral cannulation. The aim of the study was to evaluate the frequency of stenosis after prolonged femoral cannulation. METHODS: The 24 patients incorporated in the study were divided into two groups. Group 1 consisted of 10 end-stage kidney failure patients (four females and six males, aged 32-75 years, average 55.6+/-13.6 years) in whom femoral catheters were maintained for less than 2 weeks (5-14 days, average 9.3+/-3.6 days). Group 2 included 14 chronic haemodialysis patients (six females and eight males aged 23-65 years, average 49.5+/-13.27 years). The time of catheter maintenance ranged from 2 to 16 weeks (average 6.4+/-4.2 weeks). Femoral and iliac vein status was evaluated using magnetic resonance imaging. RESULTS: A feature of venous stenosis of both the femoral and iliac veins was disclosed in four patients in whom femoral cannulation lasted more than 4 weeks. There were no stenoses in group 1. CONCLUSION: Long-term femoral cannulation for more than 4 weeks may be associated with a significant risk of stenosis in the femoral and/or external iliac veins.     

Circulating Plasma Micro RNAs in Patients with Major Depressive Disorder Treated with Antidepressants: A Pilot Study

ObjectiveSignificant progress was made in the understanding etiopathogenic factors related to MDD, including through research on the role of micro RNAs (miRs). We investigated plasma miRs as potential markers for MDD in patients treated with antidepressants.MethodsAt the initiation and at the end of twelve weeks of treatment, blood samples were collected and a structured diagnostic interview and a standardized depression rating scale for the presence and severity of major depression were done. The average decrease in HAMD score was 76.89%. Plasma miR expression profiling was performed by real time PCR. The lists of up-regulated (cut-off=2) and down-regulated miRs were imported into the miRWalk2.0 algorithm and used for target predictions. KEGG database pathways analysis was used to retrieve the pathways significantly targeted by at least two of the miRs.ResultsOf the 222 miRs detected in plasma samples of MDD patients, 40 were differentially expressed after treatment. Twenty-three miRs were significantly overexpressed with fold changes between 1.85 and 25.42, and 17 miRs were significantly downregulated with fold changes from 0.28 to 0.68. Pathway analysis revealed a list of 29 pathways for up-regulated miRs, and 20 pathways for down-regulated miRs. Six dysregulated miRs are common to all the top five pathways (Wnt signaling, Cancer, Endocytosis, Axon guidance, MAPK signaling): miR-146a-5p, miR-146b-5p, miR-221-3p, miR-24-3p, miR-26a-5p.ConclusionOverall, our miRWalk analysis of changes in plasma microRNAs after treatment of patients with major depression might open a new avenue for the understanding of Escitalopram mode of action and for its side effects.     

The contribution of inner and outer retinal photoreceptors to infra‐slow oscillations in the rat olivary pretectal nucleus

A subpopulation of olivary pretectal nucleus (OPN) neurons discharges action potentials in an oscillatory manner, with a period of approximately two minutes. This ‘infra‐slow’ oscillatory activity depends on synaptic excitation originating in the retina. Signals from rod‐cone photoreceptors reach the OPN via the axons of either classic retinal ganglion cells or intrinsically photosensitive retinal ganglion cells (ipRGCs), which use melanopsin for photon capturing. Although both cell types convey light information, their physiological functions differ considerably. The aim of the present study was to disentangle how rod‐cone and melanopsin photoresponses contribute to generation of oscillatory activity. Pharmacological manipulations of specific phototransduction cascades were used whilst recording extracellular single‐unit activity in the OPN of anaesthetized rats. The results show that under photopic conditions (bright light), ipRGCs play a major role in driving infra‐slow oscillations, as blocking melanopsin phototransmission abolishes or transiently disturbs oscillatory firing of the OPN neurons. On the other hand, blocking rod‐cone phototransmission does not change firing patterns in photopic conditions. However, under mesopic conditions (moderate light), when melanopsin phototransmission is absent, blocking rod‐cone signalling causes disturbances or even the disappearance of oscillations implying that classic photoreceptors are of greater importance under moderate light. Evidence is provided that all photoreceptors are required for the generation of oscillations in the OPN, although their roles in driving the rhythm are determined by the lighting conditions, consistent with their relative sensitivities. The results further suggest that maintained retinal activity is crucial to observe infra‐slow oscillatory activity in the OPN.     

Elderly dialysis patients: analysis of factors affecting long-term survival in 4-year prospective observation

Purpose

To assess factors influencing the long-term survival of elderly dialysis patients.

Methods

The study group consisted of 51 prevalent dialysis patients aged over 70?years (32 F and 19?M, all caucasians), who had been on a chronic hemodialysis (27) or peritoneal dialysis program (24) for at least 2?months; median age was 77?years, median time on dialysis before inclusion was 16?months, and median residual diuresis was 600?ml. The patients were prospectively followed up to 4?years, and an analysis of factors affecting survival was performed.

Results

Thirteen patients from the initial cohort of 51 (25.5?%) survived the whole 48-month observation period: 10 HD patients (37?%) and 3 PD patients (12.5?%). Annual mortality rate was 28.2?%: 37.4?% on PD vs. 20.9?% on HD. The dialysis modality had a significant impact on patients?? survival (p?=?0.049; Cox F-test). The independent mortality risk factors in the Cox proportional hazard regression model were higher plasma pro-atrial natriuretic peptide (pro-ANP) (p?=?0.006), lower residual diuresis (p?=?0.048), and lower systolic blood pressure (BP) value (p?=?0.039).

Conclusions

Paramount for the survival of the elderly on dialysis is adequate extracellular volume control. Residual renal function is a protective factor for the survival of elderly HD patients. This observation is novel, not previously reported in an elderly dialysis population.     

Effect of combination of fractional CO<Subscript>2</Subscript> laser and narrow-band ultraviolet B versus narrow-band ultraviolet B in the treatment of non-segmental vitiligo

The present study was designed to evaluate the effect of combining fractional CO₂ laser with narrow-band ultraviolet B (NB-UVB) versus NB-UVB in the treatment of non-segmental vitiligo. The study included 20 patients with non-segmental stable vitiligo. They were divided into two groups. Group I received a single session of fractional CO₂ laser therapy on the right side of the body followed by NB-UVB phototherapy twice per week for 8 weeks. Group II received a second session of fractional CO₂ laser therapy after 4 weeks from starting treatment with NB-UVB. The vitiligo lesions were assessed before treatment and after 8 weeks of treatment by VASI. At the end of the study period, the vitiligo area score index (VASI) in group I decreased insignificantly on both the right (?2.6%) and left (?16.4%) sides. In group II, VASI increased insignificantly on the right (+14.4%) and left (+2.5%) sides. Using Adobe Photoshop CS6 extended program to measure the area of vitiligo lesions, group I showed a decrease of ?1.02 and ?6.12% in the mean area percentage change of vitiligo lesions on the right and left sides, respectively. In group II the change was +9.84 and +9.13% on the right and left sides, respectively. In conclusion, combining fractional CO₂ laser with NB-UVB for the treatment of non-segmental vitiligo did not show any significant advantage over treatment with NB-UVB alone. Further study of this combination for longer durations in the treatment of vitiligo is recommended.     

Facet joint violation after open and percutaneous posterior instrumentation: a comparative study

Purpose

Posterior instrumentation is the state-of-the-art surgical treatment for fractures of the thoracic and lumbar spine. Options for pedicle screw placement comprise open or minimally invasive techniques. Open instrumentation causes large approach related muscle detachment, which minimally invasive techniques aim to reduce. However, concerns of accurate pedicle screw placement are still a matter of debate. Beside neurological complications due to pedicle screw malplacement, also affection of the facet joints and thus motion dependent pain is known as a complication. The aim of this study was to assess accuracy of pedicle screw placement concerning facet joint violation (FJV) after open- and minimally invasive posterior instrumentation.

Methods

A retrospective data analysis of postoperative computer tomographic scans of 219 patients (1124 pedicle screws) was conducted. A total of 116 patients underwent open screw insertion (634 screws) and 103 patients underwent minimally invasive, percutaneous screw insertion (490 screws).

Results

In the lumbar spine (segments L3, L4, L5), there were significantly more and higher grade (open = 0.55 vs. percutaneous = 1.2; p = 0.001) FJV’s after percutaneously compared to openly inserted screws. In the thoracic spine, no significant difference concerning rate and grade of FJV was found (p > 0.56).

Conclusion

FJV is more likely to occur in percutaneously placed pedicle screws. Additionally, higher grade FJV’s occur after percutaneous instrumentation. However, in the thoracic spine we didn’t find a significant difference between open and percutaneous technique. Our results suggest a precise consideration concerning surgical technique according to the fractured vertebrae in the light of the individual anatomic structures in the preop CT.

     

Ultrasound-guided supraclavicular cannulation of left brachiocephalic versus right internal jugular vein: Comparative analysis of central venous catheter-associated complications

Aims

Central venous catheters are essential for the management of pediatric cardiac surgery patients. Recently, an ultrasound-guided access via a supraclavicular approach to the brachiocephalic vein has been described. Central venous catheters are associated with a relevant number of complications in pediatric patients. In this study, we evaluated the frequency of complications of left brachiocephalic vein access compared with right internal jugular vein standard access in children undergoing cardiac surgery.

Methods

Retrospective analysis of all pediatric cases at our tertiary care university hospital over a two-year period receiving central venous catheters for cardiac surgery. Primary endpoint: Frequency of complications associated with central venous catheters inserted via the left brachiocephalic vein vs. right internal jugular vein. Complications were defined as: chylothorax, deep vein thrombosis, sepsis, or delayed chest closure. Secondary endpoints: Evaluation of the insertion depth of the catheter using a height-based formula without adjustment for side used.

Results

Initially, 504 placed catheters were identified. Following inclusion and exclusion criteria, 480 placed catheters remained for final analysis. Overall complications were reported in 68/480 (14.2%) cases. There was no difference in the frequency of all complications in the left brachiocephalic vein vs. the right internal jugular vein group (15.49% vs. 13.65%; OR = 1.16 [0.64; 2.07]), nor was there any difference considering the most relevant complications chylothorax (7.7% vs. 8.6%; OR = 0.89 [0.39; 1.91]) and thrombosis (5.6% vs. 4.5%; OR = 1.28 [0.46; 3.31]). The mean deviation from the optimal insertion depth was left brachiocephalic vein vs. right internal jugular vein 5.38 ± 13.6 mm and 4.94 ± 15.1 mm, respectively.

Conclusions

Among children undergoing cardiac surgery, there is no significant difference between the supraclavicular approach to the left brachiocephalic vein and the right internal jugular vein regarding complications. For both approaches, a universal formula can be used to determine the correct insertion depth.