MRI as complementary tool added to ultrasound in the diagnosis of fetal renal abnormalities – any added value?

Purpose

To assess the potential role of magnetic resonance imaging (MRI) as a complementary diagnostic tool to ultrasonography (US) in the diagnosis of fetal renal anomalies in pregnant women with oligohydramnios in the absence of amniotic membrane rupture.

Methods

Ninety pregnant women, with oligohydramnios were prospectively evaluated using both US and MRI. Prenatal findings were correlated with the babies’ outcome.

Results

MRI studies of diagnostic quality were obtained in all fetuses. The US and MRI findings were concordant in 79 (87.8%) of the fetuses. MRI modified and changed the diagnosis in 11 fetuses (12.2%), these were five fetuses in which US diagnosis was inconclusive, five cases in which the diagnosis changed from bilateral renal agenesis to unilateral agenesis with the other kidney multicystic dysplastic kidney (MCDK), and in the remaining fetuses the modification was from bilateral renal agenesis to unilateral agenesis with the other kidney structurally normal.Concordant findings for the prenatal US and MRI scans were seen in 100% of the autosomal recessive polycystic kidney disease (APCKD), 96% of MCDK, and 92.9% of bilateral normal kidneys.

Conclusion

MRI is of value in cases of oligohydramnios in limited circumstance when US findings were inconclusive.     

Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in relation to geographic locations and in migrant populations

Over the past two decades a worldwide increase in the incidence of skin cancer to near epidemic proportions has led to increased morbidity and appreciating cost. Well known risk factors include UV radiation, x or gamma irradiation, chemical carcinogens, genetic aberrations, and immunosuppression. This article reviews and analyzes the evidence for UV radiations role in the pathogenesis of nonmelanoma skin cancer (NMSC). Observations on the incidence of NMSC among migrants to temperate regions show an increase in both basal cell carcinoma and squamous cell carcinoma. There is also an increase in NMSC in areas with lower latitudes. Irradiation of human skin grafted to animals and animal models that develop NMSC lend further support to the role of UV radiation in the pathogenesis of NMSC. In the forthcoming Part II of this review, epidemiologic evidence will be presented attesting to the relationship between UV radiation and NMSC.     

Polysialylation and lipopolysaccharide‐induced shedding of E‐selectin ligand‐1 and neuropilin‐2 by microglia and THP‐1 macrophages

Microglia are tissue macrophages and mediators of innate immune responses in the brain. The protein‐modifying glycan polysialic acid (polySia) is implicated in modulating microglia activity. Cultured murine microglia maintain a pool of Golgi‐confined polySia, which is depleted in response to lipopolysaccharide (LPS)‐induced activation. Polysialylated neuropilin‐2 (polySia‐NRP2) contributes to this pool but further polySia protein carriers have remained elusive. Here, we use organotypic brain slice cultures to demonstrate that injury‐induced activation of microglia initiates Golgi‐confined polySia expression in situ. An unbiased glycoproteomic approach with stem cell‐derived microglia identifies E‐selectin ligand‐1 (ESL‐1) as a novel polySia acceptor. Together with polySia‐NRP2, polySia‐ESL‐1 is also detected in primary cultured microglia, in brain slice cultures and in phorbol ester‐induced THP‐1 macrophages. Induction of stem cell‐derived microglia, activated microglia in brain slice cultures and THP‐1 macrophages by LPS, but not interleukin‐4, causes polySia depletion and, as shown for stem cell‐derived microglia, a metalloproteinase‐dependent release of polySia‐ESL‐1 and polySia‐NRP2. Moreover, soluble polySia attenuates LPS‐induced production of nitric oxide and proinflammatory cytokines. Thus, shedding of polySia‐ESL‐1 and polySia‐NRP2 after LPS‐induced activation of microglia and THP‐1 macrophages may constitute a mechanism for negative feedback regulation. GLIA 2016 GLIA 2016;64:1314–1330     

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.     

Predictors for moderate to severe acute postoperative pain after total hip and knee replacement

Purpose

The ability to identify and focus care to patients at higher risk of moderate to severe postoperative pain should improve analgesia and patient satisfaction, and may affect reimbursement. We undertook this multi-centre cross-sectional study to identify preoperative risk factors for moderate to severe pain after total hip (THR) and knee (TKR) replacement.

Methods

A total of 897 patients were identified from electronic medical records. Preoperative information and anaesthetic technique was gained by retrospective chart review. The primary outcomes were moderate to severe pain (pain score ≥ 4/10) at rest and with activity on postoperative day one. Logistic regression was performed to identify predictors for moderate to severe pain.

Results

Moderate to severe pain was reported by 20 % at rest and 33 % with activity. Predictors for pain at rest were female gender (OR 1.10 with 95 % CI 1.01–1.20), younger age (0.96, 0.94–0.99), increased BMI (1.02, 1.01–1.03), TKR vs. THR (3.21, 2.73–3.78), increased severity of preoperative pain at the surgical site (1.15, 1.03–1.30), preoperative use of opioids (1.63, 1.32–2.01), and general anaesthesia (8.51, 2.13–33.98). Predictors for pain with activity were TKR vs. THR (1.42, 1.28–1.57), increased severity of preoperative pain at the surgical site (1.11, 1.04–1.19), general anaesthesia (9.02, 3.68–22.07), preoperative use of anti-convulsants (1.78, 1.32–2.40) and anti-depressants (1.50, 1.08–2.80), and prior surgery at the surgical site (1.28, 1.05–1.57).

Conclusions

Our findings provide clinical guidance for preoperative stratification of patients for more intensive management potentially including education, nursing staffing, and referral to specialised pain management.     

The effect of low-intensity pulsed ultrasound on callus maturation in tibial distraction osteogenesis

Callus distraction is currently the most popular method of bone lengthening. Prolonged treatment time is one of its major problems. In this study, we investigated the effect of low-intensity pulsed ultrasound on tibial distraction osteogenesis. We managed 20 patients with tibial defects ranging from 5 cm to 8 cm with distraction osteogenesis using the Ilizarov external fixator. After the completion of distraction, ten patients received daily 20 min of low-intensity pulsed ultrasound stimulation (30 mW/cm²) onto the bone lengthening site (group A) while rigid fixation was maintained in the remaining patients (group B). All patients were followed with weekly radiographs to determine the formation of an external cortex and an intramedullary canal, at which time the fixator was removed. The mean healing index in group A was 30 (27–36) days/cm while it was 48 (42–75) days/cm in group B. In group B, one patient failed to consolidate the regenerated bone. Low-intensity pulsed ultrasound stimulation is highly effective in achieving maturation of bone and reducing time of distraction osteogenesis.

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Résumé La distraction du cal est la méthode dallongement de los la plus populaire actuellement. La longueur du traitement est un de ses problèmes majeurs. Nous avons étudié leffet des ultrasons pulsés de basse intensité sur lostéogenèse dans la distraction tibiale.Nous avons traité 20 malades présentant un défaut tibial de 5 à 8 centimètres avec ostéogenèse de distraction utilisant un fixateur externe dIlizarov. Après lachèvement de la distraction 10 malades ont reçu quotidiennement une stimulation par ultrasons (30 mW/cm²) sur lemplacement de lallongement osseux pendant 20 minutes (groupe A), pendant que la fixation rigide était maintenue pour le restant des malades (groupe B). Tous les malades ont été suivis avec des radiographies hebdomadaires pour déterminer la formation dun cortex périphérique et dun canal intramédullaire au moment ou le fixateur a été enlevé. Lindex de consolidation moyen dans le groupe A était 30 (27–36) jours/cm pendant quil était 48 (42–75) jours/cm dans le groupe B. Dans le groupe B un malade na pas consolidé los régénéré. La stimulation par ultrasons pulsés de basse intensité est très efficace pour favoriser la maturation osseuse et réduire le temps dostéogenèse dans la distraction.

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None of the authors received financial support for this study.     

Effects of JAK3 inhibition with CP-690,550 on immune cell populations and their functions in nonhuman primate recipients of kidney allografts

BACKGROUND: Janus Kinase (JAK) 3 is a tyrosine kinase essential for proper signal transduction downstream of selected cytokine receptors and for robust T-cell and natural killer cells activation and function. JAK3 inhibition with CP-690,550 prevents acute allograft rejection. To provide further insight into the mechanisms of efficacy, we investigated the immunomodulatory effects of CP-690,550 in vitro and in vivo in nonhuman primates. METHODS: Pharmacodynamic assessments of lymphocyte activation, function, proliferation and phenotype were performed in three settings: in vitro in whole blood isolated from untransplanted cynomolgus monkeys (cynos), in vivo in blood from untransplanted cynos dosed with CP-690,550 for 8 days, and in vivo in blood from transplanted cynos immunosuppressed with CP-690,550. Cell surface activation markers expression, IL-2- enhanced IFN-gamma production, lymphocyte proliferation and immune cell phenotype analyzes were performed with multiparametric flow cytometry. RESULTS: In vitro exposure to CP-690,550 resulted in significant reduction of IL-2-enhanced IFN-gamma production by T-cells (maximum inhibition of 55-63%), T-cell surface expression of CD25 (50% inhibitory concentration (IC50); 0.18 microM) and CD71 (IC50; 1.6 microM), and T-cell proliferative capacities measured by proliferating cell nuclear antigen expression (IC50; 0.87 microM). Similar results were observed in animals dosed with CP-690,550. In addition, transplanted animals displayed significant reduction of NK cell (90% from baseline) and T-cell numbers whereas CD8 effector memory T-cell populations were unaffected. CONCLUSIONS: Potent in vitro and in vivo immunomodulatory effects of the JAK3 inhibitor CP-690,550 likely contribute to its efficacy in the prevention of organ allograft rejection.     

Can diffusion tensor imaging predict motor power affection after moderate traumatic brain injury?

Objective

To determine whether commissural and projection fibers fractional anisotropy (FA) abnormalities can help in the prediction of long-term outcome of motor power affection after moderately severe traumatic brain injury (TBI).

Methods

MRI protocol included diffusion tensor imaging (DTI) and was performed for 32 patients with moderate TBI and 32 matched control subjects. Regions of interests were applied in the FA maps in the corpus callosum, internal capsules posterior limb, and cerebral peduncles. Results were compared in patients with motor power affection and patients without motor power affection to the control group.

Results

All patients had FA values lower than the control group with significance differences in the corpus callosum. Patient group with weakness had FA values lower than the control groups with significance differences in the posterior limb of the left internal capsules (p = 0.001) and left cerebral peduncles (p < 0.001). Significant differences were found when comparing the posterior limb of the left internal capsule (p = 0.002) and left cerebral peduncle (p = 0.022) to the right side in the weakness group.

Conclusion

FA values measured in the acute stage provided information about associated and projectional fibers disruptions, which have a prognostic value about motor power affection.     

Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats

Bone marrow stem cells participate in tissue repair processes and may have a role in wound healing. Diabetes is characterised by delayed and poor wound healing. We investigated the potential of bone marrow-derived mesenchymal stromal cells (BMSCs) to promote healing of fascial wounds in diabetic rats. After manifestation of streptozotocin (STZ)-induced diabetic state for 5 weeks in male adult Sprague-Dawley rats, healing of fascial wounds was severely compromised. Compromised wound healing in diabetic rats was characterised by excessive polymorphonuclear cell infiltration, lack of granulation tissue formation, deficit of collagen and growth factor [transforming growth factor (TGF-beta), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor PDGF-BB and keratinocyte growth factor (KGF)] expression in the wound tissue and significant decrease in biomechanical strength of wounds. Treatment with BMSC systemically or locally at the wound site improved the wound-breaking strength (WBS) of fascial wounds. The improvement in WBS was associated with an immediate and significant increase in collagen levels (types I-V) in the wound bed. In addition, treatment with BMSCs increased the expression of growth factors critical to proper repair and regeneration of the damaged tissue moderately (TGF-beta, KGF) to markedly (EGF, VEGF, PDGF-BB). These data suggest that cell therapy with BMSCs has the potential to augment healing of the diabetic wounds.     

Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.