Idiopathic intracranial hypertension: A possible complication in the natural history of advanced prostate cancer

Idiopathic intracranial hypertension is a variety of intracranial hypertension that is extremely rare in men. Obesity and hypogonadism are the most important predictive factors. Etiological hypotheses include increased central venous pressure, and various hormonal and metabolic changes commonly found in obese patients. We described the case of an obese man with prostate cancer who showed a consistent bodyweight increase during treatment with taxanes and prednisone. He was hospitalized because of a severe loss of vision as a consequence of idiopathic intracranial hypertension. A complete symptom remission was obtained after 3 weeks of anti‐edema therapies (steroids, acetazolamide). Castration‐resistant prostate cancer is a risk factor for idiopathic intracranial hypertension. Long‐term androgen deprivation therapy, bodyweight increase, and fluid retention during chronic steroid administration and taxane chemotherapy might favor the disease onset. This severe complication has a good outcome, and should be suspected in the presence of symptoms and signs of intracranial hypertension.     

ASCO 2013: bevacizumab and glioblastoma – a marriage dissolution?

The prognosis of patients affected by glioblastoma (GBM) is grim albeit the integrated therapeutic approaches now available. Standard surgery followed by chemoradiation median overall survival (OS) reaches 15 months in clinical trials. Despite primary treatment, recurrence is the rule in patients with GBM and for them OS ranges from 6 to 9 months. In recent years, the therapeutic scenario has been profoundly changed in view of the promising results obtained by bevacizumab (Avastin ), the most promising anti-angiogenesis agent, in two clinical trials. The results of both trials were presented at the last ASCO meeting in Chicago. Progression free survival was significantly improved with an acceptable safety and tolerability profile but surprisingly quality of life was preserved only in the AVAGlio trial. However, both studies showed that overall survival was not improved adding bevacizumab to temozolomide and radiotherapy.     

Nutrient Intake in Italian Infants and Toddlers from North and South Italy: The Nutrintake 636 Study

We performed a cross-sectional study to compare the intake of energy, macronutrients, fiber, sodium and iron and the anthropometric status of infants and toddlers living in North (Milano) and South Italy (Catania). Nutrient intake was evaluated using a 7-day weighed food record. Out of 400 planned children aged 6 to 36 months, 390 (98%) were recruited, 189 in Milano and 201 in Catania. The mean (standard deviation) age was 17 (9) months in Milano and 17 (10) months in Catania. Anthropometry, energy intake and macronutrient intake were similar in Milano and Catania. However, iron intake was 27% lower and fiber intake 16% higher in Milano than in Catania. Despite normal anthropometry and energy intake, in the pooled sample there was a high intake of proteins, simple carbohydrates, saturated fats and sodium, and a low intake of iron and fiber compared to Italian reference values. This is the first study to report the macro- and micro-nutrient intake of children aged <12 months using the 7-day weighed food record and one of the very few studies that have employed such reference method in children from the general population.     

Allopregnanolone modulation of HPA axis function in the adult rat

Rationale

GABAergic neuronal circuits regulate neuroendocrine stress response, and the most potent positive endogenous modulator of GABA_A receptor function is allopregnanolone. This neurosteroid acts in a nongenomic manner to selectively increase the inhibitory signal meditated by GABA_A receptors; in addition, it also induces long-lasting changes in the expression of specific GABA_A receptor subunits in various brain regions, with consequent changes in receptor function.

Objective

The objective of this review is to summarize our findings on emotional state and stress responsiveness in three animal models in which basal brain concentrations of allopregnanolone differ. It is postulated that individual differences in allopregnanolone levels can influence general resilience.

Results

The results showed that there is an apparent correlation between endogenous levels of brain allopregnanolone and basal and stress-stimulated HPA axis activity.

Conclusion

The relationship between endogenous brain levels of allopregnanolone and HPA axis activity and function sustains the therapeutic potential of this neurosteroid for the treatment of stress-associated disorders.     

Analysis of potential influence factors on background urinary benzene concentration among a non-smoking,non-occupationally exposed general population sample

Objectives

Analytical difficulties and lack of a biological exposure index and reference values have prevented using unmetabolized urinary benzene (UB) excretion as a biomarker of low-level environmental exposure. To explore what environmental factors beyond active smoking may contribute to environmental exposure to benzene, we monitored UB excretion in a non-smoking, non-occupationally exposed sample of the general population.

Methods

Two spot urine samples were obtained from 86 non-smoking, non-occupationally exposed subjects, selected among a random sample of the general population of the metropolitan area of Cagliari (Sardinia, Italy), at 8:00 a.m. (UBm) and 8:00 p.m. (UBe). UB was measured by headspace solid-phase microextraction (HS-SPME) followed by gas chromatography–mass spectrometry analysis. Questionnaire information on personal and environmental exposures during the sampling day was gathered with personal interviews. Multivariate analysis of variance and multiple regression model were applied to investigate the role of such variables on the level of UB.

Results

The ninety-fifth percentile of UBe in this population was 311.5 ng/L, which is tentatively proposed as the UB guidance value for unexposed populations. UBm and urban residence were the only predictors of a significant increase in UBe excretion. Self-reported residential vehicular traffic will not account for the excess median value among urban residents; commuting time among urban residents showed a suggestive nonsignificant linear correlation with UBe, but the small sample size prevented reliable inference to be drawn. Age, environmental tobacco smoking, employment status and body mass index did not affect UB excretion.

Conclusions

Our findings support the use of unmetabolized UB as a specific and sensitive biomarker of low-level environmental exposure to benzene.     

Multimodality ultrasound assessment of the spleen: Normal appearances and emergency abnormalities

This paper summarizes the main splenic emergencies and their ultrasonographic findings to orient appropriate patient management. US requires minimal preparation time and allows to examine the parenchyma and to detect intraperitoneal fluid collections, which may be indirect evidence of solid organ injuries. In this paper, we analyze the role of B-mode, Doppler and Contrast-Enhanced Ultrasound in the diagnosis of splenic emergencies, with a particular focus on splenic infarction, infection, traumatic injuries and vascular splenic anomalies.     

Thymic Stromal Lymphopoietin Is Up‐Regulated in the Skin of Patients With Systemic Sclerosis and Induces Profibrotic Genes and Intracellular Signaling That Overlap With Those Induced by Interleukin‐13 and Transforming Growth Factor β

Objective

To explore the expression of thymic stromal lymphopoietin (TSLP) in patients with diffuse cutaneous systemic sclerosis (dcSSc) and compare its effects in vivo and in vitro with those of interleukin‐13 (IL‐13) and transforming growth factor β (TGFβ).

Methods

Skin biopsy specimens from patients with dcSSc (n = 14) and healthy controls (n = 13) were analyzed by immunohistochemistry and immunofluorescence for TSLP, TSLP receptor, CD4, CD8, CD31, and CD163 markers. Wild‐type, IL‐4Rα1–, and TSLP‐deficient mice were treated with TGFβ, IL‐13, poly(I‐C), or TSLP by osmotic pump. Human fibroblasts and peripheral blood mononuclear cells (PBMCs) were stimulated with TGFβ, IL‐13, poly(I‐C), or TSLP. Microarray analysis and quantitative polymerase chain reaction were performed to determine gene expression, and protein levels of phospho‐Smad2 and macrophage marker CD163 were tested.

Results

TSLP was highly expressed in the skin of dcSSc patients, more strongly in perivascular areas and in immune cells, and was produced mainly by CD163+ cells. The skin of TSLP‐treated mice showed up‐regulated clusters of gene expression that overlapped strongly with those in IL‐13– and TGFβ‐treated mice. TSLP up‐regulated specific genes, including CXCL9, proteasome, and interferon (IFN)–regulated genes. TSLP treatment in IL‐4Rα1–deficient mice promoted similar cutaneous inflammation as in wild‐type mice, though TSLP‐induced arginase 1, CCL2, and matrix metalloproteinase 12 messenger RNA levels were blocked. In PBMCs, TSLP up‐regulated tumor necrosis factor α, Mx‐1, IFNγ, CXCL9, and mannose receptor 1 gene expression. TSLP‐deficient mice treated with TGFβ showed less fibrosis and blocked expression of plasminogen activator inhibitor 1 and osteopontin 1. Poly(I‐C)–treated mice showed high levels of cutaneous TSLP.

Conclusion

TSLP is highly expressed in the skin of dcSSc patients and interacts in a complex manner with 2 other profibrotic cytokines, TGFβ and IL‐13, strongly suggesting that it might promote SSc fibrosis directly or indirectly by synergistically stimulating profibrotic genes, or production of these cytokines.

     

Albuminuria According to Status of Autoimmunity and Insulin Sensitivity Among Youth With Type 1 and Type 2 Diabetes

OBJECTIVE

To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes.

RESEARCH DESIGN AND METHODS

SEARCH is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA⁺/insulin-sensitive (IS) (n = 1,351); DAA⁺/insulin-resistant (IR) (n = 438); DAA⁻/IR (n = 379); and DAA⁻/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.

RESULTS

Adjusted UACR means across the four groups were as follows: DAA⁺/IS = 154 μg/mg; DAA⁺/IR = 137 μg/mg; DAA⁻/IR = 257 μg/mg; and DAA⁻/IS = 131 μg/mg (P < 0.005). Only DAA⁻/IR was significantly different. We performed post hoc multivariable regression analysis restricted to the two IR groups to explore the contribution of DAA status and insulin sensitivity (continuous) to the difference in UACR between the IR groups. Only insulin sensitivity was significantly associated with UACR (β = −0.54; P < 0.0001).

CONCLUSIONS

In youth with diabetes, the DAA⁻/IR group had a greater UACR than all other groups, possibly because of the greater magnitude of insulin resistance. Further exploration of the relationships between severity of insulin resistance, autoimmunity, and albuminuria in youth with diabetes is warranted.Previous reports suggested that the clinical course and factors contributing to the development and progression of diabetic nephropathy did not differ by diabetes type and that diabetic nephropathy was preceded by albuminuria that worsened over time (1,2). More recent data have further elucidated the natural history of diabetic kidney disease. In the absence of albuminuria, a significant number of people with diabetes, especially type 2, still develop a decline in glomerular filtration rate (3,4). Thus, there may be identifiable differences in the natural history of nephropathy inherent to the underlying diabetes type. Multiple pediatric diabetes cohorts have found a higher prevalence of albuminuria and progressive kidney failure in youth with a clinical diagnosis of type 2 diabetes than with type 1 diabetes (5–7). Such data suggest that insulin resistance, a key component of the pathophysiology of type 2 diabetes, may be an important contributor to diabetic nephropathy in youth with diabetes.The epidemic of overweight and obesity has made it increasingly difficult to clinically diagnose diabetes type, because insulin resistance and autoimmunity often coexist (8,9). Cohort studies of youth with type 1 diabetes have found a significant increase in microvascular and macrovascular diseases in those with concurrent insulin resistance (10–12). The prevalence of albuminuria in insulin-resistant (IR) individuals with type 1 diabetes has not been compared with individuals with type 2 diabetes. Thus, the role of autoimmunity and insulin resistance across the spectrum of diabetes types and the risk for microvascular complications warrant investigation. Herein, we investigate the magnitude of albuminuria according to the status of autoimmunity and insulin resistance in youth with newly diagnosed type 1 and type 2 diabetes.     

Prevalence and Potentially Reversible Factors Associated With Anorexia Among Older Nursing Home Residents: Results from the ULISSE Project

ObjectiveThe principal aims of the present study were to explore the prevalence of anorexia and the factors correlated to anorexia in a large population of older people living in nursing home. Secondary, we evaluated the impact of anorexia on 1-year survival.MethodsData are from baseline evaluation of 1904 participants enrolled in the Un Link Informatico sui Servizi Sanitari Esistenti per l’Anziano study, a project evaluating the quality of care for older persons living in an Italian nursing home. All participants underwent a standardized comprehensive evaluation using the Italian version of the inter Resident Assessment Instrument Minimum Data Set (version 2.0) for Nursing Home. We defined anorexia as the presence of lower food intake. The relationship between covariates and anorexia was estimated by deriving ORs and relative 95% CIs from multiple logistic regression models including anorexia as the dependent variable of interest. Hazard ratios and 95% CIs for mortality by anorexia were calculated.ResultsMore than 12% (240 participants) of the study sample suffered from anorexia, as defined by the presence of decreased food intake or the presence of poor appetite. Participants with functional impairment, dementia, behavior problems, chewing problems, renal failure, constipation, and depression, those treated with proton pump inhibitors and opioids had a nearly 2-fold increased risk of anorexia compared with participants not affected by these syndromes. Furthermore, participants with anorexia had a higher risk of death for all causes compared with nonanorexic participants (hazard ratio 2.26, 95% CI: 2.14–2.38).ConclusionsThe major finding is that potentially reversible causes, such as depression, pharmacologic therapies, and chewing problems, were strongly and independently associated with anorexia among frail older people living in nursing home. Furthermore, anorexia was associated with higher rate of mortality, independently of age and other clinical and functional variables.     

Exercise training early after acute myocardial infarction reduces stress-induced hypoperfusion and improves left ventricular function

Purpose

Exercise training might exert its beneficial effects on myocardial perfusion by inducing coronary vascular adaptations or enhancing collateralization. We evaluated whether long-term exercise-based cardiac rehabilitation started early after ST-elevation acute myocardial infarction (STEMI) improves myocardial perfusion and left ventricular (LV) function.

Methods

Forty-six patients with recent STEMI and residual inducible hypoperfusion were randomized into two groups: 25 enrolled in a 6-month outpatient exercise-based cardiac rehabilitation programme (group T) and 21 discharged with generic instructions for maintaining physical activity and correct lifestyle (group C). All patients underwent cardiopulmonary exercise test and dipyridamole rest gated myocardial perfusion single photon emission computed tomography within 1 week after STEMI and at 6-month follow-up.

Results

At follow-up, group T showed an improvement in peak oxygen consumption, oxygen pulse and in the slope of increase in ventilation over carbon dioxide output (all p?<?0.01) associated with a reduction of stress-induced hypoperfusion (p?<?0.01) and an improvement in resting and post-stress wall motion score indexes (both p?<?0.01), resting and post-stress wall thickening score indexes (both p?<?0.05) and resting and post-stress LV ejection fraction (both p?<?0.05). On the contrary, no changes in cardiopulmonary indexes, myocardial perfusion and LV function parameters were observed in group C at follow-up.

Conclusion

Exercise training started early after STEMI reduces stress-induced hypoperfusion and improves LV function and contractility. Exercise-induced changes in myocardial perfusion and function were associated with the absence of unfavourable LV remodelling and with an improvement of cardiovascular functional capacity.