Association between Mediterranean diet adherence and peripheral artery disease in type 2 diabetes mellitus: An observational study.

INTRODUCTION: To evaluate the relationship between adherence to the Mediterranean diet (MD) and periphereal artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM). METHODS: An observational sectional study was conducted with 174 patients diagnosed with T2DM, of which 78 patients had PAD. A patient was considered to have PAD if they obtained an ankle-brachial index (ABI) < 0.9 and/or absence of both distal pulses in one of the two feet. Data on sociodemographic and anthropometric variables, physical activity, smoking habits, biochemical blood parameters, and comorbidities were recorded. Good adherence to the MD was considered with a score ≥ 9 in MEDAS-14. Vascular factors independently associated with adherence to the MD in patients with T2DM were identified through multivariate logistic regression analysis. RESULTS: ABI, DFU, intermittent claudication and pedal pulse absence correlated with MD adherence. DFU, intermittent claudication and posterior tibial pulse absence were associated with the final score obtained in the MEDAS-14. Nut consumption, white meat preference and sautéed dish intake were associated with PAD presence. Multivariate analysis linked MD adherence to sex (OR = 0.044, 95 % CI 0.003-0619), age (OR = 0.139, 95 % CI 0.029-0.666), duration of T2DM (OR = 7.383, 95 % CI 1.523-35.779) and age at diagnosis of T2DM (OR = 6082, 95 % IC 1.415-26.136), as well as the presence of DFU (OR = 0.000, 95 % IC 0.000-0.370) and intermittent claudication (OR = 0.004, 95 % IC 0.000-0.534). CONCLUSIONS: Adherence to the MD is associated with a reduction in vascular complications in T2DM, highlighting its potential as a dietary intervention strategy.

Systemic Inflammation In Asymptomatic Hyperuricemia With Sonographic Crystal Deposits, Including A Comparison With Normouricemia And Gout.

OBJECTIVE: To describe the inflammatory profile of asymptomatic hyperuricemia (AH) with ultrasound evidence of monosodium urate (MSU) crystals (AH-MSUpos), vs AH without deposits (AH-MSUneg), intercritical gout, and normouricemia. METHODS: Based on serum urate levels, musculoskeletal ultrasound, and history of flares, we divided 122 participants into four groups: normouricemia, AH-MSUneg, AH-MSUpos, and intercritical gout. We tested four ultrasound definitions for MSU deposition in AH: grade 2-3 (G2-3) double contour and/or tophi, G1-3 double contour and/or tophi, G1-3 Stewart scheme (double contour sign in knee cartilage and/or first metatarsophalangeal joint and/or tophi in first metatarsophalangeal joint), and G2-3 Stewart scheme. Serum acute phase reactants, cytokines, pyroptosis derivates, and neutrophil-related proteins were measured and compared between groups. A linear regression model was fitted to correlate crystal and inflammatory burden (measured by ultrasound) with inflammatory markers in hyperuricemics. RESULTS: Rates of MSU deposition in AH ranged from 26.0% to 68.8%, depending on the definition used. Levels of CRP, leukocytes, IL-1RA, IL-6, sIL-6R, IL-18, TNF-α, TGF-ß, and galectin-3 were higher in hyperuricemics vs normouricemics. Sex, obesity, and comorbidity scores influenced some comparisons. We saw no differences comparing AH-MSUpos  vs AH-MSUneg groups, except for higher calprotectin using G1-3 sonographic definitions and higher CRP and TGF-ß when restricted to women and obese participants. CONCLUSIONS: Hyperuricemia is associated with substantial inflammation and some degree of active pyroptosis. Four different ultrasound definitions for AH with MSU deposits yielded similar findings, although we noted some differences in calprotectin, CRP, and TGF-ß. Sex, obesity, and comorbidities influenced some inflammatory responses.

Prevalence of crystal deposits in asymptomatic hyperuricemia according to different scanning definitions: A comparative study.

BACKGROUND/AIM: The appropriate sonographic protocol for assessing urate crystal deposits in asymptomatic hyperuricemia (AH) is undefined, as well as how the choice would impact on deposit rates and accompanying sonographic, clinical and laboratory features. METHODS: Patients with AH (serum urate ≥7 mg/dL) underwent musculoskeletal ultrasound of 10 locations for OMERACT elementary gout lesions (double contour [DC] signs, tophi, aggregates). Different definitions for AH with deposits were applied, varying according to deposits (any deposits; only DC and/or tophi); gradation (any grade; only grade 2-3 deposits), location (10 locations; 4-joint scheme including knees and 1MTPs; >1 location with deposits), or pre-defined definitions (DC sign in femoral condyles/1MTP and/or tophi in 1MTP). We evaluated crystal deposits rates and compared between other sonographic features, clinical and laboratory variables. RESULTS: Seventy-seven participants with AH showed a median 1 location (IQR 0-2) with tophi, 1 (IQR 1-2) with aggregates, and 0 locations (IQR 0-1) with DC sign. The deposition rate ranged from 23.4% (in >1 location with grade 2-3 DC or tophi) to 87.0% (in any deposit in all 10 locations). Accompanying inflammation - assessed by a positive power-Doppler (PD) signal - and erosions were found in 19.5% and 28.4% of participants, respectively. Positive PD signal was better discriminated by criteria requiring grade 2-3 or >1 location with lesions. Erosions and the different clinical and laboratory variables were similar among protocols. CONCLUSION: Rates of sonographic deposition in AH varied dramatically among studied protocols, while some could discriminate accompanying inflammation, all highlighting the need for a validated, consensus-based definition.

Exploring the influence of dietary habits on foot risk in type 2 diabetes patients: An observational study.

BACKGROUND & AIM: To date, there are no studies demonstrating the impact of the Mediterranean diet on the risk of diabetic foot ulcer. The aim of this research was to examine the connection between adherence to the Mediterranean diet and the level of risk of diabetic foot ulcers in individuals with type 2 diabetes. METHODS: Observational pilot study collecting sociodemographic, anthropometric, lifestyle, and type 2 diabetes-related data. Loss of protective sensation was assessed using the Semmes Weinstein 5.07-10 g monofilament, considered altered when not perceived in four points. Vascular status was assessed by palpating pulses and ankle-brachial index, indicating peripheral arterial disease if ankle-brachial index was less than 0.9 or if both pulses were absent. Foot deformities were recorded. The risk of diabetic foot ulcers was stratified into two categories: no risk and risk of diabetic foot ulcers. Adherence to the Mediterranean diet was evaluated using the Mediterranean Diet Adherence Screener-14 questionnaire (good adherence with score >7). RESULTS: Of the 174 patients with type 2 diabetes mellitus who participated (61.5% men and 38.5% women) with a mean age of 69.56 ± 8.86 years and a mean duration of type 2 diabetes of 15.34 ± 9.83 years. Non-adherent patients to the Mediterranean diet exhibited a higher association of diabetic foot ulcers (p = 0.030) and a lower average score on the Mediterranean Diet Adherence Screener-14 (p = 0.011). Additionally, a lower incidence of diabetic foot ulcers was observed in those who consumed nuts three or more times a week (p = 0.003) and sautéed foods two or more times a week (p = 0.003). Multivariate analysis highlighted the importance of physical activity (OR = 0.25, 95% CI 0.11-0.54; p < 0.001), podiatric treatment (OR = 2.59, 95% CI 1.21-5.56; p = 0.014), and duration of type 2 diabetes (OR = 3.25, 95% CI 1.76-5.99; p < 0.001) as significantly associated factors related to the risk of diabetic foot ulcers. CONCLUSIONS: Adhering to the Mediterranean diet correlates with a lower incidence of diabetic foot ulcers in individuals diagnosed with type 2 diabetes mellitus. Furthermore, factors such as regular physical activity, podiatric treatment, and the duration of type 2 diabetes mellitus emerge as pivotal in preventing diabetic foot ulcers.

Contribution of molecular analysis to the typification of the non-functioning pituitary adenomas.

AIM: The WHO Classification of Tumours of Endocrine Organs considers the inmunohistochemical characterization of pituitary adenomas (PA) as mandatory for patient diagnosis. Recent advances in the knowledge of the molecular patterns of these tumours could complement this classification with gene expression profiling. METHODS: Within the context of the Spanish Molecular Registry of Pituitary Adenomas (REMAH), a multicentre clinical-basic research project, we analysed the molecular phenotype of 142 PAs with complete IHC and clinical information. Gene expression levels of all pituitary hormones, type 1 corticotrophin-releasing hormone receptor, dopamine receptors and arginine vasopressin receptor 1b were measured by quantitative real-time polymerase chain reaction. In addition, we used three housekeeping genes for normalization and a pool of nine healthy pituitary glands from autopsies as calibration reference standard. RESULTS: Based on the clinically functioning PA (FPA: somatotroph, corticotroph, thyrotroph and lactotroph adenomas), we established the interquartile range of relative expression for all genes studied in each PA subtype. That allowed molecularly the different PA subtypes, including the clinically non-functioning PA (NFPA). Afterwards, we estimated the concordance of the molecular and immunohistochemical classification with clinical diagnosis in FPA and between them in NFPA. The kappa values were higher in molecular than in immunohistochemical classification in FPA and showed a bad concordance in all NFPA subtypes. CONCLUSIONS: According to these results, the molecular characterization of the PA complements the IHC analysis, allowing a better typification of the NFPA.

Severe sleep apnea-hypopnea syndrome is related to left ventricle dysfunction and hypertrophy in acromegalic patients.

OBJECTIVE: To assess whether sleep apnea-hypopnea syndrome (SAHS) is a risk factor for development of acromegalic cardiomyopathy. METHODS: A descriptive, cross-sectional study of 32 patients with acromegaly (15 categorized as non-controlled-NCA and 17 as controlled-CA) compared to 20 matched controls (by sex, age, and BMI) referred to the pulmonology department for suspected SAHS. Polysomnography, echocardiography (M-mode, 2-dimensional, and Doppler), and 12-lead electrocardiography were performed in all participants. Development of cardiac morbidity (ischemia heart disease or heart failure) was evaluated after 7 years. RESULTS: SAHS was diagnosed in 81.3% of patients with acromegaly and 85% of controls. Mild SAHS was more common in CA than in NCA patients (31.3% vs. 0%, p=0.048). There was a trend to greater prevalence of left ventricular diastolic dysfunction (LVDD) in acromegalic patients as compared to controls (58.1% vs. 30%, p=0.05). Presence of severe SAHS in patients with acromegaly was related to greater risk of LVDD (90.9% vs. 40%, p=0.008; OR 2.3 [1.3-4.0]), LV hypertrophy (55.6% vs. 10.5%, p=0.02; OR 5.3 [1.3-22.2]), and cardiac events (87.5% vs. 35.6%; p=0.01; OR 7.53 [1.07-53.24]). CONCLUSION: SAHS is highly prevalent in patients with acromegaly. Only in these patients was severe SAHS associated to hypertrophy, LV diastolic dysfunction, and cardiac events.

Pituitary tumor transforming gene and insulin-like growth factor 1 receptor expression and immunohistochemical measurement of Ki-67 as potential prognostic markers of pituitary tumors aggressiveness.

INTRODUCTION AND OBJECTIVE: The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. MATERIALS AND METHODS: In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46±36 months. RESULTS: Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGF1R expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69±3.84 NCN vs. 5.44±3.55 NCN, p=0.014). CONCLUSIONS: Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.

Over-expression of vascular endothelial growth factor in pituitary adenomas is associated with extrasellar growth and recurrence.

Some pituitary adenomas (PA) demonstrate aggressive behavior with local invasion and recurrences. Angiogenesis is regarded as an essential step in the formation of solid tumors. The aim of this study is to find out whether angiogenic factors may have information about the aggressiveness of PA that could be useful in determining the frequency of follow-up and whether adjuvant therapy is necessary. In this retrospective descriptive study, we evaluated vascular endothelial growth factors (VEGF) and VEGF receptor (KDR) mRNA expression by RT-PCR analysis on 46 human PA samples. Clinical data, histological subtype and radiologic characteristics were studied to determine the associations between the variables and the pre-operative behavior of the tumor. In addition, we monitored 12 patients without adjuvant post-operative therapies over 46 months after surgery, determining progression of tumor remnants and its association with these markers. VEGF expression correlates with KDR expression (r = 0.40, p = 0.006). VEGF demonstrates different expression between histological subtypes (p = 0.036). The extension at magnetic resonance imaging showed that VEGF expression was related to suprasellar extension (p = 0.007), being expressed more on tumors with extrasellar growth than intrasellar ones (p = 0.008). Our results demonstrate a 27.5 times increased risk of extrasellar growth when VEGF expression exceeds 0.222 normalized copy number (NCN) (p = 0.002). Likewise, tumors with KDR greater than 0.750 NCN had less recurrence-free survival time (p = 0.032). Our results suggest that the expression of VEGF and its receptor could be a marker for poor outcome after partial tumor resection. These data should be considered in future studies evaluating angiogenic factors as therapeutic targets in patients with PA.

Effects of recombinant human growth hormone therapy in adults with Prader-Willi syndrome: a meta-analysis.

OBJECTIVE: Prader-Willi syndrome (PWS) is associated with GH deficiency, deleterious changes in body composition and function. As the effects of recombinant human GH (rhGH) in PWS adults have not been well established, we sought to conduct a meta-analysis of pertinent studies. DESIGN: Meta-analysis of studies examining the effects of rhGH therapy in PWS adults. PATIENTS: One hundred and thirty four PWS adults (75 men, 59 women). MEASUREMENTS: Literature searches, including publications (PubMed, EMBASE and the Cochrane Register), and abstracts presented at meetings through July 2011 describing studies of rhGH therapy in PWS adults; 8/1194 articles, describing unique cohorts, were included. Two authors independently extracted data and examined study quality. RESULTS: rhGH therapy for 12 months led to [weighted mean difference (95% CI)] decreased body fat [-2·91% (-3·90, -1·91)], visceral [-32·97 cm(2) (-55·67, -10·26)] and subcutaneous adiposity [-55·24 cm(2) (-89·05, -21·44)], and increased lean body mass (LBM) [2·41 Kg (1·32, 3·49)]. Similar changes in body fat [-2·89% (-4·69, -1·07)] and LBM [2·82 Kg (1·31, 4·33)] were found in longer studies. There were no changes in body mass index (BMI) or lipids. There was a small increase in fasting glucose [0·27 mmol/l (0·05, 0·49)] and trends towards higher fasting insulin [20·24 pmol/l (-0·55, 41·02)] and insulin resistance [HOMA: 0·60 (-0·04, 1·24)] after rhGH therapy for 12 months. CONCLUSIONS: In PWS adults, rhGH therapy led to decreased body adiposity and increased LBM without changes in BMI or lipids. There was a small increase in fasting glucose and trends towards higher insulin and insulin resistance.

Validation of the human chorionic gonadotropin immunoassay in cerebrospinal fluid for the diagnostic work-up of neurohypophyseal germinomas.

BACKGROUND: The measurement of human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) is useful for the differential diagnosis of suprasellar lesions. However, the concentrations that prove diagnostic for neurohypophyseal germinoma have not been well defined. In addition, the immunoassays used for such measurements are the same as those applied in serum, and few studies have been performed regarding the validation of such techniques in CSF. The present study aims to apply the Elecsys(®) hCG + ß immunoassay from Roche Diagnostics to measure hCG in CSF, as a useful tool in the diagnosis of neurohypophyseal germinomas in children and young adults. METHODS: Validation of the immunoassay involved calculation of the functional sensitivity and reference values for hCG in CSF in 35 controls in the absence of pregnancy, trophoblastic disease or tumour pathology. For the clinical application study, three patients diagnosed with neurohypophyseal germinoma have been reviewed. RESULTS: The functional sensitivity obtained was 0.4 IU/L. The reference values for hCG in CSF ranged from undetectable values to 0.7 IU/L. The hCG concentrations in CSF in the three studied patients, with confirmed diagnosis of neurohypophyseal germinoma, were 21.1, 32.6 and 23 IU/L, respectively. CONCLUSIONS: The Elecsys® hCG + ß immunoassay from Roche Diagnostics can be used to detect hCG in CSF with high precision. According to our results, CSF-hCG concentrations that exceed the established reference interval (undetectable values to 0.7 IU/L) in the presence of suprasellar lesions and hypophyseal stalk thickening must be considered pathological, establishing the need to exclude the presence of germinoma.

[Response to adjuvant therapy with potassium perchlorate in amiodarone-induced thyrotoxicosis: observations on three cases]. / A propósito de tres casos. Respuesta a la terapia adyuvante con perclorato potásico en la tirotoxicosis inducida por amiodarona.

INTRODUCTION: Amiodarone-induced thyrotoxicosis (AIT) is a common clinical disorder that may be life threatening and whose clinical manifestations and response to treatment may vary among patients. METHODS: We present three patients treated with amiodarone for atrial fibrillation who developed AIT at least 36 months after beginning the treatment. Thyrotoxicosis worsened the underlying cardiac disorders and was resistant to treatment based on the combination of dexamethasone 8-12 mg/day i.v., thioamides 45 mg/day p.o., beta blockers and potassium perchlorate at doses of 800 to 1000 mg per day p.o. Two of the patients attained sustained euthyroidism after 12 and 32 days of combined treatment, while the third required total thyroidectomy. CONCLUSION: The combination of thioamides with potassium perchlorate is an appropriate form of therapy for AIT in patients resistant to thioamides. The use of this combination should be evaluated in patients with mixed AIT or AIT of unclear etiology.

[Rol of pituitary tumour-transforming gene (PTTG) in the pituitary adenomas]. / Papel de pituitary tumour-transforming gene (PTTG) en los adenomas hipofisarios.

The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours.

Treatment of Graves' ophthalmopathy with high-dose intravenous methylprednisolone: a comparison of two dosing regimens.

RATIONALE AND OBJECTIVE: The treatment of active moderate-severe Graves' ophthalmopathy (GO) is based on the administration of highdose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens. MATERIAL AND METHODS: We carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderatesevere GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv (n=13); and regimen B (16 weeks): 4 cycles of 15 mg/kg, followed by 4 cycles of 7.5mg/kg, for a cumulative dose of 90 mg/kg (range, 4.9-7.4 g) (n=11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence). RESULTS: Mild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension - with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p>0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO. CONCLUSIONS: The treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A.