Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case-control study.

PURPOSE: Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs. METHODS: We performed a retrospective case-control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors. RESULTS: Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31-3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39-4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18-2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08-0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05-5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08-5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28-5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11-3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38-4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08-3.33, p = 0.026). CONCLUSION: This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.

NECI: N-Electron Configuration Interaction with an emphasis on state-of-the-art stochastic methods.

We present NECI, a state-of-the-art implementation of the Full Configuration Interaction Quantum Monte Carlo (FCIQMC) algorithm, a method based on a stochastic application of the Hamiltonian matrix on a sparse sampling of the wave function. The program utilizes a very powerful parallelization and scales efficiently to more than 24 000 central processing unit cores. In this paper, we describe the core functionalities of NECI and its recent developments. This includes the capabilities to calculate ground and excited state energies, properties via the one- and two-body reduced density matrices, as well as spectral and Green's functions for ab initio and model systems. A number of enhancements of the bare FCIQMC algorithm are available within NECI, allowing us to use a partially deterministic formulation of the algorithm, working in a spin-adapted basis or supporting transcorrelated Hamiltonians. NECI supports the FCIDUMP file format for integrals, supplying a convenient interface to numerous quantum chemistry programs, and it is licensed under GPL-3.0.

Thyroid profile during the alternative Sunitinib dosing 2/1 schedule in metastatic renal cell carcinoma.

PURPOSE: Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival. METHODS: We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months. RESULTS: Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 µI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 µI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285). CONCLUSIONS: This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 µI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.

Gender in Endocrine Diseases: Role of Sex Gonadal Hormones.

Gender- and sex- related differences represent a new frontier towards patient-tailored medicine, taking into account that theoretically every medical specialty can be influenced by both of them. Sex hormones define the differences between males and females, and the different endocrine environment promoted by estrogens, progesterone, testosterone, and their precursors might influence both human physiology and pathophysiology. With the term Gender we refer, instead, to behaviors, roles, expectations, and activities carried out by the individual in society. In other words, "gender" refers to a sociocultural sphere of the individual, whereas "sex" only defines the biological sex. In the last decade, increasing attention has been paid to understand the influence that gender can have on both the human physiology and pathogenesis of diseases. Even the clinical response to therapy may be influenced by sex hormones and gender, but further research is needed to investigate and clarify how they can affect the human pathophysiology. The path to a tailored medicine in which every patient is able to receive early diagnosis, risk assessments, and optimal treatments cannot exclude the importance of gender. In this review, we have focused our attention on the involvement of sex hormones and gender on different endocrine diseases.

Projector Quantum Monte Carlo Method for Nonlinear Wave Functions.

We reformulate the projected imaginary-time evolution of the full configuration interaction quantum Monte Carlo method in terms of a Lagrangian minimization. This naturally leads to the admission of polynomial complex wave function parametrizations, circumventing the exponential scaling of the approach. While previously these functions have traditionally inhabited the domain of variational Monte Carlo approaches, we consider recent developments for the identification of deep-learning neural networks to optimize this Lagrangian, which can be written as a modification of the propagator for the wave function dynamics. We demonstrate this approach with a form of tensor network state, and use it to find solutions to the strongly correlated Hubbard model, as well as its application to a fully periodic ab initio graphene sheet. The number of variables which can be simultaneously optimized greatly exceeds alternative formulations of variational Monte Carlo methods, allowing for systematic improvability of the wave function flexibility towards exactness for a number of different forms, while blurring the line between traditional variational and projector quantum Monte Carlo approaches.

Algoplus performance to detect pain in depressed and/or demented old patients.

BACKGROUND: Algoplus detects acute pain in non-verbal old patients (NVOP) with good psychometric properties. However, depression or dementia might modify the Algoplus score and/or item expression. Algoplus performances on demented and/or depressed old populations were tested. METHODS: This multicentre cross-sectional study included patients ≥65 years old with or without pain assigned to depression, dementia, depression & dementia or control groups. Each group was subjected to the Numerical Rating Scale (NRS) and behavioural scales (Algoplus, Doloplus). Depression and/or dementia status was rated and confirmed by blinded experts. Algoplus psychometric properties tested were: discriminant validity, convergent validity, item analysis, sensitivity to change after pain treatment and threshold determination. RESULTS: The analysis included 171 patients (mean age 82.3 ± 6.3 years). Patients with and without pain in each group were comparable for age in all subgroups, except the older dementia subgroup. The mean Algoplus score was significantly higher for patients with than without pain, regardless of group assignment (Wilcoxon signed-rank test, p < 0.001). Algoplus and NRS or Doloplus had high convergent validity (respective Spearman correlation coefficients 0.79 and 0.87). The mean Algoplus score decreased significantly after starting pain management, regardless of group assignment. Some behaviours (i.e. "look") occurred more often in depressed patients, even those without pain. A threshold of 2 yielded respective sensitivity and specificity values of 95% and 96% for dementia patients, 62% and 79% for depressed patients, 96% and 71% for dementia & depressed patients, and 80% and 100% for controls. CONCLUSION: Algoplus accurately detected pain in depressed and/or dementia patients; and was sensitive to change after pain treatment. WHAT DOES THIS STUDY ADD?: Algoplus accurately detects pain in depressed and/or demented patients. A cut-off score of 2 accurately detects the need for pain management in these populations. Algoplus is sensitive to change after treating pain.

Propionyl-L-carnitine, L-arginine and niacin in sexual medicine: a nutraceutical approach to erectile dysfunction.

The application of nutraceuticals in the field of male sexual function -in particular for erectile dysfunction (ED)--remains relatively underexplored. In a group of 54 unselected men (35-75 years), consecutively presenting to our ED clinic and naive to other ED treatments, we carried out a single-blind, one-arm study to evaluate the effects of a 3-month supplementation with propionyl-L-carnitine, L-arginine and niacin on their sexual performance. All patients had the short-international index of erectile function (IIEF) questionnaire, global assessment questions (GAQs) and routine laboratory testing, at baseline and 3 months afterward. 51 (92%) patients of 54 completed the entire study period. After 3 months of treatment, a small, but statistically significant improvement in total and single items of the IIEF was found (Δ = 5.7 ± 4.1 P < 0.01). Analyses on GAQs revealed that treatment improved erections in 40% of cases, with a partial response occurring in up to 77% of subjects enrolled. These preliminary findings indicate that the favourable cardiovascular effects of nutraceuticals might also reflect on male sexual function with possible implication in the treatment and prevention of ED. This study documents a considerable patient's interest toward nutritional supplementation--as first-line or adjunctive treatment to PDE5 inhibitors--that goes beyond the measurable increment in penile rigidity.

[Hashimoto's thyroiditis and autoimmunity parameters: descriptive study]. / Tiroidite di Hashimoto e parametri di autoimmunità. Studio descrittivo.

AIM: Aim of the study is a prospective evaluation of the simultaneous presence of antinuclear antibodies (ANA) in patients with Hashimoto's thyroiditis as a sign of a possible occurrence of another autoimmune disease. METHODS: Thirty two patients with Hashimoto's thyroiditis have been selected. No other immunological parameters have been used for the selection. All the patients have been submitted to ANA research and to thyroid colour-Doppler ultrasonography. Moreover, subgroups of patients have been submitted to the research of other autoimmunity parameters: 25 patients to AMA (anti-mitochondrial antibodies), ASMA (anti-smooth muscle antibodies), ENA (extractable nuclear antigens) and anti-double stranded-DNA; 7 patients to anti-gastric mucosa; 8 patients to ACA (anti-cardiolipin antibodies) IgM and IgG; 12 patients to rheuma-screen. Twenty five patients were under L-thyroxine therapy at the time of the samples. RESULTS: Forty-seven percent of the patients were ANA positive. Of them 60% showed a title of 1:40. The most frequent sonography picture was pseudo-nodular (66%) with predominance in ANA negative subgroups (71%) than in ANA positive one (60%). On the basis of all the autoimmune parameters evaluated in every subgroups, 72% of our patients were positive to at least one autoimmunity parameter and/or have an autoimmune disease besides Hashimoto's thyroiditis. CONCLUSION: The conclusion is drawn that the patient with Hashimoto's thyroiditis should be considered as an autoimmune patient. Thus, it is necessary to carry out an autoimmune screening with ANA in every new diagnosed patients and to study in depth the familiar and phatological history. Periodical checking of the autoimmune parameters should not be underestimated in these patients.