Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection.

BACKGROUND: Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare subtype of lung cancer with poor clinical outcomes. Data on recurrence-free survival (RFS) in early and locally advanced pure LCNEC after complete resection (R0) are lacking. This study aims to evaluate clinical outcomes in this subgroup of patients and to identify potential prognostic markers. METHODS: Retrospective multicenter study including patients with pure LCNEC stage I-III and R0 resection. Clinicopathological characteristics, RFS, and disease-specific survival (DSS) were evaluated. Univariate and multivariate analyses were performed. RESULTS: 39 patients (M:F = 26:13), with a median age of 64 years (44-83), were included. Lobectomy (69.2%), bilobectomy (5.1%), pneumonectomy (18%), and wedge resection (7.7%) were performed mostly associated with lymphadenectomy. Adjuvant therapy included platinum-based chemotherapy and/or radiotherapy in 58.9% of cases. After a median follow-up of 44 (4-169) months, the median RFS was 39 months with 1-, 2- and 5-year RFS rates of 60.0%, 54.6%, and 44.9%, respectively. Median DSS was 72 months with a 1-, 2- and 5-year rate of 86.8, 75.9, and 57.4%, respectively. At multivariate analysis, age (cut-off 65 years old) and pN status were independent prognostic factors for both RFS (HR = 4.19, 95%CI = 1.46-12.07, p = 0.008 and HR = 13.56, 95%CI 2.45-74.89, p = 0.003, respectively) and DSS (HR = 9.30, 95%CI 2.23-38.83, p = 0.002 and HR = 11.88, 95%CI 2.28-61.84, p = 0.003, respectively). CONCLUSION: After R0 resection of LCNEC, half of the patients recurred mostly within the first two years of follow-up. Age and lymph node metastasis could help to stratify patients for adjuvant therapy.

Using network analysis to explore the association between eating disorders symptoms and aggressiveness in Bulimia nervosa.

Aggressive behaviors have been reported to be more frequent in people with eating disorders (ED), especially bulimia nervosa (BN). Network Analysis (NA) is particularly useful or examining the interactions among symptoms of comorbid conditions through the identification of "bridge symptoms," defined as those symptoms playing a key role in the connection between two syndromic clusters. The aim of the present study was to investigate the association of ED core symptoms and ED-related psychopathology with aggressiveness in a clinical sample of women with BN through NA. Two hundred and seventy-nine women with BN completed the Eating Disorder Inventory-2 and the Buss-Durkee Hostility Inventory. A NA was conducted, including ED symptoms and aggressiveness measures. The bridge function was implied to identify symptoms bridging ED symptoms and aggressiveness. The most connected nodes among communities were asceticism and impulsivity from ED-related psychopathology, drive for thinness from ED-core psychopathology and guilt and suspicion from aggressiveness domain. In particular, drive for thinness connected ED-core community to verbal hostility, while impulsivity connected ED-related symptoms to guilt and suspicion of aggressiveness community. In conclusion the present study showed that in people with BN guilt is the specific negative emotion of the hostile dimensions that may be bidirectionally associated with ED symptoms.

Cortisol awakening response in bipolar patients with comorbid type 2 diabetes mellitus.

OBJECTIVES: Bipolar disorder (BD) is frequently associated with type 2 diabetes mellitus (T2DM). The functioning of the hypothalamic-pituitary-adrenal (HPA) axis has been never investigated in BD with respect to the glucose metabolic status. Therefore, we assessed the cortisol awakening response (CAR) in bipolar patients with or without comorbid T2DM. METHODS: Twenty euglycemic bipolar patients [12 males and eight females; mean age (±SD): 47.4 ± 14.4 years; mean (±SD) duration of illness: 18.3 ± 12.1 years], 16 BD patients with T2DM [11 males and five females; mean age (±SD): 63.6 ± 12.8 years; mean (±SD) duration of bipolar illness: 17.1 ± 10.8 years; mean (±SD) duration of T2DM: 5.2 ± 5.3 years], 18 healthy subjects [seven males and 11 females; mean age (±SD): 45.0 ± 12.1 years] and 12 non-psychiatric subjects with T2DM [eight males and four females; mean age (±SD): 56.7 ± 11.2 years; mean (±SD) duration of T2DM: 5.2 ± 3.5 years] were recruited. Saliva cortisol was measured at awakening and after 15, 30, and 60 min. RESULTS: With respect to both healthy controls and controls with T2DM, euglycemic and diabetic BD patients exhibited a CAR occurring at significantly lower levels. No significant difference emerged in the CAR between the two groups of bipolar patients. Controls with T2DM had an overall post-awakening cortisol production significantly higher than healthy controls. CONCLUSIONS: Our results show that the CAR of patients with BD is reduced in terms of overall cortisol production but normal in terms of cortisol reactivity independently from the occurrence of comorbid T2DM. The dampened CAR points to a tuning down of the functioning of the HPA axis. in both euglycemic and diabetic BD patients, which may be a factor of vulnerability, since a preserved HPA axis functioning is essential to deal with stressors, which may precipitate affective episodes.

How Is the History of Early Traumatic Exposure Associated With the Psychopathological Outcomes of COVID-19 Related Lockdown and Subsequent Re-opening in People With Eating Disorders?

The negative impact of COVID-19 pandemic on people with Eating Disorders (EDs) has been documented. The aim of this study was to evaluate whether a history of traumatic experiences during childhood or adolescence was associated with a higher degree of psychopathological worsening during COVID-19 related lockdown and in the following re-opening period in this group of people. People with EDs undergoing a specialist ED treatment in different Italian services before the spreading of COVID-19 pandemic (n = 312) filled in an online survey to retrospectively evaluate ED specific and general psychopathology changes after COVID-19 quarantine. Based on the presence of self-reported traumatic experiences, the participants were split into three groups: patients with EDs and no traumatic experiences, patients with EDs and childhood traumatic experiences, patients with EDs and adolescent traumatic experiences. Both people with or without early traumatic experiences reported retrospectively a worsening of general and ED-specific psychopathology during the COVID 19-induced lockdown and in the following re-opening period. Compared to ED participants without early traumatic experiences, those with a self-reported history of early traumatic experiences reported heightened anxious and post-traumatic stress symptoms, ineffectiveness, body dissatisfaction, and purging behaviors. These differences were seen before COVID-19 related restrictions as well as during the lockdown period and after the easing of COVID-19 related restrictions. In line with the "maltreated ecophenotype" theory, these results may suggest a clinical vulnerability of maltreated people with EDs leading to a greater severity in both general and ED-specific symptomatology experienced during the exposure to the COVID-19 pandemic.

Perceived parental bonding and cortisol awakening response in people with eating disorders.

It is widely acknowledged that early life experiences may have an impact on hypothalamic-pituitary-adrenal (HPA) axis functioning in eating disorders (EDs). Parental bonding is defined as the parental contribution of care and control to parent-child relationships. We evaluated whether perceived care and protection of parental bonding in childhood and adolescence were associated with HPA axis functioning in adult patients with EDs. Sixty-four women with EDs participated in the study, 37 with anorexia nervosa and 27 with bulimia nervosa. Parental care and control (separately for the mother and father) were evaluated by the Parental Bonding Instrument. The activity of the HPA axis was assessed by measuring the salivary cortisol awakening response (CAR). Parental care and control did not differ significantly between the two diagnostic groups. High and low maternal care were associated with significantly different time patterns of CAR without any significant difference in the overall post-awakening production of cortisol. Maternal control, paternal care and paternal control were not associated with any difference in the CAR. Our results showed for the first time an association of perceived maternal care with the time pattern of CAR in female patients with EDs, while perceived parental control was not associated with any CAR feature. These findings support the idea that perceived characteristics of parental bonding in childhood and adolescence may influence the HPA axis activity in adults with EDs.

Childhood maltreatment and clinical response to mood stabilizers in patients with bipolar disorder.

OBJECTIVE: The association between childhood maltreatment (CM) and clinical response to mood stabilizers has been scarcely investigated in bipolar disorder (BD). Therefore, we assessed whether CM affects the response to lithium or anticonvulsant treatments in BD patients. METHODS: A retrospective assessment of clinical response to mood stabilizers was conducted in 97 euthymic patients with BD by means of the Alda scale. History of CM was investigated through the Childhood Trauma Questionnaire. RESULTS: Thirty-seven patients (24 with a history of CM and 13 without CM) were on stable lithium treatment while sixty (35 with a history of CM and 25 without CM) were on stable anticonvulsant treatment. Clinical response to drug treatment did not differ between BD with CM and those without CM in the whole sample as well as in the anticonvulsant-treated subgroup. In the lithium-treated subgroup, a significant negative correlation emerged between childhood physical abuse and clinical response and patients with CM showed a significantly reduced Alda score. CONCLUSIONS: In BD patients, CM did not influence the clinical response to anticonvulsant mood stabilizers whereas it was associated with a poorer response to lithium with childhood physical abuse playing a major role in this effect.

The impact of COVID-19 lockdown and of the following "re-opening" period on specific and general psychopathology in people with Eating Disorders: the emergent role of internalizing symptoms.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on specific Eating Disorder (ED) and general psychopathology in people with an ED diagnosis during the lockdown period and after the end of the related containment measures. METHODS: People with clinically defined diagnosis and undergoing treatment for an ED completed an online survey, which included adapted questions from standardized psychometric scales. Data relative to three different time periods (before, during and after the end of lockdown) were collected. Psychopathological changes over these periods were investigated and compared through one-way analysis of variance or covariance with repeated measures. RESULTS: Three hundred twelve people completed the survey (57.4% diagnosed with Anorexia Nervosa (AN) or atypical AN, 20.2% with Bulimia Nervosa, 15.4% with Binge Eating Disorder, 7.05% with Other Specified Feeding or Eating Disorders). The severity of both specific and general psychopathology increased during the lockdown and the rise of general symptoms persisted in the following re-opening phase, except for suicide ideation. Almost all of these findings were not affected by ED diagnosis, participants' age and illness duration. LIMITATIONS: The retrospective nature of data collection is the main limitation of the study. CONCLUSIONS: People with EDs showed a COVID-19 emergency-induced worsening of both general and specific psychopathology. The effect on general psychopathology persisted in the re-opening period. These findings suggest a high stress vulnerability of ED individuals with important effects on internalizing symptoms, which are worth of attention by clinicians.

The Gut Microbiome and Metabolomics Profiles of Restricting and Binge-Purging Type Anorexia Nervosa.

Alterations in the gut microbiome and fecal metabolites have been detected in anorexia nervosa (AN), but differences in those profiles between restricting AN (ANR) and binge-purging AN (ANBP) type have not been explored. We made a secondary analysis of our previous data concerning microbiome and metabolomics profiles of 17 ANR women, six ANBP women and 20 healthy controls (HC). Twelve fecal metabolites differentiating ANR patients, ANBP patients and HC were identified. Both patient groups showed decreased intra-individual bacterial richness with respect to healthy controls (HC). Compared to ANR subjects, ANBP patients had a significant increase in relative abundances of Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, and Eubacteriacae and a significant decrease in relative abundances of Odoribacter, Haemophilus, Pasteurellaceae, and Pasteurellales. The heatmaps of the relationships of selected fecal metabolites with microbial families showed different structures among the three groups, with the heatmap of ANBP patients being drastically different from that of HC, while that of ANR patients resulted more similar to HC. These findings, although preliminary because of the relatively small sample size, confirm the occurrence of different gut dysbiosis in ANR and ANBP and demonstrate different connections between gut microorganisms and fecal metabolites in the two AN types.

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study.

PURPOSE: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. METHODS: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. RESULTS: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends' relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. CONCLUSIONS: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. LEVEL OF EVIDENCE IV: Evidence obtained from multiple time series analysis such as case studies.

Multi-omics data integration in anorexia nervosa patients before and after weight regain: A microbiome-metabolomics investigation.

BACKGROUND & AIMS: We have recently reported specific fecal metabolomic changes in acute and short-term weight restored patients with anorexia nervosa (AN). In this study we explored the association between those metabolomic changes and patients' gut microbiome composition. METHODS: The gut microbiome of AN women was sequenced in both the underweight phase (n = 21) and after short-term weight restoration (n = 16) and compared to that of 20 healthy women. According to a multi-omics approach, microbiome data were correlated with 49 relevant fecal metabolites previously characterized in our participants by an untargeted metabolomic procedure. RESULTS: Compared to healthy women, AN patients showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at phylum, class, order, family and genus levels. These changes were observed in both the underweight and weight-restored condition. Moreover, the relationships among the 49 previously selected fecal metabolites and bacteria genera showed structures of different complexity among the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acutely ill patients with respect to the weight-restored ones or normal controls. Finally, in acutely ill patients 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome. CONCLUSIONS: These data confirm a profound perturbation in the gut microbiome composition of AN patients. Moreover, for the first time, they provide the evidence that in AN gut bacteria are connected with several fecal metabolites in a different way from normal controls and with divergent directions in the acute phase with respect to the weight-restored phase.

Longitudinal Course of Depressive, Anxiety, and Posttraumatic Stress Disorder Symptoms After Heart Surgery: A Meta-Analysis of 94 Studies.

OBJECTIVE: This study aimed to analyze the longitudinal course of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms in patients with cardiac disease after heart surgery (HS). METHODS: We conducted a systematic review and random-effects meta-analysis of cohort studies in patients undergoing HS, measuring anxiety, depressive, and PTSD symptoms before and at least 30 days thereafter. Subgroup and meta-regression analyses, investigation of publication bias, and quality assessment were undertaken. RESULTS: We included 94 studies relating to 15,561 patients. HS included coronary artery bypass graft surgery, valve replacement, implantable cardioverter-defibrillator placement, left ventricular assist device placement, heart transplantation, and other types of HS. Across studies, symptoms of depression (g = 0.32; 95% confidence interval [CI] = 0.25 to 0.39; p < .001) and anxiety improved after HS (g = 0.52; 95% CI = 0.43 to 0.62; p < .001), whereas PTSD symptoms worsened (g = -0.42; 95% CI = -0.80 to -0.04; p = .032). The reduction of depression and anxiety levels was more pronounced for patients with underlying coronary artery disease and heart failure and persisted for 1 year after HS, whereas the increase in PTSD symptoms returned to baseline after 6 months. Depression improvement was inversely associated with older age, diabetes, hypertension, and dyslipidemia and positively with baseline heart failure. No additional clinical or demographic variables were associated with the course of anxiety symptoms. Quality of included studies was low overall. Publication bias was nonsignificant. CONCLUSIONS: Depressive and anxiety symptoms improve for 1 year after HS, whereas PTSD symptoms might worsen. Older patients and those with metabolic comorbidities, valve disease, or ventricular arrhythmias are at higher risk for continued depressive and anxiety symptoms and should be monitored closely.

Alexithymia and cortisol awakening response in people with eating disorders.

OBJECTIVES: Alexithymia, which is the inability to recognise and describe one's own emotions, is a transdiagnostic feature across eating disorders (EDs) and it has been associated with prolonged stress exposure. Therefore, we evaluated whether alexithymia was associated with hypothalamus-pituitary-adrenal (HPA) axis functioning, the main endogenous stress response system, in patients with anorexia nervosa (AN) or bulimia nervosa (BN). METHODS: 26 women with AN and 26 with BN participated in the study. Alexithymia was evaluated by the Toronto Alexithymia Scale-20 and eating-related psychopathology was measured by the Eating Disorder Inventory-2. The activity of the HPA axis was assessed by measuring the salivary cortisol awakening response (CAR). RESULTS: The prevalence of alexithymia did not differ significantly between the two diagnostic groups. Alexithymia was associated with more severe eating-related psychopathology in AN women but not in BN women. A significant reduction in the magnitude of CAR occurred in alexithymic patients with BN compared to non-alexithymic patients, but not in alexithymic women with AN. CONCLUSIONS: These results confirm the presence of a more severe specific psychopathology in alexithymic individuals with AN and show, for the first time, an association between alexithymia and a dampened basal activity of the HPA axis in BN.

Clinical and neuroendocrine correlates of childhood maltreatment history in adults with bipolar disorder.

OBJECTIVES: Childhood maltreatment has been associated to an increased risk of developing bipolar disorder (BD). A role of the hypothalamus-pituitary-adrenal (HPA) axis in mediating trauma-related risk for adult psychopathology has been suggested but scarcely investigated in BD. Therefore, we explored the impact of childhood maltreatment on clinical features of BD and on the activity of the HPA axis. METHODS: One hundred and six patients participated in the study. On the basis of their history of childhood trauma, as assessed by the Childhood Trauma Questionnaire (CTQ), they were divided into a group with a history of childhood maltreatment (CM+) and a group without (CM-). Twenty-nine participants (16 with a history of childhood trauma and 13 without) underwent the cortisol awakening response (CAR) test. RESULTS: Sixty-two patients had a history of childhood maltreatment and 44 had not. Maltreatment was significantly more frequent in females than males. CM+ patients showed a significant higher body mass index, a significant higher number of suicide attempts, and more severe mania symptoms than CM- ones. Logistic regression indicated a significant association between lifetime suicide attempts and any type of childhood maltreatment and between emotional abuse and the presence of psychotic symptoms or mixed mood episodes. CM+ individuals with BD exhibited a significantly reduced CAR with respect to CM- ones. DISCUSSION: Our results add to literature findings showing a worse clinical course in BD patients with a history of childhood maltreatments and show for the first time that childhood trauma exposure is associated to an impaired CAR in adults with BD.

Recurring sequences of multimodal non-verbal and verbal communication during a human psycho-social stress test: A temporal pattern analysis.

BACKGROUND: The Trier Social Stress Test (TSST) is a widely used protocol to study human psycho-social stress responses. Quantitative reports of non-verbal behaviors have been carried out by means of the Ethological Coding System for Interviews (ECSI). However, no data have described whether and how non-verbal and verbal behaviors take part in the composition of multimodal sequences of communication during the test. METHOD: Five non-verbal ECSI categories and four verbal behaviors related with communication were included in the Ethogram. A focal sampling was employed to ensure a high temporal resolution of the behavioral annotation. T-Pattern Analysis was employed to detect statistically-grounded behavioral sequences. RESULTS: As a first step, frequency, overall duration and mean time length were reported for each component of the Ethogram. Besides, T-Pattern Analysis revealed that communication during TSST is organized according to a complex temporal patterning. We found 51 different sequences (T-patterns): 8 T-patterns included exclusively non-verbal behaviors; 17 T-patterns included verbal behaviors and 26 T-patterns encompassed mixed non-verbal and verbal behaviors. T-patterns were discussed depending on their putative functional meaning since non-verbal behaviors almost did not overlap within patterns. CONCLUSIONS: The implementation of an Ethogram including non-verbal and verbal components highlights the multimodal human communication in TSST. T-Pattern Analysis unveils the real-time interplay among these components. In this study results are discussed according to Jakobson's six constitutive factors of communication.

Early traumatic experiences impair the functioning of both components of the endogenous stress response system in adult people with eating disorders.

Childhood trauma is a non-specific risk factor for eating disorders (EDs). It has been suggested that this risk is exerted through trauma-induced long-lasting changes in the body stress response system. Therefore, we explored the activity of the hypothalamus-pituitary-adrenal axis and of the sympathetic nervous system in adult ED patients with or without a history of childhood trauma exposure. Salivary cortisol and alpha-amylase, a marker of the sympathetic nervous system activity, were measured at awakening and after 15, 30 and 60 min in 35 women with EDs. The Childhood Trauma Questionnaire (CTQ) was employed to assess exposure to childhood trauma and, according to the CTQ cut-off scores, 21 ED women were classified as maltreated (Mal) participants and 14 women as no-maltreated (noMal) ED participants. Compared to noMal ED women, Mal ED participants showed significantly decreased cortisol awakening response (between group difference: p = 0.0003) and morning salivary alpha-amylase secretion (between group difference: p = 0.02). Present results confirm that the cortisol awakening response of adult ED patients with childhood trauma exposure is lower than that of adult ED patients without childhood trauma experiences and show for the first time that also the morning secretion of salivary alpha-amylase is decreased in adult ED patients who have been exposed to early traumatic experiences. These results point for the first time to a dampening in the basal activity of both components of the endogenous stress response system in childhood maltreated adult ED women.

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study.

BACKGROUND: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. METHODS: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. RESULTS: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. CONCLUSIONS: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.

Improvement of Bone Physiology and Life Quality Due to Association of Risedronate and Anastrozole.

The endocrine therapy is the new frontiers of many breast cancers hormone sensitive. Hormone therapy for treating women with hormone receptor-positive cancer suppresses breast cancer growth either by reducing estrogen synthesis or by interfering with the action of estrogen within tumor cells. In this prospective randomized observational study we investigate the effect of adjuvant anastrozole in monotherapy or associated with risedronate on bone physiology and quality of life in postmenopausal, hormone-sensitive early breast cancer women at mild to moderate risk of fragility fractures. Methods : 84 women were randomly assigned to receive anastrozole alone (group A) or anastrozole plus oral risedronate (group A+R). At baseline and after 24 months lumbar spine (LS) and femoral neck (FN) BMD were evaluated with dual-energy x-ray absorptiometry and health-related quality of life (HRQoL) was examined using the short-form healthy survey. Results : After 24 months, the group A+R has showed a significant increase in T-score for LS (p < 0.05) and for FN (p < 0.05) whereas women of group A had a statistically significant rate of bone loss both in LS T-score (p < 0.05) and in FN (p < 0.05). A significant change in T-score BMD was seen for group A+R compared with group A at the LS (p = 0.04) and at FN (p = 0.04). Finally, group A+R showed an overall significant improvement of health profile (SF-36) in group A (p = 0.03). Conclusion : Postmenopausal breast cancer women with osteopenia during treatment with anastrozole have considerable risk of developing osteoporosis during the first 2 years; preventive measures such as healthy lifestyle and daily supplements of calcium and vitamin D alone seem to be insufficient in holding their bones healthy. Our findings suggest the usefulness of addition of risedronate in order to prevent aromatase inhibitors-related bone loss, not only in case of high-risk of fractures, but also for women at mild-moderate risk. This determines a significant improvement in bone health and a positive impact on HRQoL.

Differences in Cortisol Awakening Response between Binge-Purging and Restrictive Patients with Anorexia Nervosa.

Malnutrition and childhood trauma were shown to affect in opposite way the cortisol awakening response (CAR) of patients with anorexia nervosa (AN). To assess the influence of binge-purging behaviour on the CAR of AN patients, we measured the CAR of restrictive AN (ANR) or binge-purging AN (ANBP) patients without history of childhood maltreatment. Seventeen ANBP women, 18 ANR women and 42 healthy women collected saliva samples at awakening and after 15, 30 and 60 min, and filled in the Eating Disorder Inventory-2 (EDI-2). ANR and ANBP patients exhibited a CAR significantly higher than healthy women. Moreover, the CAR of ANBP women was even higher than that of ANR women and positively correlated with the bulimia subitem scores of the EDI-2. Present findings show, for the first time, differences in the CAR between ANBP and ANR subtypes, which may suggest a possible connection between the HPA axis functioning and binge-purging. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Role of (68)Ga-DOTATATE PET/CT in patients with multiple endocrine neoplasia type 1 (MEN1).

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome predisposing to many endocrine and neuroendocrine tumors (NET). Conventional imaging (CI) cannot provide satisfactory results for all the different types of MEN1-related tumors. Objective of this prospective observational study was to evaluate the role of (68)Ga-DOTATATE PET/CT in MEN1 compared to CI. Diagnostic performance of (68)Ga-DOTATATE PET/CT for the detection of NET was evaluated as well as the prognostic role of SUVmax. Eighteen patients with genetically confirmed MEN1 were evaluated by (68)Ga-DOTATATE PET/CT, endoscopic ultrasounds, multidetector-row computed tomography, magnetic resonance imaging, and hormone/markers serum measurements. Four MEN1-related tumor sites (pancreas, pituitary, parathyroids, adrenals) were considered. Sensitivity and specificity of (68)Ga-DOTATATE PET/CT for the detection of NET were calculated. There was (68)Ga-DOTATATE PET/CT uptake in 11/11 patients with pancreatic lesions, in 9/12 with pituitary adenoma, in 5/15 with parathyroid enlargements, and in 5/7 with adrenal lesions. (68)Ga-DOTATATE PET/CT showed sensitivity and specificity of 100 and 100 % in pancreas, 75 and 83 % in pituitary, 28 and 100 % in parathyroids, and 62.5 and 100 % in adrenals, respectively. Compared with CI, no significant difference in sensitivity for pancreas, pituitary, and adrenals was found, while CI had a better sensitivity for parathyroids (p = 0.002). On the ROC analysis, progression of pancreatic lesions was significantly associated to SUVmax <12.3 (p < 0.05). (68)Ga-DOTATATE PET/CT is greatly helpful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. There is also a prognostic role of (68)Ga-PET in patients with MEN1-pancreatic lesions.

Prognostic role of the CDNK1B V109G polymorphism in multiple endocrine neoplasia type 1.

CDKN1B encodes the cyclin-dependent kinase inhibitor p27/Kip1. CDKN1B mutations and polymorphisms are involved in tumorigenesis; specifically, the V109G single nucleotide polymorphism has been linked to different tumours with controversial results. Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome, characterized by the development of different types of neuroendocrine tumours and increased incidence of other malignancies. A clear genotype-phenotype correlation in MEN1 has not been established yet. In this study, we assessed whether the CDKN1B V109G polymorphism was associated with the development of aggressive tumours in 55 consecutive patients affected by MEN1. The polymorphism was investigated by PCR amplification of germline DNA followed by direct sequencing. Baseline and follow-up data of tumour types and their severity were collected and associated with the genetic data. MEN1-related aggressive and other malignant tumours of any origin were detected in 16.1% of wild-type and 33.3% of polymorphism allele-bearing patients (P = NS). The time interval between birth and the first aggressive tumour was significantly shorter in patients with the CDKN1B V109G polymorphism (median 46 years) than in those without (median not reached; P = 0.03). Similarly, shorter was the time interval between MEN1 diagnosis and age of the first aggressive tumour (P = 0.02). Overall survival could not be estimated as 96% patients were still alive at the time of the study. In conclusion, CDKN1B V109G polymorphism seems to play a role in the development of aggressive tumours in MEN1.