"Ariadne's Thread": Psycho-educational Empowerment Intervention for Patients with Metastatic Breast Cancer.

"Ariadne's thread" is a psycho-educational intervention designed by the Breast Unit and the Clinical Psychology Unit of an Italian Comprehensive Cancer Center and aims to promote empowerment in patients with metastatic breast cancer. It consists of 8 online meetings led by a psycho-oncologist in which informative sessions by patients' referring physicians alternate with moments of stress management techniques. This study aims to investigate (1) the feasibility of the "Ariadne's thread" pilot intervention and (2) the satisfaction and perceived benefits of the pilot intervention. We used a mixed method approach in which (1) it was detected: the number of acceptance to the single session of the intervention by both patients and professionals, the number of help requests by patients, and the number of change of date requests by professionals; (2) semi-structured interviews were conducted with the professionals who participated in the intervention; (3) 2 focus groups were conducted with patients, and (4) a questionnaire was submitted to each of them. The intervention is sustainable from the perspective of the organization, professionals, and patients. In particular, the patients declared perceiving benefits in many aspects: improved relationships with doctors, acceptance of their illness, learning of a relaxation technique, possibility to look at the world with trust and hope, etc. The questionnaires show an improvement in empowerment and satisfaction as a result of the intervention. "Ariadne's thread" is a psycho-educational intervention that effectively addresses the needs of patients with MBC. It can be applied to other contexts (1) if it has been confirmed that similar needs exist or (2) if it can be modified to accommodate other needs.

Psychological and Structural Barriers to Immigrant Community Participation: The Experience of Peruvians in Santiago de Chile.

Community participation can be considered a pillar for the promotion of social justice and well-being for immigrants in new countries. Participation may be influenced by different forms of oppression which decrease opportunities for immigrants to be engaged. The present study explores the difficulties that Peruvian immigrants encountered and still encountering to participate in Santiago de Chile through in-depth qualitative interviews. Eighteen semi-structured interviews were conducted with Peruvian leaders of Ethnic Community Based Organizations (ECBOs) in Santiago de Chile. Interviews focused on the community engagement of Peruvians highlighting the difficulties they encountered when deciding whether to engage and throughout the process of carrying out their commitment, along with their perceptions when trying to engage their compatriots. The present study contributes to the literature in three aspects. First, it focused on the phenomenon of South-South migration. Secondly, it delved into the psychological and structural barriers that immigrants' experience, considering their disadvantaged conditions. Thirdly, it used Situational Analysis, along with the constructionist drift of Grounded Theory, which is widely used in critical, qualitative research, and is sensitive to producing situated knowledge. Coding and mapping analysis identified experiences related to historical trauma, transnational bonds, and dominant master narratives in both countries as well as challenges due to balancing time and priorities, surviving institutional deterrents, and inter-organizations competitiveness. Finally, transnational commitments, mechanisms of social disconnection, and under valuated rights that Peruvians may live in Chile were pointed out. These results intend to have practical implications for immigrants and for community psychologists.

Fear of cancer recurrence in haematological cancer patients: exploring socio-demographic, psychological, existential and disease-related factors.

PURPOSE: This study aims to explore the relation between the dimension of fear of cancer recurrence (FCR) in haematological cancer patients relapse-free for at least 2 years and socio-demographic, related to the disease, psychological and existential factors. METHODS: A sample of 75 haematological cancer patients agreed to participate in the study through a self-reported online questionnaire (51.9% males). A total of 70.1% had a low recurrence risk. The questionnaire included socio-demographic (gender, age, civil status, level of education and number of children), related to the disease (diagnosis, therapeutic line and years since diagnosis), psychological (anxiety and depression), existential (purpose in life; PIL) factors and Fear of Cancer Recurrence Concerns Inventory (FCRI). Simple and multiple linear regressions were conducted for the analyses, and we performed some preliminary analysis on the reliability of the FCRI. FINDINGS: A total of 53.3% of participants showed clinical levels of FCR on the severity dimension, which was higher than found in previous research in other cancer patients. The coping strategies, triggers, severity and psychological distress dimensions showed higher mean values. Women, patients with indolent non-Hodgkin lymphomas, years since diagnosis, anxiety and purpose in life are significantly related to one or more dimensions of FCRI. IMPLICATIONS: It is important that the clinicians have at their disposal multiple possibilities to help patients cope with haematological cancer. If future research will confirm the results of this study, the negative correlation between FCR and PIL can suggest indications for planning interventions based on a salutogenic approach.

Sexual function after vaginal erbium laser: the results of a large, multicentric, prospective study.

The aim of this multicentric, prospective study was to evaluate the effects of vaginal erbium laser (VEL-SMOOTH®) on sexual function in postmenopausal women suffering from the genitourinary syndrome of menopause (GSM). This study was performed on an outpatient basis without anesthesia or drug use before or after the intervention, using an erbium laser (XS Fotona Smooth®, Fotona, Ljubljana, Slovenia) in 1081 postmenopausal women (age 54.3 ± 3.9 years) treated with up to three laser applications every 30 days. Patients were assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). No adverse events were recorded during the study. The FSDS-R scores (n = 554), from basal values of 25.5 ± 3.5, were 11.5 ± 3.0, 10.5 ± 3.5 and 11.5 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Individual FSFI domain scores (n = 569) significantly (p < 0.001) increased after VEL-SMOOTH® treatment and remained significantly higher up to the 24th week after the end of treatment. The total scores, from basal values of 15.5 ± 1.5, were 27.5 ± 2.5, 27.6 ± 2.7and 27.0 ± 3.5 at the 4-, 12- and 24-week follow-ups, respectively (p < 0.01 vs. corresponding basal values). Albeit not randomized, this large, prospective study shows that VEL-SMOOTH® treatment may improve sexual function in postmenopausal women suffering from GSM.

Clinical and Socio-demographic Variables Associated with the Outcome of Vocational Rehabilitation Programs: A Community-Based Italian Study.

This study aims to identify clinical and socio-demographic variables associated with the outcome of vocational rehabilitation programs (VRPs). All users of an Italian Community Mental Health Centre (CMHC) included in VRPs delivered according to the model of Supported Employment in years 2011-2016 were retrospectively enrolled. Fifty users who ended the program with employment were compared with fifty users who dropped out, with respect to clinical and socio-demographic variables. VRPs lasting less than 6 months and oriented toward the competitive labor market had a higher probability of employment. Among users who successfully ended the VRP, the median of health interventions significantly decreased after employment. In the same group of users, less non-health interventions strictly linked to the VRP were required, when compared with users who dropped out. We conclude that employment is associated with improvement of users' clinical conditions and reduced workload for the CMHC.

Expert consensus on a train-the-trainer curriculum for robotic colorectal surgery.

AIM: Robotic techniques are being increasingly used in colorectal surgery. There is, however, a lack of training opportunities and structured training programmes. Robotic surgery has specific problems and challenges for trainers and trainees. Ergonomics, specific skills and user-machine interfaces are different from those in traditional laparoscopic surgery. The aim of this study was to establish expert consensus on the requirements for a robotic train-the-trainer curriculum amongst robotic surgeons and trainers. METHOD: This is a modified Delphi-type study involving 14 experts in robotic surgery teaching. A reiterating 19-item questionnaire was sent out to the same group and agreement levels analysed. A consensus of 0.8 or higher was considered to be high-level agreement. RESULTS: Response rates were 93-100% and most items reached high levels of agreement within three rounds. Specific requirements for a robotic faculty development curriculum included maximizing dual-console teaching, theatre team training, nontechnical skills training, patient safety, user-machine interface training and telementoring. CONCLUSION: A clear need for the development of a train-the-trainer curriculum has been identified. Further research is needed to assess feasibility, effectiveness and clinical impact of a robotic train-the-trainer curriculum.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients.

BACKGROUND: Ipilimumab improves the survival of metastatic melanoma patients. Despite documented, durable objective responses, a significant number of patients fails to benefit from treatment. The aim of this study was to identify an upfront marker for treatment benefit. METHODS: A total of 187 metastatic melanoma patients treated in three Italian Institutions with 3 mg kg(-1) ipilimumab, and 27 patients treated with 10 mg kg(-1) ipilimumab, were evaluated. Neutrophil-to-lymphocyte ratio (NLR) was calculated from pre-therapy full blood counts. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method, and multivariate Cox models were applied, adjusting for confounders and other prognostic factors. RESULTS: In the training cohort of 69 patients treated at European Institute of Oncology, pre-therapy NLR was identified as the strongest and independent marker for treatment benefit in multivariate analyses. Patients with baseline NLR<5 had a significantly improved PFS (HR=0.38; 95% CI: 0.22-0.66; P=0.0006) and OS (HR=0.24; 95% CI: 0.13-0.46; P<0.0001) compared with those with a NLR⩾5. Associations of low NLR with improved survival were confirmed in three validation cohorts of patients. CONCLUSION: Our findings show that baseline NLR is strongly and independently associated with outcome of patients treated with ipilimumab, and may serve to identify patients most likely to benefit from this therapy.

Impact of muscle mass loss on outcomes in advanced or metastatic gastric cancer patients receiving a second-line treatment.

OBJECTIVE: Sarcopenia is a frequent disorder among cancer patients. It commonly leads to muscle mass wasting and poor clinical outcomes, even though it is rarely recognized and often undertreated. The relationship between skeletal muscle depletion and chemotherapy toxicity or postoperative complications is well known. The aim of the present study was to analyze the impact of sarcopenia on clinical outcomes of pretreated metastatic gastric cancer (GC) patients. PATIENTS AND METHODS: 88 pretreated GC patients were retrospectively analyzed. Patients were divided into two groups according to their skeletal mass index (SMI): sarcopenic patients with low SMI (≤39 cm2/m2 for women and ≤55 cm2/m2 for men) and non-sarcopenic patients with normal/high SMI value. The two groups were compared according to outcomes and adverse events. RESULTS: Progression-free survival (PFS) was significantly higher in patients with normal/high SMI than in those with low SMI (6 vs. 3.5 months, respectively; HR 0.52). Similarly, the overall response rate (ORR) was higher in the subgroup with normal/high SMI (41% vs. 20%; p=0.02). Overall survival (OS) was not significantly different, but multivariate analysis demonstrated that both SMI and performance status were associated with OS. In the sarcopenic group, the patients treated in the second line with paclitaxel and ramucirumab regimen showed a better outcome profile. Overall, adverse events (AEs) were more frequent in the group of patients with low SMI (p<0.0001). CONCLUSIONS: Early recognition of sarcopenia may contribute to personalizing second or further lines of treatment in advanced GC and to weigh up the potential risk of serious toxicities.

Complications related to hyperthermia during hypertermic intraoperative intraperitoneal chemiotherapy (HIPEC) treatment. Do they exist?

BACKGROUND AND OBJECTIVES: Hyperthermia, either alone or in combination with anticancer drugs, is becoming more and more a clinical reality for the treatment of far advanced gastrointestinal cancers, acting as a cytotoxic agent at a temperature between 40-42.5 degrees C. Although hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is demonstrated to have some benefit in selected patients with peritoneal seeding, there are not enough data on the risk of damage of normal tissue that increases as the temperature rises, with possible serious and, sometimes, lethal complications. MATERIALS AND METHODS: We searched on medline words like "intraoperative intraperitoneal chemohyperthermia and morbidity", focusing our attention on studies (published since 1990) which reported morbidity as bowel obstruction, bowel perforation or anastomic leak, during intraoperative intraoperitoneal chemotherapy in hyperthermia (HIPEC). RESULTS: Heat acts increasing cancer cell killing after exposure to ionizing radiation, inhibiting repairing processes of radiation-induced DNA lesions (radiosensitization), and also sensitizing cancer cells to chemotherapeutic drugs, particularly to alkylating agents (chemosensitization). The peritoneal carcinomatosis (a frequent evolution of advanced digestive cancer) represents one of the main indication to hypertermic treatment. In the last fifteen years, in fact, different methods were developed for the surgery treatment (peritonectomy) and for loco-regional chemotherapic treatment of the carcinomatosis (intraperitoneal intra/post-operative iper/normothermic chemotherapy) to act directly on neoplastic seeding. We found, as result of different studies, 9 articles, written about perforation after HIPEC. CONCLUSION: The aim of the present study is to present the review of the literature in terms of peri-operative complications related to the hyperthermia during intraoperative chemohyperthermia procedure.

Re-activating life skills in cancer patients through expressive-creative workshops: A qualitative exploratory study.

BACKGROUND: Cancer strongly impacts on patients' lives, undermining their life skills. This research aimed to explore the perception of efficacy of participants in a series of expressive-creative workshops (ArtLab) designed to reactivate life skills in cancer patients. METHODS: Quotations of two semi-structured focus groups with ten participants in ArtLab (Mean Age = 59; SD = 11.19) enrolled at [Fondazione IRCCS Istituto Nazionale dei Tumori] have been analyzed through a priori (top-down) thematic analysis which allowed us to identify life skills provided by WHO 1948: Emotional, Relational and Cognitive. RESULTS: Thematic analysis showed ArtLab program's effectiveness, especially regarding Emotional and Relational life skills. Cognitive skills, instead, seemed to be only partially expressed. Sub-themes articulation for each life skill has been discussed. CONCLUSION: This study provides encouraging results with respect to the effectiveness of expressive-creative group workshops among cancer patients.

Cancer-related fatigue and depression: a monocentric, prospective, cross-sectional study in advanced solid tumors.

BACKGROUND: Cancer-related fatigue (CRF) is common in patients with advanced solid tumors and several risk factors are described. The possible role of depression is reported by clinicians despite the association with CRF being unclear. MATERIAL AND METHODS: In this monocentric, cross-sectional, prospective study we recruited patients with advanced solid tumors who were hospitalized at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. The primary objective was to assess the correlation between CRF and depression. Secondary objectives were the estimation of CRF and depression prevalence and the identification of associated clinical risk factors. CRF and depression were evaluated through the Functional Assessment of Cancer Therapy-Fatigue subscale and the Zung Self Depression Scale (ZSDS) questionnaires. The Cochran-Armitage trend test was used to demonstrate the primary hypothesis. Univariate and multivariate logistic regression models were used to investigate the impact of clinical variables. RESULTS: A total of 136 patients were enrolled. The primary analysis found a linear correlation (P < 0.0001) between CRF and depression. The prevalence of CRF and of moderate to severe depressive symptoms was 43.5% and 29.2%, respectively. In univariate analysis, patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), anemia, distress, pain, and receiving oncological treatment were at a significantly higher risk for CRF, whereas poor ECOG PS, pain, and distress were risk factors for depression. In multivariate analysis, high levels of ZSDS were confirmed to be correlated to CRF: odds ratio of 3.86 [95% confidence interval (CI) 0.98-15.20) and 11.20 (95% CI 2.35-53.36) for ZSDS of 50-59 and 60-100, respectively (P value for trend 0.002). Moreover, the ECOG PS score was confirmed to be significantly associated with CRF (OR 7.20; 95% CI 1.73-29.96; P = 0.007). CONCLUSIONS: Our data suggest a strong correlation between CRF and depression in patients with advanced solid tumors. Further investigations are needed to better understand this relationship and if depressive disorder therapeutic strategies could also impact on CRF.

Management of Small Bowel Obstruction (SBO) in older adults (>80 years): a propensity score-matched analysis on predictive factors for a (un)successful non-operative management (NOM).

OBJECTIVE: Small Bowel Obstruction (SBO) is a common emergency in older patients. The most appropriate treatment strategy is still matter of debate. The aim of this study was to compare a non-operative management (NOM) vs. a surgical procedure for patients ≥ 80 years with SBO. PATIENTS AND METHODS: All patients ≥ 80 years admitted to our Emergency Department (ED) for SBO between January 1st, 2015, and December 31st, 2020 were included in this study. In order to correct for baseline covariates and factors associated to clinical management, we used a 1:1 propensity score matching (PSM) analysis. The primary outcome was to compare the overall in-hospital mortality. Secondary outcomes included occurrence of major complications and in-hospital length of stay (LOS). RESULTS: A total of 561 patients were enrolled. After propensity score matching (PSM) analysis, 302 patients (151 each group) were included in the analysis. Mortality did not differ between the two groups. After PSM mechanical ventilation, sepsis, cumulative major complications, and LOS were significantly higher in the operative treatment group [15.9% vs. 1.5%, 9.4% vs. 4.1%, 27.6% vs. 19.2%, and 9.4 (6.4-14.3) days vs. 8.1 (4.5-13.3) days, respectively; p<0.001, p=0.013, p=0.025, and p=0.003, respectively]. CONCLUSIONS: In patients ≥ 80 years with SBO, a NOM could yield similar results, in terms of overall mortality, compared to a surgical management. Thus, particularly in patients with multiple comorbidities or functional impairments, a conservative approach should always be considered.

Development of the Functional Assessment of Chronic Illness Therapy - Liver Transplant (FACT-LT) Scale.

Background: This study aims to propose an initial development of the FACT-Liver Transplant (FACT-LT) scale to assess the major physical and emotional concerns of patients before and after Orthotopic Liver transplant (OLT) due to acute and chronic liver failure and hepatocellular carcinoma. Methods: The FACT-LT was developed in two phases. In Phase I, items were generated: 1) through interviews with 10 OLT experts and 15 candidates for or recipients of both oncological and non-oncological OLT which identified relevant topics; 2) from the FACIT item bank. In Phase II, a questionnaire to assess item frequency, applicability, and comprehension was administered to 20 OLT experts and, to assess item difficulty, embarrassment and content irrelevance, to 30 transplant recipients or candidate patients (15 oncological, 15 non-oncological). Results: In Phase I, 44 items were formulated/reviewed, and 30 items were maintained. All the healthcare professionals interviewed rejected the recommendation to develop two different modules for cancer and non-cancer patients. In Phase II, the majority of the experts and patients expressed an overall satisfaction with the questionnaire, indicating that the items were relevant, comprehensible and not embarrassing (range 75% - 99%). The first version of the FACT-LT includes 28 items defining four QOL domains: 5 items relating to Physical Well-Being, 8 to Functional Well-Being, 13 to Emotional Well-Being, and 2 to Social/Family Well-Being. Conclusion: The preliminary results obtained were promising; however further studies are needed, in order to proceed with a FACT-LT validation process.

Role of oxidized regenerated cellulose in preventing infections at the surgical site: prospective, randomized study in 98 patients affected by a dirty wound.

AIM: The aim of this study was to evaluate whether oxidized regenerated cellulose (ORC), applied to "dirty" surgical wounds, is able to reduce the microbial load and, consequently, the infection rate as compared to conventional local wound treatment. METHODS: The study included 98 patients who underwent intestinal recanalization procedures between December 2003 and December 2008, with the stoma as the surgical site. Authors considered several risk factors for SSI. The patients were divided into two groups. In group A (50 patients), the surgical wound, previous site of the stoma, was packed with ORC, whereas in group B (48 patients) gauze soaked in iodine was used. Microbial contamination was evaluated with three swabs (in subcutaneous tissue and the dermis), in the operating room before wound packing and on the 2nd and 3rd postoperative day (before suturing the skin). RESULTS: There were no cases of wound dehiscence and no clinically evident superficial or deep surgical site infections in either group. Analysis of all data revealed that there was no or reduced bacterial contamination in the second and third swab in 33 patients (66%) of Group A versus 12 patients (25%) of Group B. CONCLUSION: Although it is necessary to consider all factors which can have an influence on SSI and use all the means shown to be effective to reduce the risk of SSI, there is a rationale for using ORC to prevent this kind of infection, especially in patients who undergo "dirty" surgery.

Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib.

PURPOSE: Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described. METHODS: From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan-Meier method and compared with log-rank test. RESULTS: Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963-1.065; p = 0.62). CONCLUSION: Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.

Noradrenergic fibers are associated with beta-cell dedifferentiation and impaired beta-cell function in humans.

AIMS/HYPOTHESIS: Type 2 diabetes (T2D) is characterized by a progressive loss of beta-cell function, and the "disappearance" of beta-cells in T2D may also be caused by the process of beta -cell dedifferentiation. Since noradrenergic innervation inhibits insulin secretion and density of noradrenergic fibers is increased in type 2 diabetes mouse models, we aimed to study the relation between islet innervation, dedifferentiation and beta-cell function in humans. METHODS: Using immunohistochemistry and electron microscopy, we analyzed pancreata from organ donors and from patients undergoing pancreatic surgery. In the latter, a pre-surgical detailed metabolic characterization by oral glucose tolerance test (OGTT) and hyperglycemic clamp was performed before surgery, thus obtaining in vivo functional parameters of beta-cell function and insulin secretion. RESULTS: The islets of diabetic subjects were 3 times more innervated than controls (0.91 ±â€¯0.21 vs 0.32 ±â€¯0.10, n.fibers/islet; p = 0.01), and directly correlated with the dedifferentiation score (r = 0.39; p = 0.03). In vivo functional parameters of insulin secretion, assessed by hyperglycemic clamp, negatively correlated with the increase in fibers [beta-cell Glucose Sensitivity (r = -0.84; p = 0.01), incremental second-phase insulin secretion (r = -0.84, p = 0.03) and arginine-stimulated insulin secretion (r = -0.76, p = 0.04)]. Moreover, we observed a progressive increase in fibers, paralleling worsening glucose tolerance (from NGT through IGT to T2D). CONCLUSIONS/INTERPRETATION: Noradrenergic fibers are significantly increased in the islets of diabetic subjects and this positively correlates with beta-cell dedifferentiation score. The correlation between in vivo insulin secretion parameters and the density of pancreatic noradrenergic fibers suggests a significant involvement of these fibers in the pathogenesis of the disease, and indirectly, in the islet dedifferentiation process.