Short-term dietary changes can result in mucosal and systemic immune depression.

Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to 'feast diets', mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4+ T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma.

INTRODUCTION: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate. MATERIALS AND METHODS: We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase. RESULTS: The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93×10-8 in the overall meta-analysis), reaching genome-level statistical significance. 15q26.1-rs12905855 decreases the methylation of a 'C-phosphate-G' (CpG) site located in the promoter region of the RCCD1 antisense (RCCD1-AS1) gene which, when expressed, decreases the expression of the RCC1 domain-containing (RCCD1) gene (part of a histone demethylase complex). Thus, it is possible that the rs12905855 C-allele has a protective role in PDAC development through an increase of RCCD1 gene expression, made possible by the inactivity of RCCD1-AS1. CONCLUSION: We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation.

Perioperative management of pancreatic exocrine insufficiency-evidence-based proposal for a paradigm shift in pancreatic surgery.

BACKGROUND: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT). METHODS: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured. RESULTS: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT. CONCLUSION: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly.

Challenges in the interdisciplinary treatment of leakages after left-sided colorectal surgery: endoscopic negative pressure therapy, open-pore film drainage therapy and beyond.

PURPOSE: The treatment of anastomotic leakage after left colorectal surgery remains challenging. Since its introduction, endoscopic negative pressure therapy (ENPT) has proven to be advantageous, reducing the necessity of surgical revision. The aim of our study is to present our experience with endoscopic treatment of colorectal leakages and to identify potential factors influencing treatment outcome. METHODS: Patients who underwent endoscopic treatment of colorectal leakage were retrospectively analyzed. Primary endpoint was the healing rate and success of endoscopic therapy. RESULTS: We identified 59 patients treated with ENPT between January 2009 and December 2019. The overall closure rate was 83%, whereas only 60% of the patients were successfully treated with ENPT and 23% needed further surgery. The time between diagnosis of leakage and uptake of endoscopic treatment did not influence the closure rate, but patients with chronic fistula (> 4 weeks) showed a significantly higher reoperation rate than those with an acute fistula (94% vs 6%, p = 0.01). CONCLUSION: ENPT is a successful treatment option for colorectal leakages, which appears to be more favorable when started early. Further studies are still needed to better describe its healing potential, but it deserves an integral role in the interdisciplinary treatment of anastomotic leakages.

Predictors of Defensive Practices among Italian Psychiatrists: Additional Findings from a National Survey.

Background: Defensive medicine is characterized by medical decisions made primarily as a precaution against potential malpractice claims. For psychiatrists, professional responsibility encompasses not only the appropriateness of diagnosis and treatment but also the effects of their interventions on patients and their behaviors. Objective: To investigate the socio-demographic, educational, and occupational characteristics and work-related attitudes that may serve as predictors of defensive medicine among Italian psychiatrists. This research extends the results of a previous analysis based on a national survey. Methods: A secondary analysis of the database of a national survey on attitudes and behaviors of Italian psychiatrists regarding defensive medicine and professional liability was performed for this study. Results: Among 254 surveyed psychiatrists, 153 admitted to practicing defensive medicine, while 101 had this attitude with less than half of their patients. The first group was predominantly comprised of women (p = 0.014), who were younger in age (43.34 y 9.89 vs. 48.81 y 11.66, p < 0.001) and had fewer years of professional experience (12.09 y ± 9.8 vs. 17.46 y ± 11.2, p < 0.001). There were no significant differences in prior involvement in complaints (p = 0.876) or the usual place of work (p = 0.818). The most prominent predictors for practicing defensive medicine were (1) considering guidelines and good clinical practices not only for their clinical efficacy but also or exclusively for reducing the risk of legal complaints for professional liability (OR = 3.62; 95%CI, 1.75-7.49), and (2) hospitalizing patients with violent intentions even if not warranted according to their mental state (OR = 2.28; 95%CI, 1.50-3.46, p < 0.001). Prioritizing protection from professional liability over patients' actual needs in prescribing or adjusting drug dosages and in involuntary hospitalization, as well as prescribing lower dosages than recommended for pregnant patients, were identified as additional predictors. Finally, years of professional experience exhibited a protective function against defensive practices. Conclusions: Psychiatrists advocate the need to implement a 'risk management culture' and the provision of more balanced duties in order to ensure ethical and evidence-based care to their patients. A particular source of concern stems from their professional responsibility towards not only the health of patients but also their behavior. However, these aspects conflict with a limited potential for assessment and intervention based on effective clinical tools. A reform of professional liability that considers the specificities of patients cared for by mental health services could contribute to reducing the risk of defensive medicine.

Management of intra-thoracic anastomotic leakages after esophagectomy: updated systematic review and meta-analysis of endoscopic vacuum therapy versus stenting.

Despite a significant decrease of surgery-related mortality and morbidity, anastomotic leakage still occurs in a significant number of patients after esophagectomy. The two main endoscopic treatments in case of anastomotic leakage are self-expanding metal stents (SEMS) and the endoscopic vacuum therapy (EVT). It is still under debate, if one method is superior to the other. Therefore, we performed a systematic review and meta-analysis of the existing literature to compare the effectiveness and the related morbidity of SEMS and EVT in the treatment of esophageal leakage. We systematically searched for studies comparing SEMS and EVT to treat anastomotic leak after esophageal surgery. Predefined endpoints including outcome, treatment success, endoscopy, treatment duration, re-operation rate, intensive care and hospitalization time, stricture rate, morbidity and mortality were assessed and included in the meta-analysis. Seven retrospective studies including 338 patients matched the inclusion criteria. Compared to stenting, EVT was significantly associated with higher healing (OR 2.47, 95% CI [1.30 to 4.73]), higher number of endoscopic changes (pooled median difference of 3.57 (95% CI [2.24 to 4.90]), shorter duration of treatment (pooled median difference - 11.57 days; 95% CI [- 17.45 to - 5.69]), and stricture rate (OR 0.22, 95% CI [0.08 to 0.62]). Hospitalization and intensive care unit duration, in-hospital mortality rate, rate of major and treatment related complications, of surgical revisions and of esophago-tracheal fistula failed to show significant differences between the two groups. Our analysis indicates a high potential for EVT, but because of the retrospective design of the included studies with potential biases, these results must be interpreted with caution. More robust prospective randomized trials should further investigate the potential of the two procedures.

Endoscopic vacuum therapy versus stenting for postoperative esophago-enteric anastomotic leakage: systematic review and meta-analysis.

BACKGROUND: Esophageal anastomotic leakage still represents a challenging complication after esophageal surgery. Endoscopically placed self-expandable metal stents (SEMS) are the treatment of choice, but since the introduction of endoscopic vacuum therapy (EVT) for esophageal leakage 10 years ago, increasing evidence has demonstrated that EVT might be a superior alternative. Therefore, we performed a systematic review and meta-analysis to compare the effectiveness and related morbidity of SEMS and EVT in the treatment of esophageal leak. METHODS: We systematically searched for studies comparing SEMS and EVT to treat anastomotic leakage after esophageal surgery. Predefined end points including outcome, treatment success, endoscopy, treatment duration, hospitalization time, morbidity, and mortality were assessed and included in the meta-analysis. RESULTS: Five retrospective studies including 274 patients matched the inclusion criteria. Compared with stenting, EVT was significantly associated with a higher rate of leak closure (odds ratio [OR] 3.14, 95 % confidence interval [CI] 1.23 to 7.98), more endoscopic device changes (pooled median difference of 3.09; 95 %CI 1.54 to 4.64]), a shorter duration of treatment (pooled median difference -11.90 days; 95 %CI -18.59 to -5.21 days), and a lower mortality rate (OR 0.39, 95 %CI 0.18 to 0.83). There were no significant differences in short-term and major complications. CONCLUSIONS: Owing to the retrospective quality of the studies with potential biases, the results of the meta-analysis must be interpreted with caution. However, the analysis indicates the potential benefit of EVT, which should be further investigated with standardized and prospectively collected data.

Fruit position within the canopy affects kernel lipid composition of hazelnuts.

BACKGROUND: The aim of this research was to study the variability in kernel composition within the canopy of hazelnut trees. RESULTS: Kernel fresh and dry weight increased linearly with fruit height above the ground. Fat content decreased, while protein and ash content increased, from the bottom to the top layers of the canopy. The level of unsaturation of fatty acids decreased from the bottom to the top of the canopy. Thus, the kernels located in the bottom layers of the canopy appear to be more interesting from a nutritional point of view, but their lipids may be more exposed to oxidation. The content of different phytosterols increased progressively from bottom to top canopy layers. CONCLUSION: Most of these effects correlated with the pattern in light distribution inside the canopy. The results of this study indicate that fruit position within the canopy is an important factor in determining hazelnut kernel growth and composition. © 2017 Society of Chemical Industry.

Investigation of Oxytocin Secretion in Anorexia Nervosa and Bulimia Nervosa: Relationships to Temperament Personality Dimensions.

Published studies suggested an implication of oxytocin in some temperament characteristics of personality. Therefore, we measured oxytocin secretion in 23 women with anorexia nervosa (AN), 27 with bulimia nervosa (BN) and 19 healthy controls and explored the relationships between circulating oxytocin and patients' personality traits. Plasma oxytocin levels were significantly reduced in AN women but not in BN ones. In healthy women, the attachment subscale scores of the reward dependence temperament and the harm avoidance (HA) scores explained 82% of the variability in circulating oxytocin. In BN patients, plasma oxytocin resulted to be negatively correlated with HA, whereas no significant correlations emerged in AN patients. These findings confirm a dysregulation of oxytocin production in AN but not in BN and show, for the first time, a disruption of the associations between hormone levels and patients' temperament traits, which may have a role in certain deranged behaviours of eating disorder patients.

Childhood trauma and cortisol awakening response in symptomatic patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: Exposure to trauma during childhood is a risk factor for eating disorders (EDs) in adulthood. The biological mechanisms underlying such increased risk seem to involve the endogenous stress response system (i.e., the hypothalamic-pituitary-adrenal [HPA] axis), which undergoes trauma-induced functional changes that may persist later in life. In the present study, we examined the effects of childhood trauma experiences on HPA-axis activity, comparing saliva cortisol awakening response (CAR) in adult patients with anorexia nervosa (AN) or bulimia nervosa (BN) with CAR in adult healthy controls. METHOD: Twenty-three patients with symptomatic AN, 21 patients with symptomatic BN, and 29 healthy women collected saliva samples at awakening and again after 15, 30, and 60 min. Participants also completed the Childhood Trauma Questionnaire and eating-related psychopathological rating scales. RESULTS: According to the Childhood Trauma Questionnaire, 13 individuals with AN and 12 individuals with BN, but none of the healthy women, reported childhood maltreatment. Compared with the control group, the non-maltreated AN patient group exhibited an enhanced CAR, whereas the group of non-maltreated BN patients showed a normal CAR. Moreover, both AN and BN patient groups with childhood maltreatment exhibited statistically significant blunting of CAR compared with non-maltreated groups. DISCUSSION: The present findings add to the evidence supporting the concept that there is a dysregulation of HPA-axis activity in symptomatic patients with EDs and suggest that childhood trauma exposure may contribute to such dysregulation.

Different effects of cholestyramine on postprandial secretions of cholecystokinin and peptide YY in women with bulimia nervosa.

OBJECTIVE: Patients with bulimia nervosa (BN) are reported to have decreased postprandial levels of cholecystokinin (CCK) and peptide YY (PYY). Fatty nutrients are the most powerful stimulus for releasing these peptides. Cholestyramine is an anion exchanger which adsorbs bile salts and reduces the digestion of lipids, affecting the secretion of both CCK and PYY. To further characterise the physiology of these peptides in BN, we aimed to investigate the effects of cholestyramine (12 g, per os) or placebo administered with a high-fat meal on CCK and PYY secretions in bulimic versus healthy women. RESULTS: Postprandial CCK levels significantly increased in both healthy and bulimic women after placebo + the high-fat meal, without any significant difference between the two groups. Cholestyramine administration significantly increased postprandial CCK responses in both healthy and bulimic women; however, significantly lower CCK levels were observed in BN. Postprandial PYY levels significantly increased after placebo administration in healthy women after the high-fat meal, whereas no significant changes were found in bulimic women. Cholestyramine, administered with the high-fat meal, significantly reduced postprandial PYY response in healthy women, but not in bulimic women. Finally, there was a negative correlation of the area under the curve with respect to the increase of PYY (after placebo administration) with binge frequency in the bulimic women. CONCLUSION: In BN an altered postprandial secretion of CCK may be evidenced when cholestyramine is combined with a high-fat meal. Instead, the postprandial secretion of PYY is significantly blunted and not affected by cholestyramine administration.

Early Canopy Management Practices Differentially Modulate Fruit Set, Fruit Yield, and Berry Composition at Harvest Depending on the Grapevine Cultivar.

The size and number of the berries and the rachis length are the main elements that define bunch compactness in grapevine (Vitis vinifera L.). This trait is of scientific and commercial interest because it strongly influences phytosanitary status and quality of the fruits. In this work, we investigated the effect of different canopy management strategies based on apical shoot and/or leaf removal applied at the early stage (pre-bloom) in altering the key determinants of bunch compactness. Specifically, we compared apical defoliation (removal of the first half of the shoot leaves from the top), basal defoliation (removal of the second half), and shoot trimming (removal of the apical half of the shoot) to untreated controls. The work was carried out in two red varieties ('Aglianico' and 'Casavecchia') that have contrasting bunch compactness (compact and loose, respectively). We measured relevant morphological traits, photosynthetic rates, fertility, fruit set, bunch architecture, and fruit main compositional parameters. This study demonstrates that the position of the removed shoot leaves along with the shoot trimming differentially modified fruit set, the number of berries per bunch, and berry fresh weight and composition at harvest. Nonetheless, the influence on bunch compactness was limited mainly because of photosynthetic and morphological factors strongly associated with the cultivar.

Metacognition in schizophrenia: A practical overview of psychometric metacognition assessment tools for researchers and clinicians.

Metacognition refers to the cognitive ability to control, monitor and modulate cognitive processes thus guiding and orienting behavior: a continuum of mental activities that ranges from more discrete ones, such as the awareness of the accuracy of others' judgment, to more integrated activities, such as the knowledge of cognitive processes. Metacognition impairment in schizophrenia, which is considered a core feature of the illness, has become a growing research field focusing on a wide range of processes including reasoning, autobiographical memory, memory biases, cognitive beliefs and clinical insight. There is a well-established relationship between metacognition and schizophrenia symptoms severity, as well as between impaired metacognitive functioning and specific symptomatic sub-domains, such as positive symptoms, negative symptoms, or disorganization. The development of specific cognitive-derived psychotherapies for metacognitive deficits in schizophrenia has been ongoing in the last years. Although sharing a metacognitive feature, these treatments focus on different aspects: false or unhelpful beliefs for metacognitive therapy; cognitive biases for metacognitive training; schematic dysfunctional beliefs for cognitive behavioral therapy (CBT) for psychoses; metacognitive knowledge and sense of identity for MERIT; interpersonal ideas or events triggering delusional thinking for MIT-P. This article reviews the instruments designed to assess metacognitive domains and functions in individuals with schizophrenia, providing mental health professionals with an overview of the heterogeneous current scenario ranging from self-administered scales to semi-structured interviews, which are supported by a variety of theoretical frameworks. Future directions may address the need for more specific and refined tools, also able to follow-up psychotherapeutic-induced improvements.

Vox clamantis in deserto: a survey among Italian psychiatrists on defensive medicine and professional liability.

Due to recent events, professional liability for psychiatrists in Italy is currently a matter of lively debate. Specifically, overwhelming pressure on psychiatrists' duties has been brought by regulatory developments, such as the closure of forensic psychiatric hospitals, with the consequent return of offenders to community-based care, and the mental health consequences of the pandemic. According to Italian courts, psychiatrists are not only responsible for diagnostic and therapeutic appropriateness but also for the effects of their interventions on patients, and their behaviors. The aim of this study was to explore the attitude and behaviors of Italian psychiatrists regarding defensive medicine and professional liability. A total sample of 254 psychiatrists was surveyed by means of a quantitative online questionnaire. Most psychiatrists reported practicing defensive medicine (no. 153/254, 60.2%) and felt that their position of guarantee compromised their work in healthcare for patients (no. 138/253, 54.3%). Age correlated inversely with acknowledgment of defensive practices (r = -0.245, p < 0.001), with younger physicians more prone to defensive medicine (p = 0.013), particularly for patients at risk of suicide or violence. Psychiatrists in 'closed' settings (hospital wards, residential and rehabilitation centers, mental health service units in prison) reported more malpractice claims (p = 0.037) and complaints (p = 0.031), as well as a greater propensity to act defensively. In the treatment of patients with violent behavior, suicidal ideation, dual diagnoses, and criminal convictions, defensive practices were associated more with perceived legal risks (r = 0.306, p < 0.001) than actual legal involvement (p > 0.05). Anxiety, anger, and restlessness were common reactions to legal complaints, involving no. 50/254 (19.7%) respondents, with 40% reporting impaired functioning. Most psychiatrists (no. 175/253, 68.9%) were concerned about both civil and criminal laws regarding their professional responsibility, but many were not fully informed about recent legislative regulations and younger physicians resulted scarcely trained in risk management (p < 0.001). In conclusion, our findings suggest that defensive medicine is a common phenomenon among psychiatrists and their position of guarantee drives this attitude. Education on legal implications and risk management should be provided starting from the university and continuing over time, to improve the knowledge of young and senior doctors on professional liability and inform their decision-making processes. This would also reduce defensive practices and improve the quality of healthcare. Considering the concerns of younger physicians, as well as of professionals working in acute and high-intensity medical care facilities, there is also an urgent need for a revision of the medical liability to ensure the sustainability of the National Health Service.

Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH.

A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of fibrosis remain unclear. In addition, a gut-liver axis has been suggested to play a role in NASH, but the role of CD4+ T cells in this axis has just begun to be investigated. Combining single-cell RNA sequencing and multiple-parameter flow cytometry, we provide the first cell atlas to our knowledge focused on liver-infiltrating CD4+ T cells in patients with NAFLD and NASH, showing that NASH is characterized by a population of multicytokine-producing CD4+ T cells. Among these cells, only those with a Th17 polarization state were enriched in patients with advanced fibrosis. In parallel, we observed that Bacteroides appeared to be enriched in the intestine of NASH patients and to correlate with the frequency of multicytokine-producing CD4+ T cells. In short, we deliver a CD4+ T cell atlas of NAFLD and NASH, providing the rationale to target CD4+ T cells with a Th17 polarization state to block fibrosis development. Finally, our data offer an early indication to test whether multicytokine-producing CD4+ T cells are part of the gut-liver axis characterizing NASH.

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis.

Metastasis is a cancer-related systemic disease and is responsible for the greatest mortality rate among cancer patients. Interestingly, the interaction between the immune system and cancer cells seems to play a key role in metastasis formation in the target organ. However, this complex network is only partially understood. We previously found that IL-22 produced by tissue resident iNKT17 cells promotes cancer cell extravasation, the early step of metastasis. Based on these data, we aimed here to decipher the role of IL-22 in the last step of metastasis formation. We found that IL-22 levels were increased in established metastatic sites in both human and mouse. We also found that Th22 cells were the key source of IL-22 in established metastasis sites, and that deletion of IL-22 in CD4+ T cells was protective in liver metastasis formation. Accordingly, the administration of a murine IL-22 neutralizing antibody in the establishment of metastasis formation significantly reduced the metastatic burden in a mouse model. Mechanistically, IL-22-producing Th22 cells promoted angiogenesis in established metastasis sites. In conclusion, our findings highlight that IL-22 is equally as important in contributing to metastasis formation at late metastatic stages, and thus, identify it as a novel therapeutic target in established metastasis.

The acute salivary ghrelin response to a psychosocial stress is enhanced in symptomatic patients with bulimia nervosa: a pilot study.

BACKGROUND: Stress is a precipitating factor for both binge eating and bulimia nervosa (BN); however, the biological mechanisms through which it may trigger binge eating are poorly understood. There is evidence that the adrenal hormone cortisol and the gastric peptide ghrelin might be involved in stress-induced food ingestion. We hypothesized that symptomatic patients with BN might disclose deranged responses of ghrelin and/or cortisol to stressors and that this could be related to their binge-eating behaviour. METHODS: Here we investigated salivary cortisol and ghrelin responses to the Trier Social Stress Test (TSST) in 10 women with acute BN and 10 age-matched healthy females. Eating-related psychopathology and behaviours were assessed by self-report measures. RESULTS: No significant differences emerged between bulimic patients and healthy controls in the pre-stress salivary levels of both cortisol and ghrelin. The BN patients displayed normal cortisol but enhanced ghrelin responses to TSST. No significant correlations emerged between stress-induced salivary hormone changes and self-report measures of binge eating. CONCLUSION: To our knowledge, this is the first study showing deranged salivary ghrelin reactivity to a psychosocial stressor in symptomatic patients with BN. The extent to which this could contribute to the binge-eating behaviour of BN subjects awaits clarification.

Combined endoscopic-percutaneous treatment of upper gastrointestinal enterocutaneous fistula using vacuum therapy and resorbable plug insertion (Vac-Plug).

After gastrointestinal resections, leakages can occur, persist despite conventional therapy and result in enterocutaneous fistulae. We developed a combination method using flexible endoscopic techniques to seal the enteric orifice with an absorbable plug in addition to a percutaneously and fistuloscopically guided open-pore film drainage (Vac-Plug method). We retrospectively searched our endoscopy database to identify patients treated with the outlined technique. The clinical and pathological data were assessed, the method analyzed and characterized and the technical and clinical success determined. We identified 14 patients that were treated with the Vac-Plug method (4 females, 10 males with a mean age of 56 years, range 50-74). The patients were treated over a time period of 23 days (range 4-119) in between one to thirteen interventions (mean n = 5). One patient had to be excluded due to short follow-up after successful closure. Seventy-seven percent (10/13) were successfully treated with a median follow-up of 453 days (range 35-1246) thereafter. No treatment related complications occurred during the therapy. The data of the analysis showed that the Vac-Plug therapy is safe and successful in a relevant proportion of the patients. It is easy to learn and to apply and is well tolerated. In our opinion, it is a promising addition to the armamentarium of interventional methods of these difficult to treat patients. Of course, its usefulness must be further validated in larger prospective studies.

Circulating Cancer Associated Macrophage-like Cells as a Potential New Prognostic Marker in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Circulating Cancer Associated Macrophage-like cells (CAMLs) have been described as novel liquid biopsy analytes and unfavorable prognostic markers in some tumor entities, with scarce data for Pancreatic Ductal Adenocarcinomas (PDAC). METHODS: Baseline and follow-up blood was drawn from resected curative (n = 36) and palliative (n = 19) PDAC patients. A microfluidic size-based cell enrichment approach (ParsortixTM) was used for CAML detection, followed by immunofluorescence staining using pan-keratin, CD14, and CD45 antibodies to differentiate between CAMLs, circulating tumor cells (CTCs), and leukocytes. RESULTS: CAMLs were detectable at baseline in 36.1% of resected patients and 47.4% of palliative PDAC patients. CAML detection was tumor stage independent. Follow-up data indicated that detection of CAMLs (in 45.5% of curative patients) was an independent prognostic factor for shorter recurrence-free survival (RFS) (HR: 4.3, p = 0.023). Furthermore, a combined analysis with CTCs showed the detectability of at least one of these cell populations in 68.2% of resected patients at follow-up. The combined detection of CAMLs and CTCs was also significantly associated with short RFS (HR: 8.7, p = 0.003). CONCLUSIONS: This pilot study shows that detection of CAMLs in PDAC patients can provide prognostic information, either alone or even more pronounced in combination with CTCs, which indicates the power of liquid biopsy marker analyses.