Endoscopic ultrasound-guided drainage of pancreatic fluid collections: The impact of evolving experience and new technologies in diagnosis and treatment over the last two decades

Background: Endoscopic ultrasound (EUS)-guided drainage is the preferred approach for drainage of pan- creatic uid collections (PFCs) due to the better experience and signi cant progress using newer stents and access devices during last decade. This study aimed to evaluate the role of the evolving experience and possible in uence of new technological devices on the outcome of patients evaluated for PFCs and submitted to EUS-guided drainage during two different periods: the early period at the beginning of experience when a standardized technique was used and the late period when the increased experience of the operator, combined with different stents quality were introduced in the management of PFCs. Methods: We retrospectively analyzed the clinical data of a cohort of 91 consecutive patients, who underwent EUS-guided drainage of symptomatic PFCs from October 2001 to September 2017. Demographic, therapeutic results, complications, and outcomes were compared between early years’ group (2001 2008) and late years’ group (2009 2017). Results: Endoscopic treatment was successfully achieved in 55.6% (20/36) of patients in the early years’ group, and in 96.4% (53/55) in the late years’ group. Eighteen patients (12 in early years’ and 6 in the late year’s group) required additional open surgery. Procedural complications were observed in 5 patients, 4 in early years’ and 1 in late years’ group. Mortality was registered in two patients (2.2%), one for each group. Conclusions: During our long-term survey using EUS-guided endoscopic drainage of PFCs, signi cantly better outcomes in term of improved success rate and decrease complications rate were observed during the late period.

Stroke and depression: A bidirectional link

A number of studies have assessed the influence of depression on the risk of cardiovascular disease. A growing literature indicates a link between depression and cerebrovascular events, although the direction of this association remains unclear. Numerous data have emerged suggesting an association between depressive symptoms and subsequent risk of stroke, thus leading to the hypothesis that a direct causality between depression and stroke exists. Notwithstanding, how depression may act as a risk factor for stroke is still unclear. Depression might be linked to stroke via neuroendocrine and inflammation effects, through correlation with major comorbidities such as hypertensionand diabetes or by intervention of lifestyle behavioral mediators. Finally, antidepressant medications have recently drawn attention for a possible association with increased risk of stroke, although such findings remain uncertain. Depression has been also established as an important consequence after stroke, exerting a significant adverse impact on the course of motor recovery, social functioning and, overall, on quality of life. Post stroke depression occurs in nearly one third of stroke cases, but the exact mechanism leading to depression after stroke is still incompletely understood. In this article, we will review contemporary epidemiologic studies, discuss potential mechanisms and specific aspects of the complex relation between depression and stroke.

Effects of Exposure to Extremely Low Frequency Electro-magnetic Fields on Circadian Rhythms and Distribution of Some Leukocyte Differentiation Antigens in Dairy Cows

Objective To investigate the effects of extremely low frequency magnetic and electric fields （ELFEMFs） emitted from 380 kV transmission lines on some leukocyte differentiation antigens in dairy cows. Methods The study was carded out in 5 cows exposed to 1.98-3.28 μT of ELFEMFs and in 5 control cows exposed to 0.2-0.7 μT of ELFEMFs. Following haematological and immunologic parameters were measured in both groups： WBC, CD45R, CD6, CD4, CD8, CD21, and CD11B leukocyte antigen expression. Results Some of the haematological and immunologic parameters under investigation were similar in both groups. However, CD8 （T lymphocyte surface antigen） was higher in the exposed group （1.35 ±0.120 vs 0.50 ±0.14×10^3/mL）. Furthermore, the CD4/CD8 ratio （0.84 ±0.05 and 2.19±0.16 for exposed and not exposed cows respectively） and circadian rhythm were different between the two groups. Conclusion Exposure to ELFEMFs is responsible of the abnormal temporal variations and distribution of some haematological and immunological parameters in dairy cows.

Apple as a Source of Dietary Phytonutrients: Bioavailability and Evidence of Protective Effects against Human Cardiovascular Disease

The dietary consumption of fruit and vegetable is associated with a lower incidence of degenerative diseases such as cardiovascular disease. Most recent interest has focused on the bioactive phenolic compounds in vegetable products. All varieties of apple contain several antioxidants and polyphenols that possess many biological activities, such as antioxidant and anti-inflammation properties. The review describes the nutritional properties of apples and their derivatives, with a particular attention to polyphenol compounds. Moreover, the health benefits of apples and the potential molecular mechanisms against cardiovascular disease are reviewed.

Risk for gastric neoplasias in patients with chronic atrophic gastritis:A critical reappraisal

Chronic atrophic gastritis （CAG） is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue （non-metaplastic atrophy） or by glandular structures inappropriate for location （metaplastic atrophy）. Epidemiological data suggest that CAG is associated with two different types of tumors： Intestinal-type gastric cancer （GC） and type I gastric carcinoid （T I GC）. The pathophysiological mechanisms which lead to the development of these gastric tumors are different, It is accepted that a multistep process initiating from Helico- bacterpylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The T I GC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of T I GC. Thus, several events occur in the gastric mucosa before the development of intestinatype GC and/ or T I GC and these take several years. Knowledge ofCAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors as- sociated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

Prevalence of overweightedness in patients with gastro-esophageal reflux

AIM: To evaluate whether the prevalence of overweight and obese conditions is increased in gastro-esophageal reflux disease (GERD) patients (with 24-h pathological pH recordings) in comparison to general population. METHODS: A total of 196 consecutive patients (103 females, age range 18-83 years) with symptoms of gastro-esophageal reflux (GER) and 24-h pathological esophageal pH-metry. Body mass index (BMI) of the patients was calculated and its distribution (%) was compared with that of the Italian general population as assessed by National Bureau of Census (ISTAT). To evaluate the association of GERD with weight categories, the binomial test was employed. P < 0.05 was considered statistically significant. RESULTS: In males, overweightedness (BMI 25-25.9) was present in 43% of GERD patients vs 41.8% of Italian population (IP) (ns), obesity (BMI ≥ 30) in 10.9% vs 9.1% (ns). In females overweight was present in 34.9% of GERD patients vs 25.7% of IP (P < 0.01), obesity in 13.6% of GERD patients vs 9.1% of IP (P < 0.01). No statistically significant differences were noted in different age classes. CONCLUSION: In comparison to the Italian general population, the prevalence of overweightedness and obesity is increased in female but not in male patients with ascertained gastro-esophageal reflux disease.

Functional topography of the corpus callosum investigated by DTI and f MRI

This short review examines the most recent functional studies of the topographic organization of the human corpus callosum, the main interhemispheric commissure. After a brief description of its anatomy, development, microstructure, and function, it examines and discusses the latest findings obtained using diffusion tensor imaging(DTI) and tractography(DTT) and functional magnetic resonance imaging(f MRI), three recently developed imaging techniques that have significantly expanded and refined our knowledge of the commissure. While DTI and DTT have been providing insights into its microstructure, integrity and level of myelination, f MRI has been the key technique in documenting the activation of white matter fibers, particularly in the corpus callosum. By combining DTT and f MRI it has been possible to describe the trajectory of the callosal fibers interconnecting the primary olfactory, gustatory, motor, somatic sensory, auditory and visual cortices at sites where the activation elicited by peripheral stimulation was detected by fMRI. These studies have demonstrated the presence of callosal fiber tracts that cross the commissure at the level of the genu, body, and splenium, at sites showing f MRI activation. Altogether such findings lend further support to the notion that the corpus callosum displays a functional topographic organization that can be explored with f MRI.

Rapid determination of anti-estrogens by gas chromatography/mass spectrometry in urine:Method validation and application to real samples

A fast screening protocol was developed for the simultaneous determination of nine antiestrogenic agents (aminoglutethimide, anastrozole, clomiphene, drostanolone, formestane, letrozole, mesterolone, tamoxifen, testolactone) plus five of their metabolites in human urine. After an enzymatic hydrolysis, these compounds can be extracted simultaneously from urine with a simple liquid–liquid extraction at alkaline conditions. The analytes were subsequently analyzed by fast-gas chromatography/ mass spectrometry (fast-GC/MS) after derivatization. The use of a short column, high-fiow carrier gas velocity and fast temperature ramping produced an efficient separation of all analytes in about 4 min, allowing a processing rate of 10 samples/h. The present analytical method was validated according to UNI EN ISO/IEC 17025 guidelines for qualitative methods. The range of investigated parameters included the limit of detection, selectivity, linearity, repeatability, robustness and extraction efficiency. High MSsampling rate, using a benchtop quadrupole mass analyzer, resulted in accurate peak shape definition under both scan and selected ion monitoring modes, and high sensitivity in the latter mode. Therefore, the performances of the method are comparable to the ones obtainable from traditional GC/MS analysis. The method was successfully tested on real samples arising from clinical treatments of hospitalized patients and could profitably be used for clinical studies on anti-estrogenic drug administration.

BRCA mutations and gastrointestinal cancers:When to expect the unexpected?

BRCA1/2 pathogenic variants are widely known as major risk factors mainly for breast and ovarian cancer,while their role in gastrointestinal(GI)malignancies such as colorectal cancer(CRC),gastric cancer and oesophageal cancer(OeC)is still not well established.The main objective of this review is to summarise the available evidence on this matter.The studies included in the review were selected from PubMed/GoogleScholar/ScienceDirect databases to identify published articles where BRCA1/2 pathogenic variants were assessed either as a risk factor or a prognostic/predictive factor in these malignancies.Our review suggests that BRCA1/2 might have a role as a risk factor for colorectal,gastric and OeC,albeit with differences among these diseases:In particular BRCA1 seems to be much more frequently mutated in CRC whereas BRCA2 appears to be much more closely associated with gastric and OeC.Early-onset cancer seems to be also associated with BRCA1/2 mutations and a few studies suggest a positive prognostic role of these mutations.The assessment of a potentially predictive role of these mutations is hampered by the fact that most patients with these diseases have been treated with platinum compounds,where it is expected that a higher probability of response should be seen.A few clinical trials focused on poly(ADPribose)polymerase inhibitors use in GI cancers are currently ongoing.

Secondary prevention of ischaemic stroke

In spite of a documented reduction in incidence in highincome countries over the last decades, stroke is still a leading cause of death and disability worldwide. With the ageing of the population stroke-related economic burden is expected to increase, because of residual disability and its complications, such as cognitive impairment, high risk of falls and fractures, depression and epilepsy. Furthermore, because of the substantial rate of early and long-term vascular recurrences after the first event, secondary prevention after cerebral ischaemia is a crucial issue. This is even more important after minor stroke and transient ischaemic attack(TIA), in order to reduce the risk of potentially more severe and disabling events. To accomplish this aim, acute long-term medical and surgical treatments as well aslifestyle modifications are strongly recommended. However, apart from the well-established indications to thrombolysis, studies in acute phase after a first stroke or TIA are scarce and evidence is lacking. More trials are available for long-term secondary prevention with different classes of drugs, including antithrombotic medications for ischaemic events of arterial and cardiac origin, especially related to atrial fibrillation(antiplatelets and anticoagulants, respectively), lipid lowering agents(mainly statins), blood pressure lowering drugs, surgical and endovascular revascularization procedures.

HIV Infection in Pregnancy and the Risk of Gestational Hypertension and Preeclampsia

The objective of this study was to evaluate the association between HIV infection and hypertensive disorders of pregnancy, comparing the rates of preeclampsia and gestational hypertension in a HIV-infected pregnant group and in a HIV-negative control pregnant group matched for age and parity. Furthermore, we aimed to compare the rates of hypertensive disorders in a subgroup of HIV-positive and HIV-negative African-American Black women. Patients and Methods: This was a prospective observational cohort study conducted at two University Departments of Obstetrics and Gynecology, Salesi Hospital, Ancona, and Sant’Orsola Hospital, Bologna. The HIV-infected patients’ group consisted of 126 pregnant women;140 HIV-negative pregnant women matched for age and parity served as controls. Gestational hypertension and preeclampsia were diagnosed according to NHBPEP-ISSHP criteria. Categorical data were analyzed using the Fisher exact test. Statistical significance was set at a p value < 0.05. Results: Gestational hypertension and preeclampsia were diagnosed in 3 of 126 HIV-positive patients (2.38%) and in 14 of 140 HIV-negative patients (10%), with a relative risk of 0.24 (p = 0.0112). In the subgroup of African-American Black women, gestational hypertension and preeclampsia were diagnosed in 2 out of 43 HIV-positive (4.7%) and in 3 out of 18 HIV-negative patients (16.7%) with a relative risk of 0.28, not statistically significant (p = 0.1887). Conclusion: Pregnant women with HIV infection seem to be protected against gestational hypertension and preeclampsia and this protective effect remains also in a high risk population, such as African-American Black ethnic group. The effect is present independently from treatment received and virus copies. The lack of immune response present since the conception period should account for unopposed trophoblast invasion resulting in a better placentation.

How to impute study-specific standard deviations in metaanalyses of skewed continuous endpoints?

AIM： To compare four methods to approximate mean and standard deviation （SD） when only medians and interquartile ranges are provided.METHODS： We performed simulated meta-analyses on six datasets of 15, 30, 50, 100, 500, and 1000 trials, respectively. Subjects were iteratively generated from one of the following seven scenarios： five theoreti-cal continuous distributions [Normal, Normal （0, 1）, Gamma, Exponential, and Bimodal] and two real-life distributions of intensive care unit stay and hospital stay. For each simulation, we calculated the pooled estimates assembling the study-specific medians and SD approximations： Conservative SD, less conservativeSD, mean SD, or interquartile range. We provided a graphical evaluation of the standardized differences.To show which imputation method produced the best estimate, we ranked those differences and calculated the rate at which each estimate appeared as the best, second-best, third-best, or fourth-best.RESULTS： Our results demonstrated that the best pooled estimate for the overall mean and SD was provided by the median and interquartile range （mean standardized estimates： 4.5 ± 2.2, P = 0.14） or by the median and the SD conservative estimate （mean standardized estimates： 4.5 ± 3.5, P = 0.13）. The less conservative approximation of SD appeared to be the worst method, exhibiting a significant difference from the reference method at the 90% confidence level. The method that ranked first most frequently is the interquartile range method （23/42 = 55%）, particularly when data were generated according to the Standard Normal, Gamma, and Exponential distributions. The second-best is the conservative SD method （15/42 = 36%）, particularly for data from a bimodal distributionand for the intensive care unit stay variable. CONCLUSION： Meta-analytic estimates are not signi-fcantly affected by approximating the missing values ofmean and SD with the correspondent values for medianand interquartile range.

p53 functional loss,stemness and hepatocellular carcinoma

The tumor suppressor p53 is a key player in the control of genomic integrity and homeostasis in connection with p63 and p73,the two other members of the p53 family.Loss of functional p53 leads to the proliferation and survival of mature cells and progenitor or stem cells that accumulate genetic alterations,thus favoring tumorigenesis.p53 loss of function,observed in a wide variety of human tumor types,is frequently caused by missense mutations more frequently found in the DNA binding domain,but can also be due to the expression of a plethora of viral and cellular negative regulators.Human hepatocellular carcinoma(HCC)represents a specific situation,first because the TP53 gene mutations pattern exhibits a“hot spot”rarely found in other tumor types that is linked to Aflatoxin B1 exposure and,second,because many HCCs do not exhibit any TP53 mutation.Here,we provide an overview of the current knowledge about the inhibition of p53 functions by the N-terminal(ΔN)truncated forms of the family,and their role in the emergence and maintenance of pre-malignant cells with stem cell characteristics and in HCC development.We focus in particular on the Nanog-IGF1R-ΔNp73 axis that is associated with stem-like features in HCC cells and that may provide an attractive new therapeutic target and help to develop new biomarkers for HCC risk stratification,as well as preventive strategies.