Habitual coffee drinkers display a distinct pattern of brain functional connectivity.

Coffee is the most widely consumed source of caffeine worldwide, partly due to the psychoactive effects of this methylxanthine. Interestingly, the effects of its chronic consumption on the brain's intrinsic functional networks are still largely unknown. This study provides the first extended characterization of the effects of chronic coffee consumption on human brain networks. Subjects were recruited and divided into two groups: habitual coffee drinkers (CD) and non-coffee drinkers (NCD). Resting-state functional magnetic resonance imaging (fMRI) was acquired in these volunteers who were also assessed regarding stress, anxiety, and depression scores. In the neuroimaging evaluation, the CD group showed decreased functional connectivity in the somatosensory and limbic networks during resting state as assessed with independent component analysis. The CD group also showed decreased functional connectivity in a network comprising subcortical and posterior brain regions associated with somatosensory, motor, and emotional processing as assessed with network-based statistics; moreover, CD displayed longer lifetime of a functional network involving subcortical regions, the visual network and the cerebellum. Importantly, all these differences were dependent on the frequency of caffeine consumption, and were reproduced after NCD drank coffee. CD showed higher stress levels than NCD, and although no other group effects were observed in this psychological assessment, increased frequency of caffeine consumption was also associated with increased anxiety in males. In conclusion, higher consumption of coffee and caffeinated products has an impact in brain functional connectivity at rest with implications in emotionality, alertness, and readiness to action.

Gastroesophageal Reflux Disease Diagnosis by New Consensus in Clinical Practice: The Additional Value of Mean Basal Impedance.

BACKGROUND: Recently, Lyon consensus and ROME IV were published as there was a need to create a more objective evaluation for gastroesophageal reflux disease (GERD) in order to better predict treatment outcomes. However, with classical pH-impedance measures, some patients would still have diagnostic uncertainty, and new metrics, such as mean nocturnal basal impedance (MNBI), have emerged to corroborate with GERD diagnosis. The aim of the present study was to describe the prevalence of GERD, functional heartburn (FH), reflux hypersensitivity (RH), and undetermined diagnosis using current consensuses and to evaluate if MNBI could be considered a supportive measure for the diagnosis of GERD. METHODS: Patients who underwent pH-multichannel intraluminal impedance (MII-pH) for suspected GERD between 2013 and 2018 were included. Subjects with previous diagnosis of GERD (e.g., esophagitis grade C or D according to Los Angeles classification, Barrett's esophagus, or peptic stricture), atypical symptoms, major esophageal motor disorder, eosinophilic esophagitis, or under proton pump inhibitor were excluded from the analysis. RESULTS: We included 75 patients. The prevalence of GERD, FH, RH and undetermined diagnosis was 44%, 14.7%, 12%, and 29.3%, respectively. MNBI was lower in patients with GERD (GERD: 1,307.5 ± 817.9 Ω vs. FH: 3,039.6 ± 1,040.8 Ω, RH: 2,617.1 ± 1,342.2 Ω, undetermined: 2,351.9 ± 1,018.2, p < 0.001), although it was similar between patients with FH and RH (p = 0.44) or between undetermined diagnosis and FH/RH (p = 0.15). More patients with a GERD diagnosis had a MNBI under 2,292 Ω (GERD: 93.9% vs. non-GERD: 31.7%, p < 0.001). CONCLUSION: In our study, using MII-pH criteria, less than half of the patients had a GERD diagnosis. MNBI showed additional value as another metric for the diagnosis of GERD.

Prediction of adenoma recurrence after piecemeal endoscopic mucosal resection: interobserver agreement and utilization of the Sydney EMR recurrence tool.

Background and aims: Piecemeal endoscopic mucosal resection (pEMR) allows resection of larger non-invasive colorectal lesions. Adenoma recurrence is an important limitation and occurs in ≤20%. The present study aimed to validate the Sydney EMR recurrence tool (SERT) score as a predictor of both endoscopic and histologic recurrence and evaluate interobserver agreement in adenoma recurrence based on endoscopic scar assessment, among nonexperts in EMR.Methods: Retrospective cohort and cross-sectional study, in which all patients submitted to pEMR in a tertiary care center in Portugal, between 2012 and 2018 were included. SERT-score was calculated for all lesions and compared with the SMSA (size, morphology, site, access) score already validated as a predictor of adenoma recurrence. Image based offline analysis was performed to evaluate adenoma recurrence prediction and assess the interobserver agreement within a heterogeneous group of participants, mostly composed by nonexperts in EMR.Results: There was a moderate positive correlation between the SERT and SMSA scores (p <.001; r = 0.61). SERT-score was significantly associated with endoscopic recurrence (p =.005) and histologic recurrence (p = .015). Endoscopic prediction of recurrence had high coefficient of agreement (k-0.806; p < .001).Conclusion: Histologic recurrence after pEMR can be predicted by SERT score and optical diagnosis of recurrent adenoma has high interobserver agreement between nonexperts in EMR.

Coherent-hybrid STED: high contrast sub-diffraction imaging using a bi-vortex depletion beam.

Stimulated emission depletion (STED) fluorescence microscopy squeezes an excited spot well below the wavelength scale using a doughnut-shaped depletion beam. To generate a doughnut, a scale-free vortex phase modulation (2D-STED) is often used because it provides maximal transverse confinement and radial-aberration immunity (RAI) to the central dip. However, RAI also means blindness to a defocus term, making the axial origin of fluorescence photons uncertain within the wavelength scale provided by the confocal detection pinhole. Here, to reduce the uncertainty, we perturb the 2D-STED phase mask so as to change the sign of the axial concavity near focus, creating a dilated dip. By providing laser depletion power, the dip can be compressed back in three dimensions to retrieve lateral resolution, now at a significantly higher contrast. We test this coherent-hybrid STED (CH-STED) mode in x-y imaging of complex biological structures, such as the dividing cell. The proposed strategy creates an orthogonal direction in the STED parametric space that uniquely allows independent tuning of resolution and contrast using a single depletion beam in a conventional (circular polarization-based) STED setup.

Infectious proctitis due to syphilis and chlamydia: an exuberant presentation.

Infectious proctitis by sexually transmitted diseases are increasing in incidence and should be considered in men who have sex with men with rectal symptoms. In this case, we show an exuberant form of syphilitic and chlamydial proctitis that could be diagnosed as another anorectal disease such as inflammatory proctitis or even as a neoplasm if the clinical history is not taken into account.

What's next after failure of OTSC® for the closure of gastrostomy fistula? Another OTSC®?

A 55-year-old female patient was diagnosed with squamous cell carcinoma of the nasopharynx stage in 2016 and proposed for radical chemo/radiotherapy. A percutaneous endoscopy gastrostomy was performed in 2016 because of the patient´s difficulty in swallowing. The patient had good response to therapy with disease´s remission so the gastrostomy tube was removed in 2018. After two weeks of conservative management, the patient maintained a gastrocutaneous fistula with extravasation of liquid contents. Endoscopic closure with over the scope clip (OTSC®) was performed.

Diagnostic yield of endoscopic ultrasonography for dilation of common bile duct of indeterminate cause.

INTRODUCTION: with the widespread use of abdominal imaging, common bile duct (CBD) dilation is a common problem in the daily practice. However, the significance of a dilated CBD as a predictor of underlying disease has not been well elucidated and there are currently no guidelines for its approach. METHODS: this was a retrospective study of patients who underwent endoscopic ultrasonography (EUS) from 2010 to 2017 due to a dilated CBD detected by transabdominal ultrasonography TUS (CBD ≥ 7 mm) or computed tomography (CT) (CBD ≥ 10 mm), with no identified cause (n = 56). The aims were to assess the diagnostic yield of EUS and to identify predictors for a positive EUS. RESULTS: the majority of patients (n = 39) had normal findings on EUS. Abnormal EUS findings were found in 30% (n = 17) of the patients, which included choledocholithiasis (n = 6), ampuloma (n = 3), choledochal cyst (n = 2), benign CBD stenosis (n = 2), cyst of the head of the pancreas (n = 1), cholangiocarcinoma (n = 1), chronic pancreatitis (n = 1) and CBD compression due to adenomegaly (n = 1). Factors that positively related with findings on EUS were increased levels of gamma glutamyl transferase (331 U/l vs 104 U/l, p = 0.039), alkaline phosphatase (226 U/l vs 114 U/l, p = 0.041), total bilirubin (TB) (6.5 g/dl vs 1.2 g/dl, p = 0.035) and the presence of signs/symptoms (p = 0.042). Of the 21 patients (38%) who were asymptomatic with normal liver biochemical tests, four (19%) had findings on EUS. CONCLUSIONS: the majority of patients with a dilation of the CDB have a normal EUS. Increased cholestasis enzymes, increased TB and the presence of signs and symptoms are predictors of a positive EUS.

Choledocholithiasis in elderly patients with gallbladder in situ - is ERCP sufficient?

INTRODUCTION: Along with increased life expectancy, the proportion of elderly patients with choledocholithiasis will increase and with this, the need for endoscopic cholangiopancreatography (ERCP). Current recommendations suggest laparoscopic cholecystectomy in all patients with choledocholithiasis to prevent biliary events. However, adherence to these recommendations is low, especially in older patients. METHODS: Retrospective study that included non-cholecystectomized patients aged > =75 years who underwent ERCP for choledocholithiasis from 2013-2016 (n = 131). A new biliary event was defined as the need for a new ERCP, cholecystitis, cholangitis or gallstone pancreatitis. AIM: The aim of this study was to compare the outcomes of new biliary events and mortality in cholecystectomized vs non-cholecystectomized patients after ERCP. RESULTS: Cholecystectomy was performed in 22% of the patients (92% laparoscopic). The post-cholecystectomy complication rate was 13% and the mortality rate was 7%. During the follow-up period (669 ± 487 days) a new biliary event occurred in 20% of patients - 10% new ERCP, 9% cholecystitis, 9% cholangitis and 2% pancreatitis. Cholecystectomized patients had fewer events (7% vs 24%, p = .048) and longer time to event (p = .016). There was no statistically significant difference in all-cause mortality (14% vs 27%, p = .13), mortality related to lithiasis (0% vs 9%, p = .11) or time to mortality from all causes (p = .07) and related to biliary events (p = .07). CONCLUSIONS: In this group of elderly patients, cholecystectomy after ERCP prevented the occurrence of new biliary events but resulted in a non-statistically significant difference in mortality.

Predictive factors of an incomplete examination and inadequate small-bowel cleanliness during capsule endoscopy.

AIM: the aim of this study was to determine predictive factors for an incomplete capsule endoscopy and an inadequate small-bowel preparation in capsule endoscopy. METHODS: predictive factors for an incomplete capsule endoscopy were evaluated. Therefore, all patients with incomplete examinations performed between June 2009 and February 2016 were retrospectively included and compared with all patients with complete procedures performed between January 2014 and February 2016. Predictive factors of an inadequate small-bowel cleanliness were assessed. Therefore, the subset of patients that underwent capsule endoscopy between January 2014 and February 2016, including incomplete examinations, were evaluated. Small-bowel cleanliness was evaluated according to a quantitative index and a qualitative evaluation scale. Data with regard to patient and capsule endoscopy was analyzed. RESULTS: 31 incomplete and 122 complete capsule endoscopies were included in the analysis of predictive factors for an incomplete capsule endoscopy. The degree of dependency (OR = 4.67; p = 0.028), performance of a capsule endoscopy in hospitalized patients (OR = 4.04; p = 0.006) and prior abdominal surgery (OR = 3.45; p = 0.012) were independent predictive factors of an incomplete procedure. 130 patients were included in the analysis of predictive factors for an inadequate small-bowel cleanliness. The mean quantitative index value was 7.3 (s.d. ± 2.3); 41.6% and 58.5% of capsule endoscopies were classified as poor-fair and good/excellent respectively, according to the qualitative evaluation. Independent predictive factors for an inadequate preparation according to the quantitative index included male gender (Beta = -0.79; p = 0.028), small-bowel transit time (Beta = -0.007; p < 0.0001) and cardiac disease (Beta = -1.29; p = 0.001). Associated factors according to the qualitative evaluation included male gender (OR = 0.406; p = 0.027) and small-bowel transit time (SBTT) (OR = 0.993; p < 0.0001). CONCLUSION: inpatient status, higher degrees of dependency and abdominal surgery are predictive factors for an incomplete capsule endoscopy; male gender and higher small-bowel transit time are predictive factors for an inadequate cleanliness.

Fecal microbiota transplantation in refractory or recurrent Clostridium difficile infection: a real-life experience in a non-academic center.

AIM: this study aimed to describe the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of refractory and recurrent Clostridium difficile infection (CDI). METHODS: this was an observational study of patients with refractory or recurrent CDI treated with FMT between June 2014 and January 2017. Primary and secondary outcomes were the resolution of diarrhea without CDI recurrence within two months after one or more FMT. A descriptive analysis was performed. RESULTS: thirty-four FMT were performed in 28 patients, 88.2% (n = 30) using an upper route with a gastroscopy and 11.8% (n = 4) with colonoscopy; 50% (n = 17) of FMT were due to recurrent CDI and 50% (n = 17) were due to refractory CDI. The overall cure rate of upper FMT was 87.5% (21/24) and 100% (4/4) when colonoscopy was performed. A cure was achieved after one FMT in 88% (22/25) of cases and after two or more FMT in 8% (2/25) of cases, resulting in an overall cure rate of 96% (24/25). No severe adverse events were reported. CONCLUSION: FMT constitutes an effective and safe approach for the management of refractory and recurrent CDI, with an overall cure rate of 96% and no reported severe adverse events.

Negative video capsule enteroscopy - what's the next step?

Video capsule endoscopy (VCE) is a reliable noninvasive method for examination of small-bowel mucosa. However, it has some limitations. The aim of this article was to review the approach in patients with negative VCE. It is clear that a negative VCE should be interpreted based on the indication. In suspected small bowel bleeding (SSBB), patients with ongoing/recurrent overt bleeding, or occult bleeders who experience significant declines in hemoglobin after a negative VCE should proceed small bowel study; on the other hand, patients with occult SSBB and only mild-moderate anemia should be managed with supportive care. In inflammatory bowel disease, a normal VCE has a very high sensitivity and negative predictive value. In small bowel tumor suspicion there is a high risk of false negative results, so another imaging modality should be considered. In polyposis syndromes, if VCE is negative, patients should continue screening within 2-3 years.

Evaluation and comparison of capsule endoscopy scores for assessment of inflammatory activity of small-bowel in Crohn's disease.

INTRODUCTION: Capsule endoscopy (CE) has the highest sensitivity in the evaluation of small-bowel mucosa in Crohn's disease (CD). Recent guidelines recommend the use of validated CE scores to assess small-bowel inflammatory activity in CD. Lewis score (LS) and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) are the currently available validated scores, but comparative studies are scarce. Moreover, correlation of these endoscopic scores with biomarkers and clinical activity is lacking. This study aims to compare LS with CECDAI, to determine cutoff values for CECDAI similar to those of LS (135-790), and to correlate LS and CECDAI with biomarkers and symptoms. STUDY: All patients with CD who underwent CE between March/2010 and February/2016 were included. LS and CECDAI were determined after analysis of each CE. In patients with small-bowel CD, C-reactive protein (CRP) and Harvey-Bradshaw index (HBI) were evaluated. STATISTICAL ANALYSIS: descriptive statistics, Spearman's correlation coefficient and linear regression analysis. SIGNIFICANCE: p<0.05. RESULTS: Fifty-three patients were included and the mean values obtained for LS were 1147±1453, CECDAI 11.3±6.9, CRP 0.92±1.5mg/dL and HBI 2.4±2.8. There was a very strong correlation between LS and CECDAI (rs=0.878; p<0.0001) and thresholds values of 135-790 in LS corresponded to 7.7-10.3 cutoff values in CECDAI, respectively. Neither CRP correlated with LS (rs=0.068; p=0.72) or CECDAI (rs=-0.004; p=0.98), nor HBI with LS (rs=-0.15; p=0.40) or CECDAI (rs=-0.10; p=0.23). CONCLUSION: Correlation between the two CE activity scores was very strong, with LS thresholds of 135-790 corresponding to CECDAI values of 7.7-10.3. HBI and CRP had no correlation with CECDAI and LS.

Hypersensitivity to azathioprine in a patient with Crohn's disease: a case report.

Azathioprine (AZA) is commonly used in inflammatory bowel disease and many other medical diseases. The most common adverse events of AZA include gastrointestinal effects, hepatotoxicity, myelotoxicity and pancreatitis.

Validation of SPICE, a method to differentiate small bowel submucosal lesions from innocent bulges on capsule endoscopy.

BACKGROUND AND AIMS: Small bowel submucosal lesions (SBSL) and innocent bulges may have an identical appearance and be difficult to distinguish on small bowel capsule endoscopy (SBCE). Recently, Girelli et al. proposed a score, smooth, protruding lesion index on capsule endoscopy (SPICE), in order to differentiate between the two. We aimed to evaluate and validate SPICE as a differentiation method between innocent bulges and SBSLs. METHODS: We evaluated all SBCEs performed in our department between January 2005 and September 2015, and selected the ones with a smooth, round, protruding lesion in the small bowel. Lesions with suspicious characteristics were excluded. A video clip of the region of interest was created and SPICE was assigned blindly and independently by two endoscopists. We determined the discriminative ability of SPICE using the definitive diagnosis of each patient as the standard criteria. RESULTS: We included 30 SBCEs corresponding to 12 SBSLs (four gastrointestinal stromal tumors, two neuroendocrine tumors, four lipomas and two polypoid lymphangiectasias) and 18 innocent bulges. SPICE scores ranged from 0 to 4, allowing the distinction between SBSLs and innocent bulges (p < 0.001). SPICE > 2 had a 66.7% sensitivity, 100.0% specificity, 100.0% positive predictive value and 78.3% negative predictive value, and the area under the curve was 0.88 (95% CI, 0.73-1.00; p < 0.001) for the diagnosis of SBSL. CONCLUSIONS: Our data support SPICE, namely a score > 2, as a predictive method of SBSLs. Taking into account its simplicity, it may be very useful in the distinction between SBSLs and innocent bulges on SBCE.

The Baveno VI criteria for predicting esophageal varices: validation in real life practice.

BACKGROUND AND AIMS: According to the Baveno VI consensus, patients with liver stiffness < 20 kPa and a platelet count > 150,000 ul have very low risk of clinically significant varices and do not need a screening endoscopy. The aim of this study was to evaluate non-invasive methods as predictors of esophageal varices according to the Baveno VI recommendations, in real life clinical practice. METHODS: Retrospective evaluation of patients with chronic liver disease who underwent transient elastography between January 2013 and December 2015. RESULTS: One hundred and four patients were included in the study, the median age was 56.8 years and 69.2% were male. The etiology of liver disease was hepatitis C in 80% of patients (including 20% with HIV co-infection), alcohol in 12%, hepatitis B in 4% and other causes in 5%. Varices were present in 25% of patients. A liver stiffness < 20 kPa had a sensitivity of 92.3% and a specificity of 84.6%. When considering high risk varices (small with red wales or large varices), a liver stiffness < 20 kPa had 100% sensitivity. A platelet count > 150,000/l had a sensitivity of 84.6% and a specificity of 64.1%. Four patients with a platelet count (PLT) > 150,000/l had esophageal varices. When both criteria were applied to the patient cohort, according to the Baveno VI consensus, the sensitivity was 100% and the specificity, 61.5%. CONCLUSION: In this study, the Baveno VI criteria had 100% sensitivity but a relatively low specificity for the non-invasive diagnosis of esophageal varices. In clinical practice, all patients with varices are identified but many patients have a subsequent negative endoscopy.

The pronociceptive dorsal reticular nucleus contains mostly tonic neurons and shows a high prevalence of spontaneous activity in block preparation.

Despite the importance and significant clinical impact of understanding information processing in the nociceptive system, the functional properties of neurons in many parts of this system are still unknown. In this work we performed whole cell patch-clamp recording in rat brain stem blocks to characterize the electrophysiological properties of neurons in the dorsal reticular nucleus (DRt), a region known to be involved in pronociceptive modulation. We also compared properties of DRt neurons with those in the adjacent parvicellular reticular nucleus and in neighboring regions outside the reticular formation. We found that neurons in the DRt and parvicellular reticular nucleus had similar electrophysiological properties and exhibited mostly toniclike firing patterns, whereas neurons outside the reticular formation showed a larger diversity of firing patterns. Interestingly, more than one-half of the neurons also showed spontaneous activity. While the general view of the reticular formation, being a loosely associated mesh of groups of neurons with diverse function, and earlier reports suggests more electrophysiological heterogeneity, we showed that this is indeed not the case. Our results indicate that functional difference of neurons in the reticular formation may mostly be determined by their connectivity profiles and not by their intrinsic electrophysiological properties. The dominance of tonic neurons in the DRt supports previous conclusions that these neurons encode stimulus intensity through their firing frequency, while the high prevalence of spontaneous activity most likely shapes nociceptive modulation by this brain stem region.

Image Significance in the Diagnosis of Another Case of Herpetic Encephalitis.

Herpes simplex virus 1 (HSV-1) causes necrotizing encephalitis, usually located in the temporal lobes and with a high mortality rate if not diagnosed and treated early. Cranial computed tomography (CT) scan, although not very sensitive, can help by highlighting hemorrhagic foci and edema in the frontotemporal lobes, given the tropism of the virus for these areas. We present the case of a 70-year-old male who came to the emergency department (ED) with fever and confusion. Despite an unclear cerebrospinal fluid (CSF) result, the CT scan showed a spot of hypodensity in the mesial aspect of the left temporal lobe. He was given 21 days of intravenous acyclovir, and his neurological condition normalized. These cranial CT alterations, although not pathognomonic, indicate a strong suspicion of herpetic encephalitis.

Maternal and Fetal Outcomes after Multiple Cesarean Deliveries.

Background/Objectives: Cesarean delivery (CD) is a common procedure, but it can be associated with some increasing risks as the number of previous CD increases. Although women undergoing multiple CDs is very unusual in Spain, our center serves pregnant women with a history of three or more previous CDs with some frequency. We aimed to assess whether women who undergo multiple CDs (≥4) have more risks than those who undergo a third CD. Material and Methods: A retrospective cohort study was conducted with 161 pregnant women who had undergone ≥ 2 previous CDs and were monitored during their next pregnancy. The primary endpoint was to evaluate the obstetric hemorrhage rate in the multiple CD group and compare it with that in the third CD group. Secondary outcomes regarding maternal and neonatal complications were also analyzed. Results: Hemorrhage (7% and 10%; p = 0.522) and transfusion (3% and 8%; p = 0.141) rates were similar in both groups. The risk of dehiscence of the uterine segment (6% and 24%; p < 0.006), as well as hysterectomy (0 and 6.6%, p = 0.019), difficult abdominal opening (49% and 82%; p = 0.001), peritoneal adhesions (3% and 22%; p < 0.001), and difficult bladder separation (36% and 73%; p < 0.001), was higher in the multiple CD group. No uterine rupture or maternal-neonatal mortality was observed in either of the groups. Conclusions: Since undergoing multiple CD is uncommon, our study may be the largest sample in our environment. Our findings suggest that despite the potential risks of undergoing multiple CDs, maternal and neonatal outcomes are overall favorable.

Symptom provocation in obsessive-compulsive disorder: Validation of the Braga Obsessive Compulsive image set (BOCIS).

Symptom provocation paradigms are paramount to understand a heterogeneous disorder as obsessive-compulsive disorder (OCD). The main aim of our work was to develop and validate an open-access set of OCD-related images comprising three main subtypes: washing, checking, and symmetry. Twenty-six OCD patients and 25 controls provided valence and arousal ratings for a set of OCD-related, aversive, and neutral images. Linear mixed model analyses were used to estimate the main effects of group, image category, and group-image category interaction in image ratings. All main effects were found to be significant for both arousal and valence ratings, except for the group in arousal ratings. Path analysis confirmed our hypothesis that the OCI-R subscales influenced the subjective ratings of the corresponding image categories, particularly among patients. Independent samples t-tests were performed for each OCD picture to compose the set. Arousal demonstrated a greater capacity to distinguish controls and patients, thus sustaining our choice of using these ratings for the final Braga Obsessive-Compulsive Image Set (BOCIS). Our study demonstrated that the stimuli of the BOCIS reliably portray OCD-like triggers for washing, checking and symmetry subtypes. Its open-access availability will facilitate significant progress in both clinical and research settings.