Development and validation of the Ex-Care BR model: a multicentre initiative for identifying Brazilian surgical patients at risk of 30-day in-hospital mortality.

BACKGROUND: Surgical risk stratification is crucial for enhancing perioperative assistance and allocating resources efficiently. However, existing models may not capture the complexity of surgical care in Brazil. Using data from various healthcare settings nationwide, we developed a new risk model for 30-day in-hospital mortality (the Ex-Care BR model). METHODS: A retrospective cohort study was conducted in 10 hospitals from different geographic regions in Brazil. Data were analysed using multilevel logistic regression models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), Brier score, and calibration plots. Derivation and validation cohorts were randomly assigned. RESULTS: A total of 107,372 patients were included, and 30-day in-hospital mortality was 2.1% (n=2261). The final risk model comprised four predictors related to the patient and surgery (age, ASA physical status classification, surgical urgency, and surgical size), and the random effect related to hospitals. The model showed excellent discrimination (AUROC=0.93, 95% confidence interval [CI], 0.93-0.94), calibration, and overall performance (Brier score=0.017) in the derivation cohort (n=75,094). Similar results were observed in the validation cohort (n=32,278) (AUROC=0.93, 95% CI, 0.92-0.93). CONCLUSIONS: The Ex-Care BR is the first model to consider regional and organisational peculiarities of the Brazilian surgical scene, in addition to patient and surgical factors. It is particularly useful for identifying high-risk surgical patients in situations demanding efficient allocation of limited resources. However, a thorough exploration of mortality variations among hospitals is essential for a comprehensive understanding of risk. CLINICAL TRIAL REGISTRATION: NCT05796024.

Troponin elevation as a marker of short deterioration and one-year death in a high-risk surgical patient cohort in a low and middle income country setting: a postoperative approach to increase surveillance.

PURPOSE: Myocardial injury after noncardiac surgery is common and mostly asymptomatic. The ideal target population that will benefit from routine troponin measurements in low and middle income countries (LMICs) is unclear. This study aims to evaluate the clinical outcomes of a cohort of high-risk surgical patients according to high-sensitivity troponin T (hsTnT) in an LMIC setting. METHODS: We conducted a prospective cohort study of 442 high-risk patients undergoing noncardiac surgery at a Brazilian hospital between February 2019 and March 2020. High-sensitivity troponin T levels were measured preoperatively, 24 hr, and 48 hr after surgery and stratified into three groups: normal (< 20 ng·L-1); minor elevation (20-65 ng·L-1); and major elevation (> 65 ng·L-1). We performed survival analysis to determine the association between myocardial injury and one-year mortality. We described medical interventions and evaluated unplanned intensive care unit (ICU) admission and complications using multivariable models. RESULTS: Postoperative myocardial injury occurred in 45% of patients. Overall, 30-day mortality was 8%. Thirty-day and one-year mortality were higher in patients with hsTnT ≥ 20 ng·L-1. One-year mortality was 18% in the unaltered troponin group vs 31% and 41% for minor and major elevation groups, respectively. Multivariable analysis of one-year survival showed a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.22 to 3.09) for the minor elevation group and a HR of 2.73 (95% CI, 1.67 to 4.45) for the troponin > 65 ng·L-1 group. Patients with altered troponin had more unplanned ICU admissions (13% vs 5%) and more complications (78% vs 48%). CONCLUSION: This study supports evidence that hsTnT is an important prognostic marker and a strong predictor of all-cause mortality after surgery. Troponin measurement in high-risk surgical patients could potentially be used as tool to scale-up care in LMIC settings. STUDY REGISTRATION: ClinicalTrials.gov (NCT04187664); first submitted 5 December 2019.

RéSUMé: OBJECTIF: Les lésions myocardiques après une chirurgie non cardiaque sont courantes et la plupart du temps asymptomatiques. Nous ne connaissons pas la population cible idéale qui bénéficierait de mesures régulières de la troponine dans les pays à revenu faible et intermédiaire (PRFI). Cette étude vise à évaluer les issues cliniques d'une cohorte de patient·es de chirurgie à haut risque grâce à la troponine T à haute sensibilité (hsTnT) dans un contexte de PRFI. MéTHODE: Nous avons mené une étude de cohorte prospective auprès de 442 patient·es à haut risque bénéficiant d'une chirurgie non cardiaque dans un hôpital brésilien entre février 2019 et mars 2020. Les taux de troponine T à haute sensibilité ont été mesurés avant l'opération, 24 heures et 48 heures après la chirurgie, et stratifiés en trois groupes : normaux (< 20 ng·L−1), élévation mineure (20­65 ng·L−1) et élévation majeure (> 65 ng·L−1). Nous avons réalisé une analyse de survie pour déterminer l'association entre les lésions myocardiques et la mortalité à un an. Nous avons décrit les interventions médicales et évalué les admissions non planifiées à l'unité de soins intensifs (USI) ainsi que les complications à l'aide de modèles multivariables. RéSULTATS: Une lésion myocardique postopératoire est survenue chez 45 % des patient·es. La mortalité globale à 30 jours était de 8 %. La mortalité à trente jours et à un an était plus élevée chez les patient·es avec une hsTnT ≥ 20 ng·L−1. La mortalité à un an était de 18 % dans le groupe troponine inchangée vs 31 % et 41 % pour les groupes à élévation mineure et majeure de la troponine, respectivement. L'analyse multivariée de la survie à un an a montré un rapport de risque (RR) de 1,94 (intervalle de confiance [IC] à 95 %, 1,22 à 3,09) pour le groupe d'élévation mineure et un RR de 2,73 (IC 95 %, 1,67 à 4,45) pour le groupe avec une troponine > 65 ng·L−1. Les admissions non planifiées à l'USI étaient plus fréquentes chez les patient·es présentant une troponine altérée (13 % vs 5 %), tout comme les complications (78 % vs 48 %). CONCLUSION: Cette étude soutient les données probantes selon lesquelles la hsTnT est un marqueur pronostique important et un prédicteur fort de la mortalité toutes causes confondues après la chirurgie. La mesure de la troponine chez la patientèle chirurgicale à risque élevé pourrait potentiellement être utilisée comme outil pour intensifier les soins dans les PRFI. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04187664); soumis pour la première fois le 5 décembre 2019.

Few and feasible preoperative variables can identify high-risk surgical patients: derivation and validation of the Ex-Care risk model.

BACKGROUND: The development of feasible preoperative risk tools is desirable, especially for low-middle income countries with limited resources and complex surgical settings. This study aimed to derive and validate a preoperative risk model (Ex-Care model) for postoperative mortality and compare its performance with current risk tools. METHODS: A multivariable logistic regression model predicting in-hospital mortality was developed using a large Brazilian surgical cohort. Patient and perioperative predictors were considered. Its performance was compared with the Charlson comorbidity index (CCI), Revised Cardiac Risk Index (RCRI), and the Surgical Outcome Risk Tool (SORT). RESULTS: The derivation cohort included 16 618 patients. In-hospital death occurred in 465 patients (2.8%). Age, with adjusted splines, degree of procedure (major vs non-major), ASA physical status, and urgency were entered in a final model. It showed high discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.926 (95% confidence interval [CI], 0.91-0.93). It had superior accuracy to the RCRI (AUROC, 0.90 vs 0.76; P<0.01) and similar to the CCI (0.90 vs 0.82; P=0.06) and SORT models (0.90 vs 0.92; P=0.2) in the temporal validation cohort of 1173 patients. Calibration was adequate in both development (Hosmer-Lemeshow, 9.26; P=0.41) and temporal validation cohorts (Hosmer-Lemeshow 5.29; P=0.71). CONCLUSIONS: The Ex-Care risk model proved very efficient at identifying high-risk surgical patients. Although multicentre studies are needed, it should have particular value in low resource settings to better inform perioperative health policy and clinical decision-making.

Development of bovine embryos in vitro in coculture with murine mesenchymal stem cells and embryonic fibroblasts.

Despite the progress on development of new culture media, in vitro-produced embryos still display lower quality when compared to the in vivo-produced counterparts. Coculture has been reconsidered as an alternative to improve embryo quality. Mesenchymal stem cells (MSC) and murine embryonic fibroblasts (MEF) have been extensively used as feeder layers due to their capacity to release growth factors. In the present study we investigated the effect of these feeder layers in oocyte maturation and/or embryo development under in vitro conditions. Oocytes were matured in control (CTRL) conditions or in coculture with MSC or MEF. In vitro fertilization and embryo culture until fourth day were performed in CTRL condition for all groups. Embryos from fourth day on were then cultured until the eighth day in CTRL or in coculture system. No significant differences for metaphase II stage and apoptosis in oocytes were found among the groups. There was also no difference among the groups when we evaluated blastocyst formation on the seventh and eighth day, with exception of a higher hatched blastocyst rate in the group maturated and cultivated in CTRL condition when compared to the group matured and cocultured with MSC. Also no difference was observed in the number of cells in the whole embryos, in the inner cell mass, in the trophoblast and at apoptotic stage on the eighth day. We conclude that coculture with MSC or MEF during maturation and/or embryo development do not enhance the in vitro production of bovine embryos.

Are endoscopic ultrasonography imaging characteristics reliable for the diagnosis of small upper gastrointestinal subepithelial lesions?

PURPOSE OF THE STUDY: To compare the accuracy of endoscopic ultrasonography (EUS) imaging with histopathology in the diagnosis of upper gastrointestinal subepithelial lesions. METHODS: Thirty-seven patients (21 female; mean age: 55 y) underwent endoscopic submucosal resection (ESMR) of upper gastro intestinal subepithelial lesions at a tertiary care facility. All patients underwent EUS before ESMR of the lesion. Information regarding location, size, echogenecity, layer of origin, presumptive diagnosis based on EUS imaging, and histopathology diagnosis after ESMR of the subepithelial lesion was recorded. RESULTS: Twenty-seven subepithelial lesions were resected from the stomach, 5 from the esophagus, and 5 from the duodenum. The mean size of the lesions was 9 mm (range, 6-18 mm). Thirty-six lesions originated from the submucosa, and 1 from the muscularis propria. Using histopathology as the gold standard, the overall diagnostic accuracy of EUS imaging was 49% (18 out of 37). The accuracy of EUS imaging for the diagnosis of esophageal, gastric, and duodenal subepithelial lesions was 20%, 56%, and 40%, respectively. One patient developed a microperforation, and 1 developed bleeding during the ESMR procedure. No complications were reported with the EUS procedure. CONCLUSIONS: The diagnostic accuracy of EUS imaging is inferior to histopathology in the diagnosis of small upper gastrointestinal subepithelial lesions. Endoluminal resection is a relatively safe and noninvasive modality that not only provides tissue sample for accurate diagnostic interpretation, but also aids in the complete removal of small subepithelial lesions of the upper gastrointestinal tract.

Pancreato-biliary malignancy diagnosed by endoscopic ultrasonography in absence of a mass lesion on transabdominal imaging: prevalence and predictors.

BACKGROUND AND AIMS: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Pancreatic cancer is diagnosed in some patients by endoscopic ultrasonography (EUS) even in the absence of an obvious mass lesion on transabdominal imaging studies. The purpose of this study was to estimate the prevalence of PBM on EUS-FNA in patients with no obvious mass on transabdominal imaging and identify possible predictors of PBM in this cohort of patients. METHODS: Three hundred and twenty-six patients (219 female; mean age: 57) with no obvious neoplastic lesion on trans-abdominal imaging underwent EUS. Demographic data, indication of EUS, history of weight loss, smoking, alcohol use, diabetes, cholecystectomy status, CT and USG findings, and liver function tests (LFTs) were reviewed. RESULTS: Thirty patients (9%) were diagnosed with a PBM by EUS-FNA (27 pancreatic adenocarcinoma, three ampullary adenocarcinoma). The mean age of patients diagnosed with PBM was significantly (P < 0.01) higher than controls. The mean size of the tumor was 2.8 cm (range: 0.9-7 cm). Male gender, presence of jaundice, abnormal LFTs, weight loss, and nonspecific trans-abdominal imaging results such as dilated common bile duct (CBD), and abnormal appearing pancreas predicted the presence (P < 0.05) of PBM, whereas patients with previous cholecystectomy and abdominal pain were less likely to have this diagnosis. CONCLUSIONS: Normal trans-abdominal imaging does not completely exclude the presence of PBM. Nonspecific pancreatic abnormalities and CBD dilation on trans-abdominal imaging, with jaundice, abnormal LFTs, weight loss, and lack of abdominal pain are predictors of PBM.

Small intestinal bacterial overgrowth in gastroparesis: are there any predictors?

BACKGROUND: There is some degree of overlap in the symptomatic spectrum of patients with gastroparesis and small intestinal bacterial overgrowth (SIBO) and some of the etiologies for gastroparesis, such as diabetes mellitus and vagotomy are known to predispose to SIBO. The aims of our study were to measure the prevalence of SIBO in a cohort of gastroparetic patients with prominence of abdominal pain and bloating and try to identify predictors with regard to demographics, concurrent use of medications such as prokinetics, proton pump inhibitors, and opiate analgesics, and predominant bowel movement abnormality. METHODS: Glucose breath testing (GBT) for SIBO was performed in 50 patients (41 females) with gastroparesis. Demographic data, medication profiles, baseline and peak measurements of hydrogen or methane gas on the GBT, and results of the most recent gastric emptying scintigraphy test were recorded. RESULTS: Thirty of fifty (60%) patients had a positive GBT for SIBO on the basis of hydrogen (63%), methane (27%), or both criteria (10%). SIBO was more likely (P=0.001) in patients with gastroparetic symptoms of greater duration (mean 5 y; 95% CI: 4-6 y). No significant differences were noted in both groups with regard to age, sex, or etiology of gastroparesis. Gastric emptying was similar in the SIBO and non-SIBO group (P>0.05). After adjusting for tegaserod and opiate analgesic use, 14/23 (61%) had a positive GBT. CONCLUSIONS: SIBO is very common in gastroparetics with predominance of abdominal pain and bloating, especially those with a longer duration of gastroparesis. Awareness of SIBO in the setting of gastroparesis will facilitate separation of the 2 entities and allow appropriate therapies to be instituted.

Efficacy of tricyclic antidepressant therapy in adults with cyclic vomiting syndrome: a two-year follow-up study.

AIM: To investigate the effects of prolonged tricyclic antidepressants (TCAs) therapy on the frequency and duration of episodes of cyclic vomiting syndrome (CVS) in adults, and the global assessment of clinical improvement and the number of emergency department (ED) visits and/or hospitalizations. METHOD: An open labeled study was conducted in adult CVS patients treated with a TCA and followed for up to 2 years. Demographic data, TCA dosage, duration and frequency of CVS episodes, ED visits, and hospitalizations at baseline and during TCA therapy were recorded, and patients were monitored for any adverse events. RESULTS: Forty-six patients initially met the inclusion criteria and 41 patients (22 male) with mean age of 35 years (range: 18 to 63 y) on TCA were able to be followed for 1 year and 23 were evaluated for 2 years. Mean age of onset of CVS symptoms was 26 years (range: 10 to 52 y) and mean age for making the diagnosis of CVS was 32 years (range: 15 to 63 y). The frequency and duration of an episode and ED visits related to CVS were all significantly reduced after both the first and second year of TCA therapy (P<0.05). Eighty-eight percent reported an improved clinical status by subjective global assessment. Mild side effects were reported in 34% not necessitating stoppage of the TCA. CONCLUSIONS: Long-term TCA therapy significantly reduces the frequency and duration of CVS episodes, ED visits, and hospitalizations (P<0.05), and improves overall clinical well-being providing evidence that they are effective therapy for adult CVS.

Small intestinal bacterial overgrowth in irritable bowel syndrome: are there any predictors?

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a condition in which excessive levels of bacteria, mainly the colonic-type species are present in the small intestine. Recent data suggest that SIBO may contribute to the pathophysiology of Irritable bowel syndrome (IBS). The purpose of this study was to identify potential predictors of SIBO in patients with IBS. METHODS: Adults with IBS based on Rome II criteria who had predominance of bloating and flatulence underwent a glucose breath test (GBT) to determine the presence of SIBO. Breath samples were obtained at baseline and at 30, 45, 60, 75 and 90 minutes after ingestion of 50 g of glucose dissolved in 150 mL of water. Results of the glucose breath test, which measures hydrogen and methane levels in the breath, were considered positive for SIBO if 1) the hydrogen or methane peak was >20 ppm when the baseline was <10 ppm, or 2) the hydrogen or methane peak increased by 12 ppm when baseline was >or=10 ppm. RESULTS: Ninety-eight patients were identified who underwent a GBT (mean age, 49 y; 78% female). Thirty-five patients (36%) had a positive GBT result suggestive of SIBO. A positive GBT result was more likely in patients >55 years of age (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4-9.0) and in females (OR, 4.0; 95% CI, 1.1-14.5). Hydrogen was detected more frequently in patients with diarrhea-predominant IBS (OR, 8; 95% CI, 1.4-45), and methane was the main gas detected in patients with constipation-predominant IBS (OR, 8; 95% CI, 1.3-44). There was no significant correlation between the presence of SIBO and the predominant bowel pattern or concurrent use of tegaserod, proton pump inhibitors, or opiate analgesics. CONCLUSIONS: Small intestinal bacterial overgrowth was present in a sizeable percentage of patients with IBS with predominance of bloating and flatulence. Older age and female sex were predictors of SIBO in patients with IBS. Identification of possible predictors of SIBO in patients with IBS could aid in the development of successful treatment plans.

Efficacy of gastric electrical stimulation in improving functional vomiting in patients with normal gastric emptying.

The objective of this study is to evaluate the utility of gastric electrical stimulation (GES) in the subgroup of patients with refractory nausea and vomiting in the presence of normal gastric emptying. Eighteen patients (15 females) underwent GES implantation for dyspeptic symptoms in the presence of normal gastric emptying. Upper gastrointestinal (UGI) symptom score, health-related quality of life (HR-QOL), nutritional status and weight, and medication use (prokinetics and antiemetics) were assessed at baseline and at 1 year after GES placement. Twelve patients (two males) were included in the final analysis. All patients had normal gastric emptying scintigraphy at baseline. After 1 year of GES, there was a significant reduction in the UGI symptom score from 18 to 10 (P = 0.001). The physical component score (PCS) of the HR-QOL was also significantly increased from 25 to 42 (P = 0.04). Gastric emptying actually became slower in 29% of those who repeated the test after 1 year. No adverse events related to GES placement were recorded. Results of our study suggest that GES improves dyspeptic symptoms in patients with medically refractory nausea and vomiting independent of its effect on gastric emptying and could be considered as a potential therapy in this clinical setting.

Disturbances of esophageal motility in eosinophilic esophagitis: a case series.

Esophageal manometry (EM) findings were reviewed in 14 (13 male) adults diagnosed with eosinophilic esophagitis (EE). One had complete nonperistaltic contractions (amplitude range = 30-180 mmHg) and incomplete relaxation of the lower esophageal sphincter (LES), suggesting vigorous achalasia. After 6 months of steroid therapy the repeat EM showed near-normal findings. One had total aperistalsis with contraction amplitudes less than 10 mmHg and a weak LES pressure (8 mmHg), criteria suggesting scleroderma. Two had low-amplitude (<30 mmHg) nonperistaltic contractions limited to the mid-esophagus. Criteria for nutcracker esophagus were met in two patients. Isolated low LES pressure (<15 mmHg) was observed in four patients who were also receiving proton pump inhibitors, and the remainder had normal EM findings. Our results found that EE can mimic all the categories of EM disturbances, with approximately 50% of our patients having a major impairment of smooth muscle function. The EM abnormality can be reversed to normal in some cases with appropriate treatment for EE.

Endoscopic pyloric injection of botulinum toxin-A for the treatment of postvagotomy gastroparesis.

OBJECTIVES: To evaluate the efficacy of botulinum toxin-A in the treatment of postvagotomy gastroparesis. METHODS: This open-labeled trial identified and recruited 11 subjects who developed symptomatic gastroparesis after a vagotomy (9 fundoplication, 1 trauma, and 1 exploratory laparotomy). Gastroparesis was defined as an abnormal solid-phase gastric emptying test using the standardized 4-hour radionuclide eggbeater meal method and vagotomy was confirmed with a sham meal challenge test. To complete the study, subjects should have completed the 6-month follow-up visit after their pylorus was injected with botulinum toxin-A injection in a 4-quadrant manner. Patients either received 100 (n = 2) or 200 (n = 9) units of botulinum toxin. Questionnaires recorded symptom severity of gastroparesis at baseline and at monthly intervals for 6 months after the therapy was completed by the patients. RESULTS: Of the 11 subjects initially recruited, 10 finished the 6-month follow-up visit (7 women). Mean age was 51 years (range, 31-84 years). Mean symptom score at baseline was 16 (95% CI 13-19) and showed a numerical decline to 9 (P > 0.05) over the 6-month period after the procedure (95% CI 5-13). Seven (70%) patients observed >30% improvement in the total symptom score. No complications were recorded. CONCLUSIONS: In conclusion, this open-label study in patients with postvagotomy gastroparesis patients reveals a reduction of gastroparetic symptoms at 1 and 3 months after treatment with pyloric injection of botulinum toxin-A, with return of symptoms by 6 months. Thus, botulinum toxin treatment does not produce a sustained reduction in gastroparetic symptoms in this clinical setting.

Comparison of anorectal manometry to endoanal ultrasound in the evaluation of fecal incontinence.

BACKGROUND: Fecal incontinence (FI) is a common clinical condition with a negative impact on the quality of life. Commonly performed tests to evaluate FI include anorectal manometry (ARM) and endoanal ultrasonography (EAU). Objective of our study was to compare the results of these 2 tests in a cohort of patients with FI. METHODS: Retrospective study of 27 patients (20 women) referred to the gastrointestinal motility clinic for FI. EAU and ARM were performed in all patients. Demographic data and information regarding etiology of FI was also recorded. RESULTS: Mean age of the patients was 56 years (range 26-87 years). Etiology of FI was obstetric trauma in 4, pelvic surgery in 9, pelvic trauma in 3, pelvic radiation in 1, and idiopathic in 8. Based on the ARM data, 14 of 27 had a weak external sphincter squeeze pressure and 3 had impaired rectal sensation, whereas with the EAU there was thinning of the external anal sphincter in 3 and complete disruption in 1, and abnormalities of the internal anal sphincter (IAS) in 7 of 27 with thinning, and defects. Overall, only 2 of 27 had normal findings by combined ARM and EAU. CONCLUSIONS: Although the yield of finding major sphincter defects was low, only a small percentage of patients had a normal ARM or EAU. When there are degrees of external anal sphincter thinning or partial or complete disruption of the sphincters, a good correlation with ARM is achieved. EAU and ARM are complimentary investigations for the thorough assessment of the anal sphincter apparatus.

Effects of Transcranial Direct Current Stimulation Block Remifentanil-Induced Hyperalgesia: A Randomized, Double-Blind Clinical Trial.

Background: Remifentanil-induced hyperalgesia (r-IH) involves an imbalance in the inhibitory and excitatory systems. As the transcranial Direct Current Stimulation (tDCS) modulates the thalamocortical synapses in a top-down manner, we hypothesized that the active (a)-t-DCS would be more effective than sham(s)-tDCS to prevent r-IH. We used an experimental paradigm to induce temporal summation of pain utilizing a repetitive cold test (rCOLDT) assessed by the Numerical Pain Score (NPS 0-10) and we evaluated the function of the descending pain modulatory system (DPMS) by the change on the NPS (0-10) during the conditioned pain modulation (CPM)-task (primary outcomes). We tested whether a-tDCS would be more effective than s-tDCS to improve pain perception assessed by the heat pain threshold (HPT) and the reaction time during the ice-water pain test (IPT) (secondary outcomes). Methods: This double-blinded, factorial randomized trial included 48 healthy males, ages ranging 19-40 years. They were randomized into four equal groups: a-tDCS/saline, s-tDCS/saline, a-tDCS/remifentanil and s-tDCS/remifentanil. tDCS was applied over the primary motor cortex, during 20 min at 2 mA, which was introduced 10 min after starting remifentanil infusion at 0.06 µg⋅kg-1⋅min-1 or saline. Results: An ANCOVA mixed model revealed that during the rCOLDT, there was a significant main effect on the NPS scores (F = 3.81; P = 0.01). The s-tDCS/remifentanil group presented larger pain scores during rCOLDT, [mean (SD) 5.49 (1.04)] and a-tDCS/remifentanil group had relative lower pain scores [4.15 (1.62)]; showing its blocking effect on r-IH. a-tDCS/saline and s-tDCS/saline groups showed lowest pain scores during rCOLDT, [3.11 (1.2)] and [3.15 (1.62)], respectively. The effect of sedation induced by remifentanil during the rCOLDT was not significant (F = 0.76; P = 0.38). Remifentanil groups showed positive scores in the NPS (0-10) during the CPM-task, that is, it produced a disengagement of the DPMS. Also, s-tDCS/Remifentanil compared to a-tDCS showed lower HPT and larger reaction-time during the IPT. Conclusion: These findings suggest that effects of a-tDCS prevent the summation response induced by r-IH during rCOLDT and the a-tDCS blocked the disengagement of DPMS. Thereby, tDCS could be considered as a new approach to contra-regulate paradoxical mechanisms involved in the r-IH. Clinical trials identification: NCT02432677. URL:https://clinicaltrials.gov/.

Chk2 activation dependence on Nbs1 after DNA damage.

The checkpoint kinase Chk2 has a key role in delaying cell cycle progression in response to DNA damage. Upon activation by low-dose ionizing radiation (IR), which occurs in an ataxia telangiectasia mutated (ATM)-dependent manner, Chk2 can phosphorylate the mitosis-inducing phosphatase Cdc25C on an inhibitory site, blocking entry into mitosis, and p53 on a regulatory site, causing G(1) arrest. Here we show that the ATM-dependent activation of Chk2 by gamma- radiation requires Nbs1, the gene product involved in the Nijmegen breakage syndrome (NBS), a disorder that shares with AT a variety of phenotypic defects including chromosome fragility, radiosensitivity, and radioresistant DNA synthesis. Thus, whereas in normal cells Chk2 undergoes a time-dependent increased phosphorylation and induction of catalytic activity against Cdc25C, in NBS cells null for Nbs1 protein, Chk2 phosphorylation and activation are both defective. Importantly, these defects in NBS cells can be complemented by reintroduction of wild-type Nbs1, but neither by a carboxy-terminal deletion mutant of Nbs1 at amino acid 590, unable to form a complex with and to transport Mre11 and Rad50 in the nucleus, nor by an Nbs1 mutated at Ser343 (S343A), the ATM phosphorylation site. Chk2 nuclear expression is unaffected in NBS cells, hence excluding a mislocalization as the cause of failed Chk2 activation in Nbs1-null cells. Interestingly, the impaired Chk2 function in NBS cells correlates with the inability, unlike normal cells, to stop entry into mitosis immediately after irradiation, a checkpoint abnormality that can be corrected by introduction of the wild-type but not the S343A mutant form of Nbs1. Altogether, these findings underscore the crucial role of a functional Nbs1 complex in Chk2 activation and suggest that checkpoint defects in NBS cells may result from the inability to activate Chk2.

Gastroparesis secondary to a demyelinating disease: a case series.

BACKGROUND: Gastroparesis has a number of etiologies. The main ones are secondary to a complication from diabetes mellitus, related to post vagotomy or post gastric surgical resections, or idiopathic when the etiology is unclear. Gastroparesis secondary to a demyelinating disease of the brain is unusual. CASE PRESENTATION: A 22-year-old woman was referred for acute onset of intractable nausea and vomiting. She also had cerebellar deficits, dysphagia and paresthesias. Magnetic resonance imaging (MRI) of the brain revealed an isolated area of demyelination in the medullary region. Another 24-year-old woman had a similar presentation with right hemiplegia and MRI of the brain revealed a distal medullary region. Both these patients had an abnormal gastric emptying test. Gastroparesis and neurological deficits improved with intravenous corticosteroids. While the former patient has had no further recurrences, the latter patient developed multiple sclerosis within three months of presentation. CONCLUSION: A demyelinating disease is a rare cause gastropareis, but should be suspected when symptoms of gastroparesis are associated with neurological deficits. MRI might help in the diagnosis and intravenous coriticosteroids can address the underlying disease process and improve gastric emptying, especially when used early during the course of the disease.

Efficacy of rifaximin, a nonabsorbed oral antibiotic, in the treatment of small intestinal bacterial overgrowth.

INTRODUCTION: Rifamixin is an orally administrated, nonabsorbed antibiotic whose utility in eradication of small intestinal bacterial overgrowth (SIBO) is currently being evaluated. PURPOSE: The aim of this study was to investigate efficacy and safety of rifaximin in relieving symptoms and normalizing the glucose breath test (GBT) in patients with SIBO. METHODS: Symptom score assessment, consisting of frequency and severity of bloating, gas, abdominal pain, and bowel movements and the GBT were performed before and after treatment with rifaximin 800 mg/d for 4 weeks. SUBJECTS: Twenty consecutive symptomatic patients (16 women and 4 men; mean age, 47.8 years; range, 19 to 85 years) who had a positive GBT were prospectively studied in an open-labeled fashion. Fourteen patients (70.0%) presented with diarrhea, 3 (15.0%) with bloating and gas, and 3 (15.0%) with constipation as the dominant symptom. RESULTS: : Eleven patients were hydrogen producers, 8 exclusively methane, and 1 patient produced both gases by the GBT. Among patients with diarrhea, 12 of 14 (85.7%) reported improvement in symptom scores of more than 50%; 1 between 25% and 50%, 1 had no response after 4 weeks of rifamixin. Among patients with bloating and gas or constipation as the main symptom: 2 of 6 (33.3%) had improvement between 50% and 75%; 3 (50%) had 25% to 50% improvement, and 1 (16.7%) had no response. Repeat GBT at the end of the 4 weeks showed that 54.5% of hydrogen formers and 50.0% of methane producers were eradicated, and there was a significant reduction (P <0.05) in the area under the concentration-time curve and peak values. No adverse effects were observed. CONCLUSIONS: Rifaximin in a dose of 800 mg per day for 4 weeks: 1) was safe and effective treatment in reducing symptoms in patients with SIBO of multiple etiologies, especially when diarrhea was the dominant symptom; and 2) normalized the GBT in approximately 50% of patients. Data support a future therapeutic role for rifaximin in SIBO.

Radiographic evaluation of teeth subjected to high temperatures: experimental study to aid identification processes.

The radiographic evaluation of dental remains represents a significant aspect in the forensic identification process, particularly after an exposure to fire. The aim of this "in vitro" study was to evaluate the radiographic features of unrestored, endodontically treated and restored teeth after exposure to an experimental range of high temperatures. Ninety human teeth were divided into two groups: (1) unrestored teeth, as a control group and (2) teeth endodontically treated (condensation technique) and restored with amalgam or composite fillings. Before testing the high temperatures, periapical radiographs of all teeth were performed. The tests of exposure to heat were carried out in an oven for six different temperatures (200, 400, 600, 800, 1000 and 1100 degrees C (392, 752, 1112, 1472, 1832, 2012 degrees F)). After each exposure, periapical radiographs of all the teeth were taken. The radiographic appearance of all the teeth before and after the thermal stresses were evaluated and the differences were recorded. The results of the radiographic examination showed that a number of significant radiographic details were conserved: the composite fillings were in place maintaining the shape till 600 degrees C (1112 degrees F), the amalgam fillings were in place maintaining the shape till 1000 degrees C (1832 degrees F) and the endodontic treatments were recognisable till 1100 degrees C (2012 degrees F).

Observations on dental prostheses and restorations subjected to high temperatures: experimental studies to aid identification processes.

In large scale disasters associated with fire the damage caused by heat can make medico-legal identification of human remains difficult. Teeth, restorations and prostheses, all of which are resistant to even quite high temperatures can be used as aids in the identification process. In this project the behaviour and morphology of teeth and dental prostheses exposed to a range of high temperatures was studied. Healthy teeth, dental restorations and prostheses were placed in a furnace and heated at a rate of 30 degrees C/min and the effects of the predetermined temperatures 200, 400, 600, 800, 1000 and 1100 degrees C were examined by stereomicroscopy and scanning electron microscopy (SEM). Our observations show that some prostheses and restorative materials resist higher temperatures than theoretically predictable and that even when a restoration is lost because of detachment or change of state its ante-mortem presence can be confirmed and detected by both stereomicroscopic examination and SEM of the residual cavity. We further conclude that a reasonably reliable estimation of the temperature of exposure can be made from an analysis of the teeth and restorative materials.