Prevalence of non-coeliac gluten sensitivity and assessment of the response to gluten-free diet in a cohort of patients with fibromyalgia.

OBJECTIVES: To establish the prevalence of non-coeliac gluten sensitivity (NCGS) in a cohort of fibromyalgia patients and to evaluate their clinical response to a six-week gluten-free diet (GFD), the improvement in their symptoms, the percentage of diet responders who did not fulfil the diagnostic criteria for NCGS and the baseline characteristics that were associated with diet response and diagnostic criteria fulfilment. METHODS: Uncontrolled prospective experimental study in a cohort of patients with fibromyalgia from a specialized hospital unit. The percentage of patients that fulfilled the Salerno Experts' Criteria, that responded to GFD, that improved their symptomatology and baseline characteristics associated with GFD response and diagnostic criteria fulfilment was analysed. RESULTS: In total, 142 patients were selected and a NCGS prevalence of 5.6% was observed. A total of 21.8% responded to GFD due to their improvement in intestinal symptoms. In total, 74.2% of the responders did not fulfil the Salerno Experts' Criteria. The presence of diarrhoea and intraepithelial lymphocytosis and lower levels of anxiety were predictive factors of GFD response. No predictive factors of NCGS criteria fulfilment were found due to the low number of discriminators between gluten and placebo. CONCLUSIONS: A NCGS prevalence similar to that estimated in the general population was found. A GFD cannot be systematically recommended to all patients with fibromyalgia, although it could be evaluated in those with diarrhoea or intraepithelial lymphocytosis to evaluate if there are improvements in their intestinal symptoms.

Endoscopic variceal ligation as primary prophylaxis for upper GI bleeding in children.

BACKGROUND AND AIMS: Variceal hemorrhage can be a life-threatening adverse event of chronic liver disease. In contrast to the well-described guidelines for the management of portal hypertension (PH) in adults, there is limited evidence about the optimal prophylactic management of variceal bleeding in children. This study was carried out to assess the efficacy of endoscopic variceal ligation (EVL) as primary prophylaxis to prevent upper GI bleeding in children with PH. METHODS: From January 2014 to April 2018, all pediatric patients with PH disease and medium to large esophageal varices or reddish spots, regardless of the grade of the varix, were prospectively included in the protocol of primary prophylaxis with EVL. A second retrospective group of patients was made after reviewing medical records of 32 pediatric patients with PH that presented esophageal varices in the upper endoscopy and had received propranolol as primary prophylaxis. RESULTS: Twenty-four patients (75%) reached varices eradication in the EVL group, with a median of 2 procedures (range, 1-4) before eradication and a median time to eradication of 3.40 months (range, 1.10-13.33). No EVL-related adverse events were observed. Statistically significant differences were observed in the bleeding rate at 3 years between propranolol and EVL groups (6/32 [21.9%] vs 1/32 [3.2%], P < .02). The hazard ratio for bleeding for patients treated with propranolol compared with those treated with EVL was 2.6 (95% confidence interval, 1.53-3.67). CONCLUSIONS: EVL is a safe and effective treatment to prevent upper GI bleeding in pediatric patients with PH. (Clinical trial registration number: NCT03943784.).

Effectiveness of combined pharmacologic and ligation therapy in high-risk patients with acute esophageal variceal bleeding.

OBJECTIVES: After an acute variceal bleeding, early decision for aggressive management of patients with worse prognosis may improve outcomes. The effectiveness of currently recommended standard therapy (drugs plus endoscopic ligation) for different risk subgroups and the validity of available risk criteria in clinical practice are unknown. METHODS: We analyzed data of 301 consecutive cirrhotic patients admitted with esophageal variceal bleeding. All patients received antibiotics, somatostatin, and in 263 early endoscopic therapy. A stratified 6-week mortality assessment according to risk (low-risk: Child-Pugh B without active bleeding or Child-Pugh A; high-risk: Child-Pugh B with active bleeding or Child-Pugh C) was performed. A multivariate analysis was conducted to elaborate a new risk classification rule. RESULTS: Among the 162 patients receiving emergency ligation, 14% rebled and 16% died. Standard therapy was very effective in all risk strata, even in high-risk patients, specially if eligible for therapeutic trials (child <14, age ≤75 years, creatinine ≤3.0 mg/dl, no hepatocellular carcinoma, or portal thrombosis), showing this stratum a 10% mortality. In patients receiving ligation, Child-Pugh C patients with baseline creatinine <1.0 mg/dl showed similar mortality to Child-Pugh A or B patients (8% vs. 7%, respectively). Only Child-Pugh C patients with creatinine ≥1.0 were at a significant higher risk (Child-Pugh C: 46% mortality if creatinine ≥1.0 vs. 8% if creatinine <1.0, P=0.006). CONCLUSIONS: The combination of somatostatin, antibiotics, and endoscopic ligation after an acute variceal bleeding in a real-life situation is associated with very low mortality. Child-Pugh C patients with baseline creatinine ≥1.0 mg/dl should be considered high-risk patients in this setting.

Predicting early mortality after acute variceal hemorrhage based on classification and regression tree analysis.

BACKGROUND & AIMS: Available prognostic models for mortality after an acute variceal hemorrhage have limitations that restrict their clinical value. We assessed the performance of a novel prognostic approach based on classification and regression tree (CART) analysis. METHODS: Logistic regression (LR) and CART analyses were performed to identify prognostic models for mortality at 6 weeks in a single-center cohort of 267 consecutive patients with acute variceal bleeding. Receiver operating characteristic (ROC) curves were constructed to assess the performance of the models. Prognostic models were fitted and validated by split-sample technique (training set, 164 patients, 2001-2005; test set, 103 patients, 2006-2008). RESULTS: After 6 weeks, 21% of patients experienced rebleeding and 24% died. The best LR model was based on Child-Pugh score, creatinine level, bacterial infection, and hepatocellular carcinoma. CART analysis provided a simple algorithm based on the combined use of just 3 variables (Child-Pugh score, creatinine level, and bacterial infection), allowing accurate early discrimination of 3 distinct prognostic subgroups with 8% (low risk), 17% (intermediate), and 50% to 73% (high) mortality. Its accuracy was similar to the LR model (area under the ROC curves, 0.81 vs 0.84; P = .17) and better than that of Child-Pugh (0.75; P = .05) and model for end-stage liver disease (0.74; P = .05). The prognostic accuracy of both LR and CART models was validated in the test set (area under the ROC curve values, 0.81 and 0.83, respectively). CONCLUSIONS: A simple CART algorithm based on Child-Pugh score, creatinine level, and infection allowed an accurate predictive assessment of 6-week mortality after acute variceal bleeding.

[Treatment of pain in chronic pancreatitis]. / Tratamiento del dolor en la pancreatitis crónica.

Abdominal pain is the most frequent symptom in patients with chronic pancreatitis. Between 70 and 90% of patients experience pain at some point in the course of their disease. In patients with alcoholic pancreatitis, pain is usually experienced at disease onset. Two distinct forms of idiopathic chronic pancreatitis can be distinguished: in early-onset (juvenile) idiopathic chronic pancreatitis, pain occurs initially, while in late-onset (senile) idiopathic chronic pancreatitis, pain is delayed or may even be absent. According to several authors, between 27 and 67% of patients require surgery due to lack of response to medical treatment. Pain may reoccur in more than 30% of patients who have undergone surgery and consequently, reintervention is not uncommon. Several treatment options are currently available: medical, endoscopic and surgical. The most appropriate treatment for each patient should be chosen on an individualized basis.

Long-term safety and effectiveness of levodopa-carbidopa intestinal gel infusion.

INTRODUCTION: Levodopa-carbidopa intestinal gel (LCIG) infusion has demonstrated to improve motor fluctuations. The aim of this study is to assess the long-term safety and effectiveness of LCIG infusion in advanced Parkinson's disease (PD) patients with motor fluctuations and its effect in nonmotor symptoms. METHODS: Adverse events (AE) and their management, clinical motor, and nonmotor aspects were assessed up to 10 years. Thirty-seven patients were treated with LGIC; in three subsets of patients, specific batteries of tests were used to assess cognitive and behavior assessment for 6 months, quality of sleep for 6 months, and quality of life and caregiver burden for 1 year. RESULTS: There was a high number of AE, but manageable, most of mild and moderate severity. All patients experienced significant improvement in motor fluctuations with a reduction in mean daily off time of 4.87 hr after 3 months (n = 37) to 6.25 hr after 9 years (n = 2). Diskynesias remained stables in 28 patients (75.7%) and improved in 5 patients (13.5%). There was no neuropsychological deterioration, but an improvement in attentional functions, voluntary motor control, and semantic fluency. Quality of sleep did not worsen, and there was an improvement in the subjective parameters, although overnight polysomnography did not change. There was a significant sustained improvement of 37% in PD-Q39 after 3 months and to 1 year, and a significant reduction in caregiver burden of 10% after 3 months. CONCLUSION: LCIG infusion is a safe and efficacious treatment for the control of motor fluctuations, and for improvement or nonworsening of nonmotor aspects, long-term sustained, and feasible for use in routine care.

Surgical Trauma Caused by Different Abdominal Access Routes-Comparison of Open Surgical, Laparoscopic, and NOTES Transgastric Techniques in a Porcine Model.

BACKGROUND: Investigations indicate that natural orifice translumenal endoscopic surgery (NOTES) procedures induce a less pronounced postoperative inflammatory response than open or laparoscopic surgery, inflicting less trauma. In NOTES procedures, no skin incision is performed. We compare the inflammatory response added by the type of incision by measuring C-reactive protein (CRP) and tumors necrosis factor-alfa (TNF-α). METHODS: Twenty-seven pigs were randomized to open surgical, laparoscopic, or transgastric NOTES abdominal access. After completion of the accesses, no surgery was performed. All accesses were left open for 40 minutes followed by closure, animals were survived for 7 days. Blood samples were drawn at the start of the accesses, at 20 and 40 minutes during the procedure, and at postoperative day (POD) 1, 3, and 7. Analyses of CRP and TNF-α were performed. RESULTS: CRP increased in all animals until POD1. This increase was greater in the open group (P = .006). No significant differences in CRP-levels were found at POD 1, 3, or 7. TNF-α showed a peak during the procedure, at 20 and 40 minutes, with normalization at POD1 for 1/3 of the open and laparoscopic animals, but not for the NOTES animals. Due to variations within the groups, no statistical difference was shown between them. At postmortem, 1/3 of the pigs in the laparoscopic and open groups had wound infections, while no NOTES animals showed infections. CONCLUSIONS: This study provides no statistically significant differences in inflammatory response after the different abdominal accesses. However, the lack of a TNF-α-peak in the NOTES group might indicate a less pronounced response, supporting the initial theories.

Adding banding ligation is effective as rescue therapy to prevent variceal rebleeding in haemodynamic non-responders to pharmacological therapy.

BACKGROUND: It is unknown which is the best therapy to treat haemodynamic non-responders to pharmacological therapy after variceal bleeding. AIM: To evaluate the efficacy of adding banding ligation to drugs to prevent variceal rebleeding in haemodynamic non-responders to drugs. METHODS: Fifty-three cirrhotic patients with variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were then titrated to maximum tolerated doses. A second HVPG was taken 14 days later. Responders (HVPG ≤12 mm Hg or ≥20% decrease from baseline) were maintained on drugs and non-responders had banding ligation added to drugs. RESULTS: Mean follow-up was 28 months. In 5 patients the second HVPG could not be performed because of early rebleeding. The remaining 48 patients were classified as responders (n=24) and non-responders (n=24), who had banding added. No baseline differences were observed between groups. Variceal rebleeding occurred in 12% of the 48 patients whose haemodynamic response was assessed. Responders on drug therapy presented a 16% rebleeding rate, whilst non-responders rescued with banding showed an 8% rebleeding rate. Rebleeding-related mortality was not different between groups. CONCLUSION: In a HVPG-guided strategy, adding banding ligation to drugs is an effective rescue strategy to prevent rebleeding in haemodynamic non-responders to drug therapy.

Risk factors for recurrence of acute gastrointestinal bleeding from angiodysplasia.

BACKGROUND AND AIMS: Recurrent bleeding from gastrointestinal (GI) angiodysplasia remains a therapeutic challenge. Identification of factors predicting poor outcome of haemorrhage from angiodysplasia would help us to select the patients who may likely benefit from further therapy. Thus, we analysed risk factors for recurrence of acute GI haemorrhage from angiodysplasia. PATIENTS AND METHODS: 62 patients admitted consecutively with acute GI bleeding from angiodysplasia, between June 2002 and June 2006, were included. Bivariate, multivariate and survival analysis were performed to identify risk factors for recurrence of bleeding after hospital discharge. RESULTS: Recurrence of acute haemorrhage after hospital discharge occurred in 17 of 57 (30%) patients (38 men; mean age: 74+/-6 years), after a mean follow-up (33+/-40 months). On Cox analysis, earlier history of bleeding with a high bleeding rate, over anticoagulation and the presence of multiple lesions were predictive factors of recurrence in a multivariate analysis. In contrast, endoscopic argon plasma coagulation (APC) therapy was not associated with lower rates of recurrent bleeding. CONCLUSION: In patients with acute GI haemorrhage from angiodysplasia, earlier bleeding with a high bleeding rate, over anticoagulation and multiple angiodisplasic lesions predict an increased risk of recurrent bleeding. Although there is a trend towards better management with endoscopic APC therapy for the prevention of recurrence of bleeding, endoscopic APC therapy is not predictive of a lower rate of recurrence.

Capsule endoscopy versus computed tomographic or standard angiography for the diagnosis of obscure gastrointestinal bleeding.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is superior to push enteroscopy and small bowel barium radiography in detecting the source of obscure GI bleeding. We now compared whether CE has a superior diagnostic yield than CT angiography (CTA) or standard mesenteric angiography (ANGIO) in patients with obscure GI bleeding. METHODS: From June 2004 to October 2005, consecutive patients admitted for OGIB underwent both CTA and ANGIO, followed by CE, performed blindly by independent examiners within the next 7 days. The primary end point of the study was the diagnostic yield for each technique, defined as the frequency of detection of lesions with a high probability of bleeding. RESULTS: Twenty-eight patients (16 men and 12 women, mean age 74 +/- 2 yr) with OGIB (overt bleeding in 20 cases and chronic occult in 8) were prospectively evaluated. CTA or standard angiography could be performed in 25 of 28 patients (applicability 86%), because of contrast allergy (1 patient) and chronic renal failure (2 patients). A source of bleeding was detected by CE in a greater proportion of patients, 72% (18 of 25, 95% CI 50.6-87.9%), than CTA, 24% (6 of 25, 95% CI 9.4-45.1%, P= 0.005 vs CE), or ANGIO, 56% (14 of 25, 95% CI 34.9-75.6%, P= NS). Similarly, CE was able to diagnose 100% of patients diagnosed by CTA and 86% of patients diagnosed by ANGIO. Moreover, CE was positive in 12 of 19 (63%) negative cases on CTA and in 6 of 11 (55%) negative cases on ANGIO. As a result of the CE findings, therapeutic intervention was undertaken in 9 of 19 (47%) patients with positive results. CONCLUSION: CE detects more lesions than CTA or standard mesenteric angiography in patients with obscure GI bleeding and has a therapeutic impact in almost half of the patients with positive findings.

Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study.

The clinical usefulness of assessing hemodynamic response to drug therapy in the prophylaxis of variceal rebleeding is unknown. An open-labeled, uncontrolled pilot trial was performed to evaluate the feasibility and efficacy of using the hemodynamic response to pharmacological treatment to guide therapy in this setting. Fifty patients with acute variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were initiated, and a second HVPG was measured 15 days later. Responder patients (> or =20% decrease in HVPG from baseline) were maintained on drugs, partial responders (> or =10% and <20%) had banding ligation added to the drugs, and nonresponders (<10%) received a transjugular intrahepatic portal-systemic shunt (TIPS). Mean follow-up was 22 months. Eight patients (16%) did not receive the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42 patients, 24 were classified as responders (57%); 10 as partial responders (24%), who had banding added; and 8 as nonresponders (19%), who received a TIPS. Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended to present more early rebleedings, less response to drugs and needed more TIPS. Variceal rebleeding occurred in 22% of all patients but only in 12% of patients whose hemodynamic response was assessed. The 3 therapeutic groups were not different. In conclusion, using hemodynamic response to pharmacological treatment to guide therapy in secondary prophylaxis to prevent variceal bleeding is feasible and effectively protects patients from rebleeding. In this context, viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis.

Tratamiento del dolor en la pancreatitis crónica / Treatment of pain in chronic pancreatitis

El dolor abdominal es el síntoma que presentan de forma más frecuente los pacientes con pancreatitis crónica. El 70–90% de los pacientes lo experimentan en algún momento de la evolución de la enfermedad; en el caso de los pacientes con pancreatitis alcohólica generalmente esto ocurre al inicio, en los pacientes con pancreatitis idiopática hay una forma de inicio precoz (juvenil), en la que el dolor se presenta en la fase inicial de la enfermedad, y una forma de inicio tardío (senil), en la que el dolor es de instauración tardía o incluso puede no aparecer nunca. Según diferentes autores, entre un 27 y un 67% de los pacientes precisa tratamiento quirúrgico por falta de respuesta al tratamiento médico, y se sabe también que el dolor puede recidivar en más del 30% de los pacientes operados, por lo que no es infrecuente una segunda intervención. Hoy en día disponemos de varias posibilidades de tratamiento (médico, endoscópico o quirúrgico) y es importante elegir de forma individualizada el método más apropiado para cada paciente(AU)

Abdominal pain is the most frequent symptom in patients with chronic pancreatitis. Between 70 and 90% of patients experience pain at some point in the course of their disease. In patients with alcoholic pancreatitis, pain is usually experienced at disease onset. Two distinct forms of idiopathic chronic pancreatitis can be distinguished: in early-onset (juvenile) idiopathic chronic pancreatitis, pain occurs initially, while in late-onset (senile) idiopathic chronic pancreatitis, pain is delayed or may even be absent.According to several authors, between 27 and 67% of patients require surgery due to lack of response to medical treatment. Pain may reoccur in more than 30% of patients who have undergone surgery and consequently, reintervention is not uncommon. Several treatment options are currently available: medical, endoscopic and surgical. The most appropriate treatment for each patient should be chosen on an individualized basis(AU)