Hepatic veno-occlusive disease complicated with extreme hyperammonaemia (920 µmol/L) treated with defibrotide, lactulose, rifampin and haemodialysis.

Hepatic veno-occlusive disease (VOD)/sinusoidal obstructive syndrome (SOS) is a severe complication that can occur following haematopoietic stem cell transplant (HSCT) with high-intensity conditioning chemotherapy regimens. Severe VOD/SOS, often characterised by multiorgan failure, is associated with a high mortality rate. This case report details the complex clinical course of a male patient in his mid-20s, recently diagnosed with B cell acute lymphoblastic leukaemia, who underwent allogeneic HSCT. Based on the 2023 European Society for Blood and Marrow Transplantation (EBMT) criteria, the patient developed very severe VOD/SOS, prompting immediate treatment with defibrotide. Unexpectedly, he developed profound hyperammonaemia exceeding 900 µmol/L, leading to encephalopathy and cerebral oedema. Despite aggressive interventions including defibrotide, lactulose, rifampin and haemodialysis, the patient passed away due to cerebral oedema and pulseless electrical activity arrest. We theorise the hyperammonaemia is disproportionate to his hepatic dysfunction and is possibly secondary to an acquired defect of the urea synthesis consistent with idiopathic hyperammonaemia, a rare complication in patients receiving intense conditioning chemotherapy.

Diagnosis and Management of Cirrhosis and Its Complications: A Review.

Importance: Cirrhosis affects approximately 2.2 million adults in the US. From 2010 to 2021, the annual age-adjusted mortality of cirrhosis increased from 14.9 per 100 000 to 21.9 per 100 000 people. Observations: The most common causes of cirrhosis in the US, which can overlap, include alcohol use disorder (approximately 45% of all cases of cirrhosis), nonalcoholic fatty liver disease (26%), and hepatitis C (41%). Patients with cirrhosis experience symptoms including muscle cramps (approximately 64% prevalence), pruritus (39%), poor-quality sleep (63%), and sexual dysfunction (53%). Cirrhosis can be diagnosed by liver biopsy but may also be diagnosed noninvasively. Elastography, a noninvasive assessment of liver stiffness measured in kilopascals, can typically confirm cirrhosis at levels of 15 kPa or greater. Approximately 40% of people with cirrhosis are diagnosed when they present with complications such as hepatic encephalopathy or ascites. The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively. Among people with ascites, the annual incidence of spontaneous bacterial peritonitis is 11% and of hepatorenal syndrome is 8%; the latter is associated with a median survival of less than 2 weeks. Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20%. In a 3-year randomized clinical trial of 201 patients with portal hypertension, nonselective ß-blockers (carvedilol or propranolol) reduced the risk of decompensation or death compared with placebo (16% vs 27%). Compared with sequential initiation, combination aldosterone antagonist and loop diuretics were more likely to resolve ascites (76% vs 56%) with lower rates of hyperkalemia (4% vs 18%). In meta-analyses of randomized trials, lactulose was associated with reduced mortality relative to placebo (8.5% vs 14%) in randomized trials involving 705 patients and reduced risk of recurrent overt hepatic encephalopathy (25.5% vs 46.8%) in randomized trials involving 1415 patients. In a randomized clinical trial of 300 patients, terlipressin improved the rate of reversal of hepatorenal syndrome from 39% to 18%. Trials addressing symptoms of cirrhosis have demonstrated efficacy for hydroxyzine in improving sleep dysfunction, pickle brine and taurine for reducing muscle cramps, and tadalafil for improving sexual dysfunction in men. Conclusions and Relevance: Approximately 2.2 million US adults have cirrhosis. Many symptoms, such as muscle cramps, poor-quality sleep, pruritus, and sexual dysfunction, are common and treatable. First-line therapies include carvedilol or propranolol to prevent variceal bleeding, lactulose for hepatic encephalopathy, combination aldosterone antagonists and loop diuretics for ascites, and terlipressin for hepatorenal syndrome.

Polyethylene glycol combined with lactulose has better efficacy than polyethylene glycol alone in bowel preparation before colonoscopy: A meta-analysis.

BACKGROUND: The accuracy of diagnosis and the safety of treatment in colonoscopy depends largely on the quality of bowel cleansing. This study aimed to compare the efficacy and adverse reactions of Polyethylene Glycol (PEG) combined with lactulose with that of PEG alone in bowel preparation before colonoscopy. METHODS: The authors searched a number of databases including EMBASE, MEDLINE, Cochrane Library, and China Academic Journals Full-text Database. The authors screened according to literature inclusion and exclusion criteria, assessed the quality of the included literature, and extracted the data. The meta-analysis of included literature used RevMan 5.3 and Stata 14.0 software. RESULTS: A total of 18 studies, including 2274 patients, were enrolled. The meta-analysis showed that PEG combined with lactulose had a better efficacy (OR = 3.87, 95% CI 3.07‒4.87, p = 0.000, and I2 = 36.2% in the efficiency group; WMD = 0.86, 95% CI 0.69‒1.03, p = 0.032 and I2 = 0% in the BBPS score group) in bowel preparation for patients with or without constipation. Moreover, PEG combined with lactulose had fewer adverse reactions, including abdominal pain (OR = 1.42, 95% CI 0.94‒2.14, p = 0.094), nausea (OR = 1.60, 95% CI 1.13‒2.28, p = 0.009) and vomiting (OR = 1.77, 95% CI 1.14‒2.74, p = 0.011), than PEG alone. No significant reduction in the incidence of abdominal distention was observed. CONCLUSION: PEG combined with lactulose may be a better choice for bowel preparation before colonoscopy compared with PEG alone.

Laser acupuncture improving functional chronic constipation in children: a randomized controlled trial.

Functional chronic constipation (FCC) is a disorder caused by low fiber consumption, lack of fluid intake, lack of mobility, or side effects of medications. The objective of this study was to compare the effects of laser acupuncture and the commonly used osmotic laxative, lactulose (as the control), both combined with behavioral therapy and dietary modification, on children with FCC in a randomized controlled trial (RCT). Forty children were randomly chosen, aged 5-15 years with FCC, and randomized into two equal groups (gender ratio (50% male; 50% female), mean ± SD weight (24.2 ± 6.27 kg and 25.7 ± 7.47 kg for groups A and B, respectively)). Study group (group A): used laser acupuncture (650 nm), 30 mW, 0.15 cm2 spot size, 90 s per acupuncture point (ST25, ST36, ST37, BL25, and LI11). Control group (group B): lactulose syrup (1 to 3 mL/kg/day) orally, in divided doses 3 times weekly for 4 weeks, and behavioral training for both groups. Evaluations were conducted before and after the study to assess the efficacy of the therapy. Median value frequency significantly increased in groups A and B post-treatment (4 (6.75-3) and 3 (3.75-2), respectively) compared to pre-treatment (2 (2-1) and 2 (2-0.25), respectively) (p = 0.0001), in favor of group A (p = 0.01). Significant improvement of stool consistency according to Bristol stool scale (BSS) in groups A and B (p = 0.0001), (p = 0.002) respectively in favor of group A (p = 0.03). T-test, Fisher, and Wilcoxon signed rank tests were conducted to compare groups. Non-invasive, painless laser acupuncture therapy can be considered as an alternative therapy for patients with FCC.

Effect of Bacillus coagulans Unique IS2 with Lactulose on Functional Constipation in Adults: a Double-Blind Placebo Controlled Study.

In the present double-blind randomised study, the efficacy of combination of Bacillus coagulans Unique IS2 and lactulose was evaluated in the treatment of functional constipation in adults. One-fifty participants diagnosed with functional constipation (Rome III criteria) were randomised (1:1:1) and supplemented daily with 15 mL suspension of probiotic (B. coagulans Unique IS2, 2 × 109 spores) with lactulose (10 g) (group 1) or lactulose (10 g) (group 2) or placebo (water) (group 3) for 4 weeks. The primary (stool frequency) and secondary outome measures (stool consistency, sensation of incomplete evacuation, defecation- and abdominal-pain) were recorded weekly for up to 4 weeks. Bacillus coagulans Unique IS2 with lactulose showed significant changes in stool frequency as compared to lactulose treatment; however, at the end of the trial, it was found insignificant due to the gradual increase of stool frequency score of lactulose treatment. The changes observed in stool consistency were early (2nd week) and remained consistent up to end of the trial. The significant reduction of sensation of incomplete evacuation, defecation-, and abdominal-pain correlated with the strains ability to produce short-chain fatty acids. No adverse events were observed in any of the groups, and all the vital parameters were normal during the course of the study. Overall, results indicated that B. coagulans Unique IS2 addition to lactulose reduced time required to relieve constipation as compared to lactulose alone. In conclusion, B. coagulans Unique IS2 with lactulose is more effective than lactulose alone to relieve symptoms of constipation in a shorter period. Trial registration: CTRI/2018/11/016399, dated 22/11/2018.

Colonoscopic laxative instillation for the fecal-loaded colon: a case series

Context: Postoperative, critically ill, and elderly patients often have fecal loading or impaction. In a few such patients, disimpaction of fecalomas and colon cleansing are difficult. Bowel obstruction, megacolon, lower gastrointestinal bleeding, and gut perforation are complications that may ensue. Oral laxatives or enemas may only be partially effective. Surgical intervention may be needed for salvage or to treat complications. Series and Design: Fourteen hospitalized cases with defecation disorder due to fecal loading of the colon were enrolled for retrospective analysis. Colonoscopic instillation of mannitol and/or lactulose was undertaken as an intervention when the use of oral laxatives was either ineffective or unfeasible, and enema had yielded poor results. Results: Ten patients had satisfactory outcomes for fecal clearance, whereas four patients with poor or incomplete responses underwent repeat interventions or surgery. No significant complications were encountered due to this therapy. Conclusion: Colonoscopic instillation of mannitol or lactulose in fecal-loaded critically ill patients results in a safe and satisfactory fecal clearance. (AU)

Efficacy evaluation of probiotics combined with prebiotics in patients with clinical hypothyroidism complicated with small intestinal bacterial overgrowth during the second trimester of pregnancy.

Objective: To explore the effect of probiotics combined with prebiotics on clinical hypothyroidism during pregnancy combined with small intestinal bacterial overgrowth. Methods: (1) In total, 441 pregnant women were included in this study. A total of 231 patients with clinical hypothyroidism during the second trimester of pregnancy and 210 normal pregnant women were enrolled in the lactulose methane-hydrogen breath test. The positive rate of intestinal bacterial overgrowth (SIBO), gastrointestinal symptoms, thyroid function and inflammatory factors were compared between the two groups by chi-square test and two independent sample t-test. (2) SIBO-positive patients in the clinical hypothyroidism group during pregnancy (n=112) were treated with probiotics combined with prebiotics based on conventional levothyroxine sodium tablets treatment. The changes in the methane-hydrogen breath test, gastrointestinal symptoms, thyroid function and inflammatory factors were compared before treatment (G0) and 21 days after treatment (G21) by chi-square test and paired sample t test. Results: (1) The positive rates of SIBO in pregnant women in the clinical hypothyroidism group and control group were 48.5% and 24.8%, respectively. (2) The incidence of abdominal distention and constipation in the clinical hypothyroidism group was significantly higher than that in the control group, and the risk of abdominal distention and constipation in SIBO-positive pregnant women was higher than that in SIBO-negative pregnant women. (3) The serum levels of hypersensitive C-reactive protein (hsCRP), IL-10, IL-6, TNF-α, low-density lipoprotein (LDL), total cholesterol (TC), free fatty acids (FFAs) and apolipoprotein B (ApoB) in the hypothyroidism group during pregnancy were higher than those in the control group. (4) After 21 days of probiotics combined with prebiotics, the incidence of pure methane positivity in the methane-hydrogen breath test in the G21 group was significantly reduced, and the average abundance of hydrogen and methane at each time point in the G21 group was lower than that in the G0 group. (5) The incidence of constipation in the G21 group was significantly lower than before treatment. (6) The levels of serum TSH, hsCRP, IL-6, TNF-α, TC and LDL in pregnant women after probiotics combined with prebiotics were lower than those before treatment. Conclusion: Probiotics combined with prebiotics are effective in the treatment of pregnant patients with clinical hypothyroidism complicated with SIBO, providing a new idea to treat pregnant patients with clinical hypothyroidism complicated with SIBO.

The potential role of lactulose pharmacotherapy in the treatment and prevention of diabetes.

The non-absorbable disaccharide lactulose is mostly used in the treatment of various gastrointestinal disorders such as chronic constipation and hepatic encephalopathy. The mechanism of action of lactulose remains unclear, but it elicits more than osmotic laxative effects. As a prebiotic, lactulose may act as a bifidogenic factor with positive effects in preventing and controlling diabetes. In this review, we summarized the current evidence for the effect of lactulose on gut metabolism and type 2 diabetes (T2D) prevention. Similar to acarbose, lactulose can also increase the abundance of the short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Bifidobacterium as well as suppress the potentially pathogenic bacteria Escherichia coli. These bacterial activities have anti-inflammatory effects, nourishing the gut epithelial cells and providing a protective barrier from microorganism infection. Activation of peptide tyrosine tyrosine (PYY) and glucagon-like peptide 1 (GLP1) can influence secondary bile acids and reduce lipopolysaccharide (LPS) endotoxins. A low dose of lactulose with food delayed gastric emptying and increased the whole gut transit times, attenuating the hyperglycemic response without adverse gastrointestinal events. These findings suggest that lactulose may have a role as a pharmacotherapeutic agent in the management and prevention of type 2 diabetes via actions on the gut microbiota.

Constipation in Children and Adolescents: Evaluation and Treatment.

Constipation in children is usually functional constipation without an organic cause. Organic causes of constipation in children, which include Hirschsprung disease, cystic fibrosis, and spinal cord abnormalities, commonly present with red flag signs and symptoms. A history and physical examination can diagnose functional constipation using the Rome IV diagnostic criteria. The first goal of managing constipation is to treat fecal impaction, and then maintenance therapy is used to prevent a recurrence. Polyethylene glycol is the first-line treatment for constipation. Second-line options include lactulose and enemas. Increasing dietary fiber and fluid intake above usual daily recommendations and adding probiotics provide no additional benefits for treating constipation. Frequent follow-up visits and referrals to a psychologist can assist in reaching some treatment goals. Clinicians should educate caregivers about the chronic course of functional constipation, frequent relapses, and the potential for prolonged therapy. Clinicians should acknowledge caregivers' specific challenges and the negative effects of constipation on the child's quality of life. Referral to a pediatric gastroenterologist is recommended when there is a concern for organic causes or constipation persists despite adequate therapy.

Cost-Effectiveness of Linaclotide Compared to Osmotic Laxatives in the Treatment of Irritable Bowel Syndrome with Constipation in China.

INTRODUCTION: Linaclotide, a selective agonist of guanylate cyclase C, was highly recommended for the treatment of irritable bowel syndrome with constipation (IBS-C). However, the cost-effectiveness of linaclotide in Chinese is not known, and this study aimed to assess the cost-effectiveness of linaclotide for patients with IBS-C. METHODS: An economic evaluation was conducted with a Markov model from a societal perspective. The Markov model was structured to simulate the discontinuation and continuation of medication in IBS-C patients in clinical practice, as well as the revisit and non-visit of non-responding patients. The cycle of the model was 4 weeks, and the time horizon was 1 year. The efficacy data in the model was from the risk ratios obtained by the meta-analysis and the calculation of the response rate of the three medications. The utility, discontinuation rate of the medication, and revisit rate data were from published literature, while the cost data were obtained from experts' opinions and published literature. A series of sensitivity analyses was performed on parameters potentially having impact on the model outputs. RESULTS: The QALYs (quality-adjusted life years) gained for 1-year treatment with linaclotide, polyethylene glycol, and lactulose were 0.821, 0.795, and 0.781, respectively. The corresponding total costs were CNY 7,721 (USD 1,120), CNY 8,797 (USD 1,276) and CNY 9,481 (USD 1,375). In both comparisons, linaclotide was dominant. Compared with polyethylene glycol and lactulose, the likelihood of linaclotide being cost-effective was 100% for both, using 1 times per capita GDP per QALY as willingness-to-pay threshold. CONCLUSIONS: IBS-C seriously affects the quality of life of patients with IBS-C, and linaclotide can improve symptoms and quality of life at less cost.

Refractory Hyperammonemic encephalopathy in Fibrolamellar hepatocellular carcinoma, a case report and literature review.

Fibrolamellar hepatocellular carcinoma is a rare type of hepatocellular carcinoma with unclear etiology. Its prevalence ranges from 0.6%-5%. One of the rare manifestations of FHCC includes hyperammonemic hepatic encephalopathy (HAE). Data regarding HAE in FHCC is limited to case reports, and much is unknown, including its precipitating factors, clinical course, and management. We have reported one such case of FHCC associated HAE and presented an extensive literature review on the topic. We report the case of a 26-year-old Pakistani male who was diagnosed with fibrolamellar hepatocellular carcinoma. On day five after the first chemotherapy, he presented with nausea, vomiting, and confusion. His serum ammonia level was raised, and he was treated with lactulose and rifaximin. The patient continued chemotherapy and had recurrent admissions with HAE. A detailed workup revealed acquired ornithine transcarbamylase deficiency. Ammonia level peaked at 694 umol/L during the clinical course of his disease. He received treatment with multiple ammonia scavengers, including sodium benzoate + phenylacetate, with relief of symptoms and reduction in ammonia level. The patient was eventually lost to follow-up. HAE presents as a paraneoplastic manifestation of FHCC. Patients have laboratory features suggestive of acquired ornithine transcarbamylase deficiency. There is a variable frequency of episodes reported in the literature. Most patients respond well to ammonia scavenger therapies rather than conventional HE management with lactulose or rifaxmin.

Use of Lactulose to Treat Hyperammonemia in ICU Patients Without Chronic Liver Disease or Significant Hepatocellular Injury.

OBJECTIVES: To review ICU patients with elevated ammonia without a clear hepatic etiology, to compare outcomes between those who received lactulose and those who did not. DESIGN: Retrospective observational study. SETTING: Medical, surgical, and subspecialty intensive care units at Wake Forest Baptist Medical Center, Winston-Salem, North Carolina between December 2012 and August 2016. PATIENTS: Adults with ammonia levels above 50 µmol/L, excluding those with known chronic liver disease, inborn error of metabolism, active use of valproic acid, total bilirubin ≥ 2 µmol/L, or alanine aminotransferase ≥ 100 units/L. INTERVENTIONS: Comparison in ICU length of stay (LOS), hospital LOS, in-hospital mortality, and mortality at 30 and 90 days. MEASUREMENTS AND MAIN RESULTS: Criteria for inclusion were met in 103 cases. Mean ammonia level was 75 µmol/L, with undetermined etiology in the majority of subjects. Lactulose was given in 48 cases (46.6%), with a median of 9.5 doses given. There were no significant differences in outcomes between the lactulose and non-lactulose groups. Among subjects with multiple data points, lactulose did not have a dose-dependent effect on ammonia level, and was not associated with faster ammonia normalization compared to non-lactulose. When analyzed separately, patients with moderate hyperammonemia (60-99 µmol/L) who received lactulose had longer hospital and ICU length of stay compared to non-lactulose (417.8 hours vs. 208.4 hours, P = 0.003, and 229.2 hours vs. 104.7 hours, P = 0.025; respectively), though confounders were present. CONCLUSIONS: Routine use of lactulose to treat mild to moderate hyperammonemia in this patient population was not associated with improved outcomes.

L-ornithine L-aspartate in acute treatment of severe hepatic encephalopathy: A double-blind randomized controlled trial.

BACKGROUND AND AIMS: Data on the use of intravenous L-ornithine L-aspartate (LOLA) in the treatment of overt HE (OHE) is limited. We evaluated the role of intravenous LOLA in patients of cirrhosis with OHE grade III-IV. APPROACH AND RESULTS: In a double-blind randomized placebo-controlled trial, 140 patients were randomized to a combination of LOLA, lactulose, and rifaximin (n = 70) or placebo, lactulose, and rifaximin (n = 70). LOLA was given as continuous intravenous infusion at a dose of 30 g over 24 h for 5 days. Ammonia levels, TNF-α, ILs, and endotoxins were measured on days 0 and 5. The primary outcome was the improvement in the grade of HE at day 5. Higher rates of improvement in grade of HE (92.5% vs. 66%, p < 0.001), lower time to recovery (2.70 ± 0.46 vs. 3.00 ± 0.87 days, p = 0.03), and lower 28-day mortality (16.4% vs. 41.8%, p = 0.001) were seen in the LOLA group as compared with placebo. Levels of inflammatory markers were reduced in both groups. Significantly higher reductions in levels of blood ammonia, IL-6, and TNF-α were seen in the LOLA group. CONCLUSIONS: Combination of LOLA with lactulose and rifaximin was more effective than only lactulose and rifaximin in improving grades of HE, recovery time from encephalopathy, with lower 28-day mortality.

Gastrointestinal dysmotility in a patient with advanced lung cancer: paraneoplastic or drug-induced?

A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.

External use of Mirabilite combined with Lactulose improves postoperative gastrointestinal mobility among older patients undergoing abdominal surgery.

AIMS: To evaluate the feasibility and efficacy of Mirabilite combined with Lactulose in older patients after abdominal surgery. DESIGN: It is a retrospective observational cohort study with a pre and post intervention group. METHODS: Medical records were retrospectively reviewed of postoperative Intensive Care patients with postoperative gastrointestinal tract dysfunction (aged >60 years) in the Surgical Intensive Care Unit from January 2017-December 2018. RESULTS: One hundred and sixty-seven post-surgical Intensive Care patients with postoperative gastrointestinal tract dysfunction were analysed; 74 patients received Mirabilite + Lactulose treatment and 93 patients received Lactulose treatment. The recovery rate of bowel sounds was better in the Mirabilite + Lactulose group (62.16%) compared with the Lactulose group (37.63%) after 3-day treatment (p = 0.002) and the relative risk (RR) was 1.65 (95% CI, 1.20, 2.27). Moreover 70.27% patients in the Mirabilite + Lactulose group finally had flatus or defecation compared with 46.24% patients in Lactulose group (p = 0.003) and the RR was 1.52 (1.17, 1.98). The abdominal girth and Inter Abdominal Pressure in Mirabilite + Lactulose group showed significantly greater decrease over a 3-day period compared with Lactulose group (4.86 vs. 3.46 cm, p = 0.027; 4.80 vs. 3.11 mmHg, p = 0.002 respectively). The pain score had greater decrease from the baseline in Mirabilite + Lactulose group than in Lactulose group (2.40 vs. 1.11; p < 0.01). Patients in the Mirabilite + Lactulose group had shorter hospital stay than the Lactulose group 12.5 (SD 3.51) versus 13.9 (SD 5.14), p = 0.05. CONCLUSIONS: This study demonstrated that external use of Mirabilite combined with Lactulose can be considered as an easy intervention to improve postoperative gastrointestinal mobility in older intensive care patients who suffer from postoperative gastrointestinal tract dysfunction after surgery. IMPACT: Our results provide a great option to alleviate the sufferings of postoperative patients. The externally use Mirabilite is a painless and safe interventions that is easy to implement by ICU nurses.

Hyperammonemic encephalopathy during XELOX regimen. Is it capecitabine or oxaliplatin responsible?

Hyperammonemic encephalopathy represents a rare adverse effect of several chemotherapeutic agents, occurring in about 0.7% of patients treated with fluoropyrimidines, and it is independent from dihydropyrimidine dehydrogenase deficiency. Instead, its physiopathology is linked to the inhibition of Krebs cycle by fluoroacetate, leading to decreased ATP production, and to the inhibition of the urea cycle. Oxaliplatin seems to induce hyperammonemic encephalopathy in a similar way, acting on mitochondria. Here, we report the intriguing case of acute hyperammonemic encephalopathy in a 65-year-old patient with preserved liver function, who was treated with oxaliplatin and capecitabine for a metastatic, G1, atypical lung carcinoid. We reviewed the literature and found very few reports of oxaliplatin or capecitabine-induced hyperammonemic encephalopathy. Out of five cases of capecitabine-related hyperammonemic encephalopathy analyzed (four plus our case), median time to hyperammonemic encephalopathy onset was 6 days, with median serum ammonia levels of 213 µmol/L. Oxaliplatin-related hyperammonemic encephalopathy analyzed cases were three (two plus ours), with a median time to hyperammonemic encephalopathy of 11 days and median serum ammonia levels of 167 µmol/L. Identified predisposing factors for chemotherapy-induced hyperammonemia, such as dehydration, liver and renal impairment, infections, and sarcopenia were absent in our case. We hypothesize that the combination of a platinum-derivative and a fluoropyrimidine multiplies the risk of hyperammonemic encephalopathy, even in the absence of predisposing factors nor impaired liver function. We therefore suggest to always consider the risk of hyperammonemia when starting fluoropyrimidines-based chemotherapy, especially combined with platinum-derivatives, and to timely investigate neurologic symptoms monitoring ammonia serum levels.

Prognostic significance of hepatic encephalopathy in patients with cirrhosis treated with current standards of care.

BACKGROUND: Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM: To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS: All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS: 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 ± 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- and 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION: Despite advances made in the management of HE patients continue to have poor survival. Thus, in all patients presenting with HE the appropriateness of orthotopic liver transplantation should be considered.

[Physiological effects, mechanisms of action and application of lactulose].

The discovery of lactulose as a bifidogenic factor became the background for the appearance of the prebiotics concept. Currently, lactulose is the most studied in terms of medical use oligosaccharide with a high prebiotic index. The exact mechanisms of action of lactulose remain largely unknown despite a number of new researches based on modern methods of molecular biology, genetics, and bioinformatics. The aim of this review to summarize and analyze the actual information about biological activity, probable mechanisms of action, and possible uses of lactulose in human nutrition. Results. The structure of lactulose, methods for its determination and preparation are briefly described. Promising methods for producing lactulose include enzymatic synthesis from lactose using ß-galactosidase or epimerase. Information on the physiological effects of lactulose and the mechanisms of its action on the human organism is presented. The works confirming the ability of lactulose to stimulate the growth of bifidobacteria and to influence the metabolism of the intestinal microbiota are summarized. The results of studies of the ability of lactulose to have antitoxic and anticarcinogenic effects are presented. The mechanisms of the positive effect of the prebiotic on the absorption of minerals, increased absorption of Ca and Mg in the human organism are described. The effect of lactulose on immunity and the possibility of its use to reduce the glucose blood level in patients with type 2 diabetes mellitus are shown. The main directions of the use of lactulose in food production are systematized. The data confirming the possibility of using lactulose as a growth factor for probiotics, as well as a protective agent to increase the survival of some starter cultures, are presented. Brief information on the doses and forms of lactulose apply in medicine is presented. The dependence of the effects of lactulose on the dose, health condition and age of patients has been established. Conclusion. Perspective directions of lactulose using in combination with probiotics, other prebiotics, and as an encapsulating ingredient for vitamins and other functional nutrition ingredients are determined. In this regard, the study of lactulose interaction with the components of complex products is relevant.

Chronic Constipation in the United States: Results From a Population-Based Survey Assessing Healthcare Seeking and Use of Pharmacotherapy.

OBJECTIVES: Chronic idiopathic constipation (CIC) is characterized by unsatisfactory defecation and difficult or infrequent stools. CIC affects 9%-20% of adults in the United States, and although prevalent, gaps in knowledge remain regarding CIC healthcare seeking and medication use in the community. We recruited a population-based sample to determine the prevalence and predictors of (i) individuals having discussed their constipation symptoms with a healthcare provider and (ii) the use of constipation therapies. METHODS: We recruited a representative sample of Americans aged 18 years or older who had experienced constipation. Those who met the Rome IV criteria for irritable bowel syndrome and opioid-induced constipation were excluded. The survey included questions on constipation severity, healthcare seeking, and the use of constipation medications. We used multivariable regression methods to adjust for confounders. RESULTS: Overall, 4,702 participants had experienced constipation (24.0% met the Rome IV CIC criteria). Among all respondents with previous constipation, 37.6% discussed their symptoms with a clinician (primary care provider 87.6%, gastroenterologist 26.0%, and urgent care/emergency room physician 7.7%). Age, sex, race/ethnicity, marital status, employment status, having a source of usual care, insurance status, comorbidities, locus of control, and constipation severity were associated with seeking care (P < 0.05). Overall, 47.8% of respondents were taking medication to manage their constipation: over-the-counter medication(s) only, 93.5%; prescription medication(s) only, 1.3%; and both over-the-counter medication(s) and prescription medication(s), 5.2%. DISCUSSION: We found that 3 of 5 Americans with constipation have never discussed their symptoms with a healthcare provider. Furthermore, the use of prescription medications for managing constipation symptoms is low because individuals mainly rely on over-the-counter therapies.