Percutaneous glycerol rhizolysis of the trigeminal ganglion for the treatment of idiopathic and classic trigeminal neuralgia: Outcomes and complications.

BACKGROUND AND PURPOSE: Patients with idiopathic trigeminal neuralgia (TN) with absent arterial contact or venous contact only and classic TN with morphological changes of the trigeminal nerve secondary to venous compression are not routinely recommended microvascular decompression at our institution. In patients with these anatomical subtypes of TN, limited data exists describing the outcomes of percutaneous glycerol rhizolysis (PGR) of the trigeminal ganglion (TG). METHODS: We performed a retrospective single-center cohort study and analyzed outcomes and complications after PGR of the TG. Clinical outcome after PGR of the TG was assessed via the Barrow Neurological Institute (BNI) Pain Scale. RESULTS: Forty-five patients underwent a total of 66 PGRs of the TG. At short-term follow-up, 58 procedures (87.9%) resulted in a BNI score of I (i.e., freedom from pain without medication). At a median follow-up of 3.07 years, 18 procedures (27.3%) resulted in a BNI score of I, 12 procedures (18.1%) resulted in BNI score of IIIa, and 36 procedures (54.5%) resulted in a BNI score of IIIb-V. The median length of freedom from pain without medication was 1.5 years. Eighteen procedures (27.3%) caused hypesthesia and two (3.0%) caused paresthesias. There were no serious complications. CONCLUSION: In patients with these anatomical subtypes of TN there was a high rate of short-term pain relief for the first 1-2 years and thereafter a large proportion of patients experienced pain relapse. In this patient group, PGR of the TG represents a safe procedure that is efficacious in the short term.

Clinical Outcomes of Medical Management Options for Chronic Anal Fissures in a Long-Term Follow-up: Systematic Review and Meta-Analysis.

BACKGROUND: Topical treatments and botulinum toxin injections are valid options for the management of patients with chronic anal fissures (CAF), but little is known about the efficacy of these techniques in long-term follow-up. The aim of this meta-analysis was to evaluate the effectiveness, given to clinical outcomes, of medical treatments with calcium antagonists, nitroglycerin, and botulinum toxin on CAF treatment in adults. METHOD: A systemic review and meta-analysis developed according to PRISMA [PLoS Med. 2009 Jul 21;6(7):e1000100; BMJ. 2010 Mar 23;340:c332] and registered in PROSPERO (Registration number: CRD42020120386). A systematic literature search was conducted through MEDLINE, EMBASE, Web of Science, and Cochrane Library databases. Randomized control trials that compared medical treatment were identified; publications had to have a clinical definition of CAF with at least one of the following signs or symptoms: visible sphincter fibers at the base of the fissure, anal papillae, sentinel piles, and indurated margins. The symptoms had to be chronic for at least 4 weeks. Data were independently extracted for each study, and a meta-analysis was drawn using fixed- and random-effects models. RESULTS: 17 randomized trials met the inclusion criteria. Diltiazem showed a superior effect compared with glycerin (RR = 1.16 [95% CI = 1.05-1.30]; I2 = 18%) and with fewer adverse effects (RR = 0.13 [95% CI = 0.04-0.042]; I2 = 87%). Similar results were evidenced with the use of nifedipine compared with lidocaine (RR = 4.53 [95% CI = 2.99-6.86]; I2 = 28%). Botulinum toxin did not show statistically significant differences compared to glycerin (RR = 0.81 [95% CI = 0.02-29.36]; I2 = 93%) or isosorbide dinitrate (RR = 1.45 [95% CI = 0.32-6.54]; I2 = 85%). Regarding recurrence, nifedipine was superior to lidocaine (RR = 0.18 [95% CI = 0.08-0.44]; I2 = 31%). CONCLUSIONS: Calcium channel blockers performed well regarding the healing of CAF when compared to others in long-term follow-up. The superiority of botulinum toxin was not evidenced compared to topical treatments. More studies are needed to better assess recurrence rates.

Can 595-nm Pulsed Dye Laser in Conjunction With an Optical Clearing Agent Improve the Treatment of Port-Wine Stains?

BACKGROUND: Studies have demonstrated that glycerol can act as an optical clearing agent (OCA) to increase the light penetration through the skin and laser deposition to the target chromophore, thus potentially increasing the efficacy of laser treatment. OBJECTIVE: To evaluate whether a pulsed dye laser (PDL) in combination with an OCA can increase the efficacy in treating port-wine stains (PWSs). METHODS: Thirteen patients with untreated PWSs underwent 3 treatment sessions at 6-week intervals. Each PWS was divided into OCA + PDL sites (PDL treatment after topical use of 0.5 mL hydrous glycerol for 5 minutes), PDL sites, and untreated sites. The chromametric evaluation and visual evaluation (VAS) of the efficacy and the assessment of side effects were conducted 3 months after the final treatment. RESULTS: Visual evaluation was 2.69 versus 2.07 (p = .025) and 3.38 versus 3.07 (p = .04) for OCA + PDL and PDL-only sites after the first and second sessions. After the third session, the chromameter and VAS indicated no significant difference between the 2 sites. Permanent side effects were not observed. CONCLUSION: Greater efficacy was observed after the first 2 treatments on the OCA + PDL sites. Although after multiple sessions, the OCA + PDL treatment did not improve efficacy over just PDL alone.

Symptomatic Diethylene Glycol Ingestion Successfully Treated with Fomepizole Monotherapy.

BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.

Thermofluor-Based Optimization Strategy for the Stabilization of Recombinant Human Soluble Catechol-O-Methyltransferase.

Catechol-O-methyltransferase (COMT) has been involved in a number of medical conditions including catechol-estrogen-induced cancers and a great range of cardiovascular and neurodegenerative diseases such as Parkinson's disease. Currently, Parkinson's disease treatment relies on a triple prophylaxis, involving dopamine replacement by levodopa, the use of aromatic L-amino acid decarboxylase inhibitors, and the use of COMT inhibitors. Typically, COMT is highly thermolabile, and its soluble isoform (SCOMT) loses biological activity within a short time span preventing further structural and functional trials. Herein, we characterized the thermal stability profile of lysate cells from Komagataella pastoris containing human recombinant SCOMT (hSCOMT) and enzyme-purified fractions (by Immobilized Metal Affinity Chromatography-IMAC) upon interaction with several buffers and additives by Thermal Shift Assay (TSA) and a biological activity assessment. Based on the obtained results, potential conditions able to increase the thermal stability of hSCOMT have been found through the analysis of melting temperature (Tm) variations. Moreover, the use of the ionic liquid 1-butyl-3-methylimidazolium chloride [C4mim]Cl (along with cysteine, trehalose, and glycerol) ensures complete protein solubilization as well as an increment in the protein Tm of approximately 10 °C. Thus, the developed formulation enhances hSCOMT stability with an increment in the percentage of activity recovery of 200% and 70% when the protein was stored at 4 °C and -80 °C, respectively, for 12 h. The formation of metanephrine over time confirmed that the enzyme showed twice the productivity in the presence of the additive. These outstanding achievements might pave the way for the development of future hSCOMT structural and biophysical studies, which are fundamental for the design of novel therapeutic molecules.

[Identification of GPAT1-dependent mitochondrial metabolism as a novel therapeutic target for AML].

Recent studies have demonstrated that cancer-specific metabolism plays a crucial role in a variety of malignancies, including acute myeloid leukemia (AML). To identify a novel therapeutic target for AML, we conducted a metabolite screen on AML cells and normal hematopoietic stem/progenitor cells (HSPCs) and detected that the metabolism of glycerol-3-phosphate (G3P) is reprogrammed in AML. Glycerol-3-phosphate acyltransferases (GPATs), the first and rate-limiting enzymes in the lipid biosynthesis pathway, convert G3P into lysophosphatidic acid (LPA). Among various GPAT isozymes, GPAT1 was highly expressed in AML cells and silencing it inhibited the cell growth of AML. GPAT1 is located on the outer membrane of the mitochondria and regulates mitochondrial fusion and oxidative phosphorylation (OXPHOS). Silencing GPAT1 promoted mitochondrial fission and reduced OXPHOS. In AML, the GPAT1 inhibitor also suppressed cell proliferation and mitochondrial metabolism. However, this inhibitor had no effect on normal hematopoiesis in vivo. In conclusion, these findings indicate that targeting GPAT1 may be a promising therapeutic strategy for AML, since it suppresses leukemia-specific metabolism without impairing normal HSPCs.

Comparative efficacy and safety of glycerol versus mannitol in patients with cerebral oedema and elevated intracranial pressure: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Glycerol is thought to be superior to mannitol in the treatment of cerebral oedema and elevated intracranial pressure (ICP), particularly with safety concerns. However, the current evidence remains insufficient. Therefore, we aimed to compare the efficacy and safety of glycerol versus mannitol in this meta-analysis. METHODS: PubMed, EMBASE, Web of Science, CENTRAL, China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP information, ClinicalTrials.gov, and the reference lists of relevant articles were searched for randomized controlled trials comparing glycerol and mannitol in patients with brain oedema and elevated ICP. Two investigators independently identified the articles, assessed the study quality and extracted data. Data analyses were performed using RevMan software. RESULTS AND DISCUSSION: Thirty trials involving 3144 patients met our inclusion criteria. Pooled data indicated that glycerol and mannitol had comparable effectiveness in controlling cerebral oedema (RR, 1.00; 95% CI, 0.97 to 1.03; p = .97), but the risks of acute kidney injury and electrolyte disturbances were significantly lower with glycerol (RR, 0.21; 95% CI, 0.16 to 0.27 and RR, 0.23; 95% CI, 0.17 to 0.30, respectively) than mannitol. Moreover, there seemed to be a lower probability of rebound ICP after the withdrawal of glycerol. Neither haemolysis nor elevated blood glucose levels were observed in the glycerol group. WHAT IS NEW AND CONCLUSION: Regarding the balance between efficacy and safety, glycerol could be an effective and more tolerable alternative therapy for cerebral oedema and elevated ICP than mannitol, especially for high-risk populations of renal failure.

Natural remedies for acute post-viral cough in children.

The post-viral acute cough is the most common symptom in childhood. Consequently, the use of cough relievers is frequent. Many products for treating cough contain natural components. An ancient tradition has always established herbal medicine and honey as effective and safe means to relieve cough. Nevertheless, very few studies adequately investigated the real effectiveness and safety of natural products in treating acute cough. There is some evidence, provided by pediatric randomized controlled trials, about honey, one multicomponent product (containing Plantagolanceolata, Grindelia robusta, Helichrysum italicum, and honey), and Pelargonium sidoides. Other group of substances, including glycerol and isolated natural compounds, can help manage cough but robust evidence still lacks in children. There is an urgent need to perform rigorous studies that confirm the natural products' efficacy and safety for relieving post-viral acute cough.Key points: Acute post-viral cough is prevalent in childhood and adolescence. There is a growing interest concerning the use of natural remedies for post-viral cough. Many herbal medicines could be used satisfactorily for this issue.

Acute cough in children and adolescents: A systematic review and a practical algorithm by the Italian Society of Pediatric Allergy and Immunology.

The current systematic review presented and discussed the most recent studies on acute cough in pediatric age. After that, the Italian Society of Pediatric Allergy and Immunology elaborated a comprehensive algorithm to guide the primary care approach to pediatric patients, such as infants, children, and adolescents, with acute cough. An acute cough is usually consequent to upper respiratory tract infections and is self-resolving within a few weeks. However, an acute cough may be bothersome, and therefore remedies are requested, mainly by the parents. An acute cough may significantly affect the quality of life of patients and their family.Several algorithms for the management of acute cough have been adopted and validated in clinical practice; however, unlike the latter, we developed an algorithm focused on pediatric age, and, also, in accordance to the Italian National Health System, which regularly follows the child from birth to all lifelong. Based on our findings, infants from 6 months, children, and adolescents with acute cough without cough pointers can be safely managed using well-known medications, preferably non-sedative agents, such as levodropropizine and/or natural compounds, including honey, glycerol, and herb-derived components.

Achieving effective patient outcomes with PolyMem® Silicone Border.

Clinicians are under increasing pressure to provide high-quality patient outcomes at a reduced cost. Increasingly, community staff must acquire knowledge on advanced wound care products to cope with the growing caseload demands. This article describes the use of PolyMem® dressings to reduce pain, inflammation, oedema and bruising and their ability to debride and absorb exudate while providing an optimum healing environment. The PolyMem range includes multifunctional dressings for various painful chronic wounds. This article also presents five case studies with particularly good patient outcomes where PolyMem dressings were the primary dressing. All five patients were holistically assessed to enable consistent evidence-based treatment decisions. In four cases, the new PolyMem Silicone Border dressing was used. The patients found the PolyMem Silicone Border dressing comfortable and gentle on removal even when the skin was extremely fragile. The right dressing used at the right time on the right patient can improve patient outcomes.

Impact of Diagnosis and Therapy on Cognitive Function in Urea Cycle Disorders.

OBJECTIVE: Individuals with urea cycle disorders (UCDs) often present with intellectual and developmental disabilities. The major aim of this study was to evaluate the impact of diagnostic and therapeutic interventions on cognitive outcomes in UCDs. METHODS: This prospective, observational, multicenter study includes data from 503 individuals with UCDs who had comprehensive neurocognitive testing with a cumulative follow-up of 702 patient-years. RESULTS: The mean cognitive standard deviation score (cSDS) was lower in symptomatic than in asymptomatic (p < 0.001, t test) individuals with UCDs. Intellectual disability (intellectual quotient < 70, cSDS < -2.0) was associated with the respective subtype of UCD and early disease onset, whereas height of the initial peak plasma ammonium concentration was inversely associated with neurocognitive outcomes in mitochondrial (proximal) rather than cytosolic (distal) UCDs. In ornithine transcarbamylase and argininosuccinate synthetase 1 deficiencies, we did not find evidence that monoscavenger therapy with sodium or glycerol phenylbutyrate was superior to sodium benzoate in providing cognitive protection. Early liver transplantation appears to be beneficial for UCDs. It is noteworthy that individuals with argininosuccinate synthetase 1 and argininosuccinate lyase deficiencies identified by newborn screening had better neurocognitive outcomes than those diagnosed after the manifestation of first symptoms. INTERPRETATION: Cognitive function is related to interventional and non-interventional variables. Early detection by newborn screening and early liver transplantation appear to offer greater cognitive protection, but none of the currently used nitrogen scavengers was superior with regard to long-term neurocognitive outcome. Further confirmation could determine these variables as important clinical indicators of neuroprotection for individuals with UCDs. ANN NEUROL 2019.

Long-term safety and efficacy of glycerol phenylbutyrate for the management of urea cycle disorder patients.

INTRODUCTION: Glycerol phenylbutyrate (GPB) is currently approved for use in the US and Europe for patients of all ages with urea cycle disorders (UCD) who cannot be managed with protein restriction and/or amino acid supplementation alone. Currently available data on GPB is limited to 12 months exposure. Here, we present long-term experience with GPB. METHODS: This was an open-label, long-term safety study of GPB conducted in the US (17 sites) and Canada (1 site) monitoring the use of GPB in UCD patients who had previously completed 12 months of treatment in the previous safety extension studies. Ninety patients completed the previous studies with 88 of these continuing into the long-term evaluation. The duration of therapy was open ended until GPB was commercially available. The primary endpoint was the rate of adverse events (AEs). Secondary endpoints were venous ammonia levels, number and causes of hyperammonemic crises (HACs) and neuropsychological testing. RESULTS: A total of 45 pediatric patients between the ages of 1 to 17 years (median 7 years) and 43 adult patients between the ages of 19 and 61 years (median 30 years) were enrolled. The treatment emergent adverse events (TEAE) reported in ≥10% of adult or pediatric patients were consistent with the TEAEs reported in the previous safety extension studies with no increase in the overall incidence of TEAEs and no new TEAEs that indicated a new safety signal. Mean ammonia levels remained stable and below the adult upper limit of normal (<35 µmol/L) through 24 months of treatment in both the pediatric and adult population. Over time, glutamine levels decreased in the overall population. The mean annualized rate of HACs (0.29) established in the previously reported 12-month follow-up study was maintained with continued GPB exposure. CONCLUSION: Following the completion of 12-month follow-up studies with GPB treatment, UCD patients were followed for an additional median of 1.85 (range 0 to 5.86) years in the present study with continued maintenance of ammonia control, similar rates of adverse events, and no new adverse events identified.

Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.

PURPOSE OF REVIEW: Hepatic encephalopathy is one of the most debilitating clinical manifestations of cirrhosis and associated with increased morbidity and mortality. Treatment modalities available include the nonabsorbable disaccharides (lactulose) and the nonabsorbable antibiotics (rifaximin). RECENT FINDINGS: Newer therapeutic targets under evaluation include ammonia scavengers (ornithine phenylacetate) and modulation of gut microbiota (fecal microbiota transplantation). SUMMARY: This review will focus on the pathophysiology of hepatic encephalopathy along with an update on therapeutic targets under investigation.

Role of Aquaporin-3 in Intestinal Injury Induced by Sepsis.

Aquaporin-3 (AQP3) is expressed in various parts of the intestine, where it regulates the proliferation and migration of intestinal epithelial cells and the transport of glycerol and hydrogen peroxide. Our study aimed to investigate the effect on the expression of AQP3 of intestinal injury in septic mice and whether oral administration of glycerol can reduce intestinal epithelial injury and barrier disorder by acting as a partial substitute for the function of AQP3. We established a sepsis model by cecal ligation and perforation (CLP) in mice. Sepsis induced intestinal injury, as demonstrated by the disordered destruction of the morphology of the intestinal mucosa, time-dependent increases in Chiu's score (p < 0.05), significantly increased (p < 0.05) plasma concentrations of determination of the levels of diamine oxidase (DAO) and intestinal fatty acid-binding protein 2 (FABP2), and time-dependent downregulation of the expression of AQP3 and occluding (p < 0.05). While the administration of oral glycerol partially ameliorated the sepsis-induced injury of the intestinal mucosa, as shown by the partial recovery of the morphological structure, with decreased Chiu's score, decreased plasma concentrations of DAO and intestinal-type FABP2, upregulated expression of occludin and decreased mortality rate (Sepsis vs. Sepsis + Glycerol, p < 0.05). The results showed that the expression levels of AQP3 and occludin were downregulated after septic intestinal injury, while treatment with glycerol, which acts as a substitute for AQP3, partly ameliorated intestinal injury and improved the survival rate. This preliminary experiment suggests that AQP3 may protect the intestinal tract against the effects of sepsis.

Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.

BACKGROUND: Hepatic encephalopathy is a common complication of cirrhosis, with high related morbidity and mortality. Its presence is associated with a wide spectrum of change ranging from clinically obvious neuropsychiatric features, known as 'overt' hepatic encephalopathy, to abnormalities manifest only on psychometric or electrophysiological testing, 'minimal' hepatic encephalopathy. The exact pathogenesis of the syndrome is unknown but ammonia plays a key role. Drugs that specifically target ammonia include sodium benzoate, glycerol phenylbutyrate, ornithine phenylacetate, AST-120 (spherical carbon adsorbent), and polyethylene glycol. OBJECTIVES: To evaluate the beneficial and harmful effects of pharmacotherapies that specifically target ammonia versus placebo, no intervention, or other active interventions, for the prevention and treatment of hepatic encephalopathy in people with cirrhosis. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three other databases to March 2019. We also searched online trials registries such as ClinicalTrials.gov, European Medicines Agency, WHO International Clinical Trial Registry Platform, and the Food and Drug Administration for ongoing or unpublished trials. In addition, we searched conference proceedings, checked bibliographies, and corresponded with investigators. SELECTION CRITERIA: We included randomised clinical trials comparing sodium benzoate, glycerol phenylbutyrate, ornithine phenylacetate, AST-120, and polyethylene glycol versus placebo or non-absorbable disaccharides, irrespective of blinding, language, or publication status. We included participants with minimal or overt hepatic encephalopathy or participants who were at risk of developing hepatic encephalopathy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included reports. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I2 statistic values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary domains and the certainty of the evidence using GRADE. MAIN RESULTS: We identified 11 randomised clinical trials that fulfilled our inclusion criteria. Two trials evaluated the prevention of hepatic encephalopathy while nine evaluated the treatment of hepatic encephalopathy. The trials assessed sodium benzoate (three trials), glycerol phenylbutyrate (one trial), ornithine phenylacetate (two trials), AST-120 (two trials), and polyethylene glycol (three trials). Overall, 499 participants received these pharmacotherapies while 444 participants received a placebo preparation or a non-absorbable disaccharide. We classified eight of the 11 trials as at 'high risk of bias' and downgraded the certainty of the evidence to very low for all outcomes.Eleven trials, involving 943 participants, reported mortality data, although there were no events in five trials. Our analyses found no beneficial or harmful effects of sodium benzoate versus non-absorbable disaccharides (RR 1.26, 95% CI 0.49 to 3.28; 101 participants; 2 trials; I2 = 0%), glycerol phenylbutyrate versus placebo (RR 0.65, 95% CI 0.11 to 3.81; 178 participants; 1 trial), ornithine phenylacetate versus placebo (RR 0.73, 95% CI 0.35 to 1.51; 269 participants; 2 trials; I2 = 0%), AST-120 versus lactulose (RR 1.05, 95% CI 0.59 to 1.85; 41 participants; 1 trial), or polyethylene glycol versus lactulose (RR 0.50, 95% CI 0.09 to 2.64; 190 participants; 3 trials; I2 = 0%).Seven trials involving 521 participants reported data on hepatic encephalopathy. Our analyses showed a beneficial effect of glycerol phenylbutyrate versus placebo (RR 0.57, 95% CI 0.36 to 0.90; 178 participants; 1 trial; number needed to treat for an additional beneficial outcome (NNTB) 6), and of polyethylene glycol versus lactulose (RR 0.19, 95% CI 0.08 to 0.44; 190 participants; 3 trials; NNTB 4). We did not observe beneficial effects in the remaining three trials with extractable data: sodium benzoate versus non-absorbable disaccharides (RR 1.22, 95% CI 0.51 to 2.93; 74 participants; 1 trial); ornithine phenylacetate versus placebo (RR 2.71, 95% CI 0.12 to 62.70; 38 participants; 1 trial); or AST-120 versus lactulose (RR 1.05, 95% CI 0.59 to 1.85; 41 participants; 1 trial).Ten trials, involving 790 participants, reported a total of 130 serious adverse events. Our analyses found no evidence of beneficial or harmful effects of sodium benzoate versus non-absorbable disaccharides (RR 1.08, 95% CI 0.44 to 2.68; 101 participants; 2 trials), glycerol phenylbutyrate versus placebo (RR 1.63, 95% CI 0.85 to 3.13; 178 participants; 1 trial), ornithine phenylacetate versus placebo (RR 0.92, 95% CI 0.62 to 1.36; 264 participants; 2 trials; I2 = 0%), or polyethylene glycol versus lactulose (RR 0.57, 95% CI 0.18 to 1.82; 190 participants; 3 trials; I2 = 0%). Likewise, eight trials, involving 782 participants, reported a total of 374 non-serious adverse events and again our analyses found no beneficial or harmful effects of the pharmacotherapies under review when compared to placebo or to lactulose/lactitol.Nine trials, involving 733 participants, reported data on blood ammonia. We observed significant reductions in blood ammonia in placebo-controlled trials evaluating sodium benzoate (MD -32.00, 95% CI -46.85 to -17.15; 16 participants; 1 trial), glycerol phenylbutyrate (MD -12.00, 95% CI -23.37 to -0.63; 178 participants; 1 trial), ornithine phenylacetate (MD -27.10, 95% CI -48.55 to -5.65; 231 participants; 1 trial), and AST-120 (MD -22.00, 95% CI -26.75 to -17.25; 98 participants; 1 trial). However, there were no significant differences in blood ammonia concentrations in comparison with lactulose/lactitol with sodium benzoate (MD 9.00, 95% CI -1.10 to 19.11; 85 participants; 2 trials; I2 = 0%), AST-120 (MD 5.20, 95% CI -2.75 to 13.15; 35 participants; 1 trial), and polyethylene glycol (MD -29.28, 95% CI -95.96 to 37.39; 90 participants; 2 trials; I2 = 88%). FUNDING: Five trials received support from pharmaceutical companies while four did not; two did not provide this information. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the effects of these pharmacotherapies on the prevention and treatment of hepatic encephalopathy in adults with cirrhosis. They have the potential to reduce blood ammonia concentrations when compared to placebo, but their overall effects on clinical outcomes of interest and the potential harms associated with their use remain uncertain. Further evidence is needed to evaluate the potential beneficial and harmful effects of these pharmacotherapies in this clinical setting.

Randomized controlled trial of the effectiveness of three different oral moisturizers in palliative care patients.

Most patients in palliative care have problems with dry mouth caused by medication or as a direct result of their condition. Dry mouth may cause problems that affect the primary disease negatively and contribute to poorer quality of life in palliative patients. This randomized controlled trial compared the efficacy of three different oral moisturizers: 17% watery solution of glycerol; oxygenated glycerol triester (marketed as Aequasyal in Europe and as Aquoral in the USA); and a newly developed product, Salient. Of the three products, glycerol provided the best relief from xerostomia directly after application, but had no effect after 2 h. By contrast, the effects of Aequasyal and Salient were largely maintained over the same period. The findings for oral discomfort and pain and speech problems showed a similar pattern. Despite its poor effect after 2 h, patients preferred glycerol over Salient and Aequasyal, probably because of the unpleasant taste of Aequasyal and the consistency and mode of application of Salient. Within the limitations of this study, none of the three products tested was found to be clinically completely adequate. However, the glycerol solution was preferred by this group of patients, and its short-lived effect can be compensated for by frequent applications.

Effect of glycerol on reconstructed human oral mucosa.

The majority of severely ill patients experience dry mouth. For institutionalized patients, this condition is commonly treated using glycerol as a lubricant. However, because of its possibly desiccating effect, some countries do not advocate the use of glycerol. This study aimed to investigate dose-dependent effects of glycerol on homeostasis and tissue integrity of in vitro-reconstructed normal human buccal mucosa (RNHBM). Primary keratinocytes and fibroblasts were isolated and expanded from biopsies of mucosa from eight healthy volunteers. Ninety-six samples of RNHBM were prepared and exposed for 24 h to 17%, 42.5%, or 85% glycerol, or to distilled H2 O (control). Sections were stained with haematoxylin and eosin (H&E) to evaluate epithelial thickness or used for immunohistochemistry to measure expression of Ki67 (proliferation), cleaved caspase-3 (apoptosis), and E-cadherin (tissue-integrity). Positive cells and cell layers, as detected by immunohistochemistry, were counted. Epithelial thickness, proliferation, and apoptosis were significantly increased by exposure to 42.5% and 85% glycerol. No significant differences in apoptosis or proliferation were found between controls and RNHBM exposed to 17% glycerol. E-cadherin expression was not significantly affected by exposure to any of the concentrations of glycerol tested. This study shows that glycerol affects tissue homeostasis, but not tissue integrity, of RNHBM at glycerol concentrations above 42.5%.

Treatment of Facial Telangiectases With Glycerin Sclerotherapy.

BACKGROUND: Sclerotherapy is used to treat varicosities and telangiectases. Glycerin is a sclerosing agent that has been used off-label for years with a favorable adverse effect profile. However, the treatment of facial telangiectases with sclerotherapy is controversial given the potential for necrosis and embolization in relation to the complex vascular anatomy of the face. OBJECTIVE: To determine the safety and efficacy of glycerin sclerotherapy for the treatment of facial telangiectases. MATERIALS AND METHODS: The authors report a series of 8 patients with facial telangiectases treated with glycerin sclerotherapy. Glycerin mixed with lidocaine and epinephrine was used. The telangiectases were measured and identified as targets for treatment. RESULTS: The patients ranged in age from 45 to 88 years. Between 0.5 and 1 mL was used to treat telangiectases of the nose and malar cheek area per session. Five of the patients achieved satisfactory results after 1 treatment, whereas patients with more extensive telangiectases required up to 3 sessions with 4-week intervals between each session. Injection site pain was the only reported adverse effect, and no evidence of necrosis or blindness was observed. CONCLUSION: Glycerin sclerotherapy seems to be a safe and effective modality for the treatment of facial telangiectases.

Clinical and radiographic outcomes of chitosan-glycerol phosphate/blood implant are similar with hyaluronic acid-based cell-free scaffold in the treatment of focal osteochondral lesions of the knee joint.

PURPOSE: To determine the clinical and radiographic efficacy of chitosan-glycerol phosphate/blood implant versus hyaluronic acid-based cell-free scaffold in patients with focal osteochondral lesion of the knee joint. METHODS: Clinical data of 46 patients surgically treated using either chitosan-glycerol phosphate/blood implant (25 patients, Group 1) or hyaluronic acid-based cell-free scaffold (21 patients, Group 2) in combination with microfracture were retrospectively evaluated. All lesions were Outerbridge grade III or IV with a mean lesion size of 3.3 ± 0.7 cm2. The mean follow-up time was 24.4 months. Visual analogue scale (VAS), Lysholm knee score, and Tegner activity scale were the instruments to evaluate the clinical status. Magnetic resonance observation of cartilage repair tissue (MOCART) system was used to analyze the characteristics of repair tissue. RESULTS: No significant differences were detected between the groups regarding VAS, Lysholm, and Tegner scores at any time interval during the whole follow-up. The mean post-operative VAS and Lysholm scores at the latest follow-up was significantly better in cases with the lesion size ≤ 3 cm2 in Group 1 (p = 0.001, p < 0.001, respectively). However, no significant differences according to the lesion size were detected in Group 2 (n.s.). Complete repair with the filling of the defect was achieved in 7 (28%) of the knees in Group 1 and it was 7 (33.3%) of the knees in Group 2 according to MOCART system at the latest follow-up. CONCLUSION: Single-stage regenerative cartilage surgery using chitosan-glycerol phosphate/blood implant combined to microfracture for focal osteochondral lesions of the knee revealed similar clinical and radiographic outcomes with hyaluronic acid-based cell-free scaffold at short-term follow-up. However, clinical outcomes of hyaluronan scaffold were less sensitive to defect size than chitosan. With the advantages of no hypertrophic repair tissue formation as well as no need to arthrotomy during surgery, chitosan is an effective choice especially in patients with the lesion size ≤ 3 cm2. LEVEL OF EVIDENCE: III.

Polyglycerol Hyperbranched Polyesters: Synthesis, Properties and Pharmaceutical and Biomedical Applications.

In a century when environmental pollution is a major issue, polymers issued from bio-based monomers have gained important interest, as they are expected to be environment-friendly, and biocompatible, with non-toxic degradation products. In parallel, hyperbranched polymers have emerged as an easily accessible alternative to dendrimers with numerous potential applications. Glycerol (Gly) is a natural, low-cost, trifunctional monomer, with a production expected to grow significantly, and thus an excellent candidate for the synthesis of hyperbranched polyesters for pharmaceutical and biomedical applications. In the present article, we review the synthesis, properties, and applications of glycerol polyesters of aliphatic dicarboxylic acids (from succinic to sebacic acids) as well as the copolymers of glycerol or hyperbranched polyglycerol with poly(lactic acid) and poly(ε-caprolactone). Emphasis was given to summarize the synthetic procedures (monomer molar ratio, used catalysts, temperatures, etc.,) and their effect on the molecular weight, solubility, and thermal and mechanical properties of the prepared hyperbranched polymers. Their applications in pharmaceutical technology as drug carries and in biomedical applications focusing on regenerative medicine are highlighted.