Clival-Meckel's Cave Angle: A Predictor of Glycerol Displacement in Percutaneous Glycerol Rhizotomy for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: Percutaneous glycerol rhizotomy successfully treats trigeminal neuralgia although failure rates and durability of the procedure are variable. Some of this variability in clinical outcome might be due to egress of glycerol from Meckel's cave (MC) because of surgical positioning and individual patient anatomy. In this article, we quantitatively analyzed the anatomic variances that affect glycerol fluid dynamics to better predict patients more amenable for percutaneous glycerol injections. METHODS: Computed tomography imaging of 11 cadaveric heads was used to calculate bilateral Clival-Meckel's cave (CMC) and sella-temporal (ST) angles. Twenty-two cadaveric percutaneous injections of dyed glycerol into the Meckel's cave were performed using Härtel's approach, and the fluid movement was documented at prespecified intervals over 1 hour. The relationship between the angles and glycerol migration was studied. RESULTS: Specimens with basal cistern involvement by 60 minutes had significantly greater CMC angles (median [IQR]: basal cistern involvement = 74.5° [59.5°-89.5°] vs no basal cistern involvement = 58.0° [49.0°-67.0°]), U = 6.0, P < .001. This model may predict which patients will experience glycerol migration away from the Gasserian ganglion (area under the curve: 0.950, SE: 0.046, CI: 0.859-1.041, P < .001). Increased ST angle was associated with lateral flow of glycerol (r s = 0.639, P = .001), and CMC angle was associated with total area of dispersion (r s = -0.474, P = .026). CONCLUSION: Anatomic variation in skull base angles affects glycerol migration. Specifically, a more obtuse CMC angle was associated with a higher risk of posterior migration away from the Gasserian ganglion. This may be a reason for differing rates of surgical success. These results suggest that anterior head flexion for 60 minutes may prevent percutaneous glycerol rhizotomy failures and some patients with large CMC angles are more likely to benefit from postinjection head positioning. However, this clinical effect needs validation in vivo.

Legal Performance-enhancing Drugs Alter Course and Treatment of Rhabdomyolysis-induced Acute Kidney Injury.

INTRODUCTION: Rhabdomyolysis-induced acute kidney injury (RIAKI) can interrupt physical training and increase mortality in injured warfighters. The legal performance-enhancing drugs caffeine and ibuprofen, which can cause renal injury, are widely used by service members. Whether caffeine or ibuprofen affects RIAKI is unknown. Cilastatin treatment was recently identified as an experimental treatment to prevent RIAKI at injury. To determine potential interacting factors in RIAKI treatment, we test the hypothesis that caffeine and ibuprofen worsen RIAKI and interfere with treatment. MATERIALS AND METHODS: In mice, RIAKI was induced by glycerol intramuscular injection. Simultaneously, mice received caffeine (3 mg/kg), ibuprofen (10 mg/kg), or vehicle. A second cohort received volume resuscitation (PlasmaLyte, 20 mL/kg) in addition to caffeine or ibuprofen. In a third cohort, cilastatin (200 mg/kg) was administered concurrently with drug and glycerol administration. Glomerular filtration rate (GFR), blood urea nitrogen (BUN), urine output (UOP), renal pathology, and renal immunofluorescence for kidney injury molecule 1 were quantified after 24 hours. RESULTS: Caffeine did not worsen RIAKI; although BUN was modestly increased by caffeine administration, 24-hour GFR, UOP, and renal histopathology were similar between vehicle-treated, caffeine-treated, and caffeine + PlasmaLyte-treated mice. Ibuprofen administration greatly worsened RIAKI (GFR 14.3 ± 19.5 vs. 577.4 ± 454.6 µL/min/100 g in control, UOP 0.5 ± 0.4 in ibuprofen-treated mice vs. 2.7 ± 1.7 mL/24 h in control, and BUN 264 ± 201 in ibuprofen-treated mice vs. 66 ± 21 mg/dL in control, P < .05 for all); PlasmaLyte treatment did not reverse this effect. Cilastatin with or without PlasmaLyte did not reverse the deleterious effect of ibuprofen in RIAKI. CONCLUSIONS: Caffeine does not worsen RIAKI. The widely used performance-enhancing drug ibuprofen greatly worsens RIAKI in mice. Standard or experimental treatment of RIAKI including the addition of cilastatin to standard resuscitation is ineffective in mice with RIAKI exacerbated by ibuprofen. These findings may have clinical implications for the current therapy of RIAKI and for translational studies of novel treatment.

Comparing the effectiveness of topical dexamethasone emollient, lidocaine gel, and glycerin emollient on the endotracheal tube for postoperative hoarseness of voice, sore throat, and laryngospasm.

During general anesthesia, inserting a relatively stiff endotracheal tube using a metallic laryngoscope through the soft tissues of the pharynx and larynx, along with applying a pressured cuff, can result in varying degrees of tissue trauma and adverse outcomes. Anesthesiologists commonly encounter post-operative issues such as hoarseness, sore throat, and laryngospasm. This study aimed to compare the effectiveness of topical applications of dexamethasone emollient, lidocaine gel, and glycerin emollient in reducing these complications. One hundred patients were randomly assigned to four groups of 25 patients each: the control group (Group C), lidocaine gel group (Group L), glycerin emollient group (Group G), and dexamethasone emollient group (Group D). The assigned medication was topically applied to the endotracheal tube, and patients were monitored for postoperative laryngospasm, hoarseness, and sore throat within the first 24 hours. No statistically significant differences were found among the four groups in terms of demographic characteristics, postoperative sore throat, hoarseness, or laryngospasm (p>0.05). Lidocaine gel was an effective drug that can be used to attenuate the incidence rate of post-operative sore throat.

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.

High amplitude propagated contractions with Glycerin versus Bisacodyl: A within-subject comparison in children undergoing colonic manometry.

BACKGROUND: The presence of high amplitude propagated contractions (HAPCs) measured by colonic manometry (CM) reflect an intact neuromuscular function of the colon. Bisacodyl and Glycerin are colonic stimulants that induce HAPCs and are used for the treatment of constipation. HAPCs characteristics with each drug have not been compared before. We aimed to compare the HAPC characteristics with Bisacodyl and Glycerin in children undergoing CM for constipation. METHODS: This is a prospective single-center cross-over study of children aged 2-18 years undergoing CM. All patients received both Glycerin and Bisacodyl during CM. They were randomized to group A with Bisacodyl first (n = 22) and group B with Glycerin first (n = 23), with 1.5 hours in between each dose. Differences in patient and HAPC characteristics between groups were summarized using descriptive statistics and compared using Chi-square test or Wilcoxon rank sum test as appropriate. KEY RESULTS: A total of 45 patients were included. HAPCs post Bisacodyl had a longer duration of action (median of 40 vs 21.5 min, p < 0.0001), longer propagation (median of 70 vs 60 cm, p = 0.02), and more HAPCs (median of 10 vs 5, p < 0.0001) compared Glycerin. No differences were found in the HAPC amplitude and onset of action between both medications.

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.

Early intervention with ColdZyme mouth spray after self-diagnosis of common cold: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Previous clinical and in vitro investigations have supported the efficacy of a glycerol throat spray containing cold-adapted cod trypsin (ColdZyme) against respiratory viruses causing the common cold bycreating a protective mucosal barrier shown to deactivate common cold virus in vitro and decrease pharyngeal rhinovirus load. METHODS AND FINDINGS: This was a double-blind, randomized, parallel-group, placebo-controlled study conducted at 10 German sites to evaluate the efficacy of the medical device ColdZyme, a glycerol mouth spray containing cold-adapted cod trypsin for a naturally occurring common cold versus placebo spray. Adults experiencing a minimum of three common colds during the previous year, but otherwise healthy, were enrolled to begin treatment with the mouth spray or placebo six times daily at first sign of a common cold. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) quality of life (QoL) domain and a sore throat scale were recorded daily by subjects, as well as any use of allowed rescue treatment. Between January and April 2019, 701 subjects were enrolled and randomly assigned to the ColdZyme group (n = 351) or the placebo group (n = 350). Of the 701 subjects, 438 (62.5%) subjects developed symptoms typical of common cold, and all 438 started study treatment (n = 220 in the ColdZyme group and n = 218 in the placebo group). The demographic profile of the treatment groups were comparable with 68.1% female and almost all subjects being Caucasian (98.4%). The age ranged between 18 and 70 years with a mean age of 41.3 (±14.4) years. There were no differences between the groups in primary and major secondary endpoints, however, the assessment using the WURSS-21 QoL domain and Jackson score suggests a slightly faster recovery with ColdZyme as symptoms and complaints affecting the quality of life were shortened by about 1 day. The beneficial effect of ColdZyme was particularly noticeable on the fifth day of the common cold. A positive difference between treatment groups was also seen for the subjects' assessments of global efficacy of the investigational product A robust safety profile for ColdZyme was demonstrated throughout the study. CONCLUSION: The safety and tolerability of ColdZyme have been confirmed in a large study population and further establishes evidence of a faster recovery from common cold symptoms. Early self-diagnosis and early use of ColdZyme mouth spray is a safe alternative for treatment of naturally occurring colds.

Topical glycerine for corneal clouding during retinal laser photocoagulation for retinopathy of prematurity.

AIM: To document the use of topical glycerine to reduce corneal edema in cases of retinopathy of prematurity (ROP) undergoing laser photocoagulation (PHC). METHODS: Thirty-two eyes of 16 babies (9 males) with a mean gestational age of 30 weeks, mean gestational weight of 1242 grams underwent PHC for Type 1 (zone 1 disease) retinopathy of prematurity. All babies received a single PHC session. Twenty eyes of 10 babies received intravitreal anti-VEGF injection, 1-3 weeks before PHC session. All patients received a single drop of glycerine during the PHC session to clear the corneal clouding. All patients underwent PHC to the avascular area right up to the ora serrata. Patients were seen at one week and one month to assess the adequacy of laser PHC. RESULTS: We were able to complete the PHC for all babies in a single session without any ocular or systemic adverse events. We did not find any skip lesions at follow-up, and the second session of laser PHC was not required in any eyes. CONCLUSION: Topical glycerine is safe and effective to clear corneal clouding in eyes undergoing laser PHC for retinopathy of prematurity.

Effects of Calcium Hydroxide Paste in Different Vehicles on Bacterial Reduction during Treatment of Teeth with Apical Periodontitis.

INTRODUCTION: This clinical study evaluated the antibacterial effects of calcium hydroxide associated with different vehicles during the treatment of infected teeth with apical periodontitis. METHODS: Bacteriologic samples were taken from 90 necrotic root canals of teeth with apical periodontitis before (S1) and after preparation with a rotary nickel-titanium instrument system and 2.5% sodium hypochlorite irrigation (S2). The teeth were distributed in 3 groups according to the intracanal medication used, which consisted of a calcium hydroxide paste in glycerin, camphorated paramonochlorophenol/glycerin (CHPG), or 2% chlorhexidine for 1 week, and then another sample was taken (S3). The frequency of bacteria-positive cases and the reduction of bacterial counts were evaluated by quantitative real-time polymerase chain reaction. RESULTS: Substantial intracanal bacterial reduction was observed after preparation in the 3 groups (P < .001). After calcium hydroxide paste in glycerin medication, the number of bacteria-positive cases decreased from 20/29 (69%) to 17/29 (59%); however, the mean bacterial counts increased 8.4% from S2 to S3. Medication with CHPG reduced the number of bacteria-positive cases from 17/29 (59%) to 15/29 (52%), with a significant mean S2-S3 reduction of 71% (P < .05). In the chlorhexidine group, the number of bacteria-positive cases decreased from 21/30 (70%) to 17/30 (57%) after medication, with a mean S2-S3 reduction of 55%, which, however, was not statistically significant (P > .05). Intergroup comparisons showed no significant differences (P > .05). CONCLUSION: Comparison between the 3 calcium hydroxide pastes showed no significant differences in antibacterial effectiveness in the main root canal. However, only the CHPG paste showed a significant reduction in bacterial counts when postpreparation and postmedication samples were compared.

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.

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.

Early intervention with a glycerol throat spray containing cold-adapted cod trypsin after self-diagnosis of common cold: A randomised trial.

BACKGROUND: A glycerol throat spray containing cold-adapted cod trypsin (GCTS) deactivates common cold virus in vitro and decreases pharyngeal rhinovirus load after inoculation in humans. We relied on early self-diagnosis and evaluated two different scales to detect a treatment effect in naturally occurring common colds. METHODS: Adults were enrolled in this randomised, prospective, parallel group, single-blind study to begin treatment six times daily at first sign of a common cold or were assigned to a non-treated group. Jackson's symptom scale and the 9-item Wisconsin Upper Respiratory Symptom Survey (WURSS)-21 quality of life (QoL) domain were recorded daily by subjects and area under the curve over 12 days (AUC1-12) calculated. RESULTS: Treatment resulted in reduced symptoms with an AUC1-12 of 45.1 ± 32.5 for Jackson scores compared to 53.8 ± 35.7 in the controls (p = 0.023). AUC1-12 for the 9-item WURSS-21 QoL domain was likewise improved, 113.6 ± 107.7 and 152.7 ± 126.3 (p = 0.006), respectively. During the first four days fewer of the treated subjects (35.3%) used rescue medication than did the control group (50.4%, p = 0.014). CONCLUSIONS: Reduction in common cold symptoms was seen with treatment with a glycerol throat spray containing cold-adapted cod trypsin. This effect was best detected with the 9-item WURSS-21 QoL domain.

Fasting Substrate Concentrations Predict Cardiovascular Outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS).

OBJECTIVE: To examine whether the circulating substrate mix may be related to the incidence of heart failure (HF) and cardiovascular (CV) mortality and how it is altered by canagliflozin treatment. RESEARCH DESIGN AND METHODS: We measured fasting glucose, free fatty acids (FFA), glycerol, ß-hydroxybutyrate, acetoacetate, lactate, and pyruvate concentrations in 3,581 samples from the CANagliflozin cardioVascular Assessment Study (CANVAS) trial at baseline and at 1 and 2 years after randomization. Results were analyzed by univariate and multivariate Cox proportional hazards models. RESULTS: Patients in the lowest baseline FFA tertile were more often men with a longer duration of type 2 diabetes (T2D), higher urinary albumin excretion, lower HDL-cholesterol levels, higher history of CV disease (CVD), and higher use of statins and insulin. When all seven metabolites were used as predictors, FFA were inversely associated with incident hospitalized HF (hazard ratio [HR] 0.33 [95% CI 0.21-0.55]), while glycerol was a positive predictor (2.21 [1.45-3.35]). In a model further adjusted for 16 potential confounders, including prior HF and CVD and pharmacologic therapies, FFA remained a significant negative predictor. FFA and glycerol also predicted CV mortality (HR 0.53 [95% CI 0.35-0.81] and 1.81 [1.26-2.58], respectively) and all-cause death (0.50 [0.36-0.70] and 1.64 [1.22-2.18]). When added to these models, background insulin therapy was an independent positive predictor of risk of death. Canagliflozin treatment significantly increased plasma FFA and ß-hydroxybutyrate regardless of background antihyperglycemic therapy. CONCLUSIONS: A constitutive metabolic setup consisting of higher lipolysis may be beneficial in delaying or preventing hospitalized HF; a further stimulation of lipolysis by canagliflozin may reinforce this influence.

Hydrogen helps to ameliorate Staphylococcus aureus-induced mastitis in mice.

Many studies have shown that hydrogen has anti-inflammatory and anti-oxidant effects. Because of its ability to quickly pass through cell membranes, hydrogen has become a hot spot in the research of inflammatory diseases. Vitamin E glycerin (VEG) and hydrogen-rich Vitamin E glycerin (HR-VEG) were prepared, aiming to explore their anti-inflammatory activities in mice mastitis induced by Staphylococcus aureus (S. aureus). In the early part of this study, the prepared vitamin E medium (VEM) and hydrogen-rich vitamin E medium (HR-VEM) were added to mammary epithelial cells infected with S. aureus. HR-VEM was found to be more effective in reducing the phosphorylation of p65 and p38 and in reducing the production of interleukin-1 beta (IL-1ß) than VEM. Whereafter, the mice model of mastitis was established by injecting S. aureus from the mammary duct. Then VEG and HR-VEG were applied to the mammary gland for seven consecutive days. After that, the clinical symptoms, histopathology, bacterial load, inflammatory factors, as well as the related pathway were analyzed. The results showed that HR-VEG can more significantly alleviate the damage of mammary tissue than VEG, and reduce the production of tumor necrosis factor-alpha (TNF-α), IL-1ß and interleukin 6 (IL-6). In addition, HR-VEG inhibited the TLR2 and Nod2 signaling pathways and reduced the phosphorylation level of MAPK and NF-κB signaling pathways in S. aureus-induced murine mastitis. This study indicates that hydrogen helps to ameliorate S. aureus-induced mastitis in mice through attenuating TLR2 and Nod2 mediated NF-κB and MAPK activation.

[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.

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.

Glycerin Suppositories and Enemas in Premature Infants: A Meta-analysis.

BACKGROUND AND OBJECTIVES: Premature infants are often given glycerin suppositories or enemas to facilitate meconium evacuation and the transition to enteral feeds. We reviewed the best-available evidence for the use of glycerin suppositories and enemas in premature infants. METHODS: We searched MEDLINE, Embase, and Cochrane Central for randomized controlled trials (RCTs) of premature infants treated with glycerin suppositories or enemas through January 2022. Studies were screened and data extracted independently and in duplicate. We included RCTs of premature infants <32 weeks gestation and/or birth weight <1500 g who were treated with glycerin suppositories or enemas. Meta-analysis was performed using random effects and reported as relative risk or mean difference. RESULTS: We identified 6 single-center, RCTs of 389 premature infants treated with glycerin suppositories (n = 207) or enemas (n = 182). Mortality rates ranged from 0% to 17%, and the meta-analysis revealed no differences between treatment groups (P = .86). Active treatment was associated with earlier meconium evacuation (mean, 1.5 days; 95% confidence interval, 3.0 to 0.01; P = .05) but not a faster time to enteral feeds (mean, 0.5 days; P = .48). We identified 1 ongoing trial with a target recruitment of 220 premature infants. The quality of evidence was very low to moderate because of inadequate statistical power and other methodologic issues. CONCLUSIONS: The use of glycerin suppositories and enemas in premature infants is associated with earlier meconium evacuation, but the clinical significance of this finding is uncertain. Treatment has no definitive effects on mortality, necrotizing enterocolitis, or enteral feeds.

Study protocol: a randomised controlled proof-of-concept real-world study - does maximising time in range using hybrid closed loop insulin delivery and a low carbohydrate diet restore the glucagon response to hypoglycaemia in adults with type 1 diabetes?

INTRODUCTION: People with type 1 diabetes (T1D) develop an impaired glucagon response to hypoglycaemia within 5 years of diagnosis, increasing their risk of severe hypoglycaemia. It is not known whether eliminating hypoglycaemia and hyperglycaemia allows recovery of this glucagon response. Hybrid closed loop (HCL) technologies improve glycaemic time in range (TIR). However, post-prandial glycaemic excursions are still evident. Consuming a low carbohydrate diet (LCD) may minimise these excursions. METHODS AND ANALYSIS: This feasibility study will assess if maximising TIR (glucose ≥3.9 mmol/L≤10 mmol/L) using HCL systems plus an LCD (defined here as <130 g carbohydrate/day) for >8 months, restores the glucagon response to insulin-induced hypoglycaemia. Adults (n=24) with T1D (C-peptide <200 pmol/L), naïve to continuous glucose monitoring (CGM) and HCL systems, will be recruited and randomised to: group 1 (non-HCL) to continue their standard diabetes care with intermittent blinded CGM; or group 2 (HCL-LCD) to use the HCL system and follow a LCD. Baseline data on diet and glycaemia will be collected from all participants. The HCL-LCD group will then enter a 2-week run-in to acclimatise to their devices. Throughout, the HCL-LCD group will have their glucose closely monitored and adjusted aiming for glycaemic TIR >70%. Participants will have their glucagon response to hypoglycaemia measured at the beginning and 8 months later at the study end using a stepped hyperinsulinaemic hypoglycaemic clamp, in combination with the stable isotopes 6,6-2H2-glucose (D2-glucose) and 1,1,2,3,3-2H5-glycerol (D5-glycerol) to assess glucose and glycerol kinetics. The impact of hypoglycaemia on symptoms and cognitive function will be assessed during each clamp study. The primary outcome is the difference in the glucagon response to hypoglycaemia between and within groups at baseline versus study end. ETHICS AND DISSEMINATION: Ethical (20/SS/0117)/institutional review board (2021/0001) approval has been obtained. The study will be disseminated by peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04614168.

Effectiveness of topical glyceryl trinitrate in treatment of tendinopathy - systematic review and meta-analysis.

PURPOSE: The objective of this meta-analysis was to evaluate the evidence on the effectiveness of glycerin trinitrate (NTG) measured by pain severity. MATERIALS AND METHODS: CENTRAL, MEDLINE, EMBASE, SCOPUS, and WEB of SCIENCE databases were searched in November 2020. The study selection was performed by two independent reviewers. The risk of systematic bias was assessed according to the Cochrane Collaboration's domain-based evaluation framework. RESULTS: Of 87 identified records, the meta-analysis was conducted on eight RCTs. When grouping by the type of tendinopathy and combining the estimates obtained from all available time points, the pooled standardized difference in means (SMD) was -0.80 (95% CI -1.34 to -0.26), and the number needed to treat 3.53 (95% upper confidence limit 12.4). When combining all the available data (all types of tendinopathy and all time points), the pooled SMD was -1.57 (95% CI -2.47 to -0.67). Overall heterogeneity was high. The risk of systematic bias was low in most of the selected studies. CONCLUSIONS: There is no evidence that NTG is more effective to reduce pain in tendinopathy than placebo. The effects of NTG were insignificant or borderline significant (probably insignificant clinically) concerning rotator cuff tendinopathy, Achilles tendinopathy, patellar tendinopathy, and lateral epicondylitis.IMPLICATIONS FOR REHABILITATIONA meta-analysis conducted on eight RCTs found no evidence that topical glycerin trinitrate is more effective to reduce pain in tendinitis than placebo.The effects were insignificant or borderline significant concerning rotator cuff tendinitis, Achilles tendinitis, patellar tendinitis, and lateral epicondylitis.The effects were independent of the dosage used.

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.