Serum fibrosis biomarkers predict death and graft loss in liver transplantation recipients.

Noninvasive serum fibrosis biomarkers predict clinical outcomes in pretransplant patients with chronic liver disease. We investigated the role of serum fibrosis biomarkers and of changes in biomarkers in predicting death and graft loss after liver transplantation (LT). We included 547 patients who underwent LT between 1991 and 2012 and who met the following criteria: patient and graft survival > 12 months; serum fibrosis biomarkers aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis score 4 (FIB-4), and nonalcoholic fatty liver disease (NAFLD) fibrosis score available at 1 year after LT; and a minimum follow-up of 1 year. Delta of fibrosis biomarkers was defined as (end of follow-up score--baseline score)/follow-up duration. Baseline and delta fibrosis biomarkers were associated with death: APRI > 1.5 (adjusted hazard ratio [aHR], 2.2; 95% confidence interval [CI], 1.4-3.3; P < 0.001) and delta APRI > 0.5 (aHR, 5.3; 95% CI, 3.4-8.2; P < 0.001); FIB-4 > 3.3 (aHR, 1.9; 95% CI, 1.3-2.8; P = 0.002) and delta FIB-4 > 1.4 (aHR, 2.4; 95% CI, 1.4-4.1; P = 0.001); and NAFLD fibrosis score > 0.7 (aHR, 1.9; 95% CI, 1.3-2.9; P = 0.002) and delta NAFLD fibrosis score (aHR, 3.7; 95% CI, 2.6-5.4; P < 0.001). Baseline and delta fibrosis biomarkers were associated also with graft loss. In conclusion, serum fibrosis biomarkers 1 year after LT and changes in serum fibrosis biomarkers predict death and graft loss in LT recipients. They may help in risk stratification of LT recipients and identify patients requiring closer monitoring.

Benign Non-Odontogenic Pathology in Children.

This article provides a comprehensive overview of benign non-odontogenic pathologies. Bone-derived lesions like osteoma, osteoid osteoma, osteoblastoma, and osteochondroma are discussed in detail, emphasizing their radiographic features, locations, and treatment strategies. Cartilage-derived lesions such as chondroma, chondroblastoma, and chondromyxoid fibroma are also examined, noting their typical presentation and management approaches. The article then delves into fibroconnective tissue lesions. Mesenchymal and vascular lesions are detailed regarding their clinical and radiographic characteristics and treatment options. Lastly, nerve-derived lesions like schwannoma and neurofibroma are covered, providing insights into their association with diseases like neurofibromatosis and preferred management strategies.

Perioperative Management in Neuromuscular Diseases: A Narrative Review.

Patients with neuromuscular diseases are particularly vulnerable in the perioperative period to the development of pulmonary and cardiac complications, or medication side effects. These risks could include hypoventilation, aspiration pneumonia, exacerbation of underlying cardiomyopathy, arrhythmias, adrenal insufficiency, prolonged neuromuscular blockade, issues related to thermoregulation, rhabdomyolysis, malignant hyperthermia, or prolonged mechanical ventilation. Interventions at each of the perioperative stages can be implemented to mitigate these risks. A careful pre-operative evaluation may help identify risk factors so that appropriate interventions are initiated, including cardiology consultation, pulmonary function tests, initiation of noninvasive ventilation, or implementation of preventive measures. Important intraoperative issues include positioning, airway and anesthetic management, and adequate ventilation. The postoperative period may require correction of electrolyte abnormalities, control of secretions with medications, manual or mechanical cough assistance, avoiding the risk of reintubation, judicious pain control, and appropriate medication management. The aim of this review is to increase awareness of the particular surgical challenges in this vulnerable population, and guide the clinician on the various evaluations and interventions that may result in a favorable surgical outcome.

Treatments for obstructive sleep apnea: CPAP and beyond.

Treatment options for obstructive sleep apnea include positive airway pressure and alternatives such as behavioral interventions, oral appliances, nasal expiratory positive airway pressure, negative pressure interventions, and surgical procedures. Certain drugs are also promising. An important aspect of the treatment includes troubleshooting the reasons for poor adherence to positive airway pressure treatment, discussing alternatives based either on individual preference or on phenotypic characterization of the sleep apnea, and managing expectations.

Oral Endotracheal Tube Stabilization for Facial Burns in Infants-Report of Two Techniques.

Establishing a secure airway is critical in the acute phase of facial burns. This case report involving a 9-month-old infant with facial burns describes two techniques of securing an oral airway-trans-alveolar wiring and the application of an intermaxillary fixation (IMF) screw. The use of an IMF screw was more reliable than trans-alveolar wiring, as it allowed a secure airway through the patient's hospitalization, which involved seven additional surgical interventions including five separate facial skin grafts over a 3-month period.

Pediatric Le Fort, Zygomatic, and Naso-Orbito-Ethmoid Fractures.

Fractures of the pediatric midface are infrequent, particularly in children in the primary dentition, due to the prominence of the upper face relative to the midface and mandible. With downward and forward growth of the face, there is an increasing frequency of midface injuries seen in children in the mixed and adult dentitions. Midface fracture patterns seen in young children are quite variable; those in children at or near skeletal maturity mimic patterns seen in adults. Non-displaced injuries can typically be managed with observation. Displaced fractures require treatment with appropriate reduction and fixation and longitudinal follow-up to evaluate growth.

Sleep-Related Hypoxia, Right Ventricular Dysfunction, and Survival in Patients With Group 1 Pulmonary Arterial Hypertension.

BACKGROUND: Group 1 pulmonary arterial hypertension (PAH) is a progressive fatal condition characterized by right ventricular (RV) failure with worse outcomes in connective tissue disease (CTD). Obstructive sleep apnea and sleep-related hypoxia may contribute to RV dysfunction, though the relationship remains unclear. OBJECTIVES: The aim of this study was to prospectively evaluate the association of the apnea-hypopnea index (AHI) and sleep-related hypoxia with RV function and survival. METHODS: Pulmonary Vascular Disease Phenomics (National Heart, Lung, and Blood Institute) cohort participants (patients with group 1 PAH, comparators, and healthy control participants) with sleep studies were included. Multimodal RV functional measures were examined in association with AHI and percentage of recording time with oxygen saturation <90% (T90) per 10-unit increment. Linear models, adjusted for demographics, oxygen, diffusing capacity of the lungs for carbon monoxide, pulmonary hypertension medications, assessed AHI and T90, and RV measures. Log-rank test/Cox proportional hazards models adjusted for demographics, oxygen, and positive airway pressure were constructed for transplantation-free survival analyses. RESULTS: Analysis included 186 participants with group 1 PAH with a mean age of 52.6 ± 14.1 years; 71.5% were women, 80.8% were Caucasian, and there were 43 events (transplantation or death). AHI and T90 were associated with decreased RV ejection fraction (on magnetic resonance imaging), by 2.18% (-2.18; 95% CI: -4.00 to -0.36; P = 0.019) and 0.93% (-0.93; 95% CI: -1.47 to -0.40; P < 0.001), respectively. T90 was associated with increased RV systolic pressure (on echocardiography), by 2.52 mm Hg (2.52; 95% CI: 1.61 to 3.43; P < 0.001); increased mean pulmonary artery pressure (on right heart catheterization), by 0.27 mm Hg (0.27; 95% CI: 0.05 to 0.49; P = 0.019); and RV hypertrophy (on electrocardiography), 1.24 mm (1.24; 95% CI: 1.10 to 1.40; P < 0.001). T90, but not AHI, was associated with a 17% increased 5-year risk for transplantation or death (HR: 1.17; 95% CI: 1.07 to 1.28). In non-CTD-associated PAH, T90 was associated with a 21% increased risk for transplantation or death (HR: 1.21; 95% CI: 1.08 to 1.34). In CTD-associated PAH, T90 was associated with RV dysfunction, but not death or transplantation. CONCLUSIONS: Sleep-related hypoxia was more strongly associated than AHI with measures of RV dysfunction, death, or transplantation overall and in group 1 non-CTD-associated PAH but only with RV dysfunction in CTD-associated PAH. (Pulmonary Vascular Disease Phenomics Program [PVDOMICS]; NCT02980887).

Physical Examination for the Detection of Pulmonary Hypertension: A Systematic Review.

We performed a systematic review to determine whether the physical examination can reliably assist in the diagnostic approach for patients suspected of having pulmonary hypertension (PH). Using dual extraction, two investigators independently searched PubMed, Ovid MEDLINE, Cochrane Library, and Embase for studies that compared physical examination findings with a right heart catheterization, from inception until July 10, 2021. We obtained data from four studies that evaluated physical examination findings in patients receiving a right heart catheterization to diagnose PH. Pooled diagnostic odds ratios (DOR) were calculated for right ventricular heave, a loud pulmonic component of the second heart sound (P2), jugular venous pressure (JVP) 3 cm above sternal angle, and a palpable P2. Three physical examination findings had DOR that supports the diagnosis of PH: the JVP > 3 cm above the sternal angle (5.90, 95% CI 2.57, 13.57), a loud P2 (2.91, 95% CI 1.38, 6.10), and a right ventricular heave (2.78, 95% CI 1.12, 6.89). The palpable P2 had a DOR less than one and was not able to be conclusive in diagnosing PH. Our systematic review found a small body of evidence supporting the use of physical examination tests in the diagnostic evaluation of pulmonary hypertension. The JVP > 3 cm above the sternal angle was the most accurate physical examination sign for the diagnosis of PH. Larger cohort studies using a combination of tests may shed more light on the role of the physical examination in the diagnosis and early detection of pulmonary hypertension.

Ion Release From Prototype Surface Pre-Reacted Glass Ionomer (S-PRG) Sealer and EndoSequence BC Sealer.

OBJECTIVE: Bioactive ions, when incorporated in an endodontic sealer, can contribute to the long-term success of endodontic therapy by combating the re-infection of a tooth and promoting the healing of the periapical bone. The objective of this study was to measure the release of boron, strontium, and silicon ions from surface pre-reacted glass ionomer (S-PRG) filler containing prototype endodontic sealer over a sustained period in comparison to EndoSequence BC sealer in a simulated clinical model using extracted human teeth in vitro. METHODS: Twelve extracted human anterior teeth were instrumented using ProTaper Next (Dentsply Sirona, Johnson City, TN, USA) files up to size X3 (#30/variable taper) with copious 2.5% NaOCl irrigation. Teeth were obturated using a single-cone technique with a matching size tapered gutta-percha point and one of two endodontic sealers: prototype S-PRG (Shofu Inc., Kyoto, Japan) or EndoSequence BC (Brasseler, Savannah, GA, USA). The teeth were soaked in phosphate-buffered saline (PBS) solution for 336 hours. Periodically, 1-mL samples of the PBS were analyzed via an inductively coupled plasma mass spectrometer to determine the concentrations of ions released by the sealers. RESULTS: The average (S.D.) cumulative release (ng/ml) of boron, silicon, and strontium ions over 2 weeks for the prototype S-PRG sealer was 8614.9 (1264.3), 35758.9 (5986.5), and 3965.2 (145.6), and for EndoSequence BC sealer was 1860.5 (82.7), 164648.7 (16468.1), and 227.7 (4.7). Generalized linear mixed model analysis showed significant differences in ion concentration among boron, silicon, and strontium over time between the two sealer groups (Boron: P<0.0001, Silicon: P=0.010, Strontium: P=0.028). Of the three ions, strontium had the lowest amount of release for both sealers. The prototype S-PRG sealer showed a rapid initial burst followed by a slow, continuous release of strontium ions. CONCLUSION: The prototype S-PRG sealer released boron and strontium ions in higher cumulative concentrations over 2 weeks compared to the EndoSequence BC sealer. Both the prototype S-PRG and EndoSequence BC sealers released silicon ions, although significantly more were eluted from the EndoSequence BC sealer. Antimicrobial and osteogenic ion release from sealers is expected to positively influence the post-treatment control of microbial infections to improve periapical healing.

Comprehensive review of current endodontic sealers.

Endodontic sealers for non-surgical root canal treatment (NSRCT) span many compositions and attributes. This comprehensive review discusses current types of endodontic sealers by their setting reaction type, composition, and properties: zinc oxide-eugenol, salicylate, fatty acid, glass ionomer, silicone, epoxy resin, tricalcium silicate, and methacrylate resin sealers. Setting time, solubility, sealing ability, antimicrobial, biocompatibility, and cytotoxicity are all aspects key to the performance of endodontic sealers. Because sealing ability is so important to successful outcomes, the relative degree of microleakage among all the relevant sealers was calculated by way of a meta-analysis of relevant literature. Compared to AH Plus, tricalcium silicate sealers show the lowest relative microleakage among the sealers assessed, followed by silicone sealers and other non-AH Plus epoxy resin sealers. Tricalcium silicate sealers also exhibit the most favorable antimicrobial effect and excellent biocompatibility. Future sealers developed should ideally combine a hermetic seal with therapeutic effects.

Incidence and Predictors of Advanced Liver Fibrosis by a Validated Serum Biomarker in Liver Transplant Recipients.

Background and Aims. Serum fibrosis biomarkers have shown good accuracy in the liver transplant (LT) population. We employed a simple serum biomarker to elucidate incidence and predictors of advanced fibrosis after LT over a long follow-up period. Methods. We included 440 consecutive patients who underwent LT between 1991 and 2013. Advanced liver fibrosis was defined as FIB-4 > 3.25 beyond 12 months after LT. Results. Over 2030.5 person-years (PY) of follow-up, 189 (43%) developed FIB-4 > 3.25, accounting for an incidence of 9.3/100 PY (95% confidence interval [CI], 8.1-10.7). Advanced fibrosis was predicted by chronic HCV infection (adjusted hazard ratio (aHR) = 3.96, 95% CI 2.92-5.36, p < 0.001), hypoalbuminemia (aHR = 2.31, 95% CI 1.72-3.09; p < 0.001), and hyponatremia (aHR = 1.48, 95% CI 1.09-2.01; p = 0.01). LT recipients with more than 1 predictor had a higher incidence of advanced fibrosis, the highest being when all 3 predictors coexisted (log-rank: p < 0.001). Conclusions. Chronic HCV infection, hypoalbuminemia, and hyponatremia predict progression to advanced liver fibrosis following LT. Patients with these risk factors should be serially monitored using noninvasive fibrosis biomarkers and prioritized for interventions.

Systematic review: Preventive and therapeutic applications of metformin in liver disease.

Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review, we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The PubMed and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeSH terms: metformin and mammalian target of rapamycin, hepatitis B virus (HBV), hepatitis B virus (HCV), non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level III evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.

Thioredoxin reductase activity may be more important than GSH level in protecting human lens epithelial cells against UVA light.

This study compares the abilities of the glutathione (GSH) and thioredoxin (Trx) antioxidant systems in defending cultured human lens epithelial cells (LECs) against UVA light. Levels of GSH were depleted with either L-buthionine-(S,R)-sulfoximine (BSO) or 1-chloro-2,4-dinitrobenzene (CDNB). CDNB treatment also inhibited the activity of thioredoxin reductase (TrxR). Two levels of O2 , 3% and 20%, were employed during a 1 h exposure of the cells to 25 J cm(-2) of UVA radiation (338-400 nm wavelength, peak at 365 nm). Inhibition of TrxR activity by CDNB, combined with exposure to UVA light, produced a substantial loss of LECs and cell damage, with the effects being considerably more severe at 20% O2 compared to 3%. In contrast, depletion of GSH by BSO, combined with exposure to UVA light, produced only a slight cell loss, with no apparent morphological effects. Catalase was highly sensitive to UVA-induced inactivation, but was not essential for protection. Although UVA light presented a challenge for the lens epithelium, it was well tolerated under normal conditions. The results demonstrate an important role for TrxR activity in defending the lens epithelium against UVA light, possibly related to the ability of the Trx system to assist DNA synthesis following UVA-induced cell damage.