An international, multicenter, survey-based analysis of practice and management of acute liver failure.

INTRODUCTION: Acute liver failure (ALF) is an acute liver dysfunction with coagulopathy and hepatic encephalopathy in a patient with no known liver disease. As ALF is rare and large clinical trials are lacking, the level of evidence regarding its management is low-moderate, favoring heterogeneous clinical practice. In this international multicenter survey study, we aimed to investigate the current practice and management of patients with ALF. METHODS: An online survey targeting physicians who care for patients with ALF was developed by the International Liver Transplantation Society ALF Special-Interest Group. The survey focused on management and liver transplantation (LT) practices of ALF. Survey questions were summarized overall and by geographic region. RESULTS: A total of 267 physicians completed the survey with a survey response rate of 21.36%. Centers from all continents were represented. More than 90% of physicians were specialized in either transplant hepatology/surgery or anesthesiology/critical care. Two hundred and fifty-two (94.4%) respondents' institutions offered LT. A total of 76.8% of respondents' centers had a dedicated liver- or transplant- intensive care unit (p<0.001). Median time to LT was within 48 hours in 12.7% of respondents' centers, 72 hours in 35.6%, one week in 37.6%, and more than one week in 9.6% (p<0.001). Deceased-donor liver graft (49.6%) was the most common type of graft offered. For consideration of LT, 84.8% of physicians used King's College Criteria and 41.6% used Clichy Criteria. Significant differences were observed between Asia, Europe, and North America for offering LT, number of LTs performed, volume of ALF patients, admission to a dedicated intensive care unit, median time to LT, type of liver graft, monitoring hepatic encephalopathy and intracranial pressure, management of coagulopathy, and utilization of different criteria for LT. DISCUSSION: In our study, we observed significant geographic differences in the practice and management of ALF. As ALF is rare multicenter studies are valuable to identify global practice.

A Longitudinal Analysis of Mortality Related to Chronic Viral Hepatitis and Hepatocellular Carcinoma in the United States.

(1) Background: Hepatocellular carcinoma (HCC) contributes to the significant burden of cancer mortality in the United States (US). Despite highly efficacious antivirals, chronic viral hepatitis (CVH) remains an important cause of HCC. With advancements in therapeutic modalities, along with the aging of the population, we aimed to assess the contribution of CVH in HCC-related mortality in the US between 1999-2020. (2) Methods: We queried all deaths related to CVH and HCC in the multiple-causes-of-death files from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database between 1999-2020. Using the direct method of standardization, we adjusted all mortality information for age and compared the age-adjusted mortality rates (AAMRs) across demographic populations and by percentile rankings of social vulnerability. Temporal shifts in mortality were quantified using log-linear regression models. (3) Results: A total of 35,030 deaths were identified between 1999-2020. The overall crude mortality increased from 0.27 in 1999 to 8.32 in 2016, followed by a slight reduction to 7.04 in 2020. The cumulative AAMR during the study period was 4.43 (95% CI, 4.39-4.48). Males (AAMR 7.70) had higher mortality rates compared to females (AAMR 1.44). Mortality was higher among Hispanic populations (AAMR 6.72) compared to non-Hispanic populations (AAMR 4.18). Higher mortality was observed in US counties categorized as the most socially vulnerable (AAMR 5.20) compared to counties that are the least socially vulnerable (AAMR 2.53), with social vulnerability accounting for 2.67 excess deaths per 1,000,000 person-years. (4) Conclusions: Our epidemiological analysis revealed an overall increase in CVH-related HCC mortality between 1999-2008, followed by a stagnation period until 2020. CVH-related HCC mortality disproportionately affected males, Hispanic populations, and Black/African American populations, Western US regions, and socially vulnerable counties. These insights can help aid in the development of strategies to target vulnerable patients, focus on preventive efforts, and allocate resources to decrease HCC-related mortality.

Recipient Survival among Living Donor vs. Deceased Donor Liver Transplants for Acute Liver Failure in the United States.

Objectives: Acute liver failure (ALF) is associated with high morbidity and mortality. Timely liver transplantation (LT) is the only universally accepted therapy for ALF that is non-responsive to medical therapy. Data regarding the use of living donor LT (LDLT) for this indication in the US is scarce. Materials and Methods: United Network of Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) data from January 2002 to December 2020 were reviewed. Adult and pediatric recipients listed as status 1 were included. Demographics, clinical and laboratory data, and post-LT survival rates were compared for LDLT vs. DDLT recipients. Results: There were 180 LDLT (3.6%) and 4779 DDLT (96.4%) recipients with a diagnosis of ALF. The majority of recipients in the LDLT group were pediatric (n = 164, 91%) compared to the DDLT group (n = 1455, 30%), p < 0.001. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients (p = 0.15). Five-year post-LT survival was higher for pediatric recipients compared to adults in the LDLT group (84.2% vs. 62.5%, respectively, p < 0.001) and the DDLT group (82.8% vs. 78.7%, respectively, p < 0.001). Adults had a higher hazard of death compared to pediatric recipients in the LDLT group (HR = 3.560, 95% CI 1.612-7.844, p = 0.002) and the DDLT group (HR = 1.472, 95% CI 1.290-1.679, p < 0.001). In multivariate analysis results, the type of LT and age group were not associated with higher post-LT mortality. Conclusions: In the US, LDLT constitutes 3.6% of LTs for ALF. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients. Overall, there were superior post-LT outcomes for pediatric recipients compared to adults for LDLT and DDLT.

Brain Abscess Secondary to Streptococcus Intermedius Following an EGD with Biopsy in a Patient with Eosinophilic Esophagitis.

Brain abscess is a rare complication of esophagogastro- duodenoscopy (EGD) with few reported cases in the literature. In this report, we discuss a patient presenting with altered mental status, headache, and dysarthria due to brain abscess caused by S. intermedius shortly after an EGD with an esophageal biopsy showing a new diagnosis of eosinophilic esophagitis. We highlight the rare association of EGD and brain abscess, and discuss the importance of prompt diagnosis and treatment.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Comparison of matrix metalloproteinase 9 and 14 levels in vitreous samples in diabetic and non-diabetic patients: a case control study.

BACKGROUND: MMP-9 plays a prominent role in inflammation and MMP-14 take part in angiogenesis. The objective of this study is to compare MMP-9 and MMP-14 levels between diabetic and non-diabetic patients. METHODS: The patients who scheduled for pars plana vitrectomy were included in our study. Patients are divided into 2 groups: the diabetic group and non-diabetic group. Age, gender, intraocular pressure(IOP), visual acuity (VA) were reported. Color fundus photography, fundus fluorescein angiography, optic coherence tomography (OCT) were performed before and after the operation. MMP-9 and MMP-14 levels in vitreous samples were analyzed with a reader device by ELISA method. Mann-Whitney U test and logistic regressions were used in statistical analysis, p < 0.05 accepted as statistically significant. RESULTS: 70 eyes of 70 patients who received pars plana vitrectomy were enrolled in the study and divided into 2 groups: 34 patients in the diabetic group, 36 patients in the non-diabetic group. The average age of diabetic patients was 60.14 ± 10.20, and non-diabetic patients was 64.22 ± 11.16, respectively. The average MMP-9 (0.67 ± 0.66 ng/ml) and MMP-14 (0.16 ± 0.45 ng/ml) values in the diabetic group were significantly higher than the average MMP-9 (0.21 ± 0.05 ng/ml) and MMP-14 (and 0.07 ± 0.02 ng/ml) values in the non-diabetic group (P < 0.01). Also, it was observed that MMP-9 and MMP-14 levels increases as the diabetic disease duration increases. The risk of diabetes incidence increased with high levels of MMP-9 and MMP-14. CONCLUSION: Due to the higher levels of MMP-9 and MMP-14 in the pathogenesis of diabetic retinopathy, these proteins may probably be among the therapeutic targets in the prevention and treatment of retinopathy.

Impact of revised EORTC/MSGERC 2020 criteria on diagnosis and prognosis of invasive pulmonary aspergillosis in patients with hematological malignancies undergoing bronchoscopy.

INTRODUCTION: The first consensus definitions for invasive fungal diseases (IFD) were published in 2002. Advances in diagnostic tests and a clear need for improvement in certain areas led to a revision of these definitions in 2008. However, growing data on Aspergillus galactomannan (GM) thresholds and the introduction of new polymerase chain reaction-based diagnostic tests resulted in a further update by EORTC and Mycoses Study Group Education and Research Consortium (MSGERC) in 2020. Compared to the 2008 version, the 2020 EORTC/MSGERC criteria have stricter definitions, especially regarding GM levels, which should lead to improved specificity. Thus, our study aimed to evaluate diagnostic changes, based on GM levels, resulting from these new definitions and ascertain the impact of the new classification on mortality rates. METHOD: Patients hospitalized in a single tertiary care center with hematologic malignancies and undergoing bronchoscopy for suspected IPA between April 2004 and December 2019 were included in this retrospective study. RESULTS: The study population consisted of 327 patients with 31 patients (nine patients with proven IPA and 22 patients with no IPA) excluded from the study. 194 patients were classified as probable IPA cases according to 2008 EORTC/MSG criteria. However, 53 (27.3%) of these patients were re-classified as possible IPA according to 2020 EORTC/MSGERC criteria, due to novel galactomannan cut-off levels. Compared to re-classified possible IPA patients, those remaining in the probable IPA category experienced a higher incidence of septic shock (34.0% vs 16.9%, p=0.02), and required more non-invasive (12.0% vs 0.0%, p=0.004) and invasive (44.6 vs 24.5%, p=0.01) mechanical ventilation. There was a higher in-hospital mortality rate in probable IPA patients than in the re-classified possible IPA group (42.5% vs 22.6%, p=0.01). Patients reassigned to possible IPA had similar underlying diseases, radiological features and prognosis to patients already classified as possible IPA. Independent risk factors for mortality were classification as probable IPA according to 2020 EORTC/MSGERC criteria, lack of remission from hematologic malignancy, and number of nodules in Thorax CT. CONCLUSION: The use of 2020 EORTC/MSGERC criteria resulted in a 27.3% significant reduction in probable IPA diagnoses and created a more homogeneous category of patients with respect to treatment response, prognosis and mortality. Therefore, 2020 EORTC/MSGERC criteria afford more reliable mortality prediction than 2008 EORTC/MSG criteria.

The Most Cited Top 100 Articles in Shoulder Arthroscopy.

PURPOSE OF THE STUDY The purpose of this study was to identify and analyze the current most cited top-100 articles in shoulder arthroscopy literature. MATERIAL AND METHODS This retrospective analysis obtained bibliometric information from the Web of Science (WoS) database and analyzed the data via VOSviewer through software package. RESULTS The citation count of the most-cited articles varied from 122 to 923 on WoS. Altogether, the top 100 articles were cited 19,726 times; the average number of citations among the articles was 197.26. According to an abstract analysis, the most frequent terms were rotator cuff tear, tear, instability, and pain. A total of 73 of the top-100 cited articles were published between 2000-2014, while the oldest article was published in 1986. The most productive year was in 2007 (15 publications), and the most productive countries were the United States of America (63 publications) and France (15 publications). CONCLUSIONS Shoulder arthroscopy has been increasingly performed as an outpatient procedure in recent years. Our study may provide insights into trending topics in shoulder arthroscopy, the qualities which make an article relevant to global peers in the specialty, and may also serve to inspire relevant future articles. Clinical Relevance: The most cited top 100 articles in shoulder arthroscopy may give some insights on what qualities make an article relevant to global peers in the specialty and also inspire further relevant research in the future. Key words: arthroscopy, shoulder arthroscopy, bibliometric study, the most cited articles.

Effects of atorvastatin on talinolol absorption: A potential drug-drug interaction.

In this study, we aimed to determine the drug-drug interaction potential between atorvastatin (ATOR), and talinolol (TAL). Concentration-dependent effects of ATOR on the intestinal permeability of TAL were investigated by an in situ intestinal perfusion method. Dose-dependent effects of ATOR on TAL exposure were evaluated by measuring plasma concentrations after oral administration in rats. ATOR slightly changed the intestinal secretion of TAL in jejunum but not in colon. Plasma AUC levels of TAL were elevated by co-administration of ATOR at low and high doses whereas medium doses of ATOR resulted in a decrease in TAL bioavailability. However, these changes were not statistically significant. In our study, the pharmacokinetics of TAL were not affected by the concurrent use of ATOR in rats. In conclusion, it should be considered that complex interplay between the efflux and uptake transporters in the tissues and inhibition of these transporters by modulating agents may overshadow individual effects of each other.

Communications of the median nerve in foetuses.

BACKGROUND: Communications between the median, ulnar and musculocutaneous nerves in the arm, forearm and hand were reported in adult cadaveric and electrophysiological studies. These communicant branches may lead conflicting clinical and electrodiagnostic outcomes. While there are many studies on adult patients or cadavers, there is poor regarding foetuses. The present study was conducted to examine the frequencies of these communications and their coexistences in human foetuses. MATERIALS AND METHODS: Anterior aspect of the forearms of 50 foetuses (29 females, 20 males, and 1 unknown) were dissected bilaterally (totally 100 sides) for this purpose. RESULTS: Communications between the median and the musculocutaneous nerves in the arm were found unilaterally in 4%. Communications from the median to the ulnar nerve in the forearm were encountered unilaterally in 22%, and bilaterally in 12%; from the ulnar to the median nerve in the hand unilaterally in 28%, and bilaterally in 12%. Coexistence of all these variations was not encountered in any foetus. But coexistence of two different types of communicant branch was encountered in 4%. CONCLUSIONS: Precise knowledge of nerve communications, variations and rate of coexistences in foetuses may have significance for clinicians and researchers dealing with subjects in foetal period.

The importance of some angiogenic markers in spontaneous abortion.

AIM: In this study, the authors aimed to determine the serum levels of vascular endothelial growth factor (VEGF), angiopoietin-l (ang-1) and angiopoietin-2 (ang-2) factors as indicators of placental angiogenesis and vasculogenesis in abortion cases. Materials and Meth- ods: This study was conducted in 40 women who were pregnant for 7-20 weeks and diagnosed with an incipient abortion and 40 pregnant healthy women with similar ages, gestational weeks, and body mass index (BMI) values. Serum VEGF, ang-1, and ang-2 levels were measured with ELISA methods. RESULTS: The authors found that the serum VEGF levels were higher and ang-1 levels were significantly lower in pregnant women whose pregnancies failed with abortion, compared to control group. There was no significani difference in terms of ang-2 levels between groups. CONCLUSION: A strong relationship was found between VEGF and ang-I early pregnancy loss, and significant changes of these factors may also be associated with the physiopathology of abortion incipience. Evaluating these factors may be benefical for prediction and designing of treatment modalities on spontaneous abortion.

Pharmacokinetics of talinolol is modified by barnidipine: implication of P-glycoprotein modulation.

Concomitant administration of P-glycoprotein substrates and inhibitors may cause pharmacokinetic drug interactions leading to increased concentrations associated with serious side effects and toxicities. Barnidipine is a longacting calcium-channel blocker and potent inhibitor of P-glycoprotein in vitro, and talinolol is a beta-blocker and probe substrate of P-glycoprotein. This study was designed to investigate the effects of single and repeated oral doses of barnidipine on talinolol pharmacokinetics in rats. In the single-dose study, talinolol (20 mg/kg) alone and with barnidipine at low (1 mg/kg) and high doses (10 mg/kg) were orally administered to rats. In the repeated-dose study, rats were treated with barnidipine (1 mg/kg/day) or vehicle only for four days, then with talinolol (20 mg/kg, on day 5). Blood samples were collected at 0.5, 1, 2, 4, 6 h following last dose and plasma talinolol levels were determined by HPLC. Compared to the control, Cmax of talinolol elevated 10% (p=0.79) and 110% (p<0.05); plasma AUC0-6h increased 33% (p=0.41) and 46% (p<0.05) following low and high single doses of barnidipine co-administration, respectively. In the repeated-dose study, Cmax and AUC0-6h of talinolol increased 131% (p<0.05) and 130% (p<0.05) respectively, following co-administration of a low barnidipine dose. Double-peaks were observed when single or repeated low doses of barnidipine were co-administered. There may be coupling between occurrence of double-peak phenomenon and P-glycoprotein inhibition. Increment of talinolol bioavailability upon low and high doses of barnidipine co-administration may be due to P-glycoprotein inhibition. The higher increase of talinolol plasma AUC0-6h due to the repeated doses of barnidipine may be explained by downregulation of P-glycoprotein.

Preparation and evaluation of furosemide containing orally disintegrating tablets by direct compression.

The purpose of this research was to develop and prepare orally disintegrating tablets (ODTs) containing furosemide by direct compression method. Furosemide, microcrystalline cellulose (MCC), low-substituted hydroxypropylcellulose LH-11 (L-HPC), aspartame, sodium stearyl fumarate were used for ODT formulation. MCC and L-HPC were used in ratios of 1:9 (ODT1) and 1:4 (ODT2). The results of the quality control parameters obtained for bulk powders (angle of repose, compressibility index, Hausner ratio, bulk density and volume, apparent density and volume, swelling of superdisintegrants and powder moisture) were taken as an indication of good compressibility of tablets. Both ODT1 and ODT2 disintegrated within 15 s and fulfilled the required disintegration time given by the European Pharmacopoeia (3 min). The average weight variation was less than 5% for both tablets. The friability of the tablets was less than 1%. Wetting time of both tablets was in the range of 12-21.7 s. Water absorption ratio was 1.41±0.03 for ODT1 and 1.96±0.10 for ODT2. Dissolution studies revealed that more than 85% of furosemide was dissolved in 15 min from both ODTs. Based on cell culture studies, permeability of furosemide was low (Papp=1x10-5 cm/s) but increased when prepared in the ODT form (ODT1: Papp=2x10-5 cm/s; ODT2: Papp=3.6x10-5 cm/s). Collectively, all these results showed that ODT formulations of furosemide were developed successfully. To improve patient compliance, ODT approach can be suggested for development and manufacturing of furosemide ODTs.

Evaluation of serum HGF and CK18 levels in patients with esophageal cancer.

Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is involved in the formation of intracellular cytoskeleton, and has been considered a promising apoptosis marker in gastrointestinal carcinomas. Growth factors, including hepatocyte growth factor (HGF), may provide a microenvironment for malignant cells. In this study, we aimed to compare serum HGF and CK18 levels between esophageal squamous cell carcinoma patients and healthy controls. The study included 41 adult patients (20 male, 21 female) diagnosed with esophageal squamous cell carcinoma, with a mean age of 63.54 ± 10.88 years (range, 41-82 years). We also recruited 39 age and gender-matched healthy control subjects. Venous blood samples were taken; serum HGF and CK18 concentrations were determined via ELISA. Results indicated that serum HGF levels were higher in patients (1.37 ± 0.63 ng/mL) as compared to the healthy subjects (0.41 ± 0.29 ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 ± 1.33 ng/mL) than in the control group (0.34 ± 0.23 ng/mL) (P < 0.001). In addition, serum HGF and CK18 levels were positively correlated with metastasis stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To our knowledge, this is the first study to evaluate serum HGF and CK18 levels in patients with esophageal squamous cell carcinoma. The results suggest that serum CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers of esophageal squamous cell carcinoma.

Investigation of venous drainage patterns of rabbit peripheral nerves.

In this study, the venous drainage patterns of white New Zealand rabbits' peripheral nerves were examined in an effort to provide an animal model for studies focusing on the venous drainage of the healing nerves. Extremities of rabbits sacrificed via intraarterial lead oxide-gelatin solution, and thus had their peripheral bloods pushed out of the arteries and into the veins were dissected for the venous drainage of radial, median, ulnar, femoral, sciatic, tibial and fibular nerves. The observations revealed that white New Zealand rabbit was a feasible model due to its consistent venous anatomy draining the major nerves and accessibility and workability of them. Of those dissected, the most suitable set of nerves suitable for such studies seem to be the Median nerve of the anterior extremity, and Sciatic nerve of the posterior extremity (Fig. 12, Ref. 16). Text in PDF www.elis.sk. Text in PDF www.elis.sk.

Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B.

BACKGROUND: Results are conflicting with respect to the renal effects of anti-viral agents used for hepatitis B virus infection. AIM: To compare short and long-term renal effects in real-life settings and to determine risk factors for renal impairment during treatment. METHODS: 2221 treatment-naïve patients were enrolled. Among these, 895 (302 lamivudine, 27 telbivudine, 282 entecavir, 273 tenofovir and 11 adefovir initiated patients) had 'repeated measures' of creatinine (baseline, 1st, 6th, 12th and 24th month of treatment). Telbivudine and adefovir groups were excluded from further analysis because of the low number of patients. We calculated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula at each time point. Hypophosphataemia was also recorded. Risk factors for renal impairment were analysed. RESULTS: Tenofovir caused a decline in GFR at each time point when compared to baseline levels. However, lamivudine and entecavir did not change GFR. GFR-shifting from ≥90 to 60-89 mL/min/1.73 m(2) was comparable among groups. The proportion of patients whose baseline creatinine increased more than 25% was comparable among all anti-virals. GFR showed a decline in patients who switched from entecavir to tenofovir. One patient with compensated cirrhosis needed to change from tenofovir because of renal safety. Seven and three patients developed transient hypophosphataemia in the tenofovir and lamivudine groups, respectively. CONCLUSIONS: Although tenofovir caused a decline in GFR, differences between the anti-viral agents do not appear to be so impressive. In patients with and without renal risk factors at baseline, there is no impact of anti-virals, including tenofovir.