Hepatobiliary Research Articles

Atypical Primary Sclerosing Cholangitis Findings on a 99mTc-Mebrofenin Scan

Abstract We present an 80-year-old woman with cholestatic liver disease. Ultrasound, CT, and MR cholangiopancreatography showed no substantial findings. The patient was referred for a hepatobiliary scan to examine the physiological pathway of bilirubin and to determine for any level of obstruction. The findings on the hepatobiliary scan suggested intrinsic pathology affecting the entire biliary tree, and histology was recommended. Histology confirmed primary sclerosing cholangitis (PSC). Although hepatobiliary scintigraphy in biliary stasis is well-known and well-published, hepatobiliary scintigraphy in PSC in adults is not well-documented. The hepatobiliary scintigraphy provided the primary and definitive imaging technique in directing the management and diagnosis of PSC in our patient.

HEPATOPROTECTIVE EFFECT OF GOLDEN VOLODUSHKA (BUPLEURUM AUREUM L.) HERB EXTRACT OF DRY IN EXPERIMENTAL TOXIC HEPATITIS IN RATS

Introduction. The search for new medicines, including those of plant origin, for the treatment of diseases of the hepatobiliary system is relevant and timely. A promising source for the development of hepatoprotective drugs is golden volodushka (Bupleurum aureum L.). To date, a large evidence base has been accumulated for the biochemical study of this plant, its pharmacological activity has been scien-tifically proven. Good stocks of golden volodushka in the wild, the simplicity of its harvesting and the possibility of cultivation were noted. The VILAR State Medical University has developed a method for obtaining volodushka golden herb extract of dry. Aim. The study of the pharmacotherapeutic efficacy of volodushka golden (Bupleurum aureum L.) herb extract of dry in case of liver damage under experimental conditions. Material and methods. In the studies, white non-linear male rats with a body weight of 180-200 g were used. Volodushka extract was studied at doses of 50 and 100 mg/kg. The comparison drug was silimar at a dose of 100 mg/kg. Experimental CCl4 – induced hepatitis in rats was caused by a single subcutaneous injection of 50% carbon tetrachloride oil solution one hour after the last administration of the studied extract and the comparison drug. After 48 hours, blood was taken from the tail vein of rats, serum was obtained and its biochemical analysis was carried out. Next, the rats eu-thanized in a CO2 chamber and the liver extracted for pathophysiological evaluation. Tetracycline hepatitis was caused by intragastric administration of tetracycline to animals at a dose of 500 mg/kg. Then, after 48 hours, blood was taken from the animals, serum was obtained and its biochemical analysis was carried out. Results. Volodushka golden grass dry extract on a model of carbon tetrachloride hepatitis exhibits a hepatoprotective effect, which is confirmed by a comparative pathophysiological study and a study of the activity of enzyme markers of the morphofunctional state of the liver in rat blood serum. In the tetracycline hepatitis model, the studied extract also has a hepatoprotective effect, which is confirmed by biochemical studies. Conclusions. Studies of volodushka extract in conditions of experimental liver lesions have shown that the studied extract in experimental therapeutic doses has a pronounced hepatoprotective effect and is promising for the creation of a herbal medicine for the prevention and treatment of diseases of the digestive system.

Epidemiology, survival and new treatment modalities for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is a rare biliary tract cancer with increasing incidence and poor survival rates. This study aims to evaluate the incidence and survival trends of iCCA patients over 20 years using a national cancer database, and assess the temporal association between survival and landmark clinical trials. Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rates (AAIRs) were calculated from 2000 to 2020. Overall survival was analyzed based on diagnosis time and disease stage. Subgroup analysis was performed for patients diagnosed between 2015 and 2020. Landmark clinical trials were reviewed to determine temporal changes in survival. In this analysis of 28,918 iCCA patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 [annual percent change (APC) 6.94, 95% confidence interval (CI): 6.32 to 7.56], with a notable decline from 2019 to 2020. Incidence rates overall displayed an uptrend course across subgroups divided by sex, race, age, and disease stage. The age-adjusted median overall survival (mOS) improved from 5.28 months in 2000 to 9.3 months in 2013, then stabilized between 8.0-9.0 months after 2013. Using 2010 as a cutoff, when the ABC-02 trial was published, the decade-based mOS increased from 6.55 months in 2000-2010 to 9.06 months in 2010-2020. During 2015-2020, the overall mOS was 8.8 months, with mOS of 24.3, 12.1, and 5.4 months for local, regional, and distant stages, respectively. The study indicates a steady rise in iCCA incidence since 2000 across all subgroups. Survival rates improved since 2000 but stabilized after 2013, following the ABC-02 trial publication in 2010. The impact of more recent clinical trials on survival rates requires further analysis in the coming years.

Safety and efficacy of hepaticoduodenostomy for biliary reconstruction after extrahepatic mid-bile duct cancer surgery.

Bile duct resection and reconstruction for bile duct cancer (BDC) is a complex surgical and oncologic procedure that requires extensive resection and reconstruction of the biliary tract. Hepaticojejunostomy is commonly performed for biliary reconstruction after extrahepatic mid-bile duct resection, while hepaticoduodenostomy (HD) is performed only rarely due to the risk of ascending cholangitis. However, the efficacy of HD has not been well-established in extrahepatic mid-BDC surgery. In this study, we aimed to analyze the outcomes of HD in patients who underwent bile duct resection for extrahepatic mid-BDC. We retrospectively analyzed 38 extrahepatic mid-BDC patients who underwent bile duct resection in our center between January 2018 and June 2023. We compared postoperative outcomes, cancer recurrence, and patient survival between hepaticojejunostomy (n=20) and HD (n=18) groups. Operation time for the HD group was significantly shorter than that of the hepaticojejunostomy group (188 vs. 206 min, P=0.044) with no significant differences in postoperative outcomes. Regression analysis showed that a HD was not associated with a significantly high risk of cancer recurrence or decrease in patient survival. HD appears to have comparable operative benefits, postoperative complications, and oncologic outcomes to hepaticojejunostomy in extrahepatic mid-BDC patients.

Extracts of the Canadian goldenrod (Solidago Canadensis L.) – promising agents with antimicrobial, anti-inflammatory and hepatoprotective activity

S. canadensis L. and S. virgaurea L. are the most common species of Solidago L. in Europe and with a long tradition of use in medicine for various therapeutic purposes: diseases of the urinary tract, gastrointestinal tract, diabetes, allergies and antiseptic purposes. Therefore, the research of species of the Solidago genus, which have a rich content of natural BACs, and the development of new effective medicinal products of plant origin are relevant. The aim. The method of work is the phytochemical and pharmacological study of extracts of the Canadian goldenrod herb, obtained by ethanol solutions of various concentrations, for the innovative perspective of creating new medicines based on them with antimicrobial, anti-inflammatory and hepatoprotective activity. Materials and methods. The objects of the study were extracts of herb from Canadian goldenrod, obtained using purified water, 40 %, 70 % and 90 % ethanol. Phytochemical study of the extracts was performed by TLC and spectrophotometry. Study of acute toxicity, antimicrobial, anti-inflammatory and hepatoprotective activity of extracts was carried out according to standard methods. Research results. A study of the phytochemical composition and pharmacological activity of extracts of herb from Canadian goldenrod obtained with different solvents. It was established that extracts of herb from Canadian goldenrod show anti-inflammatory activity. The most pronounced antiexudative activity is shown by the extract of the Canadian goldenrod herb (extractant - 40 % ethanol), reducing the degree of swelling by 24.77 %. Herb extracts from from Canadian goldenrod in acute toxic liver damage show moderate hepatoprotective activity, which is somewhat inferior to the comparative drug "Silibor". A more intense and effective effect on the hepatobiliary system was shown by the extract of the Canadian goldenrod herb (extractant - 40 % ethanol). Conclusions. The perspective of creation based on herb of Canadian goldenrod new drugs with hepatoprotective activity. The most promising substance turned out to be an extract of herb from Canadian goldenrod obtained with a 40 % ethanol solution.

Recommendations on the surveillance and supplementation of vitamins and minerals for upper gastrointestinal cancer survivors: a scoping review.

Early-stage upper gastrointestinal (UGI) cancer patients, after surgery, have altered gastrointestinal functions, compromising their nutritional status and health outcomes. Nutritional care provision to UGI survivors rarely focuses on long-term survivorship. Here, we explore recommendations for surveillance of micronutrient deficiency and supplementation for UGI cancer survivors after surgery. A scoping review, based on the Joanna Briggs Institute methodology for scoping reviews. Six databases (Medline, Embase, CINAHL, Cochrane, Scopus, and PsycINFO) and 21 cancer-related organisation websites were searched. Publications between 2010 and March 2024 with recommendations aimed at adult UGI cancer (oesophageal, gastric, pancreatic, small bowel, and biliary tract) survivors were included. Twenty-six publications met the selection criteria: 11 reviews (8 narrative reviews, 2 systematic, 1 meta-analysis), 7 expert opinions, 6 guidelines, and 2 consensus papers. Twenty-two publications recommended monitoring of micronutrient deficiencies, and 23 suggested supplementation, with 8 lacking details. Most were targeted at patients with gastric cancer (n = 19), followed by pancreatic cancer (n = 7) and oesophageal cancer (n = 3) with none for biliary tract and small bowel cancers. Vitamin B12 and iron were the most consistently recommended micronutrients across the three tumour groups. Limited publications recommend surveillance of micronutrient status in UGI cancer survivors during the survivorship phase, especially for oesophageal and pancreatic cancer survivors; most were narrative reviews. These recommendations lacked details, and information was inconsistent. Long-term UGI cancer survivors are at risk of micronutrient deficiency after surgery. A standardised approach to prevent, monitor, and treat micronutrient deficiencies is needed.

Evaluation of a Ten-Antigen Immunodot Test in Autoimmune Hepatitis and Primary Biliary Cholangitis: Lessons Learned for a Tertiary Care Academic Hospital.

Autoimmune diseases of the liver and biliary tract require timely and accurate diagnosis. This study evaluates the D-tek panel (D-Tek, Mons, Belgium) of 10 immunodot antigens for its effectiveness in diagnosing autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). We retrospectively analysed serum samples from 111 patients who had undergone routine testing, including indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISA), to confirm or exclude autoimmune liver or biliary tract disease. The panel tested for M2/nPDC, M2/OGDC-E2, M2/BCOADC-E2, M2/PDC-E2, gp210, sp100, LKM1, LC1, SLA, and F-actin antigens. Results showed that all positive IIF+ELISA results were confirmed by the immunodot panel, except for two samples from patients who had never been diagnosed with AIH. The immunodot test identified over 20 additional autoantibodies in samples initially negative by IIF, corroborated by laboratory imaging and medical history. The immunodot technique proved to be a quick, sensitive, and specific method with high overall accuracy. This study suggests that the immunodot technique may be an effective screening and confirmatory method for autoimmune liver diseases, potentially improving diagnostic efficiency and accuracy in clinical practice.

Abdominal ultrasound has inconsistent agreement with subsequent surgery or necropsy findings in dogs and cats with septic peritonitis.

To evaluate whether abdominal ultrasound correctly diagnosed septic peritonitis and correctly identified its causative lesion in dogs and cats. 84 client-owned dogs and 10 cats that underwent an abdominal ultrasound and had confirmation of septic peritonitis via exploratory laparotomy or necropsy. This retrospective case series documented abdominal ultrasound findings, surgical or necropsy findings, and method for initial diagnosis of septic peritonitis, if different from surgery or necropsy. The surgical report and necropsy findings were compared to sonography results to confirm a diagnosis of septic peritonitis. The frequency at which sonography diagnosed septic peritonitis and its causative lesion was calculated for each type of lesion pathology and organ system. Secondary aims included evaluating the effect of patient characteristics (body weight and species) on sonographic results and whether lesion type or location affected mortality. Most lesions causing septic peritonitis (70.2%) were gastrointestinal in origin and were nonneoplastic ulcerations or perforations (50%). Abdominal ultrasound diagnosed 56.3% of cases of subsequently confirmed septic peritonitis and correctly identified 67% of the causative lesions. Lesions of the gastrointestinal tract and ulcerations/perforations were the most frequent correct sonographic diagnoses and most likely to lead to a correct sonographic diagnosis of septic peritonitis. Lesions located in the hepatobiliary system and lesion types other than neoplasia or ulcerations/perforations were the most frequently missed by abdominal ultrasound. Abdominal ultrasound often fails to diagnose septic peritonitis or the underlying causative lesion, and its accuracy depends on the affected organ and type of lesion.

Recent and anticipated novel drug approvals (3Q 2024 through 2Q 2025).

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by sharing new and anticipated novel drug approvals. Selected drug approvals anticipated in the 12-month period covering the third quarter of 2024 through the second quarter of 2025 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics selected from 54 novel drugs awaiting US Food and Drug Administration approval. New cell therapies for treating cancers continue to enter the drug pipeline, while novel targeted therapies for biliary tract, gastric, pancreatic, and breast cancers, as well as 3 subcutaneous versions of already approved drugs given intravenously, are awaiting approval. Additionally, many novel drugs are being developed for treatment of rare and ultra-rare diseases such as hereditary angioedema, macular telangiectasia, congenital adrenal hyperplasia, and Barth syndrome. Two new subcutaneous drugs for hemophilia, a new oral medication for hereditary angioedema, a novel monoclonal antibody for atopic dermatitis, and the first oral penem antibiotic are also in the pipeline. New drugs with various indications for cancers and rare diseases continue to strengthen the drug pipeline.

Clinical Characteristics of Abdominal Infections Caused by Raoultella Spp.: A Retrospective Study.

Background: In recent years, Raoultella spp. have attracted clinical attention as a new type of pathogen. The most common of human infection with Raoultella are bacteremia, urinary tract infections, abdominal infections, etc. Abdominal infection is a serious and complex infection problem. However, there have been no systematic reports of abdominal infections caused by Raoultella. The objective of this study was to explore the clinical characteristics of Raoultella abdominal infections and provide a reference for clinical practice. Methods: A review of publications on abdominal infections caused by the genus Raoultella between 2009 and 2024 is carried out. This review studied seven parameters: infection type, number of cases, gender, age, comorbidities, treatment, and outcome, and descriptive statistical methods were used to analyze the results. Results: A total of 40 cases (16 Raoultella ornithinolytica and 24 Raoultella planticola) were analyzed: 20 cases of biliary tract infection, 5 cases of liver infection, and 4 cases of peritonitis. Fever and abdominal pain were the main symptoms, and some patients present with multiple skin flushes, systemic erythema. Of the 40 cases, 92.5% of patients had underlying diseases. Among them, malignant disease, immunodeficiency, and invasive operations increase the risk of infection. On the basis of the drug susceptibility results, the preferred antibiotics are quinolone, third generations of cephalosporins, carbapenems, and aminoglycoside. Last, patients with abdominal infections caused by Raoultella spp. mostly have a good prognosis after early use of sensitive antibiotics. Conclusions: According to existing literature reports, the main type of abdominal infection caused by Raoultella is biliary tract infection, and most patients have other underlying diseases. Malignancy, immune deficiency, and invasive procedures are risk factors for bacterial infections. This review also emphasizes that Raoultella spp. is a rarely found opportunistic pathogen, which can cause a high incidence of healthcare-associated infections after invasive procedures.

Classic Lesions of the Biliary Tree.

Abnormal findings in the biliary tree are frequently encountered in response to acute and chronic exposures to various compounds. The more common findings are described here in an overview of previous publications such as the INHAND Proliferative and Nonproliferative Lesions of the Rodent Liver and the Liver-Nonneoplastic Lesion Atlas NTP with comments regarding current considerations. This was presented at the 2023 Annual Meeting of the Society of Toxicologic Pathology. Histologic descriptions and some discussions regarding the pathogenesis of the various categories of non-neoplastic lesions in the biliary tree are presented. Discussions regarding the use of the term oval cell versus ductular reaction and the potentially neoplastic nature of cholangiofibrosis are presented in some detail.

A prospective multicentre study evaluating the performance of the modified simple biliary atresia scoring system in predicting biliary atresia.

Early diagnosis of biliary atresia (BA) is critical for best outcomes, but is challenged by overlapping clinical manifestations with other causes of obstructive jaundice in neonates. We evaluate the performance of the modified Simple BA Scoring System (SBASS) in diagnosing BA. We performed a prospective, cross-sectional study on infants with cholestatic jaundice (June 2021-December 2022). Modified SBASS scoring was applied and compared to the eventual diagnosis (as per intraoperative cholangiogram (IOC) and liver histopathology). The score (0-6), consists of gall bladder length < 1.6cm (+ 1), presence of triangular cord sign (+ 1), conjugated bilirubin:total bilirubin ratio > 0.7(+ 2), gamma-glutamyl transferase (GGT) ≥ 200 U/L (+ 2). 73 were included: Fifty-two (71%) had BA. In the non-BA group, 6 (28%) had percutaneous cholangiography (PTC) while 15 (72%) had intraoperative cholangiogram (IOC). At a cut-off of 3, the modified SBASS showed sensitivity of 96.2%, specificity of 61.9% and overall accuracy of 86.3% in diagnosing BA. Area under receiver operating characteristic curve was 0.901. GGT had the highest sensitivity (94.2%), while triangular cord sign showed the highest specificity at 95.2%. The SBASS provides a bedside, non-invasive scoring system for exclusion of BA in infantile cholestatic jaundice and reduces the likelihood of negative surgical explorations.

Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer.

Recent advancements in biliary tract cancer (BTC) treatment have expanded beyond surgery to include adjuvant therapy, yet the prognosis remains poor. Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC. To determine transmembrane serine protease 4 (TMPRSS4) utility as a prognostic biomarker of radical resection for BTC. Medical records of patients who underwent radical resection for BTC, excluding intrahepatic cholangiocarcinoma, were retrospectively reviewed. The associations between TMPRSS4 expression and clinicopathological factors, overall survival, and recurrence-free survival were analyzed. Among the 85 patients undergoing radical resection for BTC, 46 (54%) were TMPRSS4-positive. The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9 (CA19-9) values and greater lymphatic invasion than the TMPRSS4-negative group (P = 0.019 and 0.039, respectively). Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group (median survival time: 25.3 months vs not reached, P < 0.001; median survival time: 28.7 months vs not reached, P = 0.043, respectively). Multivariate overall survival analysis indicated TMPRSS4 positivity, pT3/T4, and resection status R1 were independently associated with poor prognosis (P = 0.032, 0.035 and 0.030, respectively). TMPRSS4 positivity correlated with preoperative CA19-9 values ≥ 37 U/mL and pathological tumor size ≥ 30 mm (P = 0.016 and 0.038, respectively). TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

Lynch syndrome screening in patients with young-onset extra-colorectal Lynch syndrome-associated cancers.

Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers. Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts. There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes. We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers.

Current Gallstone Treatment Methods, State of the Art.

This study aims to provide valuable references for clinicians in selecting appropriate surgical methods for biliary tract stones based on patient conditions. In this paper, the advantages and disadvantages of various minimally invasive cholelithiasis surgical techniques are systematically summarized and innovative surgical approaches and intelligent stone removal technologies are introduced. The goal is to evaluate and predict future research priorities and development trends in the field of gallstone surgery. In recent years, the incidence of gallstone-related diseases, including cholecystolithiasis and choledocholithiasis, has significantly increased. This surge in cases has prompted the development of several innovative methods for gallstone extraction, with minimally invasive procedures gaining the most popularity. Among these techniques, PTCS, ERCP, and LCBDE have garnered considerable attention, leading to new surgical techniques; however, it must be acknowledged that each surgical method has its unique indications and potential complications. The primary challenge for clinicians is selecting a surgical approach that minimizes patient trauma while reducing the incidence of complications such as pancreatitis and gallbladder cancer and preventing the recurrence of gallstones. The integration of artificial intelligence with stone extraction surgeries offers new opportunities to address this issue. Regarding the need for preoperative preparation for PTCS surgery, we recommend a combined approach of PTBD and PTOBF. For ERCP-based stone extraction, we recommend a small incision of the Oddi sphincter followed by 30 s of balloon dilation as the optimal procedure. If conditions permit, a biliary stent can be placed post-extraction. For the surgical approach of LCBDE, we recommend the transduodenal (TD) approach. Artificial intelligence is involved throughout the entire process of gallstone detection, treatment, and prognosis, and more AI-integrated medical technologies are expected to be applied in the future.

Update on the Role of Imaging in the Diagnosis, Staging, and Prognostication of Gallbladder Cancer

AbstractGallbladder cancer (GBC) is a highly aggressive malignancy with dismal prognosis. GBC is characterized by marked geographic predilection. GBC has distinct morphological types that pose unique challenges in diagnosis and differentiation from benign lesions. There are no specific clinical or serological markers of GBC. Imaging plays a key role not only in diagnosis and staging but also in prognostication. Ultrasound (US) is the initial test of choice that allows risk stratification in wall thickening and polypoidal type of gallbladder lesions. US findings guide further investigations and management. Computed tomography (CT) is the test of choice for staging GBC as it allows comprehensive evaluation of the gallbladder lesion, liver involvement, lymph nodes, peritoneum, and other distant sites for potential metastases. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography allow better delineation of the biliary system involvement. Contrast-enhanced US and advanced MRI techniques including diffusion-weighted imaging and dynamic contrast-enhanced MRI are used as problem-solving tools in cases where distinction from benign lesion is challenging at US and CT. Positron emission tomography is also used in selected cases for accurate staging of the disease. In this review, we provide an up-to-date insight into the role of imaging in diagnosis, staging, and prognostication of GBC.

Comparative Analysis of Digestion Methods for Bile Proteomics: The Key to Unlocking Biliary Biomarker Potential.

Bile's potential to reflect the health of the biliary system has led to increased attention, with proteomic analysis offering deeper understanding of biliary diseases and potential biomarkers. With the emergence of normothermic machine perfusion (NMP), bile can be easily collected and analyzed. However, the composition of bile can make the application of proteomics challenging. This study systematically evaluated various trypsin digestion methods to optimize proteomics of bile from human NMP livers. Bile was collected from 12 human donor livers that were accepted for transplantation after the NMP viability assessment. We performed tryptic digestion using six different methods: in-gel, in-solution, S-Trap, SMART, EasyPep, and filter-aided sample purification, with or without additional precipitation before digestion. Proteins were analyzed using untargeted proteomics. Methods were assessed for total protein IDs, variation, and protein characteristics to determine the most optimal method. Methods involving precipitation surpassed crude methods in protein identifications (4500 vs 3815) except for in-gel digestion. Filtered data (40%) resulted in 3192 versus 2469 for precipitated and crude methods, respectively. We found minimal differences in mass, cellular components, or hydrophobicity of proteins between methods. Intermethod variability was notably diverse, with in-gel, in-solution, and EasyPep outperforming others. Age-related biological comparisons revealed upregulation of metabolic-related processes in younger donors and immune response and cell cycle-related processes in older donors. Variability between methods emphasizes the importance of cross-validation across multiple analytical approaches to ensure robust analysis. We recommend the in-gel crude method for its simplicity and efficiency, avoiding additional precipitation steps. Sample processing speed, cost, cleanliness, and reproducibility should be considered when a digestion method is selected for bile proteomics.

Analysis of rehabilitation of individuals after cholecystectomy in sanatorium-resort conditions as a prerequisite for the development of the concept of physical therapy

Laparoscopic cholecystectomy (LCС) is the most commonly performed surgical intervention. The presence of diseases of several body systems in individuals may indicate metabolic syndrome. The consequences of cholecystectomy are manifested by various symptoms and are generally called postcholecystectomy syndrome. The purpose of the article is to analyze the methods and means of rehabilitation of patients after LCC at the sanatorium stage on the example of the functioning of the Department "Lavanda Sanatorium" of CJSC "Ukrprofozdorovnytsia" of the sanatorium-resort complex "Morshynkurort". Research methods: analysis and synthesis of scientific and methodological literature, analysis of methods and means of rehabilitation of patients after LCC for one calendar year. A total of 1296 people diagnosed with gallbladder and biliary tract diseases received rehabilitation services, including those after LCC. Patients undergoing rehabilitation in the post-acute and long-term stages after surgical interventions are treated at the Lavanda Sanatorium department. The treatment period is from 18-24 days at the patient's request. The criteria for the quality of rehabilitation services were as follows: improvement of health, disappearance of pain, dyspeptic phenomena, increased appetite, normalization of bowel movements, normalization of instrumental and laboratory blood tests, etc. Patients after LCC have signs of metabolic and postcholecystectomy syndromes. In addition to the dysfunction of the gastrointestinal tract, there are also limitations of other various body systems, their functions, activities and participation. Therefore, it is necessary to use the international assessment tool "International Classification of Functioning and Participation" and, according to the established disorders, to set individual rehabilitation goals for patients. The use of mineral therapeutic water from well No. 3 in the village of Horishne, Stryi district, Lviv region, in a dilution of 3.0-3.4 g/dm3 on the functional state of the liver of patients after LCC in the conditions of the Morshynkurort sanatorium-resort complex leads to an improvement in liver function, which is confirmed by the results of biochemical studies of patients' blood. Conclusions. Preformed physical factors (physical procedures), heat therapy, various baths, mud therapy, reflexology, microclysters, exercise therapy and massage are traditionally the most popular in the prescription department. However, the use of such remedies, in addition to the use of mineral healing water, is a matter of great debate among the professional community and requires more detailed study in terms of evidence-based practice in health care.

Impact of multiple comorbidities on long-term mortality in older patients following transcatheter aortic valve replacement

BackgroundOlder candidates for transcatheter aortic valve replacement (TAVR) frequently present with both cardiac and noncardiac comorbidities. There are few risk scores that evaluate a wide range of comorbidities. MethodsPatients who underwent TAVR for severe aortic stenosis were retrospectively evaluated. A new prediction model (Cardiac and nonCardiac Comorbidities risk score: 3C score) was determined based on coefficient in the multivariate Cox regression analysis for two-year all-cause mortality. C-statistics were assessed to compare the predictive abilities of the 3C score, the Charlson Comorbidities Index (CCI) score, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, and the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score. ResultsThe present study included 226 patients (age, 86 ± 5 years; males, 38 %). The values of the CCI score, EuroSCORE II, and MELD-XI score were 2 (1–3), 3.36 (2.12–4.58), and 5.35 (3.05–8.55), respectively. Multivariate Cox regression analysis identified two cardiac (left ventricular ejection fraction [LVEF] <40 % [2 points]; pulmonary hypertension [1 point]) and three noncardiac comorbidities (hepatobiliary system impairment [3 points]; estimated glomerular filtration rate <30 ml/min/1.73 m2 [1 point]; cachexia [1 point]). The C-statistics of the 3C score, EuroSCORE II, MELD-XI score, and CCI score were 0.767 (0.666–0.867), 0.610 (0.491–0.729), 0.580 (0.465–0.696), and 0.476 (0.356–0.596), respectively (p < 0.001). ConclusionsAmong cardiac and noncardiac comorbidities, special attention should be given to hepatobiliary system impairment and reduced LVEF in older patients following TAVR. The 3C score may contribute to the risk stratification.

Comparative Cost-Effectiveness of Gemcitabine and Cisplatin in Combination with S-1, Durvalumab, or Pembrolizumab as First-Line Triple Treatment for Advanced Biliary Tract Cancer.

The clinical effectiveness of triple chemotherapy consisting of gemcitabine, cisplatin plus either S-1 (GCS), durvalumab (DGC), or pembrolizumab (PGC) as first-line treatment for advanced biliary tract cancer (BTC) has been reported. However, their comparative cost-effectiveness is unclear. We conducted a model-based cost-effectiveness analysis from the perspective of Japanese healthcare payer. A 10-year partitioned survival model was constructed by comparing the time-dependent hazards of the KHBO1401-MITSUBA, TOPAZ-1, and KEYNOTE-966 trials. The cost and utility came from previously published reports. Quality-adjusted life years (QALY) were used to measure the effects on health. Costs for direct medical care were taken into account. There was a one-way analysis and a probability sensitivity analysis. A willingness-to-pay threshold of 7.5 million yen (57,034 USD) per QALY was defined. The incremental costs per QALY for GCS, DGC, and PGC in the base case study were 3,779,374 JPY (28,740 USD), 86,058,056 JPY (65,4434 USD), and 28,982,059 JPY (220,396 USD), respectively. No parameter had an influence beyond the threshold in a one-way sensitivity analysis. A probabilistic sensitivity analysis revealed that the probability of GCS, DGC, and PGC being cost-effective at the threshold was 85.6%, 0%, and 0%, respectively. Given the current circumstances, it is probable that triple therapy utilizing GCS will emerge as a plausible and efficient primary chemotherapy strategy for patients with advanced BTC in the Japanese healthcare system, as opposed to DGC and PGC.