Safety and efficacy of continuous terlipressin infusion in HRS-AKI in a transplant population.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p <0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p =0.12; D90: 78% vs. 68%, p =0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p <0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

INFUSE: Rationale and design of a multi-center, open label, collaborative study to treat HRS-AKI with continuous terlipressin infusion.

Background: Hepatorenal syndrome-acute kidney injury (HRS-AKI) carries significant morbidity and mortality among those with end-stage liver disease. Bolus terlipressin for treatment of HRS-AKI received FDA approval in September 2022. US implementation of terlipressin, however, is hindered by the paucity of local data on the optimal patient population and administration mode, as well as the effect on transplant priority. The INFUSE study is designed to evaluate the use of continuous terlipressin infusion among transplant candidates with advanced liver disease and HRS-AKI. Methods: Fifty prospective patients with HRS-AKI will receive a single bolus of terlipressin 0.5 mg followed by continuous infusions of terlipressin from 2 to 8 mg/day for up to 14 days. The cohort will be enriched with those listed, in evaluation, or eligible for liver transplantation, while those with ACLF grade 3, MELD ≥35, and serum creatinine >5.0 mg/dL will be excluded. Fifty patients who received midodrine plus octreotide or norepinephrine for HRS-AKI will serve as a retrospective comparator cohort. Conclusion: The INFUSE study aims to assess the safety and efficacy of continuous terlipressin infusion among largely transplant-eligible patients with HRS-AKI, and to provide US-based data on transplant outcomes. This novel study design simultaneously mitigates terlipressin adverse events while providing renal benefits to patients, thus addressing the unmet medical need of those with HRS-AKI who have limited treatment options and are awaiting liver transplantation in the US.

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

Current Concepts of Cirrhotic Cardiomyopathy.

Cirrhotic cardiomyopathy (CCM) connotes systolic and/or diastolic dysfunction in patients with end-stage liver disease in the absence of prior heart disease. Its prevalence is variable across different studies but recent data suggest that CCM may affect up to one third of liver transplant candidates. The etiology of CCM is multifactorial. CCM defining features were recently revised to improve the diagnostic and prognostic yield of CCM criteria and inform candidate selection for liver transplantation. CCM appears to increase the risk for unfavorable outcomes pre- and post-transplant. Close clinical and echocardiographic follow-up of patients with CCM may mitigate adverse cardiac outcomes.

Neurologic Toxicities Associated with Tumor Necrosis Factor Inhibitors and Calcineurin Inhibitors.

The calcineurin inhibitors cyclosporine and tacrolimus are used for their immunosuppressive effects. Neurotoxic side effects include tremor, paresthesia, and headache. Rarer neurotoxicities include seizure, posterior reversible encephalopathy syndrome, and encephalopathy. Tacrolimus tends to be more neurotoxic than cyclosporine. Management of toxicities associated with calcineurin inhibitors includes dose reduction, switching between calcineurin inhibitors, or switching to a calcineurin-free regimen. Tumor necrosis factor (TNF) inhibitors are used in autoimmune diseases. Management of demyelinating conditions among patients treated with anti-TNF should follow standard of care and withdrawal of the anti-TNF. This drug class should be avoided in patients with a history of demyelinating conditions.

Initial experience with a novel EUS-guided core biopsy needle (SharkCore): results of a large North American multicenter study.

BACKGROUND AND AIMS: The ability to safely and effectively obtain sufficient tissue for pathologic evaluation by using endoscopic ultrasound (EUS) guidance remains a challenge. Novel designs in EUS needles may provide for improved ability to obtain such core biopsies. The aim of this study was to evaluate the diagnostic yield of core biopsy specimens obtained using a novel EUS needle specifically designed to obtain core biopsies. PATIENTS AND METHODS: Multicenter retrospective review of all EUS-guided fine-needle biopsies obtained using a novel biopsy needle (SharkCore FNB needle, Medtronic, Dublin, Ireland). Data regarding patient demographics, lesion type/location, technical parameters, and diagnostic yield was obtained. RESULTS: A total of 250 lesions were biopsied in 226 patients (Median age 66 years; 113 (50 %) male). Median size of all lesions (mm): 26 (2 - 150). Overall, a cytologic diagnosis was rendered in 81 % specimens with a median number of 3 passes. When rapid onsite cytologic evaluation (ROSE) was used, cytologic diagnostic yield was 126/149 (85 %) with a median number of 3 passes; without ROSE, cytologic diagnostic yield was 31/45 (69 %, P = 0.03) with a median number of 3 passes. Overall, a pathologic diagnosis was rendered in 130/147 (88 %) specimens with a median number of 2 passes. Pathologic diagnostic yield for specific lesion types: pancreas 70/81 (86 %), subepithelial lesion 13/15 (87 %), lymph node 26/28 (93 %). Ten patients (10/226, 4 %) experienced adverse events: 4 acute pancreatitis, 5 pain, 1 fever/cholangitis. CONCLUSIONS: Initial experience with a novel EUS core biopsy needle demonstrates excellent pathologic diagnostic yield with a minimum number of passes.

[Surgical problems in acute acalculous cholecystitis]. / Chirurgická problematika akutní akalkulózní cholecystitidy.

The authors report on the prevalence of acute cholecystitis in the absence of calculi with special attention paid to the development of this disease as a complication of prolonged parenteral nutrition. In 1990-1993 at the Surgical Clinic in Plzen 125 cases of acute cholecystitis were operated, incl. 14 acalculous ones (11.2%). These 14 patients comprised 5 (28.6%) who were on parenteral nutrition for a prolonged period. The authors analyze the causes of the development of acute acalculous cholecystitis. They deal with the problem of diagnosis where in severe postoperative and posttraumatic cases ultrasonography proved useful.

[Unusual injuries of the abdominal aorta]. / Neobvyklé poranení brisní aorty.

A 23-year-old patient was admitted after a car accident with multiple fractures of the extremities, contusion of the brain and a sonographically confirmed haematoma in the retroperitoneum. After 24 hours laparotomy was indicated on account of suddenly developed hypotension. On operation a haemoperitoneum was found and an extensive haematoma in the retroperitoneum, the cause of which was injury of the abdominal aorta due to rupture of the lower mesenteric and lumbar artery. The authors demonstrate the not quite typical picture of an injury of a major artery and recommended early angiography.

[Injuries of the diaphragm]. / Poranení bránice.

The author presents an analysis of 27 injuries of the diaphragm treated at the surgical Clinic of the Faculty Hospital in Plzen in 1969-1992. There was a total of 22 closed injuries, all part of multiple injuries. In five instances an open injury was involved. The total mortality was 22.2%. The authors analyze the causes of injuries of the diaphragm, affections of different parts of the body in relation to multiple injuries and discuss the problem of assessment of the diagnosis. In the diagnosis in addition to common X-ray methods, sonography and CT and in exceptional cases angiography of the hepatic artery proved useful. The authors draw attention to the difference between prolapse of internal organs and post-traumatic diaphragmatic hernia and emphasize the importance of early operation after the diagnosis was established. They discuss approaches to surgical repair, treatment of injured internal organs and the diaphragm.

[Esophageal injuries]. / Poranení jícnu.

The authors present an analysis of 33 oesophageal injuries treated at the surgical clinic of Faculty Hospital Plzen in 1976-1991. Iatrogenic injuries predominated (a total of 24 cases). Of these seven developed during oesophagoscopy performed on account of dysphagic complaints caused by benign or malignant disease. Ten injuries developed in conjunction with endoscopic extraction of a foreign body, three occurred during operation of hiatus hernia, two during sclerotization of oesophageal varices and one each during insertion of a nasogastric tube and oesophageal endoprosthesis. In the remaining cases perforation occurred during traumatic injury of the neck four times, twice as a result of a swallowed bone, and three perforations were spontaneous. The total mortality was 27.3%. The authors analyze factors which influence the morbidity and mortality--the site of injury, the time which elapsed between injury and treatment, the patient's age, mode of injury, associated diseases and method of treatment. They found that the most frequent complication and most frequent cause of death was septicaemia from mediastinitis and empyema of the chest.

[Reoperation in Crohn's disease]. / Opakované operace pro Crohnovu chorobu.

In 1967-1992 at the surgical clinic in Plzen 101 patients were operated with histologically confirmed Crohn's disease. A total of 32 urgent operations were performed. Due to the possibility to provide complete parenteral nutrition from this number during the past 6 years only three patients were operated. During the next and subsequent period 70 patients were reoperated. Relapses occurred most frequently four years after the first operation. As to the extent of resection, the authors agree with the view that 20 cm from the macroscopic borderline of the affection are sufficient without special regard to lymph nodes. Nevertheless it is important to keep in mind that Crohn's disease is a systemic disease and even by radical removal of the affected part this disease cannot be cured by surgery.