Phase 1-2 Trial of AAVS3 Gene Therapy in Patients with Hemophilia B.

BACKGROUND: FLT180a (verbrinacogene setparvovec) is a liver-directed adeno-associated virus (AAV) gene therapy that uses a synthetic capsid and a gain-of-function protein to normalize factor IX levels in patients with hemophilia B. METHODS: In this multicenter, open-label, phase 1-2 trial, we assessed the safety and efficacy of varying doses of FLT180a in patients with severe or moderately severe hemophilia B (factor IX level, ≤2% of normal value). All the patients received glucocorticoids with or without tacrolimus for immunosuppression to decrease the risk of vector-related immune responses. After 26 weeks, patients were enrolled in a long-term follow-up study. The primary end points were safety and efficacy, as assessed by factor IX levels at week 26. RESULTS: Ten patients received one of four FLT180a doses of vector genomes (vg) per kilogram of body weight: 3.84×1011 vg, 6.40×1011 vg, 8.32×1011 vg, or 1.28×1012 vg. After receiving the infusion, all the patients had dose-dependent increases in factor IX levels. At a median follow-up of 27.2 months (range, 19.1 to 42.4), sustained factor IX activity was observed in all the patients except one, who resumed factor IX prophylaxis. As of the data-cutoff date (September 20, 2021), five patients had normal factor IX levels (range, 51 to 78%), three patients had levels from 23 to 43%, and one had a level of 260%. Of the reported adverse events, approximately 10% were related to FLT180a and 24% to immunosuppression. Increases in liver aminotransferase levels were the most common FLT180a-related adverse events. Late increases in aminotransferase levels occurred in patients who had received prolonged tacrolimus beyond the glucocorticoid taper. A serious adverse event of arteriovenous fistula thrombosis occurred in the patient with high factor IX levels. CONCLUSIONS: Sustained factor IX levels in the normal range were observed with low doses of FLT180a but necessitated immunosuppression with glucocorticoids with or without tacrolimus. (Funded by Freeline Therapeutics; ClinicalTrials.gov numbers, NCT03369444 and NCT03641703; EudraCT numbers, 2017-000852-24 and 2017-005080-40.).

Extensive splanchnic vein thrombosis after SARS-CoV-2 vaccination: A Vascular Liver Disease Group (VALDIG) initiative.

BACKGROUND AND AIMS: Since the introduction of SARS-CoV-2 vaccines, several cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) have been described, especially cerebral vein thrombosis. We aimed to retrospectively collect all new cases of acute onset first or recurrent splanchnic vein thrombosis (SVT) following a recent SARS-CoV-2 vaccination within the Vascular Liver Disease Group network. APPROACH AND RESULTS: New cases of SVT were identified from April 2021 to April 2022; follow-up was completed on December 31, 2022. Criteria to define VITT were derived from previous studies. Data from a pre-COVID cohort of patients with SVT (N=436) were used for comparison of clinical presentation, etiology, and outcome. Twenty-nine patients were identified with SVT occurring with a median of 11 days (range 2-76) after the first (48%), second (41%), or third (10%) vaccination (ChAdOx1 nCov-19 (n=12) or BNT162b2 (n=14), other (n=3) Only 2 patients(7%) fulfilled criteria for definite VITT. Twenty (69%) had SVT at multiple sites, including 4 (14%) with concomitant extra-abdominal thrombosis. Only 28% had an underlying prothrombotic condition, compared to 52% in the pre-COVID SVT cohort ( p =0.01). Five patients (17%) underwent bowel resection for mesenteric ischemia, compared with 3% in pre-COVID SVT ( p <0.001). Two patients died shortly after diagnosis (7%). CONCLUSIONS: Although definite VITT was rare, in 72% of cases, no other cause for SVT could be identified following SARS-CoV-2 vaccination. These cases were different from patients with nonvaccine-related SVT, with lower incidence of prothrombotic conditions, higher rates of bowel ischemia, and poorer outcome. Although SVT after SARS-CoV-2 vaccination is rare in absolute terms, these data remain relevant considering ongoing revaccination programs.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Bacterascites confers poor patient prognosis beyond MELD prediction.

Spontaneous bacterial peritonitis (SBP) is a well-recognized clinical entity with a poor prognosis. In comparison, the prevalence, microbiological flora, and prognostic significance of bacterascites (BA) (the presence of organism on culture but ascitic PMN <250 cells/mm³) is largely unknown. We, therefore, assessed the prognosis and predictors of outcome in patients with BA in comparison with those with SBP. Ascitic fluid cultures from consecutive patients with cirrhosis from 2008 to 2018 were reviewed retrospectively, and patients with SBP and BA were identified. Baseline demographic, laboratory, and microbiological data were collated and analyzed as prognostic indicators, and clinical outcomes were recorded. Patients were censored at the time of LT, death, or last follow-up. For this study 176 and 213 cases of SBP and BA, respectively, were identified and included. Patients with SBP had significantly higher Model for End-Stage Liver Disease (MELD) ( p =<0.01), peripheral blood WCC ( p < 0.01), and higher rates of Enterobacteriaceae ( p < 0.01) and multi-drug resistant pathogens ( p < 0.01). Survival at 1 and 3 months was lower in patients with SBP ( p < 0.01) when compared with BA but at 6 months and beyond, no significant difference remained. After the exclusion of deaths within 30 days of presentation, survival between SBP and BA was equivocal at all time points. Mortality was substantially higher across all MELD groupings for both SBP and BA when compared with the predicted mortality calculated by the MELD score alone. BA has a negative impact on patient survival above that predicted by the MELD score. It has similar impact to SBP on patient survival beyond 1 month suggesting it should be seen as a poor prognostic marker and prompt consideration of LT where appropriate. Further studies evaluating the role of secondary prophylaxis in this group are required.

Parsimonious methodology for synthesis of silver and copper functionalized cellulose.

Metal nanomaterials, such as silver and copper, are often incorporated into commercial textiles to take advantage of their Antibacterial and antiviral properties. The goal of this study was to identify the most parsimonious method for the synthesis of silver, copper, or silver/copper bimetallic treated textiles. To accomplish this eight different methods were employed to synthesize silver, copper, and silver/copper functionalized cotton batting textiles. Using silver and copper nitrate as precursors, different reagents were used to initiate/catalyze the deposition of metal, including: (1) no additive, (2) sodium bicarbonate, (3) green tea, (4) sodium hydroxide, (5) ammonia, (6, 7) sodium hydroxide/ammonia at a 1:2 and 1:4 ratio, and (8) sodium borohydride. The use of sodium bicarbonate as a reagent to reduce silver onto cotton has not been used previously in literature and was compared to established methods. All synthesis methods were performed at 80 °C for one hour following textile addition to the solutions. The products were characterized by x-ray fluorescence (XRF) analysis for quantitative determination of the metal content and x-ray absorption near edge structure (XANES) analysis for silver and copper speciation on the textile. Scanning electron microscopy (SEM) with energy dispersive x-ray (EDX) and size distribution inductively coupled plasma mass spectrometry (ICP-MS) were used to further characterize the products of the sodium bicarbonate, sodium hydroxide, and sodium borohydride synthesis methods following ashing of the textile. For the silver treatment methods (1 mM Ag +), sodium bicarbonate and sodium hydroxide resulted in the highest amounts of silver on the textile (8900 mg Ag/kg textile and 7600 mg Ag/kg textile) and for copper treatment (1 mM Cu +) the sodium hydroxide and sodium hydroxide/ammonium hydroxide resulted in the highest amounts of copper on the textile (3800 mg Ag/kg textile and 2500 mg Ag/kg textile). Formation of copper oxide was dependent on the pH of the solution, with 4 mM ammonia and other high pH solutions resulting in majority of the copper on the textile existing as copper oxide, with smaller amounts of ionic-bound copper. The identified parsimonious methods will lend themselves to the efficient manufacturing of antibacterial and antiviral textiles, or the development of multifunctionalized smart textiles. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-023-05099-7.

Achilles tendon disorders: An overview of diagnosis and conservative treatment.

ABSTRACT: Achilles tendon-related pain affects up to 6% of the US population during their lifetime and is commonly encountered by primary care providers. An accurate diagnosis and early conservative management can improve patient quality of life and reduce unnecessary surgical consultations, saving healthcare dollars. Achilles tendon pathologies can be categorized into acute (pain lasting less than 6 weeks), chronic (pain lasting more than 6 weeks), and acute on chronic (worsening of pain with preexisting chronic Achilles tendon pathology). This article describes the diagnosis, conservative management, indications for imaging, and indications for surgical referral for acute and chronic Achilles tendon rupture, Achilles tendinitis, gastrocnemius strain, plantaris rupture, insertional Achilles tendinopathy, Haglund deformity, and noninsertional Achilles tendinopathy.

How do surgeons decide when to treat proximal humerus fractures with operative versus nonoperative management?

PURPOSE: The objective of this study was to determine the underlying factors that drive the decision for surgeons to pursue operative versus nonoperative management for proximal humerus fractures (PHF) and if fellowship training had an impact on these decisions. METHODS: An electronic survey was distributed to members of the Orthopaedic Trauma Association and the American Shoulder and Elbow Surgeons Society to assess differences in patient selection for operative versus nonoperative management of PHF. Descriptive statistics were reported for all respondents. RESULTS: A total of 250 fellowship trained Orthopaedic Surgeons responded to the online survey. A greater proportion of trauma surgeons preferred nonoperative management for displaced PHF fractures in patients over the age of 70. Operative management was preferred for older patients with fracture dislocations (98%), limited humeral head bone subchondral bone (78%), and intraarticular head split (79%). Similar proportions of trauma surgeons and shoulder surgeons cited that acquiring a CT was crucial to distinguish between operative and nonoperative management. CONCLUSION: We found that surgeons base their decisions on when to operate primarily on patient's comorbidities, age, and the amount of fracture displacement when treating younger patients. Further, we found a greater proportion of trauma surgeons elected to proceed with nonoperative management in patients older than the age of 70 years old as compared to shoulder surgeons.

Retention of PFOS and PFOA Mixtures by Trapped Gas Bubbles in Porous Media.

The transport of per- and polyfluoroalkyl substances (PFAS) in soil and groundwater is important for site investigation, risk characterization, and remediation planning. The adsorption of PFAS at air-water interfaces has been shown to significantly contribute to PFAS retention, with subsequent effects on concentrations and the time scales of transport. In this study, column experiments were conducted to investigate the transport of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 6:2 fluorotelomer sulfonate (6:2 FTS) individually and in binary mixtures in the presence of a trapped gas phase, using clean sands to isolate adsorption to air-water interfaces. Consistent with previous studies, the transport of PFOS, PFOA, and 6:2 FTS was retarded by adsorption at the air-water interface, with greater retention of PFOS due to its higher affinity for the air-water interface. Chromatographic separation occurred in the experiments using binary mixtures of PFOS and PFOA, with greater retention at lower influent concentrations. The mixture experiments also showed enhanced breakthrough of PFOA in the presence of PFOS, where effluent concentrations of PFOA were temporarily greater than the influent concentration prior to the breakthrough of PFOS. This enhanced breakthrough was attributed to competition between PFOS and PFOA for adsorption to the air-water interface.

Understanding postoperative rehabilitation preferences in operatively managed proximal humerus fractures: do trauma and shoulder surgeons differ?

BACKGROUND: Proximal humerus fractures (PHFs) are common, and their incidence is increasing as the population ages. Despite this, postoperative rehabilitation remains unstandardized and little is known about surgeon preferences. The aim of this study was to assess differences in postoperative rehabilitation preferences and patient education between orthopedic trauma and shoulder surgeons. METHODS: An electronic survey was distributed to members of the Orthopaedic Trauma Association and the American Shoulder and Elbow Surgeons to assess differences in postoperative rehabilitation preferences and patient counseling. Descriptive statistics were reported for all respondents, trauma surgeons, and shoulder surgeons. Chi-square and unpaired 2-sample t tests were used to compare responses. Multinomial regression was used to further elucidate the influence of fellowship training independent of confounding characteristics. RESULTS: A total of 293 surgeons completed the survey, including 172 shoulder and 78 trauma surgeons. A greater proportion of trauma surgeons preferred an immediate weightbearing status after arthroplasty compared to shoulder surgeons (45% vs. 19%, P = .003), but not after open reduction and internal fixation (ORIF) (62% vs. 75%, P = .412). A greater proportion of shoulder surgeons preferred home exercise therapy taught by the physician or using a handout following reverse shoulder arthroplasty (RSA) (21% vs. 2%, P = .009). A greater proportion of trauma surgeons began passive range of motion (ROM) <2 weeks after 2-part fractures (70% vs. 41%, P < .001). Conversely, a greater proportion of shoulder surgeons began passive ROM between 2 and 6 weeks for 2-part (57% vs. 24%, P < .001) and 4-part fractures (65% vs. 43%, P = .020). On multinomial regression analysis, fellowship training in shoulder surgery was associated with preference for a nonweightbearing duration of >12 weeks vs. 6-12 weeks after ORIF. Similarly, fellowship training in shoulder surgery was associated with increased odds of preferring a nonweightbearing duration of <6 weeks vs. no restrictions and >12 weeks vs. 6-12 weeks after arthroplasty. Training in shoulder surgery was associated with greater odds of preferring a nonweightbearing duration prior to beginning passive ROM of 2-6 weeks vs. <2 weeks or >6 weeks for 2-part fractures, but not 4-part fractures. CONCLUSION: Trauma surgeons have a more aggressive approach to rehabilitation following operative PHF repair compared to shoulder surgeons regarding time to weightbearing status and passive ROM. Given the increasing incidence of PHFs and substantial variations in reported treatment outcomes, differences in rehabilitation after PHF treatment should be further evaluated to determine the role it may play in the outcomes of treatment studies.

Factors influencing surgical management of proximal humerus fractures: do shoulder and trauma surgeons differ?

BACKGROUND: Proximal humerus fractures (PHFs) are managed with open reduction and internal fixation (ORIF), hemiarthroplasty (HA), reverse shoulder arthroplasty (RSA), or nonoperatively. Given the mixed results in the literature, the optimal treatment is unclear to surgeons. The purpose of this study was to survey orthopedic shoulder and trauma surgeons to identify the patient- and fracture-related characteristics that influence surgical decision-making. METHODS: We distributed a 23-question closed-response email survey to members of the American Shoulder and Elbow Surgeons and Orthopaedic Trauma Association. Questions posed to respondents included demographics, surgical planning, indications for ORIF and arthroplasty, and the use of surgical augmentation with ORIF. Numerical and multiple-choice responses were compared between shoulder and trauma surgeons using unpaired t-tests and χ2 tests, respectively. RESULTS: Respondents included 172 shoulder and 78 trauma surgeons. When surgery is indicated, most shoulder and trauma surgeons treat 2-part (69%) and 3-part (53%) PHFs with ORIF. Indications for managing PHFs with arthroplasty instead of ORIF include an intra-articular fracture (82%), bone quality (76%), age (72%), and previous rotator cuff dysfunction (70%). In patients older than 50 years, 90% of respondents cited a head-split fracture as an indication for arthroplasty. Both shoulder and trauma surgeons preferred RSA for treating PHFs presenting with a head-split fracture in an elderly patient (94%), pre-existing rotator cuff tear (84%), and pre-existing glenohumeral arthritis with an intact cuff (75%). Similarly, both groups preferred ORIF for PHFs in young patients with a fracture dislocation (94%). In contrast, although most trauma surgeons preferred to manage PHFs in low functioning patients with a significantly displaced fracture or nonreconstructable injury nonoperatively (84% and 86%, respectively), shoulder surgeons preferred either RSA (44% and 46%, respectively) or nonoperative treatment (54% and 49%, respectively) (P < .001). Similarly, although trauma surgeons preferred to manage PHFs in young patients with a head-split fracture or limited humeral head subchondral bone with ORIF (98% and 87%, respectively), shoulder surgeons preferred either ORIF (54% and 62%, respectively) or HA (43% and 34%, respectively) (P < .001). CONCLUSIONS: ORIF and HA are preferred for treating simple PHFs in young patients with good bone quality or fracture dislocations, whereas RSA and nonoperative management are preferred for complex fractures in elderly patients with poor bone quality, rotator cuff dysfunction, or osteoarthritis. The preferred management differed between shoulder and trauma surgeons for half of the common PHF presentations, highlighting the need for future research.

Pediatric hallux valgus: An overview of history, examination, conservative, and surgical management.

Pediatric hallux valgus (PHV), while relatively rare, is still often encountered by general pediatricians. Herein, we concisely summarize the existing literature regarding the pathogenesis, associated conditions, clinical diagnosis, radiographic characteristics, conservative management, and surgical management of PVH. Though PHV is generally considered benign, the progression of hallux valgus can result in complications. The presence of an open physis in the pediatric age group delineates first line treatment choices, whenever possible, as nonoperative. The general exception to this recommendation is for children with neuromuscular and connective tissues disease who may benefit from earlier surgical management. If conservative approaches fail prior to skeletal maturity, the risk of recurrence and need for revision surgery should be discussed with patients and their families before surgical referral is made. The current review was conducted to aid primary care providers in better understanding the pathogenesis, associated conditions, and intervention options available to manage PHV.

Which surgical approach is optimal for joint preparation in talonavicular fusion - A cadaver study.

BACKGROUND: Fusion of the talonavicular joint has proven challenging in literature. The optimal surgical approach for talonavicular arthrodesis is still uncertain. This study compares the amount of physical joint preparation between dorsal and medial approaches to the talonavicular joint. METHODS: Twenty fresh frozen cadaver specimens were randomly assigned to receive either a dorsal or medial operative approach to the talonavicular joint. The joint surface was prepared, and the joint was disarticulated. Image analysis, using ImageJ, was performed by two blinded reviewers to assess the joint surface preparation and this was compared by surgical approach. RESULTS: The dorsal approach had a higher median percentage of talar and total talonavicular joint surface area prepared (75% vs. 59% (p = .007) and 82% vs. 70% (p = .005)). Irrespective of approach, the talus was significantly more difficult to prepare than the navicular (62% vs 88% (p = .001)). CONCLUSION: The dorsal approach provides superior talonavicular joint preparation. The lateral »th of the talar head was the most difficult surface to prepare, and surgeons performing double or triple arthrodesis may prepare the lateral talar head from the lateral approach. LEVEL OF EVIDENCE: Level V.

Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding.

BACKGROUND & AIMS: Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic shunt (TIPS) improves survival in patients with failure to control OGVB and ACLF. METHODS: Data on 174 consecutive eligible patients, with failure to control OGVB between 2005 and 2015, were collected from a prospectively maintained intensive care unit registry. Rescue TIPS was defined as technically successful TIPS within 72 hours of presentation with failure to control OGVB. Cox-proportional hazards regression analyses were applied to explore the impact of ACLF and TIPS on survival in patients with failure to control OGVB. RESULTS: Patients with ACLF (n = 119) were significantly older, had organ failures and higher white cell count than patients with acute decompensation (AD, n = 55). Mortality at 42-days and 1-year was significantly higher in patients with ACLF (47.9% and 61.3%) than in those with AD (9.1% and 12.7%, p <0.001), whereas there was no difference in the number of endoscopies and transfusion requirements between these groups. TIPS was inserted in 78 patients (AD 21 [38.2%]; ACLF 57 [47.8%]; p = 0.41). In ACLF, rescue TIPS insertion was an independent favourable prognostic factor for 42-day mortality. In contrast, rescue TIPS did not impact on the outcome of patients with AD. CONCLUSIONS: This study shows that in patients with failure to control OGVB, the presence and severity of ACLF determines the risk of 42-day and 1-year mortality. Rescue TIPS is associated with improved survival in patients with ACLF. LAY SUMMARY: Variceal bleeding that is not controlled by initial endoscopy is associated with high risk of death. The results of this study showed that in the occurrence of failure of the liver and other organs defines the risk of death. In these patients, insertion of a shunt inside the liver to drain the portal vein improves survival.

Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): An International Observational Study.

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.

Transjugular intrahepatic portosystemic stent-shunt in the management of portal hypertension.

These guidelines on transjugular intrahepatic portosystemic stent-shunt (TIPSS) in the management of portal hypertension have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the Liver Section of the BSG. The guidelines are new and have been produced in collaboration with the British Society of Interventional Radiology (BSIR) and British Association of the Study of the Liver (BASL). The guidelines development group comprises elected members of the BSG Liver Section, representation from BASL, a nursing representative and two patient representatives. The quality of evidence and grading of recommendations was appraised using the GRADE system. These guidelines are aimed at healthcare professionals considering referring a patient for a TIPSS. They comprise the following subheadings: indications; patient selection; procedural details; complications; and research agenda. They are not designed to address: the management of the underlying liver disease; the role of TIPSS in children; or complex technical and procedural aspects of TIPSS.

Sarcopenia Does Not Worsen Survival in Patients With Cirrhosis Undergoing Transjugular Intrahepatic Portosystemic Shunt for Refractory Ascites.

INTRODUCTION: The impact of sarcopenia in patients undergoing transjugular intrahepatic portosystemic shunt (TIPSS) insertion for refractory ascites is unknown. METHODS: All adult patients who underwent TIPSS insertion for refractory ascites between 2010 and 2018 were included. Skeletal muscle index at L3 was used to determine sarcopenia status. RESULTS: One hundred seven patients were followed for 14.2 months. Sarcopenia was present in 57% of patients. No patient had history of pre-TIPSS hepatic encephalopathy (HE). De novo HE occurred in 30% of patients. On multivariate analysis, only platelet count and L3-SMI predicted de novo HE. On multivariate analysis, age and model for end-stage liver disease with sodium predicted mortality, whereas L3-SMI and sarcopenia did not. In patients with repeat imaging, L3-SMI improved significantly post-TIPSS compared with baseline. DISCUSSION: Sarcopenia should not be considered as a contraindication to TIPSS insertion in refractory ascites because it is not associated with de novo HE or increased mortality.

Remediation of PFAS-Contaminated Soil and Granular Activated Carbon by Smoldering Combustion.

This study explored smoldering combustion for remediating polyfluoroalkyl substance (PFAS)-impacted granular activated carbon (GAC) and PFAS-contaminated soil. GAC, both fresh and PFAS-loaded, was employed as the supplemental fuel supporting smoldering in mixtures with sand (≈175 mg PFAS/kg GAC-sand), with PFAS-spiked, laboratory-constructed soil (≈4 mg PFAS/kg soil), and with a PFAS-impacted field soil (≈0.2 mg PFAS/kg soil). The fate of PFAS and fluorine was quantified with soil and emission analyses, including targeted PFAS and suspect screening as well as hydrogen fluoride and total fluorine. Results demonstrated that exceeding 35 g GAC/kg soil resulted in self-sustained smoldering with temperatures exceeding 900 °C. Post-treatment PFAS concentrations of the treated soil were near (2 experiments) or below (7 experiments) detection limits (0.0004 mg/kg). Further, 44% of the initial PFAS on GAC underwent full destruction, compared to 16% of the PFAS on soil. Less than 1% of the initial PFAS contamination on GAC or soil was emitted as PFAS in the quantifiable analytical suite. Results suggest that the rest were emitted as altered, shorter-chain PFAS and volatile fluorinated compounds, which were scrubbed effectively with GAC. Total organic fluorine analysis proved useful for PFAS-loaded GAC in sand; however, analyzing soils suffered from interference from non-PFAS. Overall, this study demonstrated that smoldering has significant potential as an effective remediation technique for PFAS-impacted soils and PFAS-laden GAC.

Double-balloon enteroscopy-facilitated cyanoacrylate-injection endotherapy of small-bowel varices: an international experience from 2 European tertiary centers (with videos).

BACKGROUND AND AIMS: Small-bowel varices (SBVs) are an uncommon consequence of portal hypertension. Radiologic intervention is usually considered for first-line management. When radiologic intervention is not possible, management options become very limited. The aim of this study was to evaluate the usefulness of double-balloon enteroscopy (DBE)-facilitated cyanoacrylate-injection endotherapy of SBVs. METHODS: This was a retrospective review of DBE-facilitated cyanoacrylate-injection endotherapy of SBVs (December 2015 to October 2016). RESULTS: Ten DBEs were performed in 6 patients (4 women; median age, 68.5 years). No radiologic or surgical options were deemed feasible. Thirteen nests of SBVs were identified and injected with cyanoacrylate glue without hemorrhagic or embolic adverse events. At the 30-day follow-up after therapy, only 1 patient had experienced a mild recurrence of mid-gut bleeding; this was managed conservatively. One patient presented with acute GI bleeding 7 months later, and a repeat DBE with cyanoacrylate-injection endotherapy was successfully performed. One patient succumbed to his underlying advanced cholangiocarcinoma after 2 months. The remaining patients had a median follow-up of 12 months without any recurrent GI bleeding. CONCLUSIONS: DBE-facilitated cyanoacrylate-injection endotherapy of SBVs appears to be a safe and effective option when other first-line options are not feasible.

Cardiovascular morbidity and mortality is increased post-liver transplantation even in recipients with no pre-existing risk factors.

BACKGROUND/AIMS: Post-liver transplant (LT) metabolic syndrome (PTMS) and cardiovascular (CVS) mortality are becoming increasingly prevalent following sustained improvements in post-LT survival. We investigated the prevalence and predictors of PTMS and CVS complications in a cohort of consecutive LT recipients. METHODS: We reviewed prospectively collected data of patients (n = 928) who underwent LT (1995-2013) and survived at least 1-year post-LT or died before that due to a major CVS complication. RESULTS: Median follow-up was 85 months (IQR = 106). The prevalence of PTMS was 22.4% and it developed de novo in 183 recipients (19.7%). A total of 187 (20.2%) patients developed at least one CVS event post-LT within a median of 49 months (IQR = 85). Overall mortality rate was 22.6% (n = 210). Causes of death were CVS events (n = 45, 21.4%), malignancies (21%), liver-related deaths (20%) and infections (6.7%). Independent predictors of major CVS events were: documented CVS disease pre-LT (Hazard Ratio (HR) = 3.330; 95% CI = 1.620-6.840), DM (HR = 1.120; 95% CI 1.030-1.220), hypertension (HR = 1.140; 95% CI 1.030-1.270), dyslipidaemia (HR = 1.140; 95% CI 1.050-1.240) and creatinine levels at 1 year (HR = 1.010; 95% CI = 1.005-1.013). Among LT recipients without pre-LT CVS disease or MS components (n = 432), 85 recipients developed ≥1 CVS events (19.7%) with independent predictors being DM (HR = 1.150; 95% CI = 1.010-1.320), creatinine levels at 1 year (HR = 1.020; 95% CI = 1.010-1.030) and hypertension (HR = 1.190; 95% CI = 1.040-1.360). CONCLUSIONS: Post-LT patients are at increased risk of CVS morbidity even in the absence of pre-existing metabolic risk factors. Renal sparing immunosuppressive protocols might reduce CVS events post-LT.