Managing viral hepatitis in cancer patients under immune checkpoint inhibitors : should we take the risk?

More patients with chronic hepatitis B and C infection are being exposed to immune checkpoint inhibitors (ICIs), but the safety and efficacy of ICIs in patients with chronic viral hepatitis are still poorly described. To explore this interaction, we identified eight studies of cancer patients with viral hepatitis treated with one or more ICIs, formally assessed tumor responses and safety by grading liver dysfunction. ICIs appear to be relatively safe in HBV/HCV-infected patients, and hepatitis related to viral reactivation is rare. In some patients, viral load regressed during ICI treatment, so immune checkpoints may play a role in viral clearance. HBV/HCV do not appear to be a contraindication to ICIs, although careful clinical and biochemical follow-up is recommended and, whenever necessary, antiviral therapy commenced

Aortic valve repair with patch in non-rheumatic disease: indication, techniques and durability†

OBJECTIVES: To analyse the long-term outcomes of aortic valve (AV) repair with biological patch in patient with non-rheumatic valve disease. METHODS: From 1995 to 2011, 554 patients underwent elective (AV) repair; among them, 57 (mean age 45 ± 17 years) had cusp restoration using patch for non-rheumatic valve disease. Seven (12%) patients had unicuspid valve, 30 (53%) patients had bicuspid valve and 20 (35%) had tricuspid valve. Autologous pericardium was used in 26 patients (7 treated, 19 non-treated), bovine pericardium in 26, autologous tricuspid valve leaflet in 4 and aortic homograft cusp in 1. Patching was used to repair perforation (n = 20, 35%), commissural defect (n = 18, 32%), raphe repair (n = 17, 30%) or for cusp extension (n = 2, 3.5%). Echocardiographic and clinical follow-up was 98% complete and mean follow-up was 72 ± 42.5 months. RESULTS: No hospital mortality. At 8 years, overall survival was 90 ± 5% and freedom from valve-related death was 96 ± 3%. Two patients (3.5%) needed early reoperation for aortic regurgitation (AR); they underwent re-repair and the Ross procedure, respectively. Late reoperation was necessary in 9 patients (16%) for AR (n = 4), stenosis (n = 3) or mixed disease (n = 2). They had the Ross procedure (n = 6) or prosthetic valve replacement (n = 3) with no mortality. At 8 years, freedom from reoperation was 75 ± 9%. Freedom from reoperation was slightly higher in tricuspid compared with non-tricuspid valves (92 ± 7 vs 68 ± 11%, P = 0.18) and slightly higher for bovine (95 ± 5%) compared with autologous pericardium (73 ± 11%, P = 0.38), but differences were statistically not significant. In tricuspid valves, freedom from reoperation was higher in perforation repair compared with other techniques (100 vs 50 ± 35%, P = 0.02). In bicuspid valves, freedom from reoperation was similar between different repair techniques (P = 0.38). Late echocardiography showed AR 0-1 in 30 (53%) patients, AR 2 in 12 (21%) and no AR ≥ 3. Three patients presented a mean transvalvular gradient of 30-40 mmHg. Thromboembolic events occurred in 2 patients (0.6%/patient-year), bleeding events in 1 (0.3% /patient-year) and no endocarditis occurred. CONCLUSIONS: AV repair with biological patch is feasible for various aetiologies. The techniques are safe and medium-term durability is acceptable, even excellent for perforation repair in tricuspid valve morphology. Bovine pericardium is a good alternative to autologous pericardium

Outcome of patch materials used in aortic valve repair : examining CorMatrix® bioscaffold as suitable cardiac tissue substitute

Aortic valve repair’s longevity is affected by failure mechanisms such as fibrosis, calcification and degeneration. New generation engineered patches such as CorMatrix® (SIS-ECM) are appealing options with much publicized potentials and advantages to aid growth and longevity. We developed clinical and experimental studies investigating the current clinical status of AV patch repair, then we took the clinical question to laboratory benches for experimental investigation on the potentials of CorMatrix® patch. This thesis contributes to the knowledge on the subject and affords evidence of originality. We studied the long-term outcome of patch use in non-rheumatic AV repair and found no differences between autologous or bovine pericardial patches. We established the safety of variable surgical techniques and identified multiple patches and valve-patient related influencing factors. Our progressive and chronic experimental studies examined CorMatrix® in couple of novel complex models. We revealed new data on its in vivo reaction and observed consistent lack of remodelling in allograft models; questioning the true potential and safety of the CorMatrix® for cardiac repair.(MED - Sciences médicales) -- UCL, 201

Comparing the Host Reaction to CorMatrix and Different Cardiac Patch Materials Implanted Subcutaneously in Growing Pigs.

BACKGROUND: Comparing the structural changes, and local host reactions to CorMatrix (CorMatrix Cardiovascular Inc., Roswell, Georgia, United States) and different biomaterials implanted subcutaneously in growing pig model. METHODS: Four pigs harboring implanted patches of CorMatrix, Vascutek porcine pericardium (Vascutek; Scotland, United Kingdom), SJM bovine pericardium (St. Jude Medical, Inc., Minnesota, United States), and Gore-Tex (W. L. Gore & Associates GmbH, Flagstaff, Arizona, United States) were studied for 1, 3, 6, and 12 months. The explants were examined histologically. RESULTS: CorMatrix showed gradual and consistent patch resorption and subsiding inflammatory and fibrosis process. Full scaffold degradation and replacement by mild fibrosis and subcutaneous tissue were seen by 1 year. Xenopericardial patches remained intact, and the initially severe inflammatory and fibrotic reactions reduced gradually to moderate fibrosis and chronic inflammation. Gore-Tex showed foreign body reaction. CONCLUSIONS: Patches were biotolerated by pigs. Xenopericardial patches elicited encapsulating fibrosis and no remodeling. CorMatrix resorbs completely and degrades consistently without leaving residues. Lack of encapsulating fibrosis toward CorMatrix allows tissue ingrowth and matrix remodeling

Calcific Degeneration of CorMatrix 4 Years After Bicuspidization of Unicuspid Aortic Valve.

We report the long-term outcomes of a 12-year-old boy who underwent bicuspidization of a severely stenotic unicuspid aortic valve with CorMatrix small intestinal submucosal extracellular matrix (CorMatrix Cardiovascular, Roswell, GA). CorMatrix supported favorable immediate surgical and echocardiographic outcomes and maintained stable growing functional dynamics for 2 years. At 52.5 months in situ, however, the valve failed with severe calcification, fibrosis, and retraction necessitating a redo operation. Reconstructive operations with CorMatrix are feasible, but this result questions its capacity for constructive remodeling in left-sided valve repair

How to perform valve sparing reimplantation in a tricuspid aortic valve.

Aortic valve sparing procedures are increasingly being used to treat aortic root pathologies. Reimplantation of the aortic valve, first described by Dr Tirone David, is a technically demanding procedure whose long-term results are critically dependent on perfect intraoperative restoration of valve anatomy and function. There exists significant variation in how this procedure is performed by different surgeons, which is likely contributory to the heterogeneity in reported results. We describe a systematic approach to aortic valve reimplantation procedure focusing on key technical aspects

Experimental Aortic Valve Cusp Extension with CorMatrix in a Porcine Model.

BACKGROUND : We tested the feasibility of using porcine small intestinal submucosal extracellular matrix (CorMatrix) for aortic valve (AV) repair in porcine model examining its resorption and remodeling potential. METHODS : The non-coronary cusp was replaced with CorMatrix in four animals for 120 days. Valve function was assessed by echocardiography. Explants were examined by histology, immunohistochemistry, and collagen assessment. RESULTS : CorMatrix was almost totally replaced with tissue resembling the native cusp with a partial two-layer architecture. However, function was lost due to thickening and calcification. CONCLUSIONS : Tested in high-pressure AV position in a pig model, CorMatrix degrades and remodels, but also loses function

Small intestinal submucosa extracellular matrix (CorMatrix®) in cardiovascular surgery: a systematic review.

Extracellular matrix (ECM) derived from small intestinal submucosa (SIS) is widely used in clinical applications as a scaffold for tissue repair. Recently, CorMatrix® porcine SIS-ECM (CorMatrix Cardiovascular, Inc., Roswell, GA, USA) has gained popularity for 'next-generation' cardiovascular tissue engineering due to its ease of use, remodelling properties, lack of immunogenicity, absorbability and potential to promote native tissue growth. Here, we provide an overview of the biology of porcine SIS-ECM and systematically review the preclinical and clinical literature on its use in cardiovascular surgery. CorMatrix® has been used in a variety of cardiovascular surgical applications, and since it is the most widely used SIS-ECM, this material is the focus of this review. Since CorMatrix® is a relatively new product for cardiovascular surgery, some clinical and preclinical studies published lack systematic reporting of functional and pathological findings in sufficient numbers of subjects. There are also emerging reports to suggest that, contrary to expectations, an undesirable inflammatory response may occur in CorMatrix® implants in humans and longer-term outcomes at particular sites, such as the heart valves, may be suboptimal. Large-scale clinical studies are needed driven by robust protocols that aim to quantify the pathological process of tissue repair