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First pancreas transplant performed at University of Minnesota in ____
Majority of pancreas transplant recipients are ____, between the age of 35-52 with increased numbers in ___, ____, and ____
MALE; AA, hispanic, asian
patients with T2DM can receive a pancreas txp if _____ > 2ng/mL and BMI < ____kg/m2
c-peptide (released when body makes insulin) and 30
To be listed for pancreas transplant you must have 3 criteria: ____ + ___ insufficiency + requirement of procurement of transplantation of part of a multiple organ transplant for technical reasons
Dx of diabetes, pancreas exocrine
SPK listing must have ___ OR ____ + renal insufficiency defined as GFR < ____ml/min
DM or pancreas exocrine insufficiency; < 20ml/min
Graft failure occurs more frequently (9.2% vs. 7.1/7.3%) in which type of pancreas transplant?
PAK (pancafter kidney)
Mortality is highest in which type of pancreas transplant?
Rejection at 1 year is highest in what type of pancreas transplant?
Cause of pancreas graft failure is most often chronic rejection for which 2 types of panc transplant?
Cause of pancreas graft failure is death in which type of panc transplant?
2018 definition of graft failure includes: graft pancreatectomy, patient death, recipient re-registers for a pancreas transplant, recipient re-registers for a ___ transplant after pancreas tdxp, total insulin use of ___mg/kg/day for 90 consecutive days post transplant or fasting _____
islet cell, 0.5, hyperglycemia
___ recipient age and ___ infection are common immunological risk factors
Pancreas specific risk factors for immunological risk include DM (___ drug absorption due to gastroparesis and enteropathy), as well as autoimmunity
which type of pancreas transplant carries increased immunological risk
Which function exocrine/endocrine rejects first?
exocrine (elevated amylase and lipase)
Monitoring post pancreas transplant includes monitoring for autoantibodies including: ____ (aids in diagnosis of DM) islet cell antibodies (ICA), anti-tyrosine _____ (anti-IA2- found in 78% of type 1 diabetics) and anti-____ antibodies
anti-glutamic acid decarboxylase (GAD), anti-tyrosine phosphatase, and anti-insulin
Enzyme leak, infected fluid/abscess, thrombosis, ileum, and acute rejection are causes of elevated pancreatic enzymes how long post-transplant
early ( < 45 days)
Acute rejection, SBO, pseudocyst, constipationk, Abscess, and CMV pancreatitis are causes of elevated pancreatic enzymes how long post transplant
Mid postoperative (45 days - 1 year)
Acute rejection, chronic rejection, SBO/ventral hernia, intrinsic pancreatic abnormality, native pancreatitis, CMV pancreatitis cause elevated pancreatic enzymes how long post-transplant?
Late (> 1 year post transplant)
Pancreas transplant via endocrine venous drainage occurs via systemic venous drainage through ____ or external/common ____ arteries - MOST COMMON endocrine drainage
Portal venous drainage occurs via the ______ then undergoes first pass metabolism through the liver
SMV (superior mesenteric vein)
Exocrine duct drainage occurs via ___ drainage or ___ drainage (most common). Patient and graft survival are similar
Complications of a bladder drained pancreas include: metabolic ____, UTI, _____, reflux _____
acidosis, UTI, cystitis, reflux pancreatitis
What lab test can you look at to monitor for rejection in a bladder drained pancreas transplant
Most common reason for early technical pancreas graft failure is _______ which occurs most frequently in which type of pancreas transplant
graft thrombosis; PAK
For graft thrombosis prophylaxis strategies when comparing ASA alone given 81mg on POD1 vs. UFH POD 0 at 500 u/hr reduced by 100 units/hr every day + ASA 81 on POD 5 which group had improved rates of graft thrombosis and graft survival?
UFH + ASA (0% graft thrombosis and 100% graft survival) with no difference in PRBCs, leaks, or hemorrhage
When comparing UFH vs. LMWH for graft thrombosis prophylaxis in pancreas transplant which strategy had statistically significantly lower rates of graft thrombosis and better 1 year graft survival?
LMWH (7% thrombosis vs. 17%) and 89.6% vs. 74.4% graft survival with no difference in major bleeding
In one study of 13 KTx and SPK recipients given lovenox + ASA resulted in a high risk of ____ complications
Other panc graft thrombosis prophylaxis strategies may include: ____, ____, or a ____
Warfarin, Plavix, or DOAC
Second most common complication post pancreas transplant is
____ graft pancreatitis occurs 30 min-72 hours after reperfusion. Present with increased amylase/lipase in surgical drain and increased CRP. Risk factors include: increased CIT, donor age, and microvascular disease of the graft. Management includes: avoid HoTN at reperfusion, _____ (drug), and _____ at procurement
physiologic acute graft pancreatitis; CCB, steroids at procurement
___ graft pancreatitis occurs 0-3 months post transplant and is a common cause of graft loss
early graft pancreatitis
which graft pancreatitis p/w pain, increased amylase lipase and hematuria and is managemed with TPN, bowel rest, antithrombotic therapy, and treatment of concurrent infections
early graft pancreatitis
Which graft pancreatitis is an Uncommon cause of graft loss?
Late graft pancreatitis (> 3 months post transplant)
Late graft pancreatitis p/w pain, increased amylase/lipase and _____, fever, vomiting, diarrhea, and ____
Conservative management of late graft pancreatitis includes: ____ rest, ____ and ____. Surgical management includes percutaneous ____ and enteric conversion
bowel, hydration, antibiotics. perc drainage
This complication of pancreas transplant occurs early days-weeks post operative and can be caused by autonomic neuropathy, polyuria in bladder drainage, and hyperinsulinemia in enteric draining
breakdown of anastomosis of graft to the bladder or intestine and subsequent fistula formation accounting for 10% cases of technical failure
The efficacy for ____ as a prophylaxis agent for pancreatic leak is conflicting
Autoimmune recurrence of T1DM post pancreas transplant has about a ___% incidence. No standard treatment options and graft loss reported as 2.5-11.8%
Time to development of PTDM post pancreas transplant was about ___ days in one study
SPK has a favorable outcome for DM complications including slowing the progression of _____, SPK has been shown to be protective from early structural changes from DM nephropathy with higher GFR (vs. LURT/LRRT) and reduced proteinuria from baseline. SPK has also shown to improve ____ (improved nerve conduction velocities) and lower risk of ___, ____ or amputations compared to DDRT or LRRT.
retinopathy; neuropathy, MI, CVA, or ampuations
in 1893 pieces of sheep pancreas were given to 13 year old dying from ketoacidosis. In 1972 glycemic control occurred with infusion of ___into a diabetic rat. In ___ was the first auto-islet cell transplant in 10 patients with surgically induced DM- insulin independence was achieved in 3 patients at 1, 9, and 38 months
1988 the ____ chamber was discovered and in 1990 the first case of insulin independence after all-transplant with IS occurred
Long term islet cell transplant outcomes: insulin independence lost by __-___ years, but ___% with C peptide secretion and A1c < 7%
3-5 years; 80%
Indications for islet cell transplant include: T1DM complicated by ____ unawareness, severe ____ episodes AND/OR glycemic liability
hypoglycemic unawareness; severe hypoglycemia episodes
Considerations for Islet cell transplant include: T1DM > ___ years and >/= ___ years of age, Avoid in BMI > ____kg/m2, weight > ____kg and daily insulin requirement of > ___ unit/kg
5 years; 18 years of age; 30, 90kg, 1.0 unit/kg
Auto islet cell transplant is indicated when?
chronic pancreatitis with total pancreatectomy
UNOS listing criteria for islet cell transplant includes ____ and A1c > ____%
insulin dependence and A1c > 6.5%
Donor selection for islet cell transplant is similar to solid pancreas transplant with increased allowable _____. Donor age 25-___ years BMI > ____ with A1c < _____ and normal BG at time of donation
BMI. 25-50; BMI > 30, A1c < 6.5%
Islet cells are isolated, enzyme digestion removes islets from donor pancreas, purified via centrifuge and incubated. > 7000 islet equivalents/kg is preferred. For the transplant the islet cell culture is suspended in transplant media in a sterilee bag and infused by gravity via percutaneous cauterization of the _____
Islet cell transplant complications include: Bleeding (thrombostatic paste), ____ thrombosis (heparin infusion x 48h, Lovenox ___mg BID x 7 days or ____ x 14 days), Pain, MOST COMMON at site of intrahepatic catheter
PV thrombosis, lovenox 30mg BID or ASA 81
Mild ___/____ elevations occur in islet cell transplant in about 50% of patients which resolves by 1 month
Sensitization to HLA antigens can occur in islet cell transplant and there is increased risk with ___ donors. Use of ___ induction and ___ maintenance may mitigate
more donors; depleting induction and tacrolimus maintenance
Peri-transplant management of islet cell transplant includes Anti-____ therapy, ____ and IL-1RA therapy ______
TNF; Etanercept; Anakinra
Dosing of Etanercept in islet cell transplant includes: 50mg IV x1 pre-transplant then 25mg _____ twice weekly x 2 weeks or 50mg IV x1 pre-transplant then 25mg ____ on days ____, ____ and ___
SUBQ 3, 7, 10
Dosing of Anakinra in islet cell transplant is _____ mg IV x1 pre, then _____mg SQ daily x 7 days
100mg IV x 1 pre operatively, 100mg SQ daily x 7 days
____infusion is used to prevent thrombosis induced by islets and ___ is postulated to have anti-inflammatory properties (modified Edmonton protocol in 2005)
One study done in Transplantation in 2010 found that intensive ___ and ___ were associated with enhanced islet cell transplant outcomes likely due to mitigation of the effects of the instant blood-mediated inflammatory reaction
intensive insulin and heparin (insulin >1unit/hr then SQ and heparin x 48 hours with goal aPTT 70-90s)
One study found that ____ given for 3 months post islet cell transplantation can stimulate ____secretion and ___ insulin dose in others. It may also delay the need to start
exenatide (GLP 1 R agonist)
When comparing the Edmonton (daclizumab, sirolimus, tacrolimus) protocol vs. UIC (Edmonton + exenatide and etanercept) the authors found that the UIC protocol allowed for a much lower number of _____ to allow for insulin independence
islets (1 transplant vs. 2-3 in Edmonton)
When comparing PTA vs. ITA in T1DM insulin independence was achieved in 76% of ____vs. 57% of ____ (73% w/ tacrolimus)
PTA vs. ITA
In terms of hospitalization LOS this was significantly longer for ITA or PTA?
Higher rates of RBC given, relaparatomy, pancreatectomy, thrombosis, and CMV reactivation were seen in _____
PTA vs. ITA
Pancreas transplant carries a high ____ risk but islet cell transplant is a less invasive alternative but is a/w decreased incidence of insulin ____
This type of transplant involves transplantation of the jejunoileum with systemic drainage to the vena cava
Isolated small intestine graft (ITx)
This type of transplant includes the duodenum and an intact biliary system and portal circulation w the native forgut preserved
composite liver small intestine graft (LITx)
This transplant involves the liver, stomach, duodenum, pancreas and small intestine. Can also include the colon and/or kidney
1 year graft survival is higher for intestinal transplant alone or intestinal-liver?
3 year, 5 year and 10 year graft survival is higher for intestinal alone or intestinal-liver?
Patient survival is highest for ____ transplant in pediatric patients and lowest for ___ transplant in adults
intestinal alone; intestinal-liver
___ is the gold standard treatment for benign chronic intestinal failure
About ___% of adult patients w/ benign chronic intestinal failure can achieve enteral autonomy within the first 2 years. After that singificant adaptation occurs, up to 94% of the adult patients have the probabili9ty of permanent _____
50% intestinal failure
In ___ patients intestinal adaptation and enteral autonomy can occur over a prolonged period
pediatric (sharp contrast with adults)
2001 CMS memorandum defined PN failure the following way as indication for intestinal transplant 1. impending or apparent ____ failure because of PN related injury. 2 Central venous catheter-related thrombosis of ____central veins (jugular, subclavian, femoral). 3. frequent central line sepsis ___ episodes/yr of systemic sepsis 2/2 line infections req. hospitalization; a single episode of line related _____; septic shock or ARDS. 4 Frequent episodes of severe ___ despite IV fluids in addition to PN
liver; 2; 2; fungemia; dehydration
Additional indications for intestinal transplant from the AST include: ____ tumors associated w/ familial adenomatous polyposis, congenital ____ disorders (microvillus atrophy and intestinal epithelial dysplasia), ____ bowel syndrome defined as residual small bowel < 10cm in infants and 20cm in adults, IF with high morbidity, or patients unwillingness to accept long term ___ (young patients)
Desmoid, mucosal, ultrashort ; PN
Intestinal organ allocation Status ____ includes liver function test abnormalities, no longer has vascular access for IV feeds, and medical indications warrant intestinal organ transplant on a urgent basis
Combined intestine-liver allocation is according to the ____allocation system
Most common etiology of intestinal failure is ____
Short gut syndrome
____ transplant candidates: pseudo obstruction, necrotizing enterocolitis, and non-congenital short gut syndrome
____ candidates: enteropathies and congenital short gut syndrome
___ candidates were more often status 1 than ___ candidates
Pharmacologic gut rehab can occur with which medication?
What is the MOA of Teduglutide (FDA labeled indication for short bowel syndrome)
binds to GLP-2 (growth hormone) receptors in the intestinal cells resulting in release of multiple mediators including IGF-1, NO, and keratinocyte growth factor
Tedglutide can cause acceleration of ___growth, intestinal obstruction, and increased absorption of ____ meds
Dosing of Tedglutide is 0.05mg/kg (ABW) SQ _____ or if CrCl < 60 ____mg/kg SQ daily
After intestinal transplant, the immune cells in the gut are repopulated with ___cells an the epithelium genotype remains largely that of the ____ making the organ highly____ and _____
recipient immune cells; donor; chimeric; immunogenic
Loss of immunologic protection makes the augmented immunosuppression required to treat rejection for intestinal transplant particularly ______
The immunologic response to the donor intestinal transplant is naive T cells infiltrate the allograft and undergo priming and activation in the ____ mesenteric lymph nodes as Peyer's patches
DONOR (other organs, priming occurs in RECIPEINT lymph tissue)
Immunologic response to donor allograft (intestine): Donor APC ingest and display foreign graft antigens in a/w MHC class I and II molecules. APC are then stimulated to express ______ effectors to arm naive CD8 and CD4 cells. (Th). The CD8 cells attack certain donor cell targets and produce substances to lead to ____ cell apoptosis. Armed Th1 cells produce an _____state driven by cytokine production
costimulatory; crypt cell; inflammatory
The ____ cell maintains immune defenses of the intestinal epithelium by regulation of antmicrobial peptide, human defense 5, from Paneth cells by means of NOD2-dependent circuits
The first intestinal transplant in a human (unpublished) was in 19____ but published ____
The cyclosporine era was between 1985-1989; intestinal graft survival was between ____days and ____months. Only 2 patients had graft survival > 1 year.
10 days and 49 months
Tacrolimus Era was ~1998, Graft survival at 1,3,5 years was ____ compared to cyclosporine. Comparing patient survival at 1,3,5 years to patient survival without transplant at 1 and 2 years which was higher?
much higher (66%, 48%, 48%); transplant
Most common induction for intestinal transplant is _____>______>______
T cell depleting (59%), no induction (30%), IL2RA (14%)
What is the most common maintenance therapy for intestinal transplant?
Tac + steroids (vs. tac/mmf/steroids and other combos)
Acute rejection at 1 year in 2015-2016 was highest in ____ ____ recipients (60.5%) and lowest in ____ ____ recipients (31.1)
pediatric intestine; adult liver-intestine
When comparing alemtuzumab vs. daclizumab or other induction therapies in intestinal transplantation, which agent had lower incidence of ACR?
alemtuzumab in all 3 trials ('04, '06, 2010)
When comparing no induction, IL2RA and OKT3 in intestinal transplant which agent was a/w significantly fewer rejection and infection episodes along with age-normalized lower SCr?
When rATG was used for induction in intestinal transplant, ACR in the first month occur in ~ _____% and 1 and 2 year patient and graft survival were 100% and 94%
When rATG was compared with Rituximab for induction in intestinal transplant, one year patient and graft survival were higher in which group?
Similar (81% and 76%)
When looking at a study of 500 intestinal and MV transplants at a single center the best outcome was with the ____allografts.
When looking at a study of 500 intestinal and MV transplants at a single center, which immunosuppression strategy was associated with significant improvement in outcome with 92% and 70% 1 and 5 year patient survival?
rATG or alemtuzumab induction w/ tacrolimus mono therapy and BM augmentation
When comparing induction therapy and looking at acute rejection rates following intestinal transplant multivariable predictors were a/w less ACR and less severe ACR development these were: _____ transplant, ___/____ induction, or ____ induction
MVTx, Ritux/rATG, Campath
rATG/Ritux and Alemtuzumab were found to be ____ during the 1st 6 months post intestinal transplant for graft loss due to ____
_____ induction (intestinal transplant) 2020 transplantation study was found to be a/w decreased rates of graft loss due to infection
When looking at intestinal transplantation comparing tac, steroids, daclizumab or OKT3 vs. tac, steroids, basiliximab and sirolimus, the authors found that the incidence of BPAR in the first 30 days was _____ in patients on ______ as well as higher 1 year graft survival. Rates of patient survivial were similar between groups.
When looking at intestinal transplant and steroids the number of rejection episodes were ___ between patietns on < 20mg/day or > 20mg/day of prednisone.
When looking at intestinal transplant and steroid maintenance patients with a mean dosage of prednisone of ___ experienced LOWER graft and patient survival rates. ___ were more frequent with steroid administration
When looking at various intestinal and MVTx IS protocols a study done by Trevizol et al found that Alemtuzumab and tacrolimus vs. daclizumab with tac/steroids or rAtG/rituximab + tacrolimus had the lowest rate of ______.
acute cellular rejection
When looking at various intestinal and MVTx IS protocols a study done by Trevizol et al found that the infection rates were considerably lower in which group (dacliz+ tac/steroids, alemtuzumab+ tacrolimus, or rAtG/Ritux + tacrolimus)?
rATG/ritux + tacrolimus
When looking at various intestinal and MVTx IS protocols a study done by Trevizol et al found that 1 and 3 year patient survival rates were highest in which group? (dacliz+ tac/steroids, alemtuzumab+ tacrolimus, or rAtG/Ritux + tacrolimus)
rATG/Ritux + tacrolimus
When looking at the intestinal transplant global activity and trends these things were associated with better graft survival: 1. waiting ____ for ITx, ___therapy, inclusion of a ___component, and _____maintenance therapy
waiting at home for ITx, induction therapy, inclusion of a liver component, and maintenane therapy w/ sirolimus/rapamycin
The grading of intestinal allograft rejection is as follows: Grade IND receives a score of ____, Grade 1/mild is a score of ____, Grade 2/moderate is a score of ____, Grade 3/severe is a score of _____
Grade IND- score=1, Grade 1/mid- score -2, Grade 2/moderate -score 3, Grade 3/severe -score of 4
What agent is first line for mild rejection in intestinal transplant?
pulse dose steroids
Which agents are reserved for severe or steroid resistance rejections for intestinal transplant
____ and ___ can be used as salvage theraoy for AMR(intestinal transplant) in case reports
____ and ______ can be used as salvage therapy for steroid resistant rejection seen in case reports of intestinal transplant rejection
anti-TNF alpha or vedolizumab (Entyvio)
____ has been used in induction and rejection treatment settings in intestinal transplant and can mitigate graft associated inflammation responses and deplete recipient effector memory CD8 T cells
Infliximab (3mg/kg x 4 doses)
_____ has been used by several groups for four main indications: particularly chronic inflammatory mucosal lesions and ileal ulcerations as well as late onset resistant rejections w/ significant success
humanized monclonal antibody that binds to alpha 4 beta 7 integrin and inhibits T lymphocyte from biding to adhesion molecules expressed in the small bowel and colon. Can be used for intestinal transplant rejection.
mortality after steroid resistant or chronic rejection of the intestine is ____
high (50%, 60%)
Ten patients died after steroid resistant ACR or chronic rejction in a study by Lauro et al in intestinal transplant adults mostly due to ____
the difference in survival between steroid resistant and chronic rejection population vs. no ACR or steroid sensitive ACR in intestinal transplant (study by Lauro A et al) did _______
NOT achieve SS
_____DSA increased risk of early graft failure in a study by Cheng et al in intestinal transplanation whereas ____DSA created accelerated graft loss
preformed DSA - increased risk of early graft failure; de-novo DSA = accelerated graft loss
HLA-_____mismatch is a significant risk factor for de novo DSA in intestinal transplant and the persistence of DSA of any type is predicted by strength and specificity
in terms of re-transplantation isolated intestinal transplantation patient survival was ____ for re-transplant when compared to primary ITx
In terms of L-ITx retransplant patient survival was ___ when comparing primary and re-transplant
Infectious complications post intestinal transplant are _____ which was diagnosed at a median of 76 days post-ITx, _____ which occur more commonly in children, are primarily gram positive, and are higher risk if liver graft and pre-operative billirubin > 5 as well as _____ disease and viremia which disease was a/w 11.1x higher risk of death and shorter time to death in intestinal transplantation
infectious enteritis, bloodstream infections, CMV disease and viremia
when looking at hypogammaglobulinemia (HGG) in intestinal transplant study it was found that relative to pre-ITx levels a SS decrease in _____ were seen post ITx.
when looking at hypogammaglobulinemia (HGG) in intestinal transplant study a numerically higher incidence of HGG was seen in the following patients: isolated ITx vs. MVTx? Male vs. Female ? Adult vs. Peds? rATG vs. IL-2RA induction?
ITx, male, adults, rATG
Other immune complications of intestinal transplant include GVHD which has a high mortality. Mitigation strategies include: _____ or ____ immunosuppresion (limited options currently)
intensifying or modifying
IBD or de novo autoimmune disorders can occur post intestinal transplant which occurs _____x that of the general population. It is unclear if IBD is autonomous or a different phenotype of ACR. ____ and ____ may have a role in this complication
10x that of general population. vedolizumab/infliximab
Food allergies can occur post ITx and ____ is associated with eosinophillic gastroenterocolitis secondary to food allergy, asymptomatic eosinophilia and elevatd total and specific IgE levels
after intestinal transplant there is some concern for ___syndrome and foods containing insoluable cellulose or those that are high in sugar and simple carbs can worsen this
dumping syndrome (food moves too quickly through GI tract)
Risk factors for the development of PTLD in intestinal transplant include: ____ transplant recipients (up to 32%), ____ infection, ___ and ___ induction therapy, ____recipient age
ITx, Primary EBV, OKT3 and rATG (polyclonal antibody use), young recipient age (i.e, infants and young children)
Severe CKD can be seen post-ITx. Risk factors associated with development of severe CKD post ITx include: ___gender, ____age, ____ related sepsis, _____maintenance IS, graft failure, ACR, prolonged requirement for _____, TPN, and diabetes
female, older age, catheter related sepsis, STEROID maintenance IS, IV fluids
Risk factors associated with LESS CKD post ITx include: higher____ at time of transplant, _____ immunosuppresion, and _______
GFR, induction IS, tacrolimus
Another study by Reyes, et all found that ___containing grafts increased risk for ESRD post ITx
liver contianing grafts
Immunosuppresion regimens for intestinal transplant are highly variable but most often consist of ____induction and _____ + ____ maintenance
rATG induction and tac w/ steroid maintenance
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