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Journal of Nuclear Cardiology :... May 2024Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine...
BACKGROUND
Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion.
METHOD
Consecutive LT candidates (n=114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n=41) initially used was changed to dobutamine (n=73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n=102 for dipyridamole, n=29 for dobutamine) RESULTS: Prevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,p<0.001). CFR was higher during dipyridamole stress without-caffeine vs. with-caffeine (2.22±0.80 vs. 1.55±0.37,p=0.048) but lower than dobutamine stress (2.22±0.80 vs. 2.82±1.02,p=0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group.
CONCLUSIONS
We demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.
PubMed: 38761831
DOI: 10.1016/j.nuclcard.2024.101884 -
Transplantation Proceedings May 2024Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that, in immunocompromised patients, can progress to respiratory failure and death. Since...
Pneumocystis jirovecii Pneumonia in a Liver Transplant Recipient With an Adverse Reaction to Trimethoprim/Sulfamethoxazole Treated With a Sulfonamide Desensitization Protocol: Case Report.
BACKGROUND
Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that, in immunocompromised patients, can progress to respiratory failure and death. Since trimethoprim/sulfamethoxazole (TMP/SMX) chemoprophylaxis has become a standard management, the prognosis has improved. However, there are patients with a history of TMP/SMX intolerance who cannot receive chemoprophylaxis.
BACKGROUND
We report on a 53-year-old male liver recipient treated with a standard triple immunosuppressive regimen in whom TMP/SMX was waived because of a history of allergy manifested as a generalized rash with edema more than 30 years ago. At transplantation, the immunologic risk was assessed as low, and liver graft function was normal. In the third month after engraftment, he developed dyspnea at rest required constant passive oxygen therapy. Ceftriaxone, azithromycin, and clindamycin were implemented. Mycophenolate acid was stopped, and tacrolimus was reduced. High-resolution computed tomography revealed interstitial pneumonia. Pneumocystis jirovecii pneumoniae was diagnosed from bronchoalveolar lavage. Instead of TMP/SMX, pentamidine and caspofungin were also used for PJP, with no improvement. After 3 weeks, the patient deteriorated. Because of his life-threatening condition, TMP/SMX was introduced in the sulfonamide desensitization protocol, including hydrocortisone and clemastinum. Within 4 days, the patient stabilized with no signs of TMP/SMX intolerance. Pneumonia subsided within a month, and TMP/SMX was prescribed lifelong.
CONCLUSIONS
Prophylaxis for PJP with TMP/SMX still remains an important issue in transplant recipients. Adverse reaction to TMP/SMX in the past is not always a contraindication to reintroducing prophylaxis. The decision of prophylaxis avoidance should be analyzed carefully; in uncertain cases, a sulfonamide desensitization protocol should be considered.
PubMed: 38760300
DOI: 10.1016/j.transproceed.2024.03.022 -
Surgery May 2024Clinically relevant postpancreatectomy hemorrhage occurs in 10% to 15% of patients after pancreaticoduodenectomy, mainly in association with clinically relevant...
BACKGROUND
Clinically relevant postpancreatectomy hemorrhage occurs in 10% to 15% of patients after pancreaticoduodenectomy, mainly in association with clinically relevant postoperative pancreatic fistula. Prevention of postpancreatectomy hemorrhage by arterial coverage with a round ligament plasty or an omental flap is controversial. This study assessed the impact of arterial coverage with an original retromesenteric omental flap on postpancreatectomy hemorrhage after pancreaticoduodenectomy.
METHODS
This single-center retrospective study included 812 open pancreaticoduodenectomies (2012-2021) and compared 146 procedures with arterial coverage using retromesenteric omental flap to 666 pancreaticoduodenectomies without arterial coverage. The Fistula Risk Score was calculated. The primary endpoint was a 90-day clinically relevant postpancreatectomy hemorrhage rate according to the International Study Group of Pancreatic Surgery classification.
RESULTS
There were more patients with a Fistula Risk Score ≥7 in the arterial coverage-retromesenteric omental flap group: 18 (12%) versus 48 (7%) (P < .01). Clinically relevant postpancreatectomy hemorrhage was less frequent in the arterial coverage- retromesenteric omental flap group than in the no arterial coverage group: 5 (3%) versus 66 (10%), respectively (P = .01). Clinically relevant postoperative pancreatic fistula occurred in 28 (19%) patients in the arterial coverage- retromesenteric omental flap group compared with 165 (25%) in the no arterial coverage group (P = .001). There were fewer reoperations for postpancreatectomy hemorrhage or postoperative pancreatic fistula in the arterial coverage- retromesenteric omental flap group: 1 (0.7%) versus 32 (5%) in the no arterial coverage group (P = .023). In multivariate analysis, arterial coverage with retromesenteric omental flap was an independent protective factor of clinically relevant postpancreatectomy hemorrhage (odds ratio 0.33; 95% confidence interval [0.12-0.92], P = .034) whereas postoperative pancreatic fistula of any grade (odds ratio = 10.1; 95% confidence interval: 5.1-20.3, P < .001) was predictive of this complication.
CONCLUSION
Arterial coverage with retromesenteric omental flap can reduce rates of clinically relevant postpancreatectomy hemorrhage after pancreaticoduodenectomy. This easy and costless technique should be prospectively evaluated to confirm these results.
PubMed: 38760227
DOI: 10.1016/j.surg.2024.03.039 -
GE Portuguese Journal of... Jun 2024Acute liver failure (ALF), although rare in children, is a complex progressive pathology, with multisystem involvement and high mortality. Isolated variables or those...
INTRODUCTION
Acute liver failure (ALF), although rare in children, is a complex progressive pathology, with multisystem involvement and high mortality. Isolated variables or those included in prognostic scores have been studied, to optimize organ allocation. However, its validation is challenging. This study aimed to assess the accuracy of several biomarkers and scores as predictors of prognosis in pediatric ALF (PALF).
METHODS
An observational study with retrospective data collection, including all cases of ALF, was defined according to the criteria of the Pediatric Acute Liver Failure Study Group, admitted to a pediatric intensive care unit (PICU) for 28 years. Two groups were defined: spontaneous recovery (SR) and non-SR (NSR) - submitted to liver transplantation (LT) or death at PICU discharge.
RESULTS
Fifty-nine patients were included, with a median age of 24 months, and 54% were female. The most frequent etiologies were metabolic (25.4%) and infectious (18.6%); 32.2% were undetermined. SR occurred in 21 patients (35.6%). In NSR group ( = 38, 64.4%), 25 required LT (42.4%) and 19 died (32.2%), 6 (15.7%) of whom after LT. The accuracy to predict NSR was acceptable for lactate at admission (AUC 0.72; 95% CI: 0.57-0.86; = 0.006), ammonia peak (AUC 0.72; 95% CI: 0.58-0.86; = 0.006), and INR peak (AUC 0.70; 95% CI: 0.56-0.85; = 0.01). The cut-off value for lactate at admission was 1.95 mmol/L (sensitivity 78.4% and specificity 61.9%), ammonia peak was 64 μmol/L (sensitivity 100% and specificity 38.1%), and INR peak was 4.8 (sensitivity 61.1% and specificity 76.2%). Lactate on admission was shown to be an independent predictor of NSR on logistic regression model. Two prognostic scores had acceptable discrimination for NSR, LIU (AUC 0.73; 95% CI: 0.59-0.87; = 0.004) and PRISM (AUC 0.71; 95% CI: 0.56-0.86; = 0.03). In our study, the PALF delta score (PALF-ds) had lower discrimination capacity (AUC 0.63; 95% CI: 0.47-0.78; = 0.11).
CONCLUSIONS
The lactate at admission, an easily obtained parameter, had a similar capacity than the more complex scores, LIU and PRISM, to predict NSR. The prognostic value in our population of the promising dynamic score, PALF-ds, was lower than expected.
PubMed: 38757064
DOI: 10.1159/000531269 -
Transplantation Direct Jun 2024MELD 3.0 introduces changes to address waitlist disparities for liver transplant (LT) candidates. Ascites and hepatic encephalopathy (HE) are important milestones in the...
BACKGROUND
MELD 3.0 introduces changes to address waitlist disparities for liver transplant (LT) candidates. Ascites and hepatic encephalopathy (HE) are important milestones in the natural history of cirrhosis regardless of the Model for End-Stage Liver Disease (MELD) score. We aim to assess the impact of ascites and HE and its interaction with MELD 3.0 on waitlist mortality.
METHODS
This is a retrospective study of patients listed for LT in the Organ Procurement and Transplantation Network database from 2016 to 2021. The primary outcome was waitlist mortality (death/delisting for too sick to LT). Ascites/HE were classified as moderate ascites without moderate HE (mAscites), moderate HE without moderate ascites (mHE), both moderate ascites/HE (mBoth), and neither. MELD 3.0 scores were categorized as <20, 20-29, 30-39, and ≥40.
RESULTS
Of 39 025 candidates, 29% had mAscites, 3% mHE, and 8% mBoth. One-year waitlist mortality was 30%, 38%, and 47%, respectively, compared with 17% (all < 0.001) for those with neither. In multivariable Cox regression, the adjusted risk of waitlist mortality associated with mAscites (versus neither) was a hazard ratio (HR) of 1.76 (95% confidence interval [CI], 1.55-2.00) when the MELD 3.0 score was <20, significantly higher than when the MELD 3.0 score was 20-29 (HR 1.40; 95% CI, 1.27-1.54), 30-39 (HR 1.19; 95% CI, 1.04-1.35), and ≥40 (HR 1.14; 95% CI, 0.91-1.43, interaction < 0.05 for all). A similar pattern was observed by MELD 3.0 for both moderate ascites/HE.
CONCLUSIONS
The presence of moderate ascites alone, or combined with moderate HE, not only increases the risk of waitlist mortality but also has a differential effect by MELD 3.0, especially at lower MELD scores. Earlier strategies addressing this group and improving treatment plans or access to LT regardless of MELD remain needed.
PubMed: 38757050
DOI: 10.1097/TXD.0000000000001625 -
Transplantation Direct Jun 2024Failure to close the abdominal wall after intestinal transplantation (ITx) or multivisceral Tx remains a surgical challenge. An attractive method is the use of...
BACKGROUND
Failure to close the abdominal wall after intestinal transplantation (ITx) or multivisceral Tx remains a surgical challenge. An attractive method is the use of nonvascularized rectus fascia (NVRF) in which both layers of the donor abdominal rectus fascia are used as an inlay patch without vascular anastomosis. How this graft integrates over time remains unknown. The study aims to provide a multilevel analysis of the neovascularization and integration process of the NVRF.
METHODS
Three NVRF-Tx were performed after ITx. Clinical, radiological, histological, and immunological data were analyzed to get insights into the neovascularization and integration process of the NVRF. Moreover, cryogenic contrast-enhanced microfocus computed tomography (microCT) analysis was used for detailed reconstruction of the vasculature in and around the NVRF (3-dimensional histology).
RESULTS
Two men (31- and 51-y-old) and 1 woman (49-y-old) underwent 2 multivisceral Tx and 1 combined liver-ITx, respectively. A CT scan showed contrast enhancement around the fascia graft at 5 days post-Tx. At 6 weeks, newly formed blood vessels were visualized around the graft with Doppler ultrasound. Biopsies at 2 weeks post-Tx revealed inflammation around the NVRF and early fibrosis. At 6 months, classical 2-dimensional histological analysis of a biopsy confirmed integration of the fascia graft with strong fibrotic reaction without signs of rejection. A cryogenic contrast-enhanced microCT scan of the same biopsy revealed the presence of microvasculature, enveloping and penetrating the donor fascia.
CONCLUSIONS
We showed clinical, histological, and microCT evidence of the neovascularization and integration process of the NVRF after Tx.
PubMed: 38757048
DOI: 10.1097/TXD.0000000000001624 -
Brain Communications 2024Autosomal recessive pathogenetic variants in the gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance,...
Autosomal recessive pathogenetic variants in the gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance, consequently, leading to quantitative and/or qualitative impairment of mitochondrial DNA synthesis. Typically, patients present early-onset liver failure with or without neurological involvement and a clinical course rapidly progressing to death. This is an international multicentre study aiming to provide a retrospective natural history of deoxyguanosine kinase deficient patients. A systematic literature review from January 2001 to June 2023 was conducted. Physicians of research centres or clinicians all around the world caring for previously reported patients were contacted to provide followup information or additional clinical, biochemical, histological/histochemical, and molecular genetics data for unreported cases with a confirmed molecular diagnosis of deoxyguanosine kinase deficiency. A cohort of 202 genetically confirmed patients, 36 unreported, and 166 from a systematic literature review, were analyzed. Patients had a neonatal onset (≤ 1 month) in 55.7% of cases, infantile (>1 month and ≤ 1 year) in 32.3%, pediatric (>1 year and ≤18 years) in 2.5% and adult (>18 years) in 9.5%. Kaplan-Meier analysis showed statistically different survival rates ( < 0.0001) among the four age groups with the highest mortality for neonatal onset. Based on the clinical phenotype, we defined four different clinical subtypes: hepatocerebral (58.8%), isolated hepatopathy (21.9%), hepatomyoencephalopathy (9.6%), and isolated myopathy (9.6%). Muscle involvement was predominant in adult-onset cases whereas liver dysfunction causes morbidity and mortality in early-onset patients with a median survival of less than 1 year. No genotype-phenotype correlation was identified. Liver transplant significantly modified the survival rate in 26 treated patients when compared with untreated. Only six patients had additional mild neurological signs after liver transplant. In conclusion, deoxyguanosine kinase deficiency is a disease spectrum with a prevalent liver and brain tissue specificity in neonatal and infantile-onset patients and muscle tissue specificity in adult-onset cases. Our study provides clinical, molecular genetics and biochemical data for early diagnosis, clinical trial planning and immediate intervention with liver transplant and/or nucleoside supplementation.
PubMed: 38756539
DOI: 10.1093/braincomms/fcae160 -
Liver Cancer Jun 2024Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma...
INTRODUCTION
Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy.
METHODS
This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival, overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥1 dose of study treatment.
RESULTS
The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib: 234, sorafenib: 225). At the interim analysis, the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to the early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups.
CONCLUSION
Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.
PubMed: 38756145
DOI: 10.1159/000533650 -
JPGN Reports May 2024The goal of this longitudinal study was to reduce anxiety and pain in children with chronic conditions from the gastrointestinal tract during venipuncture. These...
Interventions to alleviate anxiety and pain during venipuncture in children with chronic gastrointestinal and/or liver disease: A single-center prospective observational study.
OBJECTIVES
The goal of this longitudinal study was to reduce anxiety and pain in children with chronic conditions from the gastrointestinal tract during venipuncture. These children undergo regular venipuncture as part of their medical management and the procedure is often accompanied with anxiety and pain. In addition, children as well as their parents and health care professionals (HCPs) often suffer "compassionate pain" because of emotional interference.
METHOD
In a realistic clinical setting, different psychological and medical interventions were examined: (1) Psychoeducational brochures and (2) four different medical-technical interventions during venipuncture. In a large hospital in Germany, 169 children, their parents, and HCPs were asked to rate anxiety and pain during venipuncture before and after the intervention.
RESULTS
Children showed a clear preference for some of the medical-technical interventions. Using anxiety and pain rated by the children themselves showed no significant reduction. However, parents and HCPs reported a significant reduction. Age, gender, and status of liver transplantation were associated with a reduction in anxiety and pain in most of the analyses.
CONCLUSION
Both psychoeducational brochures and medical-technical interventions had a positive impact on anxiety and pain. However, effectivity for the medical-technical interventions was lower than in previous studies utilizing individual interventions. Reasons for this difference as well as possibilities to improve the intervention are discussed. In addition, this study provides practical day-to-day information about the implementation of interventions for the work in pediatric units such as when and how to provide psychoeducational materials.
PubMed: 38756111
DOI: 10.1002/jpr3.12053 -
JPGN Reports May 2024Pediatric acute liver failure is a rare but serious complication of Coronavirus infections. Our patient is a previously healthy 8-year-old male who presented with acute...
Pediatric acute liver failure is a rare but serious complication of Coronavirus infections. Our patient is a previously healthy 8-year-old male who presented with acute liver failure in the setting of human coronavirus HKU1 (HCoV-HKU1) infection while asymptomatic from a respiratory perspective. During the hospital course, he developed acute hepatic encephalopathy and was listed for liver transplantation, but fortunately recovered remaining status 7 (inactive) on the transplant list. With a negative diagnostic evaluation other than his viral infection and hyperdense CD8 T-cells on liver immunohistochemical staining, pediatric acute liver failure (PALF) immune dysregulation phenotype was diagnosed.
PubMed: 38756108
DOI: 10.1002/jpr3.12065