The impact of advanced patient age in liver transplantation: a European Liver Transplant Registry propensity-score matching study

BackgroundThe futility of liver transplantation in elderly recipients remains under debate in the HCV eradication era.MethodsThe aim was to assess the effect of older age on outcome after liver transplantation. We used the ELTR to study the relationship between recipient age and post-transplant outcome. Young and elderly recipients were compared using a PSM method.ResultsA total of 10,172 cases were analysed. Recipient age >65 years was identified as an independent risk factor associated with reduced patient survival (HR:1.42 95%CI:1.23–1.65,p < 0.001). After PSM, 2124 patients were matched, and the same association was found between elderly recipients and patient survival and graft survival (p < 0.001). As hepatocellular carcinoma and alcoholic cirrhosis were independent prognostic factors for patient and graft survival a propensity score-matching was performed for each. Patient and graft survival were significantly worse (p < 0.05) in the alcoholic cirrhosis elderly group. However, patient and graft survival in the hepatocellular carcinoma cohort were similar (p > 0.05) between groups.ConclusionLiver transplantation is an acceptable and safe curative option for elderly transplant candidates, with worse long-term outcomes compare to young candidates. The underlying liver disease for liver transplantation has a significant impact on the selection of elderly patients.     

The Impact of Left Atrial Reduction During Surgical Ablation of Atrial Fibrillation

The left atrial Reduction group revealed decreased risk of overall stroke compared to the left atrial Preservation group, adjusted by inverse probability of treatment weighting. Which implicates that reduction of left atrial wall during surgical ablation of atrial fibrillation may reduce the risk of stroke in patients with left atrial anteroposterior diameter ≥50 mm. Schematic illustration of left atrial reduction plasty, and IPTW-adjusted Kaplan-Meier survival plot for stroke comparing 2 groups are included in the graphical abstract. SVC, Superior vena cava; LAA, Left atrial appendage; PVs, Pulmonary veins; MV, Mitral valve; LA, Left atrium; IPTW, Inverse probability of treatment weighting.

1. Download : Download high-res image (260KB)
2. Download : Download full-size image

     

A retrospective evaluation of heparin product reactions in patients with alpha-gal allergies

BackgroundAlpha-gal allergy, also known as red meat allergy or alpha-gal syndrome, can present after bites of certain tick species that contain galactose-alpha-1,3-galactose (alpha-gal) carbohydrate. Following this exposure, patients may develop an allergic reaction after mammalian meat consumption. Some heparin products are derived from porcine intestinal tissue, and it is therefore possible that administering these medications to a patient with an alpha-gal allergy may trigger a reaction.ObjectiveThe purpose of this study was to evaluate the incidence of reactions to porcine heparin products in patients with an alpha-gal allergy.MethodsA retrospective case series was conducted by review of electronic medical record data. Patients included were between the ages of 18 and 89 years, with a documented alpha-gal or red meat allergy and an admission to a hospital in the Sentara Healthcare system. The primary outcome was the incidence of allergic reactions upon exposure to heparin products in patients with a documented alpha-gal allergy.ResultsPatients with a documented alpha-gal allergy received a heparin product in 57 of 158 hospital visits (36.1%). Heparin products were tolerated in 56 of the 57 visits (98.3%). The incidence of an alpha-gal reaction to unfractionated heparin was 2.6% (1/39) while the incidence of an alpha-gal reaction to enoxaparin was 0% (0/22).Conclusion and RelevanceHeparin products were associated with a low incidence of alpha-gal reactions among patients with documented alpha-gal allergy. It is possible that enoxaparin poses less of a risk for reaction in these patients compared to unfractionated heparin.     

Socioeconomic Deprivation and Premature Cardiovascular Mortality in the United States

ObjectiveTo determine the variability in county cardiovascular (CV) premature mortality explained by integrated metrics of socioeconomic deprivation and to explore temporal trends in CV mortality by county socioeconomic deprivation.MethodsThis is a cross-sectional analysis of US county-level death certificate data from 1999 to 2018 of age-adjusted premature (25 to 64 years) CV mortality. Integrated metrics of socioeconomic deprivation (Social Deprivation Index [SDI] and county Area Deprivation Index [ADI]) were associated with mortality using linear regression analysis. Relative change in county CV mortality from 1999 to 2018 was associated with indices using linear regression analysis.ResultsCounties with higher quartile SDI and ADI had significantly higher total, non-Hispanic Black/African American, and female premature CV mortality (P<.001). Both SDI and ADI were significantly associated with CV mortality by linear regression (P<.001) explaining 40% and 44% of county variability in CV mortality, respectively. Counties with lower deprivation indices experienced a larger decreased in premature CV mortality (P<.001).ConclusionThis study demonstrates an association between multiple integrated metrics of socioeconomic deprivation and premature cardiovascular mortality and shows potentially worsening disparities.     

Stability of Opened Durvalumab (IMFINZI) Vials. The Beginning of the End of Costly Product Wastage?

Durvalumab is a monoclonal antibody approved for the treatment of lung, urothelial and biliary tract cancers. Durvalumab is supplied in vials as a solution containing no preservatives. Monographs recommend single use of durvalumab vials, and that any leftovers be discarded within 24 h. Thus, significant portions of unused product from opened vials are wasted on a daily basis, generating considerable financial losses. The objective of the present study was to assess the physicochemical and microbiological stability of durvalumab vials kept at 4 °C or room temperature, at 7 and 14 days after opening. Following pH and osmolality measurements, turbidity and submicronic aggregation of durvalumab solution were evaluated by spectrophotometry and dynamic light scattering, respectively. Moreover, steric exclusion high performance liquid chromatography (SE-HPLC), ion exchange HPLC (IEX-HPLC) and peptide mapping HPLC were used to respectively assess aggregation/fragmentation, charge distribution and primary structure of durvalumab. Microbiological stability of durvalumab was evaluated by incubation of vial leftovers on blood agar. All experiments showed physicochemical and microbiological stability of durvalumab vial leftovers for at least 14 days when aseptically handled and kept at either 4 °C or at room temperature. These results suggest the possible extension of utilization of durvalumab vial leftovers well beyond 24 h.     

Raman Marker Bands for Secondary Structure Changes of Frozen Therapeutic Monoclonal Antibody Formulations During Thawing

In this work we use Raman spectroscopy for protein characterization in the frozen state. We investigate the behavior of frozen therapeutic monoclonal antibody IgG1 formulation upon thawing by Raman spectroscopy. Secondary and tertiary structure of the protein in three different mab formulations in the frozen state are followed through observation of marker bands for α-helix, β-sheet and random coil. We identify the tyrosine intensity ratio I₈₅₆/I₈₃₀ as a marker for mab aggregation. Upon fast cooling (40 °C/min) to –80 °C we observe a significant increase of random coil and α –helical structures, while this is not the case for slower cooling (20 °C/min) to –80 °C. Most changes in the protein's secondary structure are observed in the course of thawing in the range up to -20 °C, when passing through the glass transitions and cold-crystallization of the two types of freeze-concentrated solutions formed through macro- and microcryoconcentration. An increase of protein concentration and the addition of mannitol suppress secondary structural changes but do no impact on aggregation.     

Risk as a pattern over time: Delineation of time-dependent risk factors in biological,psychological, and social variables in cancer patients

Background

Survival in cancer patients is associated with a multitude of biological, social, and psychological factors. Although it is well established that all these factors add to overall mortality, it is not well understood how the predictive power of these parameters changes in a comprehensive model and over time.

Methods

Patients who attended the authors’ outpatient clinic were invited to participate. The authors followed 5180 mixed cancer patients (51.1% female; mean age, 59.1 years [SD = 13.8]) for up to 16 years and analyzed biological (age, sex, cancer site, anemia), psychological (anxiety, depression), and social variables (marital status, education, employment status) potentially predicting overall survival in a Cox proportional hazards model.

Results

The median survival time for the entire sample was 4.3 years (95% confidence interval, 4.0–4.7). The overall survival probabilities for 1 and 10 years were 76.8% and 38.0%, respectively. Following an empirical approach, the authors split the time interval into five periods: acute, subacute, short-term, medium-term, and long-term. A complex pattern of variables predicted overall survival differently in the five periods. Biological parameters were important throughout most of the time, social parameters were either time-independent predictors or tended to be more important in the longer term. Of the psychological parameters, only depression was a significant predictor and lost its predictive power in the long-term.

Conclusions

The findings of this study allow the development of comprehensive patient-specific models of risk and resilience factors addressing biopsychosocial needs of cancer patients, paving the way for a personalized treatment plan that goes beyond biomedical cancer care.