Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation

Background: Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital.Methods: We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival.Results: HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for allcause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002).Conclusion: HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function

Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease

Background Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Methods Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. Results All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p < 0.001) and controls (from 1194 ± 26 ms to 1273 ± 44 ms, p < 0.001). T2DM patients showed blunted relative stress non-contrast T1 response (T2DM: ΔT1 = 4.1 ± 2.9% vs. controls: ΔT1 = 6.6 ± 2.6%, p = 0.007) due to a blunted maximal T1 during adenosine stress (T2DM 1244 ± 44 ms vs. controls 1273 ± 44 ms, p = 0.045). Conclusions Patients with well controlled T2DM, even in the absence of arterial hypertension and significant CAD, exhibit blunted maximal non-contrast T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention

Oral Administration of Recombinant Live Yeast Producing Altered Peptide Ligand Derived from Insulin B:9-23 Peptide Linked to Cholera Toxin B Subunit Suppresses Development of Autoimmune Diabetes in NOD Mice

Insulin is a major autoantigen responsible for the pathogenesis of type 1 diabetes, and its B-chain peptide B:9-23 has been suggested to contain critically important epitopes in the NOD mouse. We have previously demonstrated that the altered peptide ligand of B:9-23 peptide with alanine substitutions at positions 16 and 19 (A16,19 APL) suppresses insulitis and reduces the incidence of diabetes when administered intranasally together with cholera toxin (CT). In this study, we extended the previous findings to determine whether mucosal administration of the A16,19APL without the use of toxic CT is efficacious for diabetes prevention. To this end,we linked the A16,19APL to the C-terminus of non-toxic cholera toxin (CTB) B subunit and the chimeric fusion protein was produced in methyloprophic yeast Pichia pastoris. Although intranasal administration of the recombinant CTB-A16,19APL fusion protein extracted fromthe yeast cells failed to prevent the progression to diabetes, oral administration of the live yeast cells producing the chimeric protein resulted in more than 50% reduction of the development of diabetes, albeit the fact that protective efficacy did not reach the significance level by life table analysis (P= 0.08). Furthermore, the expression of insulin autoantibodies was not altered throughout the course of oral immunization experiment. These results demonstrated that the efficacy of recombinant CTB-A16,19APL for oral immunization has much room for improvement. Nevertheless, oral administration of recombinant yeast or other edible materials such as food plants engineered to produce altered autoantigenic peptide could potentially become a novel non-invasive immunotherapeutic strategy for type 1 diabetes. (250 word

Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation

Abstract Background Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. Methods We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. Results HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for all-cause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002). Conclusion HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function

The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity

Iron-salen, i.e., μ-oxo-N,N′-bis(salicylidene)ethylenediamine iron (Fe(Salen)) was a recently identified as a new anti-cancer compound with intrinsic magnetic properties. Chelation therapy has been widely used in management of metallic poisoning, because an administration of agents that bind metals can prevent potential lethal effects of particular metal. In this study, we confirmed the therapeutic effect of deferoxamine mesylate (DFO) chelation against Fe(Salen) as part of the chelator antidote efficacy. DFO administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in cancer cells. DFO (25 mg/kg) reduced the onset of Fe(Salen) (25 mg/kg)-induced acute liver and renal dysfunction. DFO (300 mg/kg) improves survival rate after systematic injection of a fatal dose of Fe(Salen) (200 mg/kg) in mice. DFO enables the use of higher Fe(Salen) doses to treat progressive states of cancer, and it also appears to decrease the acute side effects of Fe(Salen). This makes DFO a potential antidote candidate for Fe(Salen)-based cancer treatments, and this novel strategy could be widely used in minimally-invasive clinical settings