Should Sarcopenia Increase Priority for Transplant or Is It a Contraindication?

Purpose of Review

The purpose of this review is to discuss the current evidence regarding the impact of sarcopenia on patients with cirrhosis awaiting liver transplantation and to determine if its presence should be considered a criterion for expedited transplantation or a contraindication for transplantation.

Recent Findings

Sarcopenia is a negative predictor of survival in patients on a waiting list and after liver transplant. The gut-liver axis and the liver-muscle axis have been explored to understand the complex pathophysiology of sarcopenia.

Summary

Sarcopenia is a frequent finding in patients with cirrhosis. The diagnosis is ideally based on cross-sectional image analysis (CT or MRI) and treatment consists of optimization of caloric and protein intake. To date, prioritizing tools for liver transplantation have not included nutrition or sarcopenia parameters. Patients with a low Model for End-Stage Liver Disease (MELD) or MELD-Na score and sarcopenia would benefit from prioritization for transplant in order to reduce time on waiting list and therefore mortality.

     

One-Pot Self-Assembly of Dinuclear,Tetranuclear, and H-Bonding-Directed Polynuclear Cobalt(II), Cobalt(III), and Mixed-Valence Co(II)/Co(III) Complexes of Schiff Base Ligands with Incomplete Double Cubane Core

The reaction of 2,6-diformyl-4-methylphenol (DFMF) with 1-amino-2-propanol (AP) and tris(hydroxymethyl)aminomethane (THMAM) was investigated in the presence of Cobalt(II) salts, (X = ClO₄⁻, CH₃CO₂⁻, Cl⁻, NO₃⁻), sodium azide (NaN₃), and triethylamine (TEA). In one pot, the variation in Cobalt(II) salt results in the self-assembly of dinuclear, tetranuclear, and H-bonding-directed polynuclear coordination complexes of Cobalt(III), Cobalt(II), and mixed-valence Co^IICo^III: [Co₂^III(H₂L⁻¹)₂(AP⁻¹)(N₃)](ClO₄)₂ (1), [Co₄(H₂L⁻¹)₂(µ₃-1,1,1-N₃)₂(µ-1,1-N₃)₂Cl₂(CH₃OH)₂]·4CH₃OH (2), [Co₂^IICo₂^III(HL⁻²)₂(µ-CH₃CO₂)₂(µ₃-OH)₂](NO₃)₂·2CH₃CH₂OH (3), and [Co₂^IICo₂^III (H₂L1²⁻)₂(THMAM⁻¹)₂](NO₃)₄ (4). In 1, two cobalt(III) ions are connected via three single atom bridges; two from deprotonated ethanolic oxygen atoms in the side arms of the ligands and one from the1-amino-2-propanol moiety forming a dinuclear unit with a very short (2.5430(11) Å) Co-Co intermetallic separation with a coordination number of 7, a rare feature for cobalt(III). In 2, two cobalt(II) ions in a dinuclear unit are bridged through phenoxide O and μ₃-1,1,1-N₃ azido bridges, and the two dinuclear units are interconnected by two μ-1,1-N₃ and two μ₃-1,1,1-N₃ azido bridges generating tetranuclear cationic [Co₄(H₂L⁻¹)₂(µ₃-1,1,1-N₃)₂(µ-1,1-N₃)₂Cl₂(CH₃OH)₂]²⁺ units with an incomplete double cubane core, which grow into polynuclear 1D-single chains along the a-axis through H-bonding. In 3, HL²⁻ holds mixed-valent Co(II)/Co(III) ions in a dinuclear unit bridged via phenoxide O, μ-1,3-CH₃CO₂⁻, and μ₃-OH⁻ bridges, and the dinuclear units are interconnected through two deprotonated ethanolic O in the side arms of the ligands and two μ₃-OH⁻ bridges generating cationic tetranuclear [Co₂^IICo₂^III(HL⁻²)₂(µ-CH₃CO₂)₂(µ_3-OH)₂]²⁺ units with an incomplete double cubane core. In 4, H₂L1⁻² holds mixed-valent Co(II)/Co(III) ions in dinuclear units which dimerize through two ethanolic O (μ-RO⁻) in the side arms of the ligands and two ethanolic O (μ₃-RO⁻) of THMAM bridges producing centrosymmetric cationic tetranuclear [Co₂^IICo₂^III (H₂L1⁻²)₂(THMAM⁻¹)₂]⁴⁺ units which grow into 2D-sheets along the bc-axis through a network of H-bonding. Bulk magnetization measurements on 2 demonstrate that the magnetic interactions are completely dominated by an overall ferromagnetic coupling occurring between Co(II) ions.     

Post-subarachnoid Hemorrhage Vasospasm in Patients with Primary Headache Disorders

Background

Altered cerebral vasomotor reactivity leading to vasospasm can be seen both in patients with primary headache disorders (PHD) and in patients with subarachnoid hemorrhage (SAH). The pathogenesis of vasospasm in post-SAH patients and in headache disorder sufferers may be related. To address this hypothesis, we analyzed a large cohort of SAH patients to determine whether a diagnosis of PHD predisposes to vasospasm, delayed cerebral ischemia, or worsened clinical outcome.

Methods

Prospectively collected data from patients enrolled in the SAH Outcomes Project between 1996 and 2006 were analyzed. Patients were segregated based on whether they had a diagnosis of PHD or not and were subsequently compared for differences in clinical and radiographic outcome.

Results

A total of 921 SAH patients were analyzed, 265 of which had a diagnosis of PHD. In total, symptomatic vasospasm was seen in 17 %, while angiographic vasospasm was seen in 28 %. Vasospasm rates were similar among patients with a PHD and in those without a PHD (p > 0.05). However, on multivariate analysis new ischemic infarcts were more common in patients with a PHD as compared to patients without a PHD (p = 0.015). Functional outcomes at 3 months were similar among PHD and non-PHD patients (p > 0.05).

Conclusion

A history of PHD is associated with an increased rate of ischemic infarcts during admission for SAH. Increased rates of vasospasm within small cerebral blood vessels may be implicated. Further studies are warranted to more closely link the mechanisms of vasospasm in PHD and SAH patients.     

Withdrawal of Technological Life Support Following Subarachnoid Hemorrhage

Background

Prognostication of mortality or severe disability often prompts withdrawal of technological life support in patients following aneurysmal subarachnoid hemorrhage (aSAH). We assessed admission factors impacting decisions to withdraw treatment after aSAH.

Methods

Prospectively collected data of aSAH patients admitted to our institution between 1991 and 2009 were reviewed. Patients given comfort care measures were identified, including early withdrawal of treatment (<72 h after admission). Independent predictors of treatment withdrawal were assessed with multivariable analysis.

Results

The study included 1,134 patients, of whom 72 % were female, 58 % white, and 38 % black or African-American. Mean age was 52.5 ± 14.0 years. In-hospital mortality was 18.3 %. Of the 207 patients who died, treatment was withdrawn in 72 (35 %) and comfort measures instituted early in 31 (15 %). Among patients who died, WOLST was associated with older age (63.6 ± 14.2 years, WOLST vs. 55.6 ± 13.7 years, no WOLST, p < 0.001); GCS score <8 (62 % of WOLST vs. 44 % with no WOLST, p = 0.010); HH >3 (72 % of WOLST vs. 53 % with no WOLST, p = 0.008); and hydrocephalus (81 % of WOLST vs. 63 % with no WOLST, p = 0.009). Independent predictors of WOLST were poorer Hunt and Hess grade (AOR 1.520, 95 % CI 1.160–1.992, p = 0.002) and older age (AOR 1.045, 95 % CI 1.022–1.068, p < 0.001) with the latter also impacting early WOLST decisions.

Conclusions

Older age and poor clinical grade on presentation predicted WOLST, and age predicted decisions to withdraw treatment earlier following aSAH. While based on prognosis, and in some cases patient wishes, this may also constitute a self-fulfilling prophecy in others.