[Parkinson's disease: intrinsically palliative care]. / La maladie de Parkinson, une prise en soins intrinsèquement palliative.

Multidimensional, chronic, progressive and incurable, Parkinson's disease is, by definition, a palliative disease, and this from the moment of diagnosis. This vision, relatively new to neurology, calls for a paradigm shift, as well as a dual medical-paramedical and home-hospital alliance. This approach allows us to better understand the specificities of Parkinson's disease and its treatments in terms of palliative issues.

Terminal Care in Parkinson's Disease: Real-Life Use of Continuous Subcutaneous Apomorphine Infusion to Improve Patient Comfort.

BACKGROUND: There are currently no recommendations on the therapeutic management of Parkinson's disease (PD) patients at the end of life. OBJECTIVE: To describe a cohort of patients with PD who benefited from continuous subcutaneous apomorphine infusion (CSAI) initiation at the end of their life as comfort care. METHODS: This real-life cohort includes 14 PD patients, who benefited from 24-h, low-dose CSAI (0.5-3 mg/h) in the context of terminal care. Patient's comfort (pain, rigidity, and/or ability to communicate) and occurrence of CSAI-related side-effects (nausea/vomiting, cutaneous and behavioral manifestations) were evaluated based on medical records. RESULTS: All patients (age 62-94 years, disease duration 2-32 years) presented with late-stage PD and a compromised oral route. Treatment lasted from a few hours to 39 days. CSAI led to substantial functional improvement, with a good safety profile. Overall clinical comfort was deemed improved by the medical team, the patient, and/or caregivers. CONCLUSIONS: CSAI might be a promising approach in PD terminal care, as it reduces motor symptoms and overall discomfort, with an apparent good safety profile. Use of the apomorphine pen, sublingual film or a classic syringe pump might be considered when apomorphine pumps are not available. Larger observational cohorts and randomized controlled trials are needed to establish the efficacy and tolerability of apomorphine in the context of terminal care and more broadly, in an advance care planning perspective.

Profiles of patients referred to specialized palliative care from the cardiology department at a university hospital: an 11-year longitudinal retrospective study.

BACKGROUND: Although the majority of patients with cardiovascular diseases (CVD) have a significant symptom burden and progressive course towards the end of life, only a small proportion of patients currently receive palliative care. The current referral practices to palliative care from the cardiology department need to be scrutinized. The current study aimed to examine: 1) the clinical profile; 2) time between referral to palliative care and death; and 3) place of death for CVD patients who were referred to palliative care from a cardiology department. METHODS: This retrospective descriptive study included all patients who were referred to the mobile palliative care team from the cardiology unit in the University Hospital of Besançon in France between January 2010 and December 2020. Information was extracted from the medical hospital files. RESULTS: A total of 142 patients were included, of whom 135 (95%) died. The mean age at the time of death was 76±14 years. The median time between referral to palliative care and death was 9 days. Most patients had chronic heart failure (54%). A total of 17 patients (13%) died at home. CONCLUSIONS: This study showed that referral of patients to palliative care from the cardiology department is suboptimal and a large proportion of patients die in the hospital setting. Further prospective studies are warranted to investigate whether these dispositions correspond to patients' wishes and end-of-life care needs, and should investigate how the integration of palliative care into the care of cardiovascular patients can be improved.

Compensated second-order recoupling: application to third spin assisted recoupling.

We consider the effect of phase shifts in the context of second-order recoupling techniques in solid-state NMR. Notably we highlight conditions leading to significant improvements for the Third Spin Assisted Recoupling (TSAR) mechanism and demonstrate the benefits of resulting techniques for detecting long-distance transfer in biomolecular systems. The modified pulse sequences of PAR and PAIN-CP, Phase-Shifted Proton Assisted Recoupling (AH-PS-PAR) and Phase-Shifted Proton-Assisted Insensitive Nuclei Cross Polarization (ABH-PS-PAIN-CP), still rely on cross terms between heteronuclear dipolar couplings involving assisting protons that mediate zero-quantum polarization transfer between low-γ nuclei ((13)C-(13)C, (15)N-(15)N, (15)N-(13)C polarization transfer). Using Average Hamiltonian Theory we show that phase inversion compensates off-resonance contributions and yields improved polarization transfer as well as substantial broadening of the matching conditions. PS-TSAR greatly improves on the standard TSAR based methods because it alleviates their sensitivity to precise RF settings which significantly enhances robustness of the experiments. We demonstrate these new methods on a 19.6 kDa protein (U-[(15)N, (13)C]-YajG) at high magnetic fields (up to 900 MHz (1)H frequency) and fast sample spinning (up to 65 kHz MAS frequency).

Dynamics characterization of fully hydrated bacterial cell walls by solid-state NMR: evidence for cooperative binding of metal ions.

The bacterial cell wall maintains a cell's integrity while allowing growth and division. It is made up of peptidoglycan (PG), a biopolymer forming a multigigadalton bag-like structure, and, additionally in gram-positive bacteria, of covalently linked anionic polymers collectively called teichoic acids. These anionic polymers are thought to play important roles in host-cell adhesion, inflammation, and immune activation. In this Article, we compare the flexibility and the organization of peptidoglycans from gram-negative bacteria (E. coli) with its counterpart from different gram-positive bacteria using solid-state nuclear magnetic resonance spectroscopy (NMR) under magic-angle sample spinning (MAS). The NMR fingerprints suggest an identical local conformation of the PG in all of these bacterial species. Dynamics in the peptidoglycan network decreases from E. coli to B. subtilis and from B. subtilis to S. aureus and correlates mainly with the degree of peptide cross-linkage. For intact bacterial cells and isolated cell walls, we show that (31)P solid-state NMR is particularly well adapted to characterize and differentiate wall teichoic acids of different species. We have further observed complexation with divalent ions, highlighting an important structural aspect of gram-positive cell wall architecture. We propose a new model for the interaction of divalent cations with both wall teichoic acids and carbonyl groups of peptidoglycan.

Impact of selective excitation on carbon longitudinal relaxation: Towards fast solid-state NMR techniques.

The effect of selective pulses on the apparent carbon longitudinal relaxation is investigated in three fully (13)C-labeled systems, histidine as a model system and two proteins MerP and YajG. It is shown that the longitudinal relaxation of a selectively excited carbon spin is greatly enhanced, mainly because of fast spin-diffusion. This relaxation enhancement allows reducing the time necessary for polarization recovery between two experiments. This effect can be exploited either to improve the sensitivity of NMR experiments or to reduce the experimental time. Using selective carbon excitation combined with fast pulsing on fully (13)C-labeled proteins, a sensitivity improvement of 20-45% over standard cross-polarization methods is predicted from the measured relaxation times.