Association between Vitamin D Deficiency and Prognosis after Hip Fracture Surgery in Older Patients in a Dedicated Orthogeriatric Care Pathway.

OBJECTIVES: Vitamin D deficiency is common in patients undergoing hip fracture surgery (HFS) and has been found to be associated with poor post-operative outcome in other settings. This study aimed to analyze the association between vitamin D status and prognosis after HFS. DESIGN: Observational, prospective, single-center study. SETTING AND PARTICIPANTS: All patients admitted in a peri-operative geriatric unit between 2009 and 2020 for HFS were included. MEASUREMENTS: A moderate vitamin D deficiency was defined by a vitamin D level between 25 and 75 nmol/l and a severe deficiency by a vitamin D level <25 nmol/l. Primary endpoint was mortality 6 months after surgery. Secondary endpoints were bacterial infections and delirium during hospitalization. Odds ratio (OR) and 95% confidence interval (95%CI) were computed using logistic regression models with adjustment for confounders. RESULTS: 1197 patients were included (median age 87 years, IQR [82-91]). Median vitamin D level was 55 nmol/l (IQR [30-75 nmol/l]). Moderate and severe vitamin D deficiencies were reported in 53% and 21% of patients, respectively. There was no significant association between moderate or severe vitamin D deficiencies and 6-month mortality (OR 0.91, 95%CI [0.59-1.39], and OR 1.31, 95%CI [0.77-2.22], respectively), bacterial infection (OR 0.89, 95%CI [0.60-1.31] and OR 1.55, 95%CI [0.99-2.41], respectively), nor delirium (OR 1.03, 95%CI [0.75-1.40], and OR 1.05, 95%CI [0.70-1.57], respectively). CONCLUSION: Vitamin D deficiency was not associated with mortality, bacterial infection or delirium after HFS. Our results suggest that comorbidities, functional status and post-operative complications are the main determinants of post-operative outcome after HFS.

Scurvy in hospitalized elderly patients.

OBJECTIVES: The aim of this study was to systematically screen hospitalized elderly patients for clinical symptoms of scurvy and to confirm the diagnosis with biological measures. SETTINGS: Geriatric acute care ward. MEASUREMENTS: Scurvy symptoms (one or more among perifollicular hyperkeratosis, petechiae or bruises, haemorrhagic features caused by venous puncture, severe gingivitis). We compared associated diseases, nutritional status, need for assistance for feeding, serum albumin, transthyretin, B9 and B12 vitamins, iron status and Serum Ascorbic Acid Level (SAAL) and outcome (in-hospital mortality) between scurvy and scurvy free patients. RESULTS: 18 patients with clinical symptoms of scurvy (scurvy group) were identified out of 145 consecutive patients (12%). They were compared to 23 consecutive control patients with no clinical symptoms of scurvy (scurvy-free group). SAAL was significantly lower (1.09 +/- 1.06 vs 4.87 +/- 4.2 mg x L-1, p < .001) and vitamin C deficiency more frequent (94 vs 30 %, p < .001) in the scurvy group. Moreover, in scurvy group, coronary heart disease (39 vs 9 %, p=.028), need for assistance for feeding (56 vs 13 %, p=.006) and in-hospital deaths (44 vs 9 %, p=.012) were more frequent. CONCLUSION: Ninety-four percent of patients with clinical symptoms of scurvy had vitamin C deficiency. Our results suggest that in hospitalized elderly patients, clinical symptoms allow scurvy diagnosis. Scurvy could be a frequent disease in elderly patients admitted to acute geriatric ward.

[Medical comorbidity in Alzheimer's disease: baseline characteristics of the REAL.FR Cohort]. / Comorbidités et maladie d'Alzheimer: données à l'inclusion de la cohorte gériatrique REAL.FR.

PURPOSE: Alzheimer's disease (AD) evolves over about ten years with cognitive decline that can be considered as linear. Comorbidities are frequent in geriatric population. The major objective of this study is to determine whether comorbidity influences natural history of AD. MATERIALS AND METHODS: This is a prospective, multicentric French study (REAL.FR) of a cohort of ambulatory patients suffering from AD from a mild to a moderately severe stage, with a Mini-Mental State between 10 and 26, and followed with a caregiver. We evaluated the comorbidities and they were quantified using the Charlson index. RESULTS: We analysed 579 AD patients enrolled between April 2000 and June 2002. Majority of patients were women (72%). Average age and MMS average score were respectively 77.4 +/- 7.1 and 20.1 +/- 4.5. Cardiovascular diseases were the most frequent comorbid conditions (34%), before sensorial handicap (23%), and neurological diseases (18%) apart from dementia. Four AD patients groups differed according to the comorbidities figures, from none to more than three (maximum 8). Average Charlson index was 1.5 +/- 0.9. CONCLUSION: The follow-up of the four AD patients groups, differentiated by the comorbidities figures, should allow to precise the influence of comorbidities on the AD evolution. Charlson index could be used to quantify the comorbidities in the cohort's follow-up. However, this index, validated in a cohort of cancer patients, show limits for its use in geriatric population.

[Recent neuropathology of parkinsonian syndromes]. / Données récentes sur la neuropathologie des syndromes parkinsoniens.

The understanding of the molecular mechanisms underlying Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy has made significant progress in the recent years. Lewy body appears to be principally made of alpha-synuclein, a presynaptic protein. It also contains ubiquitin and some components of the proteasome: this suggests that alteration of protein catabolism may be involved in its formation. In favor of this hypothesis, it should be noted that Parkin, a protein that is mutated in autosomal recessive Parkinson disease, is a ubiquitin ligase. Immunohistochemistry has shown that alpha-synuclein accumulates not only in the cell body of the neurones (Lewy body) but also in their processes (Lewy neurites); it has emphasized the severity of the pathology in the nucleus basalis of Meynert, amygdala, CA2-3 sector of the hippocampus and cerebral cortex. Cortical Lewy bodies are not considered any more the marker of dementia with Lewy bodies: they are, indeed, found in true Parkinson disease cases. In progressive supranuclear palsy, 4 repeats tau accumulates in the cytoplasm of neurones and glia. At electron microscopy, the accumulation is made of straight filaments. It involves not only the neurones (where it is the main constituent of the neurofibrillary tangles) but also the glia. Astrocytic tuft is to day considered the morphological marker of progressive supranuclear palsy. Tau protein accumulates in the cell body of the oligodendrocyte as a "coiled body"; the protein is also integrated in the myelin sheath, when the cytoplasm of the oligodendrocyte wraps around the axon. This explains the numerous "threads" that are visible in cases of progressive supranuclear palsy. Striato-nigral degeneration, sporadic olivo-ponto-cerebellar atrophy and primitive orthostatic hypotension are various clinico-pathologic aspects of the same disorder: multiple system atrophy. It is also characterized by a morphological marker: the accumulation of alpha-synuclein in the cytoplasm of glial cells, particularly oligodendrocytes. The term synucleinopathy has been proposed to describe both idiopathic Parkinson disease and multiple system atrophy. The reason explaining the cellular topography of alpha-synuclein accumulation, neuronal in Parkinson disease, glial in multiple system atrophy is still unknown.

[Myasthenia in the aged: a case with unusually late onset]. / Myasthénie du sujet âgé. Un cas de révélation particulièrement tardive.

BACKGROUND: Myasthenia is an uncommon autoimmune condition that can occur at any age. Peak frequency is seen around the age of 65 years. We report a case with a particularly late onset and discuss the particular conditions of myasthenia in the elderly subject. CASE REPORT: A 97-year-old patient was hospitalized for dysphonia and dysphagia associated with exercise-induced dyspnea. The general picture suggested generalized myasthenia confirmed by the electromyography exploration and a positive anticholinesterase test. Treatment with acetylcholinesterase inhibitor was effective although cure was incomplete. Further improvement was obtained with immunosuppressor therapy using azathioprine. DISCUSSION: The clinical presentation of very late onset myasthenia differs little from that in younger subjects excepting the very high frequency of brain stem involvement in the initial presentation. Diagnosis may however be more difficult as other conditions are more easily taken to be the causal element. Thus, for the elderly patient, the real problem is to envisage the diagnosis of myasthenia. Positive diagnosis is based on the same criteria as in younger subjects. Clinicians should be aware of the possibility of myasthenia in the geriatric population as specific treatment can improve functional prognosis with satisfactory efficacy.

[Pauci-symptomatic sensory polyneuropathy in Refsum's disease]. / Polyneuropathie sensitive pauci-symptomatique au cours d'une maladie de Refsum.

Refsum's disease is an autosomal recessive disease caused by defective alpha-oxidation of phytanic acid. The usual clinical presentation is the association of retinitis pigmentosa, ataxia and chronic severe sensorimotor polyneuropathy. A case of mild purely sensory neuropathy in a 40-year-old patient associated to high CSF protein level led to the diagnosis of Refsum's disease. The paucity of sensory symptoms and signs of neuropathy contrasted with severe reduction of motor and sensory nerve conduction velocities and markedly signs of sensory neuropathy observed in the nerve biopsy. Typical ring-scotomas, retinitis pigmentosa, anosmia, deafness, and high plasma phytanic acid level were present in extensive examination. There was no other case in the family.

Leuko-araiosis.

Leuko-araiosis is an unspecific radiologic sign, seen with CT scan or with MRI. It can be found as well in normal elderly persons as in pathological conditions. For the sake of clarity, CT scan and MRI images have to be distinguished. CT leuko-araiosis is linked with vascular risk factors and with age. The situation is more complex for MRI leuko-araiosis (likely on account of the higher sensitivity of MRI). Some images (caps and rims), frequently seen in normal, even young, individuals, are more frequent in aging. On the contrary, abnormal images at a distance from the ventricle are more difficult to interpret. Some of them are due to pathological well defined conditions (small infarcts, Binswanger's disease, cysts, plaques). Others may be secondary to remote pathologies (such as infarcts). Others are due to little specific conditions, such as perivascular dilatations ('état criblé' due to brain vasogenic edema, or to brain atrophy whatever its cause, and more frequently seen in the elderly). Other changes, such as incomplete infarction or myelin pallor with gliosis, have been described. At last, in some cases, no clearcut pathological lesion could be found. Leuko-araiosis may be present in primary degenerative dementia of the Alzheimer type, but it is neither necessary nor sufficient to establish the diagnosis of Alzheimer's disease, and it does not seem more frequent than in elderly controls. The mechanism of leuko-araiosis in Alzheimer's disease is likely multifactorial (for example, cerebral atrophy, amyloid angiopathy, associated hypertensive arteriolosclerosis could be involved). The relationship between leuko-araiosis, myelin pallor and white matter atrophy is poorly understood, and remains to be studied.

Disposition and metabolism of letosteine in rats.

The metabolism and disposition of letosteine, labeled either with 14C or 35S, has been investigated in Sprague-Dawley rats. In separate experiments, rats received 20 mg/kg, iv or orally, [14C]letosteine or [35S]letosteine. Radioactivity was rapidly excreted, mainly in urine, after iv and oral administration. Recovery of radioactivity from 0-72-hr excreta averaged 95% after both routes of [14C]letosteine administration, whereas only 50% was recovered when [35S]letosteine was administered. 14CO2 accounted for about 7.3% (iv) and 5.1% (po) of the dose of [14C]letosteine. Comparison of the iv and oral areas under the plasma 14C radioactivity concentration-time curves suggested that oral absorption of letosteine was complete. Analysis of the radioactivity content of urine showed that letosteine undergoes rapid and extensive metabolism. Several metabolites were identified by TLC, HPLC, and MS. The findings are consistent with a splitting of the ester group of letosteine and subsequent cleavage of the thiazolidinyl ring, yielding cysteine, hypotaurine, taurine, and inorganic sulfate. The metabolite derived from the side chain was identified in the urine as 3-(hydroxycarbonylmethylthio)propanoic acid. It undergoes further oxidation into sulfoxide and sulfone derivatives, which are also present in the urine.