Hospital volume following major surgery for gastric cancer determines in-hospital mortality rate and failure to rescue: a nation-wide study based on German billing data (2009-2017).

BACKGROUND: For many cancer resections, a hospital volume-outcome relationship exists. The data regarding gastric cancer resection-especially in the western hemisphere-are ambiguous. This study analyzes the impact of gastric cancer surgery caseload per hospital on postoperative mortality and failure to rescue in Germany. METHODS: All patients diagnosed with gastric cancer from 2009 to 2017 who underwent gastric resection were identified from nation-wide administrative data. Hospitals were grouped into five equal caseload quintiles (I-V in ascending caseload order). Postoperative deaths and failure to rescue were determined. RESULTS: Forty-six thousand one hundred eighty-seven patients were identified. There was a significant shift from partial resections in low-volume hospitals to more extended resections in high-volume centers. The overall in-house mortality rate was 6.2%. The crude in-hospital mortality rate ranged from 7.9% in quintile I to 4.4% in quintile V, with a significant trend between volume categories (p < 0.001). In the multivariable logistic regression analysis, quintile V hospitals (average of 29 interventions/year) had a risk-adjusted odds ratio of 0.50 (95% CI 0.39-0.65), compared to the baseline in-house mortality rate in quintile I (on average 1.5 interventions/year) (p < 0.001). In an analysis only evaluating hospitals with more than 30 resections per year mortality dropped below 4%. The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue (FtR) decreased significantly with increasing caseload. CONCLUSION: Patients who had gastric cancer surgery in hospitals with higher volume had better outcomes and a reduced failure to rescue rates for severe complications.

The association of children's mathematic abilities with both adults' cognitive abilities and intrinsic fronto-parietal networks is altered in preterm-born individuals.

Mathematic abilities in childhood are highly predictive for long-term neurocognitive outcomes. Preterm-born individuals have an increased risk for both persistent cognitive impairments and long-term changes in macroscopic brain organization. We hypothesized that the association of childhood mathematic abilities with both adulthood general cognitive abilities and associated fronto-parietal intrinsic networks is altered after preterm delivery. 72 preterm- and 71 term-born individuals underwent standardized mathematic and IQ testing at 8 years and resting-state fMRI and full-scale IQ testing at 26 years of age. Outcome measure for intrinsic networks was intrinsic functional connectivity (iFC). Controlling for IQ at age eight, mathematic abilities in childhood were significantly stronger positively associated with adults' IQ in preterm compared with term-born individuals. In preterm-born individuals, the association of children's mathematic abilities and adults' fronto-parietal iFC was altered. Likewise, fronto-parietal iFC was distinctively linked with preterm- and term-born adults' IQ. Results provide evidence that preterm birth alters the link of mathematic abilities in childhood and general cognitive abilities and fronto-parietal intrinsic networks in adulthood. Data suggest a distinct functional role of intrinsic fronto-parietal networks for preterm individuals with respect to mathematic abilities and that these networks together with associated children's mathematic abilities may represent potential neurocognitive targets for early intervention.

How to use the medical subject headings (MeSH).

BACKGROUND: A thorough understanding of the National Library of Medicine's Medical Subject Headings can increase the efficiency and precision of one's literature searching skills using the Medline database. AIMS: To describe how to use the Medical Subject Headings to conduct a search for literature, and how to write up a description of the search strategy. MATERIALS AND METHODS: The author interprets National Library of Medicine documentation to describe Medical Subject Headings, and shares strategies from daily literature searching. CONCLUSION: Knowing how to use Medical Subject Headings improves the efficiency and quality of one's literature searches.

Extensive and interrelated subcortical white and gray matter alterations in preterm-born adults.

Preterm birth is a leading cause for impaired neurocognitive development with an increased risk for persistent cognitive deficits in adulthood. In newborns, preterm birth is associated with interrelated white matter (WM) alterations and deep gray matter (GM) loss; however, little is known about the persistence and relevance of these subcortical brain changes. We tested the hypothesis that the pattern of correspondent subcortical WM and GM changes is present in preterm-born adults and has a brain-injury-like nature, i.e., it predicts lowered general cognitive performance. Eighty-five preterm-born and 69 matched term-born adults were assessed by diffusion- and T1-weighted MRI and cognitive testing. Main outcome measures were fractional anisotropy of water diffusion for WM property, GM volume for GM property, and full-scale IQ for cognitive performance. In preterm-born adults, reduced fractional anisotropy was widely distributed ranging from cerebellum to brainstem to hemispheres. GM volume was reduced in the thalamus, striatum, temporal cortices, and increased in the cingulate cortices. Fractional anisotropy reductions were specifically associated with GM loss in thalamus and striatum, with correlation patterns for both regions extensively overlapping in the WM of brainstem and hemispheres. For overlap regions, fractional anisotropy was positively related with both gestational age and full-scale IQ. Results provide evidence for extensive, interrelated, and adverse WM and GM subcortical changes in preterm-born adults. Data suggest persistent brain-injury-like changes of subcortical-cortical connectivity after preterm delivery.

Aseptic meningitis and ischaemic stroke in Fabry disease.

BACKGROUND: Fabry disease (OMIM 301 500) is an X-linked lysosomal storage disease. Neurological symptoms in Fabry disease mainly include stroke, acroparesthesia, cranial nerve palsies and autonomic dysfunction. We report on aseptic meningitis in Fabry patients. METHODS: Clinical analysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, treatment and outcome data were analysed in three cases of meningitis associated with Fabry disease. FINDINGS: Mean age at meningitis onset was 26.6 (24-28) years. Headache was present in all cases and fever in two cases. Meningitis was always diagnosed before Fabry disease. A familial history of Fabry disease was present in two cases. Non-neurological symptoms caused by Fabry disease were present in all cases. All patients also suffered stroke and sensorineural hearing loss. Cerebrospinal fluid (CSF) analysis showed pleocytosis (mean, 36; range: 8-76 cells/mm(3)) and a high protein level (mean, 63; range, 47-70 mg/dl). C-reactive protein blood levels and erythrocyte sedimentation rate were raised. Diagnosis was assessed by low alpha-galactosidase A dosage and/or gene mutation analysis in all cases. All patients were treated with enzyme replacement therapy (ERT). In two cases, lumbar puncture was repeatedly performed and there was no normalisation of CSF under ERT alone, at 9 and 24 months of follow-up, respectively. One patient who suffered intracranial hypertension was treated efficiently with steroids, associated with azathioprine. The fact that Fabry disease could be an auto-inflammatory disorder is discussed. INTERPRETATION: Fabry disease may cause aseptic meningitis.

Leukoencephalopathies associated with inborn errors of metabolism in adults.

The discovery of a leukoencephalopathy is a frequent situation in neurological practice and the diagnostic approach is often difficult given the numerous possible aetiologies, which include multiple acquired causes and genetic diseases including inborn errors of metabolism (IEMs). It is now clear that IEMs can have their clinical onset from early infancy until late adulthood. These diseases are particularly important to recognize because specific treatments often exist. In this review, illustrated by personal observations, we give an overview of late-onset leukoencephalopathies caused by IEMs.

[Neurological presentations of lysosomal diseases in adult patients]. / Présentations neurologiques des maladies lysosomales chez l'adulte.

Lysosomal diseases represent a large group of genetic storage disorders characterized by a defect in the catabolism of complex molecules within the lysosome. Effective treatments are now possible for some of them given progresses in bone-marrow transplantation, enzyme replacement therapy and substrate reduction therapy. Neurologists and psychiatrists are concerned by these diseases because they can present in adolescence or adulthood with progressive neuropsychiatric signs. Here we focus on late-onset clinical forms which can be met in an adult neurology or psychiatric department. Lysosomal diseases were classified into 3 groups: (1) leukodystrophies (metachromatic leukodystrophy, Krabbe's disease and Salla's disease); (2) Neurodegenerative or psychiatric-like diseases (GM1 and GM2 gangliosidoses, Niemann Pick type C disease, sialidosis type I, ceroid-lipofuscinosis, mucopolysaccharidosis type III); (3) multisystemic diseases (Gaucher's disease, Fabry's disease, alpha and B mannosidosis, Niemann Pick disease type B, fucosidosis, Schindler/Kanzaki disease, and mucopolysaccharidosis type I and II. We propose a diagnostic approach guided by clinical examination, brain MRI, electrodiagnostic studies and abdominal echography.

Psychiatric manifestations revealing inborn errors of metabolism in adolescents and adults.

Inborn errors of metabolism (IEMs) may present in adolescence or adulthood as a psychiatric disorder. In some instances, an IEM is suspected because of informative family history or because psychiatric symptoms form part of a more diffuse clinical picture with systemic, cognitive or motor neurological signs. However, in some cases, psychiatric signs may be apparently isolated. We propose a schematic classification of IEMs into three groups according to the type of psychiatric signs at onset. Group 1 represents emergencies, in which disorders can present with acute and recurrent attacks of confusion, sometimes misdiagnosed as acute psychosis. Diseases in this group include urea cycle defects, homocysteine remethylation defects and porphyrias. Group 2 includes diseases with chronic psychiatric symptoms arising in adolescence or adulthood. Catatonia, visual hallucinations, and aggravation with treatments are often observed. This group includes homocystinurias, Wilson disease, adrenoleukodystrophy and some lysosomal disorders. Group 3 is characterized by mild mental retardation and late-onset behavioural or personality changes. This includes homocystinurias, cerebrotendinous xanthomatosis, nonketotic hyperglycinaemia, monoamine oxidase A deficiency, succinic semialdehyde dehydrogenase deficiency, creatine transporter deficiency, and alpha and beta mannosidosis. Because specific treatments should be more effective at the 'psychiatric stage' before the occurrence of irreversible neurological lesions, clinicians should be aware of atypical psychiatric symptoms or subtle organic signs that are suggestive of an IEM. Here we present an overview of IEMs potentially revealed by psychiatric problems in adolescence or adulthood and provide a diagnostic strategy to guide metabolic investigations.

[Neurological manifestations of type 1 Gaucher's disease: Is a revision of disease classification needed?]. / Les manifestations neurologiques de la maladie de Gaucher de type 1: vers une remise en cause de la classification actuelle?

INTRODUCTION: Gaucher's disease (GD), the most prevalent inherited lysosomal storage disorder, is caused by deficient glucocerebrosidase activity. The resulting accumulation of glucocerebrosides in lysosomes of macrophages leads to hepatosplenomegaly, anemia, thrombocytopenia, and various bone manifestations. Gaucher's disease is classified into 3 types based on the nature of its effects on the central nervous system. Type 1, the most common variant, is classically nonneuronopathic. However, the occurrence of Parkinsonism seems to be more frequent in type I Gaucher's disease than in the general population. Furthermore, heterozygotes for certain glucocerebrosidase gene mutations have a higher risk to develop Parkinson's disease. OBSERVATIONS: We report our experience about 9 patients with Gaucher's disease and their association with neurological manifestations. CONCLUSION: These recent data may discuss Gaucher's classification and the existence of a continuum between neurologic and non-neurologic forms of the disease.

Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype.

BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed the clinical course of 22 patients homozygous for mutation P426L vs 20 patients heterozygous for mutation I179S, in which the second arylsulfatase A (ASA) mutation had also been determined. RESULTS: P426L homozygotes principally presented with progressive gait disturbance caused by spastic paraparesis or cerebellar ataxia; mental disturbance was absent or insignificant at the onset of disease but became more apparent as the disease evolved. In contrast, compound heterozygotes for I179S presented with schizophrenia-like behavioral abnormalities, social dysfunction, and mental decline, but motor deficits were scarce. Reduced peripheral nerve conduction velocities and less residual ASA activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION: The characteristic clinical differences between homozygous P426L and compound heterozygous I179S patients establish a distinct genotype-phenotype correlation in late-onset metachromatic leukodystrophy.

Sterol trafficking between the endoplasmic reticulum and plasma membrane in yeast.

We recently showed that transport of ergosterol from the ER (endoplasmic reticulum) to the sterol-enriched PM (plasma membrane) in yeast occurs by a non-vesicular (Sec18p-independent) mechanism that results in the equilibration of sterol pools in the two organelles [Baumann, Sullivan, Ohvo-Rekilä, Simonot, Pottekat, Klaassen, Beh and Menon (2005) Biochemistry 44, 5816-5826]. To explore how this occurs, we tested the role of proteins that might act as sterol transporters. We chose to study oxysterol-binding protein homologues (Osh proteins), a family of seven proteins in yeast, all of which contain a putative sterol-binding pocket. Recent structural analyses of one of the Osh proteins [Im, Raychaudhuri, Prinz and Hurley (2005) Nature (London) 437, 154-158] suggested a possible transport cycle in which Osh proteins could act to equilibrate ER and PM pools of sterol. Our results indicate that the transport of newly synthesized ergosterol from the ER to the PM in an OSH deletion mutant lacking all seven Osh proteins is slowed only 5-fold relative to the isogenic wild-type strain. Our results suggest that the Osh proteins are not sterol transporters themselves, but affect sterol transport in vivo indirectly by affecting the ability of the PM to sequester sterols.

[Adult onset hereditary leukoencephalopathies]. / Leucoencéphalopathies génétiques de l'adulte.

In clinical practice, the term "genetic leukoencephalopathy" refers to a group of genetic diseases whose common point is to give an aspect of diffuse leukoencephalopathy on MRI. With progress in diagnostic techniques including radiology, biochemistry or genetics, a large number of hereditary diseases causing leukoencephalopathy have been identified. Although generally beginning in childhood, these diseases often have more insidious clinical forms which can begin in adulthood. These forms remain poorly known. Some are accessible to treatment so their diagnosis appears essential. The diagnostic steps must be guided by clinical examination (neurological, ophthalmological and systemic), electromyography and MRI. The purpose of this review is to propose a classification of the genetic leukoencephalopathies and to give a progress report applicable in neurological practice.

[Temporary working disability among younger patients with back pain and its interaction with severity of pain, functional capacity, social factors and personality styles]. / Arbeitsunfähigkeit bei jüngeren Dorsopathie-Patienten und ihre Wechselwirkung mit Schmerzen, Funktionskapazität, sozialen Faktoren und Persönlichkeitsstilen.

The relationships between sick absenteeism and clinical measures were studied for a group of younger patients with chronic back pain (mean years of age for women and men were 41.7 and 42.2, respectively) who were sent to a rehabilitation programme. The duration of sick absenteeism during the last year as well as the momentary status of working ability were correlated with different clinical variables and personality styles. At the beginning of the rehabilitation program, the measure of functional capacity (FFbH-R, Kohlmann u. Raspe, 1996) showed the strongest correlation with temporary working disability (r = -.46) and duration of sick absenteeism during the last year (r = -.44). The severity of pain showed a lower but significant correlation with temporary working disability (r =.24) and duration of sick absenteeism (r =.25). In contrast, depression, vitality and age did not show significant correlations with temporary working disability at the beginning of the rehabilitation. In addition, some of the personality styles from the PSSI (Kuhl u. Kazén, 1997) showed significant correlations with temporary working disability and duration of sick absenteeism. When entering the variables into regression analyses, the measure of functional capacity was the most important predictor of sick absenteeism. Severity of pain, depression, vitality and age did not significantly add to the variance accounted for. In contrast, distinct personality styles from the PSSI significantly contributed to an additional proportion of variance in sick absenteeism and temporary working disability. At the end of the rehabilitation program, there were stable relationships between temporary working disability and functional capacity (r = -.45) as well as severity of pain (r =.39). In, correlations between temporary working disability and depression (r =.30) and vitality (r = -.19) were significant. This was due to the stronger improvement during therapy among patients who were able to work compared to patients who were not.

[Presenting psychiatric and cognitive disorders in adult neurolipidoses]. / Manifestations psychiatriques ou cognitives inaugurales dans les neurolipidoses de l'adulte.

Neurolipidoses may present as psychiatric illness or dementia which may be isolated for a long time without neurological manifestations. Thus the relation with a metabolic disease may be difficult to establish. In this survey, we wish to present our clinical and biological experience in relation with lysosomal or peroxisomal disorders giving rise to neurolipidoses, a review of the literature, as well as the elements which allow to present a diagnostic strategy. We report mainly on metachromatic leukodystrophy, GM2 gangliosidosis, Fabry's disease, Niemann-Pick type C, Kufs disease, adrenoleukodystrophy, cerebro-tendinous xanthomatosis. Psychiatric symptoms may overshadow subtle signs of cognitive and motor dysfunction. Careful and persistent neurodiagnostic evaluation must be performed even in cases when CT and MRI scans are considered normal. Resistance to psychotropic drugs may be an element of orientation. The biological diagnosis is mainly biochemical. Although most of the genes involved have been cloned, many of the mutations are private, except for metachromatic leukodystrophy for which specific mutations may be related to adult cases and either with predominantly motor or predominantly cognitive and psychiatric manifestations. This review discusses also other metabolic diseases which may present as isolated or predominant cognitive and psychiatric manifestations.

Extracellular ATP activates a P2 receptor in necturus erythrocytes during hypotonic swelling.

We recently reported that ATP is released from Necturus erythrocytes via a conductive pathway during hypotonic swelling and that extracellular ATP potentiates regulatory volume decrease (RVD). This study was designed to determine whether extracellular ATP exerts its effect via a purinoceptor. This was accomplished using three different experimental approaches: 1) hemolysis studies to examine osmotic fragility, 2) a Coulter counter to assess RVD, and 3) the whole-cell patch-clamp technique to measure membrane currents. We found extracellular ATP and ATPgammaS, two P2 agonists, decreased osmotic fragility, enhanced cell volume recovery in response to hypotonic shock, and increased whole-cell currents. In addition, 2-methylthio-ATP potentiated RVD. In contrast, UTP, alpha,beta-methylene-ATP, and 2'-& 3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate and the P1 agonist adenosine had no effect regardless of experimental approach. Furthermore, the P2 antagonist suramin increased osmotic fragility, inhibited RVD, and reduced whole-cell conductance in swollen cells. Consistent with a previous study that indicated cell swelling activates a K+ conductance, suramin had no effect in the presence of gramicidin (a cationophore used to maintain a high K+ permeability). We also found the P2 antagonist pyridoxal-5-phosphate-6-azophenyl-2'4-disulfonic acid (PPADS) increased osmotic fragility; however, reactive blue 2 and the P1 antagonists caffeine and theophylline had no effect. Our results show that extracellular ATP activated a P2 receptor in Necturus erythrocytes during hypotonic swelling, which in turn potentiated RVD by stimulating K+ efflux. Pharmacological evidence suggested the presence of a P2X receptor subtype.

Biology of oligodendrocyte and myelin in the mammalian central nervous system.

Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the proteolipid protein, which lead to dysmyelinating diseases in animals and human (jimpy mutation and Pelizaeus-Merzbacher disease or spastic paraplegia, respectively). Oligodendrocytes, as astrocytes, are able to respond to changes in the cellular and extracellular environment, possibly in relation to a glial network. There is also a remarkable plasticity of the oligodendrocyte lineage, even in the adult with a certain potentiality for myelin repair after experimental demyelination or human diseases.

Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study.

We conducted a double-blind, placebo-controlled, study of 19 patients fulfilling eligibility criteria for multifocal motor neuropathy with persistent conduction block. They were enrolled and divided into two groups: those who had never been treated previously with intravenous immunoglobulins (IVIg) (Group 1: 10 patients) and those who presented recurrent symptoms after previously successful treatment with IVIg (Group 2: nine patients). They were randomized prospectively to receive either IVIg or placebo at a dose of 500 mg/kg/day for 5 consecutive days, once a month for 3 months. At month 4, patients found to be responders remained on the same treatment for the 3 following months, while non-responders were switched to the alternative study drug for the 3 following months. Clinical assessment was conducted with the MRC score in 28 muscles and a self-evaluation scale (five daily motor activities scored from 0 to 5). In Group 1, nine patients completed the study, of whom initially four received IVIg and five placebo; four patients responded to IVIg (two at months 4 and 7, and a further two at month 7 after switching treatment at month 4), two patients responded to placebo at months 4 and 7, and three patients did not respond to either treatment. In Group 2, nine patients completed the study. Five patients first received IVIg and all responded at months 4 and 7. Four patients first received placebo and none responded at month 4; all were then switched to IVIg and three responded at month 7. When the 18 patients were considered together, seven out of the nine patients who received IVIg first were responders at month 4, compared with two of the nine patients who received placebo first, a difference that was statistically significant (P = 0.03). On the other hand, there was no significant difference in MRC score but a significant difference in the self-evaluation score, at month 4, between IVIg patients and placebo patients. Electrophysiological studies did not show significant differences at month 4 in motor parameters between IVIg patients and placebo patients. IgM anti-GM1 titres did not change significantly in patients treated with IVIg compared with those who received placebo, between baseline, month 4 and month 7. However, of five patients who had significantly high anti-GM1 titres (>3200) at baseline, four responded to IVIg. This trial confirms that IVIg is a promising therapeutic option for multifocal motor neuropathy.

Adult-onset leukodystrophies.

Leukodystrophies are genetic metabolic diseases which generally occur in early childhood at the time of myelination. Surprisingly, these diseases can also occur during adulthood. Adult forms have various clinical presentations which reflect degenerative diseases of the nervous system. The course may last for decades. This contribution describes the main features of adult leukodystrophies and indicates those for which a biochemical and molecular diagnosis are possible. Other articles deal with their differential diagnosis of leukoencephalopathies and with the diagnostic strategy.