Effect of statins on the clinical outcomes of patients with sepsis.

Despite numerous attempts at novel intervention and tests to aid in earlier diagnosis and improved treatment, there has been an increased incidence of overall mortality related to sepsis, despite improvements in in-hospital mortality. Statins have emerged as potential immunomodulatory and antioxidant agents that might impact on sepsis outcomes. Definitive evidence to support the routine use of statins in patients with sepsis has not yet been elicited. We retrospectively analysed data from patients who presented with sepsis, severe sepsis or septic shock, stratifiying them according to statin use into two groups (statin and no statin). Sequential Organ Failure Assessment was used to evaluate severity of illness. The primary outcome was hospital mortality. Secondary outcomes included intensive care unit (ICU) mortality, hospital and ICU length of stay, and mechanical ventilation and vasopressor therapy duration. Five hundred and sixty-eight patients were included. Patients with prior statin use (statin group) were older; more obese and had higher prevalence of smoking, diabetes and ischaemic heart disease. There was no difference in Sequential Organ Failure Assessment scores and mortality did not vary between the two groups (19.6 vs. 16.9%). Furthermore, secondary outcomes including ICU mortality, hospital and ICU length of stay, mechanical ventilation and vasopressor duration did not differ Multivariate analysis revealed age and Sequential Organ Failure Assessment score were independent predictors of survival, while history of statin use was not (p = 0.403). This current retrospective study did not find any benefit of statin use on primary and secondary outcomes of the patients admitted to an academic hospital with sepsis.

Effect of time of admission on compliance with deep vein thrombosis prophylaxis in a tertiary medical intensive care unit.

OBJECTIVE: We sought to evaluate deep vein thrombosis (DVT) prophylaxis compliance according to time of admission in a medical intensive care unit (MICU). METHODS: This was a retrospective cohort study at a closed tertiary MICU. We classified patients into three groups (week days, weekends, and week nights), according to time of admission. An unweighted risk factor score (RFS) was calculated from 20 known risk factors. We defined DVT prophylaxis compliance as any type of prophylaxis (mechanical or pharmacologic) for RFS 3. Non-compliance was defined as no prophylaxis or single-type prophylaxis for RFS > 3. RESULTS: We analyzed 105 admissions. Eighty (76.19%) patients received compliant DVT prophylaxis, and 25 (23.81%) patients received non-compliant regimens of whom 11 (10.48%) were not on any prophylaxis. DVT prophylaxis compliance was not different across the three admission groups. The non-compliant DVT prophylaxis group had a higher RFS (3.48 +/- 2.1 vs. 2.25 +/- 1.5; P = 0.011), a trend towards fewer female patients (40% vs. 60%; P = 0.079), and a higher percentage of admissions by interns at the first postgraduate year (PGY) level (28% vs. 5.4%; P = 0.01). Logistic regression revealed that only RFS and PGY level were independent predictors for compliance (P = 0.015 and 0.005 respectively). Time of admission was not a significant factor. CONCLUSIONS: Time of admission did not influence DVT prophylaxis compliance. Compliance improved with higher PGY level and lower RFS. A higher level of knowledge probably explains the association with PGY level; however, we cannot explain the inverse relationship between RFS and compliance.

Association of obesity with increased mortality in the critically ill patient.

The impact of obesity on critical care outcomes has been an issue for debate in the literature. Variable data and conflicting results have been reported. The purpose of our study is to examine the impact of obesity on the outcome of patients admitted to a tertiary closed Intensive Care Unit (ICU) in Saudi Arabia. Data was obtained from a prospectively collected database from September 2001 to May 2004. Patients younger than 18, those with burns, brain death and readmissions were excluded. The study population was stratified into six groups according to their Body Mass Index (BMI). Primary endpoints were ICU and hospital mortality, duration of mechanical ventilation and ICU length of stay. A total of 1835 patients were included in the analysis. Baseline characteristics were similar among the six groups including severity of illness scores, reflected by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. The ICU mortality was not statistically different among the groups. Hospital mortality was lower in patients with BMI 35-39.9 kg/m2 and BMI >40 kg/m2 compared to those with BMI 18.5-24.9 kg/m2. Multivariate analysis showed that a BMI >40 kg/m2 was an independent predictor of lower hospital mortality (odds ratio 0.51, 95% confidence interval 0.28-0.92, P 0.025) after adjustment for other confounding factors. In conclusion, mortality of obese critically ill patients was not higher than patients with normal weight. In fact, the hospital mortality was lower for patients with BMI >40 kg/m2 compared to the normal BMI group despite similar severity of illness. Obesity might have a protective effect, although further studies are needed to substantiate this finding.

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

X-linked adrenoleukodystrophy. The Saudi experience.

OBJECTIVES: To evaluate the clinical, biochemical, neuroradiological, and neurophysiological findings of patients with X-linked adrenoleukodystrophy. METHODS: Retrospective study evaluating the data of 10 X-linked adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. RESULTS: The common presenting symptoms were deterioration in school performance, vision and hearing, behavioral changes, and seizures. Eight patients survived 1-4 years and one patient 12 years after the initial presentation, while one patient expired. Six patients had the childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy form. Six are in an advanced stage of the disease and 3 have mild to moderate spasticity. All except 2 manifested moderate to severe dementia with variable degrees of visual loss. Decreased hearing and features of adrenal insufficiency were seen in 7 patients. Very long chain fatty acids were significantly increased in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was increased in all. The characteristic high-signal intensity of parieto-occipital white matter on brain magnetic resonance imaging T2-weighted images was observed in all patients. Two patients had functional study of the brain, which showed hypometabolic activity in gray and white matter of the occipital lobes. Various neurophysiological abnormalities were detected. The response to different treatment modalities was not promising. CONCLUSION: The disease is more common than had been previously recognized due to phenotypic variability and a wide spectrum of presentations. This report describes various aspects of this disorder and emphasizes the importance of early identification and treatment of asymptomatic but biochemically affected individuals, since all current therapeutic approaches are disappointing if overt neurological abnormalities have been already developed.

X-linked adrenoleukodystrophy. The Saudi experience.

OBJECTIVE: To evaluate the clinical, biochemical, neuroradiological, and neurophysiological findings of patients with X-linked adrenoleukodystrophy. METHODS: Retrospective study evaluating the data of 10 X-linked adrenoleukodystrophy patients diagnosed at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. RESULTS: The common presenting symptoms were deterioration in school performance, vision and hearing, behavioral changes, and seizures. Eight patients survived 1-4 years and one patient 12 years after the initial presentation, while one patient expired. Six patients had the childhood form, 3 had the adolescent form and one had the adrenomyeloneuropathy form. Six are in an advanced stage of the disease and 3 have mild to moderate spasticity. All except 2 manifested moderate to severe dementia with variable degrees of visual loss. Decreased hearing and features of adrenal insufficiency were seen in 7 patients. Very long chain fatty acids were significantly increased in seven and mildly elevated in 2 patients, however the C26 to C22 ratio was increased in all. The characteristic high-signal intensity of parieto-occipital white matter on brain magnetic resonance imaging T2-weighted images was observed in all patients. Two patients had functional study of the brain, which showed hypometabolic activity in gray and white matter of the occipital lobes. Various neurophysiological abnormalities were detected. The response to different treatment modalities was not promising. CONCLUSION: The disease is more common than had been previously recognized due to phenotypic variability and a wide spectrum of presentations. This report describes various aspects of this disorder and emphasizes the importance of early identification and treatment of asymptomatic but biochemically affected individuals, since all current therapeutic approaches are disappointing if overt neurological abnormalities have been already developed.

Pseudotumor cerebri and leukoencephalopathy in childhood lupus.

We describe an adolescent with systemic lupus erythematosus (SLE) and pseudotumor cerebri (PTC) associated with diffuse white matter lesions (leukoencephalopathy) on neuroimaging studies. Although the association between SLE and PTC has been reported previously in 21 cases, the findings of leukoencephalopathy is known in only one other patient.

Biotin-responsive basal ganglia disease: a novel entity.

We describe a novel, biotin-responsive basal ganglia disease in 10 patients. At onset, it appears as a subacute encephalopathy, with confusion, dysarthria and dysphagia with occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progresses to severe cogwheel rigidity, dystonia and quadriparesis. These symptoms disappear within a few days if biotin (5-10 mg/kg/day) is administered, and there are no neurological sequelae. They reappear within 1 month if biotin is discontinued. Patients diagnosed late, or who have had repeated episodes, suffer from residual symptoms such as paraparesis, mild mental retardation or dystonia. The numerous biochemical studies of intermediary metabolism, like the autoimmune and toxicological studies, enzyme assays including biotinidase, carboxylase and lysosomal activities, and bacterial and viral studies were all normal. The aetiology may be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiological abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This was present during the initial acute encephalopathy and remained unchanged during follow-up of 3-10 years. Although its aetiology is unknown, it is important to recognize this disease, since its symptoms may be reversed and the progression of its clinical course prevented simply by providing biotin.

Intraventricular interferon-alpha stops seizures in Rasmussen's encephalitis: a case report.

A 3.5-year-old girl had epilepsia partialis continua of the right side. Clinical and laboratory findings were consistent with Rasmussen's encephalitis. Treatment with high-dose methylprednisolone led to temporary control of seizures, but for 2 years, the seizures remained refractory to phenobarbital, phenytoin, lorazepam, carbamazepine, valproic acid, vigabatrin, gabapentin, and lamotrigine. A 6-week course, and later a 6-month course, of intraventricular interferon-alpha almost totally suppressed the seizures. Although moderately hemiparetic, the child has reasonable neurologic function with mild speech delay. She is receiving her third course of treatment, and seizures remain completely controlled.

3-Methylglutaconic aciduria: ten new cases with a possible new phenotype.

3-Methylglutaconic aciduria is an organic aciduria with diverse phenotypic presentations. In more than half of the cases it is a 'neurologic or silent organic aciduria', and, except for one subtype, the biochemical defect is unknown. This report describes 10 new patients. Four of them presented with early global neurologic involvement and arrested development. They rapidly became demented, developed myoclonus or tonic-clonic seizures, spastic quadriplegia, deafness and blindness, and died. Three had acidosis and hypoglycemia neonatally; later, myoclonus and deafness, and eventually severe mental retardation and spastic quadriplegia developed. One patient died. In three children who presented with sudden onset of extrapyramidal tract symptoms, with or without optic atrophy, the clinical presentation was significantly different from that described either for 'unspecified' type or for Costeff syndrome. All three patients showed clinical improvement soon after treatment with coenzyme Q.

Neurophysiologic correlates of organic acidemias: a survey of 107 patients.

The files of 107 patients with 19 different types of organic acidemia were reviewed retrospectively. Approximately 50% of the patients had abnormal electroencephalogram (EEG) at the time of initial study. In patients who had serial studies, the EEG deteriorated in 38% and improved in 15%. The predominant EEG abnormality encountered was slowing of the background activity in various degrees. Focal or generalized paroxysmal activity occurring in conjunction with slow background activity indicated a poor prognosis. Brainstem auditory evoked potentials (BAEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP) were analyzed. The VEP was abnormal in 44%, BAEP in 39%, and SEP in 29% of the patients. Given the magnitude and frequency by which neurophysiological abnormalities occur in organic acidemias, neurophysiology testing provides complementary functional information and has an important place in the clinical work-up of these diseases.

The clinical spectrum of biotin-treatable encephalopathies in Saudi Arabia.

Ten patients with biotin-dependent, chronic progressive encephalopathies were studied retrospectively. In four patients, the underlying disease was either total or partial deficiency of biotinidase. In one patient, the disease was caused by a lack of holocarboxylase synthetase activity. Four patients presented with Leigh encephalopathy. However, a biochemical defect could not always be confirmed. All patients required the administration of large doses of biotin to maintain normal neurologic function.

Cockayne syndrome: MRI correlates of hypomyelination.

Two siblings with Cockayne syndrome are reported who had most of the stigmata characteristic of the syndrome as it was initially described in 1936. Unusual findings are emphasized, such as the early onset of cataracts and the early detection of peripheral neuropathy. The previously reported autopsy abnormalities in this condition are correlated with the present magnetic resonance imaging findings of mild ventricular enlargement and delay in myelination of the cerebrum and cerebellum. Properly myelinated structures included the basal ganglia, thalamus, internal capsule, splenium, and genu of the corpus callosum.