Impact of the implementation of a Sepsis Code Program in medical patient management: a cohort study in an Internal Medicine ward

IntroductionSepsis is the main cause of death in hospitals and the implementation of diagnosis and treatment bundles has shown to improve its evolution. However, there is a lack of evidence about patients attended in conventional units.MethodsA 3-year retrospective cohort study was conducted. Patients hospitalized in Internal Medicine units with sepsis were included and assigned to two cohorts according to Sepsis Code (SC) activation (group A) or not (B). Baseline and evolution variables were collected.ResultsA total of 653 patients were included. In 296 cases SC was activated. Mean age was 81.43 years, median Charlson comorbidity index (CCI) was 2 and 63.25% showed some functional disability. More bundles were completed in group A: blood cultures 95.2% vs 72.5% (p < 0.001), extended spectrum antibiotics 59.1% vs 41.4% (p < 0.001), fluid resuscitation 96.62% vs 80.95% (p < 0.001). Infection control at 72 hours was quite higher in group A (81.42% vs 55.18%, odds ratio 3.55 [2.48-5.09]). Antibiotic was optimized more frequently in group A (60.77% vs 47.03%, p 0.008). Mean in-hospital stay was 10.63 days (11.44 vs 8.53 days, p < 0.001). Complications during hospitalization appeared in 51.76% of patients, especially in group B (45.95% vs 56.58%, odds ratio 1.53 [1.12-2.09]). Hospital readmissions were higher in group A (40% vs 24.76%, p < 0.001). 28-day mortality was significantly lower in group A (20.95% vs 42.86%, odds ratio 0.33 [0.23-0.47]).ConclusionsImplementation of SC seems to be effective in improving short-term outcomes in IM patients, although therapy should be tailored in an individual basis.     

The role of dominant striatum in language: a study using intraoperative electrical stimulations

BACKGROUND: The role of the striatum in language remains poorly understood. Intraoperative electrical stimulation during surgery for tumours involving the caudate nucleus or putamen in the dominant hemisphere might be illuminating. OBJECTIVES: To study the role of these structures in language, with the aim of avoiding postoperative definitive aphasia. METHODS: 11 patients with cortico-subcortical low grade gliomas were operated on while awake, and striatal functional mapping was done. Intraoperative direct electrical stimulation was used while the patients carried out motor and naming tasks during the resection. RESULTS: In five cases of glioma involving the dominant putamen, stimulations induced anarthria, while in six cases of glioma involving the dominant caudate, stimulations elicited perseveration. There was no motor effect. The striatum was systematically preserved. Postoperatively, all patients except one had transient dysphasia which resolved within three months. CONCLUSIONS: There appear to be two separate basal ganglia systems in language, one mediated by the putamen which might have a motor role, and one by the caudate which might have a role in cognitive control. These findings could have implications for surgical strategy in lesions involving the dominant striatum.     

The Spectrum of Paraneoplastic Cutaneous Vasculitis in a Defined Population: Incidence and Clinical Features

Cutaneous vasculitis may be associated with malignancies, and may behave as a paraneoplastic syndrome. This association has been reported in a variable proportion of patients depending on population selection. We conducted the current study to assess the frequency, clinical features, treatment, and outcome of paraneoplastic vasculitis in a large unselected series of 766 patients with cutaneous vasculitis diagnosed at a single university hospital.Sixteen patients (10 men and 6 women; mean age ± standard deviation, 67.94 ± 14.20 yr; range, 40–85 yr) presenting with cutaneous vasculitis were ultimately diagnosed as having an underlying malignancy. They constituted 3.80% of the 421 adult patients. There were 9 hematologic and 7 solid underlying malignancies. Skin lesions were the initial clinical presentation in all of them, and the median interval from the onset of cutaneous vasculitis to the diagnosis of the malignancy was 17 days (range, 8–50 d). The most frequent skin lesions were palpable purpura (15 patients). Other clinical manifestations included constitutional syndrome (10 patients) and arthralgia and/or arthritis (4 cases). Hematologic cytopenias (11 cases) as well as immature peripheral blood cells (6 cases) were frequently observed in the full blood cell count, especially in those with vasculitis associated with hematologic malignancies.Specific treatment for vasculitis was prescribed in 10 patients; nonsteroidal antiinflammatory drugs (4 patients), corticosteroids (3 patients), chloroquine (1 patient), antihistamines (1 patient), and cyclophosphamide (1 patient). Ten patients died due to the malignancy and 6 patients recovered following malignancy therapy. Patients with paraneoplastic vasculitis were older, more frequently had constitutional syndrome, and less frequently had organ damage due to the vasculitis than the remaining patients with cutaneous vasculitis.In summary, cutaneous paraneoplastic vasculitis is an entity not uncommonly encountered by clinicians. The most common underlying malignancy is generally hematologic. In these cases the presence of cytopenias and immature cells may be red flags for the diagnosis of cancer. In patients with paraneoplastic cutaneous vasculitis, the prognosis depends on the underlying neoplasia.     

Early Anti-inflammatory and Pro-angiogenic Myocardial Effects of Intravenous Serelaxin Infusion for 72 H in an Experimental Rat Model of Acute Myocardial Infarction

Sprague Dawley rats were subjected to acute myocardial infarction (AMI) by permanent ligation of the left anterior descending coronary artery. At the time of AMI, a subcutaneous mini-osmotic pump was implanted and animals were randomized into three groups, according to the intravenous therapy received during the first 72 h: placebo-treated (saline), serelaxin10-treated (SRLX10 = 10 μg/kg/day), or serelaxin30-treated (SRLX30 = 30 μg/kg/day). Treatment with SRLX30 reduced the expression of inflammatory cytokines and chemokines, as well as the infiltration of macrophages, and increased the expression of pro-angiogenic markers and vessel density in the infarcted myocardium after 7 days. SRLX30 did not reduce early myocardial fibrosis but reduced myocardial levels of sST2 and galectin-3. No significant effects were observed with SRLX10 treatment. A significant correlation was observed between plasma levels of serelaxin and effect measures. The results suggest serelaxin has a protective effect in early processes of cardiac remodeling after AMI.     

Cronobiología de la muerte en insuficiencia cardiaca

Introduction and objectives

In the general population, heart events occur more often during early morning, on Mondays, and during winter. However, the chronobiology of death in heart failure has not been analyzed. The aim of this study was to determine the circadian, day of the week, and seasonal variability of all-cause mortality in chronic heart failure.

Methods

This was an analysis of all consecutive heart failure patients followed in a heart failure unit from January 2003 to December 2008. The circadian moment of death was analyzed at 6-h intervals and was determined by reviewing medical records and by information provided by the relatives.

Results

Of 1196 patients (mean [standard deviation] age, 69 [13] years; 62% male), 418 (34.9%) died during a mean (standard deviation) follow-up of 29 (21) months. Survivors were younger, had higher body mass index, left ventricular ejection fraction, glomerular filtration rate, hemoglobin and sodium levels, and lower Framingham risk scores, amino-terminal pro-B type natriuretic peptide, troponin T, and urate values. They were more frequently treated with angiotensin receptor blockers, beta-blockers, mineralocorticoids receptor antagonists, digoxin, nitrates, hydralazine, statins, loop diuretics, and thiazides. The analysis of the circadian and weekly variability did not reveal significant differences between the four 6-h intervals or the days of the week. Mortality occurred more frequently during the winter (30.6%) compared with the other seasons (P = .024).

Conclusions

All cause mortality does not follow a circadian pattern, but a seasonal rhythm in patients with heart failure. This finding is in contrast to the circadian rhythmicity of cardiovascular events reported in the general population.Full English text available from:www.revespcardiol.org/en     

Relationship between responsiveness of cancer cells to Oncostatin M and/or IL-6 and survival of stage III melanoma patients treated with tumour-infiltrating lymphocytes

Immunotherapy by adoptive transfer of autologous tumour-infiltrating lymphocytes (TIL) shows promising clinical results for stage III (lymph nodes metastasis) melanoma patients, but some of them remain unresponsive. Here we analysed retrospectively the impact of resistance of melanoma cells to anti-proliferative cytokines on the clinical outcome of 24 TIL-treated metastatic melanoma patients. Patient relapse-free survival correlated significantly with Oncostatin M (OSM) and/or IL-6 sensitivity of melanoma cells, but not with interferon (IFN) gamma or tumour necrosis factor (TNF) alpha sensitivity. However, OSM/IL-6 sensitivity did not correlate with other known prognostic factors. Moreover, OSM and IL-6 were produced by TIL just before their injection to patients. In immunodeficient mice, OSM reduced human melanoma xenograft tumour growth, this effect being directly through inhibition of tumour cell proliferation rather than induction of apoptosis or necrosis. Thus, OSM/IL-6 resistance of melanoma cells appears to be a new escape mechanism to TIL treatment that could be added to the existing prognostic factors for early stage melanoma patients. This mechanism of action could be also relevant in other immunotherapy protocols, and could lead to better prognosis and anti-cancer treatments.     

Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders

Background

Autism spectrum disorders (ASD) refer to a broader group of neurobiological conditions, pervasive developmental disorders. They are characterised by a symptomatic triad associated with qualitative changes in social interactions, defect in communication abilities, and repetitive and stereotyped interests and activities. ASD is prevalent in 1 to 3 per 1000 people. Despite several arguments for a strong genetic contribution, the molecular basis of a most cases remains unexplained. About 5% of patients with autism have a chromosome abnormality visible with cytogenetic methods. The most frequent are 15q11–q13 duplication, 2q37 and 22q13.3 deletions. Many other chromosomal imbalances have been described. However, most of them remain undetectable using routine karyotype analysis, thus impeding diagnosis and genetic counselling.

Methods and results

29 patients presenting with syndromic ASD were investigated using a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Eight clinically relevant rearrangements were identified in 8 (27.5%) patients: six deletions and two duplications. Altered segments ranged in size from 1.4 to 16 Mb (2–19 clones). No recurrent abnormality was identified.

Conclusion

These results clearly show that array comparative genomic hybridisation should be considered to be an essential aspect of the genetic analysis of patients with syndromic ASD. Moreover, besides their importance for diagnosis and genetic counselling, they may allow the delineation of new contiguous gene syndromes associated with ASD. Finally, the detailed molecular analysis of the rearranged regions may pave the way for the identification of new ASD genes.Autism spectrum disorders (ASD) belong to the group of pervasive developmental disorders (PDD). According to the Diagnostic statistical manual for mental disorders—fourth edition (DSM IV) classification,¹ ASD are characterised by impairments in communication, social skills and restricted or stereotyped pattern of behaviours and interests. A diagnosis within the autism spectrum requires one or more symptoms in each of the three areas of impairment. The prevalence of ASD is estimated at about 1/1000 to 3/1000.^2,3 ASD are heterogeneous conditions which can be either isolated or syndromic—that is, associated with other clinical features such as facial dysmorphism, limb or visceral malformations, and growth abnormalities.A total of 10–20% of ASD cases are due to known medical conditions involving chromosomal imbalances, genetic disorders (X fragile syndrome and tuberous sclerosis)⁴ or environmental factors (valproate⁵ and rubella). The other cases remain unexplained. Twin and familial studies have documented a higher concordance rate in monozygotic twins (90%) than in dizygotic twins (4.5%),^6,7,8 and a 75‐fold greater risk to siblings in idiopathic patients than in the general population.^9,10 Collectively, these studies support the involvement of numerous genes in autistic disorders.About 1.7–4.8% of people with ASD have chromosome abnormalities. Almost all chromosomes have been involved, including unbalanced translocations, inversions, rings, and interstitial or terminal deletions and duplications.^11,12,13,14 The rare chromosome abnormalities that have been reported on more than one occasion are duplication of 15q,¹⁵ deletions of 18q,^16,17 Xp,^18,19 2q37,²⁰ 22q13^21,22 and the sex chromosome aneuploidies 47,XYY^23,24 and 45,X/46,XY.^25,26 This diversity of loci suggests that studying chromosomal aberrations in relationship to autism will require efficient and highly sensitive tools. In addition to the importance for diagnosis, identification of chromosomal imbalances in patients with ASD may also be instrumental for cloning disease‐causing genes. Analysis of Xp22.3 deletion has indeed allowed the identification of the NLGN4 gene.²⁷Recent technological developments, such as array‐based comparative genomic hybridisation (array‐CGH),^28,29,30 allow the investigation of the human genome at a resolution that is 5–10 times higher than that of routine chromosome analysis by karyotyping.^29,31,32,33 Array‐CGH has been used successfully for analysis of tumour samples and cell lines, and for high‐resolution analysis of patients with mental retardation and congenital anomalies.^{34,35,36,37,38}Here, we report the application of genomewide array‐CGH, at 1 Mb resolution, to the study of 29 patients with syndromic ASD. In addition to their clinical relevance, our results emphasise the importance of chromosomal imbalance in the aetiology of syndromic ASD and may help the identification of new genes involved in autistic disorders.     

Duodenal derotation as an effective treatment of superior mesenteric artery syndrome: a thirty-three year experience

We evaluated the use of duodenal derotation as a surgical option for superior mesenteric artery syndrome (SMAS) in two groups of young patients. Sixteen patients with SMAS diagnosed by barium upper gastrointestinal series (UGI) from 1974 to 2001, and six patients diagnosed by computerized tomography with three-dimensional reconstructions (3D CT) from 2001 to 2007 were referred to our surgical service, 19 of whom underwent duodenal derotation as the primary surgical treatment after a failed trial of conservative treatment. The main measured outcomes were the resolution of typical symptoms of SMAS and the development of long-term surgical complications. Of the first 16 patients, three (19%) responded to nasojejunal feedings. Of 13 patients undergoing derotation, only one (7.7%) failed derotation and required a gastrojejunostomy bypass, whereas 12 (92%) became asymptomatic after the derotation procedure. After a mean follow-up of 5.13 years (range 0.1-15), two patients (15%) presented with small bowel obstructions and were treated with a simple lysis of the adhesion. All six patients from 2001 to 2007 responded well to surgical derotation. Overall, duodenal derotations successfully relieved symptoms in 18 out of 19 (95%) patients with SMAS, with two (11%) major long-term surgical complications. No volvulus was observed in our patients at the mean follow-up of 4.37 years.