Use and Outcomes of Dexamethasone in the Management of Malignant Small Bowel Obstruction.

Objective: To describe rates of dexamethasone use in the nonoperative management of malignant small bowel obstruction (mSBO) and their outcomes. Background: mSBO is common in patients with advanced abdominal-pelvic cancers. Management includes prioritizing quality of life and avoiding surgical intervention when possible. The use of dexamethasone to restore bowel function is recommended in the National Comprehensive Cancer Network guidelines for mSBO. Yet, it is unknown how often dexamethasone is used for mSBO and whether results from nonresearch settings support its use. Methods: This is a multicenter retrospective cohort study including unique admissions for mSBO from January 1, 2019 to December 31, 2021. Dexamethasone use and management outcomes were summarized with descriptive statistics and multiple logistic regression. Results: Among 571 admissions (68% female, mean age 63 years, 85% history of abdominal surgery) that were eligible and initially nonoperative, 26% [95% confidence interval (CI) = 23%-30%] received dexamethasone treatment (69% female, mean age 62 years, 87% history of abdominal surgery). Dexamethasone use by site ranged from 13% to 52%. Among dexamethasone recipients, 13% (95% CI = 9%-20%) subsequently required nonelective surgery during the same admission and 4 dexamethasone-related safety-events were reported. Amongst 421 eligible admissions where dexamethasone was not used, 17% (95% CI = 14%-21%) required nonelective surgery. Overall, the unadjusted odds ratio (OR) for nonelective surgery with dexamethasone use compared to without its use was 0.7 (95% CI = 0.4-1.3). Using multiple logistic regression, OR after adjusting for site, age, sex, history of abdominal surgery, nasogastric tube, and Gastrografin use was 0.6 (95% CI = 0.3-1.1). Conclusion: Dexamethasone was used in about 1 in 4 eligible mSBO admissions with high variability of use between tertiary academic centers. This multicenter retrospective cohort study suggested an association between dexamethasone use and lower rates of nonelective surgery, representing a potential opportunity for quality improvement.

Freelite and Kloneus assays in free light chain measurements in patients with renal impairment.

BACKGROUND: Serum free light chain (FLC) quantification is a diagnostic criterion for monoclonal gammopathy and its values in patients with renal impairment are different from those in healthy subjects. The aim of this study was to evaluate Freelite and Kloneus assays in these patients. METHODS: In this retrospective study, serum samples from 226 patients with chronic kidney disease (CKD) of stages 2-5 were measured with a Freelite assay on the Optilite system and with a Kloneus assay on the AU5800 system and compared with controls without renal impairment. RESULTS: Both kappa FLC (K-FLC) and lambda FLC (L-FLC) concentrations increased with Kloneus and Freelite assays with each increment in CKD stage. In patients with CKD, Kloneus detected lower concentrations of K-FLC (median: 20.4 mg/L; 95% range: 9.8-57.2) than Freelite (median: 36.5 mg/L; 95% range: 16.5-137.7) and higher concentrations of L-FLC (median: 32.2 mg/L; 95% range: 14.4-96.7) than Freelite (median: 25.4 mg/L; 95% range: 11.9-86.0). This resulted in significantly different kappa/lambda ratios (K/L-FLC) in patients with CKD for the two tests. The Freelite K/L-FLC in the CKD group (median: 1.50; min-max: 0.66-3.45) was significantly increased compared with healthy controls, and the Kloneus K/L-FLC in the CKD group (median: 0.63; 95 % min-max: 0.34-1.01) was slightly lower. CONCLUSIONS: These findings demonstrate that Freelite and Kloneus assays provide higher but not parallel values when FLCs are measured in patients with CKD, so an increase in K/L-FLC was observed in the case of Freelite, and we found a slight decrease in the case of Kloneus.

Deubiquitinase USP9X loss sensitizes renal cancer cells to mTOR inhibition.

Mammalian target of rapamycin (mTOR) is a central regulator of mammalian metabolism and physiology. Aberrant hyperactivation of the mTOR pathway promotes tumor growth and metastasis, and can also promote tumor resistance to chemotherapy and cancer drugs; this makes mTOR an attractive cancer therapeutic target. mTOR inhibitors have been approved to treat cancer; however, the mechanisms underlying drug sensitivity remain poorly understood. Here, whole exome sequencing of three chromophobe renal cell carcinoma (chRCC) patients with exceptional mTOR inhibitor sensitivity revealed that all three patients shared somatic mutations in the deubiquitinase gene USP9X. The clonal characteristics of the mutations, which were amassed by studying multiple patients' primary and metastatic samples from various years, together with the low USP9X mutation rate in unselected chRCC series, reinforced a causal link between USP9X and mTOR inhibitor sensitivity. Rapamycin treatment of USP9X-depleted HeLa and renal cancer 786-O cells, along with the pharmacological inhibition of USP9X, confirmed that this protein plays a role in patients' sensitivity to mTOR inhibitors. USP9X was not found to exert a direct effect on mTORC1, but subsequent ubiquitylome analyses identified p62 as a direct USP9X target. Increased p62 ubiquitination and the augmented rapamycin effect upon bortezomib treatment, together with the results of p62 and LC3 immunofluorescence assays, suggested that dysregulated autophagy in USP9X-depleted cells can have a synergistic effect with mTOR inhibitors. In summary, we show that USP9X constitutes a potential novel marker of sensitivity to mTOR inhibitors in chRCC patients, and represents a clinical strategy for increasing the sensitivity to these drugs.

Banana in a Condom: An Unusual Cause of Small Bowel Obstruction.

An otherwise healthy, 34-year-old man presented to the emergency department with abdominal pain, nausea, and vomiting, which began a day after he ingested a banana-stuffed condom. A contrast-enhanced computed tomography (CT) abdomen and pelvis revealed a dilated small bowel with a transition point, findings consistent with small bowel obstruction. Abdominopelvic ascites was also noted on imaging, which was concerning for bowel distress. He was taken to the operating room for an exploratory laparotomy, which revealed a high-grade obstruction by a foreign body, a banana stuffed in a condom, in the mid-jejunum. An enterotomy was performed to relieve the obstruction. The postoperative course was uneventful, and he was discharged three days later.

Genomic and immune landscape Of metastatic pheochromocytoma and paraganglioma.

The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.

Design of a Low-Power Embedded System Based on a SoC-FPGA and the Honeybee Search Algorithm for Real-Time Video Tracking.

Video tracking involves detecting previously designated objects of interest within a sequence of image frames. It can be applied in robotics, unmanned vehicles, and automation, among other fields of interest. Video tracking is still regarded as an open problem due to a number of obstacles that still need to be overcome, including the need for high precision and real-time results, as well as portability and low-power demands. This work presents the design, implementation and assessment of a low-power embedded system based on an SoC-FPGA platform and the honeybee search algorithm (HSA) for real-time video tracking. HSA is a meta-heuristic that combines evolutionary computing and swarm intelligence techniques. Our findings demonstrated that the combination of SoC-FPGA and HSA reduced the consumption of computational resources, allowing real-time multiprocessing without a reduction in precision, and with the advantage of lower power consumption, which enabled portability. A starker difference was observed when measuring the power consumption. The proposed SoC-FPGA system consumed about 5 Watts, whereas the CPU-GPU system required more than 200 Watts. A general recommendation obtained from this research is to use SoC-FPGA over CPU-GPU to work with meta-heuristics in computer vision applications when an embedded solution is required.

Analysis of Telomere Maintenance Related Genes Reveals NOP10 as a New Metastatic-Risk Marker in Pheochromocytoma/Paraganglioma.

One of the main problems we face with PPGL is the lack of molecular markers capable of predicting the development of metastases in patients. Telomere-related genes, such as TERT and ATRX, have been recently described in PPGL, supporting the association between the activation of immortalization mechanisms and disease progression. However, the contribution of other genes involving telomere preservation machinery has not been previously investigated. In this work, we aimed to analyze the prognostic value of a comprehensive set of genes involved in telomere maintenance. For this study, we collected 165 PPGL samples (97 non-metastatic/63 metastatic), genetically characterized, in which the expression of 29 genes of interest was studied by NGS. Three of the 29 genes studied, TERT, ATRX and NOP10, showed differential expression between metastatic and non-metastatic cases, and alterations in these genes were associated with a shorter time to progression, independent of SDHB-status. We studied telomere length by Q-FISH in patient samples and in an in vitro model. NOP10 overexpressing tumors displayed an intermediate-length telomere phenotype without ALT, and in vitro results suggest that NOP10 has a role in telomerase-dependent telomere maintenance. We also propose the implementation of NOP10 IHC to better stratify PPGL patients.

Serum free light chain reference intervals in an Optilite and their influence on clinical guidelines.

BACKGROUND: Serum free light chain (FLC) analysis has been incorporated into the International Myeloma Working Group guidelines for the diagnosis and management of all monoclonal gammopathies. These recommendations were solely based on a single assay method (Freelite assay) and instrument. Here, we establish new reference intervals (RIs) for kappa and lambda FLC and the kappa-lambda difference and sum and a new diagnostic range for kappa/lambda FLC ratio (K/L-FLC) in an Optilite turbidimeter (The Binding Site) with the Freelite assay. METHODS: To establish new RIs, the CLSI EP28-A3C protocol was applied to 249 sample blood donors from Fuenlabrada, Spain, and the central 95% and total range were estimated. Samples from patients with polyclonal hypo- and hypergammaglobulinemia were used for the evaluation of K/L-FLC as a monoclonal proliferation index. RESULTS: The new RIs and the new K/L-FLC diagnostic range for the Optilite (0.65-2.56 mg/L) are very different from those in on the guidelines (0.26-1.65 mg/L). We propose new RIs for the K - L difference and the K + L sum. Diagnostic range validation as a monoclonal proliferation index with samples with hypo- and hypergammaglobulinemia confirms this new range. CONCLUSIONS: In this study, we present the FLC RI for Freelite reagents measured on an Optilite turbidimeter. These ranges are different from those provided by the manufacturer and from those used in most studies in the literature, which may lead to patient misclassification. Manufacturers and clinical laboratories must strive to provide RIs for the technology they are using and for their population.

Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma.

Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants.

CD133 Expression in Medullary Thyroid Cancer Cells Identifies Patients with Poor Prognosis.

CONTEXT: The identification of markers able to determine medullary thyroid cancer (MTC) patients at high-risk of disease progression is critical to improve their clinical management and outcome. Previous studies have suggested that expression of the stem cell marker CD133 is associated with MTC aggressiveness. OBJECTIVE: To evaluate CD133 impact on disease progression in MTC and explore the regulatory mechanisms leading to the upregulation of this protein in aggressive tumors. PATIENTS: We compiled a series of 74 MTCs with associated clinical data and characterized them for mutations in RET and RAS proto-oncogenes, presumed to be related with disease clinical behavior. RESULTS: We found that CD133 immunohistochemical expression was associated with adverse clinicopathological features and predicted a reduction in time to disease progression even when only RET-mutated cases were considered in the analysis (log-rank test P < 0.003). Univariate analysis for progression-free survival revealed CD133 expression and presence of tumor emboli in peritumoral blood vessels as the most significant prognostic covariates among others such as age, gender, and prognostic stage. Multivariate analysis identified both variables as independent factors of poor prognosis (hazard ratio = 16.6 and 2; P = 0.001 and 0.010, respectively). Finally, we defined hsa-miR-30a-5p, a miRNA downregulated in aggressive MTCs, as a CD133 expression regulator. Ectopic expression of hsa-miR-30a-5p in MZ-CRC-1 (RETM918T) cells significantly reduced CD133 mRNA expression. CONCLUSIONS: Our results suggest that CD133 expression may be a useful tool to identify MTC patients with poor prognosis, who may benefit from a more extensive primary surgical management and follow-up.

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

Experiencia con toxina botulínica en la migraña crónica / Experience with botulinum toxin in chronic migraine

OBJETIVO: Describir la experiencia con la administración de toxina botulínica tipo A (OnabotA) en el tratamiento de la migraña crónica (MC) en Segovia durante 16 meses, evaluar su beneficio y buscar marcadores clínicos que sirvan para predecir una mejor respuesta al tratamiento. PACIENTES Y MÉTODOS: Estudio prospectivo de pacientes con MC que recibieron infiltraciones con OnabotA durante 16 meses. Se evaluó la eficacia de OnabotA comparando la reducción en el número de días de cefalea, en la intensidad y efectos adversos. Se comparó el efecto del tratamiento con el factor tiempo mediante un análisis de la varianza de dos vías (ANOVA). Se estudió la correlación del efecto del tratamiento con el resto de las variables mediante un modelo de regresión lineal para buscar marcadores clínicos que sirvan para predecir una mejor respuesta. RESULTADOS: Se incluyó a 69 pacientes que cumplían criterios de MC. Se les realizó una media de 2 infiltraciones. La edad media fue de 43 años, el 88,4% fueron mujeres. La frecuencia de los días de cefalea y su intensidad se redujeron de forma significativa (p < 0,005) y esta mejoría se mantuvo a lo largo del tiempo. Se encontró una correlación negativa entre la reducción de la intensidad y el número de tratamientos previos a la administración de la toxina. CONCLUSIÓN: El efecto beneficioso de la OnabotA en la MC se mantiene en el tiempo, siendo un tratamiento seguro y bien tolerado. No debe retrasarse su uso en MC refractaria, ya que su beneficio podría ser mayor cuanto antes se administre

OBJECTIVE: The purposes of this study were to describe our 16-month experience with onabotulinumtoxinA (OnabotA) for the treatment of chronic migraine (CM) in the Spanish province of Segovia, evaluate its benefits, and determine clinical markers of good response to treatment. PATIENTS AND METHODS: Prospective study of patients with CM who received OnabotA for 16 months. The effectiveness of OnabotA was evaluated based on the reduction in the number of headache days, pain intensity, and side effects. We used two-way analysis of variance (ANOVA) to assess the effects of treatment according to the time factor. We studied the correlation between treatment effects and other variables using a linear regression model to establish the clinical markers of good response to treatment. RESULTS: We included 69 patients who met the diagnostic criteria for CM. Patients underwent an average of 2 infiltrations. Mean age was 43 years; 88.4% were women. The number of headache days and pain intensity decreased significantly (P < .005); improvements remained over time. We found a negative correlation between the reduction in pain intensity and the number of treatments before OnabotA. CONCLUSION: The beneficial effects of OnabotA for CM continue over time. OnabotA is a safe and well-tolerated treatment whose use for refractory CM should not be delayed since early treatment provides greater benefits

Experience with botulinum toxin in chronic migraine. / Experiencia con toxina botulínica en la migraña crónica.

OBJECTIVE: The purposes of this study were to describe our 16-month experience with onabotulinumtoxinA (OnabotA) for the treatment of chronic migraine (CM) in the Spanish province of Segovia, evaluate its benefits, and determine clinical markers of good response to treatment. PATIENTS AND METHODS: Prospective study of patients with CM who received OnabotA for 16 months. The effectiveness of OnabotA was evaluated based on the reduction in the number of headache days, pain intensity, and side effects. We used two-way analysis of variance (ANOVA) to assess the effects of treatment according to the time factor. We studied the correlation between treatment effects and other variables using a linear regression model to establish the clinical markers of good response to treatment. RESULTS: We included 69 patients who met the diagnostic criteria for CM. Patients underwent an average of 2 infiltrations. Mean age was 43 years; 88.4% were women. The number of headache days and pain intensity decreased significantly (P < .005); improvements remained over time. We found a negative correlation between the reduction in pain intensity and the number of treatments before OnabotA. CONCLUSION: The beneficial effects of OnabotA for CM continue over time. OnabotA is a safe and well-tolerated treatment whose use for refractory CM should not be delayed since early treatment provides greater benefits.

Transposon mutagenesis identifies chromatin modifiers cooperating with Ras in thyroid tumorigenesis and detects ATXN7 as a cancer gene.

Oncogenic RAS mutations are present in 15-30% of thyroid carcinomas. Endogenous expression of mutant Ras is insufficient to initiate thyroid tumorigenesis in murine models, indicating that additional genetic alterations are required. We used Sleeping Beauty (SB) transposon mutagenesis to identify events that cooperate with HrasG12V in thyroid tumor development. Random genomic integration of SB transposons primarily generated loss-of-function events that significantly increased thyroid tumor penetrance in Tpo-Cre/homozygous FR-HrasG12V mice. The thyroid tumors closely phenocopied the histological features of human RAS-driven, poorly differentiated thyroid cancers. Characterization of transposon insertion sites in the SB-induced tumors identified 45 recurrently mutated candidate cancer genes. These mutation profiles were remarkably concordant with mutated cancer genes identified in a large series of human poorly differentiated and anaplastic thyroid cancers screened by next-generation sequencing using the MSK-IMPACT panel of cancer genes, which we modified to include all SB candidates. The disrupted genes primarily clustered in chromatin remodeling functional nodes and in the PI3K pathway. ATXN7, a component of a multiprotein complex with histone acetylase activity, scored as a significant SB hit. It was recurrently mutated in advanced human cancers and significantly co-occurred with RAS or NF1 mutations. Expression of ATXN7 mutants cooperated with oncogenic RAS to induce thyroid cell proliferation, pointing to ATXN7 as a previously unrecognized cancer gene.

Functional and in silico assessment of MAX variants of unknown significance.

UNLABELLED: The presence of germline mutations affecting the MYC-associated protein X (MAX) gene has recently been identified as one of the now 11 major genetic predisposition factors for the development of hereditary pheochromocytoma and/or paraganglioma. Little is known regarding how missense variants of unknown significance (VUS) in MAX affect its pivotal role in the regulation of the MYC/MAX/MXD axis. In the present study, we propose a consensus computational prediction based on five "state-of-the-art" algorithms. We also describe a PC12-based functional assay to assess the effects that 12 MAX VUS may have on MYC's E-box transcriptional activation. For all but two of these 12 VUS, the functional assay and the consensus computational prediction gave consistent results; we classified seven variants as pathogenic and three as nonpathogenic. The introduction of wild-type MAX cDNA into PC12 cells significantly decreased MYC's ability to bind to canonical E-boxes, while pathogenic MAX proteins were not able to fully repress MYC activity. Further clinical and molecular evaluation of variant carriers corroborated the results obtained with our functional assessment. In the absence of clear heritability, clinical information, and molecular data, consensus computational predictions and functional models are able to correctly classify VUS affecting MAX. KEY MESSAGES: A functional assay assesses the effects of MAX VUS over MYC transcriptional activity. A consensus computational prediction and the functional assay show high concordance. Variant carriers' clinical and molecular data support the functional assessment.

Whole-exome sequencing reveals defective CYP3A4 variants predictive of paclitaxel dose-limiting neuropathy.

PURPOSE: Paclitaxel, a widely used chemotherapeutic drug, can cause peripheral neuropathies leading to dose reductions and treatment suspensions and decreasing the quality of life of patients. It has been suggested that genetic variants altering paclitaxel pharmacokinetics increase neuropathy risk, but the major causes of interindividual differences in susceptibility to paclitaxel toxicity remain unexplained. We carried out a whole-exome sequencing (WES) study to identify genetic susceptibility variants associated with paclitaxel neuropathy. EXPERIMENTAL DESIGN: Blood samples from 8 patients with severe paclitaxel-induced peripheral neuropathy were selected for WES. An independent cohort of 228 cancer patients with complete paclitaxel neuropathy data was used for variant screening by DHPLC and association analysis. HEK293 cells were used for heterologous expression and characterization of two novel CYP3A4 enzymes. RESULTS: WES revealed 2 patients with rare CYP3A4 variants, a premature stop codon (CYP3A4*20 allele) and a novel missense variant (CYP3A4*25, p.P389S) causing reduced enzyme expression. Screening for CYP3A4 variants in the independent cohort revealed three additional CYP3A4*20 carriers, and two patients with missense variants exhibiting diminished enzyme activity (CYP3A4*8 and the novel CYP3A4*27 allele, p.L475V). Relative to CYP3A4 wild-type patients, those carrying CYP3A4 defective variants had more severe neuropathy (2- and 1.3-fold higher risk of neuropathy for loss-of-function and missense variants, respectively, P = 0.045) and higher probability of neuropathy-induced paclitaxel treatment modifications (7- and 3-fold higher risk for loss-of-function and missense variants, respectively, P = 5.9 × 10(-5)). CONCLUSION: This is the first description of a genetic marker associated with paclitaxel treatment modifications caused by neuropathy. CYP3A4 defective variants may provide a basis for paclitaxel treatment individualization.

Obesity delays functional recovery in trauma patients.

BACKGROUND: Obesity is known to complicate trauma hospital stays. We hypothesize that obesity delays functional recovery in trauma patients. MATERIALS AND METHODS: Between 2005 and 2007, adult patients with a hospital length of stay >24 h were prospectively recruited for the study. Functional Independence Measurement (FIM) scores were calculated at the time of admission, discharge, and 6 mo after discharge. Patients were classified as nonobese (body mass index [BMI] <25), overweight (BMI ≥25 and <30), obese (BMI ≥30 and <35), and morbidly obese (BMI ≥35). Multivariate analyses were performed to determine the impact of obesity on FIM scores. RESULTS: Two hundred thirty-five patients met the study inclusion criteria. Average injury severity scores was >18. We recorded no mortality at the time of discharge and follow-up. During acute hospital stay stage, nonobese patients had an average of 24 points increase on FIM scores compared with morbidly obese patients with 16 points improvement (P = 0.023). Compared with nonobese patients, the rate of recovery was reduced by 30% in overweight (P = 0.034), 37% in obese (P = 0.025), and 48% in morbidly obese patients (P = 0.003). Alternatively, we found that for every unit increase in BMI, the functional recovery rate was reduced by 4% (P < 0.001). Changes in FIM scores during the postdischarge period were not significantly different by obesity classification, and all groups achieve similar functional outcome at follow-up (P = 0.482). CONCLUSIONS: Most trauma patients achieve full functional recovery some time after hospital discharge, but the recovery is delayed in obese patients and the delay is directly correlated with the severity of obesity.

El espectro clínico de las demencias frontotemporales: un caso de demencia rápidamente progresiva / The clinical spectrum of frontotemporal dementia: a case of rapidly progressive dementia

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