Publications by authors named "Noe Rodriguez"

19 Publications

  • Page 1 of 1

SAGES guidelines for the surgical treatment of gastroesophageal reflux (GERD).

Surg Endosc 2021 Sep 19;35(9):4903-4917. Epub 2021 Jul 19.

Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.

Background: Gastroesophageal Reflux Disease (GERD) is an extremely common condition with several medical and surgical treatment options. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of GERD with an emphasis on evaluating different surgical techniques.

Methods: Literature reviews were conducted for 4 key questions regarding the surgical treatment of GERD in both adults and children: surgical vs. medical treatment, robotic vs. laparoscopic fundoplication, partial vs. complete fundoplication, and division vs. preservation of short gastric vessels in adults or maximal versus minimal dissection in pediatric patients. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed.

Results: The panel provided seven recommendations for adults and children with GERD. All recommendations were conditional due to very low, low, or moderate certainty of evidence. The panel conditionally recommended surgical treatment over medical management for adults with chronic or chronic refractory GERD. There was insufficient evidence for the panel to make a recommendation regarding surgical versus medical treatment in children. The panel suggested that once the decision to pursue surgical therapy is made, adults and children with GERD may be treated with either a robotic or a laparoscopic approach, and either partial or complete fundoplication based on surgeon-patient shared decision-making and patient values. In adults, the panel suggested either division or non-division of the short gastric vessels is appropriate, and that children should undergo minimal dissection during fundoplication.

Conclusions: These recommendations should provide guidance with regard to surgical decision-making in the treatment of GERD and highlight the importance of shared decision-making and patient values to optimize patient outcomes. Pursuing the identified research needs may improve future versions of guidelines for the treatment of GERD.
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September 2021

Is peroral endoscopic myotomy (POEM) more effective than pneumatic dilation and Heller myotomy? A systematic review and meta-analysis.

Surg Endosc 2021 05 2;35(5):1949-1962. Epub 2021 Mar 2.

Department of Surgery, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 125, Indianapolis, IN, 46202, USA.

Background: Achalasia is a rare, chronic, and morbid condition with evolving treatment. Peroral endoscopic myotomy (POEM) has gained considerable popularity, but its comparative effectiveness is uncertain. We aim to evaluate the literature comparing POEM to Heller myotomy (HM) and pneumatic dilation (PD) for the treatment of achalasia.

Methods: We conducted a systematic review of comparative studies between POEM and HM or PD. A priori outcomes pertained to efficacy, perioperative metrics, and safety. Internal validity of observational studies and randomized trials (RCTs) was judged using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2.0 tool, respectively.

Results: From 1379 unique literature citations, we included 28 studies comparing POEM and HM (n = 21) or PD (n = 8), with only 1 RCT addressing each. Aside from two 4-year observational studies, POEM follow-up averaged ≤ 2 years. While POEM had similar efficacy to HM, POEM treated dysphagia better than PD both in an RCT (treatment "success" RR 1.71, 95% CI 1.34-2.17; 126 patients) and in observational studies (Eckardt score MD - 0.43, 95% CI - 0.71 to - 0.16; 5 studies; I 21%; 405 patients). POEM needed reintervention less than PD in an RCT (RR 0.19, 95% CI 0.08-0.47; 126 patients) and HM in an observational study (RR 0.33, 95% CI 0.16, 0.68; 98 patients). Though 6-12 months patient-reported reflux was worse than PD in 3 observational studies (RR 2.67, 95% CI 1.02-7.00; I 0%; 164 patients), post-intervention reflux was inconsistently measured and not statistically different in measures ≥ 1 year. POEM had similar safety outcomes to both HM and PD, including treatment-related serious adverse events.

Conclusions: POEM has similar outcomes to HM and greater efficacy than PD. Reflux remains a critical outcome with unknown long-term clinical significance due to insufficient data and inconsistent reporting.
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May 2021

Surgical treatment of GERD: systematic review and meta-analysis.

Surg Endosc 2021 Aug 2;35(8):4095-4123. Epub 2021 Mar 2.

Department of Surgery, University of Chicago Medicine, 5841 S. Maryland Avenue, MC 4062, Chicago, IL, 606037, USA.

Background: Gastroesophageal reflux disease (GERD) has a high worldwide prevalence in adults and children. There is uncertainty regarding medical versus surgical therapy and different surgical techniques. This review assessed outcomes of antireflux surgery versus medical management of GERD in adults and children, robotic versus laparoscopic fundoplication, complete versus partial fundoplication, and minimal versus maximal dissection in pediatric patients.

Methods: PubMed, Embase, and Cochrane databases were searched (2004-2019) to identify randomized control and non-randomized comparative studies. Two independent reviewers screened for eligibility. Random effects meta-analysis was performed on comparative data. Study quality was assessed using the Cochrane Risk of Bias and Newcastle Ottawa Scale.

Results: From 1473 records, 105 studies were included. Most had high or uncertain risk of bias. Analysis demonstrated that anti-reflux surgery was associated with superior short-term quality of life compared to PPI (Std mean difference =  - 0.51, 95%CI  - 0.63, - 0.40, I = 0%) however short-term symptom control was not significantly superior (RR = 0.75, 95%CI 0.47, 1.21, I = 82%). A proportion of patients undergoing operative treatment continue PPI treatment (28%). Robotic and laparoscopic fundoplication outcomes were similar. Compared to total fundoplication, partial fundoplication was associated with higher rates of prolonged PPI usage (RR = 2.06, 95%CI 1.08, 3.94, I = 45%). There was no statistically significant difference for long-term symptom control (RR = 0.94, 95%CI 0.85, 1.04, I = 53%) or long-term dysphagia (RR = 0.73, 95%CI 0.52, 1.02, I = 0%). Ien, minimal dissection during fundoplication was associated with lower reoperation rates than maximal dissection (RR = 0.21, 95%CI 0.06, 0.67).

Conclusions: The available evidence regarding the optimal treatment of GERD often suffers from high risk of bias. Additional high-quality randomized control trials may further inform surgical decision making in the treatment of GERD.
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August 2021

Pressure-Driven Mitochondrial Transfer Pipeline Generates Mammalian Cells of Desired Genetic Combinations and Fates.

Cell Rep 2020 12;33(13):108562

Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Generating mammalian cells with desired mitochondrial DNA (mtDNA) sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nuclear DNA (nDNA) combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (ρ0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a ρ0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogrammed non-immortal SIMR fibroblasts into induced pluripotent stem cells (iPSCs) with subsequent differentiation into diverse functional cell types, including mesenchymal stem cells (MSCs), adipocytes, osteoblasts, and chondrocytes. Remarkably, after reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble unmanipulated control fibroblasts carried through the same protocol. Thus, our MitoPunch "pipeline" enables the production of SIMR cells with unique mtDNA-nDNA combinations for additional studies and applications in multiple cell types.
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December 2020

Impact of sleeve gastrectomy and Roux-en-Y gastric bypass on biopsy-proven non-alcoholic fatty liver disease.

Surg Endosc 2020 05 29;34(5):2266-2272. Epub 2019 Jul 29.

Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, 9500 Euclid Avenue, Desk M61, Cleveland, OH, 44195, USA.

Background: Non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome. Our aim was to study the long-term effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on NAFLD/NASH.

Methods: Between 2008 and 2015, 3813 patients had an intraoperative liver biopsy performed at the time of primary RYGB and SG at a single academic center. Utilizing strict inclusion criteria, 487 patients with biopsy-proven NAFLD who had abnormal alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values (≥ 40 IU/L) at baseline were identified. Matching of SG to RYGB patients (1:4) was performed via logistic regression and propensity scores adjusting for clinical and liver histological characteristics. Changes in liver function tests (LFTs) at least 1 year after surgery were compared to baseline values and between the surgical groups.

Results: A total of 310 (weighted) patients (SG n = 62, and RYGB n = 248) with a median follow-up time of 4 years (range, 1-10) were included in the analysis. The distribution of covariates was well-balanced after propensity matching. In 84% of patients, LFT values normalized after bariatric surgery at the last follow-up time. The proportions of patients having normalized LFT values did not differ significantly between the SG and RYGB groups (82% vs. 84%, p = 0.66). The AST decreased from (SG: 49.1 ± 21.5 vs. RYGB: 49.3 ± 22.0, p = 0.93) at baseline to (SG: 28.0 ± 16.5 vs. RYGB: 26.5 ± 15.5, p = 0.33) at the last follow-up. Similarly, a significant reduction in ALT values from (SG: 61.7 ± 30.0 vs. RYGB 59.4 ± 24.9, p = 0.75) at baseline to (SG: 27.2 ± 21.5 vs. RYGB: 26.1 ± 19.2, p = 0.52) at the last follow-up was observed.

Conclusions: In patients with biopsy-proven NAFLD/NASH, abnormal LFTs are normalized in most SG and RYGB patients by the end of the first postoperative year and remain normal until the last follow-up. This study also suggests that both bariatric procedures are similarly effective in improving liver function.
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May 2020

Detection of Coxiella burnetii DNA in Peridomestic and Wild Animals and Ticks in an Endemic Region (Canary Islands, Spain).

Vector Borne Zoonotic Dis 2017 09 31;17(9):630-634. Epub 2017 Jul 31.

2 Unidad de Enfermedades Infecciosas y Medicina Tropical, Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria (CHUIMI) , Las Palmas de Gran Canaria, Spain .

Coxiella burnetii, the etiological agent of human Q fever, can infect mammals, birds, and arthropods. The Canary Islands (Spain) are considered an endemic territory, with a high prevalence in both humans and livestock. Nonetheless, there is no epidemiological information about the wild and peridomestic cycles of C. burnetii. Tissue samples from rodents on farms (100) and wild rabbits (129) were collected and assessed by PCR to detect C. burnetii DNA. In parallel, ticks were also collected from vegetation (1169), livestock (335), domestic dogs (169), and wild animals (65). Globally, eight rodents (8%) and two rabbits (1.5%) were found to be positive, with the spleen being the most affected organ. Tick species identified were Hyalomma lusitanicum, Rhipicephalus turanicus, Rhipicephalus sanguineus, and Rhipicephalus pusillus. Hyalomma lusitanicum (80%) was the main species identified in vegetation, livestock, and wild animals, whereas Rhipicephalus sanguineus was the most prevalent in domestic dogs. Overall, C. burnetii DNA was detected in 6.1% of the processed ticks, distributed between those removed from livestock (11.3%), domestic dogs (6.9%), and from wild animals (6%). Ticks from vegetation were all negative. Results suggest that, in the Canary Islands, C. burnetii develops in a peridomestic rather than a wild cycle.
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September 2017

Morbidity and mortality in severely burned children with Clostridium difficile-associated diarrhea.

Surgery 2016 06 25;159(6):1631-1637. Epub 2016 Mar 25.

Department of Surgery, Division of Plastic Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.

Background: Clostridium difficile is a key culprit underlying nosocomial infectious diarrhea. We investigated the effect of C difficile-associated diarrhea (CDAD) on morbidity and mortality in severely burned children and CDAD risk factors.

Methods: After review of 2,840 records, 288 pediatric burn patients were identified as having stool output of >10 mL•kg(-1)•min(-1) for ≥2 successive days and had stool samples immunoassayed for toxins A and B. A case control analysis was performed by matching cases to controls via logistic regression and propensity scores so that age, admission time, and time of occurrence could be controlled; the endpoints were mortality and hospitalization time.

Results: Eighteen patients tested positive for C difficile toxins (median age, 4 years; mean total body surface area burned, 59%). In the CDAD group, unadjusted in-hospital mortality was 28% (odds ratio, 5.4; 95% CI, 1.7-16.7; P = .01). Hospitalization averaged 48 days in the CDAD group and 38 days in the non-CDAD group (P = .24). Duration of stay per percent total body surface area burned was greater in the CDAD group (0.82 ± 0.4 vs 0.60 ± 0.4; P = .03), as were prolonged bouts of diarrhea complicated by acidosis (13 ± 16 vs 4 ± 5 days; P < .005). Of the 18 possible risk factors evaluated, inhalation injury diagnosed at admission occurred more often in CDAD patients than matched controls (59% vs 31%; P = .04).

Conclusion: CDAD during hospitalization is associated with greater mortality after burns. Inhalation injury increases the likelihood of C difficile infection. Whether C difficile infection is an indication of greater illness among certain burned patients is unknown.
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June 2016

Triglycerides produced in the livers of fasting rabbits are predominantly stored as opposed to secreted into the plasma.

Metabolism 2015 May 8;64(5):580-7. Epub 2015 Jan 8.

Department of Geriatrics, Center for Translational Research in Aging & Longevity, University of Arkansas Medical School, Little Rock, AR 72205, USA.

Objective: The liver plays a central role in regulating fat metabolism; however, it is not clear how the liver distributes the synthesized triglycerides (TGs) to storage and to the plasma.

Materials And Methods: We have measured the relative distribution of TGs produced in the liver to storage and the plasma by means of U-(13)C(16)-palmitate infusion in anesthetized rabbits after an overnight fast.

Results: The fractional synthesis rates of TGs stored in the liver and secreted into the plasma were not significantly different (stored vs. secreted: 31.9 ± 0.8 vs. 27.7 ± 2.6%∙h(-1), p > 0.05). However, the absolute synthesis rates of hepatic stored and secreted TGs were 543 ± 158 and 27 ± 7 nmol∙kg(-1)∙min(-1) respectively, indicating that in fasting rabbits the TGs produced in the liver were predominately stored (92 ± 3%) rather than secreted (8 ± 3%) into the plasma. This large difference was mainly due to the larger pool size of the hepatic TGs which was 21 ± 9-fold that of plasma TGs. Plasma free fatty acids (FFAs) contributed 47 ± 1% of the FA precursor for hepatic TG synthesis, and the remaining 53 ± 1% was derived from hepatic lipid breakdown and possibly plasma TGs depending on the activity of hepatic lipase. Plasma palmitate concentration significantly correlated with hepatic palmitoyl-CoA and TG synthesis.

Conclusion: In rabbits, after an overnight fast, the absolute synthesis rate of hepatic stored TGs was significantly higher than that of secreted due to the larger pool size of hepatic TGs. The net synthesis rate of TG was approximately half the absolute rate. Plasma FFA is a major determinant of hepatic TG synthesis, and therefore hepatic TG storage.
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May 2015

Stomoxys calcitrans as possible vector of Trypanosoma evansi among camels in an affected area of the Canary Islands, Spain.

Rev Soc Bras Med Trop 2014 Jul;47(4):510-2

Department of Animal Medicine and Surgery, Veterinary Faculty, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain.

Introduction: Trypanosoma evansi was first identified in the Canary Islands in 1997, and is still present in a small area of the Archipelago. To date, the disease has exclusively affected camel herds, and has not been detected in any other animal hosts. However potential vectors of Trypanosoma evansi must be identified.

Methods: One Nzi trap was placed on a camel farm located in the infected area for a period of one year.

Results: Two thousand five hundred and five insects were trapped, of which Stomoxys calcitrans was the sole hematophagous vector captured.

Conclusions: Stomoxys calcitrans could be exclusively responsible for the transmission of Trypanosoma evansi among camels in the surveyed area, as other species do not seem to be infected by S. calcitrans in the presence of camels.
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July 2014

Anatomic predisposition to ligamentous Lisfranc injury: a matched case-control study.

J Bone Joint Surg Am 2013 Nov;95(22):2043-7

Department of Orthopaedic Surgery and Rehabilitation, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0165. E-mail address for V.P. Panchbhavi:

Background: Subtle, or ligamentous, Lisfranc injuries occur following low-energy trauma to the midfoot and can be debilitating. Since they are ligamentous, they may not heal, requiring arthrodesis in some cases. Certain mortise anatomic characteristics on radiographs have been shown to be associated with a predisposition to the ligamentous subtype of Lisfranc injuries. It is not known whether there are other morphometric characteristics, such as arch height or the relative length of the second metatarsal, that can similarly influence the predisposition to these injuries.

Methods: The present retrospective matched case-control study involved fifty-two control subjects and twenty-six patients with ligamentous Lisfranc injuries treated from 2006 to 2010 at two institutions. Clinical and radiographic data (second metatarsal length relative to foot length, first intermetatarsal angle, navicular-cuboid overlap relative to cuboid vertical height, first metatarsal-talus angle, and calcaneal pitch angle) were examined for the existence of significant differences between control and Lisfranc subjects. Logistic regression analysis was then performed to evaluate potential risk for injury on the basis of these anatomic variables.

Results: Compared with matched controls, patients with a ligamentous Lisfranc injury were found to have a significantly smaller ratio of second metatarsal length to foot length (p < 0.001) on weight-bearing radiographs.

Conclusions: Occurrence of a ligamentous Lisfranc injury was shown to be associated with a smaller ratio of second metatarsal length to foot length; >50% of patients in the injury group had a ratio of <29%.
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November 2013

A transversal study on antibodies against selected pathogens in dromedary camels in the Canary Islands, Spain.

Vet Microbiol 2013 Dec 9;167(3-4):468-73. Epub 2013 Aug 9.

Servei d'Ecopatologia de Fauna Salvatge (SEFaS), Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Spain.

The Canary Islands contain the most important dromedary camel (Camelus dromedarius) population in the European Union and are the main export point of dromedaries to continental Europe and Latin America. We investigated the presence of antibodies against relevant disease agents in 100 Canarian camel sera. Selected blood samples of the same animals were also tested by PCR. Sera were tested for antibodies against Bluetongue virus (BTV; 0%), Bovine Viral Diarrhoea virus (BVDV; 0%), Camelpox virus (CPV; 8% by serum neutralization, 16% by ELISA), Peste des Petits Ruminants virus (PPRV, 0%), Rift Valley Fever virus (RVFV; 0%) and West Nile Fever virus (WNV; 3%), the bacterial pathogens Anaplasma sp. (3%), Brucella sp. (1%), Coxiella burnetii (19%), Mycobacterium avium paratuberculosis (MAP; 22%), Mycobacterium tuberculosis complex (MTC; 10%) and Rickettsia sp. (83%), and the parasites Toxoplasma gondii (36%) and Neospora caninum (86%). The most remarkable findings were the detection of antibodies against CPV and the high antibody prevalence against C. burnetii, Rickettsia sp., T. gondii and N. caninum. By PCR, we found no C. burnetii, N. caninum and Anaplasma sp. DNA in the tested samples. However, Rickettsia sp. DNA was detected in six antibody positive tested samples. These results should be taken into consideration in order to implement adequate control measures and avoid a potential dissemination of infections to other territories.
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December 2013

Acute hyperinsulinemia and reduced plasma free fatty acid levels decrease intramuscular triglyceride synthesis.

Metabolism 2013 Jan 13;62(1):44-51. Epub 2012 Aug 13.

Metabolism Unit, Shriners Hospital for Children, University of Texas Medical Branch, Galveston, TX 77550, USA.

Objective: To investigate the effect of acute hyperinsulinemia and the resulting decrease in plasma free fatty acid (FFA) concentrations on intramuscular TG synthesis.

Materials/methods: U-(13)C(16)-palmitate was infused for 3 h in anesthetized rabbits after overnight food deprivation. Arterial blood and leg muscle were sampled during the tracer infusion. Plasma samples were analyzed for free and TG-bound palmitate enrichments and concentrations. The enrichments and concentrations of palmitoyl-CoA and palmitoyl-carnitine as well as the enrichment of palmitate bound to TG were measured in muscle samples. Fractional synthetic rate (FSR) of intramuscular TG was calculated using the tracer incorporation method. The rabbits were divided into a control group and a hyperinsulinemic euglycemic clamp group. Insulin infusion decreased the rate of appearance of plasma free palmitate (2.00±0.15 vs 0.68±0.20 μmol⋅kg(-1)⋅min(-1); P<.001), decreased plasma FFA concentration (327±61 vs 72±25 nmol/mL; P<.01), decreased the total concentration of intramuscular fatty acyl-CoA plus fatty acyl-carnitine (12.1±1.6 vs 7.0±0.7 nmol/g; P<.05), and decreased intramuscular TG FSR (0.48±0.05 vs 0.21±0.06%/h; P<.01) in comparison with the control group. Intramuscular TG FSR was correlated (P<.01) with both plasma FFA concentrations and intramuscular fatty acyl-CoA concentrations.

Conclusions: Fatty acid availability is a determinant of intramuscular TG synthesis. Insulin infusion decreases plasma and intramuscular fatty acid availability and thereby decreases TG synthesis.
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January 2013

Long-term propranolol use in severely burned pediatric patients: a randomized controlled study.

Ann Surg 2012 Sep;256(3):402-11

Shriners Hospitals for Children-Galveston, Galveston, TX 77550, USA.

Objective: To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.

Background: Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear.

Methods: One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant.

Results: Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used.

Conclusions: Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at NCT00675714.
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September 2012

Molecular method for the characterization of Coxiella burnetii from clinical and environmental samples: variability of genotypes in Spain.

BMC Microbiol 2012 Jun 1;12:91. Epub 2012 Jun 1.

Laboratorio de Espiroquetas y Patógenos Especiales, Department of Bacteriology, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Ctra, de Pozuelo km 2,6, Majadahonda, Madrid, 28220, Spain.

Background: Coxiella burnetii is a highly clonal microorganism which is difficult to culture, requiring BSL3 conditions for its propagation. This leads to a scarce availability of isolates worldwide. On the other hand, published methods of characterization have delineated up to 8 different genomic groups and 36 genotypes. However, all these methodologies, with the exception of one that exhibited limited discriminatory power (3 genotypes), rely on performing between 10 and 20 PCR amplifications or sequencing long fragments of DNA, which make their direct application to clinical samples impracticable and leads to a scarce accessibility of data on the circulation of C. burnetii genotypes.

Results: To assess the variability of this organism in Spain, we have developed a novel method that consists of a multiplex (8 targets) PCR and hybridization with specific probes that reproduce the previous classification of this organism into 8 genomic groups, and up to 16 genotypes. It allows for a direct characterization from clinical and environmental samples in a single run, which will help in the study of the different genotypes circulating in wild and domestic cycles as well as from sporadic human cases and outbreaks. The method has been validated with reference isolates. A high variability of C. burnetii has been found in Spain among 90 samples tested, detecting 10 different genotypes, being those adaA negative associated with acute Q fever cases presenting as fever of intermediate duration with liver involvement and with chronic cases. Genotypes infecting humans are also found in sheep, goats, rats, wild boar and ticks, and the only genotype found in cattle has never been found among our clinical samples.

Conclusions: This newly developed methodology has permitted to demonstrate that C. burnetii is highly variable in Spain. With the data presented here, cattle seem not to participate in the transmission of C. burnetii to humans in the samples studied, while sheep, goats, wild boar, rats and ticks share genotypes with the human population.
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June 2012

The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes.

PLoS One 2012 11;7(5):e35465. Epub 2012 May 11.

Shriners Hospitals for Children, University of Texas Medical Branch, Galveston, Texas, United States of America.

Background: Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1).

Methodology/principal Findings: Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p<.001] with the initiation of treatment. However, there were no significant differences in the inflammatory response, acute-phase proteins, body composition, muscle protein breakdown or synthesis, or organ function between groups.

Conclusions: Both groups were markedly hypermetabolic and catabolic throughout the acute hospital stay. Normalization of hypercortisolemia with ketoconazole therapy had no effect on whole-body catabolism or the post-burn inflammatory or hypermetabolic response, suggesting that hypercortisolemia does not play a central role in the post-burn hypermetabolic catabolic response.

Trial Registration: NCT00675714; and NCT00673309.
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October 2012

Five-year outcomes after oxandrolone administration in severely burned children: a randomized clinical trial of safety and efficacy.

J Am Coll Surg 2012 Apr;214(4):489-502; discussion 502-4

Shriners Hospitals for Children-Galveston, Galveston, TX 77550, USA.

Background: Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy.

Study Design: Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored.

Results: Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration.

Conclusions: Administration of oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.
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April 2012

Nutrition in burns: Galveston contributions.

JPEN J Parenter Enteral Nutr 2011 Nov 5;35(6):704-14. Epub 2011 Oct 5.

Department of Surgery, The University of Texas Medical Branch and Shriners Hospitals for Children-Galveston, Galveston, Texas 77550, USA.

Aggressive nutrition support is recommended following severe burn injury. Initially, such injury results in a prolonged and persistent hypermetabolic response mediated by a 10- to 20-fold elevation in plasma catecholamines, cortisol, and inflammatory mediators. This response leads to twice-normal metabolic rates, whole-body catabolism, muscle wasting, and severe cachexia. Thus, it is relevant to review the literature on nutrition in burns to adjust/update treatment. Failure to meet the increased substrate requirements may result in impaired wound healing, multiorgan dysfunction, increased susceptibility to infection, and death. Therefore, aggressive nutrition support is essential to ensure adequate burn care, attenuate the hypermetabolic response, optimize wound healing, minimize devastating catabolism, and reduce morbidity and mortality. Here, the authors provide nutrition recommendations gained from prospective trials, retrospective analyses, and expert opinions based on the authors' practices in Galveston, Texas, and Vienna, Austria.
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November 2011

Measurement of precursor enrichment for calculating intramuscular triglyceride fractional synthetic rate.

J Lipid Res 2012 Jan 20;53(1):119-25. Epub 2011 Sep 20.

Metabolism Unit, University of Texas Medical Branch, Galveston, TX, USA.

Our goal was to assess the validity of the enrichments of plasma free palmitate and intramuscular (IM) fatty acid metabolites as precursors for calculating the IM triglyceride fractional synthetic rate. We infused U-¹³C₁₆-palmitate in anesthetized rabbits for 3 h and sampled adductor muscle of legs using both freeze-cut and cut-freeze approaches. We found that IM free palmitate enrichment (0.70 ± 0.07%) was lower (P < 0.0001) than IM palmitoyl-CoA enrichment (2.13 ± 0.17%) in samples taken by the freeze-cut approach. The latter was close (P = 0.33) to IM palmitoyl-carnitine enrichment (2.42 ± 0.16%). The same results were obtained from the muscle samples taken by the cut-freeze approach, except the enrichment of palmitoyl-CoA (2.21 ± 0.08%) was lower (P = 0.02) than that of palmitoyl-carnitine (2.77 ± 0.17%). Plasma free palmitate enrichment was ∼2-fold that of IM palmitoyl-CoA enrichment and palmitoyl-carnitine enrichment (P < 0.001). These findings indicate that plasma free palmitate overestimated IM precursor enrichment owing to in vivo IM lipid breakdown, whereas IM free palmitate enrichment underestimated the precursor enrichment because of lipid breakdown during muscle sampling and processing. IM palmitoyl-carnitine enrichment was an acceptable surrogate of the precursor enrichment because it was less affected by in vitro lipid breakdown after sampling.
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January 2012

Maternal deprivation induces a rapid decline in circulating leptin levels and sexually dimorphic modifications in hypothalamic trophic factors and cell turnover.

Horm Behav 2010 Apr 25;57(4-5):405-14. Epub 2010 Jan 25.

Department of Physiology (Animal Physiology II), Faculty of Biology, Universidad Complutense, Madrid, Spain.

Pathological outcomes, including metabolic and endocrine disturbances, of maternal deprivation (MD) in Wistar rats depend on gender and the timing of deprivation during development. We analyzed the effect of MD between postnatal days 9 and 10, a critical period in hypothalamic development, on circulating hormones and local production of trophic factors involved in this process, as well as on markers of cell turnover and maturation. Males and females were studied 12 and 24 h after MD and 12 h (MD36) after returning the dam to her pups. Circulating corticosterone levels were increased and glucose and leptin levels decreased throughout the study in both sexes. Hypothalamic mRNA levels of leptin receptor increased significantly at MD24 in both sexes, normalizing in females at MD36, but not in males. In male rats insulin-like growth factor mRNA levels were significantly decreased at MD24 and brain derived neurotrophic factor mRNA levels decreased at MD12 and MD24, with both trophic factors unaffected in females. In males cell proliferation was significantly decreased at MD36, as were the glial structural proteins, glial fibrillary acidic protein and vimentin. In females, nestin levels decreased significantly at MD24. These results indicate that MD differently affects trophic factors and cell-turnover in the hypothalamus of males and females, which may underlie the sex differences seen in the endocrine and metabolic outcome.
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April 2010