In a Setting of Esophageal Replacement, Total Gastric Pull-Up has Fewer Complications than Partial Gastric Pull-Up.

AIM: The main indications for an esophageal replacement (ER) are unresolved complex esophageal atresia (EA) and caustic strictures (CS). The use of different organs for replacement has been described. When the stomach is chosen, there are two ways to do a gastric pull-up: a partial (PGP) or a total pull-up (TGP). Few studies have been published comparing the different techniques. The aim of this study was to compare the outcomes of patients who underwent ER by PGP or by TGT. METHODS: The medical records of all patients who underwent gastric pull-up for ER in the last 18 years at the National Pediatric Hospital Prof. Dr. Juan P. Garrahan were reviewed. The study is comparative, retro-prospective and longitudinal. Patients were divided in two groups according to the ER technique (PGP or TGP). We compared the following outcomes: duration of the operation, days of hospitalization in the intensive care unit (ICU), days of total hospitalization, time to initiation of oral feedings and rate of anastomosis dehiscence, incidence of anastomotic stenosis, need for re-operations, incidence of gastroesophageal reflux disease (GERD), incidence of tracheo-esophageal fistulas (TEF), incidence of dumping syndrome, incidence of gastric necrosis and mortality. RESULTS: There were 92 patients included in the study: 70 in the PGP group (76%) and 26 in the TGP group (24%). The two groups were demographically equivalent. Patients in the TGP group had a statistically significant lower incidence of anastomotic dehiscence (22,7% versus 54,3%; p = 0.01) and dumping syndrome (13,6% versus 37,1%; p = 0.038). Patients in the TGP had lower incidence of anastomotic stenosis, although the difference was not statistically significant. There were no statistically significant differences between the groups in terms of duration of the operation, postoperative days in the ICU, time to oral feedings, GERD, TEF or overall hospital stay. There were no cases of gastric necrosis. There were 3 deaths in the PGP group and one in the TGP group. CONCLUSIONS: We observed benefits in the TGP group versus the PGP approach in terms of anastomotic dehiscence and dumping syndrome, as well as a trend toward a lower incidence of anastomotic stenosis. Based on this experience, we recommend the TGP approach for patients who need an esophageal replacement by a gastric pull-up. LEVELS OF EVIDENCE: According to the Journal of Pediatric Surgery this research corresponds to type of study level III for retrospective comparative study.

Giant omphalocele: Delayed closure using the San Martin technique following epithelialization of the membrane.

AIM: The management of patients with congenital anterior abdominal wall defects remains challenging, particularly in cases of giant omphalocele. In 1948, San Martín described a surgical technique for the repair of large midline incisional hernias in adults without the need for a mesh. The purpose of this report is to describe our experience with this technique for the delayed closure of giant omphaloceles. METHODS: We retrospectively reviewed the outcomes of all patients with giant omphalocele managed with the San Martin technique between September 2013 and March 2019. Data collected included birth weight, gestational age, associated malformations, neonatal hospital stay, age at the time of the abdominal wall closure, days on mechanical ventilation (MV) after the closure, time to initiation of enteral feedings, intra- and postoperative complications, and postoperative hospital stay. RESULTS: A total of 8 patients were included in the study. The median birth weight was 3.190 (2.150 to 3.400) grams. The median gestational age was 35 (32 to 38) weeks. The median age at surgery was 6 (5 to 13) years. The median postoperative days on MV was 3 (3 to 11) days. Enteral feeding were initiated postoperatively at a median of 4 (2 to 4) days. There was one intraoperative complication (minor vascular injury). There were no short-term or long-term complications directly related to the surgical technique. The median postoperative hospital stay was 10 (6 to 16) days. The follow-up was 18 months to 8 years. CONCLUSION: We believe that the San Martín technique is a valid alternative for the delayed closure of giant omphaloceles. LEVEL OF EVIDENCE: According to the Journal of Pediatric Surgery this research corresponds to type of study level IV for case series with no comparison group.

Histiocytic hyperplasia with hemophagocytosis and acute alveolar damage in COVID-19 infection.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

Oxidative and inflammatory effects of pulmonary rehabilitation in patients with bronchiectasis. A prospective, randomized study.

INTRODUCTION: Background: systemic inflammation and oxidative stress are important factors in the pathogenesis of bronchiectasis. Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is no data about its effect on the inflammatory and REDOX status of these patients. Aims: to investigate the effect of PR in non-cystic-fibrosis bronchiectasis (NCFB) patients, and to compare it with the effect of PR plus a hyperproteic oral nutritional supplement (PRS) enriched with beta-hydroxy-beta-methylbutyrate (HMB) on serum inflammatory and oxidative biomarkers. Materials and methods: this was an open randomized, controlled trial. Thirty individuals (65 years old or younger with a body mass index over 18.5, older than 65 years with a body mass index over 20) were recruited from September 2013 to September 2014, and randomly assigned to receive PR or PRS. Total neutrophils, and inflammatory and oxidative biomarker levels were measured at baseline, and then at 3 and 6 months. Results: in the PRS group neutrophil levels were decreased from baseline at 6 months. A significantly different fold change was found between the PR and PRS groups. In the PR group, IL-6 and adiponectin were increased by the end of the study while TNFα levels were decreased from baseline at 6 months. REDOX biomarkers remained stable throughout the study except for 8-isoprostane levels, which were increased from baseline at 6 months in both groups of patients. Conclusions: a PR program induced a pro-oxidative effect accompanied by changes in circulating inflammatory cytokine levels in NCFB patients. Our results would also suggest a possible beneficial effect of the HMB enriched supplement on neutrophil level regulation in these patients. The information provided in this study could be useful for choosing the right therapeutic approach in the management of bronchiectasis.

INTRODUCCIÓN: Introducción: la inflamación sistémica y el estrés oxidativo son factores importantes en la patogénesis de la bronquiectasia. La rehabilitación pulmonar (PR) está recomendada en los sujetos con bronquiectasias, pero no hay datos sobre sus posibles efectos sobre el estado inflamatorio y REDOX de estos pacientes. Objetivos: investigar el efecto de la PR en pacientes con bronquiectasias no asociadas a fibrosis quística (NCFB) sobre los biomarcadores oxidativos e inflamatorios, y compararlo con los efectos de la PR junto con la suplementación oral de un suplemento hiperproteico (PRS) enriquecido con beta-hidroxi-beta-metilbutirato (HMB). Material y métodos: ensayo clínico abierto, aleatorizado y controlado. Treinta pacientes (de 65 años o menos con un índice de masa corporal por encima de 18,5, y mayores de 65 años con un índice de masa corporal de más de 20) se aleatorizaron para recibir PR o PRS. Los niveles circulantes de neutrófilos totales y los de biomarcadores de estado inflamatorio y oxidativo se determinaron al inicio del estudio y a los 3 y 6 meses. Resultados: los niveles de neutrófilos en el grupo de PRS se redujeron desde el inicio a los 6 meses, presentando una tasa de cambio significativamente diferente según el tratamiento. En el grupo de PR, la IL-6 y la adiponectina aumentaron al final del estudio, mientras que los niveles de TNFα disminuyeron desde el inicio a los 6 meses. Los biomarcadores de estrés oxidativo se mantuvieron estables durante todo el estudio excepto por los niveles de 8-isoprostano, que aumentaron desde el inicio a los 6 meses en ambos grupos de pacientes. Conclusión: el programa de PR indujo un efecto pro-oxidativo acompañado de cambios en los niveles de citoquinas inflamatorias circulantes en pacientes con NCFB. Nuestros resultados también sugieren un posible efecto beneficioso del suplemento nutricional sobre la regulación de los niveles de neutrófilos de estos pacientes.

Osteopenia and Osteoporosis in Patients with Bronchiectasis: Association with Respiratory Parameters, Body Composition, Muscle Strength and Bone Remodeling Biomarkers.

The prevalence of osteopenia/osteoporosis has not been sufficiently studied in people with bronchiectasis not due to cystic fibrosis (BC), nor has its relationship with other variables (clinical, body composition and bone turnover and inflammation markers) been sufficiently studied. Our aim was to determine the prevalence of osteopenia and osteoporosis and related factors in patients with BC. We did a cross-sectional study in people with BC in a clinically stable state. Spirometric parameters, annual exacerbations and analysis with bone turnover markers (BTM) and inflammation markers were evaluated. Densitometry (DXA) was performed for body composition, bone mineral density (BMD) and handgrip strength. 123 patients were studied (65% women, mean age 49.6 ± 18.8, Body Mass Index (BMI) 24.8 ± 4.7 kg/m2). 62.8% and 62.5% of men and women, respectively, had normal bone mineral density, 30.2% and 22.2% osteopenia and 7% and 15% osteoporosis. 52 patients (56.2%) had low fat-free mass: 68.9% women and 28.6% men. Patients with decreased bone mass had significantly lower muscle strength, maximum expiratory volume in the first second (FEV1%), vitamin D, higher levels of C-terminal telopeptide of type 1 collagen (CTX) and total osteocalcin and underarboxylated osteocalcin (ucOC). We observed significant and negative correlations between BMD and the number of serious exacerbations per year CTX and undercarboxylated osteocalcin. We observed significant positive correlations between BMD, fat free mass index (FFMI) and handgrip dynamometry. The study suggest that the prevalence of osteoporosis was high in relation to the demographic characteristics. Respiratory parameters, body composition, muscle strength and bone remodeling markers were associated with a lower bone mineral density.

Inflammation and Oxidation Biomarkers in Patients with Cystic Fibrosis: The Influence of Azithromycin.

OBJECTIVE: In addition to their antibiotic effect, macrolides appear to modulate the inflammatory response in cystic fibrosis (CF) and could influence oxidative stress. The objective of this study was to assess oxidation biomarkers and levels of inflammation and to determine whether there is an association between these parameters and the intake of macrolides. MATERIALS AND METHODS: The subjects included in this cross-sectional study were, on the one hand, clinically stable patients with CF and, on the other, healthy controls. The following serum and plasma inflammatory and oxidative stress biomarkers were measured: interleukin-6 (IL-6), reactive C protein (RCP), tumor necrosis alpha (TNF-α), glutathione peroxidase (GPx), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD), together with markers of lipid peroxidation (8-isoprostanes and thiobarbituric acid reactive substances [TBARS]). Clinical, anthropometric, lung function, radiological, and analytical variables (albumin, prealbumin, vitamins, and zinc) were also recorded. RESULTS: We studied 36 adults with CF and 41 controls. No differences were observed in age, gender, or anthropometric variables. The patients had significantly higher levels of IL-6, TNF-α, RCP, TBARS, and isoprostanes, and lower levels of SOD than the controls. Twenty-three of the patients were treated with azithromycin, and they had more severe clinical and radiological parameters than those who were not but nevertheless presented significantly lower levels of TNF-α. No differences were observed in the markers of oxidation. CONCLUSION: Inflammation and oxidation biomarkers were increased in patients with CF compared with controls. The use of azithromycin was associated with reduced TNF-α levels and did not influence oxidation parameters.

Dietary fatty acids modulate adipocyte TNFa production via regulation of its DNA promoter methylation levels.

The factors regulating TNF alpha (TNFa) levels could be considered therapeutic targets against metabolic syndrome development. DNA methylation is a potent regulator of gene expression and may be associated with protein levels. In this study we investigate whether the effect of dietary fatty acids on TNFa released from adipocytes might be associated with modifications of the TNFa promoter DNA methylation status. A group of rats was assigned to three diets with a different composition of saturated, monounsaturated and polyunsaturated fatty acids. Samples of visceral adipose tissues were taken for adipocyte isolation, in which released TNFa levels were measured, and for methylation and expression studies. In addition, 3 T3-L1 cells were treated with palmitic, oleic and linoleic acids, with and without 5-Azacitydine (5-AZA). After treatments, cells and supernatants were included in the same analyses as rat samples. TNFa promoter methylation levels, gene expression and secretion were different according to the diets and fatty acid treatments associated with them. Cells treated with 5-AZA displayed higher TNFa levels than in the absence of 5-AZA, without differences between fatty acids. According to our results, dietary fatty acid regulation of adipocyte TNFa levels may be mediated by epigenetic modifications of the TNFa promoter DNA methylation levels.

Hernia diafragmática congénita bilateral de diagnóstico tardío: reporte de un caso / Late diagnosis bilateral congenital diaphragmatic hernia: a case report

La hernia diafragmática congénita (HDC) es una malformación rara, habitualmente unilateral y más frecuente del lado izquierdo. La HDC bilateral representa el 1% de todas las HDC. La mortalidad es mayor en las HDC derechas y en las bilaterales. Reportamos el caso de un paciente con HDC bilateral, cuya malformación inicialmente se diagnosticó y trató como una HDC derecha. Luego se encontró la presencia de HDC izquierda durante la cirugía de Ladd laparoscópica a los 8 meses de edad.

Congenital diaphragmatic hernia (CDH) is a rare malformation, usually unilateral and left sided. Bilateral CDH (B-CDH) represents 1% of all CDH. Mortality is higher in right side and bilateral defects. We report a case of a patient with Bilateral CDH, initially diagnosed and treated as unilateral right CDH. At 8 months during a laparoscopic Ladd procedure a left side CDH was found.

Ofatumumab in poor-prognosis chronic lymphocytic leukemia: a phase IV, non-interventional, observational study from the European Research Initiative on Chronic Lymphocytic Leukemia.

We report the largest retrospective, phase IV non-interventional, observational study of ofatumumab therapy in heavily pre-treated patients with poor-prognosis chronic lymphocytic leukemia. Total number of patients was 103; median age was 65 years (range 39-85). Median number of prior lines of therapy was 4 (range 1-13), including, in most cases, rituximab-, fludarabine- and alemtuzumab-based regimens; 13 patients had been allografted. Of 113 adverse events, 28 (29%) were considered to be directly related to ofatumumab. Grade 3-4 toxicities included neutropenia (10%), thrombocytopenia (5%), anemia (3%), pneumonia (17%), and fever (3%). Two heavily pre-treated patients developed progressive multifocal leukoencephalopathy. On an intention-to-treat analysis, the overall response rate was 22% (3 complete response, 1 incomplete complete response). Median progression-free and overall survival times were 5 and 11 months, respectively. This study confirms in a daily-life setting the feasibility and acceptable toxicity of ofatumumab treatment in advanced chronic lymphocytic leukemia. The complete response rate, however, was low. Therefore, treatment with ofatumumab should be moved to earlier phases of the disease. Ideally, this should be done in combination with other agents, as recently approved for ofatumumab plus chlorambucil as front-line treatment for patients unfit for fludarabine. This study is registered at clinicaltrials.gov identifier:01453062.

Oleic acid increases hepatic sex hormone binding globulin production in men.

SCOPE: Low circulating sex hormone-binding globulin (SHBG) is an independent risk factor for cardiovascular disease. Mediterranean diet has been associated with a decreased risk of cardiovascular disease. We aimed to test the hypothesis that the increase of circulating MUFA associated with olive oil consumption (primary fat source in Mediterranean diet) increases SHBG serum levels. METHODS AND RESULTS: A total of 315 men were included. In these patients, nutrition data and plasma samples for SHBG assessment were obtained. In vitro studies to examine the effects of oleic and linoleic acid on SHBG production using HepG2 cells were performed. We provided evidence that SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil. The SHBG levels correlated positively with MUFA (p < 0.001) and negatively with saturated fatty acids (p = 0.003). In the multiple regression analysis, MUFA were independently associated with SHBG levels and accounted for the 20.4% of SHBG variance. In vitro studies revealed that oleoyl-CoA increases SHBG production by downregulating PPAR-γ levels in HepG2 cells. CONCLUSION: Olive oil consumption is associated with elevated SHBG serum levels. PPAR-γ downregulation induced by oleoyl-CoA is an important underlying mechanism of such regulation.

[Relationship between vitamin D deficiency and metabolic syndrome]. / Relación entre déficit de vitamina D y síndrome metabólico.

BACKGROUND AND OBJECTIVE: Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome. PATIENTS AND METHODS: We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured. RESULTS: The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age. CONCLUSIONS: Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome.

C-reactive protein and incidence of type 2 diabetes in the Pizarra study.

AIM: To determine the association between serum levels of high-sensitivity C-reactive protein (hs-CRP) and the incidence of type 2 diabetes in a prospective cohort from southern Spain (Pizarra study). MATERIALS AND METHODS: The study formed part of the Pizarra cohort study, a prospective study started in 1995 with a follow-up of 11 years. Anthropometric and metabolic variables were measured at baseline and at 6 years and 11 years of follow-up. All subjects underwent an oral glucose tolerance test. Serum levels of TNFα and its receptors, hs-CRP, IL-6, leptin, adiponectin and FABP4 were measured at 6 years of follow-up. RESULTS: After adjusting for age, sex and obesity, subjects with levels of hs-CRP> 2.9 mg/L in the second study (2003-4) had a higher risk of developing type 2 diabetes by the third study (2008-9) (OR = 7.97; 95% CI = 1.72-36.89; P = 0.008), and subjects with adiponectin levels > 13.2 mg/L had a lower risk of developing type 2 diabetes (OR = 0.23, P = 0.02). High values of hs-CRP and high values of adiponectin were associated positively (OR = 8.26; 95% CI = 1.84-37.19; P = 0.006) and negatively (OR = 0.17; 95% CI = 0.04-0.69; P = 0.01), respectively, with the risk of having HbA1c ≥ 6.5% at 11 years of follow-up. CONCLUSIONS: Subjects with high serum hs-CRP levels and low serum adiponectin levels have a higher risk of developing type 2 diabetes within five years.

Umbilical arteriovenous malformation in a healthy neonate with umbilical hernia.

We describe the case of a neonate with an umbilical hernia and persistent wet umbilicus. Examination revealed a pulsatile umbilical cord with palpable thrill. Doppler ultrasound suspected umbilical arteriovenous malformation and contrast-enhanced computed tomography was performed leading to a definitive diagnosis. Surgery was successfully performed on day 27.

Children whose diet contained olive oil had a lower likelihood of increasing their body mass index Z-score over 1 year.

OBJECTIVE: Changes in eating habits may be influential in the ever-increasing rate of childhood obesity. Our aim was to determine whether those children who consume olive oil have a lower risk of weight gain compared with children who consume other oils. DESIGN AND METHODS: The study included 18 girls and 74 boys, all aged 13-166 months. A survey was completed for each subject about eating habits and physical activity. A sample of subcutaneous adipose tissue was also obtained for cellular study. Data were recorded on the mean size of the adipocytes, the number of preadipocytes, and the concentration of particular fatty acids. The weight and height of the children were measured 13 months later. RESULTS: The likelihood that after 1 year the children would have increased their body mass index (BMI) Z-score above the initial score was less in the children who consumed only olive oil (odds ratio (OR)=0.22; 95% confidence interval (CI): 0.08-0.63; P=0.005). These results remained after adjusting for age, physical activity and BMI (OR=0.19; 95% CI: 0.06-0.61; P=0.005) and after adjusting for age, physical activity and adipocyte volume (OR=0.15; 95% CI: 0.04-0.52; P=0.003). CONCLUSIONS: Diets with mono unsaturated fatty acid (MUFA)-rich olive oil could reduce the risk of obesity in childhood.

[Diagnosis and treatment of gastrointestinal bleeding in Bean syndrome]. / Diagnóstico y tratamiento de hemorragia digestiva en síndrome de Bean (Blue Rubber-Bleb Nevus Syndrome).

Blue Rubber-Bleb Nevus Syndrome (BRBNS, Bean Syndrome) is a rare disorder characterized by the presence of cutaneous and visceral vascular malformations. Although it may affect several organs, the gastrointestinal tract is one of the most frequently involved sites. It can cause gastrointestinal bleeding and chronic anemia. We report an 8-years-old girl who was admitted because of cutaneous malformations and anemia suspected to be caused by gastrointestinal bleeding. Cutaneous lesions were compatible with Blue Rubber-Bleb Nevus Syndrome. Vascular malformations were confirmed by diagnostic gastroduodenoscopy and colonoscopy and further therapeutical intervention was planned. We performed banding of 2 lesions located in the stomach and sclerotherapy of a duodenal lesion. Six colonic lesions were treated with banding and three other polypoid lesions were endoscopically resected A combined laparoscopic and endoscopic approach was performed for evaluation and treatment of small-bowel lesions. Eighteen lesions were found. We endoscopically resected 8 polipoid lesions. Eight other large transmural lesions were removed by wedge resection. Only one lesion required termino-terminal anastomosis. We consider that endoscopic treatment and laparoscopically assisted enteroscopy are safe and effective options in the treatment of gastrointestinal bleeding caused by vascular malformations.

Thoracoscopic approach for congenital esophageal stenosis.

Congenital esophageal stenosis (CES) is an infrequent entity; however, many cases have been reported during the last years. Its incidence falls between 1 per 25,000 and 1 per 50,000 live births and is associated with other congenital malformations in 17% to 33% of cases (mainly esophageal atresia). Congenital esophageal stenosis is defined as an intrinsic alteration of the esophageal wall given by the presence of ectopic tracheobronchial tissue, membranous diaphragm, muscular hypertrophy, or diffuse fibrosis of the submucosa, among other causes. The therapeutic options include endoscopic dilation and resection plus anastomosis (by either laparotomy or thoracotomy, depending on the level of the stenosis). We present the case of a 1-month-old baby boy with a CES located in the distal esophagus that is associated with anophthalmia and micropenis. We treated the lesion by means of a thoracoscopic resection of the affected segment and an esophageal end-to-end anastomosis. The patient's long-term outcome was uneventful. As far as we know, this is the first report on thoracoscopic resolution of a CES.