Does pregabalin act in pain control after lateral pharyngoplasties and tonsillectomies? A pilot study.

OBJECTIVE: Some studies have pointed to gabapentinoids as promising medications in postoperative pain control. The objective of the present study was to evaluate the efficacy of pregabalin in reducing postoperative pain in tonsillectomy and lateral pharyngoplasties. STUDY DESIGN: Double-blind randomized controlled trial. SETTING: Tertiary care center. METHODS: A double-blind randomized controlled trial was conducted with patients undergoing tonsillectomies and lateral pharyngoplasties between Aug 29, 2017, and Oct 31, 2020. Data of interest such as opioid consumption, pain scores, and adverse outcomes such as dizziness, nausea, headache, and sedation within 7 days following surgeries were analyzed. RESULTS: No statistically significant difference was observed in pain scores and opioid consumption between the groups studied in the pilot project. The use of pregabalin was associated with lower incidence of dizziness compared to controls. CONCLUSION: Gabapentinoids, especially pregabalin, are drugs whose potential for controlling pain after pharyngeal surgery, such as tonsillectomy and sleep apnea surgery, still needs to be more fully evaluated. After the conclusion of the present study, we hope to answer this question about the role of pregabalin in oropharyngeal surgeries.

Green does not always mean go: A sulfated galactan from Codium isthmocladum green seaweed reduces melanoma metastasis through direct regulation of malignancy features.

Melanoma is the most lethal form of skin cancer, with a worldwide increase in incidence. Despite the increased overall survival of metastatic melanoma patients given recent advances in targeted and immunotherapy, it still has a poor prognosis and available treatment options carry diverse severe side effects. Polysaccharides from seaweed have been shown to exert antitumor activities. Here we show in vitro and in vivo antitumor activities of a sulfated homogalactan (named 3G4S) from Codium isthmocladum seaweed in the B16-F10 murine melanoma cell line. 3G4S did not induce cytotoxicity or proliferation changes; however, it was able to reduce solid tumor growth and metastasis, while not inducing side effects in mice. B16-F10 cells traits related to the metastatic cascade were also impaired by 3G4S, reducing cell invasion, colony-forming capacity and membrane glycoconjugates. Therefore, 3G4S shows promising antitumor activities without the commonly associated drawbacks of cancer treatments and can be further explored.

Non-Cytotoxic Sulfated Heterorhamnan from Gayralia brasiliensis Green Seaweed Reduces Driver Features of Melanoma Metastatic Progression.

Melanoma is a form of skin cancer with high mortality owing to its fast progression and metastatic capacity. The treatments available nowadays are only palliative in advanced stages of the disease. Thus, alternative therapies for cancer treatment are in demand, and molecules from natural sources, such as polysaccharides, could represent new possible therapeutic approaches. Polysaccharides of freshwater and marine algae with biological activities, such as antitumor properties, are greatly reported in the scientific literature. In the present study, a sulfated heterorhamnan obtained from the green seaweed Gayralia brasiliensis (Gb1 fraction) was chemically characterized and its biological activities in the B16-F10 murine melanoma cell line were evaluated. The Gb1 polysaccharidic fraction tested concentrations presented low or absence of cytotoxicity to B16-F10 cells and neither cell proliferation nor cell cycle were altered. Interestingly, Gb1 treatment decreased B16-F10 cells migration and invasion capabilities and CD44 labeling, showing to be a promising compound for further in vitro and in vivo antitumor studies.

Malignancy and mortality in paediatric-onset inflammatory bowel disease: a 3-year prospective, multinational study from the paediatric IBD Porto group of ESPGHAN.

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.

Safe therapeutics of murine melanoma model using a novel antineoplasic, the partially methylated mannogalactan from Pleurotus eryngii.

A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by ß-d-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.

Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial.

BACKGROUND: Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS: Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS: SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS: These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.

Hiatal hernia and gastroesophageal reflux: Study of collagen in the phrenoesophageal ligament.

BACKGROUND: Gastroesophageal reflux disease (GERD) is defined by the intensity and/or quality of the reflux of gastric or duodenal contents into the esophagus. Surgical treatment of GERD has shown conflicting results and unacceptable recurrence rates, mainly due to herniation of the antireflux valve into the chest. A variety of techniques has been proposed to reduce GERD recurrence, including routine use of prosthesis in cruroplasty. The prevalence of GERD in patients with hiatal hernia (HH) can reach 94 %. It is possible that the phrenoesophageal ligament (POL) engaged in the stabilization of the gastroesophageal junction in the abdomen may be an etiological factor of HH. We conducted a study to evaluate collagen in the constitution of the POL in patients with HH and cadavers without HH. METHODS: POL samples were collected from 29 patients with HH and GERD (cases) and 32 samples from cadavers without HH (controls). Total collagen was quantified through the Picrosirius red histochemical technique, and type-I and type-III collagens were quantified immunohistochemically using a monoclonal antibody. The stained slides were photographed, and images were quantified by computer software (Image Pro Plus) to count the pixels per field. RESULTS: The mean age was 49.5 (±11.5) years for the cases and 38.5 (±13) years for the controls (p < 0.01). Seventeen cases (58.6 %) and six controls (18.75 %) were female (p < 0.01). The quantity of total (p < 0.01), type-I (p < 0.01), and type-III (p < 0.05) collagens was significantly lower by about 60 % in patients with HH compared with controls. CONCLUSION: Our data indicate that the composition of POL for patients with GERD and HH includes less total, type-I, and type-III collagens than that of the POL of cadavers without HH. The quality of the POL may be an etiological factor in the development of HH.

Bjcul, a snake venom lectin, modulates monocyte-derived macrophages to a pro-inflammatory profile in vitro.

Macrophages are cells of high plasticity and can act in different ways to ensure that the appropriate immune response remains controlled. This study shows the effects of the C-type Bothrops jararacussu venom lectin (BJcuL) on the activation of human macrophages derived from the U937 cell line. BJcuL binds on the cell surface, and this event is inhibited by its specific carbohydrate. It induced phagocytosis and production of H2O2, and expression of antigen presentation molecules. It also enhanced the production of TNF-α, GM-CSF and IL-6 by macrophages and indirectly induced T cells to an increased production of TNF-α, IFN-γ and IL-6 in the presence of LPS. Our results suggest that BJcuL can modulate macrophage functional activation towards an M1 state.

A pediatric case of gluten sensitivity with severe neurological presentation.

UNLABELLED: Neurologic manifestations are present in a reasonable proportion of adult celiac patients and can be the first sign of gluten sensitivity. In children, the risk of neurological complications is lower, and gluten sensitivity with neurological presentation seems to be rare. We report a case of gluten sensitivity with severe neurological presentation in a 3-year-old girl. In the absence of gastrointestinal symptoms, the presence of white matter lesions in cerebral magnetic resonance imaging suggested an acute disseminated encephalomyelitis. Recurrence of neurologic symptoms and cerebral lesions over a long period of time made the authors consider an autoimmune/inflammatory systemic disease. IgA anti-transglutaminase (TG) 2 was elevated and duodenal biopsy confirmed the presence of enteropathy. A gluten-free diet led to complete resolution of neurological manifestations and arrest of white matter lesions progression. CONCLUSION: In children with unclear neurologic manifestations with probable autoimmune etiology, anti-TG2 autoantibody titers should be determined considering the possibility of gluten sensitivity. Gluten-free diet remains the only effective treatment reported to date and, therefore, should be recommended to all patients with gluten sensitivity despite the type of manifestations. More studies, focusing on neurological manifestations and its response to gluten-free diet, are needed.

Influence of oily vehicles on fetal testis and lipid profile of rats exposed to di-butyl phthalate.

It has been hypothesized that oils containing high levels of omega-3 polyunsaturated fatty acids, such as canola and fish oil, could counteract some of the adverse effects induced by phthalates. In the present study, the influence of different oily vehicles on di-butyl phthalate (DBP)-induced testicular toxicity and lipid profile was investigated. Pregnant Wistar rats were treated by oral gavage from gestation days 13 to 20 with DBP (500 mg/kg/day) diluted in three different vehicles: corn, canola or fish oil. Male fetuses were analyzed on gestation day 20. DBP exposure lowered intratesticular testosterone levels and anogenital distance, regardless of the vehicle used. The percentage of seminiferous cords containing multinucleated gonocytes and cord diameter was increased in DBP-exposed groups, compared with vehicle controls, with no difference between the three DBP-exposed groups. Clustering of Leydig cells was seen in all DBP groups. Lipid profile indicated that administration of canola and fish oil can increase the content of omega-3 fatty acids in rat testis. However, content of omega-3 was diminished in DBP-treated groups. Overall, our results indicate that different oily vehicles did not alter fetal rat testicular toxicity induced by a high DBP dose.

Miotomía de Heller laparoscópica: resultados en niños / Outcome of laparoscopic heller myotomy in children

Objetivos. El presente estudio tuvo como objetivo evaluar los resultados a corto y medio plazo de la miotomía de Heller laparoscópica. Métodos. Fueron incluidos niños sometidos a cirugía desde 2002 hasta 2010. La cirugía fue propuesta tras el fracaso de las dilataciones endoscópicas. Todos los pacientes fueron sometidos a esofagocardiomiotomía (Heller) con funduplicatura anterior (Dor) por laparoscopia. La demografía, síntomas de presentación y detalles perioperatorios fueron analizados. Los resultados fueron evaluados por los registros médicos y la aplicación de un cuestionario de auto-evaluación (GIQLI modificado), cubriendo síntomas gastrointestinales superiores) con 14 preguntas cada una puntuada de 0 (peor) hasta 4 (mejor o normal).Resultados. Seis pacientes (5 varones) con una edad media de 12,2 años (rango: 0,8-14,2) fueron sometidos a cirugía. Los síntomas de presentación fueron: disfagia (83,3%), pérdida de peso (50%), vómitos (33,3%), tos (33,3%) y dolor torácico (16,7%). Todos los pacientes fueron operados por laparoscopia sin conversiones y no hubo complicaciones intra, ni postoperatorias. Con una mediana de seguimiento de 5 años (rango: 2-10), ninguno de los pacientes fue re-operado. Cinco pacientes tienen hábitos alimentarios normales; el caso restante presentó episodios recurrentes de disfagia, requiriendo dilataciones endoscópicas periódicas (cada 6 meses). El GIQLI total presentó una media de 49,3 puntos (rango, 45-52), lo que representa 88,1% del máximo posible. La puntuación para la frecuencia de episodios de disfagia fue 1,6 ± 1,4; la puntuación para el grado de disfagia fue 3 en todos los pacientes. Conclusiones. La miotomía de Heller laparoscópica es efectiva y segura en niños, ofreciendo una calidad de vida buena y duradera; a pesar de frecuentes, los episodios de disfagia son ligeros (AU)

Aim. The appropriate management of achalasia in children remains debatable. The present study aimed to evaluate the outcome of laparoscopic Heller myotomy by assessing short- and mid-term issues. Methods. Children submitted to surgery from 2002 to 2010 were included. Surgery was proposed after failure of endoscopic dilatations. All patients underwent esophagocardiomyotomy (Heller) plus anterior fundoplication (Dor) by laparoscopy. Demographics, presentation symptoms and perioperative details were analyzed. The outcomes were assessed both by medical records and the application of a 14 items (score 0-worst to 4-best/normal) self-evaluation questionnaire (modified GIQLI - covering only upper gastrointestinal symptoms).Results. Six patients (5 males) with a median age of 12.2 years (range: 0.8-14.2) were submitted to surgery. The presenting symptoms were: dysphagia (83.3%), weight loss (50%), vomiting (33.3%), chronic cough (33.3%), and chest pain (16.7%). All patients were operated on by laparoscopy with no conversions; there were no intra or postoperative complications. At a median follow-up of 5 years (range: 2-10) none of the patients were re-operated. Five patients have normal eating habits; the remaining case presented recurrent episodes of dysphagia requiring regular endoscopic dilatations (every 6 months). The total GIQLI presented a mean score of 49.3 (range, 45-52) representing 88.1% of the theoretical maximum. The score for frequency of dysphagia episodes was 1.6 ± 1.4; all patients scored 3 for the grade of dysphagia. Conclusions. Laparoscopic Heller myotomy is effective and safe for achalasia in children, offering a good and durable quality of life; although frequent, the dysphagia episodes were mild (AU)

Comparative study of shrinkage, inflammatory response and fibroplasia in heavyweight and lightweight meshes.

PURPOSE: In this manuscript, the authors describe an animal study comparing shrinkage, inflammatory response and fibroplasia in heavyweight (HW-PP) and lightweight polypropylene (LW-PP) meshes. METHODS: Both meshes were fixed on abdominal fascia of 25 Wistar rats (epifascial onlay placement). They were killed at 7, 28 and 90 days to measure the prostheses. Histological analysis was performed with hematoxylin-eosin for cellular counting and immunohistochemistry to measure collagen types I and III. RESULTS: The authors found that the LW-PP mesh presented greater median shrinkage than HW-PP mesh at 7 (P = .036), 28 (P = .674) and 90 days (P = .038) postoperatively. There were more neutrophils on LW-PP mesh (P = .008) at 7 days, gradually diminishing in both prostheses. Lymphocytes were similar between the implants at 7 days, diminishing about 50 % on LW-PP mesh (P < .001) at 90 days. Macrophages and giant cells diminished on LW-PP and increased on HW-PP meshes (P < .001). Collagen I/III ratio presented a progressive, almost fivefold rise at 90 days, on both mesh types (P < .001). The collagen I/III ratio was similar between LW-PP and HW-PP meshes at the three times studied. CONCLUSIONS: It is concluded that LW-PP showed more shrinkage than HW-PP mesh at 7 and 90 days, despite the fact that HW-PP presented more lately foreign body reaction. The collagen I/III ratio was similar between the prostheses and increased during the postimplant period.

[Outcome of laparoscopic Heller myotomy in children]. / Miotomía de Heller laparoscópica: resultados en niños.

AIM: The appropriate management of achalasia in children remains debatable. The present study aimed to evaluate the outcome of laparoscopic Heller myotomy by assessing short- and mid-term issues. METHODS: Children submitted to surgery from 2002 to 2010 were included. Surgery was proposed after failure of endoscopic dilatations. All patients underwent esophagocardiomyotomy (Heller) plus anterior fundoplication (Dor) by laparoscopy. Demographics, presentation symptoms and perioperative details were analyzed. The outcomes were assessed both by medical records and the application of a 14 items (score 0-worst to 4-best/normal) self-evaluation questionnaire (modified GIQLI - covering only upper gastrointestinal symptoms). RESULTS: Six patients (5 males) with a median age of 12.2 years (range: 0.8-14.2) were submitted to surgery. The presenting symptoms were: dysphagia (83.3%), weight loss (50%), vomiting (33.3%), chronic cough (33.3%), and chest pain (16.7%). All patients were operated on by laparoscopy with no conversions; there were no intra or postoperative complications. At a median follow-up of 5 years (range: 2-10) none of the patients were re-operated. Five patients have normal eating habits; the remaining case presented recurrent episodes of dysphagia requiring regular endoscopic dilatations (every 6 months). The total GIQLI presented a mean score of 49.3 (range, 45-52) representing 88.1% of the theoretical maximum. The score for frequency of dysphagia episodes was 1.6 +/- 1.4; all patients scored 3 for the grade of dysphagia. CONCLUSIONS: Laparoscopic Heller myotomy is effective and safe for achalasia in children, offering a good and durable quality of life; although frequent, the dysphagia episodes were mild.

The impact of tacrolimus as rescue therapy in children using a double immunosuppressive regimen after heart transplantation.

BACKGROUND: Organ transplant recipients with refractory rejection or intolerance to the prescribed immunosuppressant may respond to rescue therapy with tacrolimus. We sought to evaluate the clinical outcomes of children undergoing heart transplantation who required conversion from a cyclosporine-based, steroid-free therapy to a tacrolimus-based regimen. METHODS: We performed a prospective, observational, cohort study of 28 children who underwent conversion from cyclosporine-based, steroid-free therapy to a tacrolimus-based therapy for refractory or late rejection or intolerance to cyclosporine. RESULTS: There was complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (×100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (P ≤ .0001). There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. CONCLUSION: Tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option for pediatric patients.

Skin manifestations of obesity: a comparative study.

BACKGROUND: Obesity is one of the world's biggest health problems nowadays. Little research has been done on the skin diseases that affect obese patients. OBJECTIVE: To study the prevalence of skin manifestations in obese patients compared with a control group of normal-weight patients. METHODS: A total of 76 obese patients [body mass index (BMI) ≥30 kg/m(2) ] and 73 with normal-weight volunteers (BMI 18.5-24.9 kg/m(2) ) were included in the study and had their complete medical history and skin examination evaluated by the same examiner. All patients were investigated for the presence of metabolic syndrome. RESULTS: The dermatoses that showed a statistically significant relationship with obesity, compared with the control group were: striae (P < 0.001), plantar hyperkeratosis (P < 0.001), acrochordons (P = 0.007), intertrigo (P < 0.001), pseudoacanthosis nigricans (P < 0.001), keratosis pilaris (P = 0.006), lymphedema (P = 0.002) and bacterial infections (P = 0.05). The presence of striae, pseudoacanthosis nigricans and bacterial infections were also found to be correlated with the degree of obesity. CONCLUSIONS: Obesity is strongly related to several skin alterations that could be considered as markers of excessive weight. Skin care of obese patients deserves particular attention, not only because of the high prevalence of cutaneous alteration but mainly because many of these disorders are preventable and could be treated, improving patient's quality of life.